Multiple facial candidal abscesses after self-administered acupuncture in a patient with undiagnosed diabetes mellitus: a case report.
Facial abscess caused by Candida albicans infection is a rare condition even in immunocompromised patients, and only a few cases have been reported. To our knowledge, this is the first case of multiple facial candidal abscesses caused by self-administered acupuncture in an undiagnosed diabetes mellitus patient. A 57-year-old woman who had self-acupuncture treatment 2 weeks previously, presented with a 1-week history of progressive left eyelid swelling, erythema, and pain. Despite the antibiotic treatment, the lesion progressed. Surgical incision and drainage was performed and Candida albicans was isolated from the obtained pus culture. The patient was diagnosed with type 2 diabetes mellitus based on a random serum glucose level of 350 mg/dl and 9.2% HbA1c. The abscess resolved after seven incision and drainage cycles and 4 weeks of intravenous fluconazole treatment with an appropriate control of diabetes mellitus. Unusual organisms and underlying immunocompromised condition should be suspected in cases of recurrent abscess showing an inadequate response to antibiotic treatment.


Use of protrusive splint therapy in anterior disk displacement of the temporomandibular joint: a 1- to 3-year follow-up.
Sixty-eight patients, who were determined clinically (by the presence of audible and palpable-joint sounds) and arthrographically to have meniscus displacement with reduction, had protrusive splints constructed, and the results were evaluated for a minimum of 1 year to a maximum of 3 years. Eighteen additional patients, arthrographically determined to have meniscus displacement with reduction, served as a nontreatment group for comparison. Odds ratios were calculated to compare the proportions of subjects who experienced follow-up symptoms on the two regimens. Results indicated that with splint therapy there was a statistically significant reduction of the intensity of jaw joint pain, temporal headache, ear pain, and pain in front of the ear, and there was a decrease in the probability of a closed lock condition developing. Splint therapy is less likely to reduce frontal headache, neck pain, and clenching of teeth.


PD-L1 Regulates Inflammation in LPS-Induced Lung Epithelial Cells and Vascular Endothelial Cells by Interacting with the HIF-1α Signaling Pathway.
Sepsis-induced lung injury was the most common cause of death in patients. This study aimed to investigate whether PD-L1 regulates the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells by interacting with the HIF-1α signaling pathway. Sepsis-induced lung injury mice were constructed by cecal ligation and puncture (CLP) procedure, and lipopolysaccharide (LPS)-induced lung epithelial cells and vascular endothelial cells simulate the sepsis-induced lung injury model in vitro. Hematoxylin-eosin (HE) staining detected the morphological changes of the lung tissues, and immunohistochemistry (IHC) detected the PD-L1 expression in lung tissues. Bicinchoninic acid (BCA) assay determined the protein concentration in bronchial alveolar lavage fluid (BALF). The number of PD-1 (+) cells in blood was detected by flow cytometry. The apoptosis in lung tissues and LPS-induced cells was analyzed by TUNEL assay. The inflammatory factor levels and HIF-1α in lung tissues and LPS-induced cells were analyzed by ELISA. The transfection effects of KD-PDL1 or KD-HIF1A in lung epithelial cells and vascular endothelial cells were confirmed by qRT-PCR analysis. The protein expression related to the PD-L1- and HIF-1α-related pathway was determined by Western blot analysis. As a result, LMT-28, as an IL-6 inhibitor, alleviated lung injury and suppressed the apoptosis and inflammation in lung tissues in BALF and the number of PD-1 (+) cells in blood. Sepsis-induced lung injury activated the PD-L1- and HIF-1α-related pathway, while LMT-28 could not completely inhibit the pathway. In addition, downregulation of PD-L1 or downregulation of HIF-1α suppressed the apoptosis and alleviated the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells. Downregulation of PD-L1 had significant effects on lung epithelial cells but had greater effects on vascular endothelial cells. Downregulation of HIF-1α could decrease PD-L1 expression, and downregulation of PD-L1 could also suppress the protein expression of HIF-1α and related pathways. In conclusion, downregulation of PD-L1 alleviated the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells by suppressing the HIF-1α signaling pathway.


Relationship of microsatellite instability to mismatch repair deficiency in malignant tumors of dogs.
Microsatellite instability (MSI) is a type of genomic instability caused by mismatch repair deficiency (dMMR) in tumors. Studies on dMMR/MSI are limited, and the relationship between dMMR and MSI is unknown in tumors of dogs. We aimed to identify the frequency of dMMR/MSI by tumor type and evaluate the relationship between dMMR and MSI in tumors of dogs. In total, 101 dogs with 11 types of malignant tumors were included. We extracted DNA from fresh normal and tumor tissues. Twelve microsatellite loci from both normal and tumor DNA were amplified by PCR and detected by capillary electrophoresis. Each microsatellite (MS) was defined as MSI if a difference in product size between the tumor and normal DNA was detected. The dMMR was evaluated by immunohistochemistry with formalin-fixed paraffin-embedded tumor tissues. Next, we confirmed whether dMMR induces MSI by serial passaging of MMR gene knockout cell lines for 3 months. Microsatellite instability was detected frequently in oral malignant melanoma. The number of MSI-positive markers was higher in cases with dMMR than in those with proficient MMR (P < .0001). Statistical analysis indicated that the occurrence of MSI in FH2305 might have relevance to dMMR. Furthermore, MSI occurred in dMMR cell lines 3 months after passaging. Microsatellite instability and dMMR more frequently were found in oral malignant melanoma than in other tumors, and dMMR has relevance to MSI in both clinical cases and cell lines.


Interaction of single-strand binding protein and RecA protein at the single-stranded DNA site.
Escherichia coli single-strand binding protein (SSB), which participates in DNA replication, also plays a role in DNA repair and induction of SOS functions. We show that the formation of RecA-dATP-single-stranded DNA complexes is influenced by the presence of SSB. In equilibrium reactions with limiting bacteriophage fd DNA, the mutant SSB113 protein competes more effectively than SSB with RecA protein for sites on the DNA. This result can account for the inability of strain ssb113 to amplify RecA protein synthesis and induce lambda prophage. SSB fails to displace RecA protein completely, even at very high concentrations. Both proteins inhibit the dATPase activity of RecA protein in spite of a large proportion of RecA protein still complexed to single-stranded DNA. Analysis of the multiple RecA protein activities and how they respond to the presence of SSB suggests that they fall into two distinct classes. Those that are enhanced by SSB (proteolysis and strand assimilation) and those inhibited by SSB (NTPase, reannealing of complementary single-stranded DNA). We propose a two-state model of conformational change of RecA protein, affected by the number of available free bases in single-stranded DNA relative to the number of RecA monomers, that would explain the choice of mutually exclusive catalytic activities.


Effects of zinc chloride on gastric secretion and ulcer formation in pylorus-occluded rats.
The effects of 10-day pretreatment with i.p. injections of zinc chloride, 16 mg/kg, on gastric secretion and on gastric ulceration induced by stress or by acid accumulation were examined in pylorus-occluded rats. Zinc chloride pretreatment significantly reduced the volume of gastric secretion and the total acid output as well as the incidence of gastric ulcers induced either by stress or by acid accumulation. The findings support the idea zinc compounds may be useful in the treatment of gastric ulcers.


Putting the electro-bugs to work: A systematic review of 22 years of advances in bio-electrochemical systems and the parameters governing their performance.
Wastewater treatment using bioelectrochemical systems (BESs) can be considered as a technology finding application in versatile areas such as for renewable energy production and simultaneous reducing environmental problems, biosensors, and bioelectrosynthesis. This review paper reports and critically discusses the challenges, and advances in bio-electrochemical studies in the 21st century. To sum and critically analyze the strides of the last 20+ years on the topic, this study first provides a comprehensive analysis on the structure, performance, and application of BESs, which include Microbial Fuel Cells (MFCs), Microbial Electrolysis Cells (MECs) and Microbial Desalination Cells (MDCs). We focus on the effect of various parameters, such as electroactive microbial community structure, electrode material, configuration of bioreactors, anode unit volume, membrane type, initial COD, co-substrates and the nature of the input wastewater in treatment process and the amount of energy and fuel production, with the purpose of showcasing the modes of operation as a guide for future studies. The results of this review show that the BES have great potential in reducing environmental pollution, purifying saltwater, and producing energy and fuel. At a larger scale, it aspires to facilitate the path of achieving sustainable development and practical application of BES in real-world scenarios.


Structural modifications into diphenyl diselenide molecule do not cause toxicity in mice.
The aim of the present study was to evaluate toxicological parameters of following compounds: 1a (4,4'-dichloro-diphenyl diselenide [(ClPhSe)(2)]), 1b (3,3'-ditrifluoromethyl-diphenyl diselenide [(F(3)CPhSe)(2)]) and 1c (4,4'-dimethoxyl-diphenyl diselenide [(CH(3)OPhSe)(2)]). Calculated lethal dose (LD(50)) values for mice exposed, by oral route, to a single application of compounds 1a, 1b or 1c were estimated to be >381, 278 and >372mg/kg, respectively. Compounds 1a and 1b significantly reduced body weight gain as well as food and water intake in mice. δ-Aminolevulinate dehydratase (δ-ALA-D) and catalase activities were inhibited in mice which received the highest dose of compounds 1a or 1b. Exposure to compounds 1a, 1b and 1c did not modify lipid peroxidation, vitamin C levels, cerebral Na(+)/K(+)-ATPase activity and the biochemical parameters evaluated. The important point for medicinal chemistry is that the structural modifications are not introducing toxicity for the compounds in mice.


Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand.
The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins' active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations in heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes.


