Alcohol enhances HIV infection of cord blood monocyte-derived macrophages.
Alcohol consumption or alcohol abuse is common among pregnant HIV(+) women and has been identified as a potential behavioral risk factor for the transmission of HIV. In this study, we examined the impact of alcohol on HIV infection of cord blood monocyte-derived macrophages (CBMDM). We demonstrated that alcohol treatment of CBMDM significantly enhanced HIV infection of CBMDM. Investigation of the mechanisms of alcohol action on HIV demonstrated that alcohol inhibited the expression of several HIV restriction factors, including anti-HIV microRNAs, APOBEC3G and APOBEC3H. Additionally, alcohol also suppressed the expression of IFN regulatory factor 7 (IRF-7) and retinoic acid-inducible gene I (RIG-I), an intracellular sensor of viral infection. The suppression of these IFN regulatory factors was associated with reduced expression of type I IFN. These experimental findings suggest that maternal alcohol consumption may facilitate HIV infection, promoting vertical transmission of HIV.


Binding of calcium is sensed structurally and dynamically throughout the second calcium-binding domain of the sodium/calcium exchanger.
We report the effects of Ca(2+) binding on the backbone relaxation rates and chemical shifts of the AD and BD splice variants of the second Ca(2+)-binding domain (CBD2) of the sodium-calcium exchanger. Analysis of the Ca(2+)-induced chemical shifts perturbations yields similar K(D) values of 16-24 microM for the two CBD2-AD Ca(2+)-binding sites, and significant effects are observed up to 20 A away. To quantify the Ca(2+)-induced chemical shift changes, we performed a comparative analysis of eight Ca(2+)-binding proteins that revealed large differences between different protein folds. The CBD2 (15)N relaxation data show the CBD2-AD Ca(2+) coordinating loops to be more rigid in the Ca(2+)-bound state as well as to affect the FG-loop located at the opposite site of the domain. The equivalent loops of the CBD2-BD splice variant do not bind Ca(2+) and are much more dynamic relative to both the Ca(2+)-bound and apo forms of CBD2-AD. A more structured FG-loop in CBD2-BD is suggested by increased S(2) order parameter values relative to both forms of CBD2-AD. The chemical shift and relaxation data together indicate that, in spite of the small structural changes, the Ca(2+)-binding event is felt throughout the molecule. The data suggest that the FG-loop plays an important role in connecting the Ca(2+)-binding event with the other cytosolic domains of the NCX, in line with in vivo and in vitro biochemical data as well as modeling results that connect the CBD2 FG-loop with the first Ca(2+)-binding domain of NCX.


Novel approaches in management of perioperative coagulopathy.
The recent advances in hemostatic monitoring, and discussion of the clinical implications of hemostatic therapies based on different blood components and factor concentrates. Implementing suitable laboratory tests and transfusion protocols is highly recommended because the laboratory test guided, protocol-driven transfusion approach reduces blood component utilization, and possibly leads to improved outcomes. Timely assessment of coagulation has been difficult using conventional coagulation tests, but thrombocytopenia, fibrin polymerization defects, and fibrinolysis can be quickly assessed on thromboelastometry. The latter testing can be applied to guide the dosing of fibrinogen and prothrombin complex concentrate, which are selectively used to correct fibrinogen deficiency, and improve thrombin generation in acquired coagulopathy. These therapeutic approaches are novel, and potentially effective in reducing the exposure to allogeneic components (e.g., plasma and platelets) and side-effects of transfusion. Although the accessibility of different therapies among different countries, tranexamic acid is widely available, and is an effective blood conservation measure with a good safety profile in various surgical settings. Our understanding of perioperative coagulopathy, diagnostic tools, and therapeutic approaches has evolved in recent years. Additional multidisciplinary efforts are required to understand the optimal combinations, cost-effectiveness, and safety profiles of allogeneic components, and available factor concentrates.


Oak bark allometry and fire survival strategies in the Chihuahuan desert Sky Islands, Texas, USA.
Trees may survive fire through persistence of above or below ground structures. Investment in bark aids in above-ground survival while investment in carbohydrate storage aids in recovery through resprouting and is especially important following above-ground tissue loss. We investigated bark allocation and carbohydrate investment in eight common oak (Quercus) species of Sky Island mountain ranges in west Texas. We hypothesized that relative investment in bark and carbohydrates changes with tree age and with fire regime: We predicted delayed investment in bark (positive allometry) and early investment in carbohydrates (negative allometry) under lower frequency, high severity fire regimes found in wetter microclimates. Common oaks of the Texas Trans-Pecos region (Quercus emoryi, Q. gambelii, Q. gravesii, Q. grisea, Q. hypoleucoides, Q. muehlenbergii, and Q. pungens) were sampled in three mountain ranges with historically mixed fire regimes: the Chisos Mountains, the Davis Mountains and the Guadalupe Mountains. Bark thickness was measured on individuals representing the full span of sizes found. Carbohydrate concentration in taproots was measured after initial leaf flush. Bark thickness was compared to bole diameter and allometries were analyzed using major axis regression on log-transformed measurements. We found that bark allocation strategies varied among species that can co-occur but have different habitat preferences. Investment patterns in bark were related to soil moisture preference and drought tolerance and, by proxy, to expected fire regime. Dry site species had shallower allometries with allometric coefficients ranging from less than one (negative allometry) to near one (isometric investment). Wet site species, on the other hand, had larger allometric coefficients, indicating delayed investment to defense. Contrary to our expectation, root carbohydrate concentrations were similar across all species and sizes, suggesting that any differences in below ground storage are likely to be in total volume of storage tissue rather than in carbohydrate concentration.


Crude oil as a stranding cause among loggerhead sea turtles (Caretta caretta) in the Canary Islands, Spain (1998-2011).
We report the number of strandings caused by crude oil among loggerhead turtles (Caretta caretta) in the Canary Islands between 1998 and 2011 and analyze the impact of the designation of the Canary Islands as a Particularly Sensitive Sea Area (PSSA) in 2005. Among 1,679 stranded loggerhead turtles, 52 turtles stranded due to crude oil (3.1%). The survival rate of the turtles stranded by crude oil was 88%. All turtles that died because of crude oil stranding had signs of ingestion of crude oil and lesions, included esophageal impaction, necrotizing gastroenteritis, necrotizing hepatitis, and tubulonephrosis. The number of strandings caused by crude oil after 2005 was significantly lower than it was before 2006. We show that the designation of the Canary Islands as a PSSA in 2005 by the International Maritime Organization was associated with a reduction of sea turtle strandings caused by crude oil.


[Multidisciplinary treatment of chronic pancreatitis: an overview of current step-up approach and new options].
- Chronic pancreatitis is a progressive inflammatory disease, which leads to a severe decrease in quality of life and reduced life expectancy.- 85-90% of patients with chronic pancreatitis consult the doctor because of pain.- Pain in chronic pancreatitis has a multifactorial aetiology, with nociceptive and neuropathological components.- Current treatment of chronic pancreatitis uses a step-up approach, starting with lifestyle interventions and medication, followed by endoscopic or surgical treatment or a combination of these two.- Surgical drainage or resection is more effective than repeated endoscopic treatment for patients with advanced chronic pancreatitis who use opiates.- There are indications that early surgical intervention in painful chronic pancreatitis and a dilated pancreatic duct provides better results than the current step-up approach; this is currently being investigated in the ESCAPE trial.


Biceps tenotomy versus tenodesis: patient-reported outcomes and satisfaction.
Biceps tenotomy and tenodesis are surgical treatments for pathology of the proximal tendon of the long head of the biceps. There is debate over which procedure provides better patient outcomes. Compare patient-reported outcomes and satisfaction between biceps tenotomy and tenodesis. This retrospective cohort study including all patients undergoing arthroscopic biceps tenodesis or tenotomy as part of more extensive shoulder surgery with a single surgeon. Concomitant procedures included rotator cuff repair, subacromial decompression, acromioclavicular joint resection, and debridement. Patients 36-81 years old were contacted by phone at > 2-year post-operatively to complete a biceps-specific outcome questionnaire. Subject decision not to participate was the sole exclusion criterion. Satisfaction scores and frequencies of potential biceps-related downsides (biceps cramping/spasms, biceps pain, shoulder pain, weakness, cosmetic deformity) were analyzed for the effects of procedure, sex, and age. Satisfaction score distributions were similar between patients with tenodesis and patients with tenotomy (χ2 = 8.34, P = 0.08), although slightly more patients with tenodesis than patients with tenotomy reported being satisfied or very satisfied (96% versus 91%). Perceived downsides occurred more frequently among patients with tenotomy than in patients with tenodesis: 59% of patients with tenotomy reported ≥ 1 downside, versus 37% of patients with tenodesis (P < 0.01). In patients reporting ≥ 1 downside, distributions of total downsides differed between procedures (χ2 = 10.04, P = 0.04): patients with tenotomy were more likely to report multiple concurrent downsides than were patients with tenodesis (31% versus 16%). Each individual downside tended to be reported as present by a greater proportion of patients with tenotomy than patients with tenodesis. Sex had no effect on satisfaction or downsides, but there was a trend for older patients to report higher satisfaction and fewer downsides. Biceps tenotomy and tenodesis are both viable treatments for proximal biceps tendon pathology, yielding high patient satisfaction. There were trends toward greater satisfaction and fewer problems in patients with tenodesis. Still, younger patients with tenodesis did report perceived downsides. Alternatively, older patients tended to be more satisfied with both procedures overall. Regardless of procedure, most patients receiving either tenotomy or tenodesis would undergo their respective surgery again. Level III evidence, retrospective comparative cohort study.


