Second generation intramedullary nailing of subtrochanteric femur fractures: a biomechanical study of fracture site motion.
To compare fracture site motion between different second-generation intramedullary nails used to fix subtrochanteric fractures of the proximal femur with and without femoral neck fractures. Nondestructive mechanical testing of four types of femoral intramedullary nails was undertaken to evaluate fracture site motion using a model that simulated single-leg and double-leg stance. Three types of reconstruction nails (the Russell-Taylor Delta [Smith & Nephew, Memphis, TN], the Uniflex [Biomet, Warsaw, IN], Alta CFX [Howmedica-Osteonics, Rutherford, NJ]) and the Long Gamma nail (Howmedica-Osteonics, Rutherford, NJ), each measuring 11 x 380 mm, were inserted in fiberglass composite femurs. Four fracture patterns were studied (transverse subtrochanteric, subtrochanteric with posteromedial wedge comminution, subtrochanteric with one-centimeter gap, and a one-centimeter gap with a subcapital neck fracture). Single-and double-leg stance loading was simulated using a servohydraulic load frame (MTS, Eden Prairie, MN). Two-way analysis of variance and post hoc t tests were used to determine any statistically significant differences between groups. In single-leg stance there were significant differences in coronal plane rotation, shear, and axial translation across the subtrochanteric fracture site between the different nail types and the different fracture patterns (p < 0.001). In double-leg stance there were significant differences in coronal plane rotation and femoral head vertical motion between the different nail types and the different fracture patterns (p < 0.001), and there were significant differences in shear and axial translation between the different fracture patterns (p < 0.001) but not the different nail types (p > 0.05). For simple, well-reduced fractures the choice of implant is not critical. As fracture severity increased (comminution, gap, and combined neck fracture), the choice of implant, particularly with reference to proximal nail dimensions and implant materials, was a significant factor in reducing fracture site motion. Therefore, our laboratory data suggest that when subtrochanteric fractures are unstable (e.g., comminution, segmental bone loss) and early weight bearing is desirable, the choice of implant is critical and should be restricted to implants that allow minimal fracture site motion (Long Gamma and Russell-Taylor).


B lymphocytes: shedding new light on the pathogenesis of systemic sclerosis.
Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity and tissue fibrosis. In patients with SSc, there is a close association between the presence of specific autoantibodies and the development of clinical features. Although it is known that cytokines, including transforming growth factor-beta, can modulate the synthesis of extracellular matrix by fibroblasts, it is not clear how autoimmunity and tissue fibrosis are interrelated. Several recent lines of evidence indicate a potential role for B cells in the development of SSc. CD19 is a critical regulator of B-cell signaling thresholds, and B cells from SSc patients exhibit increased expression of CD19, a molecule that induces SSc-specific autoantibody production in transgenic mice. Both SSc patients and tight-skin mice, a genetic model of SSc, have intrinsic B-cell abnormalities characterized by chronic B-cell activation. Remarkably, CD19 loss or B-cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight-skin mice. Additionally, a recent study revealed a possible beneficial effect of antihuman CD20 antibody (rituximab) therapy for SSc patients. As B cells have a variety of functions, further investigation into the pathogenic roles of B cells, as well as trials of B-cell-targeting therapies, may shed new light on the pathogenesis of SSc.


Efficacy of Intraoperative Blood Salvage in Cerebral Aneurysm Surgery.
The use and effectiveness of intraoperative cell salvage has been analyzed in many surgical specialties. Until now, no data exist evaluating the efficacy of intraoperative cell salvage in cerebral aneurysm surgery. To evaluate the efficacy and cost effectiveness of intraoperative cell salvage in cerebral aneurysm surgery. Data were collected retrospectively for all the patients who underwent cerebral aneurysm surgery at our institution between 2013 and 2019. Routinely, we apply blood salvage through autotransfusion. The cases were divided into a ruptured cerebral aneurysm group and a unruptured cerebral aneurysm group. A total of 241 patients underwent cerebral aneurysm clipping. Of all the cerebral aneurysms, 116 were ruptured and 125 were unruptured and clipped electively. Age, location of the aneurysm, postoperative red blood cell count, intraoperative blood loss, and number of allogenic blood cell transfusions were statistically significantly different between the groups. The autotransfusion of salvaged blood could only be facilitated in eight cases with ruptured cerebral aneurysms and in none with unruptured cerebral aneurysms clipped electively (p < 0.01). Additionally, 35 patients with ruptured cerebral aneurysms and one patient with unruptured cerebral aneurysm required allogenic red blood cell transfusion after surgery, and 71 vs. 2 units of blood were transfused (p < 0.0001). In terms of cost effectiveness, a total of EUR 45,189 in 241 patients was spent to run the autotransfusion system, while EUR 13,797 was spent for allogenic blood transfusion. The use of cell salvage in patients with unruptured cerebral aneurysm, undergoing elective surgery, is not effective.


Swine influenza-like viruses in turkeys: potential source of virus for humans?
Influenza A viruses (subtype H1N1), recently isolated from turkeys in different areas of the United States, were determined to be closely related to strains typically associated with pigs. This conclusion was based on comparisons of H1N1 isolates from pigs, humans, ducks, and turkeys with polyclonal and monoclonal antibodies, RNA-RNA competitive hybridization, and replication studies. One of the H1N1 isolates from turkeys caused influenza in a laboratory technician, who displayed fever, respiratory illness, virus shedding, and seroconversion. These results suggest that turkeys as well as pigs are involved in the maintenance of these viruses and their transmission to humans.


Cadmium-induced neurotoxicity: still much ado.
Cadmium (Cd) is a highly toxic heavy metal that accumulates in living system and as such is currently one of the most important occupational and environmental pollutants. Cd reaches into the environment by anthropogenic mobilization and it is absorbed from tobacco consumption or ingestion of contaminated substances. Its extremely long biological half-life (approximately 20-30 years in humans) and low rate of excretion from the body cause cadmium storage predominantly in soft tissues (primarily, liver and kidneys) with a diversity of toxic effects such as nephrotoxicity, hepatotoxicity, endocrine and reproductive toxicities. Moreover, a Cd-dependent neurotoxicity has been also related to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and multiple sclerosis. At the cellular level, Cd affects cell proliferation, differentiation, apoptosis and other cellular activities. Among all these mechanisms, the Cd-dependent interference in DNA repair mechanisms as well as the generation of reactive oxygen species, seem to be the most important causes of its cellular toxicity. Nevertheless, there is still much to find out about its mechanisms of action and ways to reduce health risks. This article gives a brief review of the relevant mechanisms that it would be worth investigating in order to deep inside cadmium toxicity.


Firefighters Have Cerebral Blood Flow Reductions in the Orbitofrontal and Insular Cortices That are Associated with Poor Sleep Quality.
To investigate the cerebral blood flow (CBF) alterations associated with poor sleep quality and memory performance in firefighters. Thirty-seven firefighters (the FF group) and 37 non-firefighter controls (the control group) with sleep complaints were enrolled in this study. We performed brain arterial spin labeling perfusion magnetic resonance imaging (MRI) and compared the CBF between the two groups using whole-brain voxel-wise analyses. Self-reported sleep problems and actigraphy-measured sleep parameters, including the sleep efficiency, wake after sleep onset (WASO), total sleep time, and sleep latency, were assessed. Spatial working memory and learning performances were evaluated on the day of the MRI scan. The FF group, relative to the control group, had lower CBF in the right hemispheric regions: Middle temporal/lateral occipital, orbitofrontal, and insular cortices. Lower CBF in the right orbitofrontal cortex was linearly associated with poor sleep quality, as indicated by lower sleep efficiency and longer WASO. The CBF of the right insular cortex was also associated with longer WASO. Despite comparable degrees of self-reported sleep problems between the two groups, the FF group had lower sleep efficiency and longer WASO in the actigraphy, and lower spatial working memory and learning performance, relative to the control group. Poor sleep efficiency was linearly associated with lower spatial working memory performance. These results demonstrated an association of poor sleep quality with decreased brain perfusion in the right orbitofrontal and insular cortices, as well as with reduced working memory performance.


Gamma-Ray Dose From an Overhead Plume.
Standard plume models can underestimate the gamma-ray dose when most of the radioactive material is above the heads of the receptors. Typically, a model is used to calculate the air concentration at the height of the receptor, and the dose is calculated by multiplying the air concentration by a concentration-to-dose conversion factor. Models indicate that if the plume is emitted from a stack during stable atmospheric conditions, the lower edges of the plume may not reach the ground, in which case both the ground-level concentration and the dose are usually reported as zero. However, in such cases, the dose from overhead gamma-emitting radionuclides may be substantial. Such underestimates could impact decision making in emergency situations. The Monte Carlo N-Particle code, MCNP, was used to calculate the overhead shine dose and to compare with standard plume models. At long distances and during unstable atmospheric conditions, the MCNP results agree with the standard models. At short distances, where many models calculate zero, the true dose (as modeled by MCNP) can be estimated with simple equations.


