Measurement of spatiotemporal intracellular deformation of cells adhered to collagen matrix during freezing of biomaterials.
Preservation of structural integrity inside cells and at cell-extracellular matrix (ECM) interfaces is a key challenge during freezing of biomaterials. Since the post-thaw functionality of cells depends on the extent of change in the cytoskeletal structure caused by complex cell-ECM adhesion, spatiotemporal deformation inside the cell was measured using a newly developed microbead-mediated particle tracking deformetry (PTD) technique using fibroblast-seeded dermal equivalents as a model tissue. Fibronectin-coated 500 nm diameter microbeads were internalized in cells, and the microbead-labeled cells were used to prepare engineered tissue with type I collagen matrices. After a 24 h incubation the engineered tissues were directionally frozen, and the cells were imaged during the process. The microbeads were tracked, and spatiotemporal deformation inside the cells was computed from the tracking data using the PTD method. Effects of particle size on the deformation measurement method were tested, and it was found that microbeads represent cell deformation to acceptable accuracy. The results showed complex spatiotemporal deformation patterns in the cells. Large deformation in the cells and detachments of cells from the ECM were observed. At the cellular scale, variable directionality of the deformation was found in contrast to the one-dimensional deformation pattern observed at the tissue scale, as found from earlier studies. In summary, this method can quantify the spatiotemporal deformation in cells and can be correlated to the freezing-induced change in the structure of cytosplasm and of the cell-ECM interface. As a broader application, this method may be used to compute deformation of cells in the ECM environment for physiological processes, namely cell migration, stem cell differentiation, vasculogenesis, and cancer metastasis, which have relevance to quantify mechanotransduction.


[Polymorphism of Trypanosoma cruzi in the blood of a vertebrate host].
Tetramorphism of trypomastigote forms has been discovered in the blood stream of mice infected with Trypanosoma cruzi, that is C slender, C middle, S slender, S middle and forms intermediate between C and S. Regular changes of forms have been observed in the course of the infection. In the middle of the process, at the moment of maximum destruction of parasites affected by immunosystems of the host, C-forms prevailing on the whole substantially give place to S-forms, slender variants being replaced by middle ones within each of them. Polymorphism in the bloodstream of the vertebrate host is the general property of all trypanosomes, with their common biological value: immunological adaptation to parasitism in the blood and preadaptation to the continuation of the life cycle in the invertebrate host.


ARVs and ARTs: medicoscapes and the unequal place-making for biomedical treatments in sub-Saharan Africa.
Asking why some diseases gain global attention whereas others are neglected, we present two case studies that demonstrate the unequal treatment and financing options available for HIV/AIDS versus infertility treatments. We track three key phenomena central to understanding the unequal public attention given to certain ailments: peace and security, subordination of the social to the biological, and a "global" quality. Existing concepts such as global assemblages or therapeutic citizenship are quite limited when it comes to bodily conditions that result in social suffering and do not satisfy the conditions of advocacy. Since it is not enough to observe "flowing" and "moving," we propose the concept of medicoscapes, to acknowledge that such activities simultaneously entail channeling and carving out. Medicoscapes enhance the analysis of linkages between different health conditions regardless of whether they are biological or social and how they interconnect places, sites, and people.


Dietary eicosapentaenoic acid and docosahexaenoic acid are more effective than alpha-linolenic acid in improving insulin sensitivity in rats.
In the present study, we investigated whether long-term administration of high dose of alpha-linolenic acid (ALA) is able to mimic the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or a mixture of both with respect to insulin sensitivity in male Wistar rats. Furthermore, we intended to test whether these n-3 polyunsaturated fatty acids reveal differential effects on glucose and insulin levels. As a result, plasma glucose and insulin levels were lowered by 35 and 38%, respectively, in the EPA and DHA group compared to the ALA group. Insulin sensitivity was substantially improved, as indicated by a 60% decreased HOMA index after an 8-week EPA and DHA administration, as compared to the effect observed for feeding ALA. However, insulin sensitivity did not differ between animals of the EPA and the DHA group. These results demonstrate that ALA intake at the expense of EPA and DHA in a diet high in n-3 fatty acids does not represent an alternative to raising oily fish consumption with regard to insulin sensitivity. Furthermore, a differential effect of the members of the n-3 family was shown for ALA compared to EPA and DHA, but EPA and DHA revealed comparable effects on insulin sensitivity.


Using Negative Emotions to Trace the Experience of Borderline Personality Pathology: Interconnected Relationships Revealed in an Experience Sampling Study.
While emotional difficulties are highly implicated in borderline personality disorder (BPD), the dynamic relationships between emotions and BPD symptoms that occur in everyday life are unknown. The current paper examined the function of negative emotions as they relate to BPD symptoms in real time. Experience sampling methodology with 281 participants measured negative emotions and borderline symptoms, expressed as a spectrum of experiences, five times daily for two weeks. Overall, having a BDP diagnosis was associated with experiencing more negative emotions. Multilevel modeling supported positive concurrent relationships between negative emotions and BPD symptoms. Lagged models showed that even after 3 hours negative emotions and several symptoms continued to influence each other. Therefore, results indicated that negative emotions and BPD symptoms are intricately related; some evidenced long-lasting relationships. This research supports emotion-symptom contingencies within BPD and provides insight regarding the reactivity and functionality of negative emotions in borderline pathology.


Implementation of a National Workplace Wellness Program for Health Workers in Botswana.
: The Botswana workplace wellness program (WWP) for health care workers (HCWs) was initiated in 2007. WWP implementation was assessed using a sequential, explanatory, mixed methods design including a national implementation assessment (27 health districts) and in-depth interviews (n = 38). Level of implementation varied across districts with health screening, therapeutic recreation, and health promotion implemented more frequently than occupational health activities and psychosocial services. Facilitators to WWP implementation included establishment of a dedicated, diverse WWP committee; provision of administrative support, and integration of activities into organizational culture. Barriers included competing priorities related to delivery of health services to clients, limited technical ability to deliver occupation health activities and psychosocial support, receipt of health services from colleagues, and limited appreciation for personal wellness by some HCWs. Ensuring the well-being of HCWs is critical in reaching international health goals.


An overview of the taxonomy, phylogeny, and typification of nectriaceous fungi in Cosmospora, Acremonium, Fusarium, Stilbella, and Volutella.
A comprehensive phylogenetic reassessment of the ascomycete genus Cosmospora (Hypocreales, Nectriaceae) is undertaken using fresh isolates and historical strains, sequences of two protein encoding genes, the second largest subunit of RNA polymerase II (rpb2), and a new phylogenetic marker, the larger subunit of ATP citrate lyase (acl1). The result is an extensive revision of taxonomic concepts, typification, and nomenclatural details of many anamorph- and teleomorph-typified genera of the Nectriaceae, most notably Cosmospora and Fusarium. The combined phylogenetic analysis shows that the present concept of Fusarium is not monophyletic and that the genus divides into two large groups, one basal in the family, the other terminal, separated by a large group of species classified in genera such as Calonectria, Neonectria, and Volutella. All accepted genera received high statistical support in the phylogenetic analyses. Preliminary polythetic morphological descriptions are presented for each genus, providing details of perithecia, micro- and/or macro-conidial synanamorphs, cultural characters, and ecological traits. Eight species are included in our restricted concept of Cosmospora, two of which have previously documented teleomorphs and all of which have Acremonium-like microconidial anamorphs. A key is provided to the three anamorphic species recognised in Atractium, which is removed from synonymy with Fusarium and epitypified for two macroconidial synnematous species and one sporodochial species associated with waterlogged wood. Dialonectria is recognised as distinct from Cosmospora and two species with teleomorph, macroconidia and microconidia are accepted, including the new species D. ullevolea. Seven species, one with a known teleomorph, are classified in Fusicolla, formerly considered a synonym of Fusarium including members of the F. aquaeductuum and F. merismoides species complex, with several former varieties raised to species rank. Originally a section of Nectria, Macroconia is raised to generic rank for five species, all producing a teleomorph and macroconidial anamorph. A new species of the Verticillium-like anamorphic genus Mariannaea is described as M. samuelsii. Microcera is recognised as distinct from Fusarium and a key is included for four macroconidial species, that are usually parasites of scale insects, two of them with teleomorphs. The four accepted species of Stylonectria each produce a teleomorph and micro- and macroconidial synanamorphs. The Volutella species sampled fall into three clades. Pseudonectria is accepted for a perithecial and sporodochial species that occurs on Buxus. Volutella s. str. also includes perithecial and/or sporodochial species and is revised to include a synnematous species formerly included in Stilbella. The third Volutella-like clade remains unnamed. All fungi in this paper are named using a single name system that gives priority to the oldest generic names and species epithets, irrespective of whether they are originally based on anamorph or teleomorph structures. The rationale behind this is discussed.


[Promising immunonutrients in general medical practice].
The review gives data on prospects for using agents based on probiotics and trace elements for immunomodulation. It presents information on that a Lactobacillus casei rhamnosus 35-based probiotic is able to reduce the incidence and severity of viral and bacterial infections. The potential of zinc and selenium as immunotropic agents is shown.


Effects of Hydrophobicity on Antimicrobial Activity, Selectivity, and Functional Mechanism of Guanidinium-Functionalized Polymers.
In this study, a series of guanidinium-functionalized polycarbonate random co-polymers is prepared from organocatalytic ring-opening polymerization to investigate the effect of the hydrophobic side chain (ethyl, propyl, isopropyl, benzyl, and hexyl) on their antimicrobial activity and selectivity. Although the polymers exhibit similar minimum inhibitory concentrations, the more hydrophobic polymers exhibit a faster rate of bacteria elimination. At higher percentage content (20 mol%), polymers with more hydrophobic side chains suffer from poor selectivity due to their high hemolytic activity. The highly hydrophobic co-polymer, containing the hydrophobic hexyl-functionalized cyclic carbonate, kills bacteria via a membrane-disruptive mechanism. Micelle formation leads to a lower extent of membrane disruption. This study unravels the effects of hydrophobic side chains on the activities of the polymers and their killing mechanism, providing insights into the design of new antimicrobial polymers.