Global mistranslation increases cell survival under stress in Escherichia coli.
Mistranslation is typically deleterious for cells, although specific mistranslated proteins can confer a short-term benefit in a particular environment. However, given its large overall cost, the prevalence of high global mistranslation rates remains puzzling. Altering basal mistranslation levels of Escherichia coli in several ways, we show that generalized mistranslation enhances early survival under DNA damage, by rapidly activating the SOS response. Mistranslating cells maintain larger populations after exposure to DNA damage, and thus have a higher probability of sampling critical beneficial mutations. Both basal and artificially increased mistranslation increase the number of cells that are phenotypically tolerant and genetically resistant under DNA damage; they also enhance survival at high temperature. In contrast, decreasing the normal basal mistranslation rate reduces cell survival. This wide-ranging stress resistance relies on Lon protease, which is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance indicate surprising coordination between intracellular stress responses and suggest a novel hypothesis to explain high global mistranslation rates.


Cell-type-specific innate immune response to oncolytic Newcastle disease virus.
Virotherapy of cancer exploits the potential of naturally occurring and engineered oncolytic viruses to selectively replicate in and cause cytotoxicity to tumor cells without affecting healthy normal cells. The tumor selectivity of Newcastle disease virus (NDV), a member of the family Paramyxoviridae, depends on the differential type I interferon (IFN) response. Further understanding of the key mechanisms and immune effector molecules involved will aid in augmenting the oncolytic properties of NDV. Here we report on the infection kinetics and innate immune responses to a recombinant LaSota strain of NDV (rLaSota eGFP) in human tumor and normal cells. We observed varying replicative fit and cytotoxicity of rLaSota eGFP depending on the tumor cell type, with severely restricted replication in normal cells. The absence of retinoic acid-inducible gene I (RIG-I), a cytosolic RNA sensor, determined sensitivity to NDV. Productive NDV infection with a moderate IFN-α induction in human multiple myeloma cells suggested a role for IFN-independent mechanisms or lack of type I IFN reinforcement by RIG-I. Proinflammatory cytokines and chemokines were altered differentially in infected normal and tumor cells. Our results suggest that tumor selectivity is dependent on variations in the cellular antiviral response to infection with NDV and RIG-I expression.


Giant wing sphenoid meningioma with principal manifestation depression.
A 68-year-old woman with no previous mental illness presented with a three-month history of decreased energy, fatigue, feelings of hopelessness, pessimism, difficulty concentrating, and persistent feelings of "emptiness", worthlessness, insomnia, appetite loss, diminished functionality. The patient's neurological examination was normal. She was diagnosis with major depressive disorder (MDD) by Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria and received psychiatric treatment. Resistance at therapy leaded at cerebral axial computed tomography (CT) indication. Cerebral CT-scan revealed an intracranial expansive mass (EPIC) located in frontal-temporal (F-T) right lobe, size 42/45/66 mm, hyperdense lesion, without peri-lesional edema, inserted on the great sphenoid wing, image suggestive for meningioma. MRI confirmed the presence of tumor and angiography showed the arterial source of the meningioma. The neurosurgical intervention removed successfully the tumor. Grossly examination revealed a giant tumor with a maximal diameter of 7 cm. The histological aspect of the tumor was highly representative for the diagnosis of meningioma. Patient mental status was evaluated at baseline, in preoperative period and postoperative period and had been using Hamilton Depression Rating Scale (HDRS) - 17 items version, Clinical Global Impression Scale (CGI), and Global Assessment of Functioning (GAF). After neurosurgical intervention, functioning was improving with completed remission of depression symptoms at six-month postoperative evaluation. Most meningiomas are slow growing and many are found incidentally. The decision to perform a cerebral CT-scan depends on the clinician's degree of suspicion that a tumor is present. A first depressive episode is a clinical condition with principal indication for cerebral CT-scan.


Route selection for double-balloon endoscopy, based on capsule transit time, in obscure gastrointestinal bleeding.
Double-balloon endoscopy (DBE) utilizes both oral and anal routes. The proper selection of the initial route is important for more rapid management of obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to clarify the accuracy of the transit time of video capsule endoscopy (VCE) to the lesion as a predictive indicator for the decision on the initial DBE route. Of 172 patients who underwent both DBE and VCE, 65 who were diagnosed with small-intestinal hemorrhagic lesions by both means were enrolled. The relation between VCE transit time to the lesion and the DBE route by which the lesion was discovered was analyzed, distinguishing between 46 complete and 19 incomplete VCEs. Among the 46 patients with a complete VCE, the transit time and position of the lesion were strongly correlated. The best cutoff values for route selection by the VCE transit time from capsule intake and from the duodenal bulb to the lesion, determined using a receiver operating characteristic (ROC) curve, were 60% and 50%, respectively, of the transit time to the cecum. At that point, the accuracy of route selection was 90% and 94%, respectively. Positions shown by VCE for ileal lesions tended to be more proximal than those shown by surgery. In the 19 patients with incomplete VCEs, the best cutoff for transit time was 180 min from the duodenal bulb. The VCE transit time was useful for determining the route for DBE in OGIB. This parameter was most accurate when the cutoff value for the selection was half of the small-bowel transit time in the complete VCE examination.


Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy.
Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined. This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3-5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0-7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated. Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13-0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (Pinteraction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC). Dyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.


Emodin protected against synaptic impairment and oxidative stress induced by fluoride in SH-SY5Y cells by modulating ERK1/2/Nrf2/HO-1 pathway.
Excessive fluoride exposure contributes to neurotoxic effects. Emodin exhibits antioxidative functions in the central nervous system (CNS); however, its neuroprotective mechanism against fluoride remains to be elucidated. Our aim was to explore the neuroprotective efficacy and the possible mechanisms of emodin. In our study, synaptic proteins and oxidative stress damage were examined after human neuroblastoma SH-SY5Y cells were treated with high doses of NaF for 24 hours. Moreover, pretreatment with emodin was used to shed light on the neuroprotective effects in NaF-induced toxicity in SH-SY5Y cells. We found that NaF significantly lowered the protein expressions of SNAP 25, synaptophysin and PSD 95 in SH-SY5Y cells. In addition, NaF exposure increased the protein expression of p-ERK1/2 and decreased the protein expressions of Nrf2 and HO-1, as well as facilitated increasing ROS, 4-hydroxynonenal (4-HNE), and 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Pretreatment with emodin significantly recovered these alterations caused by NaF. These data implied that the neuroprotective effects of emodin and pointed to the promising utilization for protecting against neurotoxicity induced by fluoride.


Down-regulation of a single auxin efflux transport protein in tomato induces precocious fruit development.
The PIN-FORMED (PIN) auxin efflux transport protein family has been well characterized in the model plant Arabidopsis thaliana, where these proteins are crucial for auxin regulation of various aspects of plant development. Recent evidence indicates that PIN proteins may play a role in fruit set and early fruit development in tomato (Solanum lycopersicum), but functional analyses of PIN-silenced plants failed to corroborate this hypothesis. Here it is demonstrated that silencing specifically the tomato SlPIN4 gene, which is predominantly expressed in tomato flower bud and young developing fruit, leads to parthenocarpic fruits due to precocious fruit development before fertilization. This phenotype was associated with only slight modifications of auxin homeostasis at early stages of flower bud development and with minor alterations of ARF and Aux/IAA gene expression. However, microarray transcriptome analysis and large-scale quantitative RT-PCR profiling of transcription factors in developing flower bud and fruit highlighted differentially expressed regulatory genes, which are potential targets for auxin control of fruit set and development in tomato. In conclusion, this work provides clear evidence that the tomato PIN protein SlPIN4 plays a major role in auxin regulation of tomato fruit set, possibly by preventing precocious fruit development in the absence of pollination, and further gives new insights into the target genes involved in fruit set.