Key Factors for Successful General Anesthesia of Obese Adult Patients.
To study nurse anesthetists' experiences of key factors for successful airway management in general anesthesia of adult obese patients. The study was a qualitative observational study with a descriptive approach. Eight semistructured interviews were conducted. Data were analyzed using the critical incident technique. Five key factors for successful general anesthesia of adult obese patients were identified. These factors were preparing and planning the anesthesia, optimizing patient position, optimizing ventilation through proper preoxygenation and increasing positive end-expiratory pressure, quickly securing the airway, and working in teams. Knowledge of key factors that facilitate and improve the anesthesia care of obese patients is important to provide safe and quality anesthesia to this patient group as obese patients often have small margins and urgent situations can quickly arise. This knowledge enables the nurse anesthetist to be one step ahead and to be ready to take action if complications occur.


Group sex events and HIV/STI risk in an urban network.
To describe: (a) the prevalence and individual and network characteristics of group sex events (GSEs) and GSE attendees; and (b) HIV/sexually transmitted infection (STI) discordance among respondents who said they went to a GSE together. In a sociometric network study of risk partners (defined as sexual partners, persons with whom respondents attended a GSE, or drug injection partners) in Brooklyn, NY, we recruited a high-risk sample of 465 adults. Respondents reported on GSE attendance, the characteristics of GSEs, and their own and others' behaviors at GSEs. Sera and urines were collected, and STI prevalence was assayed. Of the 465 participants, 36% had attended a GSE in the last year, 26% had sex during the most recent of these GSEs, and 13% had unprotected sex there. Certain subgroups (hard drug users, men who have sex with men, women who have sex with women, and sex workers) were more likely to attend and more likely to engage in risk behaviors at these events. Among 90 GSE dyads, in which at least 1 partner named the other as someone with whom they attended a GSE in the previous 3 months, STI/HIV discordance was common [herpes simplex virus (HSV-2): 45% of dyads, HIV: 12% of dyads, and chlamydia: 21% of dyads]. Many GSEs had 10 or more participants, and multiple partnerships at GSEs were common. High attendance rates at GSEs among members of large networks may increase community vulnerability to STI/HIV, particularly because network data show that almost all members ofa large sociometric risk network either had sex with a GSE attendee or had sex with someone who had sex with a GSE attended. Self-reported GSE attendance and participation were common among this high-risk sample. STI/HIV discordance among GSE attendees was high, highlighting the potential transmission risk associated with GSEs. Research on sexual behaviors should incorporate measures of GSE behaviors as standard research protocol. Interventions should be developed to reduce transmission at GSEs.


The sequence, organization, and evolution of the Locusta migratoria mitochondrial genome.
The sequencing of the cloned Locusta migratoria mitochondrial genome has been completed. The sequence is 15,722 bp in length and contains 75.3% A+T, the lowest value in any of the five insect mitochondrial sequences so far determined. The protein coding genes have a similar A+T content (74.1%) but are distinguished by a high cytosine content at the third codon position. The gene content and organization are the same as in Drosophila yakuba except for a rearrangement of the two tRNA genes tRNAlys and tRNAasp. The A+T-rich region has a lower A+T nucleotide content than in other insects, and this is largely due to the presence of two G+C-rich 155-bp repetitive sequences at the 5'end of this section and the beginning of the adjacent small rRNA gene. The sizes of the large and small rRNA genes are 1,314 and 827 bp, respectively, and both sequences can be folded to form secondary structures similar to those previously predicted for Drosophila. The tRNA genes have also been modeled and these show a strong resemblance to the dipteran tRNAs, all anticodons apparently being conserved between the two species. A comparison of the protein coding nucleotide sequences of the locust DNA with the homologous sequences of five other arthropods (Drosophila yakuba, Anopheles quadrimaculatus, Anopheles gambiae, Apis mellifera, and Artemia franciscana) was performed. The amino acid composition of the encoded proteins in Locusta is similar to that of Drosophila, with a Dayhoff distance twice that of the distance between the fruit fly and the mosquitoes. A phylogenetic analysis revealed the locust genes to be more similar to those of the Dipterans than to those of the honeybee at both the nucleotide and amino acid levels. A comparative analysis of tRNA orders, using crustacean mtDNAs as outgroups, supported this. This high level of divergence in the Apis genome has been noted elsewhere and is possibly an effect of directional mutation pressure having resulted in an accelerated pattern of sequence evolution. If the general assumption that the Holometabola are monophyletic holds, then these results emphasize the difficulties of reconstructing phylogenies that include lineages with variable substitution rates and base composition biases. The need to exercise caution in using information about tRNA gene orders in phylogenetic analysis is also illustrated. However, if the honeybee sequence is excluded, the correspondence between the other five arthropod sequences supports the findings of previous studies which have endorsed the use of mtDNA sequences for studies of phylogeny at deep levels of taxonomy when mutation rates are equivalent.


The Effectiveness of Personal Hygiene Practices on Non-Cuffed Central Vein Catheter-Related Infection in Patients Undergoing Hemodialysis: A Randomized Controlled Trial.
Infection of the internal jugular vein (IJV) catheter continues to be a common cause of death in patients with end-stage renal disease undergoing hemodialysis (HD). The present study aimed to evaluate the effectiveness of personal hygiene on the incidence of IJV catheter-related bloodstream infection (CRBSI). A randomized, controlled, parallel, and non-inferiority trial was conducted on patients initiated on maintenance HD via right IJV catheter. Patients were randomly allocated to control and intervention group via computer-generated random table. Intervention package for the intervention group included hand washing (2-4 hourly and whenever visibly dirty), feet washing (12 hourly), and axillary shave (at any point during the study, no hair growth in axilla). Patients were provided with a pamphlet and reinforced to continue package till IJV catheter was in situ. Patients were followed up twice a week for one month from the date of catheter insertion for the incidence of CRBSI. The primary outcome of the study was percentage of patients free from CRBSI. On intention-to-treat analysis, the percentage of patients without CRBSI was 53.7% and 29.3% in the intervention and control arm, respectively [P = 0.04; 25.12% (1.43-45.28%)]. Positive blood cultures were higher in control (73.3%) as compared to the intervention group (28.6%) (P = 0.19). Personal hygiene interventions are an effective method to reduce the incidence of CRBSIs among population undergoing maintenance HD via non-cuffed IJV catheter.


Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways.
Pulmonary hypertension is a well recognised complication of chronic hypoxic lung diseases, which are among the most common causes of death and disability worldwide. Development of pulmonary hypertension independently predicts reduced life expectancy. In chronic obstructive pulmonary disease, long-term oxygen therapy ameliorates pulmonary hypertension and greatly improves survival, although the correction of alveolar hypoxia and pulmonary hypertension is only partial. Advances in understanding of the regulation of vascular smooth muscle tone show that chronic vasoconstriction plays a more important part in the pathogenesis of hypoxic pulmonary hypertension than previously thought, and that structural vascular changes contribute less. Trials of existing vasodilators show that pulmonary hypertension can be ameliorated and systemic oxygen delivery improved in carefully selected patients, although systemic hypotensive effects limit the doses used. Vasoconstrictor pathways that are selective for the pulmonary circulation can be blocked to reduce hypoxic pulmonary hypertension without causing systemic hypotension, and thus provide potential targets for novel therapeutic strategies.


Nano-quercetin mitigates triazophos-induced testicular toxicity in rats by suppressing oxidative stress and apoptosis.
The present study was designed to evaluate the testicular toxicity of triazophos in rats and to check the ameliorative effect of nano-quercetin against triazophos-induced toxicity. Nano-quercetin was synthesized from quercetin and characterized. Male Wistar rats were divided into seven groups. The control group received olive oil as a vehicle orally. The high-dose triazophos group and the low-dose triazophos group received 1/10th LD50 of triazophos (7.6 mg/kg) and 1/20th LD50 of triazophos (3.8 mg/kg), respectively. Two groups of animals were dosed with quercetin and nano-quercetin, both at 50 mg/kg body weight orally. The final two groups received high-dose triazophos with co-administration of quercetin and nano-quercetin, respectively. Triazophos disrupted the male endocrine axis by reducing the levels of steroidogenic enzymes 3-β-HSD and 17-β-HSD in testicular cells, further reducing FSH and testosterone. Also, triazophos increased the reactive oxygen species, induced lipid peroxidation, decreased the mitochondrial membrane potential, and elevated the number of apoptotic cells in rat testes. Nano-quercetin ameliorated the testicular oxidative stress and apoptotic and endocrine parameters more efficiently than quercetin. Besides, nano-quercetin alleviated the histopathological and biochemical alterations of triazophos. It is concluded that nano-quercetin has higher anti-oxidant efficacy than quercetin in protecting rats against triazophos-induced testicular toxicity.


Behavioral and cognitive effects of methylxanthines. A meta-analysis of theophylline and caffeine.
Theophylline has been extensively studied as a treatment of asthma. However, some studies have suggested that theophylline may precipitate adverse behavioral and cognitive effects on children. Other reports have evaluated the effects of caffeine, another commonly used methylxanthine, as a treatment of attention-deficit hyperactivity disorder. To present a meta-analysis of research on the behavioral and cognitive effects of methylxanthines in children. The meta-analyses were conducted on 12 studies of theophylline and nine studies of caffeine that met inclusion criteria. In contrast to popular beliefs and earlier scientific reports, meta-analyses of controlled studies did not indicate that either theophylline or caffeine resulted in significant deleterious effects on cognition or behavior. In fact, there was a small, positive effect on parental report of externalizing behavior for both methylxanthines. There is little evidence to suggest that methylxanthines have adverse cognitive or behavioral effects on children. Questions remain with regard to the identification and determinants of either responsive or sensitive subgroups, dose-response relationships, and the effects of parent-teacher expectancies on behavioral ratings.