Disruption of cardiac thin filament assembly arising from a mutation in LMOD2: A novel mechanism of neonatal dilated cardiomyopathy.
Neonatal heart failure is a rare, poorly-understood presentation of familial dilated cardiomyopathy (DCM). Exome sequencing in a neonate with severe DCM revealed a homozygous nonsense variant in leiomodin 2 (LMOD2, p.Trp398*). Leiomodins (Lmods) are actin-binding proteins that regulate actin filament assembly. While disease-causing mutations in smooth (LMOD1) and skeletal (LMOD3) muscle isoforms have been described, the cardiac (LMOD2) isoform has not been previously associated with human disease. Like our patient, Lmod2-null mice have severe early-onset DCM and die before weaning. The infant's explanted heart showed extraordinarily short thin filaments with isolated cardiomyocytes displaying a large reduction in maximum calcium-activated force production. The lack of extracardiac symptoms in Lmod2-null mice, and remarkable morphological and functional similarities between the patient and mouse model informed the decision to pursue cardiac transplantation in the patient. To our knowledge, this is the first report of aberrant cardiac thin filament assembly associated with human cardiomyopathy.


Thermal conductivity of two-dimensional BC3: a comparative study with two-dimensional C3N.
The thermal conductivities of single-layer BC3 (SLBC) sheets and their responses to environmental temperature, vacancy defects and external strain have been studied and compared with those of single-layer C3N (SLCN) sheets by molecular dynamics (MD) simulations. We found that SLBC and SLCN are isotropic in the basal plane and that their predicted thermal conductivities for infinite length sheets are 488.54 W m-1 K-1 and 799.87 W m-1 K-1, respectively. Despite many similar features in the structures of these materials, SLBC exhibits a lower thermal conductivity than SLCN due to stronger flexural acoustic phonon-defect scattering rates and weaker interatomic bonding stiffnesses. The vibrational density of states (VDOS) are calculated in both structures to elucidate their thermal conductivity differences. SLBC exhibits a more substantial redshift phenomenon in the high- and low-frequency domains than SLCN. In addition, the thermal conductivities of these materials exhibit decreasing trends in response to increases in temperature and defect ratio, and the temperature effect in SLBC is more substantial than that in SLCN, while the defect effect in SLBC is less substantial than that in SLCN. The influences of uniaxial compressive and tensile strains on the thermal conductivities of these materials are analysed separately. These two deformation modes cause different effects on the thermal transport behaviours of SLBC and SLCN: the effect of uniaxial compressive strain is slightly negative, while the effect of uniaxial tensile strain is initially positive and then negative. Moreover, the biaxial strains result in a more severe reduction in thermal conductivity than the uniaxial strains. Remarkably, the impact of uniaxial and biaxial tensile strains on thermal transport was stronger in SLBC than in SLCN. We propose that SLBC nanomembranes are promising candidates for various thermal applications.


Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway.
Quercetin is a plant flavonoid and has antioxidative properties. In this study, we evaluated the therapeutic effect of quercetin on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. LT4 was used to prepare the experimental hyperthyroidism model via the intraperitoneal injection. Quercetin was injected at a series doses (5, 50, and 100 mg/kg) to LT4-induced hypothyroidism rats once a day for 14 days. The body weight and food intake were measured once a week. The levels of thyroid hormones, liver function, oxidative stress markers, and antioxidant markers were measured using commercial enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the thyroid tissue histological changes. The levels of nuclear and total nuclear factor erythroid 2-related factor 2 (Nrf2) were determined by western blot. The liver oxidative stress markers in LT4-induced hyperthyroidism Nrf2 knockout rats were determined to evaluate the role of Nrf2 on quercetin induced protective effects. LT4 administration increased the levels of serum triiodothyronine and thyroxine, activity of oxidative stress markers with a parallel decrease in antioxidant markers and Nrf2. However, the simultaneous administration of quercetin, reversed all these effects indicating its potential in the regulation of hyperthyroidism. Furthermore, the loss function of Nrf2 diminished these effects resulting from the quercetin application, indicating the inhibitory effects caused by the quercetin may be involved in Nrf2 signaling pathway. These results indicate that quercetin could be used to protect against experimental hyperthyroidism-induced liver damage via Nrf2 signaling pathway.


[Production and characteristics of monoclonal antibodies against individual prekeratins in simple types of rat epithelium].
BALB/c mice were immunized with intermediate filaments (IF) from the rat colon mucosa, and their splenocytes were fused with myeloma cells to obtain hybridomas. Specific antibody production was assessed by indirect immunofluorescence on cultured rat hepatoma 27 containing prekeratins. The clones that stained IF in hepatoma and not in fibroblasts were judged positive. Clones E3 and E6 were shown to produce monoclonal antibodies against prekeratin with molecular mass of 40 kD (PK40), while clones E2 and E7 produced antibodies against prekeratin with molecular mass of 55 kD (PK55). This was established by immunoblotting with 125I-protein A in cell lysates from the colon, bladder, and hepatoma 27. Only PK55 was revealed in liver and salivary gland lysates. The above proteins were not detected in esophagus, fibroblast and skeletal muscle cell lysates. The monoclonal antibodies make it possible to study individual prekeratin expression in embryogenesis, differentiation and neoplastic transformation of simple epithelium.


Rule based classifier for the analysis of gene-gene and gene-environment interactions in genetic association studies.
Several methods have been presented for the analysis of complex interactions between genetic polymorphisms and/or environmental factors. Despite the available methods, there is still a need for alternative methods, because no single method will perform well in all scenarios. The aim of this work was to evaluate the performance of three selected rule based classifier algorithms, RIPPER, RIDOR and PART, for the analysis of genetic association studies. Overall, 42 datasets were simulated with three different case-control models, a varying number of subjects (300, 600), SNPs (500, 1500, 3000) and noise (5%, 10%, 20%). The algorithms were applied to each of the datasets with a set of algorithm-specific settings. Results were further investigated with respect to a) the Model, b) the Rules, and c) the Attribute level. Data analysis was performed using WEKA, SAS and PERL. The RIPPER algorithm discovered the true case-control model at least once in >33% of the datasets. The RIDOR and PART algorithm performed poorly for model detection. The RIPPER, RIDOR and PART algorithm discovered the true case-control rules in more than 83%, 83% and 44% of the datasets, respectively. All three algorithms were able to detect the attributes utilized in the respective case-control models in most datasets. The current analyses substantiate the utility of rule based classifiers such as RIPPER, RIDOR and PART for the detection of gene-gene/gene-environment interactions in genetic association studies. These classifiers could provide a valuable new method, complementing existing approaches, in the analysis of genetic association studies. The methods provide an advantage in being able to handle both categorical and continuous variable types. Further, because the outputs of the analyses are easy to interpret, the rule based classifier approach could quickly generate testable hypotheses for additional evaluation. Since the algorithms are computationally inexpensive, they may serve as valuable tools for preselection of attributes to be used in more complex, computationally intensive approaches. Whether used in isolation or in conjunction with other tools, rule based classifiers are an important addition to the armamentarium of tools available for analyses of complex genetic association studies.


Chamber bioaerosol study: human emissions of size-resolved fluorescent biological aerosol particles.
Humans are a prominent source of airborne biological particles in occupied indoor spaces, but few studies have quantified human bioaerosol emissions. The chamber investigation reported here employs a fluorescence-based technique to evaluate bioaerosols with high temporal and particle size resolution. In a 75-m(3) chamber, occupant emission rates of coarse (2.5-10 μm) fluorescent biological aerosol particles (FBAPs) under seated, simulated office-work conditions averaged 0.9 ± 0.3 million particles per person-h. Walking was associated with a 5-6× increase in the emission rate. During both walking and sitting, 60-70% or more of emissions originated from the floor. The increase in emissions during walking (vs. while sitting) was mainly attributable to release of particles from the floor; the associated increased vigor of upper body movements also contributed. Clothing, or its frictional interaction with human skin, was demonstrated to be a source of coarse particles, and especially of the highly fluorescent fraction. Emission rates of FBAPs previously reported for lecture classes were well bounded by the experimental results obtained in this chamber study. In both settings, the size distribution of occupant FBAP emissions had a dominant mode in the 3-5 μm diameter range.


Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3.
Large intronic expansions of the triplet-repeat sequence (GAA.TTC) cause transcriptional repression of the Frataxin gene (FXN) leading to Friedreich's ataxia (FRDA). We previously found that GAA-triplet expansions stimulate heterochromatinization in vivo in transgenic mice. We report here using chromosome conformation capture (3C) coupled with high-throughput sequencing that the GAA-repeat expansion in FRDA cells stimulates a higher-order structure as a fragment containing the GAA-repeat expansion showed an increased interaction frequency with genomic regions along the FXN locus. This is consistent with a more compacted chromatin and coincided with an increase in both constitutive H3K9me3 and facultative H3K27me3 heterochromatic marks in FRDA. Consistent with this, DNase I accessibility in regions flanking the GAA repeats in patients was decreased compared with healthy controls. Strikingly, this effect could be antagonized with the class III histone deactylase (HDAC) inhibitor vitamin B3 (nicotinamide) which activated the silenced FXN gene in several FRDA models. Examination of the FXN locus revealed a reduction of H3K9me3 and H3K27me3, an increased accessibility to DNase I and an induction of euchromatic H3 and H4 histone acetylations upon nicotinamide treatment. In addition, transcriptomic analysis of nicotinamide treated and untreated FRDA primary lymphocytes revealed that the expression of 67% of genes known to be dysregulated in FRDA was ameliorated by the treatment. These findings show that nictotinamide can up-regulate the FXN gene and reveal a potential mechanism of action for nicotinamide in reactivating the epigenetically silenced FXN gene and therefore support the further assessment of HDAC inhibitors (HDACi's) in FRDA and diseases caused by a similar mechanism.