Surface display of Salmonella epitopes in Escherichia coli and Staphylococcus carnosus.
Salmonella enterica serotype Enteritidis (SE) is considered to be one of the most potent pathogenic Salmonella serotypes causing food-borne disease in humans. Since a live bacterial vaccine based on surface display of antigens has many advantages over traditional vaccines, we have studied the surface display of the SE antigenic proteins, H:gm and SefA in Escherichia coli by the β-autotransporter system, AIDA. This procedure was compared to protein translocation in Staphylococcus carnosus, using a staphylococci hybrid vector earlier developed for surface display of other vaccine epitopes. Both SefA and H:gm were translocated to the outer membrane in Escherichia coli. SefA was expressed to full length but H:gm was shorter than expected, probably due to a proteolytic cleavage of the N-terminal during passage either through the periplasm or over the membrane. FACS analysis confirmed that SefA was facing the extracellular environment, but this could not be conclusively established for H:gm since the N-terminal detection tag (His6) was cleaved off. Polyclonal salmonella antibodies confirmed the sustained antibody-antigen binding towards both proteins. The surface expression data from Staphylococcus carnosus suggested that the H:gm and SefA proteins were transported to the cell wall since the detection marker was displayed by FACS analysis. Apart from the accumulated knowledge and the existence of a wealth of equipment and techniques, the results indicate the selection of E. coli for further studies for surface expression of salmonella antigens. Surface expression of the full length protein facing the cell environment was positively proven by standard analysis, and the FACS signal comparison to expression in Staphylococcus carnosus shows that the distribution of the surface protein on each cell was comparatively very narrow in E. coli, the E. coli outer membrane molecules can serve as an adjuvant for the surface antigenic proteins and multimeric forms of the SefA protein were detected which would probably be positive for the realisation of a strong antigenic property. The detection of specific and similar proteolytic cleavage patterns for both the proteins provides a further starting point for the investigation and development of the Escherichia coli AIDA autotransporter efficiency.


Induction of omega-oxidation of monocarboxylic acids in rats by acetylsalicylic acid.
The accumulation of dicarboxylic acids, particularly long chain, is a prominent feature of Reye's syndrome and diseases of peroxisomal metabolism. We assessed the omega-oxidation of a spectrum of fatty acids in rats and asked whether pretreatment of rats with aspirin, which is known to predispose children to Reye's syndrome, would affect omega-oxidation of long chain fatty acids. We found that aspirin increased liver free fatty acids and increased the capacity for omega-oxidation three- to sevenfold. Omega-oxidation of long chain substrate was stimulated to a greater degree than medium chain substrate and was apparent within one day of treatment, at serum aspirin concentrations below the therapeutic range in humans. The apparent Km for lauric acid was 0.9 microM and 12 microM for palmitate. We also found a difference in the storage stability of activity toward medium and long chain substrate. Saturating concentrations of palmitate had no effect on the formation of dodecanedioic acid, whereas laurate decreased but never eliminated the omega-oxidation of palmitate. 97% of the total laurate omega-oxidative activity recovered was found in the microsomes, but 32% of palmitate omega-oxidative activity was present in the cytosol. These results demonstrate that aspirin is a potent stimulator of omega-oxidation and suggest that there may be multiple enzymes for omega-oxidation with overlapping substrate specificity.


Wear-lines and split-lines of human patellar cartilage: relation to tensile biomechanical properties.
Articular cartilage undergoes age-associated degeneration, resulting in both structural and functional biomechanical changes. At early stages of degeneration, wear-lines develop in the general direction of joint movement. With aging, cartilage exhibits a decrease in tensile modulus. The tensile modulus of cartilage has also been related to the orientation of the collagen network, as revealed by split-lines. To determine the relative contribution of wear-line and split-line orientation on the tensile biomechanical properties of human patellar cartilage from different depths. In human patellar cartilage, wear- and split-lines are aligned parallel to each other at the proximal facet, and perpendicular to each other at the medial facet. Using superficial, middle, and deep cartilage sections from these two sites, tensile samples were prepared in two orthogonal orientations. Thus, for each depth, there were four groups of samples, with their long axes were aligned either parallel or perpendicular to wear-line direction and also aligned parallel or perpendicular to split-line direction. Uniaxial tensile tests were performed to assess equilibrium and ramp moduli. Tensile equilibrium moduli varied with wear-line orientation (P<0.05) and depth (P<0.001), in an interactive manner (P<0.05), and tended to vary with split-line orientation (P=0.16). In the superficial layer, equilibrium and ramp modulus were higher when the samples were loaded parallel to wear-lines (P<0.05). These results indicate that mild wear (i.e., wear-line formation) at the articular surface has deleterious functional effects on articular cartilage and represent an early aging-associated degenerative change. The identification and recognition of functional biomechanical consequences of wear-lines are useful for planning and interpreting tensile biomechanical tests in human articular cartilage.


Demographic, anthropometric and socioeconomic characteristics of functional constipation in Eastern Croatia.
Aim of the research is to establish the prevalence of constipation in Osjecko-baranjska County, to establish its specific characteristics and to determine the effect of demographic, anthropometric and socioeconomic factors. It is a cross-sectional study conducted in 2010. on systematic sample of 900 subjects between 20 and 69 years of age. Every subject was sent an invitation letter and a Rome III diagnostic questionnaire for one of the disorders. A scoring algorithm was used to confirm or exclude the diagnosis of functional constipation. The chi-square test (chi2 test), t-test and logistic regression were used for analysis. The prevalence of constipation in our study was 22.19%, which is higher than the prevalence in most other countries, where it ranges from 5% to 18%. In our study statistically significant variables were: place of current residence (urban), education level (high school), marital status (divorced people), a larger number of household members and a lower health status by self-assessment. According to t-test persons with constipation on average are older, have higher average BMI and lower average grade valued financial status of households and their health. There were a greater number of subjects that had at least one alarm symptom or some of the psychosocial factors and they often suffered from a chronic disease. Functional constipation presents a significant health problem. Rome III survey questionnaire proved to be an acceptable method for diagnosing this functional disorder in clinical-consilliary and primary health care, and for persons showing signs of alarm and needing further diagnostic treatment.


Pre-verbal infants perceive emotional facial expressions categorically.
Adults perceive emotional expressions categorically, with discrimination being faster and more accurate between expressions from different emotion categories (i.e. blends with two different predominant emotions) than between two stimuli from the same category (i.e. blends with the same predominant emotion). The current study sought to test whether facial expressions of happiness and fear are perceived categorically by pre-verbal infants, using a new stimulus set that was shown to yield categorical perception in adult observers (Experiments 1 and 2). These stimuli were then used with 7-month-old infants (N = 34) using a habituation and visual preference paradigm (Experiment 3). Infants were first habituated to an expression of one emotion, then presented with the same expression paired with a novel expression either from the same emotion category or from a different emotion category. After habituation to fear, infants displayed a novelty preference for pairs of between-category expressions, but not within-category ones, showing categorical perception. However, infants showed no novelty preference when they were habituated to happiness. Our findings provide evidence for categorical perception of emotional expressions in pre-verbal infants, while the asymmetrical effect challenges the notion of a bias towards negative information in this age group.


Effect of virulence factors on the photodynamic inactivation of Cryptococcus neoformans.
Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.


Baculovirus superinfection: a probable restriction factor on the surface display of proteins for library screening.
In addition to the expression of recombinant proteins, baculoviruses have been developed as a platform for the display of complex eukaryotic proteins on the surface of virus particles or infected insect cells. Surface display has been used extensively for antigen presentation and targeted gene delivery but is also a candidate for the display of protein libraries for molecular screening. However, although baculovirus gene libraries can be efficiently expressed and displayed on the surface of insect cells, target gene selection is inefficient probably due to super-infection which gives rise to cells expressing more than one protein. In this report baculovirus superinfection of Sf9 cells has been investigated by the use of two recombinant multiple nucleopolyhedrovirus carrying green or red fluorescent proteins under the control of both early and late promoters (vAcBacGFP and vAcBacDsRed). The reporter gene expression was detected 8 hours after the infection of vAcBacGFP and cells in early and late phases of infection could be distinguished by the fluorescence intensity of the expressed protein. Simultaneous infection with vAcBacGFP and vAcBacDsRed viruses each at 0.5 MOI resulted in 80% of infected cells co-expressing the two fluorescent proteins at 48 hours post infection (hpi), and subsequent infection with the two viruses resulted in similar co-infection rate. Most Sf9 cells were re-infectable within the first several hours post infection, but the re-infection rate then decreased to a very low level by 16 hpi. Our data demonstrate that Sf9 cells were easily super-infectable during baculovirus infection, and super-infection could occur simultaneously at the time of the primary infection or subsequently during secondary infection by progeny viruses. The efficiency of super-infection may explain the difficulties of baculovirus display library screening but would benefit the production of complex proteins requiring co-expression of multiple polypeptides.


