Chronic insomnia of early childhood: Phenotypes and pathophysiology.
This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding of its pathophysiology. Our hypothesis is that chronic insomnia of childhood has different phenotypical expressions, associated to different pathophysiological mechanisms. Based on a long-lasting experience in evaluating a very large number of children with specific insomnia symptoms (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings) and on published data, we hypothesize that different phenotypes of insomnia might exist with different therapeutic implications. We describe three phenotypes of insomnia in early childhood: a) insomnia with motor restlessness; b) insomnia characterized without difficulties in falling asleep but with long-lasting early morning awakenings; c) insomnia with multiple night awakenings and falling asleep difficulty. This type of categorization might have important implications for treatment, based on the different hypothetical neurotransmitter dysfunctions. The early identification of a phenotype of insomnia might guide to specific behavioral and/or pharmacological interventions with the aim to prevent chronic insomnia.


Pharmacokinetic, tissue distribution and excretion of ginsenoside-Rd in rodents.
Ginsenoside-Rd (GS-Rd) is one of the major active components of Panax ginseng, and was shown to have the protective effects against several insults. However, we still lack some basic knowledge of GS-Rd, including its pharmacokinetic, tissue distribution and excretion in vivo in experimental animal, such as mice and rats. In this study, HPLC and radioactive tracer assays were performed to determine pharmacokinetic, tissue distribution and excretion of GS-Rd in rodents. After intravascular administration with 20, 50 or 150 mg/kg GS-Rd, the dynamic changes of GS-Rd concentrations in plasma were consistent with a two-compartment model while the concentration of ³H-labeled GS-Rd was rapidly reached the peak in plasma, and distributed to various tissues, among which the highest concentration was observed in the lung.


Development and applications of molecularly imprinted polymers based on hydrophobic CdSe/ZnS quantum dots for optosensing of N(ε)-carboxymethyllysine in foods.
A novel molecularly imprinted polymer (MIP) based on hydrophobic CdSe/ZnS quantum dots (HBQDs) was synthesized via an approach that combines MIPs for the selectivity and sensitivity with semiconductor HBQDs as optosensing material (HBQDs@MIP). Here, using a one-pot water-in-oil reverse microemulsion polymerization, the HBQDs@MIP was used as a molecular recognition element to construct an N(ε)-carboxymethyllysine (CML) optosensor. The HBQDs were coated with silica to endow the nanoparticles with high dispersibility and broad compatibility with hydrophilic analytes. Under optima conditions, the relative fluorescence intensity of the HBQDs@MIP decreased linearly with increasing CML concentration in the range 5-400μgL(-1). The proposed method enables, detection procedures to be completed within 90min, with good recoveries, ranging from 85% to 106%. It can be applied to the rapid and cost-effective monitoring of CML in food samples.


Contribution of orodental status to the intensity of orofacial tardive dyskinesia: an interdisciplinary and video-based assessment.
Tardive dyskinesia (TD) is a neurological motor complication eventually arising in one-third of patients chronically exposed to antipsychotic drugs. Some orodental peripheral factors have been reported to influence TD. To measure orodental factors such as temporomandibular joint function, static occlusal contacts, and denture condition, and attempt correlations with orofacial TD intensity. In this exploratory cross-sectional pilot study, 31 subjects between 30 and 75 years of age were divided in two groups displaying minimal to mild, or moderate to severe orofacial TD, respectively, and underwent a detailed oral, dental, and prosthetic evaluation to capture various aspects of oral health compared between the two groups. Blinded video-based TD ratings along a validated scale were obtained to compare dentulous and edentulous subjects, and contrast TD intensity in complete denture wearers with and without their own prostheses. None of the factors examined tightly correlated with orofacial TD intensity. However, edentulism was associated with a higher median orofacial TD rating compared to the dentulous group (p = 0.001). Further, a significant intra-subject difference was observed in the edentulous subjects rated with their own complete dentures in place or not (p = 0.028), the dentures attenuating the mean orofacial ratings by 21.8 ± 7.3%. Of all orodental factors considered, only edentulism and complete denture wearing influenced oral TD expression, calling for the close monitoring of the dental status in antipsychotic drug-exposed patients to prevent tooth loss. Further studies to measure the impact of an adequate prosthodontic rehabilitation in edentulous subjects with orofacial TD seem warranted.


Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping.
Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment. These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.


Detection of the marine toxin okadaic acid: assessing seafood safety.
Diarrheic Shellfish Poisoning (DSP) is a gastrointestinal illness caused by consumption of shellfish contaminated with DSP toxins such as okadaic acid (OA) and dinophysistoxins (DTX). The occurrences of OA in bivalves induce not only public health problems but also economic damages to shellfish farming. Consequently, the development of fast, reliable and sensitive detection methods is an evident necessity. The mouse bioassay has been the reference and most commonly used analysis method. However, this technique suffers from low accuracy, specificity and ethical problems due to the animal experimentation. Thus, the development of alternative and efficient detection systems is required. Several biological, chemical, and immunological methods have been developed to evaluate the presence of DSP toxins in seafood. This review gives an overview of different analytical methods and new trends for the detection of OA. Over the past decade, considerable attention has been given to the development of biosensors for the efficient detection of marine toxin. Recent advances in the field of aptamers and nanomaterial offer exciting new opportunities to develop improved and more reliable devices allowing the detection of OA.


Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland.
Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.


Designer biochar with enhanced functionality for efficient removal of radioactive cesium and strontium from water.
Radioactive elements released into the environment by accidental discharge constitute serious health hazards to humans and other organisms. In this study, three gasified biochars prepared from feedstock mixtures of wood, chicken manure, and food waste, and a KOH-activated biochar (40% food waste + 60% wood biochar (WFWK)) were used to remove cesium (Cs+) and strontium (Sr2+) ions from water. The physicochemical properties of the biochars before and after adsorbing Cs+ and Sr2+ were determined using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, extended X-Ray absorption fine structure (EXAFS) spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). The WFWK exhibited the highest adsorption capacity for Cs+ (62.7 mg/g) and Sr2+ (43.0 mg/g) among the biochars tested herein. The removal of radioactive 137Cs and 90Sr exceeded 80% and 47%, respectively, in the presence of competing ions like Na+ and Ca2+. The functional groups present in biochar, including -OH, -NH2, and -COOH, facilitated the adsorption of Cs+ and Sr2+. The Cs K-edge EXAFS spectra revealed that a single coordination shell was assigned to the Cs-O bonding at 3.11 Å, corresponding to an outer-sphere complex formed between Cs and the biochar. The designer biochar WFWK may be used as an effective adsorbent to treat radioactive 137Cs- and 90Sr-contaminated water generated during the operation of nuclear power plants and/or unintentional release, owing to the enrichment effect of the functional groups in biochar via alkaline activation.


Combination povidone-iodine and alcohol formulations more effective, more convenient versus formulations containing either iodine or alcohol alone: a review of the literature.
Topical antiseptic formulations containing single active ingredients of alcohol and iodine are recognized by the Food and Drug Administration as "generally safe and effective" for "preparation of the skin prior to surgery" or "prior to an injection" including "catheter care, ostomy hygiene, and intravenous site preparation" (Federal Register, 1994). However, a synergistic effect results from the combination of ethyl or isopropyl alcohol and povidone-iodine. Because each active ingredient has different modes of action and performance characteristics, these combination formulations are faster acting with a broader spectrum of antimicrobial activity than formulations containing povidone-iodine alone, and more persistent than formulations containing ethyl or isopropyl alcohol alone.


Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway.
Neuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood. The expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion. The results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway. Based on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC.