A Significance Assessment of Diabetes Diagnostic Biomarkers Using Machine Learning.
Diabetes can be diagnosed by either Fasting Plasma Glucose or Hemoglobin A1c. The aim of our study was to explore the differences between the two criteria through the development of a machine learning based diabetes diagnostic algorithm and analysing the predictive contribution of each input biomarker. Our study concludes that fasting insulin is predictive of diabetes defined by FPG, but not by HbA1c. Besides, 28 other fasting blood biomarkers were not significant predictors of diabetes.


Distinct effects of two CD44 isoforms on tumor growth in vivo.
Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.


TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome.
To assess the frequency of TP53 alterations and their correlation with other genetic changes and outcome in acute myeloid leukemia with complex karyotype (CK-AML), we performed integrative analysis using TP53 mutational screening and array-based genomic profiling in 234 CK-AMLs. TP53 mutations were found in 141 of 234 (60%) and TP53 losses were identified in 94 of 234 (40%) CK-AMLs; in total, 164 of 234 (70%) cases had TP53 alterations. TP53-altered CK-AML were characterized by a higher degree of genomic complexity (aberrations per case, 14.30 vs 6.16; P < .0001) and by a higher frequency of specific copy number alterations, such as -5/5q-, -7/7q-, -16/16q-, -18/18q-, +1/+1p, and +11/+11q/amp11q13∼25; among CK-AMLs, TP53-altered more frequently exhibited a monosomal karyotype (MK). Patients with TP53 alterations were older and had significantly lower complete remission rates, inferior event-free, relapse-free, and overall survival. In multivariable analysis for overall survival, TP53 alterations, white blood cell counts, and age were the only significant factors. In conclusion, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category.


Telephone-Delivered Cognitive-Behavioral Therapy for Older, Rural Veterans with Depression and Anxiety in Home-Based Primary Care.
Rural, homebound older adults are at increased risk for anxiety and depression and have limited access to mental health services. These individuals face many barriers to receiving evidence-based mental health treatment and would benefit from interventions that increase access to and efficiency of care. The aim of this study was to evaluate use of a telephone-delivered, modular, cognitive behavioral therapy (CBT) intervention for both late-life depression and anxiety delivered to rural, homebound Veterans. Three cases are presented to illustrate the flexible adaptation of the intervention for use among older Veterans enrolled in home-based primary care, with varying symptom presentations and functional limitations. The Veterans received 7 to 9 sessions of the CBT intervention, with ordering of skill modules based on symptom presentation and determined collaboratively between patient and therapist. The three Veterans showed improvement in depression and/or anxiety symptoms following treatment and provided positive feedback regarding their experiences in this program. These results suggest that telephone-delivered CBT is acceptable to older adults and can be tailored to individual patient needs. Clinicians should consider telephone-delivered CBT as an alternate mode of therapy to increase access to mental health care for rural, homebound individuals with depression and anxiety.


Pitfalls in management of fingertip injuries and hand lacerations.
Fingertip injuries and lacerations of the hand are often dismissed as inconsequential, although this attitude can lead to more serious problems. Appropriate and timely treatment of these injuries prevents loss of function, preserves digital sensibility, and lessens the need for reconstructive surgery.


Adverse childhood experiences (ACEs), excessive alcohol use and intimate partner violence (IPV) perpetration among Black men: A latent class analysis.
Adverse childhood experiences (ACEs) have been linked to subsequent intimate partner violence (IPV) perpetration and alcohol use. Although higher rates of ACEs are found in racial/ethnic minority populations, there is a paucity of research examining ACEs patterns and risk for IPV perpetration and excessive alcohol use among Black men. To identify homogeneous subgroups based on ACEs among Black men using latent class analysis and assessing risk for later IPV perpetration and excessive alcohol consumption in adulthood. Using a sample of Black men (n = 2306) from Wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), we conducted latent class analysis (LCA) to examine their ACEs patterns based on 10 domains. ACE classes were used in logistic regression models to predict IPV perpetration and unhealthy alcohol use. LCA revealed three classes: (1) High Household Dysfunction & Physical Neglect; (2) Physical/Emotional Abuse; and (3) Low ACEs. Men in the High Household Dysfunction & Physical Abuse (OR = 3.95, p < 0.001), and Physical/Emotional Abuse (OR = 2.37, p < 0.001) classes had increased risk for IPV perpetration (ref: Low ACEs class) controlling for sociodemographic factors. No significant association was found between class membership and unhealthy alcohol use. Our findings highlight the need for interventions aimed at addressing ACEs among Black boys as they increase risk for negative outcomes in adulthood. Future research should explore heterogeneity in ACEs among youth and risk of IPV and explore possible causal mechanisms in the development of IPV among adults who have experienced ACEs.


A pilot single-institution predictive model to guide rib fracture management in elderly patients.
Rib fractures (RFx) remain the most prevalent injury in an elderly population that will increase from 40 to 81 million for the next 30 years. We sought to create an accurate cost-effective algorithm to triage elderly patients with RFx that accounted for both frailty and trauma burden. Retrospective analysis evaluated 400 patients older than 55 years with RFx admitted to a level 1 trauma center from 2007 to 2012. Comorbidities included chronic obstructive pulmonary disease, congestive heart failure, tobacco use, obesity, and nutrition and functional status. Trauma burden included RFx, tube thoracostomy, pulmonary contusions, and spine and extremity fractures. Patients with Glasgow Coma Scale scores lower than 13, thoracoabdominal surgery, or deaths from other causes were excluded. Comparative analysis used bivariate and logistic regression. Variables contributing to intubation (INT) and pneumonia (PNA) were then used to create a scoring system to predict the need for intensive care unit (ICU) admission. Six variables increased the risk for INT or PNA: chronic obstructive pulmonary disease, low albumin, assisted status, tube thoracostomy, Injury Severity Score, and RFx (p < 0.05). These six variables and congestive heart failure (odds ratio, 1.9; p = 0.06) were used to create a predictive model with the following scores assigned respectively: 1.4, 1.1, 1, 0.9, 0.1(n), 0.1(n), and 0.6. A score lower than 3.7 had a sensitivity and specificity of 78.5% and 78.9%. The negative predictive value was 94.5% for INT or PNA, suggesting a low risk for ICU requirement. Ninety-two ICU admissions had a score lower than 3.7. Forty had no other indication for ICU admission aside from RFx. These patients had an average ICU length of stay of 1.7 days, resulting in an increased cost of $2,200 per patient. A scoring system combining frailty and trauma burden may provide more accurate and cost-effective triage of the elderly trauma patient with RFx. Further prospective studies are required to verify our scoring system. Prognostic and epidemiologic study, level III.


Expression of Hypoxia-Inducible Factor 1α in Invasive Breast Cancer with Metastasis to Lymph Nodes: Correlation with Steroid Receptors, HER2 and EPO-R.
Expression of hypoxia-inducible factor 1α (HIF-1α) reflects the degree of cell hypoxia and its increased expression was found in most neoplasms, their metastasis as well as in some precancerous lesions. The study aimed to investigate the expression HIF-1α in invasive breast cancer with metastasis to lymph nodes in correlation with steroid receptors (ER-estrogen receptor, PR-progesterone receptor), HER2 (human epidermal growth factor receptor 2) and EPO-R (erythropoietin receptor). A total of 58 cases of invasive breast cancer with metastasis to lymph nodes were assessed for expression of HIF-1α, EPO-R, ER, PR and HER2. In our study, among all invasive breast cancers, 36.2% exhibited HIF-1α expression in the nuclei of neoplastic cells. We also assessed the correlation between histological type of cancer and basic immunohistochemical profile that included HIF-1α expression and statistical significance was noted only in the case of PR-/ER-/HER2-/ /HIF-1α-/ and PR+/ER+/HER2-/HIF-1α-/ (p = 0.028 and p = 0.008, respectively). However, only in the case of the PR+/ER+/HER2-/HIF-1α+/ immunohistochemical profile and histological grading did we note a statistical significance (p = 0.006). Expression of HIF-1α was most often noted in cancers exhibiting expression of HER2 protein (57.14%). Our study also assessed the relationship between the expression of HIF-1α in invasive breast cancers and the expression of EPO-R and areas of necrosis, demonstrating a statistically significant dependence (p = 0.003). Expression of HIF-1α was more often noted in invasive HER2+ cancers characterized by high degree of aggressiveness and poorer prognosis, which might suggest that presence of HIF-1α protein expression in HER2+ cancers could be an additional prognostic factor, the frequent occurrence of the phenotype of HIF-1α and EPO-R in cancers invasive HER2 +, in the absence of ER and PR, may suggest that HIF-1α and EPO-R may be an indicator of the aggressiveness of invasive breast cancers, indicating the need for a specific forms of treatment in this group of patients.