Protein Mediated Oxidative Stress in Patients with Diabetes and its Associated Neuropathy: Correlation with Protein Carbonylation and Disease Activity Markers.
Free radicals have been implicated as Diabetes Mellitus (DM) contributors in type 2 DM and its associated Diabetes Mellitus Neuropathy (DMN). However, the potential for protein mediated oxidative stress to contribute disease pathogenesis remains largely unexplored. To investigate the status and contribution of protein mediated oxidative stress in patients with DM or DMN and to explore whether oxidative protein modification has a role in DM progression to DM associated neuropathy. Sera from 42 DM and 37 DMN patients with varying levels of disease activities biomarkers (HbA1C, patients' age or disease duration) and 21 age- and sex-matched healthy controls were evaluated for serum levels of protein mediated oxidative stress. Serum analysis showed significantly higher levels of protein carbonyl contents in both DM and DMN patients compared with healthy controls. Importantly, not only was there an increased number of subjects positive for protein carbonylation, but also the levels of protein carbonyl contents were significantly higher among DM and DMN patients, whose HbA1C were ≥8.8 as compared with patients with lower HbA1C (HbA1C<8.8). Similar pattern of protein carbonyls formation was also observed with patients' ages or with patient's disease durations, suggesting a possible relationship between protein oxidation and disease progression. Furthermore, sera from DMN patients had higher levels of protein carbonylation compared with non-neuropathic DM patients' sera, suggesting an involvement of protein oxidation in the progression of diabetes to diabetes neuropathy. These findings support an association between protein oxidation and DM or DMN progression. The stronger response observed in patients with higher HbA1C or patients' ages or disease durations suggests, that protein mediated oxidative stress may be useful in evaluating the progression of DM and its associated DMN and in elucidating the mechanisms of these disorders pathogenesis.


Suggested Procedures for the Reproducible Synthesis of Poly(d,l-lactide-co-glycolide) Nanoparticles Using the Emulsification Solvent Diffusion Platform.
Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immisci-ble solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproduc-ibility. This study presents a simple and robust procedure for the preparation of PLGA nanoparti-cles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering). The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA na-noparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between -30 and +30 mV), with relatively narrow polydispersity. Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to sev-eral existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.


Fine needle aspiration cytology of adrenocortical carcinoma--case report.
A 49-year-old woman presented for hirsutism, deep voice and hypertension. Ultrasonography (US) revealed a solitary tumor mass, eight cm in size, of the right adrenal gland. Laboratory tests showed it to be a hormonally active, androgen secreting tumor (elevated testosterone level), which was consistent with the clinical picture of the disease. After histopathological analysis tumor was signed out as adrenocortical carcinoma, a low risk carcinoma according to Weiss' classification. One year later on regular follow up, US revealed a suspicious growth measuring 65 x 43 mm in the projection of the lower pole of the right kidney. The finding was verified by computerized tomography and the patient was reoperated on. Exploration revealed secondary growth in the region of greater omentum, without infiltration of adjacent organs. Histopathologic analysis confirmed metastatic ACC. 8 months after the second operation and after 6 chemotherapy cycles according to EAP protocol, control CT showed enlarged para-aortic lymph nodes and a node along the upper pole of the right kidney. Cytologic puncture was performed. Cytologic opinion was recidive of primary malignant disease. ACC is a rare malignant epithelial tumor of adrenal cortical cells, with high malignant potential. Morphologically (histopathology and cytology), differential diagnosis includes adenoma on the one hand, and renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) on the other hand. A combined evaluation of clinical features, size or weight, microscopic appearance, immunohistochemical and molecular genetic data is necessary to ensure a correct diagnosis. The purpose of this case report is to present clinical and cytomorphologic features of our case of adrenocortical carcinoma which is very rare in cytology practice.


Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.
Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.


Inhalational, gastrointestinal, and cutaneous anthrax in children: a systematic review of cases: 1900 to 2005.
To systematically review all published case reports of children with anthrax to evaluate the predictors of disease progression and mortality. Fourteen selected journal indexes (1900-1966), MEDLINE (1966-2005), and the bibliographies of all retrieved articles. Case reports (any language) of anthrax in persons younger than 18 years published between January 1, 1900, and December 31, 2005. Main Exposures Cases with symptoms and culture or Gram stain or autopsy evidence of anthrax infection. Disease progression, treatment responses, and mortality. Of 2499 potentially relevant articles, 73 case reports of pediatric anthrax (5 inhalational cases, 22 gastrointestinal cases, 37 cutaneous cases, 6 cases of primary meningoencephalitis, and 3 atypical cases) met the inclusion criteria. Only 10% of the patients were younger than 2 years, and 24% were girls. Of the few children with inhalational anthrax, none had nonheadache neurologic symptoms, a key finding that distinguishes adult inhalational anthrax from more common illnesses, such as influenza. Overall, observed mortality was 60% (3 of 5) for inhalational anthrax, 65% (13 of 20) for gastrointestinal anthrax, 14% (5 of 37) for cutaneous anthrax, and 100% (6 of 6) for primary meningoencephalitis. Nineteen of the 30 children (63%) who received penicillin-based antibiotics survived, and 9 of the 11 children (82%) who received anthrax antiserum survived. The clinical presentation of children with anthrax is varied. The mortality rate is high in children with inhalational anthrax, gastrointestinal anthrax, and anthrax meningoencephalitis. Rapid diagnosis and effective treatment of anthrax in children requires recognition of the broad spectrum of clinical presentations of pediatric anthrax.


Spatio-temporal variability of water pollution by chlordecone at the watershed scale: what insights for the management of polluted territories?
Chlordecone, applied on soils until 1993 to control banana weevil, has polluted water resources in the French West Indies for more than 40 years. At the watershed scale, chlordecone applications were not homogenous, generating a spatial heterogeneity of the pollution. The roles of climate, hydrology, soil, agronomy, and geology on watershed functioning generate a temporal heterogeneity of the pollution. This study questions the interactions between practices and the environment that induce such variability. We analyzed hydrological and water pollution datasets from a 2-year monitoring program on the Galion watershed in Martinique (French West Indies). We conjointly analyzed (i) weekly chlordecone (CLD) concentration monitored on 3 river sampling sites, (ii) aquifer piezometric dynamics and pollutions, and (iii) agricultural practices on polluted soils. Our results showed that chlordecone pollution in surface waters are characterized by annual trends and infra-annual variations. Aquifers showed CLD concentration 10 times higher than surface water, with CLD concentration peaks during recharge events. We showed strong interactions between rainfall events and practices on CLD pollution requiring a systemic management approach, in particular during post-cyclonic periods. Small sub-watershed with high CLD pollution appeared to be a substantial contributor to CLD mass transfers to the marine environment via rivers and should therefore receive priority management. We suggest increasing stable organic matter return to soil as well as external input of organic matter to reduce CLD transfers to water. We identified hydrological conditions-notably drying periods-and tillage as the most influential factors on CLD leaching. In particular, tillage acts on 3 processes that increases CLD leaching: organic matter degradation, modification of water paths in soil, and allophane clay degradation.


COVID-19-related organ dysfunction and management strategies on the intensive care unit: a narrative review.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence, and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume severe respiratory failure centre in London.


Managing somatization phenomena in primary care.
Patients communicating psychological distress in the form of somatic symptoms and seeking medical care for them pose difficult diagnostic and treatment dilemmas for the primary care physician. Somatization may be conceptualized as an illness-focused behavior style, with multiple etiologies, rather than a single psychiatric disorder. Somatizing behavior is associated with emotional distress, cognitive-perceptual abnormalities, and socially learned illness behaviors. Although recognition of the somatizing patient begins with thorough medical evaluation, assessment should also include careful examination of social history and the affective meaning of symptoms. Management strategies will vary according to the etiology of the psychiatric diagnosis associated with physical symptoms; however, the essential element is provision of a long-term supportive relationship with a physician, who provides effective monitoring of physical and mental health status, appropriate emotional support, and reassurance concerning symptoms.


Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.
Neurodegenerative diseases seriously affect patients' physical and mental health, reduce their quality of life, and impose a heavy burden on society. However, their treatment remains challenging. Therefore, exploring factors potentially related to the pathogenesis of neurodegenerative diseases and improving their diagnosis and treatment are urgently needed. Recent studies have shown that P2 × 7R plays a crucial role in regulating neurodegenerative diseases caused by neuroinflammation. P2 × 7R is an adenosine 5'-triphosphate ligand-gated cation channel receptor present in most tissues of the human body. An increase in P2 × 7R levels can affect the progression of neurodegenerative diseases, and the inhibition of P2 × 7R can alleviate neurodegenerative diseases. In this review, we comprehensively describe the biological characteristics (structure, distribution, and function) of this gene, focusing on its potential association with neurodegenerative diseases, and we discuss the pharmacological effects of drugs (P2 × 7R inhibitors) used to treat neurodegenerative diseases.