[Dynamics of soil phosphorus adsorption-desorption in maize/soybean relay intercropping system in purple hilly area].
Field plot experiment was carried out to study the effect of phosphorus application on soil phosphorus adsorption-desorption characteristics under three cropping patterns including maize/soybean relay intercropping (M/S), maize monoculture (M), and soybean monoculture (S). Results showed that without phosphorus fertilization, the system crop yield under M/S was increased by 9.8% and 79. 1% compared with that of M and S, respectively, and the land equivalent ratio (LER) was 1.58. With phosphate fertilizer application, the system crop yield under M/S was increased by 10.4% and 80.3% compared with that of M and S, respectively, and the LER was 1.62. The system crop yields under M/S, M and S with phosphate fertilizer application were increased by 12.7%, 12. 2% and 17. 6%, respectively, compared with that without phosphorus fertilization. Among three cropping patterns, the soil buffer capacity (SBC) values were in the order of M/S>M >S regardless of phosphate fertilizer applied or not. The SBC values of M/S, M and S without phosphate fertilizer application were reduced by 19.6%, 30.3% and 12.0% compared with phosphate fertilizer application treatments, respectively. The soil desorption per absorption (b) values of the three cropping patterns with phosphate fertilizer application were in the order of M/S>M>S, and the b values increased by 10.9%, 39.1% and -9.6%, respectively, compared with non phosphate fertilizer application. The soil phosphorus maximum absorption (Qm) and soil phosphorus desorption rate also showed the same trend.


Changes in Alprazolam Metabolism by CYP3A43 Mutants.
Alprazolam is a triazolobenzodiazepine which is most commonly used in the short-term management of anxiety disorders, often in combination with antipsychotics. The four human members of the CYP3A subfamily are mainly responsible for its metabolism, which yields the main metabolites 4-hydroxyalprazolam and α-hydroxyalprazolam. We performed a comparison of alprazolam metabolism by all four CYP3A enzymes upon recombinant expression in the fission yeast Schizosaccharomyces pombe. CYP3A4 and CYP3A5 show the highest 4-hydroxyalprazolam production rates, while CYP3A5 alone is the major producer of α-hydroxyalprazolam. For both metabolites, CYP3A7 and CYP3A43 show lower activities. Computational simulations rationalize the difference in preferred oxidation sites observed between the exemplary enzymes CYP3A5 and CYP3A43. Investigations of the alprazolam metabolites formed by three previously described CYP3A43 mutants (L293P, T409R, and P340A) unexpectedly revealed that they produce 4-hydroxy-, but not α-hydroxyalprazolam. Instead, they all also make a different metabolite, which is 5-N-O alprazolam. With respect to 4-hydroxyalprazolam, the mutants showed fourfold (T409R) to sixfold (L293P and P340A) higher production rates compared to the wild-type (CYP3A43.1). In the case of 5-N-O alprazolam, the production rates were similar for the three mutants, while no formation of this metabolite was found in the wild-type incubation.


Genome-wide mapping of 10 calving and fertility traits in Holstein dairy cattle with special regard to chromosome 18.
Over the last decades, a dramatic decrease in reproductive performance has been observed in Holstein cattle and fertility problems have become the most common reason for a cow to leave the herd. The premature removal of animals with high breeding values results in both economic and breeding losses. For efficient future Holstein breeding, the identification of loci associated with low fertility is of major interest and thus constitutes the aim of this study. To reach this aim, a genome-wide combined linkage disequilibrium and linkage analysis (cLDLA) was conducted using data on the following 10 calving and fertility traits in the form of estimated breeding values: days from first service to conception of heifers and cows, nonreturn rate on d 56 of heifers and cows, days from calving to first insemination, days open, paternal and maternal calving ease, paternal and maternal stillbirth. The animal data set contained 2,527 daughter-proven Holstein bulls from Germany that were genotyped with Illumina's BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For the cLDLA, 41,635 sliding windows of 40 adjacent single nucleotide polymorphisms (SNP) were used. At each window midpoint, a variance component analysis was executed using ASReml. The underlying mixed linear model included random quantitative trait locus (QTL) and polygenic effects. We identified 50 genome-wide significant QTL. The most significant peak was detected for direct calving ease at 59,179,424 bp on chromosome 18 (BTA18). Next, a mixed-linear model association (MLMA) analysis was conducted. A comparison of the cLDLA and MLMA results with special regard to BTA18 showed that the genome-wide most significant SNP from the MLMA was associated with the same trait and located on the same chromosome at 57,589,121 bp (i.e., about 1.5 Mb apart from the cLDLA peak). The results of 5 different cLDLA and 2 MLMA models, which included the fixed effects of either SNP or haplotypes, suggested that the cLDLA method outperformed the MLMA in accuracy and precision. The haplotype-based cLDLA method allowed for a more precise mapping and the definition of ancestral and derived QTL alleles, both of which are essential for the detection of underlying quantitative trait nucleotides.


Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin.
There is considerable interest in the identification of natural agents capable of affording protection to skin from the adverse effects of solar ultraviolet B (UVB) radiation. Pomegranate (Punica granatum L.) fruit possesses as strong antioxidant, anti-inflammatory and antiproliferative properties. Recently, we have shown that oral feeding of pomegranate fruit extract (PFE) to mice afforded substantial protection from the adverse effects of single UVB radiation via modulation in early biomarkers of photocarcinogenesis. This study was designed to investigate the photochemopreventive effects of PFE (0.2%, wt/vol) after multiple UVB irradiations (180 mJ cm(-2), on alternative day, for a total of seven treatments) to the skin of SKH-1 hairless mice. Oral feeding of PFE to SKH-1 mice inhibited UVB-induced epidermal hyperplasia, infiltration of leukocytes, protein oxidation and lipid peroxidation. Immunoblot analysis demonstrated that oral feeding of PFE to mice inhibited UVB-induced (1) nuclear translocation and phosphorylation of nuclear factor kappa B/p65, (2) phosphorylation and degradation of IκBα, (3) activation of IKKα/ΙΚΚβ and (4) phosphorylation of mitogen-activated protein kinase proteins and c-Jun. PFE consumption also inhibited UVB-induced protein expression of (1) COX-2 and iNOS, (2) PCNA and cyclin D1 and (3) matrix metalloproteinases-2,-3 and -9 in mouse skin. Taken together, these data show that PFE consumption afforded protection to mouse skin against the adverse effects of UVB radiation by modulating UVB-induced signaling pathways.


Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies.
To evaluate controlled clinical studies on the efficacy and effectiveness of Viscum album for quality of life (QoL) in cancer. The authors conducted a search of 7 electronic databases and reference lists and had extensive consultations with experts. They carried out a criteria-based assessment of methodological study quality. The authors identified 26 randomized controlled trials (RCTs) and 10 non-RCTs that investigated the influence of V album extracts (VAEs) on QoL in malignant diseases; 26 studies assessed patient-reported QoL. Questionnaires were mostly well established and validated. Half of the studies investigated VAEs concomitant with chemotherapy, radiotherapy, or surgery. Some studies were well designed, whereas others had minor or major methodological weaknesses. Among the 26 RCTs, 22 reported a QoL benefit, 3 indicated no difference, and 1 did not report any result. All the non-RCTs reported a QoL benefit. Of the studies with higher methodological quality, most reported a benefit, whereas 1 found no difference. Improvements were mainly in regard to coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being in general and, less consistently, in regard to pain, diarrhea, general performance, and side effects of conventional treatments. VAEs were well tolerated. VAEs seem to have an impact on QoL and reduction of side effects of conventional therapies (chemotherapy, radiation) in experimental trials as well as in routine daily application. The influence on fatigue especially should be investigated further.


Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts.
Repeated blast-traumatic brain injury (blast-TBI) has been hypothesized to cause persistent and unusual neurological and psychiatric symptoms in service members returning from war zones. Blast-wave primary effects have been supposed to induce damage and molecular alterations in the brain. However, the mechanisms through which the primary effect of an explosive-driven blast wave generate brain lesions and induce brain consequences are incompletely known. Prior findings from rat brains exposed to two consecutive explosive-driven blasts showed molecular changes (hyperphosphorylated-Tau, AQP4, S100β, PDGF, and DNA-polymerase-β) that varied in magnitude and direction across different brain regions. We aimed to compare, in an unbiased manner, the proteomic profile in the hippocampus of double blast vs sham rats using mass spectrometry (MS). Data showed differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs sham rats. Tandem mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before in blast studies, such as increases in MAGI3, a scaffolding protein at cell-cell junctions, which were confirmed by Western blotting analyses. Due to the absence of behavioral and obvious histopathological changes as described in our previous publications, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the hippocampus of rats repeatedly expsosed to blast waves generated by explosive-driven detonations.