Comparison of four skin preparation strategies to prevent catheter-related infection in intensive care unit (CLEAN trial): a study protocol for a randomized controlled trial.
Catheter-related infection is the third cause of infections in intensive care units (ICU), increasing the length of stay in ICU and hospital, mortality, and costs. Skin antisepsis is one of the most prevalent preventive measures. In this respect, it would appear preferable to recommend the use of alcoholic povidone iodine or chlorhexidine rather than aqueous povidone iodine. However, the data comparing chlorhexidine to povidone-iodine, both of them in alcoholic solutions, remain limited. Moreover, the benefits of enhanced cleaning prior to disinfection of skin that is not visibly soiled have yet to be confirmed in a randomized study. A prospective multicenter, 2 × 2 factorial, randomized-controlled, assessor-blind trial will be conducted in 11 intensive care units in six French hospitals. All adult patients aged over 18 years requiring the insertion of at least one peripheral arterial catheter and/or a non-tunneled central venous catheter and/or a hemodialysis catheter and/or an arterial pulmonary catheter will be randomly assigned to have all their catheters cared with one of four skin preparation strategies (2% chlorhexidine/70% isopropyl alcohol or 5% povidone iodine/69% ethanol with or without prior skin scrubbing). At catheter removal, catheter tips will be quantitatively cultured. Sets of aerobic and anaerobic blood cultures will be routinely obtained when a patient has fever, hypothermia, or other indications. In case of suspected catheter-related infection the patient's form will be reviewed by an independent adjudication committee. We plan to enroll 2,400 patients (4,800 catheters). The main objective is to demonstrate that use of 2% alcoholic chlorhexidine compared to 5% alcoholic povidone iodine in skin preparation lowers the rate of catheter-related infection. The second endpoint is to demonstrate that enhanced skin cleaning prior to disinfection of skin that is not visibly soiled does not reduce catheter colonization. Other outcomes include comparison of skin colonization at catheter insertion site, comparison of catheter colonization and catheter-related bacteremia taking place during implementation of the four strategies of skin preparation, and cutaneous tolerance, length of hospitalization, mortality, and costs. This study will help to update recommendations on the choice of an antiseptic agent to use in skin preparation prior to insertion of a vascular catheter and, by extension, of an epidural catheter and it will likewise help to update recommendations on the usefulness of skin scrubbing prior to disinfection when the skin is not visibly soiled. Clinicaltrials.gov number NCT01629550.


Concerns of pregnant women about bing tested for HIV: a study in a predominately Mexican-American population.
More than 90% of pediatric acquired immune deficiency syndrome (AIDS) cases are due to mother-to-child (vertical) transmission. Medical intervention can reduce the risk of vertical transmission human immunodeficiency virus (HIV) from 25% to less than 8%. However, studies have suggested that approximately one-fourth of women may refuse HIV testing as part of routine prenatal care. The purpose of this study was to identify concerns that pregnant women might have that would impact their decision to undergo HIV testing in pregnancy. The study is a cross-sectional survey of 413 pregnant women in south Texas. A survey questionnaire was used to assess reasons why subjects might avoid HIV testing and to assess their risks for HIV infection. The reasons for not wanting HIV testing grouped around four themes: (1) fear of being stigmatized as sexually promiscuous or as an injecting drug user; (2) denial about the possibility of being infected; (3) fatalism; and (4) of rejection leading to loss of emotional and financial support. Overall, 15% of subjects who had not been previously tested (5% of all subjects) indicated that they would refuse HIV testing, a rate which is below rates of 20%-24% in previous studies. The lower rate of refusal for HIV testing in our study may reflect a downward trend nationally in the rate of refusal for prenatal testing. Many women have concerns about HIV testing, although these concerns may not necessarily prevent them from undergoing testing. Physicians and policy makers need to be aware of women's concerns and fears when implementing HIV testing policies.


Parametric Optimization of Trochoidal Step on Surface Roughness and Dish Angle in End Milling of AISID3 Steel Using Precise Measurements.
Tool steel play a vital role in modern manufacturing industries due to its excellent properties. AISI D3 is a cold work tool steel which possess high strength, more hardenability and good wear resistance properties. It has a wide variety of applications in automobile and tool and die making industries such as blanking and forming tools, high stressed cutting, deep drawing and press tools. The novel ways of machining these steels and finding out the optimum process parameters to yield good output is of practical importance in the field of research. This research work explores an attempt to identify the optimized process parameter combinations in end milling of AISI D3 steel to yield low surface roughness and maximum dish angle using trochoidal milling tool path, which is considered as a novelty in this study. 20 experimental trials based on face centered central composite design (CCD) of response surface methodology (RSM) were executed by varying the input process factors such as cutting speed, feed rate and trochoidal step. Analysis of variance (ANOVA) was adopted to study the significance of selected process parameters and its relative interactions on the performance measures. Desirability-based multiple objective optimization was performed and the mathematical models were developed for prediction purposes. The developed mathematical model was statistically significant with optimum conditions of cutting speed of 41m/min, feed rate of 120 mm/min and trochoidal step of 0.9 mm. It was also found that the deviation between the experimental and predicted values is 6.10% for surface roughness and 1.33% for dish angle, respectively.


Clinical and reliable change in an Australian residential substance use program using the Addiction Severity Index.
Although the Addiction Severity Index (ASI) is one of the most frequently used measures in alcohol and other drug research, it has rarely been used to assess clinical and reliable change. This study assessed clients' clinical and reliable change at The Salvation Army residential substance abuse treatment centers in Australia. A total of 296 clients completed ASI interviews on admission to treatment and 3 months after discharge from treatment. Clients demonstrated significant improvement on all seven ASI composites. The range of reliable change for each ASI composite varied from 30% to 70%. More than two-thirds of clients experienced clinically significant improvement for alcohol and drug problems. Psychiatric distress was clinically reduced in 44% of clients. This research indicates that residential substance abuse treatment can make important differences in client's lives at a clinical and functional level. However, the research highlights the challenge of effectively targeting psychiatric comorbidity within alcohol and other drug abuse populations.


Edible Leafy Vegetables from West Africa (Guinea-Bissau): Consumption, Trade and Food Potential.
Wild Edible Plants are common in the diet of rural communities of sub-Saharan Africa. In Guinea-Bissau, West Africa, wild plant resources are widely used in human diet, but very few studies have addressed them. The aim of this study is to reveal: (1) the wild and semi-cultivated leafy vegetables consumed in Guinea-Bissau; and (2) the nutritional composition of those plants traded at the largest country market in Bissau. Our results revealed that 24 native or naturalized species with edible leaves are currently consumed by Guinea-Bissau population. Five of them were found at the market: dried leaves of Adansonia digitata, Bombax costatum and Sesamum radiatum, and fresh leaves and shoots of Amaranthus hybridus and Hibiscus sabdariffa. The analysis of the nutritional properties revealed that leaves contain a significant amount of protein (10.1-21.0 g/100 g, dry basis), high values of macronutrients and micronutrients, as well as of phenolic compounds (13.1-40.3 mg GAE/g) and a considerable antioxidant capacity (DPPH 111.5-681.9 mg Eq Trolox). Although price and availability vary among the leafy vegetables analyzed, these traditional foods appear to be a good dietary component that can contribute to food security in Guinea-Bissau and in other West African countries, as these species are widely distributed in this region.


The impact of NHS expenditure on health outcomes in England: Alternative approaches to identification in all-cause and disease specific models of mortality.
Several recent studies have estimated the responsiveness of mortality to English National Health Service spending. Although broadly similar, the studies differ in how they identify the outcome equation. One approach uses conventional socio-economic variables as instruments for endogenous health care expenditure, whereas the other exploits exogenous elements in the resource allocation formula for local budgets. The former approach has usually been applied to specific disease areas (e.g., for cancer and circulatory disease), whereas the other has only been applied to all-cause mortality. In this letter, we compare the two approaches by using them to estimate the direct all-cause elasticity as well as disease-specific elasticities. We also calculate the implied all-cause elasticity associated with the disease-specific results. We find that the "funding rule" approach to identification can be successfully replicated and applied to disease area models. This is important because disease area models reduce the danger of aggregation bias present in all-cause analysis, and they offer the opportunity to link estimated mortality effects to more complete measures of health outcome that reflect what is currently known about the survival and morbidity disease burden in different programmes.


Racial/ethnic differences in stroke mortality in veterans.
We examined racial-ethnic differences in all-cause mortality after stroke in a cohort of veterans living in the southeastern United States. Data on a cohort of 4115 veterans with a diagnosis of stroke were analyzed. The cohort included veterans who classified themselves as non-Hispanic White, non-Hispanic Black, or Other. All veterans had a diagnosis of ischemic or hemorrhagic stroke. All subjects were seen in Veterans Affairs facilities in the Charleston, South Carolina area and were followed from January 1, 2000 to December 31, 2006. Cox proportional hazards regression models were used to compare survival times by race/ethnicity, adjusting for relevant covariates. In 38 months of follow-up, 1232 veterans in the cohort died. Compared with non-Hispanic White veterans, Black veterans were approximately 20% more likely to die, and other ethnicities were approximately 20% less likely to die in the unadjusted model. In the adjusted model, the White-Black disparity increased somewhat, and the disparity between Whites and other ethnicities was somewhat attenuated. Age, coronary heart disease, cancer, and Charlson co-morbidity index >2 were also associated with higher mortality. Non-Hispanic Black veterans with a history of stroke in the southeastern United States had significantly higher mortality than did Non-Hispanic White veterans and veterans of other ethnicities, even after adjusting for relevant covariates.


Isolation and characterization of alkaline phosphatase-containing granules (phosphasomes) from human polymorphonuclear leucocytes.
Human polymorphonuclear leucocytes were homogenized in isotonic sucrose and subjected to analytical subcellular fractionation by centrifugation on a discontinuous sucrose density gradient to produce a phosphasome-enriched fraction, contaminated primarily by plasma membrane. Experiments to separate these membrane fractions by centrifugation on gradients of Nycodenz or Percoll, or by toroidal coil counter current chromatography, were unsuccessful. Fractionation carried out on neutrophils previously suspended in isotonic sucrose containing a low concentration of digitonin resulted in the preparation of a highly purified phosphasome fraction, free of plasma membrane components. Electron-microscope cytochemistry of the purified fraction identified the phosphasomes as regular and irregular-shaped spheres and rods, the alkaline phosphatase being associated with the inner aspect of the vesicle membrane. These granule structures were very similar to phosphasomes observed in intact neutrophils. A proportion of the endoplasmic reticulum and Golgi membrane marker enzymes remained associated with the phosphasomes throughout the separation procedures.