Plasma vitrification and heavy metals solidification of MSW and sewage sludge incineration fly ash.
Thermal plasma treatment has been considered as one of promising methods for fly ash disposal. In this study, firstly, the characteristics of municipal solid waste incineration (MSWI) fly ash and sewage sludge incineration (SSI) fly ash were analyzed, followed by the raw material formulations of low melting temperature determined by thermodynamic equilibrium calculation. Then verified experiments were carried out by thermal plasma system, focused on the formation condition of vitrified slags with various CaO-SiO2-Al2O3 ratios and the influence factors of heavy metals (Cd, Cr, Ni, Pb, Zn, Cu) transference. According to the results: During the co-treatment process of fly ashes, a lower temperature of vitrified slag formation as low as 1230 ℃ was observed. Vitrification is determined by the molten phase content during melting process, the correlation coefficient between the glass phase content of slag and the molten phase content was 0.81 (P < 0.01). CaO content of raw materials was a major element for the volatilization of Cd and Pb. High Al2O3 content can remain more Cr, Cu and Ni in slags, but it is not conducive to the solidification of Zn. The synthetic toxicity index of heavy metals would greatly reduce from 23153.15 to 663.29-820.63 after thermal plasma treatment.


Usefulness of the Killip classification for early risk stratification of patients with acute myocardial infarction in the 1990s compared with those treated in the 1980s. Israeli Thrombolytic Survey Group and the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.
The classification introduced in 1967 by Killip et al has proved to be a useful method for early risk stratification of patients with acute myocardial infarction (AMI). Over the past 3 decades the overall mortality due to AMI has decreased significantly. The present study evaluates the usefulness of the Killip classification as a method for early risk stratification of patients with AMI in the 1990s. One thousand eight hundred seventy-three consecutive AMI patients were hospitalized in 25 coronary care units operating in Israel, and were followed for 1 year. Higher Killip class was found to be associated with increased in-hospital and 1-year mortality, in thrombolysis- and nonthrombolysis-treated patients (30-day mortality for all patients was 5%, 21%, 35%, and 67% in Killip classes I to IV, respectively). The overall mortality among AMI patients in the 1990s was found to be lower for each Killip class compared with a comparable patient population with AMI, hospitalized in Israel in the 1980s. Thus, the Killip classification is a useful method for early risk stratification of AMI patients in the 1990s.


2-Chloro-N'-[4-(dimethyl-amino)-benzyl-idene]-N-[4-(3-methyl-3-phenyl-cyclo-but-yl)-1,3-thia-zol-2-yl]acetohydrazide.
The mol-ecular conformation of the title compound, C(25)H(27)ClN(4)OS, is stabilized by an intra-molecular benzyl-idine C-H⋯N(thia-zole) hydrogen bond. The thiazole ring makes dihedral angles of 12.0 (3) and 20.4 (2)°, respectively, with the phenyl and benzene rings, while the phenyl and benzene rings make a dihedral angle of 22.6 (2)°. The crystal packing involves weak inter-molecular thia-zole C-H⋯O(carbon-yl) and methyl C-H⋯π hydrogen-bonding associations.


Cuscuta reflexa Possess Potent Inhibitory Activity Against Human Malaria Parasite: An In Vitro and In Vivo Study.
Drug resistance to practically all antimalarial drugs in use necessitate the development of new chemotherapeutics against malaria. In this aspect, traditionally used plants with folklore reputation are the pillar for drug discovery. Cuscuta reflexa being traditionally used in the treatment of malaria in Odisha, India we aimed to experimentally validate its antimalarial potential. Different solvent extracts of C. reflexa or column fractions from a promising solvent extract were evaluated for in vitro anti-plasmodial activity against Plasmodium falciparum strain Pf3D7. Potent fractions were further evaluated for inhibition of parasite growth against different drug resistant strains. Safety of these fractions was determined by in vitro cyto-toxicity, and therapeutic effectiveness was evaluated by suppression of parasitemia and improvement in survival of experimental mice. Besides, their immunomodulatory effect was investigated in Pf-antigen stimulated RAW cells. GCMS fingerprints of active fractions was determined. Column separation of methanol extract which showed the highest in vitro antiplasmodial activity (IC50 = 14.48 μg/ml) resulted in eleven fractions, three of which (F2, F3, and F4) had anti-plasmodial IC50 ranging from ≤ 10 to 2.2 μg/ml against various P. falciparum strains with no demonstration of in vitro cytotoxicity. F4 displayed the highest in vivo parasite suppression, and had a mean survival time similar to artesunate (19.3 vs. 20.6 days). These fractions significantly modulated expression of inflammatory cytokines in Pf-antigen stimulated RAW cells. The findings of the study confirm the antimalarial potential of C. reflexa. Exploration of phyto-molecules in GCMS fingerprints of active fractions is warranted for possible identification of lead anti-malarial phyto-drugs.


Religious involvement, psychosocial resourcefulness, and health.
A stratified randomized sample of 525 middle age (35-64 years old) men was used to study the relationships between self-reported level of church attendance (CA), self-reported religious faith (SRRF), religious well-being (RWB), existential well-being (EWB), self-actualization (SA), health, lifestyle, and participation in physical activity (PA). Religious measures (RWB, CA, and SRRF) were found to be dependent on psychosocial variables in terms of their relationships with PA, lifestyle, and health. On the other hand, psychosocial resourcefulness (SA, EWB, social support, and stress management) showed independent relationships with lifestyle, PA, and health. These findings indicate that the positive associations of psychological and sociological constructs with health are not related to or dependent upon ego syntonic religious identity.


A pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK with a conventional slow release preparation.
The plasma concentration-time profile and hemodynamic effects of metoprolol after the administration of metoprolol CR/ZOK, a multiple-unit controlled release formulation and a conventional slow release formulation, metoprolol Durules (Astra, AB Hässle, Mölndal, Sweden) once daily, were investigated in 12 healthy men. Data were collected over one 24-hour dose interval at steady state after 5 days of treatment. The study was randomized, three-way, crossover double-blind comparison of metoprolol CR/ZOK 200 mg, metoprolol Durules 200 mg and placebo. The reduction in exercise heart rate compared with placebo treatment was used as a measure of beta 1-blockade. The metoprolol plasma concentration-time profile during treatment with metoprolol CR/ZOK was smooth and uniform, showing a more constant release profile than that obtained with metoprolol Durules. This was demonstrated by the significantly longer time period during which the plasma concentration exceeded 75% of the maximum concentration (T75), for metoprolol CR/ZOK compared with metoprolol Durules (P less than .01). The Fluctuation Index of plasma metoprolol concentration was significantly smaller for metoprolol CR/ZOK than for metoprolol Durules (P less than .001). The pharmacokinetic differences between the formulations also produced differences in the time profiles of exercise heart rate. The percentage fluctuation in exercise heart rate over the dose interval tended to be smaller for metoprolol CR/ZOK. At the start and the end of the dosing interval, the CR/ZOK formulation was significantly more effective (P less than .01). These results indicate that Metoprolol CR/ZOK has a more sustained time profile of beta 1-blockade at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of fetal growth in twins: Which method to use?
Fetal growth restriction contributes to the excess perinatal mortality and morbidity associated with twin pregnancies. Regular ultrasound monitoring for fetal growth restriction is an essential component of antenatal care of twin gestations. It is accepted that twins have divergent growth trajectories around 28-30 weeks' gestation and are born smaller compared to singletons. Despite this well-established difference in fetal growth, twin pregnancies have been traditionally managed using growth standards developed for singleton pregnancies. Numerous recent studies have demonstrated a strong case supporting the use of twin-specific growth standards, but clinical implementation has been lacking. In this paper, we will review the evidence on factors affecting fetal growth, the rationale for twin-specific reference charts, clinical evidence for their use, and future direction of research. Applying singleton growth standards to twin pregnancies inflates the abnormal growth rate, and recent clinical evidence from several studies suggests that they are too stringent for classification of twins. The association of adverse perinatal and maternal outcomes such as perinatal death, preterm birth, neonatal care unit admission, hypertensive disorders of pregnancy, and composite neonatal morbidity is stronger when classification is made using twin-specific standards compared to singletons.


Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients.
Epstein-Barr virus (EBV) T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells, including chronic active EBV infection of T/NK-cell type (CAEBV+T/NK), EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH), extranodal NK/T-cell lymphoma of nasal type (ENKTL), and aggressive NK-cell leukemia (ANKL). However, the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown. A total of 171 nonimmunosuppressed patients with EBV+T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed. The 94 gene variants, mostly located in UNC13D, LYST, ITK, and PRF1 genes were detected, and mutations covered 28/50 (56.00%) of CAEBV-T/NK, 31/51 (60.78%) of EBV+HLH, 13/28 (46.42%) of ENKTL, and 13/48 (27.09%) of ANKL. Most mutations represented monoallelic and missense. Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations (P=0.0284, P=0.0137). Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV+T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.


A gut dysbiotic microbiota-based hypothesis of human-to-human transmission of non-communicable diseases.
Non-communicable diseases (NCDs) have replaced communicable diseases as the leading cause of premature death worldwide over the past century. Increasing numbers of studies have reported a link between NCDs and dysbiotic gut microbiota. Some gut microbiota, such as Helicobacter pylori, have been implicated in person-to-person transmission. Based on these reports, we develop a hypothesis regarding dysbiotic microbiota-associated NCDs, and explore how the presence of communicable NCDs could be confirmedexperimentally. We have also reviewed reports on environmental factors, including a high-fat diet, alcohol, smoking, exercise, radiation and air pollution, which have been associated with dysbiotic microbiota, and determined whether any of these parameters were also associated with NCDs. This review discusses the potential mechanism by which dysbiotic microbiota induced by environmental factors are directly or indirectly involved in person-to-person transmission. The hypothetical interplay between the environment, gut microbiota and host can be tested through high-throughput sequencing, animal models, and cell studies, although each of these modalities presents specific challenges. Confirmation of a causative association of dysbiotic microbiota with NCDs would represent a paradigm shift in efforts to prevent and control these diseases, and should stimulate additional studies on the associations among environmental factors, gut microbiota, and NCDs.


Fluorescent and biotinylated analogues of docetaxel: synthesis and biological evaluation.
Six novel docetaxel analogues that possess a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-6-caproyl chain in position 7 or 3' (11 and 16a), a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-3-propanoyl group at 3' (16b) and a 5'-biotinyl amido-6-caproyl chain in position 7, 10 or 3', respectively, have been synthesized. These compounds exhibit activity against microtubule disassembly similar to that of docetaxel but show discrepant activities on living cells. Although addition of microtubules to 11, 16a and b enhance their fluorescence, no shift of the emission maxima was observed. The fluorescent docetaxel derivatives show a specific labeling of microtubules in living cells, demonstrating that the microtubule cytoskeleton constitutes their main subcellular localization.