E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure.
Electronic cigarette (e-cigarette) use has increased substantially in recent years. While e-cigarettes have been proposed as a potentially effective smoking cessation tool, dualuse in smokers is common and e-cigarettes are widely used by non-smokers, including youth and young-adult non-smokers. Nicotine, the primary addictive component in cigarettes, is present at varying levels in many e-liquids. E-cigarettes may lead to initiation of nicotine use in adult and youth non-smokers, re-initiation of nicotine dependence in ex-smokers or increased severity of nicotine dependence in dual-users of cigarettes and e-cigarettes. As such, there are important clinical and policy implications to understanding factors impacting nicotine exposure from e-cigarettes. However, the broad and rapidly changing range of e-liquid constituents and e-cigarette hardware which could impact nicotine exposure presents a challenge. Recent changes in regulatory oversight of e-cigarettes underscore the importance of synthesizing current knowledge on common factors which may impact nicotine exposure. This review focuses on factors which may impact nicotine exposure by changing e-cigarette use behavior, puff topography, altering the nicotine yield (amount of nicotine exiting the e-cigarette mouth piece including nicotine exhaled as vapor) or more directly by altering nicotine absorption and bioavailability. Topics reviewed include e-liquid components or characteristics including flavor additives (e.g., menthol), base e-liquid ingredients (propylene glycol, vegetable glycerin), components commonly used to dissolve flavorants (e.g., ethanol), and resulting properties of the e-liquid (e.g., pH), e-cigarette device characteristics (e.g., wattage, temperature, model) and user behavior (e.g., puff topography) which may impact nicotine exposure. E-liquid characteristics and components, e-cigarette hardware and settings, and user behavior can all contribute substantially to nicotine exposure from e-cigarettes.


Planning: supporting and optimizing clinical guidelines execution.
A crucial feature of computerized clinical guidelines (CGs) lies in the fact that they may be used not only as conventional documents (as if they were just free text) describing general procedures that users have to follow. In fact, thanks to a description of their actions and control flow in some semiformal representation language, CGs can also take advantage of Computer Science methods and Information Technology infrastructures and techniques, to become executable documents, in the sense that they may support clinical decision making and clinical procedures execution. In order to reach this goal, some advanced planning techniques, originally developed within the Artificial Intelligence (AI) community, may be (at least partially) resorted too, after a proper adaptation to the specific CG needs has been carried out.


Effectiveness of advice from physician and nurse on smoking cessation stage in Taiwanese male smokers attending a community-based integrated screening program.
A screening program provides a teachable moment for primary prevention such as encouraging smoking cessation. However, little is known about the efficacy of smoking cessation intervention delivered to the general population through a community-based screening program. A quasi-experimental untreated control design with pre-test and post-test was conducted with 42 subjects receiving advice from physician and nurses (the PNA group), 39 receiving an informational leaflet (the leaflet group), and 308 control subjects. The overall rate of reaching the action stage was 25 %, 5.7 %, and 7.8 in the PNA group, the leaflet group, and the control group, respectively. In approximately 45-60 % of all participants, the stage remained unchanged. Such an association between the intervention groups and stage changes was statistically significant (p = 0.02). The PNA group was more likely to have the improvement of stage (forward transition toward action stage) than the control group [adjusted odds ratio (aOR) = 2.27 (1.07-4.84)]. Deterioration (backward transition toward precontemplation) in the PNA intervention group was 37 % lower than that in the control group [aOR = 0.63 (0.20-2.01)]. This study demonstrated that smoking cessation advice from physician and nurse is conducive to smoking cessation, as shown by greater movement toward and less movement away from smoking cessation through a community-based integrated screening platform.


Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses.
Energy deprivation, as a result of aglycemia, leads to depression of the central synaptic transmission. Endogenous adenosine has been implicated in this depressant effect. We have studied the possible involvement of endogenous adenosine in the depression of corticostriatal excitatory transmission induced by glucose deprivation by using intracellular recordings in brain slices. After stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny neurons. Adenosine (3-300 microM) or brief periods (5-10 min) of aglycemia reduced the EPSP amplitude but did not alter the membrane potential and the resistance of the recorded cells. These inhibitory effects were not associated with an alteration of the postsynaptic sensitivity to exogenous glutamate but were coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. A delayed postsynaptic membrane depolarization/inward current was detected after 15-20 min of glucose deprivation. The presynaptic inhibitory effects induced by adenosine and aglycemia were both antagonized either by the nonselective adenosine receptor antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 microM) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nM). Conversely, these antagonists affected neither the delayed membrane depolarization/inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1 mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1 receptors mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses, whereas ATP-dependent potassium channels do not play a significant role in this presynaptic inhibition.


Evaluating the groundwater potential of Wadi Al-Jizi, Sultanate of Oman, by integrating remote sensing and GIS techniques.
Groundwater resources are highly stressed due to their overuse, especially in the arid region. This study is aimed at discovering potential groundwater resource zones using currently available data and state-of-the-art methods. This will lead to effective management of scarcely available and rapidly depleting groundwater resources in the Wadi Al-Jizi catchment, located in the Al-Batinah region. Data on terrain characteristics, geology, and geomorphology was integrated using remote sensing techniques and geographical information system (GIS). The result from this exercise was used for the identification of areas with a high potential for groundwater availability. These areas were classified into five types, namely, excellent, good, medium, low, and very low representing 11%, 59.5%, 26%, and 3.5% of the total area, respectively. The present study shows that the integration of all the weighted parameters shows promising results in the zonation of groundwater. This study shall be useful to the decision-makers in highlighting potential drilling as well as recharge sites in the area.


Evaluation of a DNA-hybridization method for detection of African and Asian strains of Neisseria gonorrhoeae in men with urethritis.
The 2.6-megadalton (MDa) cryptic plasmid and the 4.4-MDa beta-lactamase plasmid of Neisseria gonorrhoeae were radiolabeled with [32P] nucleotides and used as probes for direct detection of gonococci and beta-lactamase plasmids in urethral exudates from men with urethritis. The sensitivity and specificity of the DNA probes were compared with culture isolation of N. gonorrhoeae and biochemical tests of gonococcal isolates for beta-lactamase production. Of 216 urethral specimens, 180 were positive for N. gonorrhoeae by DNA probe and culture, 27 were negative by both tests, and 9 gave discordant results. Compared with culture and with the chromogenic cephalosporin assay, the sensitivity and the specificity of the DNA probe was 99% and 93% and that of the beta-lactamase probe assay was 91% and 96%, respectively. Electrophoresis of plasmids isolated from 90 gonococcal cultures showed that all contained the 2.6-MDa plasmid, 29 possessed a 3.2-MDa plasmid, 18 a 4.4-MDa beta-lactamase plasmid, and 11 had a 24.5-MDa conjugal plasmid. We conclude that the sensitivity of our DNA probes was comparable to that of culture for diagnosis of gonorrhea and to conventional tests for detection of beta-lactamase.


Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma.
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.


FDG PET in the Evaluation of Parkinson's Disease.
Network analysis of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is an innovative approach for the study of in movement disorders, such as Parkinson's disease (PD). Spatial covariance analysis of imaging data acquired from PD patients has revealed characteristic regional patterns associated with the motor and cognitive features of disease. Quantification of pattern expression in individual patients can be used for diagnosis, assessment of disease severity, and evaluation of novel medical and surgical therapies. Identification of disease-specific patterns in other parkinsonian syndromes, such as multiple system atrophy and progressive supranuclear palsy, has improved diagnostic accuracy in patients with difficult to diagnose parkinsonism. Further developments of these techniques are likely to enhance the role of functional imaging in investigating underlying abnormalities and potential new therapies in these neurodegenerative diseases.


Amyloid-β and tau pathology of Alzheimer's disease induced by diabetes in a rabbit animal model.
Alzheimer's disease (AD) is the major age-dependent disease of the brain, but what instigates late-onset AD is not yet clear. Epidemiological, animal model, and cell biology findings suggest links between AD and diabetes. Although AD pathology is accelerated by diabetes in mice engineered to accumulate human-sequence amyloid-β (Aβ) peptides, they do not adequately model non-inherited AD. We investigated AD-type pathology induced solely by diabetes in genetically unmodified rabbits which generate human-sequence Aβ peptides. After 15 weeks, alloxan-treated diabetic rabbits with expected high blood glucose showed ~5-fold increase in Aβ40/Aβ42 in cortex and hippocampus, and significantly, generated Aβ-derived assemblies found in human AD. Deposits of these putative pathogenic toxins were detected by Aβ/Aβ oligomer antibodies in brain parenchyma and surrounding vasculature, also co-localizing with markedly elevated levels of RAGE. Soluble brain extracts showed diabetes-induced buildup of Aβ oligomers on dot-blots. Phospho-tau also was clearly elevated, overlapping with βIII-tubulin along neuronal tracts. Indications of retina involvement in AD led to examination of AD-type pathology in diabetic retinas and showed Aβ accumulation in ganglion and inner nuclear cell layers using Aβ/oligomer antibodies, and RAGE again was elevated. Our study identifies emergence of AD pathology in brain and retina as a major consequence of diabetes; implicating dysfunctional insulin signaling in late-onset AD, and a potential relationship between Aβ-derived neurotoxins and retinal degeneration in aging and diabetes, as well as AD. AD-type pathology demonstrated in genetically unmodified rabbits calls attention to the considerable potential of the model for investigation of AD pathogenesis, diagnostics, and therapeutics.


Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients.
The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site-specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph-node-positive non-small-cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1-2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1-2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P = .025 and .033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08-3.04, P = .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph-node-positive NSCLC patients.