SERS chiral recognition and quantification of enantiomers through cyclodextrin supramolecular complexation.
We introduce here a simple approach in which a cyclodextrin, functionalized with thiols in the narrower rim, is assembled onto the silver surface of a SERS platform composed of polystyrene beads coated with silver nanoparticles. Trapping properties of the fabricated sensor are demonstrated through the retention of different enantiomers (R,R or/and S,S) of hydrobenzoin (HBZ), a molecule that has not been reported before in SERS because it has no affinity for coinage metal surfaces. Further, selective recognition of each enantiomer and semiquantification of its proportion in a racemic mixture are provided by the analysis of the SERS spectra of the HBZ-cyclodextrin complex, in full agreement with the surface selection rules.


Operations for peptic ulcer disease: paradigm lost.
Over the past several decades, the pharmacologic and endoscopic treatment of peptic ulcer disease (PUD) has dramatically improved. To determine the effects of these and other changes on the operative management of PUD, we reviewed our surgical experience with gastroduodenal ulcers over the past 20 years. A computerized surgical database was used to analyze the frequencies of all operations for PUD performed in two training hospitals during four consecutive 5-year intervals beginning in 1980. Operative rates for both intractable and complicated PUD were compared with those for other general surgical procedures and operations for gastric malignancy. In the first 5-year period (1980 to 1984), a yearly average of 70 upper gastrointestinal operations were performed. This experience included 36 operations for intractability, 15 for hemorrhage, 12 for perforation, and seven for obstruction. During the same time span, 13 resections were performed annually for gastric malignancy. By the most recent 5-year interval (1994 to 1999), the total number of upper gastrointestinal operations had declined by 80% (14 cases), although the number of operations for gastric cancer had changed only slightly. Operations decreased most markedly for patients with intractability, but the prevalence of operations for bleeding, obstruction, and perforation was also decreased. We conclude that improved pharmacologic and endoscopic approaches have progressively curtailed the use of operative therapy for PUD. Elective surgery is now rarely indicated, and emergency operations are much less common. This changed paradigm poses new challenges for training and suggests different approaches for practice.


Letter posting and orientation matching: two equivalent tasks in action and perception?
The finding that in a patient with visual form agnosia (DF), the performance level varies in a visuomotor letter-posting task and a perceptual orientation matching task was considered as part of the evidence for the perception-action model (Milner and Goodale, 1995). In this study we examined an alternative interpretation of these findings. We specifically tested whether orientation matching and letter posting can be accomplished using different strategies. Sixteen neurologically intact participants were asked to either put cards of different sizes through a target slot of a certain orientation or to simply indicate the slot's orientation. Letter-posting was performed in three different conditions varying the amount of visual feedback available. Results show that some participants apply a strategy of obstacle-avoidance in the posting task. That is, they oriented the card such that the safety margin between the edges of the target and the card was increased. This tendency became stronger with increasing card size. In contrast, in the orientation matching task, the end-orientation of the card was unaffected by its size and closer to the slot's actual orientation. The findings suggest that posting and matching can be solved using different visuo-spatial information. The perception-action dissociation reported for these tasks in DF might therefore simply indicate a difficulty in computing visual orientation, an ability that is needed for successful orientation matching but not for posting.


Fiona: a parallel and automatic strategy for read error correction.
Automatic error correction of high-throughput sequencing data can have a dramatic impact on the amount of usable base pairs and their quality. It has been shown that the performance of tasks such as de novo genome assembly and SNP calling can be dramatically improved after read error correction. While a large number of methods specialized for correcting substitution errors as found in Illumina data exist, few methods for the correction of indel errors, common to technologies like 454 or Ion Torrent, have been proposed. We present Fiona, a new stand-alone read error-correction method. Fiona provides a new statistical approach for sequencing error detection and optimal error correction and estimates its parameters automatically. Fiona is able to correct substitution, insertion and deletion errors and can be applied to any sequencing technology. It uses an efficient implementation of the partial suffix array to detect read overlaps with different seed lengths in parallel. We tested Fiona on several real datasets from a variety of organisms with different read lengths and compared its performance with state-of-the-art methods. Fiona shows a constantly higher correction accuracy over a broad range of datasets from 454 and Ion Torrent sequencers, without compromise in speed. Fiona is an accurate parameter-free read error-correction method that can be run on inexpensive hardware and can make use of multicore parallelization whenever available. Fiona was implemented using the SeqAn library for sequence analysis and is publicly available for download at http://www.seqan.de/projects/fiona. Supplementary data are available at Bioinformatics online.


Discordant expression of tissue factor and its activity in polarized epithelial cells. Asymmetry in anionic phospholipid availability as a possible explanation.
Recent studies have shown a discrepancy between the level of tissue factor (TF) expression and the level of TF procoagulant activity on the apical and basolateral surface domains of polarized epithelial cells. The present investigation was performed to elucidate possible reasons for the discordant expression of TF and its activity on the surface of polarized epithelial cells using a human intestinal epithelial cell line, Caco-2 and Madin-Darby canine kidney epithelial cells, type II (MDCK-II). Functional activity of coagulation factor VIIa (VIIa) in complex with TF was 6- to 7-fold higher on the apical than the basolateral surface in polarized Caco-2 cells. In contrast, no significant difference was found in the formation of TF/VIIa complexes between the apical and basolateral surface. Confocal microscopy of Caco-2 cells showed TF expression on both the apical and the basolateral surface domains. Studies with MDCK-II cells showed that the specific functional activity of TF expressed on the apical cell surface was 5-fold higher than on the basolateral surface. To test whether differential expression of TF pathway inhibitor (TFPI) on the apical and basolateral surface could account for differences in TF/VIIa functional activity, we measured cell-surface-bound TFPI activity in Caco-2 cells. Small but similar amounts of TFPI were found on both surfaces. Further, addition of inhibitory anti-TFPI antibodies induced a similar enhancement of TF/VIIa activity on both surface domains. Because the availability of anionic phospholipids on the outer leaflet of the cell membrane could regulate TF/VIIa functional activity, we measured the distribution of anionic phospholipids on the apical and basolateral surface by annexin V binding and thrombin generation. The results showed that the anionic phospholipid content on the basolateral surface, compared with the apical surface, was 3- to 4-fold lower. Mild acid treatment of polarized Caco-2 cells, which markedly increased the anionic phospholipid content on the basolateral surface membrane, increased the TF/VIIa activity on the basolateral surface without affecting the number of TF/VIIa complexes formed on the surface. Overall, our data suggest that an uneven expression of TF/VIIa activity between the apical and basolateral surface of polarized epithelial cells is caused by differences in anionic phospholipid content between the two surface domains and not from a polar distribution of TFPI.


Construction, figures of merit, and testing of a single-cell fluorescence excitation spectroscopy system.
Characterization of phytoplankton community composition is critical to understanding the ecology and biogeochemistry of the oceans. One approach to taxonomic characterization takes advantage of differing pigmentation between algal taxa and thus differences in fluorescence excitation spectra. Analyses of bulk water samples, however, may be confounded by interference from chromophoric dissolved organic matter or suspended particulate matter. Here, we describe an instrument that uses a laser trap based on a Nikon TE2000-U microscope to position individual phytoplankton cells for confocal fluorescence excitation spectroscopy, thus avoiding interference from the surrounding medium. Quantitative measurements of optical power give data in the form of photons emitted per photon of exposure for an individual phytoplankton cell. Residence times for individual phytoplankton in the instrument can be as long as several minutes with no substantial change in their fluorescence excitation spectra. The laser trap was found to generate two-photon fluorescence from the organisms so a modification was made to release the trap momentarily during data acquisition. Typical signal levels for an individual cell are in the range of 10(6) photons/s of fluorescence using a monochromated 75 W Xe arc lamp excitation source with a 2% transmission neutral density filter.


Diels-alder reactions with 2-(Arylsulfinyl)-1,4-benzoquinones: effect of aryl substitution on reactivity, chemoselectivity, and pi-facial diastereoselectivity
Diels-Alder reactions of (SS)-2-(2'-methoxynaphthylsulfinyl)-1, 4-benzoquinone (1b), 2-(p-methoxyphenylsulfinyl)-1,4-benzoquinone (1c), and 2-(p-nitrophenylsulfinyl)-1,4-benzoquinone (1d) with cyclopentadiene are reported. These cycloadditions allowed the highly chemo- and stereoselective formation of both diastereoisomeric endo-adducts resulting from reaction on the unsubstituted double bond C(5)-C(6) of quinones working under thermal and Eu(fod)(3)- or BF(3).OEt(2)-catalyzed conditions. The synthesis of endo-adduct [4aS,5S,8R,8aR,SS]-9d resulting from cycloaddition on the substituted C(2)-C(3) double bond was achieved in a chemo- and diastereoselective way from quinone 1d in the presence of ZnBr(2). The reactivity and selectivity of the process proved to be dependent on the electron density of the arylsulfinyl group.