Digestible sulfur amino acid requirement of starting turkeys.
Three experiments (a total of 1,020 poults) were conducted to determine the digestible sulfur amino acid (SAA) requirement for female turkey poults during the starter period. Poults were fed a standard corn-soybean meal diet (PC) that met or exceeded NRC recommendations (28% CP, 3,172 kcal MEn/kg) for 1 wk and were then randomly assigned to treatments until 22 d (Experiment 2 and 3) or 23 d (Experiment 1) of age. Dietary treatments included the PC diet and seven or nine titrated levels of methionine added to a basal corn-soybean meal diet, for a total of 0.50 to 1.33% total digestible SAA. The basal diet contained 18.4% intact crude protein. All diets contained 3,171 kcal MEn/kg. The true digestible SAA content of the basal diet without methionine additions was 0.50% based on digestibility assays of the corn and soybeans with cecectomized turkeys. Diets were formulated to contain 1.40% digestible lysine. Other amino acids were maintained at levels in relation to lysine based on previous research with turkeys and the Illinois Ideal Chick Protein. Broken-line analysis suggests that the digestible SAA requirement for female turkeys during the starter period is 0.76% for optimum body weight gain and 0.75% for optimal feed:gain at the energy levels used in these studies.


Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction.
Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.


Open capsular repair without bone block for recurrent anterior shoulder instability in patients with and without bony defects of the glenoid and/or humeral head.
Bony defects of the humeral head and glenoid have been associated with high failure rates after arthroscopic stabilization for anterior instability. Biomechanical studies have indicated that such lesions reduce stability and may predispose to failure and motion loss after capsular repair. The present investigation was designed to evaluate the effect of bony deficiency of the glenoid and/or humeral head on recurrence rates with a conventional open technique of anterior stabilization without a bone block. Case series; Level of evidence, 4. One hundred nineteen consecutive patients with recurrent anterior shoulder instability were treated by a single surgeon with an open anterior stabilization procedure. Patients were studied prospectively for recurrent instability after the presence and size of bony defects of the humeral head and/or glenoid were recorded during an arthroscopic examination before the open procedure. One hundred three patients (mean age, 20.7 years), including 98 men and 5 women, were available for 2-year minimum follow-up. Eighty-three of the patients participated in contact athletics. Eighty-four percent of the patients had demonstrable Hill-Sachs lesions at the time of arthroscopy (27% "engaging" and 57% "nonengaging"). Fourteen percent had deficiency of the anterior glenoid, 9% had large (Rowe classification) defects of the humeral head, and 4% had severe (>20%) defects of the glenoid. The overall recurrence rate was 2%. Both recurrences were noted in patients with Hill-Sachs lesions, but the recurrence rate in patients with Hill-Sachs lesions was not significantly higher (P = .71). There was 1 recurrence among the 9 patients with large defects of the humeral head (P = .17). Patients with engaging Hill-Sachs lesions did not have a statistically significant increase in recurrence (4%) (P = .47). There were no recurrences in patients with glenoid deficiency. Patients with large defects of the glenoid lost a mean of 7 degrees of external rotation (P = .001) when compared with the remaining population (12 degrees vs 5 degrees ). Patients with large defects of the humeral head lost a mean of 4 degrees more external rotation (P = .003) when compared with the remaining population (9 degrees vs 5 degrees ). Two patients in the series lost > or =20 degrees of external rotation. When contact athletes were isolated as a population, there were no statistically significant increases in recurrence due to the presence of bony lesions of the glenoid or humeral head. Bony defects of the humeral head or glenoid did not appear to result in a statistically significant increase in the risk of recurrence with conventional open techniques of stabilization. Large defects on either side of the joint were uncommon in the study population. Bone-block or grafting procedures do not appear to be necessary to restore stability in the majority of patients with bone loss. Although the loss of external rotation in patients with large defects is a relative cause for concern, the author recommends open capsular repair as the primary method of treatment given the high complication rate historically associated with bone-block techniques.


Absence of asparagine-linked oligosaccharides from glycoprotein D of herpes simplex virus type 1 results in a structurally altered but biologically active protein.
Glycoprotein D (gD) of herpes simplex virus contains three utilized sites (Asn-X-Ser/Thr) for addition of asparagine-linked carbohydrates (N-CHO). Previously, we used oligonucleotide-directed mutagenesis to alter serine or threonine residues to alanine at each N-CHO addition site. Studies with monoclonal antibodies showed that a mutant protein lacking all three sites (now designated AAA) was structurally altered because of the amino acid change at residue 96 as well as the absence of the N-CHO. In this study, we constructed additional single mutations at site 1 (residues 94 and 96) and found that in most cases, the amino acid change itself adversely affected the conformation of gD. However, changing asparagine 94 to glutamine (Q) at site 1 had the least effect on gD. We constructed a second triple mutant, QAA, which lacked all three N-CHO signals. The antigenic conformation of QAA was similar to that of gD produced in the presence of tunicamycin (TM-gD). However, binding of MAbs to the AAA protein or to single mutants altered at site 1 was reduced compared with TM-gD. Wild-type gD and QAA proteins were equally susceptible to digestion by trypsin or Staphylococcus aureus V8 protease. In contrast, the AAA protein was more sensitive to trypsin but less sensitive to V8, again suggesting conformational alterations of the AAA protein. Despite what appeared to be large changes in structure, each mutant complemented the infectivity of a virus lacking gD (F-gD beta). We conclude that the N-CHO and amino acids at N-CHO site 1 play an important role in forming and/or maintaining gD structure, but none of the N-CHO are required for gD to function in the complementation assay.


A tumor-targeting probe based on a mitophagy process for live imaging.
A glucosamine modified near-infrared cyanine dye CyT sensitive to pH was synthesized. Due to the different pH values of mitochondria and autolysosomes, the probe can simultaneously investigate mitochondria and autolysosomes in living cells. Moreover, due to the introduction of glucosamine groups, this fluorescent probe can be applied for tumor targeted imaging.


[Immunocytochemical localization of alpha-melanotropin in bovine placenta].
The immunocytochemical study of the bovine placenta has demonstrated the presence of cells containing alphamelanotropic hormones, in the decidual epithelium, since the 4th month of pregnancy. The number and the staining intensity of those cells grow up with the placental development. Since the 6th month, we observed the immunoreactional presence of cells in the foetal chorionic epithelium.


Clinical correlates of depressive symptoms in familial Parkinson's disease.
Depression is one of the most common nonmotor complications of Parkinson's disease (PD) and has a major impact on quality of life. Although several clinical factors have been associated with depression in PD, the relationship between depression and stage of illness as well as between depression and degree of disability remains controversial. We have collected clinical data on 1,378 PD cases from 632 families, using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (activities of daily living) & III (motor), the Mini-Mental State Exam, the Geriatric Depression Scale (GDS), and the Blessed Functional Activity Scale (Blessed). Analyses were performed using the 840 individuals with verified PD and without evidence of cognitive decline. Logistic regression was used to identify study variables that individually and collectively best predicted the presence of depressive symptoms (GDS >or= 10). After correcting for multiple tests, depressive symptoms were significantly associated with Hoehn and Yahr stage and other clinical measures but not with any genetic variant (parkin, LRRK2, APOE). The Blessed score, education, presence of a first degree relative with signs of depression, and UPDRS Part II were found to best predict depressive symptomatology (R(2) = 0.33; P = 4 x 10(-48)). Contrary to several reports, the results from this large study indicate that stage of illness, motor impairment, and functional disability are strongly correlated with depressive symptoms.


Predictors of drop-out in an Internet study of men who have sex with men.
Researchers have suggested the rising use of Internet to look for sexual partners is an important contributor to the resurgence in the incidence of sexually transmitted diseases (STDs) and HIV among men who have sex with men (MSM). Web-based samples of this population reflect good geographical diversity for research, but a high drop-out rate creates a significant potential for bias, misrepresentation of population, and misinterpretation of data. This study aims to describe the demographics of an Internet sample of MSM and the differences between the completers and drop-outs. We analyzed data obtained from a cross-sectional study using an online self-administered questionnaire for males, 18 years or older, who were current U.S. residents, and who had sex with men. Of 850 eligible participants, 404 (47.5%) were labeled as drop-outs. The completers and drop-outs differed significantly in age, education, country of birth, health insurance, time spent on Internet, location of computer access, types of sites visited, profile information, last homosexual experience, methods used to determine safety of partners, and type of sexual activities on real meets. Almost half of the participants dropped out before completion. Although the two groups did not differ in many of the items, high drop-out rates are a threat to the validity of such data. Drop-out constitutes a significant bias in Internet sexuality research and must be considered while interpreting the results of such studies.


