Sex and gender differences in myocarditis and dilated cardiomyopathy: An update.
In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2-4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.


[Peritoneal anionic transfers and their relationship with peritoneal transport and acid-base status].
This study was designed to assess lactate and TCO2 transfers during PET and in 24-hour drained dialysate, relating them with the membrane transport type and acid-base status. Forty PETs were studied, performed in 23 clinically stable patients maintained on CAPD for 6.5 +/- 3 months using 35 mEq/l of lactated-based dialysate. No significant changes in plasma concentration of lactate and TCO2 were observed. Lactate gain (LG) was 51.91 +/- 4.86 and 220.82 +/- 22.61 mEq and TCO2 loss was 46.49 +/- 6.9 and 183.51 +/- 32.9 mEq during PET and 24 h respectively. When analyzed these transfers according to membrane transport characteristics (High/High-average group: HHAG and low/low-average group: LLAG), LG was significantly higher (53.94 +/- 3.7 vs 48.86 +/- 4.8 mEq during TEP p < 0.01, and 228.06 +/- 15.6 vs 209.96 +/- 27.2 mEq during 24 h p < 0.05). TCO2 loss was greater (48.66 +/- 7.15 vs 43.25 +/- 5.5 mEq p < 0.05 and 187.22 +/- 27.3 vs 177.93 +/- 35.3 during PET and 24 h respectively) in HHAG vs LLAG. When evaluating transfers according to patients' acid-base status (normal and acidotic group), no significant differences were found in LG, but there was a significant difference in TCO2 loss (47.7 +/- 5.9 vs 39.76 +/- 6.1 mEq p < 0.01). We did not observe significant differences in acid-base balance during PET according to membrane transport characteristics (HHAG vs LLAG). However, acid-base balance was more positive in acidotic patients' PET than in normal patients (9.87 +/- 6.6 vs 3.92 +/- 6.8 mEq p < 0.05). TCO2 loss during PET directly correlated with plasma TCO2 concentration pre-PET (r: 0.43, p < 0.01). However no significant correlation was found between plasma lactate levels and lactate gain during PET. In conclusion, the lactate gain and bicarbonate loss account for the net dialytic base balance during PET and 24 h. However, the peritoneal membrane transport characteristics as well as the acid-base status can determine a higher or lower aionic transfer (lactate and bicarbonate).


Effect of autoclaving and physical structure of diets on their utilization by mice.
A pelleted and 2 expanded rodent diets were autoclaved at 121 degrees C for 20 minutes, and fed to DBA/1 and LACA strains of mice. Reproduction was not significantly different on any diet and autoclaving had no effect other than increasing the intervals between litters. However, apparent food consumption was greater and efficiency of food utilization (expressed as young weaned/diet consumed) was poorer in mice fed pelleted diets. Diet had no significant effect on growth, but food wastage and consequently apparent food consumption were less and food utilization more efficient when expanded diets were fed. In addition, true food consumption was lower and food conversion more efficient. Autoclaving had little effect on expanded diets but caused a significant reduction in wastage and in apparent and true consumption of the pelleted diet, perhaps because of increased hardness.


Structural analysis of pentacene thin film growth on polycrystalline Ox-Au surfaces using scanning tunneling microscopy.
In this letter, we show the feasibility to use scanning tunneling microscopy (STM) as a stand-alone technique in analyzing the structure of organic thin films grown on polycrystalline metal surfaces. At room temperature, by effectively suppressing the molecule-substrate interaction, pentacene resumes the typical quasi layer-by-layer growth with the "thin-film phase" structure due to intermolecule interaction, while substrate roughness does not play an important role. By elevating the substrate to 320 K, two different polycrystalline phases, that is, the "thin-film phase" and the "single-crystal phase" intermixed grow and form terraced and lamellar structures, respectively. Using STM distance-voltage spectroscopy, the energy level alignment of the underlying organic/metal interfaces can also be acquired.


Noise levels in a general intensive care unit: a descriptive study.
The aim of this small-scale study was to measure, analyse and compare levels of acoustic noise, in a nine-bedded general intensive care unit (ICU). Measurements were undertaken using the Norsonic 116 sound level meter recording noise levels in the internationally agreed 'A' weighted scale. Noise level data were obtained and recorded at 5 min over 3 consecutive days. Results of noise level analysis indicated that mean noise levels within this clinical area was 56.42 dB(A), with acute spikes reaching 80 dB(A). The quietest noise level attained was that of 50 dB(A) during sporadic intervals throughout the 24-h period. Parametric testing using analysis of variance found a positive relationship (p <or= 0.001) between the nursing shifts and the day of the week. However, Scheffe multiple range testing showed significant differences between the morning shift, and the afternoon and night shifts combined (p <or= 0.05). There was no statistical difference between the afternoon and night shifts (p >or= 0.05). While the results of this study may seem self-evident in many respects, what it has highlighted is that the problem of excessive noise exposure within the ICU continues to go unabated. More concerning is that the prolonged effects of excessive noise exposure on patients and staff alike can have deleterious effect on the health and well-being of these individuals.


Lymphocyte activation and expression of the human leucocyte-endothelial cell adhesion molecule 1 (Leu-8/TQ1 antigen).
The Leu-8/TQ1 antigen, recently shown to be the human equivalent of the murine MEL-14 lymph node homing receptor and now designated as leucocyte-endothelial cell adhesion molecule, LECAM-1, has been used to dissect T, B and natural killer (NK) cells into various subpopulations with different functional properties, such as suppressor-inducer (CD4+ Leu-8/TQ1+) or helper (CD4+ Leu-8/TQ1-) T lymphocytes. Diminished Leu-8/TQ1 antigen density has been reported after lymphocyte activation with B- or T-cell specific stimuli for several days. In the present study, we sought to determine the signal requirements for altered Leu-8/TQ1 expression. Exposure of freshly isolated peripheral blood lymphocytes to phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophores was found to cause rapid down-regulation of the Leu-8 antigen, with little or no Leu-8 reactivity remaining 1 hr after simultaneous addition of PMA and calcium ionophores to the culture medium. TQ1 reactivity was changed in parallel with that of Leu-8. Leu-8 expression of T and B cells was sensitive to both PMA and calcium ionophores, whereas Leu-8 expression of NK cells was affected by PMA but not by the calcium ionophore A23187. The effect of PMA on Leu-8/TQ1 expression could be antagonized by pretreatment with the protein kinase C inhibitor, H7, whereas that of A23187 could not. Partial re-expression of the Leu-8 antigen was seen 3 days after addition of PMA alone but not when it was given together with calcium ionophores. After Leu-8 down-regulation induced by 1 hr treatment with PMA or calcium ionophores. Leu-8 re-expression was observed within 24 hr when stimuli were removed by washing. Activation of T cells with anti-CD3 antibody resulted in a partial reduction of Leu-8/TQ1 expression, first detectable after 1-3 hr of stimulation and maximal at 24 hr. Fully mitogenmic concentrations of concanavalin A (Con A) did not affect Leu-8 expression within the first hours of culture. Transient reduction of Leu-8 expression was seen 24 hr after supraoptimal dosages of Con A, but Con A-stimulated lymphocytes cultured for 4-12 days with interleukin-2 (IL-2) retained Leu-8/TQ1 reactivity to a similar degree as fresh cells. In contrast to Leu-8/TQ1, CD45RA expression was not altered after 1 hr treatment with PMA and/or calcium ionophores but gradually disappeared during 1 week after Con A stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)


Grafting Techniques towards Production of Peptide-Tethered Hydrogels, a Novel Class of Materials with Biomedical Interest.
In recent years, new highly functional polymeric biomaterials are being developed to increase the therapeutic efficacy in tissue regeneration approaches. Peptides regulate most physiological processes and display several other biological activities. Therefore, their importance in the field of biomedical research and drug development is rapidly increasing. However, the use of peptides as therapeutic agents is restricted by some of their physicochemical properties. The development of improved routes of delivery of peptide-based therapeutics is crucial and is crucial and its biomedical value is expected to increase in the near future. The unique properties of hydrogels triggered their spreading as localized drug depots. Several strategies, such as the carbodiimide chemistry, have been used to successfully immobilize bioactive peptide sequences into the hydrogels backbone. Peptide tethering through the so-called "click" chemistry reactions is also a highly promising, yet underexplored, approach to the synthesis of hydrogels with varying dimensions and patterns. The present review focus on the approaches that are being used for the establishment of chemical bonds between peptides and non-peptidic hydrogels throughout the last decade.


Survival of heat-shocked Yersinia enterocolitica after irradiation in ground pork.
Earlier studies conducted in our laboratory showed that heat-shocked Yersinia enterocolitica (45 degrees C for 60 min) are more resistant to a subsequent beat treatment of 55 or 60 degrees C in ground pork than cells not previously heat-shocked. The increased thermotolerance was partly attributed to the production of stress proteins. The present study was performed to determine if the stress proteins produced by heating could also afford protection to the cells to irradiation. As part of the study, the effect of air versus vacuum packaging on survival of Yersinia to irradiation was also examined. Irradiating the inoculated pork at 1.0 kGy was sufficient to completely eliminate this pathogen. The irradiation D value for both heat-shocked and non-heat-shocked cells was statistically the same (0.15 kGy). Neither heat-shocking Yersinia nor packaging under vacuum resulted in increased resistance of this organism to irradiation. In addition, no effect was seen in virulence of the cells after these treatments, when compared with controls.