Polymer coating embolism from intravascular medical devices - a clinical literature review.
Over the past three decades, lubricious (hydrophobic and/or hydrophilic) polymer-coated devices have been increasingly adopted by interventional physicians and vascular surgeons to access and treat a wider range of clinical presentations. Recent clinical literature highlights the presence of polymer coating emboli within the anatomy - a result of coating separation from an intravascular device - and associates it with a range of adverse clinical sequelae. The 2015 U.S. Food and Drug Administration safety communication titled "Lubricious Coating Separation from Intravascular Medical Devices" acknowledges these concerns and concludes that it will work with stakeholders to develop nonclinical test methodologies, establish performance criteria, and identify gaps in current national and international device standards for coating integrity performance. Despite this communication and multiple case reports from interventional physicians, pathologists, dermatologists and other involved physician specialties, polymer coating embolism remains clinically underrecognized. This article consolidates the available literature on polymer coating embolism (1986-2016) and highlights the following relevant information for the physician: (a) the history and elusive nature of polymer coating embolism; (b) potential incidence rates of this phenomenon; (c) reported histologic findings and clinical effects of polymer emboli in the anatomy; (d) the importance of the collaborative clinician-pathologist partnership to report polymer embolism findings; and (e) the importance to study particulate release from intravascular devices so as to further understand and potentially evolve coated interventional technologies. Preliminary research on coatings highlights the potential of using iterations of coatings on medical devices that attain the desired therapeutic result and mitigate or eliminate particulates altogether.


Cost control should extend to legal services.
While a healthcare organization may consider legal services to be outside its management scope, control of legal spending is within a hospital's grasp. Whether an organization is large or active enough to merit an internal legal staff, an administrative position should be established to centralize management of legal services. A hospital may choose to undertake a cost reduction audit, which can determine the feasibility of an internal legal staff and coordinate competitive proposals from outside law firms handling litigation.


Immediate impact of COVID-19 pandemic on farming systems in Central America and Mexico.
The COVID-19 pandemic has affected all sectors and human activities around the World. In this article we present a first attempt to understand the immediate impact of COVID-19 and the sanitary measures taken by governments on farming systems in Central America and Mexico (CAM). Through a review of information generated in these initial months of the COVID-19 pandemic (webinars, blogs, electronic publications, media) and 44 interviews with key informants across the region, we have identified the main impacts felt by different types of farming systems in the region. From corporate agricultural production systems, to small and medium scale entrepreneurs and smallholder subsistence farm households, all types of farming systems were impacted, more or less severely, by the different measures implemented by governments such as reduced mobility, closure of public and private venues and restrictions in borders. Larger corporate farming systems with vertical market integration and high level of control or coordination within the supply chain, and smallholder or subsistence farming systems with important focus on production for self-consumption and little external input use, were both relatively less impacted and showed greater adaptive capacity than the medium and small entrepreneurial farming systems dependent on agriculture as their primary income and with less control over the upstream and downstream parts of their supply chain. All types of farming systems implemented a series of mechanisms to cope with the COVID-19 pandemic including the development of alternative value chains, food and agricultural products delivery systems and the exponential use of digital means to communicate and maintain the viability of the different agricultural systems. Collective action and organization of farmers also proved to be an important coping mechanism that allowed some farmers to acquire inputs and deliver outputs in the context of restricted mobility, price volatility, and general uncertainty. Some features of the CAM region played an important role in mediating the impact of COVID-19 and associated sanitary measures. We identify as particularly relevant the nature of agricultural exports, the current structure of the agricultural sector, the diversified livelihood strategies of rural households, and the importance of mobility for rural livelihoods. The results presented focus only in the immediate effect of COVID-19 pandemic and the mechanisms implemented by farmers in the first months. Whether these impacts and response mechanisms will result in a transformation of the farming systems towards greater resilience and sustainability is still an open question.


New Fusarium wilts on vegetable crops in Italy.
Three Fusarium wilts recently observed in Italy on lettuce (Lactuca sativa), wild (Diplo taxis spp.) and cultivated (Eruca sativa) rocket and lamb's lettuce (Valerianella olitoria) emerged as major production problems in Lumbardy (north-western Italy). Aspects of biology and epidemiology of the three diseases and some possibilities of disease management are discussed.


Inclusion of Older Adults in Digital Health Technologies to Support Hospital-to-Home Transitions: Secondary Analysis of a Rapid Review and Equity-Informed Recommendations.
Digital health technologies have been proposed to support hospital-to-home transition for older adults. The COVID-19 pandemic and the associated physical distancing guidelines have propelled a shift toward digital health technologies. However, the characteristics of older adults who participated in digital health research interventions to support hospital-to-home transitions remain unclear. This information is needed to assess whether current digital health interventions are generalizable to the needs of the broader older adult population. This rapid review of the existing literature aimed to identify the characteristics of the populations targeted by studies testing the implementation of digital health interventions designed to support hospital-to-home transitions, identify the characteristics of the samples included in studies testing digital health interventions used to support hospital-to-home transitions, and create recommendations for enhancing the diversity of samples within future hospital-to-home digital health interventions. A rapid review methodology based on scoping review guidelines by Arksey and O'Malley was developed. A search for peer-reviewed literature published between 2010 and 2021 on digital health solutions that support hospital-to-home transitions for older adults was conducted using MEDLINE, Embase, and CINAHL databases. The data were analyzed using descriptive statistics and qualitative content analysis. The Sex- and Gender-Based Analysis Plus lens theoretically guided the study design, analysis, and interpretation. A total of 34 studies met the inclusion criteria. Our findings indicate that many groups of older adults were excluded from these interventions and remain understudied. Specifically, the oldest old and those living with cognitive impairments were excluded from the studies included in this review. In addition, very few studies have described the characteristics related to gender diversity, education, race, ethnicity, and culture. None of the studies commented on the sexual orientation of the participants. This is the first review, to our knowledge, that has mapped the literature focusing on the inclusion of older adults in digital hospital-to-home interventions. The findings suggest that the literature on digital health interventions tends to operationalize older adults as a homogenous group, ignoring the heterogeneity in older age definitions. Inconsistency in the literature surrounding the characteristics of the included participants suggests a need for further study to better understand how digital technologies to support hospital-to-home transitions can be inclusive.


The cat as a model for visual deprivation.
Both behavioural and neurophysiological changes can be observed in cats that have experienced interference with their normal visual environment. This visual deprivation may result from alterations to the path of light forming the normal image on the retina, and includes changes that cause the image to fall on an inappropriate part of the retina so that normal binocular interactions are affected. While some neurophysiological changes can be observed at the level of the lateral geniculate nucleus they become more prominent as information reaches the visual cortex, where cells commonly receive neural excitation from both eyes and require the information to come from corresponding parts of the two retinas and that the stimulus should have appropriate orientation and direction of movement. Many of the observations of deprivation in animals have clear parallels in the human environment.


Neural and fuzzy robotic hand control.
An efficient first grasp for a wheelchair robotic arm-hand with pressure sensing is determined and presented. The grasp is learned by combining the advantages of neural networks and fuzzy logic into a hybrid control algorithm which learns from its tip and slip control experiences. Neurofuzzy modifications are outlined, and basic steps are demonstrated in preparation for physical implementation. Choice of object approach vector based on fuzzy tip and slip data and an expert supervisor, as well as training of a diagnostic neural tip and slip controller, are the focus of this work.


Investigating the role of immunotherapy in advanced/recurrent female genital tract melanoma: a preliminary experience.
immunotherapy with immune checkpoint inhibitors has become one of the standard therapeutic modalities for patients with advanced melanoma. Melanoma of the female lower genital tract is a rare and aggressive disease, with poor long-term clinical outcomes. To date, no study evaluated the role of immunotherapy in metastatic melanoma of the lower genital tract. Data of women with metastatic melanoma of the lower genital tract were prospectively collected. Survival outcomes over time was assessed using Kaplan-Meier model. Seven cases of metastatic melanoma of the lower genital tract (vulva [n=2], vagina [n=4], and uterine cervix [n=1]) treated with immune checkpoint inhibitors are reviewed. Two patients had metastatic disease at diagnosis, while 5 patients developed metastatic disease at a mean (standard deviation) time of 9.9 (±3.0) months from primary diagnosis. Four patients received an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) (ipilimumab) and 3 received an anti-programmed cell death 1 (PD-1) (pembrolizumab [n=2], nivolumab [n=1]) therapy. The response rate to immunotherapy was 28.5%. Patients receiving an anti-PD-1 experienced a better progression-free survival than patients treated with anti-CTLA4 (p=0.01, log-rank test). Although not reaching statistical significance, overall survival was better in patients having an anti-PD-1 therapy in comparison to anti-CTLA4 (p=0.15, log-rank test). Results from our series confirm the poor prognosis of women with metastatic melanoma of the lower genital tract, thus supporting the need of exploring new treatment modalities. Further studies are warranted to improve knowledge on the role of immunotherapy in metastatic melanoma of the lower genital tract.


The role of the health care sector in the U.S. economy.
This Issue Brief discusses factors that contribute to the growth of health care expenditures and the reasons that many individuals, employers, and policymakers consider health expenditures too high. In addition, it describes various industries that make up the health care delivery system and their role in the U.S. economy as employers, producers, exporters, and suppliers of research and development. The report also discusses the economic implications of rising health care expenditures for individuals, employers, and the federal government and the potential impact of proposed health care reform on the health care sector and the U.S. economy as a whole. Health care delivery industries such as pharmaceuticals and medical equipment suppliers have higher than average research and development levels, in addition to a positive balance of trade. Moreover, while the total number of jobs in the private sector declined between 1990 and 1993, the number of jobs in the relatively high paid health services sector continued to grow. In aggregate, employer spending on health care represents only 6.6 percent of total labor costs. In comparison, wages and salaries represent 83 percent of total labor costs. Consequently, the growth rate of health care expenditures has a smaller impact on the growth rate of total compensation than does the growth rate in wages and salaries. Using job multipliers developed by the U.S. Department of Commerce, it is estimated that the 18,600 health care services jobs in Rochester, Minnesota in 1993 created another 32,000 jobs in the area. Any contraction of the health care sector in cities that have a large concentration of employment in health services would result in reduced employment in restaurants, retail stores, janitorial services, and other local businesses. EBRI's simulations estimated that between 200,000 and 1.2 million workers could become unemployed as a direct result of a mandate that employers provide health benefits to their employees, assuming that wages and salaries did not adjust at all. Others find that approximately 50,000 individuals would lost their jobs, assuming that wages and other labor costs adjust downward to completely account for increased costs. As is apparent, the estimates of job loss (and of the total costs of the policy) are extremely sensitive to the assumptions used in the simulation.