COMT and BDNF interacted in bipolar II disorder not comorbid with anxiety disorder.
Bipolar disorder (BP), especially bipolar II disorder (BP-II), is highly comorbid with anxiety disorder (AD). Monoaminergic dysfunction has been implicated in the pathogenesis of BP, it may be important to investigate genes such as the catechol-O-methyltransferase (COMT), involved in monoamine metabolism and brain-derived neurotrophic factor (BDNF) genes, modulating the monoamine system. We therefore examined the association of the COMT Val158Met and BDNF Val66Met polymorphisms with BP-II with and without comorbidity of AD, and possible interactions between these genes. Seven hundred and seventy-one participants were recruited: 314 with bipolar-II without AD, 117 with bipolar-II with AD, and 340 healthy controls. The genotypes of the COMT and BDNF polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant effect of the COMT and the BDNF polymorphisms, and a significant interaction effect for the Val/Val genotypes of the BDNF Val66Met polymorphism and the COMsT Val158Met Val/Met and Met/Met genotypes (P=0.007, 0.048) discriminated between BP-II without AD patients and controls. Our findings provide initial evidence that the COMT and BDNF genes interact in bipolar-II without AD. Our findings suggest the involvement of dopaminergic pathway in the pathogenesis of bipolar-II.


Integration of three-phase microelectroextraction sample preparation into capillary electrophoresis.
A major strength of capillary electrophoresis (CE) is its ability to inject small sample volumes. However, there is a great mismatch between injection volume (typically <100 nL) and sample volumes (typically 20-1500 µL). Electromigration-based sample preparation methods are based on similar principles as CE. The combination of these methods with capillary electrophoresis could tackle obstacles in the analysis of dilute samples. This study demonstrates coupling of three-phase microelectroextraction (3PEE) to CE for sample preparation and preconcentration of large volume samples while requiring minimal adaptation of CE equipment. In this set-up, electroextraction takes place from an aqueous phase, through an organic filter phase, into an aqueous droplet that is hanging at the capillary inlet. The first visual proof-of-concept for this set-up showed successful extraction using the cationic dye crystal violet (CV). The potential of 3PEE for bioanalysis was demonstrated by successful extraction of the biogenic amines serotonin (5-HT), tyrosine (Tyr) and tryptophan (Trp). Under optimized conditions limits of detection (LOD) were 15 nM and 33 nM for 5-HT and Tyr respectively (with Trp as an internal standard). These LODs are comparable to other similar preconcentration methods that have been reported in conjunction with CE. Good linearity (R2 > 0.9967) was observed for both model analytes. RSDs for peak areas in technical replicates, interday and intraday variability were all satisfactory, i.e., below 14%. 5-HT, Tyr and Trp spiked to human urine were successfully extracted and separated. These results underline the great potential of 3PEE as an integrated enrichment technique from biological samples and subsequent sensitive metabolomics analysis.


Role of Crystal Symmetry in the Reversibility of Stacking-Sequence Changes in Layered Intercalation Electrodes.
The performance of many technologies, such as Li- and Na-ion batteries as well as some two-dimensional (2D) electronics, is dependent upon the reversibility of stacking-sequence-change phase transformations. However, the mechanisms by which such transformations lead to degradation are not well understood. This study explores lattice-invariant shear as a source of irreversibility in stacking-sequence changes, and through an analysis of crystal symmetry shows that common electrode materials (graphitic carbon, layered oxides, and layered sulfides) are generally susceptible to lattice-invariant shear. The resulting irreversible changes to microstructure upon cycling ("electrochemical creep") could contribute to the degradation of the electrode and capacity fade.


Seven-year safety and efficacy of the unrestricted use of drug-eluting stents in saphenous vein bypass grafts.
The aim was to investigate the 7-year clinical outcomes of patients treated with either drug-eluting stents (DES) or bare-metal stents (BMS) for saphenous vein graft disease (SVG). Atherosclerotic disease in SVG has several peculiarities which make it difficult to extrapolate outcomes of the use of DES as compared to BMS, from outcomes observed in native coronary arteries. To date no long-term safety and efficacy results for DES in SVG have been published. Between January, 2000 and December, 2005 a total of 250 consecutive patients with saphenous vein graft disease were sequentially treated with DES (either sirolimus- or paclitaxel-eluting stents) or with BMS. Yearly follow-up was performed. At 87 months (7.25 years), a total of 101 patients died (58 [46%] in the BMS group and 43 [42%] in the DES group, P-value= 0.4). There was no significant difference in the combined endpoint mortality or myocardial infarction. Cumulative target vessel revascularisation (TVR) was higher in the BMS group compared to the DES group (41% vs. 29%, respectively; adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI]: 0.39-1.0). The cumulative incidence of major adverse cardiac events was 73% vs. 68% in the BMS and DES groups, respectively (adjusted HR 0.93, 95% CI: 0.67-1.3). In the present study, the unrestricted use of DES for SVG lesions appeared safe and effective up to 7.25 years- and the use of DES resulted in a clinically relevant lower rate of TVR.


Involvement of the mannose phosphotransferase system of Lactobacillus plantarum WCFS1 in peroxide stress tolerance.
A Lactobacillus plantarum strain with a deletion in the gene rpoN, encoding the alternative sigma factor 54 (sigma(54)), displayed a 100-fold-higher sensitivity to peroxide than its parental strain. This feature could be due to sigma(54)-dependent regulation of genes involved in the peroxide stress response. However, transcriptome analyses of the wild type and the mutant strain during peroxide exposure did not support such a role for sigma(54). Subsequent experiments revealed that the impaired expression of the mannose phosphotransferase system (PTS) operon in the rpoN mutant caused the observed increased peroxide sensitivity.


Effect of repeated electroconvulsive shocks on isoprenaline-induced changes of the endogenous inhibitor of cAMP-dependent protein kinase in rat brain.
The effect of repeated electroconvulsive shocks (ECS) on the responsiveness to isoprenaline of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor) was tested in rat hippocampus and brainstem. Isoprenaline produced a dose-dependent decrease in the type I inhibitor activity in these brain structures. Neither the basal activity nor the isoprenaline-induced changes of type I inhibitor activity were affected by a single ECS. However, a series of 11 ECS markedly reduced the response of the type I inhibitor activity to isoprenaline. The action of isoprenaline was completely blocked by propranolol and markedly enhanced by aminophylline. The results indicate that the subsensitivity of beta-adrenoceptors is accompanied by reduced responsiveness of type I inhibitor activity to isoprenaline.


Motor dual task with eyes closed improves postural control in patients with functional motor disorders: A posturographic study.
Functional motor disorders (FMD) are highly disabling neurological conditions in which postural control deficits increase the risk of falls and disability in performing daily living activities. Scattered evidence suggests that such disturbances may depend on abnormal attentional focus and might improve with distraction. How do motor and cognitive dual tasks performed under two different sensory conditions shape postural control in patients with FMD. This posturographic study involved 30 patients with FMD (age, 45.20 ± 14.57 years) and 30 healthy controls (age, 41.20 ± 16.50 years). Postural parameters were measured with eyes open, and eyes closed in quiet stance (single task) and on a motor dual task (m-DT) and a calculation (cognitive) dual task (c-DT). The dual task effect (DTE, expressed in percentage) on motor and cognitive performance was calculated for sway area, length of Center of Pressure (CoP), and velocity of CoP displacement. There was a statistically significant three-way interaction between task, condition, and group for the DTE on sway area (p = 0.03). The mean sway area DTE on the motor task in the eyes-closed condition was increased by 70.4 % in the healthy controls, while it was decreased by 1% in the patient group (p = 0.003). No significant three-way interaction was observed for the DTE on length of CoP and velocity of CoP displacement. This study provides novel preliminary evidence for the benefit of a simple motor dual task in the eyes closed condition as a way to improve postural control in patients with FMD. These findings are relevant for the management of postural control disorders in patients with FMD.


How does the novel piezoelectric 11 Gracey Curette compare to Gracey Curette or piezoelectric scaler?
Design In vitro study.Case selection A piezoelectric 11 Gracey Curette tip that combines a piezoelectric device and manual curette was tested for root surface roughness and bacterial adhesion after instrumentation. This novel device was compared against Gracey Curette, piezoelectric scaler and untreated control.Data analysis Extracted human teeth roots (n = 36) were randomly assigned to each of the four groups, of which three groups underwent instrumentation as assigned and one served as untreated control. Profilometer was used to measure the surface roughness after instrumentation. In addition, S. mutans was inoculated to evaluate adhesion on the instrumented root surface.Results The piezoelectric 11 Gracey Curette tip demonstrated significantly lower surface roughness compared to Gracey Curette, piezoelectric scaler and untreated control groups. With regards to bacterial adhesion, there was no significant differences in CFU values between novel device tips, Gracey Curette and piezoelectric scaler.Conclusions Instrumentation with a piezoelectric 11 Gracey Curette tip resulted in a significantly smoother surface compared to instrumentation with Gracey Curette or piezoelectric scaler. As far as bacterial adherence, piezoelectric 11 Gracey Curette tip was not significantly different compared to the traditional methods. Given the limitations of in vitro research, further clinical studies need to be conducted to evaluate clinical outcomes and patient-centred outcomes.