Specificity, redundancy and dosage thresholds among gata4/5/6 genes during zebrafish cardiogenesis.
The Gata4/5/6 sub-family of zinc finger transcription factors regulate many aspects of cardiogenesis. However, critical roles in extra-embryonic endoderm also challenge comprehensive analysis during early mouse cardiogenesis, while zebrafish models have previously relied on knockdown assays. We generated targeted deletions to disrupt each gata4/5/6 gene in zebrafish and analyzed cardiac phenotypes in single, double and triple mutants. The analysis confirmed that loss of gata5 causes cardia bifida and validated functional redundancies for gata5/6 in cardiac precursor specification. Surprisingly, we discovered that gata4 is dispensable for early zebrafish development, while loss of one gata4 allele can suppress the bifid phenotype of the gata5 mutant. The gata4 mutants eventually develop an age-dependent cardiomyopathy. By combining combinations of mutant alleles, we show that cardiac specification depends primarily on an overall dosage of gata4/5/6 alleles rather than a specific gene. We also identify a specific role for gata6 in controlling ventricle morphogenesis through regulation of both the first and second heart field, while loss of both gata4/6 eliminates the ventricle. Thus, different developmental programs are dependent on total dosage, certain pairs, or specific gata4/5/6 genes during embryonic cardiogenesis.This article has an associated First Person interview with the first author of the paper.


[Socio-demographic and clinical profile of a population of patients coming for consultation to the psychiatric department of a general hospital in southern Tunisia].
mental disorders are a very common health condition and a major public health issue. The purpose of this study was to examine the epidemiological and clinical characteristics of patients coming for consultation to the psychiatric department of the Regional Hospital of Gabes, and to identify risk factors for the main mental disorders. we conducted a retrospective study, including all patients consulting the psychiatry department of Gabes for the first time between 01/01/2010 and 31/12/2013. Diagnoses were classified according to the 10th reversion of the WHO International Classification of Diseases (ICD10). one thousand one hundred and one consultation cases were included in this study. The sex ratio (M/F) was 0.96. The average age of patients was 34 years (IQR=24-47.5 years), the median time between symptom onset and consultation to the psychiatric department was 1 year (IQR=3months-2 years). The three most common diagnosed were depressive disorders (21%), followed by schizophrenia (10.6%) and mental retardation (9.7%). Depressive disorders were significantly more common among female patients (p<0.001), married patients (p<0.001) and middle-aged adults (40-65 years) (p<0.001). The prevalence of these disorders was not significantly associated with either educational level, professional activity or socio-economic level. the knowledge of the socio-demographic and clinical profile of the most frequent mental disorders and factors associated with them would make it possible to better adapt the supply of care to the demand and to identify the needs in terms of mental health training in South-East Tunisia.


Measurement and prevalence of adult physical activity levels in Arab countries.
This study aims to examine the reported prevalence of sufficient physical activity among adults in Arab countries and to determine the use of validated instruments for assessing physical activity. This is a systematic literature review. This review follows recommendations outlined in the Meta-Analysis of Observational Studies in Epidemiology guidelines. The protocol for this study was preregistered with PROSPERO. Cross-sectional, cohort and intervention studies with a minimum of 300 adults aged ≥18 years assessing physical activity using a questionnaire or other self-report measure in the Arabic language were identified from seven electronic databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, PsycINFO, SPORTDiscu and PubMed). Databases were searched from 1st January 2008 to 17th September 2018. Descriptive analysis was performed using frequency and percentages. The prevalence of physical activity was calculated as the average prevalence for the reported percentages from the studies with similar tools. Fifty studies involving 298,242 participants were included in this review. The mean (range) sample size was 5964.8.1 (323-197,681). Data were collected from participants in 16 of the 22 Arab countries. Great variation exists across the studies in determining whether adults were sufficiently active or not. Twenty studies reported usable data from the Global Physical Activity Questionnaire and the International Physical Activity Questionnaire (moderate & high categories). In these studies, prevalence of physical activity ranged from 34.2 to 96.9%. It was not possible to compare the other studies owing to variation in instruments used to assess physical activity and in the case definition used for 'physically active'. This study highlights the need for wider reporting of physical activity and the adoption of valid and reliable instruments to support the development of evidence-informed policy and programmes at both country and regional level. International tools need to be correctly validated, or context-specific tools must be developed to accurately measure physical activity.


A high-dynamic-range digital RF-over-fiber link for MRI receive coils using delta-sigma modulation.
Coaxial cables commonly used to connect radio-frequency (RF) coil arrays with the control console of an MRI scanner are susceptible to electromagnetic coupling. As the number of RF channels increases, such coupling could result in severe heating and pose a safety concern. Non-conductive transmission solutions based on fiber-optic cables are considered to be one of the alternatives but are limited by the high dynamic range (>80 dB) of typical MRI signals. A new digital fiber-optic transmission system based on delta-sigma modulation (DSM) is developed to address this problem. A DSM-based optical link is prototyped using off-the-shelf components and bench-tested at different signal oversampling rates (OSRs). An end-to-end dynamic range (DR) of 81 dB, which is sufficient for typical MRI signals, is obtained over a bandwidth of 200 kHz, which corresponds to OSR = 50. A fully integrated custom fourth-order continuous-time DSM is designed in 180 nm CMOS technology to enable transmission of full-bandwidth MRI signals (up to 1 MHz) with an adequate DR. Initial electrical test results from this custom chip are also presented.


The Potential Role of Epigenetic Mechanisms in the Development of Retinitis Pigmentosa and Related Photoreceptor Dystrophies.
Retinitis pigmentosa and related photoreceptor dystrophies (RPRPD) are rare retinal diseases caused by hereditary gene mutations resulting in photoreceptor death, followed by vision loss. While numerous genes involved in these diseases have been identified, many cases have still not been associated with any gene, indicating that new mechanisms may be involved in the pathogenesis of these photoreceptor dystrophies. Many genes associated with RPRPD regulate photoreceptor specification and maturation in the developing retina. Since retinal development begins with a population of equivalent, proliferating retinal progenitor cells (RPCs) having a specific "competence" in generating all types of retinal neurons, including cone and rod photoreceptors, we tested the epigenetic changes in promoters of genes required for photoreceptor development and genes associated with RPRPD during RPC differentiation into cone and rod photoreceptors. We found that promoters of many of these genes are epigenetically repressed in RPCs but have no epigenetic restrictions in photoreceptors. Our findings also suggest that DNA methylation as an epigenetic mark, and DNA demethylation as a process, are more important than other epigenetic marks or mechanisms in the pathogenesis of these diseases. Most notably, irregularities in the DNA demethylation process during the RPC-to-photoreceptor transition may significantly contribute to retinitis pigmentosa (RP) pathogenesis since genes with hypermethylated promoters in RPCs account for at least 40% of autosomal recessive RP cases and at least 30% of autosomal dominant RP cases. Thus, we proposed an epigenetic model according to which unsuccessful demethylation of regulatory sequences (e.g., promoters, enhancers) of genes required for photoreceptor development, maturation, and function during the RPC-to-photoreceptor transition may reduce or even eliminate their activity, leading to RPRPD without any inheritable mutations in these genes.


Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients.
The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.


Reversed anionic Hofmeister series: the interplay of surface charge and surface polarity.
We describe a two-scale modeling approach toward anion specificity at surfaces of varying charge and polarity. Explicit-solvent atomistic molecular dynamics simulations at neutral hydrophobic (i.e., nonpolar) and neutral hydrophilic (i.e., polar) self-assembled monolayers furnish potentials of mean force for Na(+) and the halide anions F(-), Cl(-), and I(-) which are then used within Poisson-Boltzmann theory to calculate ionic distributions at surfaces of arbitrary charge for finite ion concentration. On the basis of calculated long-ranged electrostatic forces and coagulation properties, we obtain the direct anionic Hofmeister series at negatively charged hydrophobic surfaces. Reversal takes place when going to negative polar or to positive nonpolar surfaces, leading to the indirect series, while for positive polar surfaces the direct series is again obtained. This is in full accordance with a recent experimental classification of colloidal coagulation kinetics and also reflects the trends of the ion specific solubility properties of proteins. A schematic Hofmeister phase diagram is proposed. Partial series reversal is understood as a transient phenomenon for surfaces of intermediate polarity or charge.


Cell cycle progression of glutathione-depleted human peripheral blood mononuclear cells is inhibited at S phase.
Glutathione (GSH) the most abundant nonprotein thiol, is involved in the maintenance of the cellular redox state. In this capacity it may influence lymphocyte responsiveness to various stimuli. We have investigated the requirement of GSH during the activation and proliferation of PBMC. The intracellular GSH content of PBMC was altered by continuous culture or pretreatment with buthionine-S,R-sulfoximine (BSO), a specific and irreversible inhibitor of GSH synthesis. Initial experiments demonstrated that the addition of BSO at the initiation of culture, or shortly thereafter (6 hr), inhibited DNA synthesis and produced a simultaneous decrease in intracellular GSH. It was necessary that the BSO be present in the culture for at least 24 hr prior to the initiation of DNA synthesis for maximal inhibition. Cell cycle analysis revealed that BSO did not affect the entry and progression of PBMC through G1 of the cell cycle, however, entry into S-phase was inhibited in a dose-dependent fashion. These results were further substantiated by the inability of BSO to inhibit IL-2 production and expression of the IL-2R. In addition the timely expression of the transferrin receptor by BSO-treated cells indicated that the block occurred at the G1/S transition. The influence of GSH on early activation events was determined by BSO pretreatments. Lowering the intracellular GSH level of PBMC to less than 10% of the initial content prior to mitogenic stimulation did not impair the ability of these cells to produce IL-2 and express IL-2R, indicating that GSH may not be involved in the generation and response to early activation signals. Furthermore, the removal of BSO from these cultures rapidly reversed its inhibitory effects on DNA and GSH synthesis. In the course of these studies we also observed a modest (17%) albeit consistent increase during activation in the total thiol levels of GSH-depleted PBMC. These thiols may have a key role in the activation process. These data support our hypothesis that GSH is required for lymphocyte proliferation and that additional thiols are involved during the activation process.


Cerebral Metabolic Changes Related to Freezing of Gait in Parkinson Disease.
Freezing of gait (FOG) in Parkinson disease (PD) often occurs during steering of gait (i.e., complex gait), which is thought to arise from executive dysfunction. Our aim was to test whether cognitive corticobasal ganglia-thalamocortical circuitry is impaired and whether alternate neural circuits are used for complex gait in PD with FOG. Methods: Eighteen individuals with idiopathic PD in the off-medication state, 9 with FOG (aged 68 ± 6 y) and 9 without FOG (aged 65 ± 5 y), were included. PET was used to measure cerebral glucose metabolism during 2 gait tasks, steering and straight walking, performed during the radiotracer uptake period. Results: During steering, there was a reduced change in cerebral glucose metabolism within the cognitive corticothalamic circuit. More specifically, those with FOG had less activation of the posterior parietal cortex, less deactivation of the dorsolateral prefrontal cortex and thalamus, and increased activation in the supplementary motor area. Interestingly, activity in the dorsolateral prefrontal cortex correlated with gait impairment (i.e., reduced stride length) in the FOG group. Conclusion: These results demonstrate decreased parietal control and an alternate control mechanism mediated by prefrontal and supplementary motor areas in PD with FOG.


[Influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits].
To explore the influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits. Forty ordinary adult New Zealand rabbits were divided into saline, necrotic tissue homogenate (NTH), putrescine, and cadaverine groups according to the random number table, with 10 rabbits in each group. Saline, NTH, 10 g/L putrescine, and 10 g/L cadaverine were respectively peritoneally injected into rabbits of corresponding group in the amount of 1 mL/kg. The blood sample in the volume of 2 mL was collected from the central artery of rabbit ears before injection and at 2, 6, 12, 24, 30, 36, 48, 60 hours post injection (PIH). Contents of TNF-α, IL-1, and IL-6 in the serum were determined with enzyme-linked immunosorbent assay. Data were processed with repeated measurement data analysis of variance and Spearman correlation analysis, and cubic model curve was applied in curve fitting for the contents of inflammatory factors. (1) The serum contents of TNF-α, IL-1, and IL-6 were increased in NTH, putrescine, and cadaverine groups in different degrees at most post injection time points. There was no significant change in the concentrations of the three pro-inflammatory factors in saline group, and they were significantly lower than those of the other three groups at most post injection time points (with F values from 3.49 to 13.58, P values all below 0.05). The serum contents of TNF-α, IL-1, and IL-6 in putrescine group began to increase at PIH 2, 6, and 6, which was similar to the trend of NTH group, but the changes were delayed compared with those of cadaverine group(all at PIH 2). The peak values of TNF-α, IL-1, and IL-6 in putrescine group were respectively (339 ± 36), (518 ± 44), and (265.9 ± 33.5) pg/mL, which were significantly lower than those of cadaverine group [ (476 ± 86), (539 ± 22), and (309.4 ± 27.1) pg/mL], with F values respectively 5.11, 1.90, and 5.56, P values all below 0.05. (2) The period of time in which contents of TNF-α, IL-1, and IL-6 began to increase (PIH 3-4) and the peaking time of the three pro-inflammatory cytokines (PIH 18-30) in putrescine group appeared later than those of cadaverine group (PIH 2 and 12-30). The duration of peaking time of the three pro-inflammatory cytokines in putrescine group was shorter than that of cadaverine group (PIH 18-30 vs. PIH 12-30). The increasing period and the duration of peaking time of TNF-α, IL-1, and IL-6 in putrescine group were close to those of NTH group (PIH 3-5 and 18-30). The correlation coefficient test analysis showed that the trends of changes in contents of three pro-inflammatory cytokines in putrescine group were significantly correlated with those of NTH group (r(TNF-α) = 0.933, P < 0.01; r(IL-1) = 0.967, P < 0.01; r(IL-6) = 0.950, P < 0.01). The obvious correlation between cadaverine group and NTH group was only found in the contents of IL-1 and IL-6 (r(IL-1) = 0.913, P < 0.01; r(IL-6) = 0.883, P < 0.05). Both exogenous putrescine and cadaverine can cause inflammatory reaction in rabbits. The trend of the inflammatory reaction induced by putrescine was similar with that by NTH, suggesting that putrescine may play a leading role in the inflammatory reaction induced by necrotic tissue decomposition.


Severe pulmonary emphysema in a girl with interstitial deletion of 2q24.2q24.3 including ITGB6.
Owing to the large size of chromosome 2, partial monosomy of the long arm of this chromosome gives rise to many specific phenotypes. We report on a 2-month-old girl with an interstitial deletion of 2q24.2q24.3, which was confirmed by microarray-based comparative genomic hybridization analysis. The patient showed delayed growth and mental retardation, early myoclonic seizures, and characteristic dysmorphic features including thick arched eyebrows, upslanting palpebral fissures, long eyelashes, depressed nasal bridge, short nose, long philtrum, small mouth, micrognathia, and low set ears. Her early myoclonic seizures were likely due to haploinsufficiency of SCN1A and SCN2A, which are included in the deletion region. When she experienced acute bronchopneumonia, she showed severe pulmonary emphysema. The deletion region of 2q24.2 includes the integrin beta6 gene (ITGB6), which may prevent acute lung injury and pulmonary emphysema. Many previously reported patients with deletions of 2q24.2 showed poor outcomes because of respiratory failure. These observations suggest the possibility of a strong relationship between haploinsufficiency of ITGB6 and pulmonary dysfunction.


Fibronectin: How Its Aberrant Expression in Tumors May Improve Therapeutic Targeting.
Fibronectin is a matrix glycoprotein which has not only been found to be over-expressed in several cancers, but has been shown to participate in several steps of tumorigenesis. The purpose of this review is to illustrate how aberrant fibronectin expression influences tumor growth, invasion, metastasis and therapy resistance. In particular, this review will focus on the interactions between cell receptor ligands and fibronectin and how this interaction influences downstream signaling events that aid tumor progression. This review will further discuss the possible implications of therapeutic drugs directed against fibronectin and/or cellular interactions with fibronectin and will additionally discuss novel approaches by which to limit intra- and extra-tumoral fibronectin expression and the cellular events which lead to aberrant fibronectin expression. It is anticipated that these studies will set a basis for future research that will not only aid understanding of fibronectin and its prognostic significance, but will further elucidate novel targets for therapeutics.


Laboratory Electrical Resistivity Studies on Cement Stabilized Soil.
Electrical resistivity measurement of freshly prepared uncured and cured soil-cement materials is done and the correlations between the factors controlling the performance of soil-cement and electrical resistivity are discussed in this paper. Conventional quality control of soil-cement quite often involves wastage of a lot of material, if it does not meet the strength criteria. In this study, it is observed that, in soil-cement, resistivity follows a similar trend as unconfined compressive strength, with increase in cement content and time of curing. Quantitative relations developed for predicting 7-day strength of soil-cement mix, using resistivity of the soil-cement samples at freshly prepared state, after 1-hour curing help to decide whether the soil-cement mix meets the desired strength and performance criteria. This offers the option of the soil-cement mix to be upgraded (possibly with additional cement) in its fresh state itself, if it does not fulfil the performance criteria, rather than wasting the material after hardening.


Valsalva retinopathy: Long-term results and management strategies.
To investigate the long-term results and efficacy of the treatment modalities for preretinal hemorrhage due to valsalva retinopathy. Retrospective review was conducted on 24 eyes of 24 patients with valsalva retinopathy who were treated between 2004 and 2019. These patients were treated with Nd:YAG laser, argon laser and vitrectomy or were only observed. Nd:YAG laser hyaloidotomy was performed in 10 eyes, argon laser was applied to two of those following failed Nd:YAG laser, and vitrectomy was performed in one eye. A conservative approach was adopted in 13 eyes. There were 15 females and nine males with mean age of 41.08 ± 12.72 (21-65) years. Mean follow-up period was 42.83 ± 23.78 (range: 12-116) months. Patients with hemorrhage size smaller than or equal to 4-disc diameter were observed for spontaneous resorption and achieved 20/20 visual acuity within 6 months. Visual acuity of all patients treated with Nd:YAG and/or argon laser, increased within the first week after the treatment. Vitrectomy was performed in only one patient with hemorrhage located away from macula. The good visual outcomes were achieved in all treatment modalities. Observation, Nd:YAG laser and argon laser seem to be safe and effective approaches for eyes with valsalva retinopathy. The size, volume and duration of hemorrhage are the most crucial factors for treatment choice, success and complications.


Organizing a practice-based research group.
There is an urgent need for more dental research to come from the 'real-life' setting of general practice in order to complement the information arising from laboratory testing and institution-based clinical trials. This paper outlines some of the problems and opportunities encountered in undertaking research in practice, and describes the experiences of one such practice-based research group.


Inflammatory response or oxidative stress induces upregulation of PTPN2 and thus promotes the progression of laryngocarcinoma.
This study aims to investigate whether inflammatory response or oxidative stress could induce upregulation of PTPN2, thus promoting the progression of laryngocarcinoma. PTPN2 levels in laryngocarcinoma tissues and normal tissues were detected. In addition, PTPN2 levels in laryngocarcinoma tissues with stage 1/2 or stage 3/4 were determined as well. In vitro abundance of PTPN2 was measured in laryngocarcinoma cells and immortalized human nasopharyngeal epithelial cells. Survival analysis was conducted in laryngocarcinoma patients with high or low expression level of PTPN2. Subsequently, M4E cells were stimulated with inflammation (IFN-γ or TNF-α treatment) or oxidative stress (H2O2 stimulation), followed by determination of the protein level of PTPN2. In M4E cells stimulated with different concentrations of H2O2, the clonality and Ki-67 positive cell ratio were detected. Finally, clonality and Ki-67 positive cell ratio in M4E cells transfected with negative control or sh-PTPN2, regardless of H2O2 stimulation, were assessed. PTPN2 was upregulated in laryngocarcinoma tissues, especially those in stage 3/4. Similarly, in vitro abundance of PTPN2 was higher in laryngocarcinoma cell lines. The high level of PTPN2 predicted poor prognosis in laryngocarcinoma patients. IFN-γ or TNF-α treatment upregulated the protein level of PTPN2. Meanwhile, H2O2 stimulation upregulated the protein level of PTPN2, dose-dependently increased clonality, and Ki-67 positive cell ratio in M4E cells. The knockdown of PTPN2 suppressed clonality and Ki-67 positive cell ratio in M4E cells stimulated by H2O2 or not. Inflammatory response or oxidative stress could induce upregulation of PTPN2, thus promoting the proliferative ability of laryngocarcinoma.


Development of MATLAB software to control data acquisition from a multichannel systems multi-electrode array.
A Multichannel Systems (MCS) microelectrode array data acquisition (DAQ) unit is used to collect multichannel electrograms (EGM) from a Langendorff perfused rabbit heart system to study sudden cardiac death (SCD). MCS provides software through which data being processed by the DAQ unit can be displayed and saved, but this software's combined utility with MATLAB is not very effective. MCSs software stores recorded EGM data in a MathCad (MCD) format, which is then converted to a text file format. These text files are very large, and it is therefore very time consuming to import the EGM data into MATLAB for real-time analysis. Therefore, customized MATLAB software was developed to control the acquisition of data from the MCS DAQ unit, and provide specific laboratory accommodations for this study of SCD. The developed DAQ unit control software will be able to accurately: provide real time display of EGM signals; record and save EGM signals in MATLAB in a desired format; and produce real time analysis of the EGM signals; all through an intuitive GUI.


Evaluation of Genetic Diversity, Population Structure, and Relationship Between Legendary Vechur Cattle and Crossbred Cattle of Kerala State, India.
The legendary Vechur cattle of Kerala, described as a very short breed, and the crossbred (CB) Sunandini cattle population exhibited great phenotypic variation; hence, the present study attempted to analyze the genetic diversity existing between them. A set of 14 polymorphic microsatellites were chosen from FAO-ISAG panel and amplified from genomic DNA isolated from blood samples of 30 Vechur and 64 unrelated crossbred cattle, using fluorescent labeled primers. Both populations revealed high genetic diversity as evidenced from high observed number of alleles, Polymorphic Information Content and expected heterozygosity. Observed heterozygosity was lesser (0.699) than expected (0.752) in Vechur population which was further supported by positive FIS value of 0.1149, indicating slight level of inbreeding in Vechur population. Overall, FST value was 0.065, which means genetic differentiation between crossbred and Vechur population was 6.5%, indicating that the crossbred cattle must have differentiated into a definite population that is different from the indigenous Vechur cows. Structure analysis indicated that the two populations showed distinct differences, with two underlying clusters. The present study supports the separation between Taurine and Zebu cattle and throws light onto the genetic diversity and relationship between native Vechur and crossbred cattle populations in Kerala state.


The roles of family, culture, and social cognitive variables in the career interests and goals of Asian American college students.
Although family and cultural factors have been assumed to play important roles in the career development of Asian Americans, theory-driven research on this topic remains limited. We examined culturally relevant factors that may contribute to Asian Americans' consideration of fields in which they are overrepresented (e.g., science, technology, engineering) and underrepresented (e.g., education, social science). Drawing from social cognitive career theory, a culture-specific, social cognitive model of career interests and choice was tested in Holland's (1997) Investigative (I) and Social (S) themes. A sample of 802 Asian American undergraduates completed measures of family support, self-efficacy, outcome expectations, interest, and career choice consideration in relation to both Holland themes. Two indicators of acculturation/enculturation (adherence to Asian values and generation status in the United States) were also obtained. The model accounted for a substantial amount of variance in Asian American college students' career consideration in both themes. Family support and acculturation played varying roles, depending on the Holland theme. For example, family support was linked to career choice consideration both directly (in the S theme) and indirectly, via other predictors (in both themes). Contrary to expectations, the acculturation variables did not moderate the relation of family support or interest to career consideration in either theme. We discuss the implications of these findings for efforts to understand and facilitate the career development of Asian American college students. (PsycINFO Database Record


A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities.
Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented. A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered.


Hypofractionated stereotactic radiotherapy for large or involving critical organs cerebral arteriovenous malformations.
The treatment of large arteriovenous malformations (AVMs) or AVMs involving eloquent regions of the brain remains a challenge. For inoperable lesions, observation, volume-staged radiosurgery or hypofractionated stereotactic radiotherapy (HFSRT) are proposed. The aim of our study was to assess the safety and efficiency of HFSRT for large AVMs located in eloquent areas of the brain. An analysis of records of 49 patients irradiated for cerebral AVMs with a mean dose of 19.9 Gy (12-28 Gy) delivered in 2-4 fractions with planned gap (at least one week) between fractions. Actuarial obliteration rates and annual bleeding hazard were calculated using Kaplan-Meier survival analysis and life tables. Annual bleeding hazard rates were 4.5% and 1.6% after one and two years of the follow-up, respectively. Actuarial total obliteration rates were 7%, 11%, and 21% and total response rate (total and partial obliterations) 22%, 41%, and 55% after one, two and three years of the follow-up, respectively. There was a trend towards larger total obliteration rate in patients irradiated with fraction dose ≥ 8 Gy and total dose > 21 Gy for lesions of volume ≤ 8.18 cm(3) which was not observed in case of partial obliterations. HFSRT results with relatively low obliteration rate but is not associated with a significant risk of permanent neurological deficits if both total and fraction doses are adjusted to size and location of the lesion. Predictive factors for total and partial obliterations can be different; this observation, however, is not firmly supported and requires further studies.


Hierarchical Growth of Supramolecular Structures Driven by Pimerization of Tetrahedrally Arranged Bipyridinium Units.
A shape-persistent molecule, featuring four bipyridinium units, has been synthesized that upon reduction undergoes intermolecular pimerization because of the rigid architecture of the molecule. The pimerization process has been investigated by a variety of techniques, such as absorption measurements, EPR spectroscopy, as well as gamma and pulse radiolysis, and compared with the behavior of a model compound. Computational studies have also been performed to support the experimental data. The most interesting feature of the tetramer is that pimerization occurs only above a threshold concentration of monoreduced species, on the contrary to the model compound. Furthermore, there is an increase of the apparent pimerization constant by increasing the concentration of reduced bipyridinium units. These results have been interpreted by the fact that pimerization is favored in the tetrahedrally shaped molecule because of a cooperative mechanism. Each multiply reduced molecule can indeed undergo multiple intermolecular interactions that enhance the stabilization of the system, also leading to hierarchical supramolecular growth. The resulting supramolecular system formed by such intermolecular pimerization should exhibit a diamond-like structure, as suggested by a simplified modeling approach. The intermolecular nature of the pimerization process occurring in the tetramer has been demonstrated by measuring the corresponding bimolecular rate constant by pulsed radiolysis experiments.


An unusual presentation of lacrimal gland dirofilariasis.
Dirofilariasis is a helminthic infection caused by filarial parasite of the genus Dirofilaria. It is a common zoonotic disease mostly affecting canines and uncommon in humans. It is endemic to Mediterranean countries, with few reports from other parts of the world. The clinical forms in humans are pulmonary, subcutaneous, and ocular. Ocular involvement is rare. We report a case of lacrimal gland dirofilariasis, an unusual ocular presentation which masquerades as a lacrimal gland tumor. Ours would be the third reported case in the world and first in India. This case was managed with excision of the lacrimal gland mass. Postoperatively the patient recovered completely and there has been no recurrence in the 1-year follow-up.


Tricuspid valve repair for severe tricuspid regurgitation due to pacemaker leads.
Tricuspid valve regurgitation due to pacemaker leads is a well-known complication. Although some reports have suggested that pacemaker leads should be surgically explanted, strongly adhered leads cannot always be removed. The aim of this study was to describe our tricuspid valve repair techniques with pacemaker leads left in situ. Our retrospective study investigated 6 consecutive patients who required tricuspid valve surgery for severe regurgitation induced by pacemaker leads. From the operative findings, we identified 3 patterns of tricuspid valve and pacemaker lead involvement. In 3 patients, the leads were caught in the chordae, in 2 patients, tricuspid regurgitation was caused by lead impingement on the septal leaflet, and in 3 patients, tricuspid valve leaflets had been perforated by the pacemaker leads. During surgery, all leads were left in situ after being separated from the leaflet or valvular apparatus. In addition, suture annuloplasty was performed for annular dilatation in all cases. In one patient, the lead was reaffixed to the annulus after the posterior leaflet was cut back towards the annulus, and the leaflet was then closed. There was one hospital death due to sepsis. The degree of tricuspid regurgitation was trivial in all surviving patients at discharge. During a mean follow-up of 21 months, one patient died from pneumonia 20 months after tricuspid valve repair. In patients undergoing tricuspid valve surgery due to severe tricuspid regurgitation caused by pacemaker leads, the leads can be left in situ after proper repair with annuloplasty.


Diastolic dysfunction in alveolar hypoxia: a role for interleukin-18-mediated increase in protein phosphatase 2A.
Chronic obstructive pulmonary disease with alveolar hypoxia is associated with diastolic dysfunction in the right and left ventricle (LV). LV diastolic dysfunction is not caused by increased afterload, and we recently showed that reduced phosphorylation of phospholamban at serine (Ser) 16 may explain the reduced relaxation of the myocardium. Here, we study the mechanisms leading to the hypoxia-induced reduction in phosphorylation of phospholamban at Ser16. In C57Bl/6j mice exposed to 10% oxygen, signalling molecules were measured in cardiac tissue, sarcoplasmic reticulum (SR)-enriched membrane preparations, and serum. Cardiomyocytes isolated from neonatal mice were exposed to interleukin (IL)-18 for 24 h. The beta-adrenergic pathway in the myocardium was not altered by alveolar hypoxia, as assessed by measurements of beta-adrenergic receptor levels, adenylyl cyclase activity, and subunits of cyclic AMP-dependent protein kinase. However, alveolar hypoxia led to a significantly higher amount (124%) and activity (234%) of protein phosphatase (PP) 2A in SR-enriched membrane preparations from LV compared with control. Serum levels of an array of cytokines were assayed, and a pronounced increase in IL-18 was observed. In isolated cardiomyocytes, treatment with IL-18 increased the amount and activity of PP2A, and reduced phosphorylation of phospholamban at Ser16 to 54% of control. Our results indicate that the diastolic dysfunction observed in alveolar hypoxia might be caused by increased circulating IL-18, thereby inducing an increase in PP2A and a reduction in phosphorylation of phospholamban at Ser16.


A new oxygenator change-out system and procedure.
Official reports relate that, in the US, one patient/month dies as a result of the emergency oxygenator change-out procedure, and the permanent injury of some patients is the result of current oxygenator change-out procedures or oxygenator failures, both in extracorporeal circulation (ECC) and extracorporeal membrane oxygenation (ECMO). The aim of this article is to evaluate a new system and procedure, dedicated to oxygenator change-out, represented by two three-way stopcocks inserted in the ECC line in use. A dedicated back-up oxygenator and circuit can be easily primed and connected to the dedicated connector on the stopcocks, then blood flow is diverted to the new oxygenator without interruption of the ECC. Tests performed showed that oxygenator change-out can be completed by perfusionists in 62.13 +/- 11.12 sec. Results obtained show that the new system and procedure allows fast, safe and reproducible oxygenator change-out without interruption of the ECC.


Electromotive Drug Administration (EMDA) in the Porcine Renal Pelvis: First Report.
Electromotive drug administration (EMDA) amplifies drug delivery deep into targeted tissues. We tested, for the first time, the ability of EMDA to deliver methylene blue into the urothelium of the renal pelvis. In an anesthetized female pig, both proximal ureters were transected two inches distal to the ureteropelvic junction. An 8Fr dual lumen catheter and a 5Fr fenestrated catheter with an indwelling silver wire were inserted into both renal pelvises following which methylene blue (0.1%) was infused at a rate of 5 ml/min for 20 minutes. In one pelvis, a 4mA positive pulsed electrical current was applied to the silver wire. In contrast to the control pelvis, the EMDA side macroscopically exhibited dense homogeneous staining; microscopy revealed penetration of methylene blue into the urothelium/lamina propria. In the porcine renal pelvis, application of EMDA increased the penetration of a charged molecule into the urothelium/lamina propria.


An adherence trilogy is essential for long-term HAART success.
Adherence is the milestone of a successful therapy. Over the last decade several authors have addressed the importance of adherence for optimal results of antiretroviral (ARV) therapy. Many health care systems are investing substantial resources to make available contemporary antiretroviral therapy. Despite the large investment in medications, insufficient investments have been made into an integrated adherence component to maximize the impact of these medications. Adherence, unlike drug therapy, cannot be defined as a single method with a defined prescription or formula. Instead, it is the result of a complex interaction between the patient, a prescribed medication and the health system. Many reports are available analyzing each of these components. We have found that critical elements of adherence include the patient's knowledge about the disease and how medications will help achieve a longer and healthier life, together with the motivation to adapt to a new style of life. A trilogy composed of information, motivation and behavioral skills is essential to achieve the maximum desired level of adherence. We have computerized this trilogy in a software program for self-administration in which each of the three components is provided to the patient as many times as necessary to transmit an understanding of the problem and to help make a rational decision to adhere to the ARV treatment program. In this review we analyze several efforts and techniques to improve adherence to any recommended medication that may interfere with the patient's lifestyle and outline how the adherence trilogy can be best used to optimize the ability of ARV therapy to durably suppress plasma HIV RNA to undetectable levels.


A Systematic Review of Literature on Caregiving Preparation of Adult Children.
With the increasing life expectancy and ageing population, long-term care has become an urgent policy issue worldwide. The informal care provided by family members, particularly adult children, is a key aspect of long-term care. However, socioeconomic transformations have resulted in changing family and demographic structures and increased geographic mobility, reducing the capacity of families to provide informal care and meet the caregiving needs of older adults. For ageing families, care preparation can be an effective method for coping with eldercare challenges, and care preparation is attracting increasing attention from researchers. This study seeks to conduct a systematic review for studies on caregiving preparation by adult children that were retrieved from six databases, to synthesise the available evidence, and to identify knowledge gaps and opportunities for future investigations. The characteristics and main themes of eighteen reviewed articles were identified and analysed. This study discussed various conceptualisations of caregiving preparation by adult children, the prevalence of caregiving preparation, the factors related to caregiving preparation, and the related consequences. On the basis of the systematic review findings, several limitations of the literature and directions for future research were proposed to promote care preparedness and the well-being of ageing families.


Milk as a source of deoxyribonucleic acid and as a substrate for the polymerase chain reaction.
Somatic cells in milk were used as a source of DNA and as a substrate for the polymerase chain reaction. Successful DNA extraction required a minimum total of 17 x 10(6) cells in the milk sample. The DNA yield per cell was highly variable but comparable, on average, with the yield from peripheral blood leukocytes. In all cases, direct polymerase chain reaction on milk samples, using a variety of primer pairs, yielded amplified products of correct size that were identical to those obtained by polymerase chain reaction of purified DNA extracted from milk or blood. Milk and DNA extracted from milk served as substrates for direct sequencing of part of the bovine growth hormone gene. Milk samples with added preservative were stored over 200 d without effect on the polymerase chain reaction. Thus, milk can often substitute for blood as a source of DNA for Southern blot analysis and is a preferred substrate for the polymerase chain reaction. The technical convenience of milk as a source of DNA can be expected to increase the field of application of marker-based methods for genetic analysis and genetic improvement of economic traits in dairy cattle.


Barreras y Soluciones: Lessons learned from integrating research-based clinical techniques into a community agency serving low-income Latinx immigrant families.
Barriers facing effective science-to-practice translation have led scholars to conduct early-stage intervention research within community organizations. We describe our experiences developing a manualized parent-youth attachment-based group therapy intervention within a community health organization dedicated to serving low-income Latinx immigrant families, Latino Health Access (LHA), in which services are rendered by trained community workers (promotores). By conducting a qualitative analysis of interviews with all members of this academic-community partnership (research [Principal Investigator, student researchers] and community agency team members [Administrators, promotores]), we discuss the challenges and opportunities that this collaboration has generated. The results led both the research and community teams to question assumptions about the basic skills, values, and attitudes that underlie the integration of science and practice. We will share the insights that have helped to promote connection and understanding among the stakeholders and the efforts made to support the progress and successes of developing community interventions.


Hydrogen-bonded dimers, chains and rings in six differently substituted 2-vinyltetrahydro-1,4-epoxy-1-benzazepines.
In (2SR,4RS)-2-exo-vinyl-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(12)H(13)NO, (I), the molecules are linked by two independent C-H...pi(arene) hydrogen bonds to form sheets, such that all of the molecules in a given sheet are of the same configuration. The molecules of (2SR,4RS)-7-chloro-2-exo-(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(14)H(16)ClNO, (II), are linked by a C-H...O hydrogen bond into C(4) chains, where all the molecules in a given chain are of the same configuration, whereas the molecules of (2SR,4RS)-8-chloro-9-methyl-2-exo-(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(15)H(18)ClNO, (III), are linked into centrosymmetric dimers by pairs of symmetry-related C-H...pi(arene) hydrogen bonds. (2RS,4RS)-8-Chloro-9-methyl-2-endo-(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(15)H(18)ClNO, (IV), is a diastereoisomer of (III) and, as for (II), a single C-H...O hydrogen bond links the molecules into C(4) chains, each containing molecules of a single configuration. The structure of (2SR,4RS)-8-chloro-9-methyl-2-exo-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(14)H(16)ClNO, (V), contains a C-H...O hydrogen bond which links pairs of molecules into centrosymmetric R(2)(2)(6) dimers. (2SR,4RS)-7,9-Dichloro-2-exo-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(13)H(13)Cl(2)NO, (VI), is an inversion twin containing both the (2S,4R) and (2R,4S) enantiomers in the space group P2(1), and a C-H...O hydrogen bond links molecules of a given configuration into simple C(3) chains.


Challenges and Advances in Rechargeable Batteries for Extreme-Condition Applications.
Rechargeable batteries are widely used as power sources for portable electronics, electric vehicles and smart grids. Their practical performances are, however, largely undermined under extreme conditions, such as in high-altitude drones, ocean exploration and polar expedition. These extreme environmental conditions not only bring new challenges for batteries but also incur unique battery failure mechanisms. To fill in the gap, it is of great importance to understand the battery failure mechanisms under different extreme conditions and figure out the key parameters that limit battery performances. In this review, the authors start by investigating the key challenges from the viewpoints of ionic/charge transfer, material/interface evolution and electrolyte degradation under different extreme conditions. This is followed by different engineering approaches through electrode materials design, electrolyte modification and battery component optimization to enhance practical battery performances. Finally, a short perspective is provided about the future development of rechargeable batteries under extreme conditions.


Effects of various factors on Doppler flow ultrasonic radial and coccygeal artery systolic blood pressure measurements in privately-owned, conscious dogs.
The purpose of this study was to assess the effects of age, body condition score (BCS) and muscle condition score (MCS) on indirect radial and coccygeal Doppler systolic arterial blood pressure (SAP) measurements in dogs. Sixty-two privately-owned dogs were enrolled between June and July 2016. The BCS and MCS were determined by two investigators. Blood pressure was measured per published guidelines and using headphones, and the order of measurement site was randomized. Dogs were positioned in right lateral recumbency for radial measurements and sternal recumbency or standing for coccygeal measurements. Associations between SAP and other variables were assessed by correlation coefficients and analysis of covariance. Radial and coccygeal SAP measurements were moderately correlated (r = 0.45, P < 0.01). Radial SAP measurements were higher than coccygeal SAP measurements (mean difference 9 mmHg, P < 0.01), but discordance occurred in both directions. No difference was observed between the first measurement taken, the average of measurements 2-6, or the average of all 6 measurements for either the radial (128, 129, and 129 mmHg; P = 0.36) or coccygeal (121, 122, and 122 mmHg; P = 0.82) site. Associations were not found between SAP measurements for either site and age, weight, BCS, MCS, anxiety score, or cuff size. Heart rate decreased significantly from the start of acclimation to the end of the first data collection series regardless of site (P < 0.01). Initial measurement site can be based on patient and operator preference given lack of associations with patient variables, but the same site should be used for serial SAP measurements given discordant results between sites.


Are prehospital deaths from trauma and accidental injury preventable? A direct historical comparison to assess what has changed in two decades.
In 1994, Hussain and Redmond revealed that up to 39% of prehospital deaths from accidental injury might have been preventable had basic first aid care been given. Since then there have been significant advances in trauma systems and care. The exclusion of prehospital deaths from the analysis of trauma registries, giv en the high rate of those, is a major limitation in prehospital research on preventable death. We have repeated the 1994 study to identify any changes over the years and potential developments to improve patient outcomes. We examined the full Coroner's inquest files for prehospital deaths from trauma and accidental injury over a three-year period in Cheshire. Injuries were scored using the Abbreviated-Injury-Scale (AIS-1990) and Injury Severity Score (ISS), and probability of survival estimated using Bull's probits to match the original protocol. One hundred and thirty-four deaths met our inclusion criteria; 79% were male, average age at death was 53.6 years. Sixty-two were found dead (FD), fifty-eight died at scene (DAS) and fourteen were dead on arrival at hospital (DOA). The predominant mechanism of injury was fall (39%). The median ISS was 29 with 58 deaths (43%) having probability of survival of >50%. Post-mortem evidence of head injury was present in 102 (76%) deaths. A bystander was on scene or present immediately after injury in 45% of cases and prior to the Emergency Medical Services (EMS) in 96%. In 93% of cases a bystander made the call for assistance, in those DAS or DOA, bystander intervention of any kind was 43%. The number of potentially preventable prehospital deaths remains high and unchanged. First aid intervention of any kind is infrequent. There is a potentially missed window of opportunity for bystander intervention prior to the arrival of the ambulance service, with simple first-aid manoeuvres to open the airway, preventing hypoxic brain injury and cardiac arrest.


[Reversible contact lesion in mitral valve endocarditis--follow-up study with transesophageal echocardiography].
This is a case report of a 59-year-old patient with an endocarditis of the mitral valve caused by streptococcus viridans. Precordial echocardiography showed a highly mobile vegetation of the anterior mitral leaflet prolapsing during systole into the left atrium. During diastole contact with the ventricular septum caudally to the left ventricular outflow tract was noted. By using transesophageal echocardiography (TEE), this zone appeared as a localized increased echogenity of the parietal endocardium and underlying myocardium. Antibiotic therapy led to a cure of the endocarditis (clinically and according to clinical chemistry). The TEE follow-up 2 months later showed persisting mitral valve vegetation, whereas neither the endocardial lesion nor the abnormal myocardial echo pattern were seen any longer. The likely inflammatory etiology of the described lesion is discussed and seems obvious.


Control of Maillard Reactions in Foods: Strategies and Chemical Mechanisms.
Maillard reactions lead to changes in food color, organoleptic properties, protein functionality, and protein digestibility. Numerous different strategies for controlling Maillard reactions in foods have been attempted during the past decades. In this paper, recent advances in strategies for controlling the Maillard reaction and subsequent downstream reaction products in food systems are critically reviewed. The underlying mechanisms at play are presented, strengths and weaknesses of each strategy are discussed, and reasonable reaction mechanisms are proposed to reinforce the evaluations. The review includes strategies involving addition of functional ingredients, such as plant polyphenols and vitamins, as well as enzymes. The resulting trapping or modification of Maillard targets, reactive intermediates, and advanced glycation endproducts (AGEs) are presented with their potential unwanted side effects. Finally, recent advances in processing for control of Maillard reactions are discussed.


Advances in clinical analysis 2012.
A report on the meeting organized by The Chromatographic Society and the Separation Science Group, Analytical Division of the Royal Society of Chemistry. Over 60 delegates and commercial exhibitors attended this event, held to celebrate the careers of Robert Flanagan and David Perrett, and acknowledge their extensive contributions in the field of clinical analysis.


Variability of vaccine responsiveness in early life.
Vaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.


Identification of ageing-associated naturally occurring peptides in human urine.
To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinarypeptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing.


Traumatic brain injuries caused by traffic accidents in five European countries: outcome and public health consequences.
Road traffic accidents (RTAs) have been identified by public health organizations as being of major global concern. Traumatic brain injuries (TBIs) are among the most severe injuries and are in a large part caused by RTA. The objective of this article is to analyse the severity and outcome of TBI caused by RTA in different types of road users in five European countries. The demographic, severity and outcome measures of 683 individuals with RTA-related TBI from Austria, Slovakia, Bosnia, Croatia and Macedonia were analysed. Five types of road users (car drivers, car passengers, motorcyclists, bicyclists and pedestrians) were compared using univariate and multivariate statistical methods. Short-term outcome [intensive care unit (ICU) survival] and last available long-term outcome of patients were analysed. In our data set, 44% of TBI were traffic related. The median age of patients was 32.5 years, being the lowest (25 years) in car passengers. The most severe and extensive injuries were reported in pedestrians. Pedestrians had the lowest rate of ICU survival (60%) and favourable long-term outcome (46%). Drivers had the highest ICU survival (73%) and car passengers had the best long-term outcome (59% favourable). No differences in the outcome were found between countries with different economy levels. TBI are significantly associated with RTA and thus, tackling them together could be more effective. The population at highest risk of RTA-related TBI are young males (in our sample median age: 32.5 years). Pedestrians have the most severe TBI with the worst outcome. Both groups should be a priority for public health action.


The Efficacy of Rosa damascena on Liver Enzymes in Nonalcoholic Fatty Liver Disease: A Randomized Double-Blind Clinical Trial.
This study aimed to appraise the potential effects of Rosa damascena preparation on nonalcoholic fatty liver disease (NAFLD). In the randomized, double-blind placebo-controlled clinical trials, seventy-four patients with NAFLD were prescribed either 1 g Rosa damascena powder or placebo three times in a day for 12 weeks. All patients were provided the lifestyle modification instructions and recommended following them precisely. ALT, AST, FBS, and lipid profiles were measured at the baseline after 12 weeks of studying. The Mann-Whitney U test was correctly used to compare the changes of variables among the groups. Seventy-two patients completed the study in two groups. Sixty-seven patients were men, and the mean ± standard deviation of age was 40.11 ± 9.05 years. The Rosa damascena group showed a considerable decrease in the serum ALT (23.83 ± 24.82 vs. 16.19 ± 27.41, p=0.042), waist circumference (99.73 ± 10.01 vs. 101.52 ± 8.84, p=0.003), triglyceride (TG) (186.29 ± 76.75 vs. 184.47 ± 73.05, p=0.001), cholesterol (167.47 ± 34.48 vs. 184.11 ± 33.54, p=0.001), low-density lipoprotein (LDL) (99.17 ± 28.66 vs. 107.52 ± 25.42, p=0.001), and elevation in serum high-density lipoprotein (HDL) (41.85 ± 6.56 vs. 39.20 ± 5.00, p < 0.007) compared to the control group. Improving fatty liver degree due to liver ultrasound was higher in the Rosa damascena group than the control group (p=0.001). Rosa damascena meaningfully improves liver function in NAFLD. Hence, it can be recommended along with lifestyle modification for these patients. Further studies are recommended with a larger sample size.


The early solar system.
Life arose on an early Earth which was the product to the conditions present, and processes operating, during formation of the solar system. The formation and early state of the solar system are reviewed in order to better understand the nature of the early Earth, and to constrain the conditions present during the origin and early evolution of life on this planet.


Effect of video game playing and a glucose preload on subjective appetite, subjective emotions, and food intake in overweight and obese boys.
Video game playing (VGP) is associated with overweight/obesity (OW/OB). VGP and caloric preloads in the pre-meal environment influence short-term food intake (FI) in healthy-weight children. Therefore, the purpose of the present study was to examine the effect of pre-meal VGP and a glucose preload on subjective emotions, subjective appetite, and FI in boys with OW/OB. On 4 separate mornings, boys with OW/OB (n = 22; mean ± SD: age = 11.9 ± 1.6 years; body mass index percentile = 94.3 ± 3.9) participated in 4 test conditions. Two hours after a standardized breakfast, boys consumed equally sweetened preloads (250 mL) of sucralose (0 kcal) or glucose (200 kcal), with or without 30 min of subsequent VGP. Immediately after each test condition, FI was evaluated during an ad libitum pizza meal. Subjective appetite was measured at 0 (baseline), 15, and 30 min. Subjective emotions (aggression, anger, excitement, disappointment, happiness, upset, and frustration) were measured at 0 and 30 min. VGP did not affect FI, but the glucose preload decreased FI compared with the sucralose control (Δ = -103 ± 48 kcal, p < 0.01). However, cumulative FI (preload kcal + meal kcal) was 9% higher after the glucose preload (p < 0.01). Subjective appetite increased with time (p < 0.05) but was not influenced by preload or VGP. Frustration was the only subjective emotion that increased following VGP (p < 0.01). A glucose preload, but not VGP, suppressed FI in boys with OW/OB, suggesting a primary role of physiological factors in short-term FI regulation.


Congenital toxoplasmosis presenting as massive neonatal ascites.
A preterm infant with isolated transudative ascites caused by Toxoplasma gondii is described. In the absence of obvious congenital malformations, toxoplasmosis should be considered in the differential diagnosis of fetal and neonatal non-immune ascites.


Enhanced complement resistance in drug-selected P-glycoprotein expressing multi-drug-resistant ovarian carcinoma cells.
Multi-drug resistance (MDR) is a major obstacle in cancer chemotherapy. There are contrasting data on a possible correlation between the level of expression of the drug transporter P-glycoprotein (P-gp) and susceptibility to complement-dependent cytotoxicity (CDC). We therefore investigated the sensitivity of human ovarian carcinoma cells and their P-gp expressing MDR variants to complement. Chemoselected P-gp expressing MDR cells showed increased resistance to CDC associated with overexpression of membrane-bound complement regulatory proteins (mCRP) and increased release of the soluble inhibitors C1 inhibitor and factor I. MDR1 gene transfection alone did not alter the susceptibility of P-gp expressing A2780-MDR and SKOV3-MDR cells to CDC. However, subsequent vincristine treatment conferred an even higher resistance to complement to these cells, again associated with increased expression of mCRP. Blocking the function of P-gp with verapamil, cyclosporine A or the anti-P-gp-antibody MRK16 had no impact on their complement resistance, whereas blocking of mCRP enhanced their susceptibility to complement. These results suggest that enhanced resistance of chemoselected MDR ovarian carcinoma cells to CDC is not conferred by P-gp, but is due at least partly to overexpression of mCRP, probably induced by treatment with the chemotherapeutic agents.


The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes.
Hemoglobin (Hb) toxicity precipitates secondary brain damage following intracerebral hemorrhage (ICH). CD163 is an anti-inflammatory Hb scavenger receptor and CD163-positive macrophages/microglia locally accumulate post-bleed, yet no studies have investigated the role of CD163 after ICH. ICH was induced in wildtype and CD163-/- mice and various anatomical and functional outcomes were assessed. At 3 d, CD163-/- mice have 43.4 ± 5.0% (p = 0.0002) and 34.8 ± 3.4% (p = 0.0003) less hematoma volume and tissue injury, respectively. Whereas, at 10 d, CD163-/- mice have 49.2 ± 15.0% larger lesions (p = 0.0385). An inflection point was identified, where CD163-/- mice perform better on neurobehavioral testing and have less mortality before 4 d, but increased mortality and worse function after 4 d (p = 0.0389). At 3 d, CD163-/- mice have less Hb, iron, and blood-brain barrier dysfunction, increased astrogliosis and neovascularization, and no change in heme oxygenase 1 (HO1) expression. At 10 d, CD163-/- mice have increased iron and VEGF immunoreactivity, but no significant change in HO1 or astrogliosis. These novel findings reveal that CD163 deficiency has distinct temporal influences following ICH, with early beneficial properties but delayed injurious effects. While it is unclear why CD163 deficiency is initially beneficial, the late injurious effects are consistent with the key anti-inflammatory role of CD163 in the recovery phase of tissue damage.


Real-Life Benefit of Omalizumab in Improving Control of Bronchial Asthma During COVID-19 Pandemic.
Biologic therapy is recommended by Global Initiative for Asthma (GINA) guidelines in asthma patients not controlled with maximal inhaled therapy corresponding to GINA step 4. Omalizumab is an anti- immunoglobulin E (IgE) monoclonal antibody and the first biological available for the add-on treatment of severe allergic asthma, approved by Food and Drug Administration (FDA) in 2003. Diagnosing and managing asthma patients during coronavirus disease 2019 (COVID-19) pandemic since early 2020 has been challenging, mainly due to the risk of contracting COVID-19 disease and to the limited access to hospital care and pulmonary function tests. We report a case of a 52-year-old female patient, diagnosed with adult-onset asthma in 2018, who was first referred to the Allergy Department of our hospital in January 2019 for dyspnea, wheezing, and worsening cough. Despite continuous inhaled therapy and good inhalation technique, she had frequent asthma symptoms, requiring short courses of oral corticosteroids (CS). Physical examination and pulmonary function tests on admission revealed broncho-obstructive syndrome and laboratory tests showed mild inflammation and high total serum IgE. She continued to have two moderate-severe exacerbations after stepping up to maximal inhaled therapy plus oral montelukast and theophylline, according to GINA step 4. By the end of 2019, we additionally started omalizumab, which resulted in prompt clinical benefits and resolution of asthma symptoms. Given the ongoing COVID-19 pandemic limiting in-person visits, virtual follow-ups indicated adequate control of his symptoms, as proved by asthma control test and no need for hospital presentation.


The participant-observer approach to research in mental retardation.
Participant-observation, which calls for long-term immersion in the world of the persons being studied yet disciplined detachment from that world, has long been utilized in various social sciences. This method of data collection was seldom used in the study of mentally retarded people until recent years; however, it has now been employed in the study of many aspects of the lives of these people and their families. Although this method of research is expensive and time consuming, it has the advantage of allowing investigators to learn how people actually behave in a variety of contexts and to grasp the meaning these activities have for them.


Poisoning with a traditional remedy containing potassium dichromate.
A fatal case of potassium dichromate ingestion is documented. A retrospective review of serum and organ levels of chromium demonstrates that charcoal haemoperfusion, peritoneal and haemodialysis are ineffective therapies for the toxin. Other treatments for this poisoning are reviewed, the poor prognosis of dichromate ingestion, and the paucity of effective therapy underlined. The application of dichromates in traditional medications is briefly discussed; this is a toxin which may be more prevalent than previously thought. It is proposed that the exposure limits of dichromate be more widely publicised.


[Trunk sap flow dynamic changes in response to the slopes of plantation of Toona ciliata var. pubescens].
The sap flow and environmental factors, including temperature, water content and water potential of soil, were continuously measured by using an auto-data collection system at the upper and lower slopes of Toona ciliata var. pubescens plantation in July to October, 2012 to investigate the relationships between the sap flow and environmental factors. The results showed that, the trunk sap flow velocity of the two positions both presented a typical single-peak curve, with high values in the daytime and low values in the nighttime. The average sap flow of the lower slope was significantly higher than that of the upper slope. Soil temperature of the upper slope was significantly higher than that of the lower slope, and soil water content and water potential were vice versa. Soil water content and water potential were the leading environmental factors affecting the trunk sap flow velocity at the lower slope, while soil temperature and water potential were the main environmental factors at the upper slope.


External fixation of pediatric femur fractures.
One-hundred and thirty-two children with 139 femur fractures were treated with external fixation from 1984 to 1993. Average age at presentation was 8.97 years. All fractures were followed until union, with an average time of external fixation of 11.4 weeks. There were no nonunions. Of 18 patients with definitive radiographic measurements at 2-year follow-up, 15 patients developed overgrowth (average, 8.7 mm) and three demonstrated shortening (average, 7.7 mm). No patient required treatment for residual leg-length discrepancy. Although pin-tract inflammation was common, pin-tract infection requiring intravenous antibiotics occurred in only six patients (4.5%). No patient developed osteomyelitis. Two fractures (1.4%) were not healed at the time of elective fixator removal, necessitating additional time in the fixator. There were two refractures (1.4%) and one fracture through a healing pin tract after fixator removal (0.7%).


Self-curing acrylic formulations containing PMMA/PCL composites: properties and antibiotic release behavior.
Partially biodegradable acrylic composites containing poly(methyl methacrylate)-poly(epsilon-caprolactone) (PMMA/PCL) systems were prepared by mixing the corresponding PMMA/PCL beads (89:11, 86:14, 83:17, and 77:23 weight ratio) used as solid phase with methyl methacrylate (MMA) (liquid phase) in a solid/liquid ratio of 1.5:1. The physical and chemical microheterogeneity of these beads influenced significantly the curing parameters, because several aspects involved in the polymerization reaction are closely related to both morphology and size distribution of the particles. In vitro behavior was studied by immersion in simulated body fluid at pH = 7.4 and 37 degrees C for more than 8 weeks and the composition was followed by 1H-nuclear magnetic resonance spectroscopy. Approximately 2% wt/wt weight loss was observed after a period of 8 weeks for the composites richest in PCL. Mechanical properties of the dry and wet specimens were evaluated by compressive and tensile tests. In all cases, the presence of PCL in the composites provided a significant decrease in both compressive strength and elastic modulus compared with plain PMMA. Tensile and compressive strength also decreased significantly after 2 weeks of immersion in simulated body fluid compared with dry specimens. The self-curing composites based on PMMA/PCL beads and loaded with 3% wt/wt vancomycin were evaluated as carriers for local release of antibiotics. The composite prepared with beads of PMMA/PCL ratio 86:14 was the most effective. It eluted 64% of the initial drug within the first 5 h, allowing progressive release of nearly the total amount of the initial drug (90%) in approximately 2 months. The results obtained suggest that the described composites can be suitable for antibiotic release in non-load bearing graft applications.


Vindesine, carmustine, doxorubicin, and prednisone (EBAP) in recurrent lymphomas: a Southwest Oncology Group study.
Seventy-eight patients with Hodgkin's disease and non-Hodgkin's lymphoma who had failed prior chemotherapy or radiation therapy were treated with a combination of vindesine, carmustine, doxorubicin, and prednisone (EBAP). Outpatient therapy was administered at 21-day intervals. Complete and partial responses were seen in 32 patients (41%). The response rate was higher for Hodgkin's disease (59%) than for non-Hodgkin's lymphoma (31%). The median duration of response was 31 weeks in both groups, with a median survival of all patients of 35 weeks (responders, 122 weeks; nonresponders, 16 weeks). Myelotoxicity was greater using EBAP than in the earlier reported program with vincristine, carmustine, doxorubicin, and prednisone, and in the absence of higher response rates does not support the use of vindesine over vincristine in combination programs using nitrosoureas, anthracyclines, and prednisone.


Restoration of the soft-tissue margin in single-tooth implant in the anterior maxilla.
Esthetic requirements for dental implant restoration have arisen in recent years. Despite several surgical techniques that have been developed, the treatment of the peri-implant soft-tissue defect is still difficult. The purpose of this clinical article is to describe a grafting technique using subepithelial connective tissue grafts to recontour soft-tissue margin discrepancy for single-tooth implant restorations in the anterior maxilla. After 2-year follow-up, this procedure shows that the use of connective tissue grafts can be a predictable approach to establish new and stable peri-implant soft-tissue margin.


A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer.
Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market. We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock. Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it.


Addressing Specific (Poly)ion Effects for Layer-by-Layer Membranes.
Layer-by-layer (LbL) assembly of the alternating adsorption of oppositely charged polyions is an extensively studied method to produce nanofiltration membranes. In this work, the concept of chaotropicity of the polycation and its counterion is introduced in the LbL field. In general, the more chaotropic a polyion, the lower its effective charge, charge availability, and hydrophilicity. Here, this is researched for the well-known PDADMAC (polydiallyldimethylammonium chloride) and PAH (poly(allylamine) hydrochloride), and the synthesized PAMA (polyallylmultimethylammonium), with two different counterions (I- and Cl-). Higher chaotropicity (PDADMAC > PAMA-I > PAMA-Cl > PAH) translates into a reduced charge availability and a more pronounced extrinsic charge compensation, resulting in more mass adsorption and a higher pure water permeability. PAMA-containing membranes show the most interesting results in the series. Due to its molecular structure, the chaotropicity of this polycation perfectly lies between PDADMAC and PAH. Overall, the chaotropicity of PAMA membranes allows for the formation of the right balance between extrinsic and intrinsic charge compensation with PSS. Moreover, modifying the nature of the counterions of PAMA (I- or Cl-) allows to tune the density of the multilayer and results in lower size exclusion abilities with PAMA-I compared to PAMA-Cl (higher MWCO and lower MgSO4 retention). In general, the contextualization of the polyion interaction within the specific (poly)ion effects expands the understanding of the influence of the charge density of polycations without ignoring the chemical nature of the functional groups in their monomer units.


Agroinfiltration as a technique for rapid assays for evaluating candidate insect resistance transgenes in plants.
Functional analysis of candidate transgenes for insect resistance in stably transformed plants is a time-consuming task that can take months to achieve in even the fastest of plant models. In this study, a rapid screening technique is described, which employs candidate transgene transient expression using agroinfiltration in Nicotiana benthamiana combined with a simple insect bioassay. Using this system the known insecticidal protein Cry1Ac is demonstrated to effectively control Helicoverpa zea. Insects fed tissue with synthesized GFP (green fluorescent protein) as a positive control were shown to have enhanced growth and development. Additionally, a Brassica oleracea proteinase inhibitor (BoPI), a less characterized insect resistance candidate, demonstrated effectiveness to decrease the growth and development of H. zea at high levels of transient expression. Bioassays performed on stable transformants showed that BoPI had a low level of insect resistance at the more typical levels of gene transcription found in stably transformed plants. This agroinfiltration-insect bioassay procedure can give a rapid assessment of insect resistance significantly decreasing the time needed for evaluation of candidate genes.


Culicoides vector species on three South American camelid farms seropositive for bluetongue virus serotype 8 in Germany 2008/2009.
Palearctic species of Culicoides (Diptera, Ceratopogonidae), in particular of the Obsoletus and Pulicaris complexes, were identified as putative vectors of bluetongue virus serotype 8 (BTV-8) on ruminant farms during the epizootic in Germany from 2006 to 2009. BTV may cause severe morbidity and mortality in ruminants and sporadically in South American camelids (SAC). However, the fauna of Culicoides spp. on SAC farms has not been investigated. Therefore, the ceratopogonid fauna was monitored on three farms with BTV-seropositive SAC in Germany. Black-light traps were set up on pastures and in stables from summer 2008 to autumn 2009. Additionally, ceratopogonids were caught in emergence traps mounted on llama dung and dung-free pasture from spring to autumn 2009. After morphological identification, selected Culicoides samples were analysed for BTV-RNA by real-time RT-PCR. The effects of the variables 'location', 'temperature' and 'humidity' on the number of Culicoides caught in black-light traps were modelled using multivariable Poisson regression. In total, 26 species of Culicoides and six other genera of biting midges were identified. The most abundant Culicoides spp. collected both outdoors and indoors with black-light traps belonged to the Obsoletus (77.4%) and Pulicaris (16.0%) complexes. The number of Culicoides peaked in summer, while no biting midges were caught during the winter months. Daily collections of Culicoides were mainly influenced by the location and depended on the interaction of temperature and humidity. In the emergence traps, species of the Obsoletus complex predominated the collections. In summary, the absence of BTV-RNA in any of the analysed Culicoides midges and in the BTV-seropositive SAC on the three farms together with the differences in the pathogenesis of BTV-8 in SAC compared to ruminants suggests a negligible role of SAC in the spread of the virus. Although SAC farms may provide similar suitable habitats for putative Culicoides vectors than ruminant farms, the results suggest that geographic and meteorological factors had a stronger influence on Culicoides abundance than the animal species.


Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus.
Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure. Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization. These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.


Bexsero® chronicle.
Neisseria meningitidis causes globally 1·2 million invasive disease cases and 135,000 deaths per year, mostly in infants and adolescents. A century of traditional vaccinology had failed the fight against the serogroup B meningococcus (MenB), mostly prevalent in developed countries. Eighteen years after the publication of the first complete genome sequence from a living organism, thanks to an innovative genome-based approach named 'reverse vaccinology', the first broadly effective MenB vaccine was licensed for use by the European Medical Agency and other authorities, and is being implemented worldwide. Here we review this long and passionate journey, from the disease epidemiology to novel antigen discovery, from vaccine clinical development to public health impact: two decades of scientific and technological innovation to defeat one of the most sudden and devastating invasive diseases.


Preventing Diabetes in Primary Care: Providers' Perspectives About Diagnosing and Treating Prediabetes.
IN BRIEF Offering patient-centered care to prevent diabetes will require collaborative decision-making between patients with prediabetes and their health care providers. From the perspective of primary care providers, prediabetes detection should be targeted to patients who are most likely to benefit from diagnosis and treatment. Improving access to lifestyle intervention programs and educating providers about evidence-based treatments for prediabetes and how to effectively discuss treatment options with patients may improve both providers' and patients' engagement in diabetes prevention.