Splenic peliosis: an unusual entity.
This case of splenic peliosis, describes a rare condition when it presents in the spleen, and is better understood when it occurs in the liver. However, the ultrasound and CT features have a wide differential diagnosis including more common aetiologies, of either a vascular, infective or neoplastic nature, which should be considered. Peliosis is an important condition to be aware of because rupture of the blood-filled cysts on the spleen surface can lead to haemorrhagic peritonitis and ultimately be fatal.


Recuperative effect of estrogen on rotenone-induced experimental model of Parkinson's disease in rats.
Parkinson's disease (PD) is described as the loss of dopaminergic neurons located in the substantia nigra (SN) region of the brain and a progressive motor failure. Increased frequency of PD in women, especially after menopause, suggests the effect of estrogen. This view has been supported with empirical studies. Therefore, the effect of estrogen in an experimental model of Parkinson's disease induced by rotenone was investigated. A total of 32 female Wistar Albino rats were randomly assigned to four groups (control group, ovariectomy group, Parkinson's group, Parkinson's + estrogen group). The Parkinson's group received rotenone subcutanously at the dose of 2.5 mg/kg bw, on the 1st, 2nd, 3rd 4th, 6th, 9th, 12th, 15th, 18th, and 21st days animals in the Parkinson's + estrogen group received retonon as in the Parkinson's group and was additionally subcutaneously given estrogen (implant containing 0.5 mg 17 β-estradiol lasting for 21 days). The rats were subjected to rotarod, pole, and swimming tests at the end of the experiment for comparison of their motor activities, and then, histopathological and biochemical analyses were performed on the tissues that were extracted. The rotarod results revealed that Parkinson's group had the shortest time (32.33 ± 3.98 sn) than the groups of control (92.50 ± 12.60 s) ovariectomy (71.42 ± 10.58 s), and Parkinson's + estrogen (71.37 ± 9.26 s). The results of pole disclosed that return and landing time prolonged for Parkinson's group when compared with other groups (return time for control 2.98 ± 0.38 s, ovariectomy 3.02 ± 0.75 s, Parkinson 5.91 ± 0.33 s, Parkinson's + estrogen 3.48 ± 0.42 s and landing time for control 5.30 ± 0.59 s, ovariectomy 5.45 ± 0.73 s, Parkinson 9.80 ± 0.90 s, Parkinson's + estrogen 5.37 ± 1.02 s). Parkinson's group had longest (90.71 ± 12.56 s) swimming time to reach the target when compared with control (33.16 ± 8.68 s), ovariectomy (47.37 ± 12.19 s), and Parkinson's + estrogen (49.82 ± 5.78 s). Histopathological examination indicated a significant difference in tyrosine hydroxylase-stained cells (dopaminergic neurons and dopamine) between the Parkinson's + estrogen group and the Parkinson's group. The biochemical analyses of Caspas-3 activation in SN and striatum (STR) was significantly different between the Parkinson's + estrogen group and the Parkinson's group, but this difference was not observed in STR while evaluating Bcl-2. The results of this study suggested that estrogen may have a recuperative effect on PD.


MAOA methylation is associated with nicotine and alcohol dependence in women.
In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. In order to examine the role of methylation at this locus, we performed quantitative methylation analysis across the promoter region of this gene in lymphoblast lines derived from 191 subjects participating in the Iowa Adoption Studies (IAS). We analyzed the resulting data with respect to genotype and lifetime symptom counts for the more common major behavioral disorders in the IAS, antisocial personality disorder (ASPD), and substance use disorders (alcohol (AD) and nicotine dependence (ND)). We found that methylation status was significantly associated with lifetime symptom counts for ND (P < 0.001) and AD (P < 0.008) in women, but not men. Furthermore, a trend was found for women homozygous for the 3,3 allele to have a higher degree of overall methylation than women homozygous for the 4,4 allele (P < 0.10). We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.


Korean version of the Cough Symptom Score: clinical utility and validity for chronic cough.
The Cough Symptom Score (CSS) is a simple, useful tool for measuring cough severity. However, there is no standard Korean version of the CSS. We developed a Korean version of the CSS and evaluated its clinical utility and validity for assessing chronic cough severity. The CSS was adapted for Korean use following a forward-backward translation procedure. Patients with chronic cough enrolled from five university hospitals were graded using the CSS and a 100-mm linear visual analog scale (VAS) of cough severity at each visit. Patients completed the Leicester Cough Questionnaire (LCQ) upon presentation and completed the LCQ and Global Rating of Change at follow-up visits after 2 to 4 weeks. The concurrent validity, repeatability, and responsiveness of the Korean version of the CSS were determined. Correlation coefficients between the CSS and LCQ, and between the CSS and VAS, were -0.66 and 0.52, respectively. There was a weak correlation between the scores for night and day symptoms (r = 0.24, p = 0.0006). The repeatability of the CSS in patients with no change in cough (n = 23) was high (intra-class correlation coefficient, 0.75; 95% confidence interval [CI], 0.51 to 0.88). Patients who reported an improvement in cough (n = 30) at follow-up visits had a significant improvement in the CSS (median, -2; 95% CI, -3 to -1; p = 0.0003). The Korean version of the CSS correlated well with other tools for accessing cough severity in chronic cough patients. Therefore, it could be a reliable method for measuring chronic cough severity.


Artificial neural networks compared to factor analysis for low-dimensional classification of high-dimensional body fat topography data of healthy and diabetic subjects.
Subcutaneous adipose tissue thickness was measured in 590 healthy subjects at 15 specific body sites by means of the new optical device, lipometer, providing a high-dimensional and partly highly intercorrelated set of data, which had been analyzed by factor analysis previously. N-2-N back-propagation neural networks are able to perform low-dimensional display of high-dimensional data as a special application. We report about the performance of such a 15-2-15 network and compare its results with the output of factor analysis. As test data for verification, measurement values on women with proven diabetes mellitus type II (NIDDM) are used. Surprisingly our 15-2-15 neural network is able to reproduce the classification pattern resulting from factor analysis very precisely. After extracting the network weights the classification of new subjects is even more simple with the neural network as compared with factor analysis. In addition, the network weights are able to cluster highly correlated body sites nicely to different groups, corresponding to different regions of the human body. Thus, the analysis of these weights provides additional information about the structure of the data. Therefore, N-2-N networks seem to be a good alternative method for analyzing high-dimensional data with strong intercorrelation.


Biological and targeted therapies of systemic lupus erythematosus: evidence and the state of the art.
Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE. Similar to the intravenous preparation, subcutaneous belimumab has been shown to be superior to placebo when added to the standard of care in SLE. However, two phase III trials of epratuzumab and blisibimod did not meet their primary endpoints. Recent data on the inhibition of type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors and combination strategies using conventional immunosuppressive agents are being tested in lupus nephritis. Finally, international groups are developing consensus definitions on disease remission and low disease activity state to explore the benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for the treatment of SLE can be expanded in the near future, so that the longevity and quality of life of patients can be further improved.


Modulators of 14-3-3 Protein-Protein Interactions.
Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein-protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as "undruggable" targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products.


Perspectives for the tissue engineering of cartilage from a biological and biomaterial point of view.
Tissue engineering has become a fast growing interdisciplinary branch of research at the interface between life and engineering sciences with important clinical end-points. In this context the regeneration of articular cartilage represents an exciting challenge since hyaline cartilage has a limited capacity for self-repair. Today the use of different scaffold materials combined with in vitro expanded chondrocytes and signalling molecules poses great hopes for an optimal treatment of articular cartilage defects. However, until today the optimal construct of scaffolds, cells and signalling molecules has not yet been found. Since repair and regeneration recapitulate in part ontogenetic processes, the present paper summarizes the regulative mechanisms of endochondral ossification in the growth plate of the long bones to identify possible new signalling molecules for the improvement of tissue engineering-based solutions in the treatment of cartilage defects. The growth plate represents a highly organized structure of chondrocytes and extracellular matrix components in distinguishable proliferation and differentiation stages. It is regulated by various paracrine and hormonal factors. In a second part we present actual trends in scaffold design based on synthetic polymers and natural polymers, stressing their potential use in the regeneration of cartilage defects from the point of view of bioactivity and biocompatibility. In conclusion, both new signalling molecules from basic research and innovative scaffold materials with variable physico-chemical properties open up new and interesting perspectives for the research in optimized tissue engineeredbased therapeutic strategies to treat cartilage defects.