Total lobectomy and total thyroidectomy in the management of thyroid lesions.
To study an unselected consecutive series of patients undergoing thyroidectomy for tumors to establish the complication rates of total lobectomy with isthmectomy and total thyroidectomy. Retrospective study. Two hundred eight consecutive, unselected patients were operated on by one surgeon from 1980 to 1990. One hundred nineteen patients (57%) had a total lobectomy and isthmectomy and 85 patients (41%) had total thyroidectomy. Four patients (2%) had partial excision for technical reasons, two with anaplastic cancers and two with advanced thyroiditis. Forty-two malignant lesions (20%) were diagnosed with a mean follow-up of 5 years. Malignant lesions were diagnosed in 15 (31%) of 48 males and 27 (17%) of 160 women. Ten patients (5%) had parathyroid adenomas. Long-term follow-up revealed that there were no deaths, permanent hypocalcemia, or recurrent laryngeal nerve damage. One patient was returned to the operating room to control bleeding. This study suggests that total thyroid lobectomy with isthmectomy and total thyroidectomy are both safe procedures in the management of thyroid tumors.


Counterpropagating path-entangled photon pair sources based on simultaneous spontaneous parametric down-conversion processes of nonlinear photonic crystal.
Ultra-bright source of entangled photons is an essential component in optical quantum information processing. Here we propose a counterpropagating path-entangled photon pair sources using a quasi-periodic modulated lithium niobate crystal. The nonlinear crystal designed by a dual-grid method, simultaneously phase-matched two spontaneous parametric down-conversion processes. Signal and idler modes have opposite propagation directions in the two spontaneous parametric down-conversion processes, which is the key to generating path-entangled photon pairs. Compared to copropagating entangled sources, the counterpropagating path-entangled sources result in a much narrower spectrum. The quantum state of the path-entanglement source is not only suited for quantum coding, but also to allow the implementation of complex quantum algorithms on a photonic chip.


Omics Approaches for Understanding Grapevine Berry Development: Regulatory Networks Associated with Endogenous Processes and Environmental Responses.
Grapevine fruit development is a dynamic process that can be divided into three stages: formation (I), lag (II), and ripening (III), in which physiological and biochemical changes occur, leading to cell differentiation and accumulation of different solutes. These stages can be positively or negatively affected by multiple environmental factors. During the last decade, efforts have been made to understand berry development from a global perspective. Special attention has been paid to transcriptional and metabolic networks associated with the control of grape berry development, and how external factors affect the ripening process. In this review, we focus on the integration of global approaches, including proteomics, metabolomics, and especially transcriptomics, to understand grape berry development. Several aspects will be considered, including seed development and the production of seedless fruits; veraison, at which anthocyanin accumulation begins in the berry skin of colored varieties; and hormonal regulation of berry development and signaling throughout ripening, focusing on the transcriptional regulation of hormone receptors, protein kinases, and genes related to secondary messenger sensing. Finally, berry responses to different environmental factors, including abiotic (temperature, water-related stress and UV-B radiation) and biotic (fungi and viruses) stresses, and how they can significantly modify both, development and composition of vine fruit, will be discussed. Until now, advances have been made due to the application of Omics tools at different molecular levels. However, the potential of these technologies should not be limited to the study of single-level questions; instead, data obtained by these platforms should be integrated to unravel the molecular aspects of grapevine development. Therefore, the current challenge is the generation of new tools that integrate large-scale data to assess new questions in this field, and to support agronomical practices.


Particles in filter effluent: the roles of deposition and detachment.
Particles in the effluent of granular media filters can be classified as influent particles that were never removed or as particles that detached after prior deposition. To determine the effects of particle size, filter media depth and filter run duration on the relative fraction of each class, laboratory experiments were performed using suspensions of four sizes of polystyrene particles (0.2, 1.2, 2.5, and 4.0 microm diameters) that were destabilized with 0.04 M calcium chloride and continuously supplied to filters after flocculation. To investigate particle attachment alone, three sizes (1.4, 4.0, and 9 microm) of fluorescent microspheres (FM) were periodically pulse injected immediately ahead of the filter media. Detachmentwas assessed as the difference between net removal (particle counts) and deposition (FM counts). FM deposition followed theory, while results show that particle detachment was significant from an early phase of filtration (100 minutes). The detached fraction of effluent particles increased with particle size (1 to 12 microm range) and filter depth. These model system results suggest that detachment plays a significant role in the origin of filter effluent particles in full-scale water treatment systems.


[Time based management in health care system: the chosen aspects].
Time-based management (TBM) is the key element of the whole management process. For many years in health care systems of highly developed countries modern and effective methods of time-based management have been implemented in both primary health care and hospitals (emergency departments and operating rooms). Over the past two decades a systematic review of Polish literature (since 1990) and peer reviewed articles published in international journals based on PubMed/Medline (2001-2011) have been carried out. The collected results indicate that the demographic and health changes in the populations are one of the main challenges facing general practitioners in the nearest future. Time-based management needs new and effective tools and skills, i.e., identification of priorities, well designed planning, delegation of the tasks, proper coordination, and creation of primary care teams that include additional members and human resources management. Proper reimbursement of health services, development of IT in health care system, better collection, storage, processing, analysis and exchange of information and research findings will also be needed. The use of innovative technologies, like telemedicine consultations, provides the possibility of reducing waiting time for diagnosis and treatment and in some cases could be applied in terms of secondary care. To improve the efficiency of operating rooms it is necessary to introduce different solutions, such as operating room coordinator involvement, application of automation to guide decision-making or use of robotic tools to assist surgical procedures. Overcrowded emergency departments have a major detrimental effect on the quality of hospital functions, therefore, efforts should be made to reduce them. Time-based management training among physicians and health care management in Poland, as well as the implementation of practice-based solutions still applied in highly developed countries seem to be necessary.


Could the United States experience rubella outbreaks as a result of vaccine refusal and disease importation?
Prenatal rubella infection early in gestation is likely to damage the fetus, leading to miscarriage, stillbirth, neonatal death, or congenital rubella syndrome (CRS). CRS is a devastating syndrome that encompasses a wide variety of disorders, including (but certainly not limited to) cataracts, congenital heart defects, deafness, and mental retardation. Elimination of rubella was declared in the United States in 2004; however, the US faces the risk of rubella outbreaks. In this article, we discuss the possibility of rubella outbreaks in the US due to refusal of measles-mumps-rubella (MMR) vaccination and importation of the disease from regions where vaccination coverage is suboptimal. To avoid the severe health consequences associated with prenatal rubella infection, continued attention should be given to the maintenance of high MMR coverage.


Docetaxel and cisplatin as primary chemotherapy for treatment of locally advanced breast cancers.
A phase II trial was designed to evaluate the effectiveness of docetaxel/cisplatin as primary or neoadjuvant chemotherapy of locally advanced breast carcinoma (LABC). Patients with newly diagnosed breast cancers > or = 5 cm in size by palpation were treated with docetaxel/cisplatin, both at 70 mg/m2 intravenously every 21 days for 4 courses. Upon completion of chemotherapy, all patients underwent modified radical mastectomy with axillary nodal dissection. Pathologic complete response (pCR) was defined as absence of any invasive carcinoma in the breast. Standard AC (doxorubicin/cyclophosphamide) at 60 mg/m2 and 600 mg/m2, respectively, for 4 cycles was given as adjuvant therapy to maximally eradicate occult distant disease. Between March 1998 and October 2001, 57 women were entered onto this trial, 28 (49%) with inoperable T4 and inflammatory cancers. Pretreatment median tumor size was 9 cm. Thirty-six patients (63%) had estrogen receptor-positive tumors and 10 patients (18%) had tumors with HER2 overexpression. All tumors became operable after neoadjuvant chemotherapy. Pathologic complete response in the breast was achieved in 15 patients (26%) and pCR in the breast and the axilla was achieved in 11 patients (20%). All neoadjuvant chemotherapy courses were administered at full doses without treatment delays caused by toxicity. The most common side effects were hyperglycemia, anemia, and mild neuropathy. The results of this study suggest that the docetaxel/cisplatin combination can be an effective and well-tolerated induction treatment of LABC, even in very large mostly HER2-nonoverexpressing tumors.


Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families.
Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). Whether the wide inter-individual variability in the plasma lipidome contributes to the genetic basis of T2D is unknown. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits. We used plasma lipidomic data (1202 pedigreed individuals, 319 lipid species representing 23 lipid classes) from San Antonio Family Heart Study in Mexican Americans. Bivariate trait analyses were used to estimate the genetic and environmental correlation of all lipid species with three T2D-related traits: risk of T2D, presence of prediabetes and homeostatic model of assessment - insulin resistance. We found that 44 lipid species were significantly genetically correlated with one or more of the three T2D-related traits. Majority of these lipid species belonged to the diacylglycerol (DAG, 17 species) and triacylglycerol (TAG, 17 species) classes. Six lipid species (all belonging to the triacylglycerol class and containing palmitate at the first position) were significantly genetically correlated with all the T2D-related traits. Our results imply that: a) not all plasma lipid species are genetically informative for T2D pathogenesis; b) the DAG and TAG lipid classes partially share genetic basis of T2D; and c) 1-palmitate containing TAGs may provide additional insights into the genetic basis of T2D.