Reference values for free 25-hydroxy-vitamin D based on established total 25-hydroxy-vitamin D reference values.
Measurements of total 25-hydroxyvitamin D (t25(OH)D) are currently primarily used to assess the vitamin D status. The lipophilic cell membrane can only be passed by the un-bound form of 25-hydroxyvitamin D: free 25-hydroxyvitamin D (f25(OH)D). It is thought that f25(OH)D does reflect its biological actions better than t25(OH)D. However, as of today, there are no established guidelines for the clinical use of f25(OH)D. We analysed 5060 patients with simultaneous measurements of free and total 25(OH). Linear regression was used to study the relationship between free 25(OH)D and total 25(OH)D. We reviewed and used the established t25(OH)D reference values and determined the slope of the relationship between them to calculate reference values for f25(OH)D. F25(OH)D and t25(OH)D showed a strong positive linear (r = 0.8395, p < 0.0001) correlation. The slope of the relationship was 0.2833 ± 0.00257. The recommended threshold level of f25(OH)D is 8.499 pg/mL, corresponding to a target concentration for t25(OH)D of at least 30 ng/mL considered as sufficient in most of the international vitamin D guidelines. The upper limit for vitamin D is less clear in the guidelines. Most experts favour an upper limit for t25(OH)D of 100 ng/mL. This is equivalent to 28.330 pg/mL f25OHD. We established based on international guidelines for t25(OH)D reference values for f25(OH)D that are urgently needed for clinical use of f25(OH)D. However, clinical studies with f25(OH)D to confirm our suggestions are needed but will take time.


Laboratory accreditation and inspection.
Clinical laboratories perform diagnostic testing in a highly regulated environment in which federal, state, and private accreditation agencies monitor the quality of testing processes. These agencies vary in the focus and stringency of their requirements, and differences exist among states. Continued accreditation requires regular inspection to assure quality of test results for physicians, insurers, and, ultimately, the patients being tested. Preparation for inspection requires understanding of the unique accreditation requirements for each institution, establishment of quality assurance and quality improvement oversight, and communication of each staff member's role in delivering quality test results for patient care.


Space tourism flow generated from social media data.
The data is for empirical studies derived from a related research article about space tourism [1], which is a conceptual article with a different aim of economic measurement scale. Most space tourism research is conceptual because data from the nascent industry is limited [2]. Thus this data is constrictive for conducting empirical studies to contribute to quantitative analysis in space tourism [3]. Data from this study were collected by recruiting 361 respondents through snowball and convenient sampling targeted to samples interested in space tourism; 339 responses were adopted after the valid screening of missing data or data bias [4]. Targeted groups of potential space tourism customers were investigated to collect data through a designed questionnaire on the platform, Wenjuanxing, with a majority population database providing functions equivalent to Amazon Mechanical Turk [2]. The reliability and validity of all constructs showed that the questionnaire was proper for measurement [3]. Data analysis applied the structural equation model with Mplus to examine the CFA model and research hypothesis. Structural equation modeling was used to conduct the hypotheses test and model fitness through the statistical tool Mplus. Results imply that the data is suitable for conducting replication studies. To enlighten space tourism emergence studies, this data shows its importance for further research models [5].


Characterization of a processed pseudogene of human psiHSP40 on chromosome 2q32.
A pseudogene for the human Hsp40 gene has been characterized (psiHSP40). The pseudogene sequence shows 90% similarity to the human Hsp40 mRNA at the nucleotide level. No introns were found in the region corresponding to the human Hsp40 cDNA, and two direct repeats flank this same region. Because of these features, the pseudogene can be classified as a processed pseudogene. PsiHSP40 was assigned to chromosome 2q32 by in situ hybridization. This is the first report of a pseudogene for a member of the DnaJ (Hsp40) family protein gene.


Overcoming Systems Factors in Case Logging with Artificial Intelligence Tools.
Case logs are foundational data in surgical education, yet cases are consistently under-reported. Logging behavior is driven by multiple human and systems factors, including time constraints, ease of case data retrieval, access to data-entry tools, and procedural code decision tools. We examined case logging trends at three mid-sized, general surgery training programs from September 2016-October 2020, January 2019-October 2020 and May 2019-October 2020, respectively. Across the programs we compared the number of cases logged per week when residents logged directly to ACGME versus via a resident education platform with machine learning-based case logging assistance tools. We examined case logging patterns across 4 consecutive phases: baseline default ACGME logging prior to platform access (P0 "Manual"), full platform logging assistance (P1 "Assisted"), partial platform assistance requiring manual data entry without data integrations (P2 "Notebook"), and resumed fully integrated platform with logging assistance (P3 "Resumed"). 31,385 cases were logged utilizing the platform since 2016 by 171 residents across the 3 programs.Intelligent case logging assistance significantly increased case logging rates, from 1.44 ± 1.48 cases by manual entry in P0 to 4.77 ± 2.45 cases per resident per week via the platform in P1 (p-value < 0.00001). Despite the burden of manual data entry when the platform's data connectivity was paused, the tool helped to increase overall case logging into ACGME to 2.85 ± 2.37 cases per week (p-value = 0.0002). Upon resuming the data connectivity, case logging levels rose to 4.54 ± 3.33 cases per week via the platform, equivalent to P1 levels (insignificant difference, p-value = 0.57). Mapping the influence of systems and human factors in high-quality case logs allows us to target interventions to continually improve the training of surgical residents. System level factors such as access to alternate automation-drive tools and operative schedule integrated platforms to assist in ACGME case log has a significant impact on the number of cases captured in logs.


The prognostic value of controlling nutritional status (CONUT) score-based nomogram on extranodal natural killer/T cell lymphoma patients.
Controlling nutritional status (CONUT) score as an original nutritional assessment tool can be used to assess the prognosis of patients with a variety of malignancies. However, the predictive power of CONUT in extranodal natural killer/T cell lymphoma (ENKTL) patients has never been demonstrated. Our retrospective multicenter study aimed to explore the prognostic value of CONUT in newly diagnosed ENKTL. A total of 1085 newly diagnosed ENKTL patients between 2003 and 2021 were retrospectively retrieved. Cox proportional hazard model was used to explore the prognostic factors of overall survival (OS). The survival rate of ENKTL was evaluated using Kaplan-Meier analysis, and log-rank test was applied to the difference between groups. We investigated the prognostic performance of CONUT, the International Prognostic Index (IPI), the Korean Prognostic Index (KPI), and the Prognostic Index of Natural Killer Cell Lymphoma (PINK) using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). The median age at diagnosis for the whole cohort was 47 years, and the male to female ratio was 2.2:1. The 5-year OS for all patients was 72.2%. Multivariable analysis showed that CONUT, age, bone marrow involvement, ECOG PS score, and Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL stage were identified as independent predictive factors for OS. Based on multivariable results, a prognostic nomogram was developed. Subgroup analysis demonstrated that patients with severe malnutrition had poorest clinical outcome. In addition, ROC curves and DCA analysis proved that compared with IPI, KPI, and PINK models, the CONUT score-based nomogram showed a better prognostic predictive efficiency of ENKTL. CONUT could effectively stratify the prognosis of ENKTL and the proposed nomogram based on CONUT was an effective prognostic model for prediction.


Serological evidence of viral or Mycoplasma pneumoniae infection in acute maxillary sinusitis.
Evidence for the involvement of viruses, Mycoplasma pneumoniae, and Chlamydia spp. was studied by the complement fixation test in paired sera from 310 young adults (297 men and 13 women) with acute maxillary sinusitis. The diagnosis of acute sinusitis was confirmed by radiography and sinus puncture. Elevated antibody titres were found in 102 patients (33%). A four fold or greater titre rise was detected in 21.5%, and a high stable titre suggestive of recent viral infection was present in a further 11.5%. Adenovirus, influenza A and B viruses, and Mycoplasma pneumoniae accounted for most of the elevated antibody titres. Elevated titres were found in 79 (32%) of the 245 patients with purulent maxillary sinusitis (pathogenic bacteria isolated in sinus secretion) and in 23 (35%) of the 65 patients with non-purulent sinusitis (no pathogenic bacteria isolated). About 90% of the fourfold or greater titre rises in bacteriologically negative cases were due to adeno- or influenza viruses. A fourfold rise in antibody titre was also found in 7 of 101 control patients (7%). The results of this study suggest that respiratory viruses and Mycoplasma pneumoniae may be potential etiological agents in acute maxillary sinusitis, either alone or in combination with the common bacterial pathogens of sinusitis.


Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional MRI and machine learning.
Commonly used for Parkinson's disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.


Pathogenicity and vaccine efficacy of two virulent infectious laryngotracheitis virus strains in Egypt.
Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease outbreak. In an earlier study, we comprehensively characterized the circulating strains in Egypt and identified both CEO-like and recombinant strains are dominant. Herein, we investigated the pathogenicity of two virulent strains representing the CEO-like (Sharkia_2018) and recombinant strain (Qalubia_2018). Additionally, we evaluated the efficacy of different commercial vaccines (HVT-LT, CEO, and TCO) against the two isolates in terms of the histopathological lesion scores and the viral (gC) gene load. A total of 270 White Leghorn-specific pathogen-free male chicks were divided into nine groups of 30 birds, each housed in separate isolators. Birds were distributed as follows; one group was non-vaccinated, non-challenged, and served as a negative control. Two groups were non-vaccinated and infected with the two isolates of interest and served as a positive control to test the pathogenicity. Six groups were vaccinated and challenged; two groups were vaccinated with vector vaccine at one day old. The other four groups were vaccinated with either the CEO- or TCO- vaccine (two groups each) at four weeks of age. Three weeks after vaccination, birds were infected with the virulent ILTV isolates. The larynx, trachea, and harderian gland samples were taken at 1, 3, and 7 days post-infection for histopathological lesion score and molecular detection. Notably, The recombinant strain was more virulent and pathogenic than CEO-like ILTV strains. Moreover, the TCO vaccine was less immunogenic than the vector and CEO vaccines.


Integrated view of molecular diagnosis and prognosis of dengue viral infection: future prospect of exosomes biomarkers.
Dengue viruses (DENVs) are the viruses responsible for dengue infection which affects lungs, liver, heart and also other organs of individuals. DENVs consist of the group of four serotypically diverse dengue viruses transmitted in tropical and sub-tropical countries of world. Aedes mosquito is the principal vector which spread the infection from infected person to healthy humans. DENVs can cause different syndromes depending on serotype of virus which range from undifferentiated mild fever to dengue hemorrhagic fever resulting in vascular leakage due to release of cytokine and Dengue shock syndrome with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. Increase in dengue cases in pediatric population is a major concern. Transmission of dengue depends on various factors like temperature, rainfall, and distribution of Aedes aegypti mosquitoes. The present review describes a comprehensive overview of dengue, pathophysiology, diagnosis, treatment with an emphasis on potential of exosomes as biomarkers for early prediction of dengue in pediatrics.


Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers.
Previous morphological and electrophysiological studies have supported the hypothesis that interstitial cells of Cajal have important regulatory (pacemaker) functions in the gut. In the current study, interstitial cells of Cajal associated with Auerbach's plexus in human small intestine were studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm) filaments. Myosin filaments were not seen. Fibroblast-like cells were distinguished by their lack of caveolae and dense bodies, the relative scarcity of smooth cisternae and intermediate filaments, and the abundant granular endoplasmic reticulum. Interstitial cells of Cajal were arranged in networks of bundles containing processes of two to seven cells with fibroblastlike cells interspersed in the bundles. The bundles were innervated by nerve elements of Auerbach's plexus and extended into both layers of smooth muscle, between muscle cells, and into septa. The bundles were closely associated with elastin fibers. The organization shown in this study strongly supports the concept of interstitial cells of Cajal as important regulatory cells also in the human small intestine. The characteristic cytology and organization of interstitial cells of Cajal may provide a basis for future morphological, electrophysiological, and pathological studies of these cells in human small intestine.


Tempol inhibits neutrophil and hydrogen peroxide-mediated DNA damage.
Inflammatory conditions characterized by neutrophil activation are associated with a variety of chronic diseases. Reactive oxygen species are produced by activated neutrophils and produce DNA damage which may lead to tissue damage. Previous studies have shown that activated murine neutrophils induce DNA strand breaks in a target plasmacytoma cell, RIMPC 2394. We studied the effect of a water soluble nitroxide anti-oxidant, Tempol, on murine neutrophil induction of DNA strand breaks in this system. Murine neutrophils were isolated from the peritoneal cavity of BALB/cAn mice after an i.p. injection of pristane oil. Neutrophils were activated by the phorbol ester PMA and co-incubated with RIMPC 2394 cells. Control alkaline elution studies revealed progressive DNA strand breaks in RIMPC cells with time. The addition of Tempol to the incubation mixture prevented DNA damage in a dose dependent fashion. Five mM Tempol provided complete protection. Tempol protection against DNA strand breaks was similar for both stimulated neutrophils and exogenously added hydrogen peroxide. Measurement of hydrogen peroxide produced by stimulated neutrophils demonstrated that Tempol did not decrease hydrogen peroxide concentration. Oxidation of reduced metals, thereby interfering with the production of hydroxyl radical, is the most likely mechanism of nitroxide protection, although superoxide dismutase (SOD) like activity and scavenging of carbon-based free radicals may also account for a portion of the observed protection. The anti-oxidant activity of Tempol inhibited DNA damage by activated neutrophils. The nitroxides as a class of compounds may have a role in the investigation and modification of inflammatory conditions.


Quantitative shotgun proteomics with data-independent acquisition and traveling wave ion mobility spectrometry: a versatile tool in the life sciences.
Data-independent acquisition (DIA) implemented in a method called MS(E) can be performed in a massively parallel, time-based schedule rather than by sampling masses sequentially in shotgun proteomics. In MS(E) alternating low and high energy spectra are collected across the full mass range. This approach has been very successful and stimulated the development of variants modeled after the MS(E) protocol, but over narrower mass ranges. The massively parallel MS(E) and other DIA methodologies have enabled effective label-free quantitation methods that have been applied to a wide variety of samples including affinity pulldowns and studies of cells, tissues, and clinical samples. Another complementary technology matches accurate mass and retention times of precursor ions across multiple chromatographic runs. This further enhances the impact of MS(E) in counteracting the stochastic nature of mass spectrometry as applied in proteomics. Otherwise significant amounts of data in typical large-scale protein profiling experiments are missing. A variety of software packages perform this function similar in concept to matching of accurate mass tags. Another enhancement of this method involves a variation of MS(E) coupled with traveling wave ion mobility spectrometry to provide separations of peptides based on cross-sectional area and shape in addition to mass/charge (m/z) ratio. Such a two-dimensional separation in the gas phase considerably increases protein coverage as well as typically a doubling of the number of proteins detected. These developments along with advances in ultrahigh pressure liquid chromatography have resulted in the evolution of a robust and versatile platform for label-free protein profiling.


Phosphorus fractions in the sediment of a tropical reservoir, India: Implications for pollution source identification and eutrophication.
Eutrophication level in lakes and reservoirs depends on both internal and external phosphorus (P) load. Characterization of sediment P fractionation and identifying the P pollution sources are important for assessing the bio-availability of P and the dominant P source, for effectively controlling the water pollution. For determining the availability and sources of sediment P and eutrophication status, spatio-temporal variation in different P fractionation of sediment of hyper-eutrophic Krishnagiri reservoir, Tamil Nadu, India, was investigated. Sediment average total P (TP) content ranged from 4.62 to 5.64 g/kg. Main phosphorus form was the inorganic P (IP), and it makes up to 73.4-87.7% of TP. Among the different P fraction, viz. calcium bound (Ca-P), iron bound (Fe-P), aluminium bound (Al-P), exchangeable (Ex-P) and Organic-P (Org-P), Ca-P was the dominating fraction in both IP and TP. Trend of IP fraction was as follows: Ca-P > Fe-P > Al-P > Ex-P in pre-monsoon season, Fe-P > Ca-P > Al-P > Ex-P in monsoon and Ca-P > Al-P > Fe-P > Ex-P in post-monsoon. Overall the trend was as follows Ca-P > Fe-P > Al-P > Org-P > Ex-P. Bio-available-P (BAP) fractions ranged from 35.2 to 64.0% of TP, indicating its comparative higher value. Pearson's correlation matrix revealed that there was strong correlation among the different P fractions. Factor analysis indicates that different fractions of P were the dominating factor than the other sediment parameters. The observed variation in sediment P fractionation indicate the differences in source and characterization of P which is very helpful for implementation of effective management practices in controlling pollution that arises due to phosphorus in this hyper-eutrophic reservoir.


Investigating the Efficacy of Modified Lipoaspirate Grafting to Improve the Appearance of Atrophic Acne Scars: A Pilot Study.
Processed lipoaspirate grafting describes several techniques theorized to leverage the inflammatory and regenerative capacities of mechanically processed adipocytes to rejuvenate and correct skin pathology. Although lipoaspirate grafting is typically leveraged to fill visible defects such as depressed scars and dermal lines, additional fat processing allows grafts to stimulate mechanisms of wound healing, including the promotion of fibroblast activation, neovascularization, and neocollagenesis. This study intends to assess the efficacy and tolerability of processed lipoaspirate grafting monotherapy to improve the clinical appearance of atrophic acne scars. Patients underwent a single autologous processed lipoaspirate grafting procedure at the site of atrophic acne scars. Objective and subjective scar analysis was performed at 3 and 6 months posttreatment. Scars were assessed with standard photography, topographic analysis, and noninvasive skin measurements. In addition, microbiopsies were obtained before and after treatment to assess histological or genetic changes. Clinical improvement was assessed with patient and clinician Global Aesthetic Improvement Scales (GAIS) and blinded photographic evaluation. Ten patients between ages 18 and 60 completed the study. Clinical evaluation demonstrated that fat grafting improved the appearance of atrophic acne scars. Clinician GAIS and patient GAIS scores showed clinical improvement at both 3- and 6-month follow-up compared with baseline (P < .05). Blinded clinician GAIS scores also showed statistically significant improvement when clinicians compared clinical photographs taken at 6-month follow-up to baseline (P < .0001). The attenuation coefficient increased at 6-month follow-up, suggesting collagen remodeling and reorganization over the study period. Patients experienced anticipated posttreatment symptoms including transient erythema and edema; however, no unexpected adverse events were reported. Micronized lipoaspirate injection is a viable and effective option to improve the appearance of facial acne scarring. Favorable improvements in atrophic acne scarring were captured by objective analysis of skin ultrastructure as well as improvement in subjective assessments of scarring.


Adductor pollicis muscle and nutritional status in heart failure patients: Is there an association?
Adductor pollicis muscle thickness (APMT) has been used as a simple index for muscle mass for the assessment of nutritional status among hospitalized patients to identify malnutrition. The aim of this study was to evaluate the association between APMT and nutritional status in clinical patients diagnosed with congestive heart failure (CHF). APMT was measured in 500 patients with CHF on the dominant side. Nutritional status was assessed means of by the Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA), which establishes four categories of CHF severity. Poisson regression was used to verify the association of APMT, malnutrition, and severity of CHF. P ≤ 0.05 was considered statistically significant. The malnutrition prevalence varied from 1.5% in patients with functional class I CHF to 96.2% in patients classified as functional class IV (P ≤ 0.001). In both sexes, APMT values were significantly lower in patients who were malnourished (P< 0.001). The proportion of patients with CHF and malnutrition was higher among women than men (47.2 versus 37.4%, P = 0.027). Malnutrition was slightly more common among patients ≥60 y of age compared with other age groups (48.3%, P ≤ 0.001). APMT is a significant protective factor for malnutrition even after controlling for sex, age, body mass index, and CHF functional class. Malnutrition is highly prevalent among patients with CHF and is associated with functional class. APMT may be used as a simple index for muscle mass for the assessment of nutritional status in these patient populations, and is also associated with malnutrition in these patients, even after controlling for other risk factors.