Evaluation of an outpatient culture device in continuous ambulatory peritoneal dialysis.
From August 1983 through August 1986, we used a dipstick culture device for outpatient dialysate cultures among patients undergoing continuous ambulatory peritoneal dialysis. The device was used in 42% of 531 peritonitis episodes. In 21% of the peritonitis episodes, patients elected to be hospitalized for treatment and, therefore, did not obtain a dialysate culture. The frequency of noncompliance was 18%. All samples were received within four days of mailing. Forty percent of isolates were gram-positive organisms, 30% were gram-negative, 3% were fungal organisms, and 27% of the cultures failed to yield a growth. Aside from a greater incidence of failure to define a bacterial growth responsible for peritonitis, the spectrum of organisms was similar to culture results obtained from the patients who elected, during this same period, to be hospitalized. We believe the dipstick device may be used effectively for outpatient dialysate cultures.


An open-source development based on photogrammetry for a real-time IORT treatment planning system.
This study presents a treatment planning system for intraoperative low-energy photon radiotherapy based on photogrammetry from real images of the surgical site taken in the operating room. The study population comprised 15 patients with soft-tissue sarcoma. The system obtains the images of the area to be irradiated with a smartphone or tablet, so that the absorbed doses in the tissue can be calculated from the reconstruction without the need for computed tomography. The system was commissioned using 3D printing of the reconstructions of the tumor beds. The absorbed doses at various points were verified using radiochromic films that were suitably calibrated for the corresponding energy and beam quality. The average reconstruction time of the 3D model from the video sequence in the 15 patients was 229,6±7,0 s. The entire procedure, including video capture, reconstruction, planning, and dose calculation was 520,6±39,9 s. Absorbed doses were measured on the 3D printed model with radiochromic film, the differences between these measurements and those calculated by the treatment planning system were 1.4% at the applicator surface, 2.6% at 1 cm, 3.9% at 2 cm and 6.2% at 3 cm. The study shows a photogrammetry-based low-energy photon IORT planning system, capable of obtaining real-time images inside the operating room, immediately after removal of the tumor and immediately before irradiation. The system was commissioned with radiochromic films measurements in 3D-printed model.


Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers.
During the course of murine neurocysticercosis (NCC), disruption of the unique protective barriers in the central nervous system (CNS) is evidenced by extravasation of leukocytes. This process varies according to the anatomical sites and diverse vascular beds analyzed. To examine mechanisms involved in the observed differences, the expression and activity of eight matrix metalloproteinases (MMPs) were analyzed in a murine model of NCC. The mRNA expression of the MMPs studied was upregulated as a result of infection, and active MMPs were mainly detected in leukocytes migrating into the brain. Polarized expression and gelatinolytic activity of several MMPs were identified in immune cells extravasating pial vessels as early as 1 day post infection. In contrast, leukocytes expressing active MMPs and extravasating parenchymal vessels were not observed until 5 weeks post infection. In ventricular areas, most of the MMP activity was detected in leukocytes traversing the ependyma from leptomeningeal infiltrates. In addition, immune cells continued to express active MMPs after exiting vessels suggesting that enzymatic activity of MMPs is not just required for diapedesis. These results correlate with our previous studies showing differential kinetics in the disruption of the CNS barriers upon infection and help document the important role of MMPs during leukocyte infiltration and inflammation.


The use of 4-(2-pyridylazo)resorcinol in studies of zinc release from Escherichia coli aspartate transcarbamoylase.
The metallochromic indicator 4-(2-pyridylazo)resorcinol (PAR) has been used at pH 7.0 to monitor the mercurial-promoted Zn2+ release from Escherichia coli aspartate transcarbamoylase and Zn2+ uptake by regulatory dimers upon displacement of the mercurial reagent with 2-mercaptoethanol. The release of Zn2+ (as reflected by a yellow to orange color change in PAR solutions) is linked to dissociation of the enzyme since the six Zn2+ bonding domains stabilize catalytic and regulatory chain contacts; the rebinding of Zn2+ produces enzyme assembly and a corresponding decrease in the amount of PAR-Zn2+ complex. Using greater than 10-fold PAR to free Zn2+ at pH 7.0, delta epsilon = 6.6 +/- 0.2 X 10(4) M-1 cm-1 at 500 nm (20 degrees C) for (PAR)2Zn2+ complex formation (beta'2 approximately equal to 10(12) M-1). In kinetic studies at pH 7.0, PAR (10(-4) M) has been used to measure the instantaneous concentration of Zn2+ released from micromolar quantities of protein; second-order k = 2 X 10(7) M-1 s-1 for forming the 1:1 PAR:Zn2+ complex. These properties of PAR-Zn2+ interactions make PAR a generally useful reagent for studying Zn2+ release from proteins.