Structural features and the reaction mechanism of cytochrome oxidase: iron and copper X-ray absorption fine structure.
X-ray edge absorption of copper and extended fine structure studies of both copper and iron centers have been made of cytochrome oxidase from beef heart, Paracoccus dentrificans, and HB-8 thermophilic bacteria (1-2.5 mM in heme). The desired redox state (fully oxidized, reduced CO, mixed valence formate and CO) in the x-ray beam was controlled by low temperature (-140 degrees C) and was continuously monitored by simultaneous optical spectroscopy and by electron paramagnetic resonance (EPR) monitoring every 30 min of x-ray exposure. The structure of the active site, a cytochrome a3-copper pair in fully oxidized and in mixed valence formate states where they are spin coupled, contains a sulphur bridge with three ligands 2.60 +/- 0.03 A from Fea3 and 2.18 +/- 0.03 A from Cua3. The distance between Fea3 and Cua3 is 3.75 +/- 0.05 A, making the sulphur bond angle 103 degrees reasonable for sp3 sulphur bonding. The Fea3 first shell has four typical heme nitrogens (2.01 +/- 0.03 A) with a proximal nitrogen at 2.14 +/- 0.03 A. The sixth ligand is the bridging sulphur. The Cua3 first shell is identical to oxidized stellacyanin containing two nitrogens and a bridging sulphur. Upon reduction with CO, the active site is identical to reduced stellacyanin for the Cua3 first shell and contains the sulphur that forms the bridge in fully oxidized and mixed valence formate states. The Fea3 first shell is identical to oxyhemoglobin but has CO instead of O2. The other redox centers, Fea and the other "EPR detectable" Cu are not observed in higher shells of Fea3. Fea has six equidistant nitrogens and Cua has one (or two) nitrogens and three (or two) sulphurs with typical distances; these ligands change only slight on reduction. These structures afford the basis for an oxygen reduction mechanism involving oxy- and peroxy intermediates.


Photosynthetic oxygenation for urine nitrification.
Human urine accounts for only a fraction of the sewage volume, but it contains the majority of valuable nutrient load in wastewater. In this study, synthetic urine was nitrified in a closed photo-bioreactor through photosynthetic oxygenation by means of a consortium of microalgae and nitrifying bacteria. In situ production of oxygen by photosynthetic organisms has the potential to reduce the energy costs linked to conventional aeration. This energy-efficient strategy results in stable urine for further nutrient recovery, while part of the nutrients are biologically recovered in the form of valuable biomass. In this study, urine was nitrified for the first time without conventional aeration at a maximum photosynthetic oxygenation rate of 160 mg O2 gVSS-1 d-1 (VSS: volatile suspended solids). A maximum volumetric nitrification rate of 67 mg N L-1 d-1 was achieved on 12% diluted synthetic urine. Chemical oxygen demand (COD) removal efficiencies were situated between 44% and 83% at a removal rate of 24 mg COD gVSS-1 d-1. After 180 days, microscopic observations revealed that Scenedesmus sp. was the dominant microalga. Overall, photosynthetic oxygenation for urine nitrification is promising as a highly electricity efficient approach for further nutrient recovery.


Direction of translation in bacteriophage S13.
Suppressible (amber-type) mutants in gene IIIa of bacteriophage S13 show polarity in reducing the activity of only the neighboring gene IIIb. The polarity implies that the genome is translated in the direction of IIIa to IIIb. From the known homology of the messenger RNA with the single-stranded DNA, the orientation of the DNA with respect to the genetic map can also be inferred.


Premature ventricular contractions in normal children.
Premature ventricular contractions (PVCs) are frequently seen in children with normal cardiac findings. The purpose of this study was to evaluate the characteristics and the prognosis of PVCs in children with normal heart. This study included 149 children with PVC who did not have systemic or cardiac disease. Their median age at diagnosis was 10 years (range 1 month to 17 years). Seventy-six children (51%) were symptomatic. Most of the patients had unifocal PVC, whereas 5 (3.1%) of them had multifocal PVCs. The patients were evaluated by repeated Holter recordings and exercise test. In the first Holter monitoring recordings, PVCs were in the form of isolated PVC in 122 (82%) patients, couplet-triplet in 14 (9%) patients and nonsustained ventricular tachycardia in 13 (9%) patients. The exercise test was performed in 105 (70.5%) patients. The frequency of PVCs decreased and disappeared in 65 (61.9%) children, increased in 8 (7.6%), and were unchanged during exercise in 32 (30.5%). There was no difference between the groups according to exercise response regarding PVC quantity. Fifty-two of 149 children (35%) were followed up for a median period of 22 months. After follow-up, PVCs of 25 of the 52 patients (48.1%) decreased and disappeared. We did not find any correlation between the frequency of PVC and treatment, age, gender or the PVC frequency decrease with exercise. In conclusion, PVCs in normal children have benign prognosis and during follow-up a considerable percent show improvement.


A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training.
Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE). Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE. A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs.


Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.
Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration.


A promising broad spectrum antimicrobial red fluorescent protein present in silkworm excreta.
The purified silkworm excretory red fluorescent protein (SE-RFP) has exhibited a potent broad spectrum antimicrobial activity. The anti-microbial assays of purified SE-RFP against several pathogenic bacterial (both Gram positive and Gram negative) and fungal strains were performed by agar cup plate method. The minimum inhibitory concentration (MIC) of SE-RFP against pathogenic bacteria and fungi was evaluated by agar dilution technique. The SE-RFP has exhibited highest activity (lowest minimum inhibitory concentration and largest zone of inhibition) against Staphylococcus aureus and Candida albicans among the tested bacteria and fungi, respectively. For the first time, we are reporting here the bioactivity of a red fluorescent protein purified from the silkworm excreta against clinically important bacteria and fungi. The bioactive SE-RFP has two absorption peaks at 280 and 603 nm and, it has exhibited fluorescence emission peaks at 334 and 619 nm upon exciting at 280 and 603 nm, respectively. The SE-RFP being an aqua-soluble, economically feasible and eco-friendly protein, it can therefore be used for the practical applications as an effective antimicrobial agent.


Longitudinal Changes and Seasonal Variation in Body Composition in Professional Australian Football Players.
To compare development and variations in body composition of early-, mid-, and late-career professional Australian Football (AF) players over 3 successive seasons. Regional and total-body composition (body mass [BM], fat mass [FM], fat-free soft-tissue mass [FFSTM], and bone mineral content [BMC]) were assessed 4 times, at the same time of each season-start preseason (SP), end preseason (EP), midseason (MS), and end season (ES)-from 22 professional AF players using pencil-beam dual-energy X-ray absorptiometry. Nutritional intake for each player was evaluated concomitantly using 3-d food diaries. Players were classified according to their age at the beginning of the observational period as either early- (<21 y, n = 8), mid- (21 to 25 y, n = 9), or late- (>25 y, n = 5) career athletes. Early-career players had lower FFSTM, BMC, and BM than mid- and late-career throughout. FM and %FM had greatest variability, particularly in the early-career players. FM reduced and FFSTM increased from SP to EP, while FM and FFSTM decreased from EP to MS. FM increased and FFSTM decreased from MS to ES, while FM and FFSTM increased during the off-season. Early-career players may benefit from greater emphasis on specific nutrition and resistance-training strategies aimed at increasing FFSTM, while all players should balance training and diet toward the end of season to minimize increases in FM.


Quantifying heterogeneity in exposure-risk relationships using exhaled breath biomarkers for 1,3-butadiene exposures.
The health effects of human exposure to 1,3-butadiene (BD) have been extensively studied using both epidemiological and animal toxicology approaches. However, various data and knowledge gaps remain, one of which is an understanding of the human heterogeneity in BD dosimetry. The objective of our study was to better understand the role of individual variability in delivered tissue dose. We designed a study of laboratory exposures of a relatively large group of healthy human subjects. Subjects were then exposed to 2.0 ppm BD through a face mask for 20 min, followed by 40 min of breathing clean air. Exhaled breath concentrations of BD were measured at ten time points during and after exposure, and a three-compartment physiologically based pharmacokinetic (PBPK) model was used to quantify the kinetic behavior of BD. We implemented a Markov chain Monte Carlo procedure to fit the model to the experimental data, and used global sensitivity analysis techniques to examine the sensitivity of exhaled breath concentrations to PBPK model parameters. Uptake during exposure was strongly influenced by rebreathing of exhaled BD during exposure; inclusion of rebreathing in the model simulations resulted in a 21% increase in the amount of BD retained in the body. We found that uptake ranged from 38% to 77% across individuals. We measured considerable intra-individual variability from 11 subjects who underwent the testing twice. Most of this variation stemmed from phase I metabolism of BD, which varied by as much as a factor of 2.6 within individuals. Overall, we have sought to quantify the sources of inter- and intra-individual variabilities in the pharmacokinetic behavior of BD. The results of our research may impact the current framework for biomarker and pharmacokinetic studies by improving our understanding of the sources of heterogeneity in response to chemical exposures.


