Added predictive value of high uric acid for cardiovascular events in the Ambulatory Blood Pressure International Study.
The prognostic value of uric acid (UA) for cardiovascular events (CVE) is still debated. Our purpose was to investigate the association between UA and CVE in 5243 participants of the ABP-International study with the main aim of identifying optimal sex-specific cut-points. In multivariable Cox analyses, the relationship between CVE and UA as a continuous variable was modeled by including both linear and nonlinear terms. Survival models were also estimated with UA as a categorical variable. Optimal UA cut-points were determined using an outcome-oriented approach. During a median follow-up of 5.9 years, there were 423 CVE (93 fatal). In age- and sex-adjusted Cox models, UA as a continuous variable was a significant predictor of CVE in all individuals and in men and women considered separately. The relationship between UA and CVE was linear (P-value for nonlinearity 0.54 and 0.80 for men and women, respectively). For each 1 mg/dL increase in UA, the relative hazard increase was 16% in men and 19% in women. In fully adjusted models, UA remained a significant predictor of CVE in the whole study cohort. The optimal cut-point best separating patients at low and high risk of CVE was 6.3 mg/dL for men and 4.4 mg/dL for women. Subjects with high UA had a 38% greater risk of CVE. In a sex-specific analysis, the association remained significant only in men (hazard ratio, 1.47; P < 0.01). In conclusion, high UA is an independent predictor for subsequent CVE and significantly improves risk discrimination and reclassification over the baseline multivariable model.


How to spot a basosquamous carcinoma: a study on demographics, clinical-dermatoscopic features and histopathological correlations.
Basosquamous carcinoma (BSC) is a relatively rare type of neoplasm originating from basal cell carcinoma with features of squamous differentiation. BSC has an aggressive local behaviour with a tendency for recurrence and a less frequent metastatic potential The primary objective was to describe the dermatoscopic features of the tumour. Secondary goals were to detect the morphological features of the tumour along with patients' characteristics and to evaluate possible dermatoscopic and histopathological correlations Twenty-two patients with 25 BSCs were enrolled. All tumours were surgically excised and diagnosis was based on histopathology. Clinical and dermatoscopic images were evaluated by two investigators based on pre-defined criteria, and a statistical analysis was performed The median age of the patients was 78 years old (range: 52-88) and the male/female ratio was 2.14. All patients reported history of either occupational (50%) or recreational (50%) intensive sun exposure and 72.73% had signs of actinic keratosis. The most common anatomical site of the tumours was the head/neck area (72%). Clinically, nodular (64%), ulcerated (88%) and non-pigmented (76%) lesions prevailed. Dermatoscopically, 92% had prominent vasculature and monomorphous arborizing vessels with a diffuse arrangement, representing the most frequently observed type. Ulceration (88%), SCC dermatoscopic criteria (56%), white strands/blotches (56%) and features of pigmentation (40%) were also detected We suggest that the most common prototype of BSC is an ulcerated, facial nodule in elderly males with photo-damaged skin, dermatoscopically displaying combined features of mostly nodular BCC and, to a less extent, SCC.


Oxprenolol and propranolol in anxiety states. A double-blind comparative study.
The efficacy of oxprenolol (Trasicor) and propranolol in controlling anxiety was compared in a double-blind study of patients with anxiety and tension. Efficacy was assessed by the investigator with the aid of a psychiatric rating scale consisting of 19 items, bythe patients using visual analogue scales, and by the investigator's and the patients' over-all assessments. Tolerance to the drugs was evaluated by over-all assessment and by means of a checklist of signs and symptoms which emerged during treatment. Little difference in the efficacy of the two drugs was observed. Both were effective in the treatment of anxiety and tension. In general, oxprenolol was significantly better tolerated than propranolol. Evidence of the intrinsic sympathomimetic activity of oxprenolol emerged during the course of the study or, alternatively, evidence that propranolol had a greater cardiac-depressant effect.


Quantifying benefits of using health information exchange to support public health STI reporting and treatment in Western New York.
To calculate average savings of using health information exchange (HIE) for demographic and treatment requests for chlamydia and gonorrhoea in Western New York, specifically the Erie County Department of Health and its catchment area. We conducted a mixed-method case study. Qualitative methods included interviews, document review, and workflow mapping, which were used as the inputs to identify time savings. Case rates, time savings, and salary averages were used to calculate average savings. The avoided demographic information requests resulted in time and money savings (range of USD$2312-USD$4624 for chlamydia and USD$809-USD$1512 for gonorrhoea) as did avoided treatment requests (range of USD$671-USD$2803 for chlamydia and USD$981-USD$1635 for gonorrhoea). HIE supported sexually transmitted infection (STI) treatment by making it easier for public health staff to identify and act upon STI diagnoses. Availability of information online resulted in less reliance on provider offices for demographic and treatment information. Results indicated that using HIE to support treatment and management of STIs can save public health staff time spent on obtaining demographic and treatment information. Other public health departments could use HIE for this and other types of disease surveillance activities. Considering public health needs in HIE development and use can improve efficiency of public health services and enhance effectiveness of activities.


Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome.
To evaluate gonadotropin release in polycystic ovary syndrome (PCO), one or more of the following hypothalamic-pituitary function tests were performed on 24 patients with the syndrome. These tests included (a) the pulsatile pattern and day-to-day fluctuation of gonadotropin release; (b) effects of exogenous estrogen and antiestrogen (clomiphene) administration on gonadotropin release; and (c) pituitary responsiveness to maximal (150 mug) and submaximal (10 mug) luteinizing hormone-releasing factor (LRF) injections. In 10 of the 14 patients sampled frequently (15 min) for 6 h, luteinizing hormone (LH) levels were elevated above the concentration seen in normal cycling women (except the LH surge). These high LH concentrations appeared to be maintained by and temporally related to the presence of exaggerated pulsatile LH release, either in the form of enhanced amplitude or increased frequency. In all subjects, levels of follicle-stimulating hormone (FSH) were low or low normal, and a pulsatile pattern was not discernible. In four patients, daily sampling revealed marked day-to-day fluctuation of LH but not FSH. That the elevated LH levels were not related to a defect in the negative-feedback effect of estrogen was suggested by the appropriate fall of LH in four patients given an acute intravenous infusion of 17beta-estradiol. This infusion had no effect on FSH levels. In addition, clomiphene elicited rises of both LH and FSH that were comparable to the ones observed in normal women given the same treatment. The clomiphene study also suggested that the positive-feed-back mechanism of estrogen on LH release was intact when the preovulatory rises of 17beta-estradiol induced appropriate LH surges. The elevated LH levels appeared to be related to a heightened pituitary responsiveness to the LRF. This was found in the 11 and 2 patients given maximal (150 mug) and submaximal (10 mug) doses of LRF, respectively. The augmented pituitary sensitivity for LH release correlated with the basal levels of both estrone (P less than 0.025) and 17beta-estradiol (P less than 0.02). The net increase in FSH was significantly greater (P less than 0.001) in the PCO patients than the normal women with maximal doses of LRF. With the smaller dose study none of the injections had a discernible effect on FSH concentrations in either subject. The disparity between LH and FSH secretion could be explained by the preferential inhibitory action of estrogen on FSH release, coupled with a relative insensitivity of FSH release. These data indicate that in these PCO patients the abnormalities of the hypothalamic-pituitary regulation of gonadotropin secretion was not an inherent defect but represented a functional derangement consequent to inappropriate estrogen feedback, which led to a vicious cycle of chronic anovulation and inappropriate gonadotropin secretion.


Response properties of macaque monkey chorda tympani fibers.
Many of the chorda tympani fibers of crab-eating monkeys respond to more than one of the four basic stimuli (NaCl, sucrose, HCl, and quinine hydrochloride) as well as cooling or warming of the tongue. Fibers could be classified into four categories depending on their best sensitivity to any one of the four basic stimuli. Sucrose-best and quinine-best fibers are rather specifically sensitive to sucrose and quinine, respectively, while salt-best and acid-best fibers respond relatively well to HCl and NaCl, respectively. Saccharin, dulcin, and Pb acetate produce a good response in sucrose-best fibers, but quinine-best and salt-best fibers also respond to saccharin. Highly significant positive correlations exist between amounts of responses to sucrose and those to saccharin, dulcin, and Pb acetate, indicating that these substances produce in the monkey a taste quality similar to that produced by sucrose. Compared with chroda tympani fibers of rats, hamsters, and squirrel monkeys, macaque monkey taste fibers are more narrowly tuned to one of the four basic taste stimuli and more highly developed in sensitivity to various sweet-tasting substances. Also LiCl and NaCl are more effective stimuli for gustatory receptors in macaque monkeys than NH4Cl and KCl. This contrasts with a higher sensitivity to KCl and NH4Cl than to NaCl in chorda tympani fibers of squirrel monkeys.