Characterization of Odorous and Potentially Harmful Substances in Artists' Acrylic Paint.
Acrylic paints are fast drying water based paints that are easy to handle and have a high covering capacity and therefore possess many characteristics that make them applicable in a wide range of applications, such as varnishes or artists paints. Due to their emitted volatile organic compounds, these paints are associated with different work-related diseases and are known to emit an unpleasant odor. In this study six acrylic paints for artists were analyzed regarding their odor-active constituents. Therefore, the samples were extracted with dichloromethane and purified via solvent assisted flavor evaporation prior to analysis of the distillates by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), and GC-GC-MS/O. Additionally all samples were sensorially characterized by a trained sensory panel. The identified odorous substances were primarily benzene derivatives (styrene, ethylbenzene, allylbenzene, propylbenzene) with a plastic-like, aromatic and solvent-like odor. Thereby, polycyclic aromatic hydrocarbons (naphthalene, indane, and tetralin derivatives) contributed to the plastic- and mothball-like odor whereas acrylic monomers (butyl acrylate) were found to be responsible for a mushroom-like and geranium leaf-like odor. As most of these substances are also known to be harmful, a reduction or replacement of these substances by less toxic and non-odor active ingredients is likely to turn out to be advisable in order to reduce the odor and potential negative physiological effects of paints.


Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations: evidence from three cohorts matched on renal function.
Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P < .0001), males 1.42 ± 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts. Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.


The role of AMPK in controlling metabolism and mitochondrial biogenesis during exercise.
Insulin resistance is associated with defects in skeletal muscle fatty acid (FA) metabolism that contribute to the development of type 2 diabetes. Endurance exercise increases FA and glucose metabolism, muscle mitochondrial content and insulin sensitivity. In skeletal muscle, basal rates of FA oxidation are dependent on AMP-activated protein kinase (AMPK) phosphorylation of acetyl-CoA carboxylase 2, the rate-limiting enzyme controlling the production of the metabolic intermediate malonyl-CoA. Likewise, AMPK is essential for maintaining muscle mitochondrial content in untrained mice; effects that may be mediated through regulation of the peroxisome proliferator-activated receptor γ co-activator-1α. However, the importance of AMPK in regulating glucose and FA uptake, FA oxidation and mitochondrial biogenesis during and following endurance exercise training is not fully understood. A better understanding of the mechanisms by which endurance exercise regulates substrate utilization and mitochondrial biogenesis may lead to improved therapeutic and preventative strategies for the treatment of insulin resistance and type 2 diabetes.


Temporal development and collapse of an Arctic plant-pollinator network.
The temporal dynamics and formation of plant-pollinator networks are difficult to study as it requires detailed observations of how the networks change over time. Understanding the temporal dynamics might provide insight into sustainability and robustness of the networks and how they react to environmental changes, such as global warming. Here we study an Arctic plant-pollinator network in two consecutive years using a simple mathematical model and describe the temporal dynamics (daily assembly and disassembly of links) by random mechanisms. We develop a mathematical model with parameters governed by the probabilities for entering, leaving and making connections in the network and demonstrate that A. The dynamics is described by very similar parameters in both years despite a strong turnover in the composition of the pollinator community and different climate conditions, B. There is a drastic change in the temporal behaviour a few days before the end of the season in both years. This change leads to the collapse of the network and does not correlate with weather parameters, C. We estimate that the number of available pollinator species is about 80 species of which 75-80% are observed in each year, D. The network does not reach an equilibrium state (as defined by our model) before the collapse set in and the season is over. We have shown that the temporal dynamics of an Arctic plant-pollinator network can be described by a simple mathematical model and that the model allows us to draw biologically interesting conclusions. Our model makes it possible to investigate how the network topology changes with changes in parameter values and might provide means to study the effect of climate on plant-pollinator networks.


Practical guide on home health in heart failure patients.
Chronic heart failure is a common condition affecting up to 15 million people in the extended Europe. Heart failure is burdensome and costly for patients in terms of decreased quality of life and poor prognosis, and it is also costly for society. Better integrated care is warranted in this population and specialised heart failure care can save costs and improve the quality of care. However, only a few European countries have implemented specialised home care and offered this to a larger number of patients with heart failure. We developed a guide on Home Health in Heart Failure patients from a literature review, a survey of heart failure management programs, the opinion of researchers and practitioners, data from clinical trials and a reflection of an international expert meeting. IN INTEGRATED HOME CARE FOR HEART FAILURE PATIENTS, IT IS ADVISED TO CONSIDER THE FOLLOWING COMPONENTS: integrated multidisciplinary care, patient and partner participation, care plans with clear goals of care, patient education, self-care management, appropriate access to care and optimised treatment. We summarised the state of the art of home-based care for heart failure patients in Europe, described the typical content of such care to provide a guide for health care providers.


Phenotypical Sub-setting of the First Episode of Severe Viral Respiratory Infection Based on Clinical Assessment and Underlying Airway Disease: A Pilot Study.
Introduction: Viral bronchiolitis is a term often used to group all infants with the first episode of severe viral respiratory infection. However, this term encompasses a collection of different clinical and biological processes. We hypothesized that the first episode of severe viral respiratory infection in infants can be subset into clinical phenotypes with distinct outcomes and underlying airway disease patterns. Methods: We included children (≤2 years old) hospitalized for the first time due to PCR-confirmed viral respiratory infection. All cases were categorized based on primary manifestations (wheezing, sub-costal retractions and hypoxemia) into mild, hypoxemia or wheezing phenotypes. We characterized these phenotypes using lung-X-rays, respiratory outcomes and nasal protein levels of antiviral and type 2 cytokines (IFNγ, IL-10, IL-4, IL-13, IL-1β, and TNFα). Results: A total of 50 young children comprising viral respiratory infection cases (n = 41) and uninfected controls (n = 9) were included. We found that 22% of viral respiratory infection cases were classified as mild (n = 9), 39% as hypoxemia phenotype (n = 16) and 39% as wheezing phenotype (n = 16). Individuals in the hypoxemia phenotype had more lung opacities, higher probability of PICU admission and prolonged hospitalizations. Subjects in the wheezing phenotype had higher probability of recurrent sick visits. Nasal cytokine profiles showed that individuals with recurrent sick visits in the wheezing phenotype had increased nasal airway levels of type 2 cytokines (IL-13/IL-4). Conclusion: Clinically-based classification of the first episode of severe viral respiratory infection into mild, hypoxemia or wheezing phenotypes provides critical information about respiratory outcomes, lung disease patterns and underlying airway immunobiology.


Understanding cultural diversity through a student exchange program.
Nursing curriculum must include multicultural experiences to prepare nurses to work with the nation's ethnically diverse population. To meet this need, a pilot project was instituted between two Bachelor's of Science in Nursing (BSN) programs. It was hypothesized that students could develop new cultural perspectives by experiencing nursing with different ethnic groups. Two senior students from each institution were selected for the experience. The exchange program provided them with opportunities to assess and care for health problems in aggregates and families with whom they might not have had practice. The authors recommend that these types of programs be encouraged to introduce students to practice in settings and with cultures other than their own.


[Refraction ring-shaped tunnel keratoplasty in the correction of high-degree myopia].
A new method has been developed for diminishing the myopic eye refraction: refraction ring-like tunnel keratoplasty. The technique is simple, virtually atraumatic, and highly effective. It has been introduced in clinical practice. The method consists in placing a ring-shaped collagen thread ++para-centrally in the surface layers of the cornea. Experimental studies of refraction ring-like tunnel keratoplasty included staining the sections with hematoxylin and eosin and Kampos' silver impregnation. Changes in the transplant shape and the host cornea, as well as the terms of their innervation were studied in histologic sections. The results of 32 surgeries are analyzed. Essential reduction of the refraction in the myopic eye--12.0-15.0 diopters, vision acuity improvement in the operated on eyes without correction (in cases without astigmatism), and a stable refraction effect were achieved. The authors recommend the new method of refraction keratoplasty for practice.


Imaging the impact of single oxygen atoms on superconducting Bi(2+y)Sr(2-y)CaCu2O(8+x).
High-temperature cuprate superconductors display unexpected nanoscale inhomogeneity in essential properties such as pseudogap energy, Fermi surface, and even superconducting critical temperature. Theoretical explanations for this inhomogeneity have ranged from chemical disorder to spontaneous electronic phase separation. We extend the energy range of scanning tunneling spectroscopy on Bi(2+y)Sr(2-y)CaCu(2)O(8+x), allowing a complete mapping of two types of interstitial oxygen dopants and vacancies at the apical oxygen site. We show that the nanoscale spatial variations in the pseudogap states are correlated with disorder in these dopant concentrations, particularly that of apical oxygen vacancies.


Salt-dependent properties of a coacervate-like, self-assembled DNA liquid.
Liquid-liquid phase separation of a polymer-rich phase from a polymer-dilute solution, known generally as coacervation, has been observed in a variety of biomolecular systems. Understanding of this process, and the properties of the resulting liquid, has been hampered in typical systems by the complexity of the components and of the intermolecular interactions. Here, we examine a single-component system comprised entirely of DNA, in which tetravalent DNA nanostar particles condense into liquids through attractive bonds formed from basepairing interactions. We measure the density, viscosity, particle self-diffusion, and surface tension of NS-liquid droplets. The sequence- and salt-dependent thermodynamics of basepairing accounts for most properties, particularly indicating that particle transport is an activated process whose barrier is the breaking of a single bond, and that very few bonds are broken at the surface. However, more complex effects are also seen. The relation of density to salt shows that electrostatic screening compacts the NS particles. Further, the interrelation of the transport properties indicates a breakdown of the Stokes-Einstein relation. This observation, in concert with the low surface tension and single-bond transport barrier, suggests this DNA liquid has a heterogeneous, clustered structure that is likely enabled by internal NS particle flexibility. We discuss these results in comparison to other coacervate systems.