Electrophoretic characteristics of monoclonal immunoglobulin G of different subclasses.
Monoclonal IgG are commonly observed in various B cell disorders, of which multiple myeloma is the most clinically relevant. In a series of serum samples, we identified by immunofixation 73 monoclonal IgG, including 63 IgG(1), 4 IgG(2), 5 IgG(3), and 1 IgG(4). The light chains were of kappa type in 45 cases, and of lambda type in 28 cases. These monoclonal IgG were further characterized by high resolution two-dimensional polyacrylamide gel electrophoresis (2-DE) in various isoelectric focusing conditions, as well as by 3-DE (2-DE of the proteins extracted from agarose after serum protein agarose electrophoresis). After 2-DE, 38 out of 73 monoclonal gamma chains (52%) were visualized using immobilized pH 3-10 gradients for isoelectric focusing. In 6 cases (8%), gamma chains were only detected using alkaline immobilized pH 6-11 gradients. In 3 cases (4%), 3-DE revealed monoclonal gamma chains hidden by polyclonal gamma chains. Finally, in 26 cases (36%), no monoclonal gamma chains were clearly visualized. Sixty-one monoclonal light chains (84%) were detected using immobilized pH 3-10 gradients, whereas 12 (16%) were not. Monoclonal gamma chains and light chains were highly heterogeneous in terms of pI and M(r). However, a statistically significant correlation (P<0.05) was observed between the position of the monoclonal IgG in agarose gel and the pI of their heavy and light chains (R=0.733, multiple linear regression). Because of the extreme diversity of their heavy and light chains, it appears that a classification of monoclonal IgG based only on their electrophoretic properties is not possible.


Some properties of the chloramphenicol resistance transposon Tn9.
We have isolated variants of the plasmid RTF which have received the transposon Tn9 from bacteriophage P1Cm. We have shown by the formation of heteroduplex molecules between one RTF:Tn9 derivative and R100.1 that Tn9 is homologous to the r-determinant region of R100.1 which carries the determinants for chloramphenicol resistance. This suggests that Tn9 was derived from an r-det like structure by deletion, possibly mediated by one of the flanking IS1 elements. In spite of the similarity in structure between Tn9 and r-det however, we have demonstrated two distinct differences in the behavior of these two elements: 1) Tn9 but not r-det, is able to amplify, by a recA dependent mechanism, when cells harboring RTF::Tn9 are grown in the presence of chloramphenicol, and 2) Tn9, unlike r-det, does not form extrachromosomal circular molecules when RTF::Tn9 is tegrated into the bacterial chromosome.


Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction in Aged Mice.
Neuroinflammation and oxidative stress coexist and interact in the progression of postoperative cognitive dysfunction (POCD) and other neurodegenerative disease. Mounting studies reveal that Dexmedetomidine (Dex) possesses anti-inflammatory and antioxidant properties. Nevertheless, whether Dex exerts neuroprotective effect on the cognitive sequelae of oxidative stress and inflammatory process remains unclear. A mouse model of abdominal exploratory laparotomy-induced cognitive dysfunction was employed to explore the underlying mechanism of neuroprotective effects exerted by Dex in POCD. Aged mice were treated with Dex (20 µg/kg) 20 min prior to surgery. Open field test (OFT) and Morris water maze (MWM) were employed to examine the cognitive function on postoperative day 3 (POD 3) or POD 7. In the present study, mice underwent surgery exhibited cognitive impairment without altering spontaneous locomotor activity, while the surgery-induced cognitive impairment could be alleviated by Dex pretreatment. Dex inhibited surgery-induced pro-inflammatory cytokines accumulation and microglial activation in the hippocampi of mice. Furthermore, Dex decreased MDA levels, enhanced SOD activity, modulated CDK5 activity and increased BDNF expression in the hippocampus. In addition, Dex remarkably reduced the surgery-induced increased ratio of Bax/Bcl-2 and apoptotic neurons in the hippocampi of aged mice. Collectively, our study provides evidence that Dex may exert neuroprotective effects against surgery-induced cognitive impairment through mechanisms involving its anti-inflammatory and antioxidant properties, as well as the suppression on the mitochondrial permeability transition pore and apoptosis-related pathway.


Evaluation of chemicals requiring metabolic activation in the EpiDerm™ 3D human reconstructed skin micronucleus (RSMN) assay.
The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDerm™ is a promising new assay for evaluating genotoxicity of dermally applied chemicals. A global pre-validation project sponsored by the European Cosmetics Association (Cosmetics Europe - formerly known as COLIPA), and the European Center for Validation of Alternative Methods (ECVAM), is underway. Results to date demonstrate international inter-laboratory and inter-experimental reproducibility of the assay for chemicals that do not require metabolism [Aardema et al., Mutat. Res. 701 (2010) 123-131]. We have expanded these studies to investigate chemicals that do require metabolic activation: 4-nitroquinoline-N-oxide (4NQO), cyclophosphamide (CP), dimethylbenzanthracene (DMBA), dimethylnitrosamine (DMN), dibenzanthracene (DBA) and benzo(a)pyrene (BaP). In this study, the standard protocol of two applications over 48h was compared with an extended protocol involving three applications over 72h. Extending the treatment period to 72h changed the result significantly only for 4NQO, which was negative in the standard 48h dosing regimen, but positive with the 72h treatment. DMBA and CP were positive in the standard 48h assay (CP induced a more reproducible response with the 72h treatment) and BaP gave mixed results; DBA and DMN were negative in both the 48h and the 72h dosing regimens. While further work with chemicals that require metabolism is needed, it appears that the RMSN assay detects some chemicals that require metabolic activation (4 out of 6 chemicals were positive in one or both protocols). At this point in time, for general testing, the use of a longer treatment period in situations where the standard 48h treatment is negative or questionable is recommended.


Functional Genomics of Epileptogenesis in Animal Models and Humans.
It has been estimated that epilepsies are among the top five neurological diseases with the highest burden of disease. In recent years, genome-wide expression studies (GWES) have been carried out in experimental models of epilepsy and in samples from human patients. In this study, I carried out meta-analyses and analyses of convergence for available GWES for epileptogenesis in humans and in mouse, rat, zebrafish and fruit fly models. Multiple lines of evidence (such as genome-wide association data and known druggable genes) were integrated to prioritize top candidate genes for epileptogenesis and a functional enrichment analysis was carried out. Several top candidate genes, which are supported by multiple lines of genomic evidence, such as GRIN1, KCNAB1 and STX1B, were identified. Druggable genes of potential interest (such as GABRA2, GRIK1, KCNAB1 and STX4) were also identified. An enrichment of genes regulated by the MEF2 and SOX5 transcription factors and the miR-106b-5p and miR-101-3p miRNAs was found. The current work is the first meta-analysis and convergent analysis of GWES for epileptogenesis in humans and in multiple animal models, integrating results from several genomic studies. Novel candidate genes and pathways for epileptogenesis were identified in this analysis.


Incidence of thromboembolism after transurethral resection of the prostate (TURP)--a study on TED stocking prophylaxis and literature review.
To assess the incidence of clinically evident pulmonary emboli and deep vein thromboses in patients undergoing transurethral resection of the prostate (TURP) with the routine use of graduated elastic compression stockings (TED) in all patients and the addition of low-dose heparin in selected high-risk patients. A retrospective analysis of clinically evident thromboembolic complications within 4 weeks of operation in 883 patients operated in a single hospital during a 4-year period. Four patients (0.45%) developed pulmonary emboli (PE), of which two (0.23%) were fatal. There was one clinically evident deep vein thrombosis (DVT) in a high-risk patient (0.11%). None of the 14 high-risk patients receiving additional low-dose heparin required a blood transfusion. Clinical thromboembolic complications following TURP are rare. TURP patients have a low risk for DVT, but an intermediate risk for pulmonary emboli. Pulmonary emboli may occur without identifiable risk factors and despite TED stocking prophylaxis.


The natural antiviral and immune stimulant effects of Allium cepa essential oil onion extract against virulent Newcastle disease virus.
Fifty broiler chicks were divided into five groups to study the antiviral and immune-stimulant effect of Allium cepa essential oils (ACEO). The effect of Allium cepa essential oils administration single or combined with NVD vaccine in broilers, more than one parameter was studied in this study i.e., the clinical symptoms that appeared on the chicks after the experimental infection with velogenic Newcastle disease virus, postmortem lesions, pathological lesions scoring, mortality rate (MR), and viral shedding, birds immunity was assessed by HI test and protection percent post-challenge with vNDV. Our result showed that mild clinical signs, lesion scoring, decreased viral shedding in ACEO treated groups 3 (G 3) more than control groups post-challenge with vNDV. Delayed onset of mild clinical signs in G3 followed by complete recovery 7th-day post-challenge (DPC). Low MR (40 and 0%) and high protection percent (100 and 60%) in ACEO treated G3 and G5, respectively. spleen, thymus, cecal tonsil, proventriculus, and cerebrum lesions scoring in G3 and G5 were significantly ((p ≤ 0.05).) lower than the control group, proving a decrease in NDV replication and effective antiviral activity of ACEO. HI titer significantly increased (p ≤ 0.05) In G3, G4 and G5 compared with control groups. There is no significant difference in HI titer in ACEO treated groups and vaccinated groups. In conclusion, oral administration of ACEO combined with NDV vaccines significantly reduces or eliminates lethal clinical signs, lesions, viral shedding, and enhances immune response and protection percent after vNDV challenge proving the natural antiviral and immune stimulant effect of ACEO onion extract. Implementing such a regime might aid NDV control in broiler flocks in endemic areas and reduce the epidemiological load of NDV in the environment.


The value of enzyme histochemical techniques in classifying fibre types of human skeletal muscle. 1. Adult skeletal muscles with no apparent disease of the neuromuscular system.
Fibre-type classification of human skeletal muscle into type I and type II fibres is mostly based on their slight or strong staining with the myosin adenosine triphosphatase reaction. In order to evaluate the reliability of this screening technique a combined histochemical and biochemical study was performed on normal and diseased skeletal muscle of human subjects. In the present investigation activities of enzymes which play a role in the aerobic and anaerobic pathways and which can characterize fibre type, were examined in muscle specimens, with no apparent disease of the neuromuscular system. Special attention is given to the maximal activities of phosphofructokinase and fructose-1,6-diphosphatase, the rate limiting enzymes for the regulation of the glycolysis and glyconeogenesis, respectively. A most important feature of the biochemical findings is the constancy of the activity ratios of the examined enzymes. From these results and from the histochemical results it can be concluded that in apparently normal adult human skeletal muscle the ATP-ase technique for type I and type II typing is reliable. For fibres with an intermediate intensity of staining with the myosin ATPase technique of typing it is also necessary to apply other enzyme histochemical techniques.