A Journey through Diastereomeric Space: The Design, Synthesis, In Vitro and In Vivo Pharmacological Activity, and Molecular Modeling of Novel Potent Diastereomeric MOR Agonists and Antagonists.
Four sets of diastereomeric C9-alkenyl 5-phenylmorphans, varying in the length of the C9-alkenyl chain, were designed to examine the effect of these spatially distinct ligands on opioid receptors. Functional activity was obtained by forskolin-induced cAMP accumulation assays and several compounds were examined in the [35S]GTPgS assay and in an assay for respiratory depression. In each of the four sets, similarities and differences were observed dependent on the length of their C9-alkenyl chain and, most importantly, their stereochemistry. Three MOR antagonists were found to be as or more potent than naltrexone and, unlike naltrexone, none had MOR, KOR, or DOR agonist activity. Several potent MOR full agonists were obtained, and, of particular interest partial agonists were found that exhibited less respiratory depression than that caused by morphine. The effect of stereochemistry and the length of the C9-alkenyl chain was also explored using molecular modeling. The MOR antagonists were found to interact with the inactive (4DKL) MOR crystal structures and agonists were found to interact with the active (6DDF) MOR crystal structures. The comparison of their binding modes at the mouse MOR was used to gain insight into the structural basis for their stereochemically induced pharmacological differences.


Nicotinoprotein (NADH-containing) alcohol dehydrogenase from Rhodococcus erythropolis DSM 1069: an efficient catalyst for coenzyme-independent oxidation of a broad spectrum of alcohols and the interconversion of alcohols and aldehydes.
Extracts from benzyl-alcohol-grown Rhodococcus erythropolis DSM 1069 showed NAD(P)-independent, N,N-dimethyl-4-nitrosoaniline (NDMA)-dependent alcohol dehydrogenase activity. The enzyme exhibiting this activity was purified to homogeneity and characterized. It appears to be a typical nicotinoprotein as it contains tightly bound NADH acting as cofactor instead of coenzyme. Other characteristics indicate that it is highly similar to the known nicotinoprotein alcohol dehydrogenase (np-ADH) from Amycolatopsis methanolica: it is a homotetramer of 150 kDa; N-terminal amino acid sequencing (22 residues) showed that 77% of these amino acids are identical in the two enzymes; it has optimal activity at pH 7.0; it lacks NAD(P)H-dependent aldehyde reductase activity; it catalyses the oxidation of a broad range of (preferably) primary and secondary alcohols, either aliphatic or aromatic, and formaldehyde, with the concomitant reduction of the artificial electron acceptor NDMA. NDMA could be replaced by an aldehyde, but not formaldehyde, the substrate specificity of the enzyme for the aldehydes reflecting that for the corresponding alcohols. The latter also applied to the low aldehyde dismutase activity displayed by the enzyme. From this, together with the results of the induction studies, it is concluded that np-ADH functions as the main alcohol-oxidizing enzyme in the dissimilation of many, but not all, alcohols by R. erythropolis and may also catalyse coenzyme-independent interconversion of alcohols and aldehydes under certain circumstances. It is anticipated that the enzyme may be of even wider significance since structural data indicate that np-ADH is also present in other (nocardioform) actinomycetes.


Sodium transport-related proteins in the mammalian distal nephron - distribution, ontogeny and functional aspects.
The mammalian distal nephron plays a pivotal role in adjusting urinary sodium excretion. Successive portions of the renal tubule are formed to adapt to this function, and an axial heterogeneity of the distal segments has been defined. The specific transport properties of these epithelia are accomplished by the expression of proteins (cotransporters, exchangers, channels) governing the movement of ions on either cell side. Molecular cloning of these proteins has had a marked impact on the study of their localization and function in the healthy and diseased kidney. Electroneutral cation-chloride cotransporters [Na(K)CC] have been localized to the thick ascending limb and the distal convoluted tubule using specific probes. Proteins implicated in the function of aldosterone target cells, such as the epithelial Na(+) channel (ENaC), the mineralocorticoid receptor (MR) and 11beta-hydroxysteroid dehydrogenase type 2 (11HSD2), an enzyme that confers mineralocorticoid specificity, have been found in the terminal portion of the nephron and the collecting duct. A mineralocorticoid-sensitive component of thiazide-sensitive NaCl transport has been identified in the distal convoluted tubule. Analysis of the ontogeny of these proteins in the maturing kidney has provided a detailed picture of epithelial differentiation and morphological specialization of the renal tubule. The study of mutations of the proteins related with NaCl transport has led to the identification of the molecular causes of inherited human diseases associated with hypo- or hypertension, and the respective sites of an impaired ion transport could be mapped to the renal tubule.


Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia.
DT(388)IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was >12.5 microg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT(388)IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT(388)IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT(388)IL3 produces remissions in patients with relapsed/refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate.


Leg cramps in relation to metabolic syndrome.
A leg cramp is a pain that comes from a leg muscle. It is due to a muscle spasm which usually occurs in a calf muscle, below and behind a knee. Leg cramps (often called night cramps) usually occur most commonly at night when in bed. Night leg cramps are involuntary painful contractions of skeletal muscles arose in the calves and soles of the feet. Although in most cases they aren't harmful and resolve easily in some instances they have a long duration and can result in intense pain, disturb normal sleep and make a person feel anxious. Pathophysiology of leg cramps is poorly understood. The aim of our study was to determine the role of metabolic syndrome in relation to night leg cramps. The study included 86 subjects aged 34 to 88 years. Metabolic syndrome group consisted of 40 subjects (10 men (25%) and 30 women (75%)); the control group consisted of 46 persons (9 men (19.5%) and 37 women (80.5%)). According to frequency and intensity of manifestation leg cramps were subdivided into less frequent and frequent leg cramps. Blood samples were analysed for lipids, fasting glucose, red blood cells and electrolytes. Persons were screened for leg vein insufficiency as well. The investigation showed that 77.5% (31/40) of patients with metabolic syndrome had leg cramps, from which 60% (24/40) had frequent leg cramps. In control group 73.9% (34/46) had leg cramps, from which 50% (23/46) had frequent leg cramps. Among known predisposing factors leg cramps most often were associated with deep vein insufficiency and superficial vein varicose. High frequency of night leg cramps in our study is due to female predominance (75% versus 25% women and men, respectively) and age distribution in our study population (from 34 to 88 years old). The investigation showed that people often experience nocturnal leg cramps. Leg cramp is slightly increasing among the patients with metabolic syndrome. Frequent leg cramps were observed in 60% of cases in metabolic syndrome group versus 50% of cases in controls.


User-identified gel characteristics: a qualitative exploration of perceived product efficacy of topical vaginal microbicides.
Research has demonstrated that certain vaginal gel products--microbicides containing antiretroviral drugs--may reduce HIV infection risk among women. But for vaginal gels to avert HIV and other sexually transmitted infections (STIs), at-risk women must be willing to use them as directed. These products must therefore be "acceptable" to women and an important component of acceptability is users' perception that the product will work to prevent infection. We sought to understand how women's perceptions of vaginal gel properties may shape their understanding of product efficacy for HIV and STI prevention. Sixteen women completed two in-depth qualitative interviews (k = 32) to identify the range and types of sensory perceptions they experienced when using two vaginal gels. We identified emergent themes and linkages between users' sensory perceptions and their beliefs about product efficacy. Users' predictions about product efficacy for preventing infection corresponded to measurable physical properties, including gel volume, location in the vagina, coating behavior, sensation of the gel in the vagina, leakage, and gel changes during coital acts. Although the women described similar sensory experiences (e.g., gel leaked from the vagina), they interpreted these experiences to have varying implications for product efficacy (e.g., leakage was predicted to increase or decrease efficacy). To improve microbicide acceptability, gel developers should investigate and deliberately incorporate properties that influence users' perceptions of efficacy. When a microbicide is approved for use, providers should educate users to anticipate and understand their sensory experiences; improving users' experience can maximize adherence and product effectiveness.


Percutaneous Coronary Intervention for Chronic Total Occlusion versus Percutaneous Coronary Intervention for Non-Complex Coronary Lesions: Is There a Different Impact on Thyroid Function?
This study assessed whether high levels of iodide administered during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) differentially influenced thyroid function compared to PCI for non-complex coronary lesions. A total of 615 patients were enrolled in the study; 205 underwent elective PCI for CTO lesions (Group I) and 410 underwent elective PCI for non-complex lesions including non-CTO, non-bifurcation, non-calcified, and non-tortuous lesions (Group II). Patients were monitored for development of incidental thyroid dysfunction between 1 and 6 months after PCI. The patients in Group I were administered a median of 255 mL of contrast medium during PCI for CTO; a median of 80 mL was administered to the patients in Group II during non-complex PCI (p =0.001). Ten (5.4%) of the 186 euthyroid patients in Group I and 19 (5%) of the 379 eu-thyroid patients in Group II developed subclinical hyper-thyroidism (p = 0.854). However, 7 (50%) of the 14 subclinical hyperthyroid patients in Group I and only 3 (12%) of the 25 subclinical hyperthyroid patients in Group II developed overt hyperthyroidism (p = 0.019). In euthyroid patients, PCI for coronary CTO lesions did not increase the risk for subclinical hyperthyroidism when compared to PCI for non-complex coronary lesions. However, in patients with subclinical hyperthyroidism at baseline, PCI for coronary CTO lesions significantly increased the development of overt hyperthyroidism when compared to PCI for non-complex coronary lesions.