Exposure to incivility hinders clinical performance in a simulated operative crisis.
Effective communication is critical for patient safety. One potential threat to communication in the operating room is incivility. Although examined in other industries, little has been done to examine how incivility impacts the ability to deliver safe care in a crisis. We therefore sought to determine how incivility influenced anaesthesiology resident performance during a standardised simulation scenario of occult haemorrhage. This is a multicentre, prospective, randomised control trial from three academic centres. Anaesthesiology residents were randomly assigned to either a normal or 'rude' environment and subjected to a validated simulated operating room crisis. Technical and non-technical performance domains including vigilance, diagnosis, communication and patient management were graded on survey with Likert scales by blinded raters and compared between groups. 76 participants underwent randomisation with 67 encounters included for analysis (34 control, 33 intervention). Those exposed to incivility scored lower on every performance metric, including a binary measurement of overall performance with 91.2% (control) versus 63.6% (rude) obtaining a passing score (p=0.009). Binary logistic regression to predict this outcome was performed to assess impact of confounders. Only the presence of incivility reached statistical significance (OR 0.110, 95% CI 0.022 to 0.544, p=0.007). 65% of the rude group believed the surgical environment negatively impacted performance; however, self-reported performance assessment on a Likert scale was similar between groups (p=0.112). Although self-assessment scores were similar, incivility had a negative impact on performance. Multiple areas were impacted including vigilance, diagnosis, communication and patient management even though participants were not aware of these effects. It is imperative that these behaviours be eliminated from operating room culture and that interpersonal communication in high-stress environments be incorporated into medical training.


[Regulation of apolipoprotein expression].
Recent data and concepts on the structure and functioning of apolipoprotein genes as well as on the role of hereditary factors in pathogenesis of atherosclerosis are reviewed. The most important variants of inherited disorders in the system of apolipoproteins promoting the development of atherosclerosis are considered. Special attention is paid to the RFLP of apolipoprotein genes which serves as a peculiar genetic background, increasing probability of the atherosclerosis development in certain individuals.


Time course of electrocortical food-cue responses during cognitive regulation of craving.
In our current obesogenic environment, exposure to visual food-cues can easily lead to craving and overeating because short-term, pleasurable effects of food intake dominate over the anticipated long-term adverse effects such as weight gain and associated health problems. Here we contrasted these two conditions during food-cue presentation while acquiring event-related potentials (ERPs) and subjective craving ratings. Female participants (n = 25) were presented with either high-calorie (HC) or low-calorie (LC) food images under instructions to imagine either immediate (NOW) or long-term effects (LATER) of consumption. On subjective ratings for HC foods, the LATER perspective reduced cravings as compared to the NOW perspective. For LC foods, by contrast, craving increased under the LATER perspective. Early ERPs (occipital N1, 150-200 ms) were sensitive to food type but not to perspective. Late ERPs (late positive potential, LPP, 350-550 ms) were larger in the HC-LATER condition than in all other conditions, possibly indicating that a cognitive focus on negative long-term consequences induced negative arousal. This enhancement for HC-LATER attenuated to the level of the LC conditions during the later slow wave (550-3000 ms), but amplitude in the HC-NOW condition was larger than in all other conditions, possibly due to a delayed appetitive response. Across all conditions, LPP amplitudes were positively correlated with self-reported emotional eating. In sum, results reveal that regulation effects are secondary to an early attentional analysis of food type and dynamically evolve over time. Adopting a long-term perspective on eating might promote a healthier food choice across a range of food types.


Atrial natriuretic peptide modulation of albumin clearance and contrast agent permeability in mouse skeletal muscle and skin: role in regulation of plasma volume.
Atrial natriuretic peptide (ANP) via its guanylyl cyclase-A (GC-A) receptor participates in regulation of arterial blood pressure and vascular volume. Previous studies demonstrated that concerted renal diuretic/natriuretic and endothelial permeability effects of ANP cooperate in intravascular volume regulation. We show that the microvascular endothelial contribution to the hypovolaemic action of ANP can be measured by the magnitude of the ANP-induced increase in blood-to-tissue albumin transport, measured as plasma albumin clearance corrected for intravascular volume change, relative to the corresponding increase in ANP-induced renal water excretion. We used a two-tracer method with isotopically labelled albumin to measure clearances in skin and skeletal muscle of: (i) C57BL6 mice; (ii) mice with endothelium-restricted deletion of GC-A (floxed GC-A x tie2-Cre: endothelial cell (EC) GC-A knockout (KO)); and (iii) control littermates (floxed GC-A mice with normal GC-A expression levels). Comparison of albumin clearances in hypervolaemic EC GC-A KO mice with normovolaemic littermates demonstrated that skeletal muscle albumin clearance with ANP treatment accounts for at most 30% of whole body clearance required for ANP to regulate plasma volume. Skin microcirculation responded to ANP similarly. Measurements of permeability to a high molecular mass contrast agent (35 kD Gadomer) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enabled repeated measures in individual animals and confirmed small increases in muscle and skin microvascular permeability after ANP. These quantitative methods will enable further evaluation of the contribution of ANP-dependent microvascular beds (such as gastro-intestinal tract) to plasma volume regulation.


Mentoring Relationships and the Mental Health of Aboriginal Youth in Canada.
We compared the mentoring experiences and mental health and behavioral outcomes associated with program-supported mentoring for 125 Aboriginal (AB) and 734 non-Aboriginal (non-AB) youth ages 6-17 participating in a national survey of Big Brothers Big Sisters community mentoring relationships. Parents or guardians reported on youth mental health and other outcomes at baseline (before youth were paired to a mentor) and at 18 months follow-up. We found that AB youth were significantly less likely than non-AB youth to be in a long-term continuous mentoring relationship. However, AB youth were more likely than non-AB youth to be in a long-term relationship ending in dissolution. AB youth were also more likely than non-AB youth to have been mentored by a female adult. AB youth were significantly more likely than non-AB youth to report a high quality mentoring relationship, regular weekly contact with their mentor, and monthly mentoring activities. Structural equation model results revealed that, relative to non-mentored AB youth, AB youth with mentors experienced significantly fewer emotional problems and symptoms of social anxiety. These relationships were not found for non-AB youth. Our findings suggest that mentoring programs may be an effective intervention for improving the health and well-being of AB youth.


Optimization of Silicon Nitride Waveguide Platform for On-Chip Virus Detection.
This work presents a rigorous and generic sensitivity analysis of silicon nitride on silicon dioxide strip waveguide for virus detection. In general, by functionalizing the waveguide surface with a specific antibodies layer, we make the optical sensor sensitive only to a particular virus. Unlike conventional virus detection methods such as polymerase chain reaction (PCR), integrated refractive index (RI) optical sensors offer cheap and mass-scale fabrication of compact devices for fast and straightforward detection with high sensitivity and selectivity. Our numerical analysis includes a wide range of wavelengths from visible to mid-infrared. We determined the strip waveguide's single-mode dimensions and the optimum dimensions that maximize the sensitivity to the virus layer attached to its surface at each wavelength using finite difference eigenmode (FDE) solver. We also compared the strip waveguide with the widely used slot waveguide. Our theoretical study shows that silicon nitride strip waveguide working at lower wavelengths is the optimum choice for virus detection as it maximizes both the waveguide sensitivity (Swg) and the figure of merit (FOM) of the sensor. The optimized waveguides are well suited for a range of viruses with different sizes and refractive indices. Balanced Mach-Zehnder interferometer (MZI) sensors were designed using FDE solver and photonic circuit simulator at different wavelengths. The designed sensors show high FOM at λ = 450 nm ranging from 500 RIU-1 up to 1231 RIU-1 with LMZI = 500 µm. Different MZI configurations were also studied and compared. Finally, edge coupling from the fiber to the sensor was designed, showing insertion loss (IL) at λ = 450 nm of 4.1 dB for the design with FOM = 500 RIU-1. The obtained coupling efficiencies are higher than recently proposed fiber couplers.


A feasibility study for a randomised controlled trial of treatment withdrawal in psoriatic arthritis (REmoval of treatment for patients in REmission in psoriatic ArThritis (RETREAT (F)).
TNF therapy is effective for all aspects of psoriatic disease, but these drugs are costly and the long-term effects are unknown. Further, methotrexate causes concern with long-term adverse events. The purpose of this pilot study was to test the feasibility of drug withdrawal from patients with psoriatic arthritis, in stable low disease state. We examined the availability of patients, their willingness to participate, study procedures, and the proportion of patients in the withdrawal arm who relapsed during the study. Low disease state was defined by minimal disease activity criteria (MDA), and relapse by failure to achieve these criteria. Patients in the withdrawal group underwent a phased withdrawal of medication where the last treatment added was the first withdrawn. Assessments were monthly for 3 months before study exit. Seventy-two patients were invited to participate, of which 57 were found to be eligible. Twenty-six (36.1 %) subsequently attended the screening visit but 9 failed eligibility criteria so that 17 patients (29.8 % of the 57 eligible patients, 95 % confidence interval (CI) 18.4, 43.4 %) were randomised at a ratio of 2:1 in favour of the withdrawal arm (11 withdrawals, 6 standard care). Six patients experienced a flare, all of whom were in the withdrawal arm (relapse rate 54.6 %, 95 % CI 23.4, 83.3 %). Four of the flares were apparent from visit 3 (8 weeks after starting withdrawal). Given the high relapse rate, an alternative trial design of partial treatment withdrawal, possibly including a patient preference arm, is recommended.