Orexin-B antagonized respiratory depression induced by sevoflurane, propofol, and remifentanil in isolated brainstem-spinal cords of neonatal rats.
Orexins (hypocretins) play a crucial role in arousal, feeding, and endocrine function. We previously reported that orexin-B activated respiratory neurons in the isolated brainstem-spinal cords of neonatal rats. We herein determined whether orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil. We recorded C4 nerve bursts as an index of inspiratory activity in a brainstem-spinal cord preparation. The preparation was superfused with a solution equilibrated with 3% sevoflurane alone for 10 min and the superfusate was then switched to a solution containing sevoflurane plus orexin-B. Sevoflurane decreased the C4 burst rate and the integrated C4 amplitude. The C4 burst rate and amplitude were reversed by 0.5 μM orexin-B, but not by 0.1 μM orexin-B. The decrease induced in the C4 burst rate by 10 μM propofol or 0.01 μM remifentanil was significantly antagonized by 0.1 μM orexin-B. Respiratory depression induced by a higher concentration (0.1 μM) of remifentanil was not restored by 0.1 μM orexin-B. These results demonstrated that orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil.


The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program.
The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3-8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291-15 417] vs. 6442 [5156-7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta -0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.


Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8.
Apoe-deficient (Apoe-/-) mice develop progressive atherosclerotic lesions with age but no severe renal pathology in the absence of additional challenges. We recently described accelerated atherosclerosis as well as marked renal injury in Apoe-/- mice deficient in the mesenchymal integrin chain Itga8 (Itga8-/-). Here, we used this Apoe-/-, Itga8-/- mouse model to investigate the sex differences in the development of atherosclerosis and concomitant renal injury. We hypothesized that aging female mice are protected from vascular and renal damage in this mouse model. Apoe-/- mice were backcrossed with Itga8-/- mice. Mice were kept on a normal diet. At the age of 12 months, the aortae and kidneys of male and female Apoe-/-Itga8+/+ mice or Apoe-/-Itga8-/- mice were studied. En face preparations of the aorta were stained with Sudan IV (lipid deposition) or von Kossa (calcification). In kidney tissue, immunostaining for collagen IV, CD3, F4/80, and PCNA and real-time PCR analyses for Il6, Vegfa, Col1a1 (collagen I), and Ssp1 (secreted phosphoprotein 1, synonym osteopontin) as well as ER stress markers were performed. When compared to male mice, Apoe-/-Itga8+/+ female mice had a lower body weight, equal serum cholesterol levels, and lower triglyceride levels. However, female mice had increased aortic lipid deposition and more aortic calcifications than males. Male Apoe-/- mice with the additional deficiency of Itga8 developed increased serum urea, glomerulosclerosis, renal immune cell infiltration, and reduced glomerular cell proliferation. In females of the same genotype, these renal changes were less pronounced and were accompanied by lower expression of interleukin-6 and collagen I, while osteopontin expression was higher and markers of ER stress were not different. In this model of atherosclerosis, the female sex is a risk factor to develop more severe atherosclerotic lesions, even though serum fat levels are higher in males. In contrast, female mice are protected from renal damage, which is accompanied by attenuated inflammation and matrix deposition. Thus, sex affects vascular and renal injury in a differential manner.


Self-terminating idiopathic ventricular fibrillation presenting as syncope: a 40-year follow-up report.
Out-of-hospital ventricular tachyarrhythmia has a high mortality. Most patients sustaining this type of arrhythmia have an organic heart disease. In this case report we present a patient with recurrent ventricular fibrillation with the clinical appearance of syncope, where no relevant organic heart disease could be found at autopsy performed 40 years later.


The effect of estrogen-progestin treatment on opioid control of gonadotropin and prolactin secretion in postmenopausal women.
Naloxone (10 mg) was given intravenously to seven postmenopausal women not receiving hormone treatment and to six postmenopausal women receiving Premarin-Provera treatment during the Premarin phase and also during the Premarin-Provera phase of therapy. Baseline estrone and estradiol levels (mean +/- SEM) were significantly lower in the group not receiving hormones (46.0 +/- 5.2 pg/ml and 28.4 +/- 3.1 pg/ml, respectively) than in the group in the Premarin phase of therapy (154 +/- 14 pg/ml and 79 +/- 13 pg/ml) and the group in the Premarin-Provera phase (135.1 +/- 8.3 pg/ml and 57.5 +/- 3.0 pg/ml) (p less than 0.005). Follicle-stimulating hormone, luteinizing hormone, and prolactin levels were 118.7 +/- 5.3 mIU/ml, 118.7 +/- 9.5 mIU/ml, and 9.2 +/- 0.7 ng/ml, respectively, with no significant change after naloxone administration in untreated women. With hormone therapy the basal follicle-stimulating hormone and luteinizing hormone levels decreased significantly while basal plasma estrone and estradiol increased significantly. In both the group in the Premarin phase of therapy and the group in the Premarin-Provera phase, luteinizing hormone levels increased significantly at 30 (135% +/- 10%, 144% +/- 8%), 45 (150% +/- 12%, 133% +/- 11%), 60 (149% +/- 15%, 128% +/- 11%), and 90 (139% +/- 15%, 132% +/- 13%) minutes after naloxone administration (p less than 0.01 to p less than 0.001). Follicle-stimulating hormone levels did not change significantly whereas prolactin levels showed a trend toward a decrease. These findings indicate that opioid inhibition of gonadotropins is reduced in postmenopausal women but increased with Premarin-Provera treatment. The effect of sex steroid on the opioid system in the postmenopausal women differs from that in the premenopausal women.


Challenges with social distancing during the COVID-19 pandemic among Hispanics in New York City: a qualitative study.
Hispanics in the United States are disproportionately affected by the novel coronavirus (COVID-19). While social distancing and quarantining are effective methods to reduce its spread, Hispanics, who are more likely to be essential workers and live in multigenerational homes than non-Hispanics, may face challenges that limit their ability to carry out these preventative efforts. We elicited the experiences of Hispanic adults with social distancing and self-quarantining during the COVID-19 pandemic in New York. In this qualitative study, Hispanic adults receiving care at a federally qualified community health center in East Harlem, New York, were recruited for remote one-on-one semi-structured interviews from 5/15/2020 to 11/17/2020. Interviews were conducted by a bilingual interviewer in Spanish or English, using a semi-structured topic guide informed by the Health Belief Model. Audio-recordings were professionally transcribed. We used thematic analysis to iteratively code the data. Each transcript was independently coded by two research team members, then reconciled by a third. Major themes and subthemes were identified. Among 20 participants, four major themes emerged; Hispanics were: (1) fearful of contracting and transmitting COVID-19, (2) engaging in practices to reduce transmission of COVID-19, (3) experiencing barriers to social distancing and quarantining, and (4) facing an enduring psychological and physical toll from COVID-19. Despite understanding the risks for contracting COVID-19 and taking appropriate precautions, Hispanics faced numerous challenges to social distancing and quarantining, such as living in crowded, multi-generational households, working as essential workers, and providing unpaid care to family members. Such challenges took a toll on their physical, emotional, and financial well-being. Our findings suggest that a tailored approach to public health messaging and interventions for pandemic planning are warranted among members of this community. Further research is needed to understand and mitigate the long term physical and psychological consequences of the pandemic among Hispanics.


The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site.
The Caulobacter crescentus cell cycle-regulated DNA methyltransferase (CcrM) methylates the adenine of hemimethylated GANTC after replication. Here we present the structure of CcrM in complex with double-stranded DNA containing the recognition sequence. CcrM contains an N-terminal methyltransferase domain and a C-terminal nonspecific DNA-binding domain. CcrM is a dimer, with each monomer contacting primarily one DNA strand: the methyltransferase domain of one molecule binds the target strand, recognizes the target sequence, and catalyzes methyl transfer, while the C-terminal domain of the second molecule binds the non-target strand. The DNA contacts at the 5-base pair recognition site results in dramatic DNA distortions including bending, unwinding and base flipping. The two DNA strands are pulled apart, creating a bubble comprising four recognized base pairs. The five bases of the target strand are recognized meticulously by stacking contacts, van der Waals interactions and specific Watson-Crick polar hydrogen bonds to ensure high enzymatic specificity.


Heat Shock Protein 90 is Required for cAMP-Induced Differentiation in Rat Primary Schwann Cells.
Schwann cells (SCs) play an important role in producing myelin for rapid neurotransmission in the peripheral nervous system. Activation of the differentiation and myelination processes in SCs requires the expression of a series of transcriptional factors including Sox10, Oct6/Pou3f1, and Egr2/Krox20. However, functional interactions among several transcription factors are poorly defined and the important components of the regulatory network are still unknown. Until now, available evidence suggests that SCs require cAMP signaling to initiate the myelination program. Heat shock protein 90 (Hsp90) is known as a chaperone required to stabilize ErbB2 receptor. In recent years, it was reported that cAMP transactivated the ErbB2/ErbB3 signaling in SCs. However, the relationship between Hsp90 and cAMP-induced differentiation in SCs is undefined. Here we investigated the role of Hsp90 during cAMP-induced differentiation of SCs using Hsp90 inhibitor, geldanamycin and Hsp90 siRNA transfection. Our results showed that dibutyryl-cAMP (db-cAMP) treatment upregulated Hsp90 expression and led to nuclear translocation of Gab1/ERK, the downstream signaling pathway of the ErbB2 signaling mechanism in myelination. The expression of myelin-related genes and nuclear translocation of Gab1/ERK following db-cAMP treatment was inhibited by geldanamycin pretreatment and Hsp90 knockdown. These findings suggest that Hsp90 might play a role in cAMP-induced differentiation via stabilization of ErbB2 and nuclear translocation of Gab1/ERK in SCs.