Protein Kinase C Inhibition Mediates Neuroblast Enrichment in Mechanical Brain Injuries.
Brain injuries of different etiologies lead to irreversible neuronal loss and persisting neuronal deficits. New therapeutic strategies are emerging to compensate neuronal damage upon brain injury. Some of these strategies focus on enhancing endogenous generation of neurons from neural stem cells (NSCs) to substitute the dying neurons. However, the capacity of the injured brain to produce new neurons is limited, especially in cases of extensive injury. This reduced neurogenesis is a consequence of the effect of signaling molecules released in response to inflammation, which act on intracellular pathways, favoring gliogenesis and preventing recruitment of neuroblasts from neurogenic regions. Protein kinase C (PKC) is a family of intracellular kinases involved in several of these gliogenic signaling pathways. The aim of this study was to analyze the role of PKC isozymes in the generation of neurons from neural progenitor cells (NPCs) in vitro and in vivo in brain injuries. PKC inhibition in vitro, in cultures of NPC isolated from the subventricular zone (SVZ) of postnatal mice, leads differentiation towards a neuronal fate. This effect is not mediated by classical or atypical PKC. On the contrary, this effect is mediated by novel PKCε, which is abundantly expressed in NPC cultures under differentiation conditions. PKCε inhibition by siRNA promotes neuronal differentiation and reduces glial cell differentiation. On the contrary, inhibition of PKCθ exerts a small anti-gliogenic effect and reverts the effect of PKCε inhibition on neuronal differentiation when both siRNAs are used in combination. Interestingly, in cortical brain injuries we have found expression of almost all PKC isozymes found in vitro. Inhibition of PKC activity in this type of injuries leads to neuronal production. In conclusion, these findings show an effect of PKCε in the generation of neurons from NPC in vitro, and they highlight the role of PKC isozymes as targets to produce neurons in brain lesions.


Involvement of the leaf-specific multidrug and toxic compound extrusion (MATE) transporter Nt-JAT2 in vacuolar sequestration of nicotine in Nicotiana tabacum.
Alkaloids play a key role in higher plant defense against pathogens and herbivores. Following its biosynthesis in root tissues, nicotine, the major alkaloid of Nicotiana species, is translocated via xylem transport toward the accumulation sites, leaf vacuoles. Our transcriptome analysis of methyl jasmonate-treated tobacco BY-2 cells identified several multidrug and toxic compound extrusion (MATE) transporter genes. In this study, we characterized a MATE gene, Nicotiana tabacum jasmonate-inducible alkaloid transporter 2 (Nt-JAT2), which encodes a protein that has 32% amino acid identity with Nt-JAT1. Nt-JAT2 mRNA is expressed at a very low steady state level in whole plants, but is rapidly upregulated by methyl jasmonate treatment in a leaf-specific manner. To characterize the function of Nt-JAT2, yeast cells were used as the host organism in a cellular transport assay. Nt-JAT2 was localized at the plasma membrane in yeast cells. When incubated in nicotine-containing medium, the nicotine content in Nt-JAT2-expressing cells was significantly lower than in control yeast. Nt-JAT2-expressing cells also showed lower content of other alkaloids like anabasine and anatabine, but not of flavonoids, suggesting that Nt-JAT2 transports various alkaloids including nicotine. Fluorescence assays in BY-2 cells showed that Nt-JAT2-GFP was localized to the tonoplast. These findings indicate that Nt-JAT2 is involved in nicotine sequestration in leaf vacuoles following the translocation of nicotine from root tissues.


Advances in natural language processing.
Natural language processing employs computational techniques for the purpose of learning, understanding, and producing human language content. Early computational approaches to language research focused on automating the analysis of the linguistic structure of language and developing basic technologies such as machine translation, speech recognition, and speech synthesis. Today's researchers refine and make use of such tools in real-world applications, creating spoken dialogue systems and speech-to-speech translation engines, mining social media for information about health or finance, and identifying sentiment and emotion toward products and services. We describe successes and challenges in this rapidly advancing area.


Periodontal Status of the Adjacent Second Molar after Impacted Mandibular Third Molar Surgical Extraction.
The purpose of this study was to evaluate the change in periodontal status of the adjacent second molar of the impacted mandibular third molar after surgical extraction and its association with the third molar condition in the presurgical stages, including position, eruption level, and local complications. The study was based on a 6-month follow-up of 38 patients (19 males and 19 females; Mean age: 21.89 ± 2.74) recruited consecutively after surgical extraction of an impacted lower third molar. The third molar's presurgical position, eruption level, and local complications were examined. Periodontal status, including Plaque Index (PI), Gingival Index (GI), and gingival bleeding on probing (BOP), of the teeth in the adjacent sextant was clinically evaluated. The pocket depth (PD) and the distance between the epithelial attachment and the adjacent second molar's occlusal surface were clinically measured; and the distance between the alveolar bone crest and cementoenamel junction (AC-CEJ) of the adjacent second molar was evaluated by the periapical film. All measures were recorded at the time of surgery and 1, 3, and 6 months after surgery. The values of PI, GI, BOP, PD, and EA-OS were significantly reduced after 1, 3, and 6 months compared to baseline data. The AC-CEJ was decreased after 1 month but significantly increased after 3 and 6 months. Presurgical local complications of the impacted third molar mostly were significantly associated with the periodontal status of the adjacent sextant. There was a significant improvement of periodontal conditions of the second molar and adjacent sextant after impacted third molar surgery.


The bovine papillomavirus E5 protein requires a juxtamembrane negative charge for activation of the platelet-derived growth factor beta receptor and transformation of C127 cells.
The bovine papillomavirus E5 gene encodes a 44-amino-acid, homodimeric transmembrane protein that is the smallest known transforming protein. The E5 protein transforms cultured fibroblasts by forming a stable complex with the endogenous platelet-derived growth factor (PDGF) beta receptor through transmembrane and juxtamembrane interactions, leading to sustained receptor activation. Aspartic acid 33 in the extracellular juxtamembrane region of the E5 protein is important for cell transformation and interaction with the PDGF beta receptor. A. N. Meyer et al. (Proc. Natl. Acad. Sci USA 91:4634-4638, 1994) speculated that this residue interacted with lysine 499 on the receptor. We constructed E5 mutants containing all possible substitutions at position 33, as well as several double mutants containing substitutions at aspartic acid 33 and at glutamic acid 36, and we examined the ability of these mutants to transform C127 mouse fibroblasts and to bind to and induce activation of the PDGF beta receptor. There was an excellent correlation between the transformation activities of the various mutants and their ability to bind to and activate the PDGF beta receptor. Analysis of the mutants demonstrated that a juxtamembrane negative charge on the E5 protein was required for cell transformation and for productive interaction with the PDGF beta receptor and indicated that aspartic acid 33 was more important for these activities than was glutamic acid 36. These results are consistent with the existence of an essential juxtamembrane salt bridge between lysine 499 on the PDGF beta receptor and an acidic residue in the C terminus of the E5 protein and lend support to our proposed model for the complex between the E5 dimer and the PDGF beta receptor.


Invasive group A streptococcal disease: Management and chemoprophylaxis.
Given the potentially devastating consequences of severe invasive group A streptococcal disease, attention has been directed toward the role of chemoprophylaxis and the optimization of management strategies. In response to this issue, Canadian guidelines were previously developed. However, the uptake of these recommendations is variable across Canada. The present document summarizes key components of the recommendations for use by Canadian physicians. The importance of penicillin in the treatment of group A streptococcal disease is reaffirmed, and the role of clindamycin is discussed. In addition, in situations in which chemoprophylaxis may be considered, the preferred agents are summarized.


Serum bcl-2 and survivin levels in melanoma.
This study was conducted to investigate the serum levels of bcl-2 and survivin in patients with melanoma and the relationship with tumour progression and known prognostic parameters. Forty-four patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly higher in patients with melanoma than in the control group (P=0.01). For the serum survivin levels, no difference was found (P=0.6). No significant correlations were found between the prognostic parameters analysed and the serum survivin concentrations. The same was true of the serum bcl-2 values, except for the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant relationship was found between the serum levels of bcl-2 and survivin (r=-0.13, P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances were unchanged after interferon-alpha-2b therapy. However, serum survivin concentrations were significantly increased in 10 patients with metastatic melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047). A similar finding was not determined for the serum bcl-2 levels. In conclusion, the results of this study suggest that decreased apoptosis is associated partly with an increase in serum bcl-2. However, much research continues in this field, and exciting new knowledge will ultimately emerge.