The social network of PELP1 and its implications in breast and prostate cancers.
Proline, glutamic acid- and leucine-rich protein 1 (PELP1) is a multi-domain scaffold protein that serves as a platform for various protein-protein interactions between steroid receptors (SRs) and signaling factors and cell cycle, transcriptional, cytoskeletal, and epigenetic remodelers. PELP1 is known to be a coregulator of transcription and participates in the nuclear and extranuclear functions of SRs, ribosome biogenesis, and cell cycle progression. The expression and localization of PELP1 are dysregulated in hormonal cancers including breast and prostate cancers. This review focuses on the interactive functions and therapeutic and prognostic significance of PELP1 in breast and prostate cancers.


Accounting for the money-made parenthood of transnational surrogacy.
In the last decade, transnational surrogacy has attracted world-wide attention for making babies and pregnancies exchangeable with money. Involuntarily childless couples and individuals travel abroad and pay to have the desired child and to become parents. Acknowledging the importance of asking into the consequences of this monetization of reproduction, the author takes issue with universalistic assumptions about money and markets, and their presumed universal effects on social relations. Instead, it is argued that we need to explore how money works, and, by extension, how transnational surrogacy works out and becomes viable to people as a way to become parents. Putting together insights from economic sociology, and the assisted reproductive technology and parenting culture literature, the author employs the notion of accounting to grasp how people make sense of the money involved in making them parents. Based on a study involving 21 interviews with Norwegian gay and straight couples and single men and women seeking surrogacy abroad, the author explores how money is accounted for in three cases, set in three different countries; India, the United States and Canada. The analysis shows how money is accounted for in particular ways to confirm parenthood. These ways differ depending on the local context and transnational relations; ultimately making differentiated monetized parenthood. This is of significance when we try to conceptualize contemporary parenthood and how money seemingly sustains parenthood in ever more radical ways.


Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina.
In the developing nervous system, progenitor cells must decide when to withdraw from the cell cycle and commence differentiation. There is considerable debate whether cell-extrinsic or cell-intrinsic factors are most important for triggering this switch. In the vertebrate retina, initiation of neurogenesis has recently been explained by a 'sequential-induction' model--signals from newly differentiated neurons are thought to trigger neurogenesis in adjacent progenitors, creating a wave of neurogenesis that spreads across the retina in a stereotypical manner. We show here, however, that the wave of neurogenesis in the zebrafish retina can emerge through the independent action of progenitor cells--progenitors in different parts of the retina appear pre-specified to initiate neurogenesis at different times. We provide evidence that midline Sonic hedgehog signals, acting before the onset of neurogenesis, are part of the mechanism that sets the neurogenic timer in these cells. Our results highlight the importance of intrinsic factors for triggering neurogenesis, but they also suggest that early signals can modulate these intrinsic factors to influence the timing of neurogenesis many cell cycles later, thereby potentially coordinating axial patterning with control of neuron number and cell fate.


Reduced cortisol levels in cerebrospinal fluid and differential distribution of 11beta-hydroxysteroid dehydrogenases in multiple sclerosis: implications for lesion pathogenesis.
Relapses during multiple sclerosis (MS) are treated by administration of exogenous corticosteroids. However, little is known about the bioavailability of endogenous steroids in the central nervous system (CNS) of MS patients. We thus determined cortisol and dehydroepiandrosterone (DHEA) levels in serum and cerebrospinal fluid (CSF) samples from 34 MS patients, 28 patients with non-inflammatory neurological diseases (NIND) and 16 patients with other inflammatory neurological diseases (OIND). This revealed that MS patients - in sharp contrast to patients with OIND - show normal cortisol concentrations in serum and lowered cortisol levels in the CSF during acute relapses. This local cortisol deficit may relate to poor local activation of cortisone via 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) or to inactivation via 11bHSD2. Accordingly, 11bHSD2 was found to be expressed within active plaques, whereas 11bHSD1 was predominantly detected in surrounding "foamy" macrophages. Our study thus provides new insights into the impaired endogenous CNS cortisol regulation in MS patients and its possible relation to MS lesion pathogenesis. Moreover, an observed upregulation of 11bHSD1 in myelin-loaded macrophages in vitro suggests an intriguing hypothesis for the self-limiting nature of MS lesion development. Finally, our findings provide an attractive explanation for the effectivity of high- vs. low-dose exogenous corticosteroids in the therapy of acute relapses.


Does mechanism of drug action matter to inform rational polytherapy in epilepsy?
When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.


Effect of diet on male reproductive tract of Podisus nigrispinus (Dallas) (Heteroptera: Pentatomidae).
The morphology and histology of the reproductive tract of males of the predator Podisus nigrispinus (Dallas) fed on different diets were studied. P. nigrispinus was fed on diets of: larvae of Alabama argillacea (Hübner), Tenebrio molitor L., Musca domestica L., and an artificial diet. The male reproductive tract, independent of diet, showed testes with intense red coloration in a compact, circular, or slightly oval structure. The vasa deferentia were similar in color to the testes and formed long filaments, which joined with the yellow-cream colored ejaculatory duct. The morphological characteristics of the male reproductive tract were similar under all diets, except for the artificial one. The histological studies demonstrated that independent of the diet the testes of P. nigrispinus were composed of four to six follicles. The testes with six follicles generally had four developed and two atrophied follicles. The morphological and histological differences of the testes of P. nigrispinus when fed with different prey are presented and discussed.


Role of Cyp1A1 in modulation of antitumor properties of the novel agent 2-(4-amino-3-methylphenyl)benzothiazole (DF 203, NSC 674495) in human breast cancer cells.
2-(4-Amino-3-methylphenyl)benzothiazole (DF 203, NSC 674495) is a candidate antitumor agent with potent and selective activity against human-derived tumor cell lines in vitro and in vivo. Only sensitive cell lines (e.g., MCF-7) were able to accumulate and metabolize DF 203, forming the main inactive metabolite, 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6-OH 203). Selective metabolism may therefore underlie its antitumor profile. DF 203 6-hydroxylase activity by MCF-7 cells was not constitutive but induced only after pretreatment of cells with DF 203, 3-methylcholanthrene, or beta-naphthoflavone. 6-Hydroxylation was strongly inhibited by either goat antirat cytochrome P450 1A1 (CYP1A1) serum or alpha-naphthoflavone. Both alpha-naphthoflavone and 6-OH 203 abrogated DF 203-induced growth inhibition. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP1A1, CYP1B1, or CYP2D6 metabolized DF 203 to 6-OH 203. Immunoblot analysis detected significantly enhanced CYP1A1 protein in a panel of sensitive breast cancer cell lines after exposure to DF 203. Neither constitutive expression nor induction of CYP1A1 protein was detected in nonresponsive breast (HBL 100, MDA-MB-435, and MCF-7/ADR) and prostate (PC 3 and DU 145) cancer cell lines. The expression of CYP1B1 was also modulated by DF 203 in the same sensitive cell lines. However, of the two isoforms, only CYP1A1 activity was irreversibly inhibited by DF 203 and significantly inhibited by 6-OH 203. In sensitive cell lines only, [14C]DF 203-derived radioactivity bound covalently to a Mr 50,000, protein which was immunoprecipitated by CYP1A1 antiserum. The covalent binding of [14C]DF 203 to recombinant CYP1A1 enzyme was NADPH-dependent and reduced by 6-OH 203 and glutathione. CYP1A1 appears essential for the metabolism of DF 203 and may have a pivotal, yet undefined, role in its antitumor activity.


The genes raw and ribbon are required for proper shape of tubular epithelial tissues in Drosophila.
The products of two genes, raw and ribbon (rib), are required for the proper morphogenesis of a variety of tissues. Malpighian tubules mutant for raw or rib are wider and shorter than normal tubules, which are only two cells in circumference when they are fully formed. The mutations alter the shape of the tubules beginning early in their formation and block cell rearrangement late in development, which normally lengthens and narrows the tubes. Mutations of both genes affect a number of other tissues as well. Both genes are required for dorsal closure and retraction of the CNS during embryonic development. In addition, rib mutations block head involution, and broaden and shorten other tubular epithelia (salivary glands, tracheae, and hindgut) in much same manner as they alter the shape of the Malpighian tubules. In tissues in which the shape of cells can be observed readily, rib mutations alter cell shape, which probably causes the change in shape of the organs that are affected. In double mutants raw enhances the phenotypes of all the tissues that are affected by rib but unaffected by raw alone, indicating that raw is also active in these tissues.