Low-Intensity Outreach to Increase Uptake of HIV Preexposure Prophylaxis Among Patients with Sexually Transmitted Infections.
We piloted a low-intensity outreach intervention to increase linkage to PrEP care among HIV-uninfected individuals with rectal sexually transmitted infections or syphilis. We sent a secure email message or letter with information about accessing PrEP. Of those sent an email, 12.4% were linked to PrEP care; linkage differed by race/ethnicity, ranging from 0% of Black individuals to 32% of Hispanic individuals (P = 0.019). No individuals sent letters were linked to PrEP care. A one-time secure email to high-risk patients is feasible to increase linkage to PrEP care. Studies are needed to evaluate scalable interventions to increase PrEP uptake in at-risk populations.


The natriuretic peptides in heart failure: diagnostic and therapeutic potentials.
The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth-inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor (NPR-B). All three peptides are cleared by the natriuretic peptide-C receptor (NPR-C) and are degraded by the ectoenzyme neutral endopeptidase 24.11 (NEP), both of which are widely expressed in the kidneys, lungs, and the vascular wall. Congestive heart failure (CHF) represents a pathological state in which the activation of the natriuretic peptides exceeds those of all other states. In this brief review, we will attempt to provide an update on important issues regarding natriuretic peptides in CHF, with a focus on their functional importance as a beneficial humoral response in asymptomatic left ventricular dysfunction (LVD), the mechanisms of natriuretic peptide hyporesponsiveness in severe heart failure, the diagnostic and prognostic significance of the natriuretic peptides in CHF, and the therapeutic potential of the natriuretic peptides in this multiorgan syndrome.


The transferability of Western concepts to other cultures: validation of the Zuckerman-Kuhlman Personality Questionnaire in a Saudi Arabic context.
The importance of medical education research in Saudi Arabia has been acknowledged increasingly and a lot of concepts used have been derived from the Western world. The question arises, however, whether Western concepts and questionnaires are transferable to societies with different cultures. The aim of this study was to investigate the instrument structure and the reliability of the Arabic version of the Zuckerman-Kuhlman Personality Questionnaire-medium (ZKPQ-m). Three statistical methods with decreased amount of strictness were used to analyse our data: Confirmatory Factor Analysis, Procrustes rotation and Principal Component Analysis. Our outcomes did not confirm the original instrument structure. Instead, we found four interpretable components: Emotional Instability, Impulse-seeking, Activeness and Self-Control. However, the amount of explained variance was not very high and the internal consistencies ranged from unsatisfactory to only moderate. The data showed a high percentage of respondents agreeing with more than three items of the Infrequency scale, which may be attributable to the collectivistic culture in Saudi Arabia. We did not succeed in replicating the ZKPQ structure in the Arabic context. Social desirability, a common characteristic in collectivistic cultures, may have reduced the replicability of the internal structure of the ZKPQ-m. Different methods to measure concepts in collectivistic cultures may help to get round social desirability.


A neighborhood-based approach to population health in the pediatric medical home.
Health care reform is increasingly focused on population health outcomes. Local strategies low-income neighborhoods could connect every newborn to a medical home and create a platform to link them with other health-promoting community resources. (1) To improve connections to the medical home for infants from one low-income neighborhood (2) To increase the number of families enrolled in a local home visiting program, and (3) To improve communication between medical staff and home visitors. The study was conducted in a neighborhood with 550 births per year and median household income of $27,000. Quality improvement methods were used to test: (1) newborn registry in the medical home, (2) proactive outreach by nursing staff, (3) standardized protocol for enrolling families in home visiting, and (4) coordination of care between medical home and home visitors. Outcomes were timeliness of well child care and enrollment in home visiting. Time series analyses compared patients from the intervention neighborhood with a demographically similar neighborhood. Mean age at newborn visit decreased from 14.4 to 10.1 days of age. Attendance at 2- and 4-month well child visits increased from 68 to 79% and 35 to 59 %, respectively. Rates did not improve for infants from the comparison neighborhood. Confirmed enrollment in home visiting increased. After spread to 2 more clinics, 43 % of infants in the neighborhood were reached. Neighborhood-based newborn registries, proactive nursing outreach, and collaboration with a home visiting agency aligned multiple clinics in a low-income neighborhood to improve access to health-promoting services.


[General and local humoral immunity and intestinal microflora in children with skin manifestations of food allergy].
The authors describe the results of studies into the common and local humoral immunological system in 60 children under one year of age suffering from atopic dermatitis of varying severity. The passive hemagglutination test with the use of a kit of erythrocytic diagnosticums devised at the Institute of Nutrition, Academy of Medical Sciences of the USSR, was used to study the degree of the child's body sensitization with cow's milk antigens and the content of IgG, IgM and IgA in the blood and that of secretory IgA in coprofiltrates. Polyvalent sensitization of the body with food antigens was found in 50% of the children examined to reveal an interplay between the degree of sensitization with the severity of the pathological process. It was demonstrated that penetration of food antigens through the epithelial barrier of the gastrointestinal tract was not related to the deficiency of the secretory IgA, since this class of immune proteins was detectable in the coprofiltrates from all the children. Besides, the content of these proteins was not reduced during the severe form of the disease. In this case, the intestine of all the children examined showed dysbacteriosis which needed correction. The blood serum manifested a decrease in the level of IgM and IgG which was more pronounced in the patients with a severe disease course.


Association of the pattern of transition between arousal states in neonates with the cord blood lead level.
In this study of 167 neonates who demonstrated a total of 1010 transitions between arousal states, we considered whether specific state transitions were associated with umbilical cord blood lead levels. We found that the arousal patterns of neonates with varying levels (<1, 1-10 and >10 microg/dL) of lead exposure could not be distinguished based on the NBAS scoring system alone, but their transition state patterns revealed striking differences. Specifically, the neonates with the highest lead levels were more fidgety, had more state transitions from state 5 or 6, and were least likely to fall from awake states back into lower states. Arousal state transition pattern is thus a novel correlate of umbilical cord blood lead that may be useful for risk stratification of the neonates.


Symposium on understanding and influencing consumer food behaviours for health: executive summary report.
Food consumption patterns in Asia are rapidly changing. Urbanization and changing lifestyles have diminished the consumption of traditional meals based on cereals, vegetables and root crops. These changes are accompa-nied by an increasing prevalence of chronic diseases among Asian populations. ILSI Southeast Asia and CSIRO, Australia jointly organized the Symposium on Understanding and Influencing Food Behaviours for Health, focusing on the use of consumer science to improve food behaviour. The goals of the Symposium were to present an understanding of Asian consumers and their food choices, examine the use of consumer research to modify food choices towards better health, illustrate how health programs and food regulations can be utilized effectively to promote healthier choices, and identify knowledge gaps regarding the promotion of healthy food behaviour in Asian populations. There is no difference in taste perception among Asians, and Asian preference for certain tastes is determined by exposure and familiarity largely dictated by culture and its underlying values and beliefs. Cross-cultural validity of consumer science theories and tools derived from western populations need to be tested in Asia. Information on consumption levels and substitution behaviours for foods and food products, obtained using consumer research methods, can guide the development of food regulations and programs that will enable individuals to make healthier choices. Existing knowledge gaps include consumer research techniques appropriate for use in Asian settings, diet-health relationships from consumption of traditional Asian diets, and methods to address the increasing prevalence of over- and undernutrition within the same households in Asia.


The Collaborative Longitudinal Personality Disorders Study: development, aims, design, and sample characteristics.
This paper describes the aims, background, design, and methods used in a collaborative longitudinal study of Axis II personality disorders (PDs). This study examines the putative stability of selected PD diagnoses and criteria, what factors affect their course, and whether their stability and course distinguishes them from a representative Axis I disorder. This article also describes the acquisition and demographics of the sample on whom the study is being done. A prospective, repeated measures investigation of the stability of PDs is now underway at multiple clinical settings in four collaborating urban sites in Boston. New Haven, New York, and Providence. Diagnostic assignments are based on semistructured interview assessments (by clinically trained raters) and confirmed by at least one additional contrasting diagnostic method. The sample consists of 668 treatment seeking and reliably diagnosed adults recruited from a broad range of clinical sites. By design, patients in the sample met standards for one of five diagnostic subgroups: (a) schizotypal (N = 86); (b) borderline (N = 175); (c) avoidant (N = 157); (d) obsessive-compulsive (N = 153) personality disorders or a control group having (e) major depressive disorder without personality disorder (N = 97).