Neuroplastic changes in depression: a role for the immune system.
Accumulating evidence suggests that there is a rich cross-talk between the neuroimmune system and neuroplasticity mechanisms under both physiological conditions and pathophysiological conditions in depression. Anti-neuroplastic changes which occur in depression include a decrease in proliferation of neural stem cells (NSCs), decreased survival of neuroblasts and immature neurons, impaired neurocircuitry (cortical-striatal-limbic circuits), reduced levels of neurotrophins, reduced spine density and dendritic retraction. Since both humoral and cellular immune factors have been implicated in neuroplastic processes, in this review we present a model suggesting that neuroplastic processes in depression are mediated through various neuroimmune mechanisms. The review puts forward a model in that both humoral and cellular neuroimmune factors are involved with impairing neuroplasticity under pathophysiological conditions such as depression. Specifically, neuroimmune factors including interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, CD4⁺CD25⁺T regulatory cells (T reg), self-specific CD4⁺T cells, monocyte-derived macrophages, microglia and astrocytes are shown to be vital to processes of neuroplasticity such as long-term potentiation (LTP), NSC survival, synaptic branching, neurotrophin regulation and neurogenesis. In rodent models of depression, IL-1, IL-6 and TNF are associated with reduced hippocampal neurogenesis; mechanisms which are associated with this include the stress-activated protein kinase (SAPK)/Janus Kinase (JNK) pathway, hypoxia-inducible factors (HIF)-1α, JAK-Signal Transducer and Activator of Transcription (STAT) pathway, mitogen-activated protein kinase (MAPK)/cAMP responsive element binding protein (CREB) pathway, Ras-MAPK, PI-3 kinase, IKK/nuclear factor (NF)-κB and TGFβ activated kinase-1 (TAK-1). Neuroimmunological mechanisms have an active role in the neuroplastic changes associated with depression. Since therapies in depression, including antidepressants (AD), omega-3 polyunsaturated fatty acids (PUFAs) and physical activity exert neuroplasticity-enhancing effects potentially mediated by neuroimmune mechanisms, the immune system might serve as a promising target for interventions in depression.


Release of superoxide radicals by mouse macrophages stimulated by oxidative modification of glycated low density lipoproteins.
Diabetic patients have high levels of glycated LDL. Although glycated LDLs are implicated in the development of atherosclerosis in such patients, convincing data are lacking. We observed release of superoxide radicals (O2-) from mouse resident peritoneal macrophages stimulated by an oxidized/glycated LDL by using a highly sensitive and specific chemiluminescence method. Oxidized/glycated LDL was achieved by an addition of low concentration of Fe3+ to glycated LDL. Macrophages took up an appreciable amount of the glycated LDL oxidized by iron, leading to the development of foam cells, while they did not take up untreated glycated LDL or the native LDL. These observations clearly indicate that the oxidized/glycated LDL reacts well with macrophages. Since an oxidation of glycated LDL may occur in vivo, the oxidized/glycated LDL might play an important role in atherogenesis.


The New York City Department of Health and Mental Hygiene School Vision Program: A description of program expansion.
This study describes how the School Vision Program (SVP) operates in NYC Public Schools, and how it has expanded to provide screening, follow-up, eye exams, and even glasses to more students in recent years. Using administrative data from the SVP, we analyze a population sample of all public-school students with non-missing demographic variables in grades Pre-K through 12, focusing on the most recent year of data, 2018-19. We tabulate rates of screening and other results across students by grade and student characteristics, highlighting the expansion of SVP in community schools beginning in 2015-16. The SVP screens about 87% of students in Pre-K through 1st Grade each school year. Of the 22% of screened students who failed the screening in 2018-19, 69% received follow-up efforts, and 39% completed eye exams. Among students with completed eye exams, 13% of students in Pre-K through 1st grade were diagnosed with amblyopia, and 70% needed glasses. Less advantaged students in terms of race, ethnicity, and socioeconomic status were less likely to pass vision screenings and less likely to receive eye exams after failing the screening. The SVP's expansion to all grades in community schools and its provision of eye exams and glasses increased the rate of eye exams to 90% of students with a failed vision screening and distributed glasses to over 22,000 students in grades Pre-K to 12 in 2018-19. The expansion of SVP services in community schools suggests large potential benefits from school districts connecting students who fail vision screenings directly to eye doctors. Otherwise, low rates of follow-up eye exams in younger grades can lead to unidentified and unmet need for vision services in older grades, especially among disadvantaged students.


Temporal evolution of threshold temperatures for extremely cold days in Spain.
In contrast to research on heat waves, there are no studies in recent years that analyze the temporal evolution of threshold temperatures (Tthreshold) for extremely cold days (ECD). It is unknown whether threshold temperatures have increased more quickly than the minimum daily temperature (Tmin) in recent years. The objective of this study was to analyze the temporal evolution of the minimum daily temperature (Tmin) in a group of Spanish provinces and compare it with the evolution of threshold temperatures. An ecological, retrospective time series study was carried out using daily observations between January 1, 1983 and December 31, 2018 (36 years) in 10 provinces that are representative of the different climate territories in Spain. For each representative observatory in each province, the values of Tmin were obtained for the winter months (November-March). The value of Tthreshold was determined for each province and each year, using dispersion diagrams for the pre-whitened series, with daily mortality due to natural causes displayed on the Y axis (CIEX: A00-R99) and Tmin grouped by 10 degree intervals on the X axis. To determine the temporal evolution of Tmin and Tthreshold for each province, linear models were fitted, with time as the independent variable. During the winter months, Tmin increased at an average rate of 0.2 °C/decade (IC95: 0.1-0.3), while Tthreshold remained practically constant during the period, at 0.1 °C/decade (IC95% -0.1 0.3). These values are much lower than those obtained in the case of heat, both in terms of the evolution of maximum daily temperature and that of Tthreshold. In conclusion, the fact that this trend has been maintained across time in a scenario of climate change, with a slow increase in minimum daily temperatures and constant values of Threshold, suggests a decrease in the number of ECD.


In the twilight zone-The head morphology of Bergrothia saulcyi (Pselaphinae, Staphylinidae, Coleoptera), a beetle with adaptations to endogean life but living in leaf litter.
The pselaphine Bergrothia saulcyi shows features seemingly linked with life in deep soil layers, such as greatly reduced and non-functional compound eyes, a sensorium of long tactile setae, long appendages, and flightlessness. However, the tiny beetles occur in forest leaf litter, together with a community of beetles with wings and well-developed eyes. We hypothesize that B. saulcyi moves into deep soil under dry conditions, and returns to upper layers when humidity increases again. Despite the evolutionary cost of a reduced dispersal capacity, this life strategy may be more efficient and less hazardous than moving to different habitats using flight and the visual sense in an environment periodically drying out. We also discuss cephalic features with potential phylogenetic relevance. Plesiomorphies of B. saulcyi include the presence of anterior tentorial arms, well-developed labral retractors, and a full set of extrinsic maxillary and premental muscles. Apomorphic cephalic features support clades Protopselaphinae + Pselaphinae, and Pselaphinae. A conspicuous derived condition, the clypeo-ocular carina, is a possible synapomorphy of Batrisitae and genera assigned to Goniaceritae. A complex triple set of cephalic glands found in B. saulcyi is similar to a complex identified in the strict myrmecophile Claviger testaceus (Clavigeritae). It is conceivable that glands linked with food uptake in free-living pselaphines were genetically re-programmed in ancestors of inquilines, to enable them to appease the host ants. We suggest that behavioral studies are necessary to understand the poorly known life habits of B. saulcyi. Additional information is required to explain why a species with irreversibly reduced visual sense and other adaptations typical of endogean or cave-dwelling beetles was only collected from the upper leaf litter layer.


Fulfilling the mission of academic medicine: training residents in the health needs of prisoners.
The single mission of academic medicine is the pursuit of health for all. This mandate serves as a reminder to focus care on vulnerable and underserved populations. The 12 million Americans who cycle through correctional facilities each year are arguably among the most vulnerable populations in this country; predominantly black, with a high burden of disease and many barriers to care after release. Medical training programs should provide exposure to the health needs of prisoners. Residents could establish care with inmates prior to release and arrange follow-up in the community. This addition to training would not only provide care to this underserved group, but also would train residents in the myriad problems prisoners face, and foster social responsibility.


Mechanisms of nitric oxide generation in living systems.
In modern chemical and biochemical studies, special attention is paid to molecular systems capable of generating nitric oxide (NO), which is one of the most important signalling molecules in the body and can trigger a whole cascade of reactions. Despite the importance of this molecule, the mechanisms of its formation in living organisms remain a subject of debate. This review combines the most important methods of releasing NO from endogenous and exogenous sources. The history of endogenous NO donors dates back more than 150 years, since the synthesis of nitroglycerin, which remains the standard vasodilator today, even though it is known that it and many other similar compounds lead to the development of a nitrate tolerance. Particular awareness is devoted to the mechanisms of NO formation without the participation of enzymes, since these methods are most important for creating exogenous sources of NO as drugs. The study of NO formation methods is centred on both the creation of new NO donors and understanding the mechanisms of tolerance to them.


Interaction of benzilylcholine mustard, benzilylcholine and lachesine with the histamine receptor in the longitudinal muscle of guinea-pig ileum.
1. The histamine receptors of longitudinal muscle strips from guinea-pig ileum were inactivated on extended exposure to concentrations of benzilylcholine mustard (BCM) above 10(-6)M. These concentrations are 3 orders of magnitude greater than those required for inactivation of the muscarinic receptors. Mepyramine (3 x 10(-8)M) afforded complete protection for the histamine receptor against the effects of BCM.2. Recovery from block at 30 degrees C was very slow with a first-order rate constant of approximately 10(-7) s(-1).3. The rate constant, k(2), for the alkylation reaction in which the reversible BCM-receptor complex is converted into an irreversible complex is much greater than the rate constant, k(-1), for dissociation of the reversible complex. The value of the rate constant, k(1), for formation of the reversible complex was 1.1 +/- 0.2 x 10(3)M(-1) s(-1).4. These observations suggested that k(1) was probably not much greater than for BCM acting on the muscarinic receptor, even though the value of k(1) was reduced by more than 2 orders of magnitude. This effect has been established for benzilylcholine and lachesine, reversible analogues of BCM. For both drugs k(1) for the histamine receptor was approximately 3 orders of magnitude less than for the muscarinic receptor, whereas k(1) was greater by a factor of only 6.