Multifaceted activities of type I interferon are revealed by a receptor antagonist.
Type I interferons (IFNs), including various IFN-α isoforms and IFN-β, are a family of homologous, multifunctional cytokines. IFNs activate different cellular responses by binding to a common receptor that consists of two subunits, IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also inhibit cell proliferation and modulate other immune responses. We characterized various IFNs, including a mutant IFN-α2 (IFN-1ant) that bound tightly to IFNAR2 but had markedly reduced binding to IFNAR1. Whereas IFN-1ant stimulated antiviral activity in a range of cell lines, it failed to elicit immunomodulatory and antiproliferative activities. The antiviral activities of the various IFNs tested depended on a set of IFN-sensitive genes (the "robust" genes) that were controlled by canonical IFN response elements and responded at low concentrations of IFNs. Conversely, these elements were not found in the promoters of genes required for the antiproliferative responses of IFNs (the "tunable" genes). The extent of expression of tunable genes was cell type-specific and correlated with the magnitude of the antiproliferative effects of the various IFNs. Although IFN-1ant induced the expression of robust genes similarly in five different cell lines, its antiviral activity was virus- and cell type-specific. Our findings suggest that IFN-1ant may be a therapeutic candidate for the treatment of specific viral infections without inducing the immunomodulatory and antiproliferative functions of wild-type IFN.


Prevalence of use study for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), and 3,4-methylenedioxy-ethylamphetamine (MDEA) in military entrance processing stations (MEPS) specimens.
The Roche Abuscreen Onlinetrade mark Amphetamine immunoassay (IA), modified to include sodium periodate, and the Microgenics DRI Ecstasy IA were used to determine the prevalence of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine specimens from applicants seeking to join the United States Armed Forces. Over a 4-month period, a total of 85,658 specimens were IA screened using the Department of Defense 500 ng/mL administrative cutoff level for AMP and MDMA. All presumptively positive specimens were confirmed using a solid-phase extraction procedure coupled with simultaneous analysis of AMP, MAMP, MDA, MDMA, and MDEA by fast gas chromatography-mass spectrometry using the same cutoff levels as the IA. The Roche Online Amphetamine IA identified 216 specimens as presumptively positive; of these, 70 specimens confirmed positive for AMP and 87 specimens confirmed positive for AMP and/or MAMP, resulting in a confirmation rate of 73%. The Microgenics DRI Ecstasy IA identified eight specimens as presumptively positive; of these, five specimens confirmed positive for MDMA and/or MDA, resulting in a confirmation rate of 63%. The total use prevalence for AMP, MAMP, MDA, MDMA, and/or MDEA in military entrance processing stations specimens over the testing period was determined to be 0.19%.


Karyotypic characterization of representatives from Melolonthinae (Coleoptera: Scarabaeidae): karyotypic analysis, banding and fluorescent in situ hybridization (FISH).
Meiotic chromosomes of Phyllophaga (Phytalus) vestita, Phyllophaga (Phyllophaga) aff capillata and Lyogenys fuscus (Melolonthinae) were analyzed by conventional staining, C-banding, fluorochromes, silver nitrate and FISH. The three species had a diploid number of 2n=20 and a sex mechanism of the (Xyp; XYp) parachute type. P. (Phytalus) vestita,P. (Phyllophaga) aff capillata and Lyogenys fuscus showed pericentromeric constitutive heterochromatin (CH) in all autosomal bivalents and on X chromosomes. Staining with CMA3 and DAPI fluorochromes showed that the CH of P. (Phytalus) vestita is not specifically rich in AT and GC-base pairs, whereas in P. (Phyllophaga) aff capillata the sex bivalent and one autosomal pair were found to be enriched in GC base pairs with CMA3, and in Lyogenys fuscus CH was positive for DAPI. Silver nitrate staining revealed nucleolar remnants in all three species. However, FISH obtained a precise identification of nucleolar organizing regions with an rDNA 18S and 25S probe. A signal of hybridization was seen in each species, being detected in the X chromosome of P. (Phytalus) vestita and Lyogenys fuscus, and in a small autosomal bivalent of P. (Phyllophaga) aff capillata.


Examining the Factor Structure and Psychometric Properties of the Chinese Version of the Life Orientation Test in Older Chinese Immigrants.
The current study examined the factor structure and psychometric properties of the Chinese version of the Revised Life Orientation Test (CLOT-R) in a sample of 342 community-dwelling older Chinese immigrants in Canada (mean age = 71.99, SD = 5.62; 58.5% female). Confirmatory factor analysis demonstrated that the CLOT-R yields a two-factor model with one item cross-loading on two latent constructs of optimism and pessimism. Analysis further revealed poor internal consistency and convergent validity. Evidence for discriminant and convergent validity was found between optimism and perceived stress, as well as optimism and quality of life. Compared with the factor structure reported in previous Chinese-speaking samples, the modified two-factor structure found in the current group of older Chinese immigrants could be attributed to the heterogeneity of the sample and possible configural variance across culture and age. Overall, the current findings suggest that the CLOT-R may not be a reliable and valid measure to assess dispositional optimism and pessimism among older Chinese immigrants. Theoretical implications and suggestions for further scale development and research is discussed.


Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof-of-concept examples.
Whole exome sequencing (WES) is a powerful tool to identify clinically undefined forms of intellectual disability/developmental delay (ID/DD), especially in consanguineous families. Here we report the genetic definition of two sporadic cases, with syndromic ID/DD for whom array-Comparative Genomic Hybridization (aCGH) identified a de novo copy number variant (CNV) of uncertain significance. The phenotypes included microcephaly with brachycephaly and a distinctive facies in one proband, and hypotonia in the legs and mild ataxia in the other. WES allowed identification of a functionally relevant homozygous variant affecting a known disease gene for rare syndromic ID/DD in each proband, that is, c.1423C>T (p.Arg377*) in the Trafficking Protein Particle Complex 9 (TRAPPC9), and c.154T>C (p.Cys52Arg) in the Very Low Density Lipoprotein Receptor (VLDLR). Four mutations affecting TRAPPC9 have been previously reported, and the present finding further depicts this syndromic form of ID, which includes microcephaly with brachycephaly, corpus callosum hypoplasia, facial dysmorphism, and overweight. VLDLR-associated cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia and moderate-to-profound intellectual disability. The c.154T>C (p.Cys52Arg) mutation was associated with a very mild form of ataxia, mild intellectual disability, and cerebellar hypoplasia without cortical gyri simplification. In conclusion, we report two novel cases with rare causes of autosomal recessive ID, which document how interpreting de novo array-CGH variants represents a challenge in consanguineous families; as such, clinical WES should be considered in diagnostic testing. © 2016 Wiley Periodicals, Inc.


Efficiency of capturing a phase image using cone-beam x-ray Talbot interferometry.
We assesses the efficiency of x-ray Talbot interferometry (XTI), a technique based on the Talbot effect for measuring a wavefront gradient, in terms of how quickly it can capture a high-quality phase image with a large signal-to-noise ratio for a given incident photon number. Photon statistics cause errors in the phase of the moiré fringes and impose a detection limit on the wavefront gradient. The relation between the incident photon number and the detection limit is determined, and a figure of merit of XTI for a monochromatic cone beam is then defined. The dependence of the figure of merit on optical system parameters, such as grating pitch and position, is then discussed. The effects of varying the pattern height and linewidth of the second grating are shown for rectangular and trapezoidal teeth. Finally, we show how to design a practical cone-beam Talbot interferometer for certain boundary conditions.


Studies on the Cx-reactive protein. III. The effect of irradiation of rabbits on the acute phase protein system.
Young adult rabbits (2 to 3 kg.) were subjected to a single total body exposure of x-radiation ranging from 50 to 1200 r and tested frequently for the presence of Cx-reactive protein in their blood. It usually appeared in two phases separated by an interval of several days. The primary phase occurred 24 to 48 hours after irradiation in almost all (92 of 97) rabbits exposed to 500 r or more and in 4 of 16 exposed to 300 r or less. The secondary phase occurred during the 2nd week in many of the rabbits irradiated with 900 r or more and in a few irradiated with 700 r. Autopsy cultures failed to demonstrate the presence of infection in rabbits which died or were sacrificed during the primary phase. Bacterial infection was demonstrated, however, in almost all (21 of 24) rabbits autopsied and cultured during the secondary phase. After the disappearance of the primary phase in rabbits exposed to 700 or 900 r, the secondary phase could be elicited by initiating bacterial infection. Within 6 to 24 hours after intravenous inoculation of E. coli, Cx-reactive protein reappeared in the blood and persisted until death or termination of the experiment. Reappearance of the protein also followed the intravenous injection of killed E. coli but it disappeared again 1 to 2 days later. The results indicate that the primary phase is elicited by radiation injury per se and the secondary phase by bacterial infection.


Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b.
It was previously reported that Cbl-b associates with Crk-L in Jurkat T cells. However, the physiological significance of such association remains unclear. Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway. We found that Cbl-b associates with, and induces, ubiquitin conjugation to Crk-L, which requires a functional RING finger. Cbl-b deficiency does not affect Crk-L stability, but its association with C3G. In Cbl-b-/- T cells, the interaction between Crk-L and C3G, and the activity of the small GTPase Rap1, are increased. Cbl-b-/- T cells also display increased adhesion and cell surface binding to ICAM-1, a finding that is supported by the enhanced clustering of LFA-1 in Cbl-b-/- T cells in response to TCR stimulation. Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells.