Cystic fibrosis transmembrane conductance regulator interacts with multiple immunoglobulin domains of filamin A.
Mutations of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) that impair its apical localization and function cause cystic fibrosis. A previous report has shown that filamin A (FLNa), an actin-cross-linking and -scaffolding protein, interacts directly with the cytoplasmic N terminus of CFTR and that this interaction is necessary for stability and confinement of the channel to apical membranes. Here, we report that the CFTR N terminus has sequence similarity to known FLNa-binding partner-binding sites. FLNa has 24 Ig (IgFLNa) repeats, and a CFTR peptide pulled down repeats 9, 12, 17, 19, 21, and 23, which share sequence similarity yet differ from the other FLNa Ig domains. Using known structures of IgFLNa.partner complexes as templates, we generated in silico models of IgFLNa.CFTR peptide complexes. Point and deletion mutants of IgFLNa and CFTR informed by the models, including disease-causing mutations L15P and W19C, disrupted the binding interaction. The model predicted that a P5L CFTR mutation should not affect binding, but a synthetic P5L mutant peptide had reduced solubility, suggesting a different disease-causing mechanism. Taken together with the fact that FLNa dimers are elongated ( approximately 160 nm) strands, whereas CFTR is compact (6 approximately 8 nm), we propose that a single FLNa molecule can scaffold multiple CFTR partners. Unlike previously defined dimeric FLNa.partner complexes, the FLNa-monomeric CFTR interaction is relatively weak, presumptively facilitating dynamic clustering of CFTR at cell membranes. Finally, we show that deletion of all CFTR interacting domains from FLNa suppresses the surface expression of CFTR on baby hamster kidney cells.


Clinical Features, Treatment, and Outcomes Among Chinese Children With Anti-methyl-D-aspartate Receptor (Anti-NMDAR) Encephalitis.
Objective: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common form of autoimmune encephalitis in pediatric patients. In this study, we aimed to investigate the clinical features and long-term outcomes of pediatric patients with anti-NMDAR encephalitis in China. Methods: We conducted a retrospective study of children (age range: 0-18 years) with anti-NMDAR encephalitis treated at Children's Hospital of Fudan University between July 2015 and November 2018. Demographic characteristics, clinical features, treatment, and outcomes were reviewed. Results: Thirty-four patients with anti-NMDAR encephalitis were enrolled (age range: 5 months to 14 years; median age: 7 years; female: 18). The median follow- up duration was 20 months (range: 6-39 months). Eighteen (52.9%) patients initially presented with seizures and 10 (29.4%) with abnormal (psychiatric) behaviors or cognitive dysfunction. Thirty (88.2%) patients exhibited more than two symptoms during the disease course. No neoplasms were detected. Twelve (35.2%) patients had abnormal cerebrospinal fluid (CSF) findings, including leukocytosis, and increased protein concentration. Eighteen (52.9%) patients exhibited normal brain MRI findings. Electroencephalography revealed abnormal background activity in 27 (79.4%) patients, and epileptiform discharges in 16 (47.0%) patients prior to immunotherapy. All patients received first-line immunotherapy, with 30 (88.2%) and four (11.8%) patients achieving good (Modified Rankin Scale [mRS] score of 0-2) and poor outcomes (mRS score of 3-5), respectively. Initial mRS scores differed significantly between the good and poor outcome groups. Fourteen out of 18 patients (77.7%) with seizures accepted anti-epileptic drug (AED) administration, and seizure freedom was achieved in 12 out of 14 (85.7%) patients at the last follow-up. Ten of these 12 (83.3%) patients withdrew from AED treatment within 1 year. Conclusions: Most patients achieved seizure freedom, so long-term use of AEDs may not be necessary for pediatric patients with anti-NMDAR encephalitis. Among our patients, 83.3% were sensitive to first-line immunotherapy and achieved good outcomes. Higher mRS scores before immunotherapy predicted poor outcomes, highlighting the need for a comprehensive assessment of patients with anti-NMDAR encephalitis.


Transformation of Alkynes into Chiral Alcohols via TfOH-Catalyzed Hydration and Ru-Catalyzed Tandem Asymmetric Hydrogenation.
A novel full atom-economic process for the transformation of alkynes into chiral alcohols by TfOH-catalyzed hydration coupled with Ru-catalyzed tandem asymmetric hydrogenation in TFE under simple conditions has been developed. A range of chiral alcohols was obtained with broad functional group tolerance, good yields, and excellent stereoselectivities.


Visually evoked potentials in eccentrically and centrally fixing amblyopes.
Visually evoked potentials to checkerboard pattern reversal were found to be nearly five times larger in eccentrically fixing amblyopic eyes than in centrally fixing amblyopic eyes when compared with the fellow non-amblyopic eye. The two groups of amblyopes had comparably poor visual acuity and differed in no other way save in their fixation behaviour. This suggests that at least two neurodevelopmental mechanisms subserve human amblyopia and that only one of these resembles the animal model of visual deprivation.


Enhanced production of IL-1 receptor antagonist by alveolar macrophages from patients with interstitial lung disease.
Alveolar macrophages (AM) produce various inflammatory and immunomodulatory cytokines. The objective of these experiments was to evaluate the production of IL-1ra, a specific receptor antagonist of IL-1, by AM from nonsmoking control subjects (n = 9), smoking control subjects (n = 6), and patients with interstitial lung disease (ILD) (n = 9). IL-1ra protein levels in cultured AM lysates and supernatants were determined by a specific ELISA; relative steady-state IL-1ra mRNA levels were measured using a specific cDNA probe. Before culture the isolated AM from all subject groups contained undetectable IL-1ra mRNA and no IL-1ra protein in the cell lysates as determined by ELISA. AM from nonsmoking control subjects spontaneously produced IL-1ra protein after a 20 h culture in medium, approximately 12 ng/ml with around half in cell lysates. AM from smoking control subjects produced levels of IL-1ra that were similar to the levels in AM from nonsmokers. In contrast, AM from nonsmoking ILD patients (n = 6) produced high levels of IL-1ra spontaneously (approximately 28 ng/ml), with no enhancement observed when cultured on adherent IgG. Interestingly, AM from smoking ILD patients (n = 3) produced lower levels of IL-1ra protein (approximately 11 ng/ml) that were comparable to levels noted in smoking control subjects. AM from all three types of subjects produced decreased amounts of IL-1ra in response to LPS and enhanced amounts in response to GM-CSF. In general, IL-1ra steady-state mRNA levels correlated with protein production.(ABSTRACT TRUNCATED AT 250 WORDS)


Unique mechanism of action of an antifungal antibiotic RI-331.
An amino acid antibiotic RI-331, (S)-2-amino-5-hydroxy-4-oxopentanoic acid, produced by a Streptomyces sp., is a novel antifungal agent. Biochemical studies on the mechanism of action of the antibiotic were carried out with a susceptible yeast Saccharomyces cerevisiae. In growing yeast cells, RI-331 inhibited protein synthesis to a greater extent than RNA or DNA synthesis. However, polypeptide synthesis by a cell-free preparation from yeasts was refractory to the antibiotic. The inhibition of protein synthesis by RI-331 was revealed to be due to the depletion of several amino acids such as threonine, methionine, isoleucine and serine in the cellular pool. These results suggest the possibility that some steps in amino acid metabolic pathways, especially those involved in biosynthesis of threonine, methionine and isoleucine, may constitute a primary target of RI-331 action.


Motives for Sex and Sexual Perpetration in College Men: An Exploratory Study.
Prior research has rarely focused on sexual motives (e.g., motives for having sex) when studying sexual violence perpetration prevention. The current study examined the role of sexual motives alongside other risk factors like alcohol expectancies in predicting sexual violence. We analyzed data from 205 male college students; 36% reported sexual perpetration of some type. Participants completed a series of questionnaires in a randomized order, including: measures of prior sexual perpetration, sexual motives, rape myth acceptance, alcohol expectancies, and a measure of social desirability. Data were analyzed using a series of T-tests and logistic regressions. With one exception (coping motives), all sexual motives (intimacy, enhancement, self-affirmation, peer approval, and partner approval) were endorsed at higher levels by individuals who perpetrated sexual violence than those who did not (p < .05, Cohen's d = .25-.56). The partner approval motive significantly predicted sexual violence perpetration on its own. The enhancement motive, both independently and in interaction with alcohol expectancies for aggression, predicted sexual violence perpetration. Two other motives, intimacy and self-affirmation, were only significant in interaction with alcohol expectancies for aggression. All sexual motives were endorsed more frequently by those who perpetrated sexual violence than those who did not. Sexual motives had a complex interaction with alcohol expectancies in predicting sexual violence perpetration. The results suggest that intervention programs should emphasize healthy, consensual sexual relationships that do not involve alcohol.


Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery.
This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.


Regression of renal hypertrophy and elevated renal Na+,K+-ATPase activity after insulin treatment in streptozotocin-diabetic rats.
The effect of insulin treatment on the renal hypertrophy and elevated renal Na+,K+-ATPase activity in rats with streptozotocin (STZ)-induced diabetes was examined. Rats with STZ-diabetes of 6- to 8-week duration had significantly lower body weights, higher plasma and urinary glucose concentrations, greater urinary volumes, increased kidney weights, and increased kidney/body weights and protein/kidney weight ratios compared to those in saline-citrate-injected controls. Specific Na+,K+-ATPase activity per mg protein in both cortical and outer medullary kidney homogenates was significantly elevated in diabetic vs. control animals, as was total renal Na+,K+-ATPase activity. One week of insulin treatment returned elevated plasma glucose, urinary volume, the protein/kidney weight ratio, and cortical and outer medullary Na+,K+-ATPase activity per mg protein to control values. Kidney weights and kidney/body weight ratios of diabetic animals remained elevated, as did absolute total renal Na+,K+-ATPase activity. After 3 weeks of insulin treatment, kidney weight and total renal Na+,K+-ATPase activity in diabetic animals returned to control values, but body weights remained lower than those in the controls, resulting in continued elevation of kidney/body weight ratios in the diabetic animals. The concurrent regression of both renal hypertrophy and elevated Na+,K+-ATPase activity to normal levels after insulin treatment of STZ-diabetic animals implicates renal growth rather than a direct effect of insulin as the primary factor controlling elevation and regression of Na+,K+-ATPase activity in the diabetic kidney. This finding demonstrates that the effect of renal hypertrophy can outweigh the intrinsic effects of insulin on an important renal transport system and that this effect may be as important as lack of hormone in determining the renal physiological responses in the disease. It is suggested that the increased renal tubular Na+,K+-ATPase activity is a key component of the renal hypertrophy and hyperfunction seen in diabetes.


Solved and Unsolved Problems of Chemoinformatics.
From humble beginnings in the Sixties chemoinformatics evolved into a scientific field of its own. Without the achievements of chemoinformatics the flood of information in chemistry would simply not be manageable and modern research in chemistry and related fields would be inconceivable. However, there are still a host of problems waiting for solutions to be found or to be improved. The impact of chemicals on human health and on the environment presents both challenges and concerns. Research in chemoinformatics could help in better understanding these topics and thus contribute to a better living.


Sorbitol causes preferential selection of Muller glial precursors from late retinal progenitor cells in vitro.
The replacement of glucose by sorbitol in growth medium causes selection of astroglial cells from heterogeneous primary cultures derived from the brains of newborn mice. The present study was undertaken to investigate the effects of sorbitol on in vitro selection of Müller glial precursors from expanded late retinal progenitor cells (RPCs). RPCs used in these studies were isolated from the neural retina of postnatal day one green fluorescent protein (GFP) transgenic mice. The resulting GFP positive neurospheres were dissociated into a single cell suspension and grown on poly-D-lysine/laminin coated tissue culture flasks or slides to generate adherent RPCs. These adherent cells were treated with glucose free medium containing 25 mM sorbitol for 7 days and the expression of retinal-specific cell markers was determined by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblot analysis In vitro studies showed that sorbitol treatment of late RPCs altered cellular morphology. Immunocytochemical studies showed an increase in the proportion of cells expressing glial cell markers, most of which co-expressed CRALBP, GFAP, and vimentin. An increase in the proportion of cells expressing PKCalpha, a bipolar cell marker, was also observed. RT-PCR analysis showed down-regulation of nestin transcripts with a concomitant increase in CRALBP, GFAP, vimentin and PKCalpha. These findings were confirmed by immunoblot analysis, where down-regulation of nestin expression with simultaneous up-regulation of CRALBP, GFAP and PKCalpha was observed. Sorbitol treatment of multipotent late RPCs, in the absence of glucose, results in the preferential selection of Müller glial precursors and their subsequent differentiation into cells that morphologically resemble Müller cells and co-express multiple glial markers.


[Graduate Medical Education - Structured, competency based training in Anesthesiology].
The "Joint Commission of BDA and DGAI for Graduate Medical Education and Further Education" presents a concept for postgraduate training in anesthesiology. Aiming at a different and demanding generation of young physicians it proposes a new approach to an attractive training in anesthesiology e. g. by simulation as one key concept. It is also intended to meet the guidelines of the German Medical Association of competency based rather than time based or procedure based graduate medical education. A clear structure and the competency based approach shall facilitate a process of professional teaching. The article describes the new concept of graduate medical education by the German Medical Association and the respective aims and objectives of the Scientific Medical Societies in Germany. An existing implementation in a hospital is given as an example of feasibility.


Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids.
Myricetin, robinetin and luteolin inhibited the mutagenic activity resulting from the metabolic activation of benzo[a]-pyrene and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene by rat liver microsomes. These naturally occurring plant flavonoids and seventeen additional flavonoids and related derivatives with phenolic hydroxyl groups inhibited the mutagenic activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), which is an ultimate mutagenic and carcinogenic metabolite of benzo[a]pyrene. Several flavonoids without phenolic hydroxyl groups or with methylated phenolic hydroxyl groups were inactive. The mutagenic activity of 0.05 nmol of BP 7,8-diol-9,10-epoxide-2 towards strain TA 100 of S. typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with myricetin (2 nmol), robinetin (2.5 nmol), luteolin (5 nmol), quercetin (5 nmol), 7-methoxyquercetin (5 nmol), rutin (5 nmol), quercetin (5 nmol), delphinidin chloride (5 nmol), morin (10 nmol), myricitrin (10 nmol), kaempferol (10 nmol), diosmetin (10 nmol), fisetin (10 nmol), or apigenin (10 nmol). Considerably less antimutagenic activity was observed for dihydroquercetin, naringenin, robinin, D-catechin, genistein, kaempferide and chrysin. Pentamethoxyquercetin, tangeretin, nobiletin, 7,8-benzoflavone, 5,6-benzoflavone, and flavone, which lack free phenolic groups, were inactive. The antimutagenic activity of hydroxylated flavonoids results from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solutions in 1:9 dioxane:water was markedly stimulated by myricetin, robinetin and quercetin. Myricetin was a highly potent inhibitor of the mutagenic activity of bay-region diol-epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene and dibenzo[a,i]pyrene, but higher concentrations of myricetin were needed to inhibit the mutagenicity of the chemically less reactive benzo[a]pyrene 4,5-oxide and bay region diol-epoxides of benz[a]anthracene, chrysene and benzo[c]phenanthrene.


Alcohol and aggression: a social information processing analysis.
The present study represents a preliminary exploration of the effects of alcohol on aggression (a hypothetical response to a videotaped provocation), using a social information processing model. Subjects were male social drinkers who received either a control beverage (ginger ale), placebo, .45 g/kg alcohol or .85 g/kg alcohol. Subjects observed a series of videotaped scenes of potential conflict occurring in the lounge of a college dormitory. In these scenes, an intruder switched the channel on a television set without asking the person watching for permission. The four groups were similar in their ability to encode and interpret social cues. Subjects in the 0.85 g/kg group were less able to generate competent (nonaggressive) solutions and were less likely than controls to select adaptive (nonaggressive) solutions. Subjects in the .85 g/kg group were more likely than control subjects to respond aggressively after being frustrated by the intruder's negative reaction to the initial attempt to resolve the conflict.


Sedation versus general anaesthesia in paediatric patients undergoing chest CT.
CT of the chest in paediatric patients often requires sedation or general anaesthesia to minimize motion artefacts. Both sedation and general anaesthesia are associated with atelectasis which obscures the underlying pulmonary pathology. We conducted a prospective study to compare these two methods with respect to degree of motion artefacts and extent of atelectasis. Nineteen patients undergoing 22 chest CT examinations were randomly selected for either sedation or general anaesthesia. The total area of atelectasis and the degree of motion artefacts were measured. The mean percentage of atelectasis was 6.67% for general anaesthesia and 0.01% for sedation (p = 0.01). There was no significant difference in the quality of the images between the sedation patients and the general anaesthesia patients. Whenever the clinical condition permits it, sedation rather than general anaesthesia should be given to paediatric patients undergoing chest CT.


Insights on Klebsiella pneumoniae Biofilms Assembled on Different Surfaces Using Phenotypic and Genotypic Approaches.
Klebsiella pneumoniae is a prominent etiological agent of healthcare associated infections (HAIs). In this context, multidrug-resistant and biofilm-producing bacteria are of special public health concern due to the difficulties associated with treatment of human infections and eradication from hospital environments. Here, in order to study the impact of medical devices-associated materials on the biofilm dynamics, we performed biofilm phenotypic analyses through a classic and a new scanning electron microscopy (SEM) technique for three multidrug-resistant K. pneumoniae isolates growing on polystyrene and silicone. We also applied whole-genome sequencing (WGS) to search for genetic clues underlying biofilm phenotypic differences. We found major differences in the extracellular polymeric substances (EPS) content among the three strains, which were further corroborated by in-depth EPS composition analysis. WGS analysis revealed a high nucleotide similarity within the core-genome, but relevant differences in the accessory genome that may account for the detected biofilm phenotypic dissimilarities, such as genes already associated with biofilm formation in other pathogenic bacteria (e.g., genes coding haemogglutinins and haemolysins). These data reinforce that the research efforts to defeat bacterial biofilms should take into account that their dynamics may be contingent on the medical devices-associated materials.


Effect of ethanol on the production of carboxypeptidase Y using the GAL10 promoter in a Saccharomyces cerevisiae gal80 mutant.
In the course of studying carboxypeptidase Y (CPY) production, we found that the expression level of the gene, which is under the control of the GAL10 promoter, increased in a Saccharomyces cerevisiae gal80 mutant grown in a medium containing ethanol as the sole carbon source. In the cultivation of the gal80 mutant KS58-2D/pCY303 carrying a multicopy plasmid, which contains the PRC1 gene fused to the GAL10 promoter, CPY production continued after the consumption of galactose. In this phase, the cells utilized ethanol as the carbon source. To increase the CPY production level, we examined the effect of carbon source feeding in a fed-batch culture. The production level in the fed-batch culture using ethanol was 1.3-fold higher than that in a batch culture and 1.6-fold higher than that in a fed-batch culture using galactose. By 5'-deletion analysis of the GAL10 promoter, the region between -256 and -232 was found to be important for the promoter activity in the gal80 mutant growing in the presence of ethanol.


An autopsy case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction.
A 78-year-old Japanese woman presented with slow progressive disorientation and memory disturbances. Pathological laughing was observed at an early disease stage and continued for several months. Around the same time, the patient began to exhibit an exaggerated startle reaction and mild myoclonus. The pathological laughing and startle reaction disappeared before the patient reached an akinetic mutism state approximately 16 months after symptom onset. MRI showed extensive hyperintensity of the cerebral cortex and striatum on diffusion-weighted images, and swelling in the cerebral cortex on T2-weighted and fluid attenuated inversion recovery images. A prion protein (PrP) gene analysis revealed a V180I mutation with methionine homozygosity at codon 129. Neuropathological examination showed extensive spongiform changes with characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebral neocortex and striatum. Gliosis and hypertrophic astrocytosis were generally mild in character. Neurons were relatively preserved in number. We believe that pathological laughing and an exaggerated startle reaction are possible pathognomonic findings of V180I genetic Creutzfeldt-Jakob disease. Based on the pathological findings of the present case, the presence of the VaSNoC-type spongiform changes with relative preservation of the neurons in the cerebral cortex and a lack of apparent brainstem involvement are associated at least in part with the pathological laughing and startle reaction.


Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes.
Type 1 diabetes (T1D) complications are responsible for much of the disease morbidity. Evidence suggests that familial factors exert an influence on susceptibility to complications. We investigated familial risk factors and gender differences for retinopathy, nephropathy, and neuropathy. This study was a case-control design nested on a cohort of T1D families. We collected data (questionnaire, medical records) starting in 1988. Follow-up has been ongoing since 2004. There were 8114 T1D patients among 6707 families. All patients had T1D onset age younger than 30 yr and required insulin treatment. Patients who remained without a complication after more than 15 yr of diabetes were considered to be without that complication for our analyses. A complication in a sibling increased the risk for that complication among probands: odds ratio 9.9 (P < 0.001) for retinopathy, 6.2 for nephropathy (P < 0.001), and 2.2 for neuropathy (P < 0.05). Compared with male probands, a female T1D proband had 1.7-fold higher retinopathy risk (P < 0.001) and 2-fold higher neuropathy risk (P < 0.001). T1D cases with onset between ages 5 and 14 yr had an increased complications risk compared with subjects diagnosed either at a very young age or after puberty. The presence of one complication significantly increased the risk for others. If a parent had type 2 diabetes, the risk for nephropathy increased (odds ratio 1.9, P < 0.01, but T1D in a parent did not increase the risk). We confirmed that familial factors influence T1D microvascular pathologies, suggesting a shared genetic basis for complications, perhaps independent of T1D susceptibility. We also found an unexpected increased female risk for complications.


Multiple B cell stimulation by individual antigen-specific T lymphocytes.
Recently, an experimental system has been described which allows for the isolation and antigenic stimulation of individual antigen-specific helper T lymphocytes in collaboration with a nonlimiting number of primary B lymphocytes. In the studies presented in this report, this system has been employed to determine whether an individual T lymphocyte has the potential to interact with more than a single B lymphocyte, when the B cells are of different antigenic specificities. The results of these studies indicate that an individual influenza virus PR 8-specific T lymphocyte has the ability to promote antibody responses of both trinitrophenyl (TNP)- and PR8-specific B lymphocytes in response to the in vitro antigen TNP-PR8. Similar results were obtained when T cells specific for the hapten TNP were used in collaboration with TNP- and PR8-specific B cells. These results demonstrate that an individual T lymphocyte has the potential to collaborate with more than one B lymphocyte, and that these B cells may differ in their antibody receptor for antigen. These results do not rule out a role for idiotype or allotype-specific T cells in antibody responses but, rather, strongly argue that antigen-specific T cells are able to independently initiate primary B cell responses of B cells with distinct antibody receptors. In addition, under these conditions, hapten-specific helper T cells can be readily demonstrated and may facilitate the response of B cells specific for the same or different determinants.


Proteomic analysis of Herbaspirillum seropedicae cultivated in the presence of sugar cane extract.
Bacterial endophytes of the genus Herbaspirillum colonize sugar cane and can promote plant growth. The molecular mechanisms that mediate plant- H. seropedicae interaction are poorly understood. In this work, we used 2D-PAGE electrophoresis to identify H. seropedicae proteins differentially expressed at the log growth phase in the presence of sugar cane extract. The differentially expressed proteins were validated by RT qPCR. A total of 16 differential spots (1 exclusively expressed, 7 absent, 5 up- and 3 down-regulated) in the presence of 5% sugar cane extract were identified; thus the host extract is able to induce and repress specific genes of H. seropedicae. The differentially expressed proteins suggest that exposure to sugar cane extract induced metabolic changes and adaptations in H. seropedicae presumably in preparation to establish interaction with the plant.


High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.
Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature.


Chronic rhinosinusitis is associated with higher prevalence and severity of bronchiectasis in patients with COPD.
Bronchiectasis revealed by high-resolution computed tomography (HRCT) is common in chronic obstructive pulmonary disease (COPD), but the causes and risk factors remain to be determined. Chronic rhinosinusitis (CRS) is closely associated with bronchiectasis or COPD, but whether it is associated with comorbid bronchiectasis in COPD (COPD-Bx) is unknown. Patients with stable COPD were enrolled consecutively and evaluated for the presence of CRS by questionnaire and paranasal sinus computed tomography. The presence and severity of bronchiectasis on lung HRCT were evaluated by the Smith and severity scores. COPD symptoms were evaluated by COPD Assessment Test (CAT) and Modified British Medical Research Council Questionnaire. The sputum cell differentials and concentrations of interleukin (IL)-6, IL-8, IL-5, matrix metalloproteinases-9 (MMP-9), and tissue inhibitor of matrix metalloproteinases-1 were measured. We enrolled 136 patients with stable COPD, of which 66 (48.5%) were diagnosed with CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) criteria. The prevalence of bronchiectasis was 57.6% in patients with CRS, but 37.1% in those without CRS (P=0.017). COPD-Bx patients with CRS showed a significantly higher severity score of bronchiectasis than those without CRS (P=0.034). COPD patients with CRS had a higher percentage of eosinophils, higher levels of IL-8, IL-6, and MMP-9 in sputum as compared to those without CRS. In COPD-Bx patients with CRS, the percentage of eosinophils and the levels of IL-6 and MMP-9 in sputum were increased as compared to those without CRS. In all the subjects, Sino-Nasal Outcome Test-20 correlated with CAT score (r=0.315, P<0.01) and in COPD patients with CRS, Lund-MacKay scores correlated with forced expiratory volume in 1 s (% pred) (r=-0.251, P<0.05). CRS was associated with COPD-Bx and this was probably due to increased airway inflammation.


Estimating the potential pool of uncontrolled DCD donors in the United States.
Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.


A gap in surface therapy: topical antihistamines.
Allergic and non-allergic rhinitis have been treated by many drugs with different modes of action such as topical disodium cromoglycate and ipratropium bromide, systemic antihistamines and corticosteroid drugs and topical corticosteroids. Yet, these therapies are not entirely satisfactory for all symptoms. The rationale for the topical, intranasal use of antihistamines in patients is discussed. Topical antihistamine agents are administered in order to avoid the side effects of systematically applied medications, and to reach higher local drug concentrations. H1 receptors of the nasal mucosa play an important role in the physiopathology of allergic and non-allergic rhinitis and even of infectious rhinitis. Most studies using topical antihistamines in rhinitis, had an experimental physiopathological aim and did not explore clinical efficacy. Recently, topical application of levocabastine--a potent H1 antagonist--yielded good clinical results in allergic conjunctivitis, seasonal allergic rhinoconjunctivitis, and non allergic perennial rhinitis.


[A Case of Papillary Renal Cell Carcinoma 40 Years after Radiation Therapy].
Here, we report a case of papillary renal cell carcinoma in a 47-year-old woman. In 1970 (at 5 years old), she was diagnosed with Wilms tumor in her right kidney, and underwent surgery. However, nephrectomy was not possible. Consequently, she received radiation therapy (61. 5 Gy) at the former hospital. Thereafter, the patient regularly visited her physician and had no further problems. In 1998 (at 33 years old), blood was detected in her urine, and renal cell carcinoma was suspected. A computed tomography (CT)-guided biopsy was performed, but tissue collection was difficult due to calcification of the renal parenchyma after radiation treatment. The patient was followed closely without treatment. Since 2003, the patient on her own volition stopped visiting the hospital. Her symptoms gradually worsened and in October 2012 (at 47 years old), she was admitted to our hospital. Based on the imaging findings, a right renal pelvic tumor was suspected. Despite various examinations, including retrograde pyelography, a definitive diagnosis could not be made. Following detailed examinations, we observed that the tumor had developed bone metastases. We started chemotherapy consisting of gemcitabine and cisplatin, but the tumor was resistant to the treatment. Renal cell carcinoma was suspected based on the biopsy results for bone metastasis, and consequently, targeted therapy (pazopanib) was started. However, the patient died in August 2014 (at 49 years old) because of progression of the disease. An autopsy revealed the definitive diagnosis to be papillary renal cell carcinoma type 2.


A prospective analysis of GERD after POEM on anterior myotomy.
Peroral endoscopic myotomy (POEM) is an emerging, minimally invasive procedure capable of overcoming limitations of achalasia treatments, but gastroesophageal reflux disease (GERD) after POEM is of concern and its risk factors have not been evaluated. This prospective study examined GERD and the association of POEM with reflux esophagitis. Achalasia patients were recruited from a single center. The pre- and postoperative assessments included Eckardt scores, manometry, endoscopy, and pH monitoring. Between September 2011 and November 2014, 105 patients underwent POEM; 70 patients were followed up 3 months after POEM. Postoperatively, significant reductions were observed in lower esophageal sphincter (LES) pressure [from 40.0 ± 22.8 to 20.7 ± 14.0 mmHg (P < 0.05)], LES residual pressure [from 22.1 ± 13.3 to 11.4 ± 6.6 mmHg (P < 0.05)], and Eckardt scores [from 5.7 ± 2.5 to 0.7 ± 0.8 (P < 0.05)]. Symptomatic GERD and moderate reflux esophagitis developed in 5 and 11 patients (grade B, n = 8; grade C, n = 3), respectively, and were well controlled with proton pump inhibitors. Univariate logistic regression analysis revealed integrated relaxation pressure was a predictor of ≥grade B reflux esophagitis. No POEM factors were found to be associated with reflux esophagitis. POEM is effective and safe in treating achalasia, with no occurrence of clinically significant refractory GERD. Myotomy during POEM, especially of the gastric side, was not associated with ≥grade B (requiring medical intervention) reflux esophagitis. Extended gastric myotomy (2-3 cm) during POEM is recommended to improve outcomes.


Balance Training With a Dynamometric Platform Following Total Knee Replacement: A Randomized Controlled Trial.
Sensorimotor training has proven to be an efficient approach for recovering balance control following total knee replacement (TKR). The purpose of this trial was to evaluate the influence of specific balance-targeted training using a dynamometric platform on the overall state of balance in older adults undergoing TKR. This was a randomized controlled clinical trial conducted at a university hospital rehabilitation unit. Patients meeting the inclusion criteria were randomly assigned to a control group or an experimental group. Both groups participated in the same 4-week postoperative rehabilitation training protocol. Participants in the experimental group performed additional balance training with a dynamometric platform consisting of tests related to stability challenges, weight-shifting, and moving to the limits of stability. The primary outcome measure was the overall state of balance rated according to the Berg Balance Scale. Secondary outcomes in terms of balance were the Timed Up and Go Test, Functional Reach Test, and Romberg open and closed-eyes tests. Data processing included between-group analysis of covariance, minimal detectable change assessment for the primary outcome measure, and effect size estimation. Confidence intervals (CIs) were set at 95%. Forty-three participants meeting the inclusion criteria and having signed the informed consent were randomly assigned to 2 groups. Thirty-seven completed the training (86.1%). Significant between-group differences in balance performance were found as measured with the Berg Balance Scale (P = .03) and Functional Reach Test (P = .04) with a CI = 95%. Significant differences were not recorded for the Timed Up and Go Test or Romberg open and closed-eyes tests (P > .05). Furthermore, Cohen's effect size resulted in a value of d = 0.97, suggesting a high practical significance of the trial. According to the Berg Balance Scale and Functional Reach Test, participants with TKR who have followed a 4-week training program using a dynamometric platform improved balance performance to a higher extent than a control group training without such a device. The inclusion of this instrument in the functional training protocol may be beneficial for recovering balance following TKR.


The Effect of UV Illumination on the Room Temperature Detection of Vaporized Ammonium Nitrate by a ZnO Coated Nanospring-Based Sensor.
The effect of UV illumination on the room temperature electrical detection of ammonium nitrate vapor was examined. The sensor consists of a self-assembled ensemble of silica nanosprings coated with zinc oxide. UV illumination mitigates the baseline drift of the resistance relative to operation under dark conditions. It also lowers the baseline resistance of the sensor by 25% compared to dark conditions. At high ammonium nitrate concentrations (120 ppm), the recovery time after exposure is virtually identical with or without UV illumination. At low ammonium nitrate concentrations (20 ppm), UV illumination assists with refreshing of the sensor by stimulating analyte desorption, thereby enabling the sensor to return to its baseline resistance. Under dark conditions and low ammonium nitrate concentrations, residual analyte builds up with each exposure, which inhibits the sensor from returning to its original baseline resistance and subsequently impedes sensing due to permanent occupation of absorption sites.


[Isopropyl myristate molecular gels and drug-loaded transdermal capability].
To prepare of isopropyl myristate (IPM) molecular gels and investigate of its transdermal capability. Microstructure of IPM gels was studied by scanning electron microscope (SEM) and optical microscope (OM). The rheology and thixotropy of IPM gels were investigated by viscosity. Triptolide was used as model drug to investigate its transdermal capability. The microstructure of IPM gels was a three-dimension network formed by the aggregation of Span 60 in IPM, which was rod-like tubular aggregate. It has good rheology and thixotropy. There was a good linear correlation between the accumulative permeated amount per unit area and the time for triptolide-loaded IPM gels. The permeation process agreed with zero order pharmacokinetics. The average permeability through rat skin for triptolide was 19.26 ng x cm(-2) x h(-1), which was 2.92 times of triptolide unguents obtained commercially available. Isopropyl myristate molercular gel can be formed by span 60 assemblies. Transdermal capability drug-loaded IPM gels was better than that of triptolide unguents.


H/D isotope effect on porphine and porphycene molecules with multicomponent hybrid density functional theory.
To analyze the H/D isotope effect on porphine and porphycene molecules including the protonic/deuteronic quantum nature and electron correlation efficiently, the authors have developed the new scheme of the multicomponent hybrid density functional theory [MC_(HF+DFT)]. The optimized geometries of porphine, porphycene, and these deuterated isotopomers by our MC_(HF+DFT) method are in good agreement with the experimental "high-symmetric" structures, contrary to the "low-symmetric" geometries optimized by pure multicomponent Hartree-Fock method. The optimized geometries for HD-porphine and HD-porphycene molecules, in which an inner hydrogen is replaced to a deuterium, are found to be low symmetric. Such drastic geometrical change induces the electronic polarization, and gives rise to the slight dipole moment values in these HD species. Their results clearly indicate that the difference of the nuclear quantum nature between inner proton and inner deuteron directly influences the molecular geometry and electronic structure.


A Comprehensive, Multimodal, Interdisciplinary Approach to Chronic Non-Cancer Pain Management in a Family Medicine Clinic: A Retrospective Cohort Review.
The complexity of chronic non-cancer pain in the setting of regulatory efforts to curb opioid usage presents a novel challenge for the medical community. Much of this burden falls on primary care clinics. We retrospectively quantified the reduction of opioid usage by patients in a multimodal, interdisciplinary, primary care clinic for chronic pain. A multimodal, interdisciplinary, chronic pain clinic embedded in a large academic military family medicine clinic operated one-half day weekly to address referrals from within the clinic at large. Appointment times were longer than typical primary care appointments. The clinic was equipped with support staff, ancillary specialty providers, and non-pharmacologic complementary treatment resources. A retrospective cohort review was conducted on 78 patients referred to this clinic from March 1, 2015 (the inception date of the clinic) through December 31, 2015. Fifty-four of 78 patients met inclusion criteria. Overall mean morphine equivalent daily dosing (MEDD) dropped from 31.5 MEDD to 20.5 MEDD (p = 0.0005) 12 months post-intervention and from 31.5 MEDD to 9.5 MEDD (p < 0.0001) 36 months post-intervention. Four patients with a high mean baseline opioid dose of 185.2 MEDD dropped to 29.9 MEDD 36 months post-intervention. The mean 0-10 pain score decreased from 5.3 ± 2.2 to 4.0 ± 2.5 (p = 0.001). A multimodal, interdisciplinary, primary care-based, chronic pain clinic equipped with extended appointment times, non-pharmacologic treatment resources, and specialty access can curb opioid usage. Leadership support for protracted appointment duration, complementary treatment resources, and interdisciplinary personnel is crucial to success.


Adoptive cell transfer therapy for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.


Repair of 4,5',8-trimethylpsoralen monoadducts and cross-links by the Escherichia coli UvrABC endonuclease.
Using an oligonucleotide model substrate, we observed two unusual mechanisms of UvrABC endonuclease in the repair of 4,5',8-trimethylpsoralen monoadducts and crosslinks. (i) UvrABC endonuclease usually incises a psoralen monoadduct only on the damaged strand. However, for one of the monoadducts we studied, incision on the complementary undamaged strand was also observed at a very low frequency, as though the adduct were on the thymine across from the damaged strand. Although the details of the erroneous incision are not yet known, such erroneous incision is potentially mutagenic. (ii) In cross-link repair, we observed that the UvrABC endonuclease incises the cross-linked DNA on either the furan side strand or the pyrone side strand. The incisions are not equally efficient. These data suggest that the structure of a psoralen cross-link, as seen by a repair enzyme, varies with the DNA sequence.


Fistula of stapes footplate caused by pulsatile cerebrospinal fluid in inner ear malformation.
Congenital malformations of the inner ear are well described, though the combination with cerebrospinal fluid (CSF) leaks remains controversial. In this paper a case of a bilateral Mondini malformation with a CSF otorrhea on one side is reported. The malformed stapes contains a perforation in the middle of the footplate and associated thinning analogous to a pothole in a mountain stream. The histological findings support the hypothesis of pulsatile flow of CSF as origin of the perforation of the footplate.


Diet-induced milk fat depression in dairy cows results in increased trans-10, cis-12 CLA in milk fat and coordinate suppression of mRNA abundance for mammary enzymes involved in milk fat synthesis.
Milk composition can be altered by diet, and one example is milk fat depression (MFD) in dairy cows. The biohydrogenation theory of MFD has implicated unique fatty acids formed by altered rumen biohydrogenation of PUFA; one example is trans-10, cis-12 conjugated linoleic acid (CLA). In the present study, we induced MFD with a high concentrate/low forage (HC/LF) diet and examined milk composition, milk fatty acid changes and mammary lipogenic mRNA abundance to determine the mechanism involved. The HC/LF diet reduced milk fat percentage by 25% and yield by 27% with no effect on dietary intake, milk production, protein or lactose. Milk fatty acids synthesized de novo in the mammary gland and fatty acids taken up from circulation were reduced to a similar extent (molar basis). MFD was also characterized by the appearance of trans-10, cis-12 CLA in the milk fat. We analyzed mammary mRNA abundance for lipogenic genes and detected reductions for acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), fatty acyl CoA ligase, glycerol phosphate acyltransferase (GPAT) and acylglycerol phosphate acyltransferase (AGPAT). There was no effect on the milk protein gene, kappa-casein. The reductions in mRNA were also correlated with the appearance of trans-10, cis-12 CLA in the milk fat for ACC, FAS, lipoprotein lipase and GPAT. This study demonstrates that diet-induced MFD involves coordinated effects on mRNA for mammary lipid synthesis pathways, and provides support for a mechanism involving alterations in transcriptional activation of these genes.


His bundle electrograms in patients with congestive cardiomyopathy.
His bundle electrograms were obtained at rest and during atrial pacing in 16 patients with congestive cardiomyopathy. Increments in heart rate during atrial pacing were associated with progressive increases in the A-H interval in all patients. Three patients had abnormal conduction (prolonged P-H) proximal to the His bundle; atrial pacing resulted in second degree A-V block (A-H block) in these three patients at paced rates below 130/min; these three patients were on digitalis at the time of the study. Two patients ahd left bundle branch block associated with a prolonged H-V interval suggesting a conduction disturbance in the contralateral bundle system either at or distal to the branching portion of the His bundle. Two patients had H-V prolongation in the presence of a normal QRS duration which suggests delay in the bundle of His. Two patients with normal H-V intervals had marked prolongation of the total intraventricular conduction time (H-S prolongation). The His bundle electrogram uncovered abnormalities in atrioventricular conduction not apparent on the standard electrocardiogram and has allowed expansion of our knowledge regarding the electrophysiologic features of congestive cardiomyopathy.


[Catalytic stability in wet air oxidation of carboxylic acids over ZnFe0.25Al1.75 O4 catalyst].
Oxalic, formic and acetic acid are main intermediate products in catalytic wet air oxidation process (CWAO). The catalytic activity and stability in CWAO of the three short-chain organic acids over ZnFe0.25Al1.75O4 catalyst were studied. Oxalic acid is the only oxidizable intermediate and the largest amount of Fe leaching is 9.5 mg L(-1) at 160 degrees C during CWAO process. Formic and acetic acid have little influence on Fe leaching. Due to the strong reducible ability of oxalic acid, the amount of Fe leaching is larger in nitrogen atmosphere than that in oxygen atmosphere. Salicylic acid can be also degraded by ZnFe0.25Al1.75O4 catalyst with a high catalytic activity and stability.


In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest.
The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.


Effect of endurance training on fatty acid metabolism during whole body exercise.
Endurance exercise training increases fat oxidation during large muscle mass exercise. Although the source of this fat has been thought to be plasma free fatty acids (FFA) released from adipose tissue, the training-induced decrease in lipolytic hormonal responses to exercise is not consistent with this concept. The purpose of this communication is to review findings, from our laboratory indicating that, in young healthy subjects, endurance exercise training reduces plasma FFA turnover and oxidation during moderate intensity prolonged 2-leg cycling while simultaneously enhancing depletion of triglycerides from the active musculature. Evidence is presented that metabolism of intramuscular triglycerides can explain the increase in total fat oxidation observed in the trained state during large muscle mass exercise. However, these results may not be applicable to exercise involving small muscle groups, a distinction that is likely to be important in explaining the apparent conflict between our findings and those from other laboratories where experimental conditions were different. In summary, for large muscle mass exercise up to 2 h in duration, plasma FFA are a less important fuel source in the trained state, and intramuscular triglycerides supply the major portion of the increase in oxidized fatty acids.


The Efficacy and Safety of Botulinum Toxin Type A Injections in Improving Facial Scars: A Systematic Review and Meta-Analysis.
Botulinum toxin type A (BTA) has a wide range of clinical applications, and its use in improving aesthetics is one of them. The aim of this study was to better assess the efficacy and safety of BTA in patients with facial scars. We extracted the data of the visual analog scale (VAS) score, Vancouver scar scale (VSS) score, scar width, observer scar assessment scale (OSAS), patient scar assessment scale (PSAS), and/or drug-related adverse events. Five studies provided the data of VAS score, and the results showed that the VAS score in the BTA group was significantly higher than that in the control group. Three randomized controlled trials (RCTs) reported the VSS score. A statistically significant difference exists between the BTA group and the control group. Three RCTs reported the scar width after BTA treatment. A more favorable change was found in the BTA group with scar width even without statistical significance. Data about the OSAS and PSAS scores were available in two trials. There was no significant difference in OSAS and PSAS scores between the BTA group and the control group. Only three studies recorded three slight adverse events. There were no reports of severe complications. In conclusions, this study demonstrated that BTA has the potential to improve facial scars with an acceptable safety profile.


Clock and clock-controlled genes are differently expressed in the retina, lamina and in selected cells of the visual system of Drosophila melanogaster.
The retina and the first optic neuropil (lamina) of Drosophila show circadian rhythms in various processes. To learn about the regulation of circadian rhythms in the retina and lamina and in two cell types, glial and the lamina L2 interneurons, we examined expression of the following clock genes; per, tim, clk, and cry and clock-controlled genes (ccgs); Atpα, nrv2, brp, Pdfr. We found that the expression of gene studied is specific for the retina and lamina. The rhythms of per and tim expression in the retina and glial cells are similar to that observed in the whole head and in clock neurons, while they differ in the lamina and L2 cells. In both the retina and lamina, CRY seems to be a repressor of clk expression. In L2 interneurons per expression is not cyclic indicating the other function of PER in those cells than in the circadian molecular clock. In contrast to per and tim, the pattern of clk and cry expression is similar in both the retina and lamina. The retina holds the autonomous oscillators but the expression of cry and ccgs, Atpα and nrv2, is also regulated by inputs from the pacemaker transmitted by PDF and ITP neuropeptides.


[Antiproteolytic activity of the blood serum in adolescents with pulmonary tuberculosis].
The antiproteolytic activity of the blood serum was examined in the course of hospital treatment of 128 adolescents with prevailingly torpid forms of pulmonary tuberculosis and in 19 adolescents with tubercular infection (control). A direct correlation has been found between the degree of clinico-roentgenological manifestations of the disease and level of serum alpha 1-inhibitor of proteinases as well as between the efficacy of treatment and normalization of the antiproteolytic activity of the blood of the patients. It proposed to use the determination of alpha 1-inhibitor of proteinases as an additional criterion of evaluation of the clinical course and outcomes of the disease in adolescents.


Collaborative study of the spectrophotometric determination of procainamide hydrochloride.
The USP analysis for procainamide-HCl is titrimetric and relatively nonspecific, capsule and tablet dyes may interfere, and the method is not applicable to coated tablets. In the spectrophotofluorometric method the sample deteriorates when exposed to a xenon source. In the ultraviolet spectrophotometric method reported here, the sample is dispersed in acid medium, possible interferences are extracted in chloroform, base is added, procainamide is extracted in chloroform, the residue is dissolved in sodium hydroxide, the compound is measured by absorption at 272 nm and comparison with a standard. Recoveries of standards added to capsule, tablet, and injection composites ranged from 99.3 to 102%. Twelve collaborators reported duplicate assay results for all 3 dosage forms with per cent standard deviations for 5 samples ranging from 1.01 to 1.27%. The method has been adopted as official first action.


Understanding the role of endothelial progenitor cells in percutaneous coronary intervention.
Percutaneous coronary intervention is associated with mechanical endovascular injury and endothelial denudation. Re-endothelialization is essential for restoration of normal vascular homeostasis and regulation of neointimal hyperplasia. The endothelial progenitor cell recently emerged as an important component of the response to vascular injury, having the potential to accelerate vascular repair through rapid re-endothelialization. There remains considerable uncertainty over the precise identity and function of endothelial progenitor cells, and harnessing their therapeutic potential remains a challenge. A better understanding of the role of circulating progenitors in the response to vascular injury is necessary if we are to develop effective strategies to enhance vascular repair after percutaneous coronary intervention. In this review, we examine the preclinical and clinical evidence of a role for bone marrow-derived putative endothelial progenitor cells after iatrogenic vascular injury associated with balloon angioplasty and stent deployment. Therapies designed to mobilize endothelial progenitors or to increase their ability to home to the site of stent implantation may have a role in the future management of patients undergoing percutaneous coronary intervention.


Neuromedin C: potential-dependent surface-enhanced Raman spectra in the far-red spectral region on silver, gold, and copper surfaces.
Neuromedin C (NMC) is a decapeptide (Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH(2)) that acts as a growth factor in a wide range of tumors including carcinomas of the pancreas, stomach, breast, prostate, and colon. We report surface-enhanced Raman spectra (SERS) of NMC on electrochemically roughened Ag, Au, and Cu electrode surfaces over an electrode potential range varying from +0.200 to -1.200 V (depending on the electrode material). We compared the SERS spectra to the Raman spectrum of the corresponding solid species. The SERS spectra were dominated by L-tryptophan (Trp) vibrations. This indicates that Trp interacted with the metallic surfaces of the electrodes, either by binding directly to the surface or by staying in close proximity to the surface. Characteristic SERS bands showed that, in the case of the Ag electrode, the Trp residue was almost perpendicular to the surface. In contrast, the Trp residue was slightly tilted with respect to the Au electrode surface, and Trp remained some distance from the surface of the Cu electrode. These differences were due to differences in surface rheology and in the type of metal (Ag vs Au vs Cu) responsible for the observed enhancement mechanism. On the other hand, variations in the electrode potentials only had a slight influence on the SERS patterns and the observed changes were mainly due to the reorientation of the Trp ring with respect to the electrode surface. These findings were fully supported by generalized two-dimensional correlation analysis (G2DCA).


Perspectives on prevention of type 2 diabetes after gestational diabetes: a qualitative study of Hispanic, African-American and White women.
Women with gestational diabetes (GDM) have a fivefold higher risk of developing type 2 diabetes (T2DM). Furthermore, Hispanic and African-American women are disproportionately affected by GDM, but their views on prevention of T2DM after gestational diabetes are largely unknown. We conducted semi-structured interviews with 23 women (8 Hispanic, 8 African-American, 7 non-Hispanic White) from two academic clinics in Chicago, IL. Interview questions elicited perspectives on prevention of T2DM; the interview protocol was developed based on the Health Belief Model. Two investigators applied template analysis to identify emergent themes. Women conceptualized risk for T2DM based on family history, health behaviors, and personal history of GDM. A subgroup of women expressed uncertainty about how GDM influences risk for T2DM. Women who described a strong link between GDM and T2DM often viewed the diagnosis as a cue to action for behavior change. T2DM was widely viewed as a severe condition, and desire to avoid T2DM was an important motivator for behavior change. Children represented both a key motivator and critical barrier to behavior change. Women viewed preventive care as important to alert them to potential health concerns. Identified themes were congruent across racial/ethnic groups. Diagnosis with GDM presents a potent opportunity for engaging women in behavior change. To fully harness the potential influence of this diagnosis, healthcare providers should more clearly link the diagnosis of GDM with risk for future T2DM, leverage women's focus on their children to motivate behavior change, and provide support with behavior change during healthcare visits in the postpartum period and beyond.


Effectiveness of seasonal malaria chemoprevention in reducing under-five malaria morbidity and mortality in the Savannah Region, Ghana.
To assess the effectiveness of seasonal malaria chemoprevention (SMC) in reducing under-five malaria morbidity and mortality. Under-five malaria data for confirmed episodes, deaths, and number of children dosed per cycle of SMC campaign were extracted from the District Health Information Management System (DHIMS-2) for 2018-2019. Data verification was done to compare extracted data with the source for completeness and consistency. Association between SMC and the main outcome variables (malaria cases and mortality) was computed from 2X2 tables and reported as rate ratios at a 95% confidence level. All seven (7) districts in Savannah Region, Ghana. Children under five years. Sulphadoxine-Pyrimethamine and Amodiaquine (SPAQ) prophylaxis given monthly, four times, durng the rainy season (July to October). SMC coverage per cycle and under-five malaria morbidity and mortality ratios. Over 370,000 dose packs of SPAQ were administered with an average cycle coverage of 93%. There was approximately 17% (p<0.01) and 67% (p=0.047) reduction in malaria-related morbidity and mortality, respectively, in the implementation year compared with the baseline. This translated into nearly 9,300 episodes of all forms of malaria and nine malaria-attributable deaths averted by the intervention. SMC (combined with existing control measures) wields prospects of accelerating the regional/national malaria elimination efforts if the implementation is optimised. Expansion of the intervention to other high-prevalence regions with seasonal variation in disease burden may be worthwhile. None declared.


The HIV/AIDS epidemic in Africa: implications for U.S. policy.
Political will or commitment toward the HIV epidemic has been lacking in most African countries. Although most countries are in denial, a few have moved into recognition of the epidemic. Only two countries, Senegal and Uganda, have moved into mobilization. Ineffectiveness is judged by increasing HIV prevalence rates and declining life expectancy. Countries without active national leadership to fight the epidemic have seen deterioration in these criteria. In addition to its toll in Africa, this epidemic threatens U.S. political, economic, and security interests. Political responses to manage the risks to the United States have revolved around much increased development assistance through traditional channels and financial support for the United Nations' Global Fund to Fight AIDS, Tuberculosis, and Malaria.


Technology acceptance of a mobile portfolio app for teacher education: Pre-service teachers views on multimedia-based note-taking and mentoring in internships.
Mobile technologies are promising tools to scaffold teaching practice. In this study, we developed and tested a mobile app for teacher education. This mobile portfolio enables multimedia-based note-taking, reflection, and discussion with peers and mentors. We conducted two studies to explore the effect of design variants and use scenarios on the app's acceptance. In the first study with N = 83 pre-service primary school teachers, technology acceptance was higher for those using the app with multimedia note-taking functionality than for those using the same app with this functionality disabled. In the second study with N = 81 pre-service teachers, those using the app together with their mentor teachers reported levels of technology acceptance similar to those who used the app exclusively among themselves. In consequence, a mobile portfolio app would be met with higher acceptance if it builds reflection upon multimedia note-taking both with and without the inclusion of mentors.


Trend of Overweight and Obesity, Based on Population Study among School Children in North West of Iran: Implications for When to Intervene.
Childhood overweight and obesity is a major public health problem in both developed and developing countries. Overweight and obesity in children may have severe consequences later in a dolescence and adulthood. The aim of current study was to determine the prevalence trend of overweight and obesity in school-aged children from 2009 to 2011. The present study was a population-based study and conducted in three consecutive years, from 2009 to 2011. The study population included all of primary, secondary and high school children in rural and urban regions of West Azerbaijan province in West-North of Iran. Body mass index (BMI), the ratio of weight to height squared [weight (kg)]/ [height (m)]2, was calculated to the nearest decimal place. Overweight and obesity were classified using CDC recommendations for age and sex: a BMI 85th- 95th percentile was classified as overweight and a BMI >95th percentile was classified as obese. All statistical analyses were performed using the Excel Software. Descriptive statistics were used to characterize the sample in different time periods. The prevalence was calculated as the ratio of number present cases to a given population number in a given subgroup at a given time. Overall, 165740, 145146 and 146203 school children were assessed at 2009, 2010 and 2011, respectively. Prevalence of overweight in primary school children among girls were 52.83, 86.93 and 116.36 and for boys were 57.07, 53.4 and 93.55 per 1000 person in 2009, 2010 and 2011 years, respectively. The prevalence of obesity in secondary school children for girls were 22.26, 27.75 and 28.43 and 26.52, 25.72 and 35.85 for boys per 1000 person in 2009, 2010 and 2011, respectively, The highest prevalence of overweight was 77.58, 142.4 and 126.46 per 1000 person among primary, secondary and high school children, respectively, in 2011. The lowest prevalence of obesity was 12.52, 24.1 and 21.61 per 1000 person among primary, secondary and high school children, respectively, in 2009. However, the rapid increase in both obesity and overweight should have a special attention. Research on prevalence trend of overweight and obesity in children is poorly reported in Iran. So that, future studies need to follow-up on the associations between overweight and obesity with health outcomes when children develop and reach adolescence and adulthood.


IrMo Nanocluster-Doped Porous Carbon Electrocatalysts Derived from Cucurbit[6]uril Boost Efficient Alkaline Hydrogen Evolution.
Electrocatalysts based on noble metals have been proven efficient for high-purity hydrogen production. However, the sluggish kinetics of the hydrogen evolution reaction (HER) in alkaline media caused by high water dissociation energy largely hampers this electrochemical process. To improve the electrocatalytic activity, we fabricate an effective porous carbon matrix derived from cucurbit[6]uril using a template-free method to support iridium-molybdenum (IrMo) nanoclusters. As proof of concept, the resulting IrMo-doped carbon electrocatalyst (IrMo-CBC) was found to boost the alkaline HER significantly. Owing to the unique in-plane hole structure and the nitrogen-rich backbone of cucurbit[6]uril as well as the ultrafine IrMo nanoclusters, IrMo-CBC exhibits pronounced alkaline HER activity with an extremely low overpotential of 12 mV at 10 mA cm-2, an ultrasmall Tafel slope (28.06 mV dec-1), a superior faradic efficiency (98%), and a TOF of 11.6 H2 s-1 at an overpotential of 50 mV, outperforming most iridium-based electrocatalysts and commercial Pt/C.


A gigantic, metastasizing keratoacanthoma. Report of a case and discussion on classification.
A case of a gigantic metastasizing keratoacanthoma in a woman who had impaired cellular immunity and autoimmune hemolytic anemia is described. The case suggests that disorders of humoral and cellular immunity may be responsible for development of recurrent and metastasizing keratoacanthomas.


Social exclusion in clients with comorbid mental health and substance misuse problems.
The concept of comorbid mental health problems and substance misuse has gained prominence in the last two decades, due in part to the closure of large psychiatric hospitals and to the increasing prevalence of drug use in the community. This client group has a dual requirement for both medical and social care needs and is at risk for social exclusion. A retrospective matched case-control study to examine aspects of social exclusion between service users who have comorbid diagnoses and those with a single diagnosis. Samples were drawn from the service users of a mental health Trust in the South-East of England, from both Adult Mental Health (n = 400) and Drug and Alcohol services (n = 190). Data were collected from Care Programme Approach assessment forms and medical records. McNemar's chi(2) and odds ratios via a conditional logit regression model are used to test for differences in the social exclusion indicators. There were significant differences in social exclusion between the comorbid and singly diagnosed clients of the Adult Mental Health service, but differences were less pronounced between the comorbid and singly diagnosed clients of the specialist Drug and Alcohol service. Recent Government policy advocates treating comorbid clients within mainstream mental health services. Health care workers need to recognise the likelihood of high levels of social exclusion among clients with comorbid problems.


Serum resistance and virulence of Escherichia coli isolated from turkeys.
Twenty-five strains of Escherichia coli isolated from turkeys were characterized for their serum resistance and virulence. An in vitro bactericidal assay was used to determine the serum resistance of E coli. Virulence was determined by survival time after IV inoculation of each strain into 3-week-old turkeys. Serum-resistant E coli strains were generally found to be virulent for turkeys, whereas serum-sensitive E coli strains were avirulent. Of the 25 strains, 18 strains were placed in the 2 categories of serum-resistant/virulent and serum-sensitive/avirulent. Five strains were serum-resistant and avirulent, and 2 strains were serum-sensitive and virulent. Serum resistance appears to be an important determinant of virulence for E coli in turkeys; however, the requirement for other virulence factors, in addition to serum resistance, was suggested by the finding that 5 serum-resistant strains were avirulent in turkeys.


High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells.
High mobility group box 1 (HMGB1) is a non-histone protein which is predominantly localised in the cell nucleus. However, stressed, dying, injured or dead cells can release this protein into the extracellular matrix passively. In addition, HMGB1 release was observed in cancer and immune cells where this process can be triggered by various endogenous as well as exogenous stimuli. Importantly, released HMGB1 acts as a so-called "danger signal" and could impact on the ability of cancer cells to escape host immune surveillance. However, the molecular mechanisms underlying the functional role of HMGB1 in determining the capability of human cancer cells to evade immune attack remain unclear. Here we report that the involvement of HMGB1 in anti-cancer immune evasion is determined by Toll-like receptor (TLR) 4, which recognises HMGB1 as a ligand. We found that HGMB1 induces TLR4-mediated production of transforming growth factor beta type 1 (TGF-β), displaying autocrine/paracrine activities. TGF-β induces production of the immunosuppressive protein galectin-9 in cancer cells. In TLR4-positive cancer cells, HMGB1 triggers the formation of an autocrine loop which induces galectin-9 expression. In malignant cells lacking TLR4, the same effect could be triggered by HMGB1 indirectly through TLR4-expressing myeloid cells present in the tumour microenvironment (e. g. tumour-associated macrophages).


Characterization of DLC-A and DLC-B, two families of cytoplasmic dynein light chain subunits.
Cytoplasmic dynein is a minus-end-directed, microtubule-dependent motor composed of two heavy chains (approximately 530 kDa), three intermediate chains (approximately 74 kDa), and a family of approximately 52-61 kDa light chains. Although the approximately 530 kDa subunit contains the motor and microtubule binding domains of the complex, the functions of the smaller subunits are not known. Using two-dimensional gel electrophoresis and proteolytic mapping, we show here that the light chains are composed of two major families, a higher M(r) family (58, 59, 61 kDa; dynein light chain group A [DLC-A]) and lower M(r) family (52, 53, 55, 56 kDa; dynein light chain group B [DLC-B]). Dissociation of the cytoplasmic dynein complex with potassium iodide reveals that all light chain polypeptides are tightly associated with the approximately 530 kDa heavy chain, whereas the approximately 74 kDa intermediate chain polypeptides are more readily extracted. Treatment with alkaline phosphatase alters the mobility of four of the light chain polypeptides, indicating that these subunits are phosphorylated. Sequencing of a cDNA clone encoding one member of the DLC-A family reveals a predicted globular structure that is not homologous to any known protein but does contain numerous potential phosphorylation sites and a consensus nucleotide-binding motif.


Mesangial proliferative lupus nephritis with podocytopathy: a special entity of lupus nephritis.
Mesangial proliferative lupus nephritis may coexist with podocytopathy, but its clinical-morphological features, treatment response and outcomes have not been compared with mesangial proliferative lupus nephritis without podocytopathy. In this study, 125 biopsies of lupus nephritis patients showing mesangial proliferation with mesangial immune deposits were collected and divided into podocytopathy group (defined as podocyte foot process effacement (FPE) >50% with nephrotic syndrome (NS)) and mesangial group (FPE ≤50%, or FPE >50% without NS). Mesangial proliferation and tubular- interstitial lesions were semi-quantitatively analyzed. We found that the incidence of renal involvement as the onset symptoms ( P < .001), nephrotic syndrome ( P < .001), acute kidney injury ( P < .001), the degree of acute tubular- interstitial lesions ( P < .001), and renal relapse (51.6% vs. 23.7%, P = .005) were significantly higher in the podocytopathy group than in the mesangial group. In contrast, the incidence of arthritis ( P < .001), fever ( P = .042), low serum C4 ( P = .008) and hematuria ( P = .033) was significantly lower in the podocytopathy group than in the mesangial group. No patients developed end stage renal disease or death during a median follow-up of 64 (interquartile range (IQR) 37-103) months in the podocytopathy group and 53 (IQR 30-83) months in the mesangial group. In conclusion, mesangial proliferative lupus nephritis with and without podocytopathy should be subdivided into two separate classes of lupus nephritis.


[Spinal cord disorders and their treatment in patients with tuberculous spondylitis over 50 years old].
A total of 157 patients aged 50-83 years who suffered from spinal tuberculosis were examined. The specific features of spinal disorders were established. A great role in the progression of paralyses was given to chronic spinal blood supply disorders. Two types of spinal lesion are clinically and roentgenologically described, these included adult and senile ones. One hundred and nineteen patients were operated on. Interventions enabled complete and partial recovery of spinal function in 88% of cases. The efficacy of the treatment depended on how early and adequately anterior spinal decompression was performed and how multimodal the postoperative therapy was, which included vasoactive, neurotrophostimulating therapy and early rehabilitation of patients.


The Clinicopathological Factors Associated with Disease Progression in Luminal A Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A Single Center in China.
This study investigated the clinicopathological factors associated with outcomes in patients with Luminal A breast cancer. Retrospective analysis of the association of clinicopathological factors and breast cancer outcome in 421 patients with newly-diagnosed Luminal-A breast cancer that were enrolled from January 2008 to December 2014. Clinicopathological data were analyzed to validate the relationship with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to analyze the value of clinicopathological factors (tumor size, node status and lymphovascular invasion), and subsequent Cox regression analysis revealed significant prognostic factors. With a median of 61 months follow-up, the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate regression analysis showed that clinical anatomic stage, tumor size, status of lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413 patients with stage I-III breast cancer, 14 presented with metastasis (3.4%) during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time after metastasis was 20.4 months. Of all the sites of distant metastasis, liver metastasis was the only factor that affected survival time after metastasis (χ2=6.263, p=0.012). Patients with Luminal A breast cancer have excellent outcomes. Liver metastasis is an important factor compressing the survival time after distant metastasis presents.


Aggressive angiomyxoma of the vulva with a sole t(5;8)(p15;q22) chromosome change.
Aggressive angiomyxoma of the vulva is uncommon and the pathogenesis remains unclear. Recently, a few cytogenetic studies demonstrated chromosomal abnormalities in aggressive angiomyxoma of the vulva. A 45-year-old Japanese woman complaining of right-side vulva tumor measuring 3 cm in diameter was referred to our hospital. The mass was located at the right side of the rectovaginal septum and was closely adherent to the rectal serosa and the levator muscle ani. The tumor was completely resected. A pathological examination demonstrated aggressive angiomyxoma of the vulva. Chromosomal analysis of the tumor demonstrated a sole t(5;8)(p15;q22) translocation. This is the first case of an aggressive angiomyxoma of the vulva with a sole t(5;8)(p15;q22) translocation.


[Incidence of left renal vein anomalies in routine abdominal CT scans].
To study the appearance and incidence of left renal vein anomalies in abdominal CT examinations. One thousand and three abdominal CT examinations were reviewed retrospectively for the presence of left renal vein anomalies. Nineteen CT scans were excluded from the study because of technical or patient-dependent factors. The course of the left renal vein was assessed on the CT slices to detect any anomalies. Left renal vein anomaly was detected in 32 (3.2%) of 984 cases. Twenty-three (2.3%) of them were a retroaortic and 9 (0.9%) of them were a circumaortic left renal vein. It is important to detect left renal vein anomalies before retroperitoneal surgery or interventional procedures. These anomalies can be identified in routine abdominal CT examinations with a careful inspection.


SESAM mode-locked red praseodymium laser.
We present the first semiconductor saturable absorber mirror (SESAM) mode-locked praseodymium solid-state laser. The laser is based on a Pr(3+):LiYF(4) crystal as gain medium and a GaInP-quantum well-based SESAM. Self-starting continuous-wave mode-locked laser operation with an average output power of 16 mW is achieved at a center wavelength of 639.5 nm. The laser operates at a repetition rate of ∼85.55 MHz and emits pulses with a duration of ∼18 ps.


Metabolic Controls on Epigenetic Reprogramming in Regulatory T Cells.
Forkhead box protein 3 (Foxp3+)-expressing regulatory T (Treg) cells are a unique CD4+T cell subset that suppresses excessive immune responses. The epigenetic plasticity and metabolic traits of Treg cells are crucial for the acquisition of their phenotypic and functional characteristics. Therefore, alterations to the epigenetics and metabolism affect Treg cell development and function. Recent evidence reveals that altering the metabolic pathways and generation of metabolites can regulate the epigenetics of Treg cells. Specifically, some intermediates of cell metabolism can directly act as substrates or cofactors of epigenetic-modifying enzymes. Here, we describe the metabolic and epigenetic features during Treg cell development, and discuss how metabolites can contribute to epigenetic alterations of Treg cells, which affects Treg cell activation, differentiation, and function.


Highly oxidizing excited states of Re and Tc complexes.
Like the Re analogue, the ligand-to-metal charge transfer (LMCT) excited-state of [Tc(dmpe)3]2+ (dmpe is bis-1,2-(dimethylphosphino)ethane) is luminescent in solution at room temperature. Surprisingly, both [M(dmpe)3]2+* species have extremely large excited-state potentials (ESPs) as oxidants-the highest for any simple coordination complex of a transition metal. Furthermore, this potential is available using a photon of visible light (calculated for M = Re(Tc); E1/2* = +2.61(2.52) V versus SCE; lambdamax = 526(585) nm). Using a Rehm-Weller analysis with a series of aromatic hydrocarbons as electron-transfer quenchers, E1/2(Re2+*/Re+) has been determined to be 2.58 V, in good agreement with the calculated value. Both [M(dmpe)3]2+* species are quenched by chloride ion and both can function as excited-state oxidants in water solution.


Silicon oxynitride stability.
Silicon oxynitride occurs as a mineral (sinoite) in meteorites. Equilibrium measurements are reported which provide information on the approximate ratios of pressures of oxygen to nitrogen required for existence of this phase under equilibrium conditions at elevated temperatures. This ratio is approximately 10-(15) at 1400 degrees to 1500 degrees C.


Structural and cathodoluminescence of Sb-doped SnO2 nanostructures.
High density Sb-doped SnO2 nanobelts and beak-like nanorods were synthesized on alumina substrates using thermal evaporation. X-ray diffraction (XRD) pattern shows that both the nanobelts and beak-like nanorods are single crystals with the tetragonal rutile structure. Transmission electron microscopy (TEM) images show that the nanobelts grow along the [110] direction, but the nanorods grow with an abrupt change from the [101] direction to the [301] direction. X-ray photoelectron spectroscopy (XPS) analysis shows that the Sb 3d 3/2 peak of not fully oxidized beak-like nanorods shifts from 540.5 eV to 535.4 eV, and the Sn 3d 3/2 peak also shifts from 496.3 eV to 492.8 eV. Room temperature cathodoluminescence (CL) measurements show that both the nanobelts and beak-like nanorods exhibit blue and orange emissions that are related to the interstitial defects and oxygen deficiencies. The comparative study of CL measurements between nanobelts and beak-like nanorods demonstrate that the optical properties can be modified by altering the oxygen deficiencies.


An "anti-Baldwin" 3-exo-dig cyclization: preparation of vinylidene cyclopropanes from electron-poor alkenes.
Stabilized carbanions undergo an uncommon 3-exodig cyclization onto propargyl halides through an SN2' substitution. Propargyl iodides as electrophiles are necessary to achieve good yields (36-95%) for most substrates, although the usefulness of chlorides and bromides is documented. A variety of monocyclic and bicyclic vinylidene cyclopropanes can be prepared. These products are not available by standard carbene methodology.


[Invasive group A streptococcal infections in the Netherlands].
Group A streptococcal (GAS) infections are caused by the Gram-positive bacterium Streptococcus pyogenes. Infection can occur via droplet infection from the throat and via (in)direct contact with infected people. GAS can cause a wide variety of diseases, ranging from superficial skin infections, pharyngitis and scarlet fever, to serious invasive diseases such as puerperal sepsis, pneumonia, necrotising soft tissue infections (NSTI) (also known as necrotising fasciitis/myositis), meningitis and streptococcal toxic shock syndrome (STSS). In invasive GAS infections, the bacteria has penetrated into a sterile body compartment (such as the bloodstream, deep tissues, or the central nervous system). Invasive GAS infections are rare but serious, with high morbidity and mortality. Since March 2022, the National Institute for Public Health and the Environment (RIVM) reported a national increase in notifiable invasive GAS infections (NSTI, STSS and puerperal fever). Particularly NSTI has increased compared to the years before the SARS-CoV-2 pandemic. Remarkably, the proportion of children aged 0 to 5 years with invasive GAS-infections is higher in 2022 than in the previous years (12% compared to 4%). While seasonal peaks occur, the current elevation exceeds this variation. To promote early recognition and diagnosis of invasive GAS infections different clinical cases are presented.


Gaze-contingent multiresolutional displays: an integrative review.
Gaze-contingent multiresolutional displays (GCMRDs) center high-resolution information on the user's gaze position, matching the user's area of interest (AOI). Image resolution and details outside the AOI are reduced, lowering the requirements for processing resources and transmission bandwidth in demanding display and imaging applications. This review provides a general framework within which GCMRD research can be integrated, evaluated, and guided. GCMRDs (or "moving windows") are analyzed in terms of (a) the nature of their images (i.e., "multiresolution," "variable resolution," "space variant," or "level of detail"), and (b) the movement of the AOI (i.e., "gaze contingent," "foveated," or "eye slaved"). We also synthesize the known human factors research on GCMRDs and point out important questions for future research and development. Actual or potential applications of this research include flight, medical, and driving simulators; virtual reality; remote piloting and teleoperation; infrared and indirect vision; image transmission and retrieval; telemedicine; video teleconferencing; and artificial vision systems.


Biological activities of dermatological interest by the water extract of the microalga Botryococcus braunii.
The use of microalgae in the skin care market is already established although the scientific rationale for their benefit was not clearly defined. In this work, the biological activities of dermatologic interest of the water extract from the microalga Botryococcus braunii (BBWE) were evaluated by a battery of in vitro assays. At concentrations ranging from 0.1 to 0.001 % (w/v) BBWE promoted adipocytes differentiation by inhibiting hormone-sensitive lipase, thus promoting triglyceride accumulation in the cells. BBWE also induced gene expression of proteins involved in the maintenance of skin cells water balance such as aquaporin-3 (AQP3), filaggrin (FLG) and involucrin (INV). 0.1 % BBWE increased the gene expression of AQP3 of 2.6-folds, that of FLG and INV of 1.5- and 1.9-folds, respectively. Moreover, it induced the biosynthesis of collagen I and collagen III by 80 and 40 %, respectively, compared to the untreated control. BBWE antioxidant activity, evaluated by oxygen radical absorbance capacity (ORAC) assay, was of 43.5 μmol Trolox per gram of extract: a quite high value among those found for other microalgae extracts. BBWE inhibited the inducible nitric oxide synthase (iNOS) gene expression and the consequent nitrite oxide (NO) production under oxidative stress. At a concentration of 0.02 % BBWE reduced by 50 % the expression of iNOS and by about 75 % the NO production. Taken together, the results demonstrated that B. braunii water extract exerted an array of biological activities concurring with the skin health maintenance; therefore, it is a potential bioactive ingredient to be included in cosmetic products.


Kinetic chain rehabilitation: a theoretical framework.
Sequenced physiologic muscle activations in the upper and lower extremity result in an integrated biomechanical task. This sequencing is known as the kinetic chain, and, in upper extremity dominant tasks, the energy development and output follows a proximal to distal sequencing. Impairment of one or more kinetic chain links can create dysfunctional biomechanical output leading to pain and/or injury. When deficits exist in the preceding links, they can negatively affect the shoulder. Rehabilitation of shoulder injuries should involve evaluation for and restoration of all kinetic chain deficits that may hinder kinetic chain function. Rehabilitation programs focused on eliminating kinetic chain deficits, and soreness should follow a proximal to distal rationale where lower extremity impairments are addressed in addition to the upper extremity impairments. A logical progression focusing on flexibility, strength, proprioception, and endurance with kinetic chain influence is recommended.


Propofol anesthesia compared to awake reduces infarct size in rats.
Propofol has not been studied directly in animals subject to cerebral ischemia in the conscious state. Strokes are usually induced in animals while they are anesthetized, making it difficult to eliminate anesthetic interactions as a complicating factor. Therefore, to compare the neuroprotective effects of propofol to the unanesthetized state, experiments were performed using a model that induces a stroke in the conscious rat. Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor endothelin. Four days before the strokes were induced, a guide cannula was implanted for the injection of endothelin. On the day of the experiment, endothelin (6.0 pmol in 3 microl) was injected into the striatum. Propofol (25 or 15 mg. kg-1. h-1) or intralipid (vehicle) were infused for 4 h starting immediately after the endothelin injection. In another series, the propofol infusion was begun 1 h after the endothelin injection and continued for 4 h. Three days later, the animals were killed, and the brains were sectioned and stained. The propofol group (25 mg. kg-1. h-1) had a significantly reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53 mm3). To exclude a direct interaction between propofol and endothelin, in thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction was examined using videomicroscopy, with or without propofol. Propofol had no effect on the magnitude or time course of the endothelin-induced vasoconstriction. The results show that concurrent or delayed administration of propofol is neuroprotective.


Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus.
Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies fail to replace the normal disc in facilitating spinal movements and absorbing load. The focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 238 differentially expressed genes in the degenerative annulus fibrosus. Seventeen of the dysregulated molecular markers showed log2-fold changes greater than ±1.5. Various dysregulated cellular functions, including cell proliferation and inflammatory response, were identified. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon pathway. This study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation, which may affect cellular function in human degenerative disc.