Weight-bearing-line analysis in supramalleolar osteotomy for varus-type osteoarthritis of the ankle.
We determined the preoperative and postoperative passing points of the mechanical axis of the lower limb at the level of the tibial plafond using a new method involving a full-length standing posteroanterior radiograph that includes the calcaneus (a hip-to-calcaneus radiograph) and correlated them to the clinical results after supramalleolar osteotomy for ankle osteoarthritis. We reviewed the hip-to-calcaneus radiographs of fifty lower limbs of forty-one patients treated for lower limb malalignment at our institution. The mechanical axis point of the ankle was the point at which the mechanical axis divides the coronal length of the plafond, expressed as a percentage. Four independent observers performed all measurements twice. Supramalleolar tibial osteotomy was performed in twenty-seven ankles (twenty-four patients) to treat moderate varus-type osteoarthritis of the ankle. The mean follow-up period was 2.8 years (range, two to 5.3 years). Clinical assessment was based on the American Orthopaedic Foot & Ankle Society (AOFAS) scale. Interobserver and intraobserver reliability in identifying the mechanical ankle joint axis point were very high. The mean postoperative mechanical axis point was 50% (range, 13% to 70%) in ankles for which the preoperative point was ≤0%, whereas the mean postoperative point was 81% (range, 48% to 113%) in ankles for which the preoperative point was >0%. The mean change in AOFAS score was significantly less for patients with a preoperative point of ≤0% than for those with a preoperative point of >0% (p=0.004). Improvement was significantly greater in ankles with a postoperative mechanical ankle joint axis point of ≥80% than in ankles with a postoperative mechanical ankle joint axis point of <60% (p=0.030). Traditional tibial correction resulted in great variation in the locations of the postoperative mechanical ankle joint axis point. In ankles with the preoperative point more medial than the tibial plafond, the point was insufficiently moved to the lateral side, and the clinical outcomes were less satisfactory.


Dynamics of adaptive change in human vestibulo-ocular reflex direction.
Adaptive modification of vestibuloocular reflex (VOR) direction was characterized in humans by recording vertical and horizontal VOR eye movements during horizontal rotations in darkness at frequencies of 0.05 to 1 Hz before and after exposure to a VOR direction adaptation procedure. This procedure paired yaw horizontal vestibular rotation at 0.25 Hz with synchronous pitch vertical optokinetic motion. Saccades were removed from eye position records and VOR gain and phase were recorded. With an onset time constant of 36 min, the VOR measured during horizontal rotation in complete darkness acquired a vertical component in phase with the optokinetic stimulus presented during adaptation. The amplitude of this newly acquired vertical VOR component was maximal during rotation at the frequency of adaptation; at other frequencies, the amplitude was lower, but still significant. Unlike VOR direction adaptation in cats, the phase of the adaptive VOR component in humans did not show significant leads or lags at test frequencies below or above the adaptation frequency. These data suggest that, like the cat, the human VOR can be directionally adapted, and the pathways involving the adaptive component of the VOR are frequency specific.


Weakly Supervised Lesion Detection From Fundus Images.
Early diagnosis and continuous monitoring of patients suffering from eye diseases have been major concerns in the computer-aided detection techniques. Detecting one or several specific types of retinal lesions has made a significant breakthrough in computer-aided screen in the past few decades. However, due to the variety of retinal lesions and complex normal anatomical structures, automatic detection of lesions with unknown and diverse types from a retina remains a challenging task. In this paper, a weakly supervised method, requiring only a series of normal and abnormal retinal images without need to specifically annotate their locations and types, is proposed for this task. Specifically, a fundus image is understood as a superposition of background, blood vessels, and background noise (lesions included for abnormal images). Background is formulated as a low-rank structure after a series of simple preprocessing steps, including spatial alignment, color normalization, and blood vessels removal. Background noise is regarded as stochastic variable and modeled through Gaussian for normal images and mixture of Gaussian for abnormal images, respectively. The proposed method encodes both the background knowledge of fundus images and the background noise into one unique model, and corporately optimizes the model using normal and abnormal images, which fully depict the low-rank subspace of the background and distinguish the lesions from the background noise in abnormal fundus images. Experimental results demonstrate that the proposed method is of fine arts accuracy and outperforms the previous related methods.


Study on the Relationship and Correlation between Turnover Tendency of Emergency Nursing Staff and Social and Work Factors.
The relationship and correlation between emergency nursing staff turnover intention and social and work factors are explored. A total of 110 nurses in the emergency department of our hospital from February 2021 to October 2021 are selected as the research subjects. A questionnaire survey is conducted among all the nurses. By comparing with the general information of the emergency nurses, the scores of turnover tendency, social support, workplace violence, and job burnout scales of the emergency nurses are calculated. Multifactor logistic regression is used to analyze the influencing factors of turnover tendency of emergency nursing staff, and Spearman correlation coefficient is used to analyze the correlation between turnover tendency of emergency nursing staff and its influencing factors. The results of the survey show that age, education level, social support, workplace violence, and job burnout can all affect the turnover tendency of emergency nursing staff. Managers should pay more attention and take reasonable measures to avoid staff turnover.


Simultaneous contrast: evidence from licking microstructure and cross-solution comparisons.
The microstructure of rats' licking responses was analyzed to investigate both "classic" simultaneous contrast (e.g., Flaherty & Largen, 1975) and a novel discrete-trial contrast procedure where access to an 8% test solution of sucrose was preceded by a sample of either 2%, 8%, or 32% sucrose (Experiments 1 and 2, respectively). Consumption of a given concentration of sucrose was higher when consumed alongside a low rather than high concentration comparison solution (positive contrast) and consumption of a given concentration of sucrose was lower when consumed alongside a high rather than a low concentration comparison solution (negative contrast). Furthermore, positive contrast increased the size of lick clusters while negative contrast decreased the size of lick clusters. Lick cluster size has a positive monotonic relationship with the concentration of palatable solutions and so positive and negative contrasts produced changes in lick cluster size that were analogous to raising or lowering the concentration of the test solution respectively. Experiment 3 utilized the discrete-trial procedure and compared contrast between two solutions of the same type (sucrose-sucrose or maltodextrin-maltodextrin) or contrast across solutions (sucrose-maltodextrin or maltodextrin-sucrose). Contrast effects on consumption were present, but reduced in size, in the cross-solution conditions. Moreover, lick cluster sizes were not affected at all by cross-solution contrasts as they were by same-solution contrasts. These results are consistent with the idea that simultaneous contrast effects depend, at least partially, on sensory mechanisms.


Preparation and characterization of 4-dimethylaminopyridine-stabilized palladium nanoparticles.
4-Dimethylaminopyridine (DMAP)-stabilized palladium nanoparticles with a mean diameter of 3.4 +/- 0.5 nm are prepared from the aqueous phase reduction of Na2PdCl4 using NaBH4 in the presence of DMAP. TEM and UV-vis spectroscopy characterization of the nanoparticle dispersion shows no obvious change in the nanoparticles several months after preparation. 1H NMR spectroscopy of the nanoparticles shows that the nanoparticle dispersion also contains a boron/DMAP complex and two palladium/DMAP complexes. One of the palladium complexes crystallizes out of the dispersion and is identified as Pd(DMAP)4(OH)2 by X-ray crystallography. Following extensive analysis, it is believed that the palladium/DMAP complexes are formed following the oxidation of the palladium nanoparticles. The prepared nanoparticle dispersion promotes selective hydrogen/deuterium (H/D) exchange on the carbon atoms alpha to the endocyclic nitrogen atom on the DMAP-stabilizing ligands through reaction with D2O. This activity is attributed to the presence of the nanoparticles rather than to the presence of the oxidized palladium/DMAP complexes.


Economic evaluation of Safer Choices: a school-based human immunodeficiency virus, other sexually transmitted diseases, and pregnancy prevention program.
To evaluate the cost-effectiveness and cost benefit of Safer Choices, a school-based human immunodeficiency virus, other sexually transmitted diseases, and unintended pregnancy prevention intervention for high school students. The baseline cost-effectiveness and cost benefit were derived in 4 steps: (1) estimation of intervention costs; (2) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted, and development of a model to translate increases in contraceptive use into cases of pregnancy averted; (3) translation of cases averted into medical costs and social costs averted; and (4) calculation of the net benefit of the program. Multivariable sensitivity analysis was performed to determine the robustness of the base-case results. Under base-case assumptions, at an intervention cost of $105,243, Safer Choices achieved a 15% increase in condom use and an 11% increase in contraceptive use within 1 year among 345 sexually active students. An estimated 0.12 cases of human immunodeficiency virus, 24.37 cases of chlamydia, 2.77 cases of gonorrhea, 5.86 cases of pelvic inflammatory disease, and 18.5 pregnancies were prevented. For every dollar invested in the program, $2.65 in total medical and social costs were saved. Results of most of the scenarios remained cost saving under a wide range of model variable estimates. The Safer Choices program is cost-effective and cost saving in most scenarios considered. School-based prevention programs of this type warrant careful consideration by policy makers and program planners. Program cost data should be routinely collected in evaluations of adolescent prevention programs.


Are psychotropic drugs at therapeutic levels a concern for cardiologists?
To review the cardiovascular effects of psychotropic drugs when used in therapeutic doses and to assess their clinical relevance for cardiologists. Information on newer psychopharmacological agents is also presented. MEDLINE was used to search the relevant English language medical literature over the past five years. Standard texts and selected earlier references were also used. Input was obtained from local experts. Many antipsychotics and antidepressants have the potential for causing malignant ventricular arrhythmias and cardiac conduction disturbances. Postural hypotension is also a common side effect with important associated morbidity. The effects of psychotropic drugs on myocardial contractile properties are not significant at therapeutic dose levels. Older agents, such as phenothiazines, tricyclic antidepressants and monoamine oxidase inhibitors, are responsible for most of the reported adverse cardiovascular effects of psychotropic drugs. Selective serotonin reuptake inhibitors are a newer class of antidepressants that are free from significant direct cardiovascular adverse effects; however, if combined with other agents such as the monoamine oxidase inhibitors, they can cause cardiovascular collapse as part of a potentially fatal 'serotonin syndrome'. These newer agents can also exaggerate the actions of certain cardiac drugs through effects on their metabolism by inhibition of cytochrome P450 isoenzymes. The adverse cardiovascular effects of psychotropic medications in therapeutic doses are a valid concern for cardiologists. Familiarity with these drugs and their interactions is essential to avoid important undesired reactions with potential fatal consequences.