Improved protocol for efficient nonviral transfection of premature THP-1 macrophages.
The human monocytic leukemia cell line THP-1 is a widely used model for investigating monocyte and macrophage biology. Successful transfection of THP-1 monocytes with subsequent phorbol 12-myristate 13-acetate (PMA)-induced differentiation into macrophages is not a trivial matter, because according to previous transfection protocols, cell viability is lost almost completely within 24 h of PMA treatment following transfection. This protocol constitutes an optimized version of a previously published protocol by our group. It describes a procedure for transfecting premature THP-1 macrophages, which subsequently can be further differentiated into mature macrophages by PMA without a loss of cell viability. Transfection of THP-1 cells with plasmids or small interfering RNA (siRNA) is achieved by electroporation using the Lonza Nucleofector technology (Basel, Switzerland). This technique allows for the efficient nonviral delivery of plasmids, DNA, RNA, or siRNA into primary cells or cell lines even if the cells are not or are only slowly proliferating. Such cells are usually rather difficult to transfect by nonviral approaches. This means that only viral approaches would be left, which are expensive and labor-intensive and require laboratories complying with the respective safety regulations. The protocol described here is an efficient and convenient alternative.


Autophagy Contributes to Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Tumors.
Metabolic reprogramming is a feature of cancers for which recent research has been particularly active, providing numerous insights into the mechanisms involved. It occurs across the entire cancer process, from development to resistance to therapies. Established tumors exhibit dependencies for metabolic pathways, constituting vulnerabilities that can be targeted in the clinic. This knowledge is of particular importance for cancers that are refractory to any therapeutic approach, such as Pancreatic Ductal Adenocarcinoma (PDAC). One of the metabolic pathways dysregulated in PDAC is autophagy, a survival process that feeds the tumor with recycled intracellular components, through both cell-autonomous (in tumor cells) and nonautonomous (from the local and distant environment) mechanisms. Autophagy is elevated in established PDAC tumors, contributing to aberrant proliferation and growth even in a nutrient-poor context. Critical elements link autophagy to PDAC including genetic alterations, mitochondrial metabolism, the tumor microenvironment (TME), and the immune system. Moreover, high autophagic activity in PDAC is markedly related to resistance to current therapies. In this context, combining autophagy inhibition with standard chemotherapy, and/or drugs targeting other vulnerabilities such as metabolic pathways or the immune response, is an ongoing clinical strategy for which there is still much to do through translational and multidisciplinary research.


Immediate and Lagged Effects of Daily Stress and Affect on Caregivers' Daily Pain Experience.
We examined the effect of daily stress, affect, and adult day service (ADS) use on the daily pain experience among caregivers of individuals with dementia (IWD). Participants were interviewed for 8 consecutive days. Caregivers utilized an ADS program on some days and provided care at home on other days. We hypothesized ADS use, care-related and noncare-related subjective stress, and affect would significantly influence and interact in ways to exacerbate or buffer the experience of daily pain. Participants were 173 family caregivers of IWDs using ADS more than 2 days per week. Participants with IWDs diagnosed with "mild cognitive impairment" were excluded. Daily telephone interviews assessed stress, affect, and pain. Multilevel models were used to examine the relation between daily stress and daily pain and interaction effects of other daily experiences within the context of ADS use. Multilevel models revealed a significant relation between care-related subjective stress and daily bodily pain as well as an interaction between noncare-related subjective stress and daily bodily pain. ADS use and affect did not predict daily pain. Lagged effects revealed a significant interaction between yesterday's ADS use and today's positive affect on today's bodily pain. Findings suggest that further studies are warranted for understanding and controlling pain among caregivers. Addressing the physical health needs through pain management interventions, positive affect maximization, and ADS use may improve the overall wellbeing of caregiving dyads.


Measurement properties of PROMIS short forms for pain and function in orthopedic foot and ankle surgery patients.
To examine the measurement properties of the German PROMIS short forms for pain intensity (PAIN), pain interference (PI) and physical function (PF) in orthopedic foot and ankle surgery patients. Patient-rated outcomes were collected from consecutive patients of our foot and ankle registry before and 6 months after surgery. Measurement properties were tested according to the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN). The German Foot Function Index (FFI-D) served as a legacy measure. 748 patients were included in our cross-sectional sample. Longitudinal and test-retest data were available for 202 and 65 patients, respectively. Construct validity of all short forms was good. All Cronbach's α and intraclass correlation coefficients were > 0.7. The smallest detectable change (SDC) was highest for PF (8.9) and lowest for PI (6.5). Minimal important change was 4 to 5 points and thus smaller than SDC for all instruments. We observed a baseline ceiling effect for PF. PI showed insufficiently correlated change scores with FFI-D disability change scores, and therefore failed the responsiveness testing. Our study showed some adequate psychometric properties, but also certain aspects regarding interpretability and responsiveness that researchers must be aware of when using PROMIS short forms of pain and function in foot and ankle surgery patients.


Postoperative CT Is Superior for Acetabular Fracture Reduction Assessment and Reliably Predicts Hip Survivorship.
Postoperative pelvic radiographs are routinely used to assess acetabular fracture reduction. We compared radiographs and computed tomography (CT) with regard to their ability to detect residual fracture displacement. We also determined the association between the quality of reduction as assessed on CT and hip survivorship and identified risk factors for conversion to total hip arthroplasty (THA). Patients were included in the study who had undergone acetabular fracture fixation between 1992 and 2012, who were followed for ≥2 years (or until early THA), and for whom radiographs and a pelvic CT scan were available. Residual displacement was measured on postoperative radiographs and CT and graded according to Matta's criteria (0 to 1 mm indicating anatomic reduction; 2 to 3 mm, imperfect reduction; and >3 mm, poor reduction) by observers who were blinded to patient outcome. Kaplan-Meier survivorship curves were plotted and log-rank tests were used to assess statistical differences in survivorship curves between adequate (anatomic or imperfect) and inadequate reductions on CT. Cox proportional hazard regression analysis was used to identify risk factors for conversion to THA. Two hundred and eleven patients were included. At mean of 9.0 years (standard deviation [SD], 5.6; median, 7.9; range, 0.5 to 23.3 years) postoperatively, 161 patients (76%) had retained their native hip. Compared with radiographs, CT showed worse reduction in 124 hips (59%), the same reduction in 79 (37%), and better reduction in 8 (4%). Of the 99 patients graded as having adequate reduction on CT, 10% underwent conversion to THA in comparison with 36% of those with inadequate reduction, and there was a significant difference between the survivorship curves (p < 0.001). Mean hip survivorship was shorter in patients ≥50 years of age (p < 0.001) and in those with an inadequate reduction on CT (p < 0.001). Independent risk factors for conversion to THA were age (hazard ratio [HR] = 4.46, 95% confidence interval [CI] = 2.07 to 9.62; p < 0.001), inadequate reduction (HR = 3.57, 95% CI = 1.71 to 7.45; p = 0.001), and posterior wall involvement (HR = 1.81, 95% CI = 1.00 to 3.26; p = 0.049). Sex, fracture type (elementary versus associated), and year of surgery did not influence hip survivorship. CT is superior to radiographs for detecting residual displacement after acetabular fracture fixation. Hip survivorship is greater in patients with adequate (anatomic or imperfect) reduction on CT. Along with older age and posterior wall involvement, an inadequate reduction on CT is a risk factor for conversion to THA. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Characterization of microRNAs differentially expressed during bovine follicle development.
Several different miRNAs have been proposed to regulate ovarian follicle function; however, very limited information exists on the spatiotemporal patterns of miRNA expression during follicle development. The objective of this study was to identify, using microarray, miRNA profiles associated with growth and regression of dominant-size follicles in the bovine monovular ovary and to characterize their spatiotemporal distribution during development. The follicles were collected from abattoir ovaries and classified as small (4-8 mm) or large (12-17 mm); the latter were further classified as healthy or atretic based on estradiol and CYP19A1 levels. Six pools of small follicles and individual large healthy (n=6) and large atretic (n=5) follicles were analyzed using Exiqon's miRCURY LNA microRNA Array 6th gen, followed by qPCR validation. A total of 17 and 57 sequences were differentially expressed (greater than or equal to twofold; P<0.05) between large healthy and each of small and large atretic follicles respectively. Bovine miRNAs confirmed to be upregulated in large healthy follicles relative to small follicles (bta-miR-144, bta-miR-202, bta-miR-451, bta-miR-652, and bta-miR-873) were further characterized. Three of these miRNAs (bta-miR-144, bta-miR-202, and bta-miR-873) were also downregulated in large atretic follicles relative to large healthy follicles. Within the follicle, these miRNAs were predominantly expressed in mural granulosa cells. Further, body-wide screening revealed that bta-miR-202, but not other miRNAs, was expressed exclusively in the gonads. Finally, a total of 1359 predicted targets of the five miRNAs enriched in large healthy follicles were identified, which mapped to signaling pathways involved in follicular cell proliferation, steroidogenesis, prevention of premature luteinization, and oocyte maturation.


Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise.
Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions. To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training. This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018. Plasma DMGV levels. The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training. Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training. Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.


Suicidality in older African Americans: findings from the EPOCH study.
The authors examined the current frequency of suicidality and associated characteristics in a sample of 835 African-American older adult residents of six urban public housing developments who consented to participate in an intervention trial of mobile outreach. The frequency of passive and active suicidal ideation was 2.5% and 1.4%, respectively. Characteristics of individuals with both active and passive suicidality included elevated anxiety, social dysfunction, somatic symptoms, low social support, lack of a confidant, and low religiosity. Characteristics of those with passive, but not active, ideation also included older age, lower levels of education, elevated depressive symptoms, poorer cognitive functioning, and having recently discussed emotional problems with a healthcare provider. The characteristics of those reporting active, but not passive, ideation included having a history of mental health treatment and reporting no instrumental support. Multivariate analyses indicated that depression and religiosity were uniquely associated with passive suicidal ideation, and life satisfaction and religiosity were uniquely associated with active suicidal ideation. The authors discuss implications of these findings and offer suggestions for research and clinical practice.


Light damage in the developing retina of the albino rat: an electroretinographic study.
The albino rat retina is severely damaged by exposure to bright light. The degree of damage depends upon the intensity of the exposure and its duration. In the present study, electroretinographic (ERG) responses were measured in rats exposed at different ages during the period of retinal development to 24 hr of bright light and then transferred to darkness for about 2 months. The ERG data indicated that if the bright-light exposure was done prior to 20 days of age, the retina was resistant to the light damage, and the dark-adapted ERG responses measured later were normal. In rats older than 20 days, light damage increased with age until, in rats exposed to light at age 30 days, the ERG was unrecordable. Further experiments showed that light exposure did damage the 15-day-old rat retina; however, complete recovery was attained within 15 days postexposure.


An approach to electrodiagnosis of peripheral neuropathies.
Peripheral neuropathies are the most common neuromuscular disorder seen by neurologists. Determining full features and characteristics based on history and physical examination alone can be difficult. Electrodiagnostic testing is an extension of the neurological examination and can assist in full characterization and provide unique information on underlying pathological processes. This article presents a practical approach to electrodiagnostic testing in patients with peripheral neuropathies.


Locked out and still knocking: predictors of excessive demands for postoperative intravenous patient-controlled analgesia.
Psychosocial factors governing the use of postoperative, intravenous patient-controlled analgesia (PCA) have received little attention in spite of the fact that PCA is the most common modality for managing pain after surgery. The motivation behind requests for analgesia during lockout periods is not known. Unrelieved pain and need for pain medication are obvious reasons but other factors may be involved. The aim of the present study was to predict PCA lockout interval demands based on preoperative psychosocial factors. Approximately one week before major abdominal gynecologic surgery, 117 women completed the impact of events scale (IES) measuring intrusive thoughts and avoidant behaviours. Pain was measured by visual analogue scale at three, six, 12, 24 and 48 hr after surgery. Measures of anxiety and negative affect were obtained 24 and 48 hr after surgery. Cumulative morphine consumption and every PCA demand (drug delivered and not delivered) were downloaded from the PCA pump. Multiple regression analyses revealed that preoperative intrusive thoughts and avoidant behaviours about the upcoming surgery positively predicted PCA lockout interval demands after controlling for postoperative pain, morphine consumption, anxiety, and negative affect (R2 = 0.45; P < 0.0001). Path analysis showed a direct pathway from preoperative IES scores to lockout interval demands (beta = 0.23, P = 0.002) which was not associated with untreated pain, anxiety, or negative affect. Excessive demands for postoperative intravenous- PCA morphine during lockout intervals appear to reflect, in part, poor preoperative adaptation to surgery involving intrusive thoughts and avoidant behaviours about the upcoming surgery.


Simultaneous bilateral tibial tubercle avulsion fracture in an adolescent: a case report.
Bilateral simultaneous avulsion fractures of the anterior tibial tubercle (ATT) are extremely rare. Since the first description in 1954, 15 similar cases have been reported. We report a further case in a 16-year-old boy who sustained simultaneous bilateral tibial tubercle avulsion fractures (Watson-Jones Type III) from jumping during a gymnastics session. The right knee presented an associated partial avulsion of the patellar tendon. Both knees were treated successfully by open reduction and internal fixation with two cannulated screws. The recovery of the patient was complete; the screws were removed six months later. After one year follow-up, the patient had no complaint and had resumed his sporting activity.


A nano-luciferase expressing human coronavirus OC43 for countermeasure development.
The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against novel emerging viruses. Antivirals with broad-spectrum activity overcome this limitation by targeting highly conserved regions or catalytic domains within viral proteins that are essential for replication. For rapid identification of small molecules with broad antiviral activity, assays with viruses representing family-wide genetic diversity are needed. Viruses engineered to express a reporter gene (i.e. luminescence, fluorescence, etc.) can increase the efficiency, sensitivity or precision of drug screening over classical measures of replication like observation of cytopathic effect or measurement of infectious titers. We have previously developed reporter virus systems for multiple other endemic, pandemic, epidemic and enzootic CoV. Human CoV OC43 (HCoV-OC43) is a human endemic CoV that causes respiratory infection with age-related exacerbations of pathogenesis. Here, we describe the development of a novel recombinant HCoV-OC43 reporter virus that expresses nano-luciferase (HCoV-OC43 nLuc), and its potential application for screening of antivirals against CoV.


Mitochondrial DNA point mutations detected in four cases of sudden infant death syndrome.
The aim of this study was to investigate the tRNA(Leu(UUR)) gene and the first part of the ND1 gene in mitochondrial DNA (mtDNA) in cases of sudden infant death syndrome (SIDS). A total of 158 cases of SIDS and 97 controls were included in the study, and the base pairs in the range 3230-3330 were investigated using polymerase chain reaction (PCR) and temporal temperature gradient electrophoresis (TTGE). If a band shift was detected by TTGE, the area investigated and the D-loop was sequenced. Three different point mutations (T3290C, T3308C and T3308G) were detected in four of the SIDS cases, while none of the controls were mutated. We also found a high D-loop substitution rate in these four cases. The findings indicate that mtDNA mutations may play a role in some cases of SIDS.


CircZBTB46 predicts poor prognosis and promotes disease progression of myelodysplastic syndromes and acute myeloid leukemia.
Circular RNAs (circRNAs) have been recently identified as important regulators of various diseases, especially cancer. However, the roles of circRNAs in hematologic malignancies have been rarely reported. This study aimed to identify a specific circRNA expression profile in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to evaluate the biological roles of circRNA in MDS and AML for understanding their clinical significance. Reverse transcription-quantitative PCR was performed to validate the expression of circZBTB46. Kruskal-Wallis test, Kaplan-Meier curves, and the Cox regression model were employed to analyze the clinical significance of circZBTB46. Two specific shRNAs as well as an expression lentiviral vector of circZBTB46 were constructed to identify the biological function of circZBTB46. The impact of circZBTB46 on leukemia cell proliferation, cell cycle distribution, and apoptosis was confirmed using cell viability assay and flow cytometry analysis. The expression of circZBTB46 gradually increased in patients with higher-risk MDS and AML, as compared to controls. CircZBTB46 expression was significantly correlated with important clinical parameters of MDS, including WHO classification, absolute neutrophil count (ANC), marrow blast, IPSS karyotype, IPSS/IPSS-R risk groups, and AML transformation. CircZBTB46 expression was also associated with ANC, marrow blast, cytogenetic risk groups, FLT3-ITD mutation, and treatment response in AML patients. Furthermore, circZBTB46 overexpression was significantly correlated with shorter overall survival (OS, P = 0.0342, median survival time 18.5 vs. 45.4 months) and leukemia-free survival (LFS, P = 0.0421) in MDS, also with the shorter OS in AML (P = 0.0293, median survival time 11.6 vs. 16.9 months). Functional studies revealed that silencing circZBTB46 expression significantly inhibited proliferation and induced apoptosis in SKM-1, THP-1, and K562 cell lines, while rescue experiments alleviated the siRNA-mediated growth inhibition and apoptosis in these leukemic cells. The present data suggested the essential oncogenic role of circZBTB46, as a progression and survival indicator in both MDS and AML.


Increased incidence of faecal coliforms with in vitro adhesive and invasive properties in patients with ulcerative colitis.
Faecal samples were collected from 23 patients with active ulcerative colitis, 15 patients with established ulcerative colitis in remission, 20 patients with active colitis of cause other than ulcerative colitis, and 20 normal control subjects. Ten coliform colonies were randomly selected from the faecal sample cultures and serotyped before the testing of each different serotype from each sample for adhesive or invasive properties on HeLa cell monolayers. In the patients with both active ulcerative colitis and ulcerative colitis in remission and those with other types of colitis one serotype tended to dominate the faecal coliform flora. In normal controls more variety was encountered. Thirty-five per cent of the patients with active ulcerative colitis and 27% of the patients with ulcerative colitis in remission had at least one adhesive or invasive faecal coliform as compared with 5% of the patients with other types of colitis and 5% of the normal controls. These findings are significant (P < 0.05) and may have aetiological and therapeutic significance.


Acorns containing deeper plumule survive better: how white oaks counter embryo excision by rodents.
Several squirrel species excise the embryo of acorns of most white oak species to arrest germination for long-term storage. However, it is not clear how these acorns counter embryo excision and survive in the arms race of coevolution. In this study, we simulated the embryo excision behavior of squirrels by removing 4 mm of cotyledon from the apical end of white oak acorns differing in embryo depths to investigate the effects of embryo excision on acorn germination and seedling performance of white oak species. The embryo depth in the cotyledons was significantly different among white oak acorns, with Quercus mongolica containing the embryo most deeply in the acorns. We found that artificial embryo excision significantly decreased acorn germination rates of Quercus variabilis, Quercus acutissima, Quercus aliena, Quercus aliena var. acutiserrata, Quercus serrata. var. brevipetiolata but not Q. mongolica. Artificial embryo excision exerted significant negative impacts on seedling performance of all oak species except Quercus aliena. Our study demonstrates the role of embryo depth of acorns in countering embryo excision by squirrels and may explain the fact that squirrels do not perform embryo excision in acorns of Q. mongolica with deeper embryos. This apparent adaptation of acorns sheds light on the coevolutionary dynamics between oaks and their seed predators.


Enhanced visual statistical learning in adults with autism.
Individuals with autism spectrum disorder (ASD) are often characterized as having social engagement and language deficiencies, but a sparing of visuospatial processing and short-term memory (STM), with some evidence of supranormal levels of performance in these domains. The present study expanded on this evidence by investigating the observational learning of visuospatial concepts from patterns of covariation across multiple exemplars. Child and adult participants with ASD, and age-matched control participants, viewed multishape arrays composed from a random combination of pairs of shapes that were each positioned in a fixed spatial arrangement. After this passive exposure phase, a posttest revealed that all participant groups could discriminate pairs of shapes with high covariation from randomly paired shapes with low covariation. Moreover, learning these shape-pairs with high covariation was superior in adults with ASD than in age-matched controls, whereas performance in children with ASD was no different than controls. These results extend previous observations of visuospatial enhancement in ASD into the domain of learning, and suggest that enhanced visual statistical learning may have arisen from a sustained bias to attend to local details in complex arrays of visual features.


Syrup of ipecac availability: before and after a poisoning.
A retrospective review was conducted of 1,230 human poison exposures in which syrup of ipecac was administered to determine the availability of this emetic. Ipecac was available in 41.1% of the homes, while 42.5% obtained it from the pharmacy. Eight and two tenths percent were referred to a health care facility, 2.9% obtained ipecac from a neighbor, 2.3% went to an emergency room prior to calling the poison center, and 3% obtained ipecac from other sources. A randomly selected sample of 150 of these 1,230 cases were contacted 6 months after their initial call to the poison center to determine any changes in the availability of syrup of ipecac in the home. Although almost 30% more homes had syrup of ipecac than previously, 22.2% of homes still did not have ipecac available, despite the previous poisoning experience. Greater effort should be made during follow-up to educate the public regarding ipecac and its use.


Simple and fast isolation of circulating exosomes with a chitosan modified shuttle flow microchip for breast cancer diagnosis.
Tumor-derived exosomes have been recognized as promising biomarkers for early-stage cancer diagnosis, tumor prognosis monitoring and individual medical treatment. However, it is a huge challenge to separate exosomes from trace biological samples in clinics for disease diagnosis. Herein, we propose a simple, quick, and label-free method for isolating circulating exosomes from serum of patients. The strategy synergistically integrates chitosan electrostatic-adsorption, micro-patterned substrates, and microfluidic shuttle flow control to enable the capture/release of circulating exosomes in a simple manner. Using this microchip, we can isolate exosomes from trace samples (10 μl) with relative purity over 90% and high RNA recovery ratio over 84% within 15 minutes, which is impossible for traditional ultracentrifugation methods. We then validate the application of the microchip using 24 serum samples from clinical breast cancer and breast fibroma patients. The isolated exosomes are subjected to miRNA sequencing and RT-PCR, followed by pathway prediction analysis. The results showed that exosomes were relevant to the invasion and metastasis of breast cancer cells and hsa-miR-18a-3p might have the potential to become a new biomarker for distinguishing breast cancer from breast fibroma (AUC = 0.83, P value = 0.019). This established method is simple, quick and easy to operate with integration. And it may pave a new way for clinical research on exosomes and tumor relevant diagnosis.


Challenges in international collaboration in child and adolescent psychiatry.
International collaboration in child and adolescent psychiatry has historically been weak and fragmented. The field has also lagged in developing remedies for improving collaboration. This article identifies barriers to successful collaboration and examines problems in the areas of finance, professional development, knowledge dissemination, professional organisations, public policy and the political environment, priority setting, nomenclature, as well as ethical challenges. The article then identifies some promising initiatives and proposes solutions to improve international collaboration in child and adolescent mental health.


Occurrence of Gastrointestinal Parasites in Small Mammals from Germany.
An increase in zoonotic infections in humans in recent years has led to a high level of public interest. However, the extent of infestation of free-living small mammals with pathogens and especially parasites is not well understood. This pilot study was carried out within the framework of the "Rodent-borne pathogens" network to identify zoonotic parasites in small mammals in Germany. From 2008 to 2009, 111 small mammals of 8 rodent and 5 insectivore species were collected. Feces and intestine samples from every mammal were examined microscopically for the presence of intestinal parasites by using Telemann concentration for worm eggs, Kinyoun staining for coccidia, and Heidenhain staining for other protozoa. Adult helminths were additionally stained with carmine acid for species determination. Eleven different helminth species, five coccidians, and three other protozoa species were detected. Simultaneous infection of one host by different helminths was common. Hymenolepis spp. (20.7%) were the most common zoonotic helminths in the investigated hosts. Coccidia, including Eimeria spp. (30.6%), Cryptosporidium spp. (17.1%), and Sarcocystis spp. (17.1%), were present in 40.5% of the feces samples of small mammals. Protozoa, such as Giardia spp. and amoebae, were rarely detected, most likely because of the repeated freeze-thawing of the samples during preparation. The zoonotic pathogens detected in this pilot study may be potentially transmitted to humans by drinking water, smear infection, and airborne transmission.


The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion.
Obesity is associated with a dysregulation of beta-cell and adipocyte function. The molecular interactions between adipose tissue and beta-cells are not yet fully elucidated. We investigated, whether or not the adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) and its enzymatic product Nicotinamide mononucleotide (NMN), which has been associated with obesity and type 2 diabetes mellitus (T2DM) directly influence beta-cell survival and function. The effect of Nampt and NMN on viability of INS-1E cells was assessed by WST-1 assay. Apoptosis was measured by Annexin V/PI and TUNEL assay. Activation of apoptosis signaling pathways was evaluated. Adenylate kinase release was determined to assess cytotoxicity. Chronic and acute effects of the adipocytokine Nampt and its enzymatic product NMN on insulin secretion were assessed by glucose stimulated insulin secretion in human islets. While stimulation of beta-cells with the cytokines IL-1β, TNFα and IFN-γ or palmitate significantly decreased viability, Nampt and NMN showed no direct effect on viability in INS-1E cells or in human islets, neither alone nor in the presence of pro-diabetic conditions (elevated glucose concentrations and palmitate or cytokines). At chronic conditions over 3 days of culture, Nampt and its product NMN had no effects on insulin secretion. In contrast, both Nampt and NMN potentiated glucose stimulated insulin secretion acutely during 1 h incubation of human islets. Nampt and NMN neither influenced beta-cell viability nor apoptosis but acutely potentiated glucose stimulated insulin secretion.


[Characteristics and mechanism of pyelorenal backflow correlated to renal pelvic pressure].
The present study was conducted to examine the characteristics of pyelo-renal backflow related with the changes in renal pelvic pressure. Forty rabbits weighting approximately 3.0 kg were used in this experiment. The renal pelvis was continuously perfused with PSP solution through the double lumen catheter placed above the ureteropelvic junction. The renal pelvic pressure was also recorded during the intrapelvic perfusion. Simultaneously, PSP concentrations in blood and urine excreted from the contralateral kidney were measured. During the intrapelvic perfusion with PSP solution, PSP blood concentration began to increase immediately and reached maximum within 1 or 2 minutes after a start of perfusion. Then, its concentration gradually decreased toward the constant, low levels. The urinary concentration of PSP showed the same change as the blood concentration with a time lag of 1 or 2 minutes. A compartment analysis showed that this backflow curve composed of an early phase and a late phase. The early phase was characterized by a rapid increase and following decrease (exponentially declining) in PSP concentration. The late phase was a portion of constant PSP concentration in the backflow curve. A maximum PSP concentration in the early phase was elevated with an increase in the increment rate of renal pelvic pressure. There was a significant, positive correlation between the maximum PSP urinary concentration and the increment rate of renal pelvic pressure (dp/dt). The constant values of PSP concentration in the late phase could be correlated with neither increment rate nor absolute values of renal pelvic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2.
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.


Microsatellite Instability with BRAF V600E Associated with Delayed Presentation but Poor Survival in Stage III Colorectal Cancer.
Colorectal cancer (CRC) has tremendous molecular and genetic heterogeneity, making it a difficult cancer to treat. Two of the key prognostic indicators of CRC include microsatellite instability (MSI) and BRAF V600E mutation. Here, we performed a retrospective survival analysis on 145 stage II and III CRC patients treated at the University of Kansas Cancer Center between 2009 and 2020. Of the 145 patients, BRAF V600E was observed in 15% patients and MSI in 28% patients. Median survival was not reached for stage II. For stage III, patients with BRAF V600E showed poor overall survival, which worsened with concurrent presence of MSI [χ2=6.4, p=0.01]. Eighty-five percent of this group was found to have right-sided CRC. For stage III, overall survival (OS) was 27 months, 37 months, 87 months and not reached for MSI-H/BRAF V600E, MSS/BRAF V600E, MSS/BRAF WT and MSI-H/BRAF WT, respectively. Although associated with poor prognosis, presence of MSI in BRAF V600E patients was associated with delayed disease presentation (mean age 77) compared to those with stable microsatellite (mean age 63) [p=0.01]. Although median survival between the groups could not be assessed for stage II due to very few deaths and/or inadequate length of study, comparison of survival trend suggests that BRAF V600E, rather than MSI, is what drives prognosis in stage II CRC. Our findings suggest that prognostic value of MSI is more relevant for stage III than stage II CRC. Patients with MSI-H and BRAF V600E have advantage of late presentation, although at the cost of poor overall prognosis.


Racial disparities in the incidence of colon cancer in patients with inflammatory bowel disease.
Studies have explored the relationship between inflammatory bowel disease (IBD) [ulcerative colitis (UC) and Crohn's disease (CD)] and colon cancer (CC). Additionally, racial disparities in the incidence of CC is well known. However, the impact of racial disparity in IBD patients who develop CC remains unclear. The aim of this study is to address the knowledge gap in this particular group of patients. A retrospective analysis was done using the National Inpatient Sample (NIS) database from 2011. We included patients with IBD over age ≥18 years with a diagnosis of CC. Patients were stratified by race, gender, age, presence of IBD and CC. Statistical analysis was performed to compare the groups. A total of 57,542 patients were included (CD: 36,357, UC: 21,001). Of all patients with and without IBD, advanced age, Black and Asian race conferred an increased risk of developing CC, whereas female gender, Hispanic and Native American race conferred a protective effect. In patients with IBD, advanced age conferred an increased risk for developing CC while female gender conferred a protective effect. In this subset of patients, black race conferred a protective effect. Racial disparity exists in the overall incidence of CC and among patients with IBD who develop CC. Interestingly, black race conferred a protective effect for patients with IBD, contrary to what is seen in the general population. These findings could be attributed to the environmental factors and genetic makeup between racial groups. Further studies are warranted to better understand these disparities.


Improving Nutrition Outcomes for Infants < 1500 Grams With a Progressive, Evidenced-Based Enteral Feeding Protocol.
Growth is essential for very low birth weight infants. The purpose of this retrospective chart review was to evaluate the impact of a new standardized, evidenced-based feeding protocol for infants born < 1500 g in correlation with growth and clinical outcomes. Growth and nutrition data was reviewed from 2 groups of infants born < 1500 g within a level III newborn intensive care unit (NICU). Epoch 1 infants (N = 32) received care following initial implementation of a standardized enteral feeding protocol. Epoch 2 infants (N = 32) received care following aggressive modification of this initial protocol based on newly available literature that promotes earlier initiation and advancement of enteral feedings. Epoch 2 infants weighed more at 36 weeks (2562 vs 2304 g) with higher discharge weight percentiles (32nd vs 15th percentile). Epoch 2 infants started and achieved full enteral feedings earlier (day of life 1 vs 4; 7 vs 22, P < 0.0001) and required less days of parenteral nutrition (5.5 vs 17.5 days, P < 0.0001), with indwelling central line for parenteral access (6 vs 17.5). There were no differences in retinopathy of prematurity (17% control vs 19% study), oxygen requirement at 36 weeks (22% epoch 1 vs 43%), necrotizing enterocolitis (3% epoch 1 vs 0%), intraventricular hemorrhage grade 3-4, periventricular leukomalacia, or death. In this sample of very low birth weight infants, a progressive standardized, evidence-based feeding protocol was associated with improved growth without increased risk for necrotizing enterocolitis.


Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases.
Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) and Strontium-89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of +/- 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.


Multiple paternity in polyandrous barn owls (Tyto alba).
In polyandrous species females produce successive clutches with several males. Female barn owls (Tyto alba) often desert their offspring and mate to produce a 2(nd) annual brood with a second male. We tested whether copulating during chick rearing at the 1(st) annual brood increases the male's likelihood to obtain paternity at the 2(nd) annual breeding attempt of his female mate in case she deserts their brood to produce a second brood with a different male. Using molecular paternity analyses we found that 2 out of 26 (8%) second annual broods of deserting females contained in total 6 extra-pair young out of 15 nestlings. These young were all sired by the male with whom the female had produced the 1(st) annual brood. In contrast, none of the 49 1(st) annual breeding attempts (219 offspring) and of the 20 2(nd) annual breeding attempts (93 offspring) of non-deserting females contained extra-pair young. We suggest that female desertion can select male counter-strategies to increase paternity and hence individual fitness. Alternatively, females may copulate with the 1(st) male to derive genetic benefits, since he is usually of higher quality than the 2(nd) male which is commonly a yearling individual.


Unusual manifestations of nervous system Borrelia burgdorferi infection.
Borrelia burgdorferi infection may show disease manifestations in different organ systems, including the skin, heart, central nervous system, peripheral nervous system, and joints. We report two hitherto unknown (to our knowledge) disease manifestations, an arteritis in the central nervous system, and a neuromyopathy of 11 years' duration. Diagnoses were made by demonstrating specific antibodies against B burgdorferi in the cerebrospinal fluid, and elevated specific antibody index. Both patients responded well to treatment, and intrathecal immunologic activity could not be demonstrated after treatment. Serologic analyses (enzyme-linked immunosorbent assay) in serum and cerebrospinal fluid should be performed widely in cases with inflammatory findings in cerebrospinal fluid combined with neurologic disease of unclear origins.


Prophylactic efficacy of lithium administered every second day: a WHO multicentre study.
To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal), India (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets being supplied from Denmark (Copenhagen). Participation in the study was conditional on the patient having been in prophylactic lithium treatment for the preceding 2-year period and having been free of depressive or manic phases during the preceding 6 months. After a 2-month baseline period during which lithium was administered every day, the treatment was changed to lithium intake every second day, this regimen in most cases being continued for 22 months. Forty-seven patients, 42 with a diagnosis of bipolar disorder and five with a diagnosis of recurrent unipolar depressive disorder, participated in the study. The number of patients from each centre ranged from six to 11. The mean lithium dose every second day was 36 mmol lithium, leading to a mean 12-h standard serum lithium concentration during the last month of treatment at 0.78+/-0.16 mmol/L. Lithium intake every second day was effective in 38 out of 47 patients. The remaining nine patients had recurrences, a number not differing from the 16 patients in the same group of 47 patients who, during the 2-year period preceding the study, had recurrences. The mean 12-h standard serum lithium concentration was lower in the patients who had recurrences than in those who stayed euthymic. The results suggest that to be effective when administered every second day, lithium must be given in a dose leading to a 12-h standard serum lithium concentration at 0.8 mmol/L or above. In the dose administered, lithium intake every second day was as effective as lithium intake every day. The amount and severity of lithium-related side effects were apparently not influenced by the change to lithium intake every second day.


Media representation of personality disorder in Jamaica - public scholarship as a catalyst of health promotion.
To ascertain whether the public scholarship of the epidemiology of personality disorder (PD) in Jamaica prompted a health promotion outcome. A January 2011 to December 2012 trawl of news media articles linking 'PD' to published public scholarship articles on the epidemiology of PD recorded titles and contents of the reports that were culled to capture the emotional responses and psychological defence mechanisms expressed. These were analysed with concomitant social, psychological or behavioural activities occurring in Jamaica, using SPSS version 17 software. Two public scholarship interventions to two major broadsheet newspapers triggered 25 contributed articles, which in turn prompted 160 responses from the public, five commentaries on leading radio stations and four Internet blogs. One hundred and sixty-six (84.2%) of the titles targeted PD in the Jamaican nation; 31 (13.7) articles targeted PD in leaders, athletes, inmates, individuals, families and productivity in Jamaica. One hundred and fifty-five (79.1%) expressed agreement with the scientific epidemiological observations, while 20.9% (n = 41) expressed disagreement. Eighty-two (41.8%) of the responses expressed rationalizations, 47 (24%) were expressions of reaction formation, 27 (13.8%) were in frank denial, while 25 (12.8%) were expressing open acting out responses or blunt projection (15, 7.7%) to the published epidemiology. The difference between 139 (70.9%) popular media responses to contemporary social problems and 57 (29.1%) reports that made no reference to social problems was statistically significant (p < 0.03). The hypothesis that public scholarship reports prompted a popular media response, generating a health promotion outcome linking contemporary social events to this medical research is confirmed.


Spatial organization of frequency preference and selectivity in the human inferior colliculus.
To date, the functional organization of human auditory subcortical structures can only be inferred from animal models. Here we use high-resolution functional magnetic resonance imaging at ultra-high magnetic fields (7T) to map the organization of spectral responses in the human inferior colliculus, a subcortical structure fundamental for sound processing. We reveal a tonotopic map with a spatial gradient of preferred frequencies approximately oriented from dorsolateral (low frequencies) to ventromedial (high frequencies) locations. Furthermore, we observe a spatial organization of spectral selectivity (tuning) of functional magnetic resonance imaging responses in the human inferior colliculus. Along isofrequency contours, functional magnetic resonance imaging tuning is narrowest in central locations and broadest in the surrounding regions. Finally, by comparing subcortical and cortical auditory areas we show that functional magnetic resonance imaging tuning is narrower in human inferior colliculus than on the cortical surface. Our findings pave the way to noninvasive investigations of sound processing in human subcortical nuclei and for studying the interplay between subcortical and cortical neuronal populations.


[Differential health resort drinking treatment of patients with chronic pancreatitis].
Examination of 71 patients with chronic pancreatitis (CP) has revealed that such patients had subnormal levels of antiproteolytic enzymes even in pancreatitis remission. Compared to women, men had higher total cholesterol (by 12.2%), triglycerides (by 13.3%), LDLP (by 19.3%), respectively, while women had higher insulin (by 22%) and cortisol (by 13.4%). Glycemia was higher in men (by 10 and 18% according to glucose tolerance test, min 30 and 60). The most effective spa regimen for CP patients was drinking mineral water from Slavyanovsky spring (56 degrees C) in a half-dose and from the spring Vladimirsky (24 degrees C) in a standard dose. The standard dose of mineral water from Slavyanovsky mineral spring has the best effect in patients with carbohydrate metabolism disorders.


[Anomalies of the thyroid cartilage and their forensic medical significance].
A total of 433 completely prepared cadaveric neck organ complexes were examined. Four variants of the thyroid cartilage structure were distinguished, with due consideration for the mobility of its attachment to the hyoid bone; three of these variants included abnormal cases. Abnormalities were revealed in 4.8% of cases, and were almost two times more incident in men than in women. The shape of the thyroid-hyoid junction notably influences the vulnerability of the neck structures. Vulnerability of the thyroid cartilage and hyoid bone differed much even among the normal variants. Abnormal or even normal thyroid-hyoid junction can be taken for a fracture by palpation; therefore, thorough complete preparation under laboratory conditions is obligatory.


Knowledge about Obstetric Danger Signs among Pregnant Women in Aleta Wondo District, Sidama Zone, Southern Ethiopia.
Raising awareness of women on danger signs of pregnancy, childbirth and the postpartum period is crucial for safe motherhood. In Ethiopia, a country where maternal morbidity and mortality is high little is known about knowledge level of pregnant women on obstetric danger signs. The objective of this study was to assess pregnant women's knowledge about obstetric danger signs in Aleta Wondo district, Sidama Zone, South Ethiopia. A community based cross-sectional study was conducted from January 18 - February 20, 2007, on a sample of 812 pregnant women selected from, 8 rural and 2 urban Kebeles. A structured pre-tested questionnaire was used to collect quantitative data on socio-demographic characteristics, obstetric history, and knowledge about danger signs of pregnancy, childbirth and post partum period. Qualitative data was collected through focus group discussion with pregnant women and in-depth interview with traditional birth attendants. The collected data were analyzed using SPSS for Windows version 12.0.1. Seven hundred forty three pregnant women participated in the study making a response rate of 92%. Out of the 743 pregnant women who participated in this study 226 (30.4%), 305(41.3%) and 279(37.7%) knew at least two danger signs during pregnancy, childbirth and postpartum period, respectively. Being urban resident was consistently found to be strongly associated with mentioning at least two danger signs of pregnancy (OR=4.1; 95% CI: 2.4, 7.0), child birth (OR=3.3; 95% CI: 1.8, 6.1), and postpartum period (OR=8.4; 95% CI: 4.5, 15.4). This study indicated that the knowledge level of pregnant women about obstetric danger signs (during pregnancy, childbirth and postpartum period) was low and affected by residential area. Therefore, the identified deficiencies in awareness should be addressed through maternal and child health services by designing an appropriate strategies including provision of targeted information, education and communication.


Predicting symptomatic intracranial haemorrhage after mechanical thrombectomy: the TAG score.
There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ2 and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.


A cell-based screening system for anti-influenza A virus agents.
Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.


The role of women's alcohol consumption in managing sexual intimacy and sexual safety motives.
Two studies, based on an alcohol myopia model, were designed to understand the role of women's alcohol consumption on vulnerability to sexual assault. We predicted that, in a high- conflict social situation, alcohol would make it more difficult to recognize sexual assault risk, lowering intentions to resist sexual advances. In Study 1, women (N = 51) were recruited in bars and classified as having a high (.06 or greater) breath alcohol concentration (BrAC) or low BrAC. They were asked to project themselves into a hypothetical scenario that portrayed interest in establishing an intimate relationship and included mild sexual aggression. In Study 2, women (N = 101) were randomly assigned to an alcohol (target BrAC: .08%), placebo, or no-alcohol condition. They responded at two time points to a similar hypothetical scenario that described mild sexual aggression (Time 1) and serious sexual aggression (Time 2). In Study 1, women with higher BrAC perceived less risk in the scenario and anticipated less resistance than women with low BrAC. In Study 2, similar results were found but only following serious aggression. There were no placebo effects. Both studies suggest that the effects of alcohol on resistance are partially mediated via risk perceptions. Alcohol appears to reduce intentions to resist sexual advances from an acquaintance while increasing intentions to pursue relationship-enhancing behaviors. Effects are not completely explained by an alcohol myopia perspective. Differences in findings between the two studies may reflect differences in methodology, context, or sample.


Corporate environmentalism and environmental innovation.
Several papers have explored the effect of tighter environmental standards on environmental innovation. While mandatory regulation remains the central tenet of US environmental policy, the regulatory landscape has changed since the early 1990s with the increased recourse by federal and state agencies to corporate environmentalism--voluntary pollution prevention (P2) by firms--to achieve environmental improvements. We therefore estimate the effects of voluntary P2 activities on the patenting of environmental technologies by a sample of manufacturing firms. With our panel data of 352 firms over the 1991-2000 period, we adopt an instrumental variable Poisson framework to account for the count nature of patents and the endogeneity of the P2 adoption decision. Our results indicate that the adoption of voluntary P2 activities in the manufacturing sector has led to a statistically and economically significant increase in the number of environmental patents, suggesting that corporate environmentalism can act as a catalyst for investments in cleaner technologies. Our findings are internationally relevant given the increasing ubiquity of corporate environmentalism in both developed and developing economies.


Web addiction in the brain: Cortical oscillations, autonomic activity, and behavioral measures.
Background and aims Internet addiction (IA) was recently defined as a disorder tagging both the impulse control and the reward systems. Specifically, inhibitory deficits and reward bias were considered highly relevant in IA. This research aims to examine the electrophysiological correlates and autonomic activity [skin conductance response (SCR) and heart rate] in two groups of young subjects (N = 25), with high or low IA profile [tested by the Internet Addiction Test (IAT)], with specific reference to gambling behavior. Methods Oscillatory brain activity (delta, theta, alpha, beta, and gamma) and autonomic and behavioral measures [response times (RTs) and error rates (ERs)] were acquired during the performance of a Go/NoGo task in response to high-rewarding (online gambling videos and video games) or neutral stimuli. Results A better performance (reduced ERs and reduced RTs) was revealed for high IAT in the case of NoGo trials representing rewarding cues (inhibitory control condition), probably due to a "gain effect" induced by the rewarding condition. In addition, we also observed for NoGo trials related to gambling and video games stimuli that (a) increased low-frequency band (delta and theta) and SCR and (b) a specific lateralization effect (more left-side activity) delta and theta in high IAT. Discussion Both inhibitory control deficits and reward bias effect were considered to explain IA.


I Want Our Relationship to Last: Strategies That People Employ in Order to Improve Their Intimate Relationships.
Intimate relationships are not always easy to keep. Accordingly, the current research has attempted to identify the strategies that people employ in order to improve their relationships with their partners. In particular, by using open-ended questionnaires in a sample of 219 Greek-speaking participants, we have identified 81 acts that people were likely to perform toward this end. Subsequently, using quantitative research methods in a sample of 511 Greek-speaking participants, we classified these acts into 14 broader relationship enhancement strategies. Trying to understand partners' needs, discussing problems with partners and showing more interest in a partner, were among the most likely to be used strategies. Moreover, we asked a sample of 367 Greek-speaking participants to rate how effective these strategies would be on them, and we found that, trying to understand partners' needs, discussing problems with partners, and showing one's love to a partner, were rated as the most effective strategies. Men and women, and people of different ages, were generally in agreement over what strategies they were willing to use, and how effective these strategies would be on improving their relationship with their partners.


[Distant informational interactions in bacteria].
Exchange of information between bacteria via physical signals, referred to as "distant interactions" (DI), is the subject of this review. All cases of DI reported to date are discussed, as well as the history of these studies and the place of DI in bacterial communication. Bacterial DI are a particular case of DI occurring in nature (in plants, animals, and fungi). Along with the chemical signals of intracellular communications, DI play a significant role in the life of microorganisms, especially during critical periods.