Calretinin is essential for mesothelioma cell growth/survival in vitro: a potential new target for malignant mesothelioma therapy?
Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy resistance, and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma; however, little is known about CR's putative functions in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway, and furthermore, SV40 early region genes are able to upregulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Downregulation of CR via lentiviral-mediated short-hairpin RNA significantly decreased the viability and proliferation of mesothelioma cells in vitro. The effect was strong in epithelioid-dominated cell lines (ZL55 and MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212 and ZL34). The specificity of the effect was confirmed by stable enhanced green fluorescent protein-CR expression in mesothelioma cell lines and subsequent downregulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72 hr postinfection via strong activation of the intrinsic caspase 9-dependent pathway. Downregulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G1 block without decreasing viability or activating apoptosis pathways. These results demonstrate that downregulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from MM. The authors anticipate these findings to reveal CR as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, as well as of the mixed and sarcomatoid type.


Rapid optimization of an ICE inhibitor synthesis using multiple reaction conditions in a parallel array.
Optimization of a 2-step reaction sequence was accomplished in 3-4 days, with over 200 different reaction conditions evaluated. Combinatorial arrays were performed using the optimized conditions to synthesize 590 new compounds which were tested for inhibition against N-His (D381E) ICE. Thirty-five compounds showed at least a tenfold improvement in activity compared to an initial standard.


Assessment of postoperative pain after single-visit root canal treatment using rotary and reciprocating file systems: an in vivo study.
Various instrument kinematics used in single-visit endodontics influence the occurrence of pain after endodontic therapy. This study aimed to evaluate the occurrence of pain after mechanical instrumentation with Hyflex EDM (HEDM) and WaveOne Gold (WOG) during single-visit endodontic therapy. Sixty patients diagnosed with asymptomatic irreversible pulpitis and normal apical tissues in mandibular premolar teeth were included in the study for single-visit root canal therapy. The patients were divided into two groups (n = 30) according to the rotary instrument used during root canal preparation (group A [HEDM] and group B [WOG]). Pain was evaluated after endodontic therapy at 8, 24, and 48 h intervals using the visual analog scale (VAS). Data obtained were analyzed using the chi-square test, independent t-test, MannWhitney U test, and Wilcoxon matched-pairs test. Statistically significant differences were observed between the two groups (P < 0.001) at 8, 24, and 48 h, with WOG exhibiting less pain than HEDM files. Postoperative pain was lower in the WOG file system than in the HEDM file system after single-visit root canal therapy at 8, 24, and 48 h.


Biodegradation and sorption of nodularin (NOD) in fine-grained sediments.
Nodularin (NOD) is a cyclic pentapeptide hepatotoxin produced by the bloom forming cyanobacterium Nodularia spumigena. The fate of the toxin in the aquatic environment has not been fully evaluated. In the current study the changes in NOD concentration caused by biodegradation and sorption in samples from the Baltic were studied. Seawater of various salinities (0, 4, 8 and 12 PSU) and three forms of fine-grained sediment (sterile wet sediment, non-sterile wet sediment, and combusted sterile sediment) were incubated with 34.7 microg of NOD. The toxin was seen to be highly stable both in sterile and non-sterile seawater. During the 21-day experiment NOD concentrations in solutions overlying the combusted sediment and the sterile wet sediment were reduced to 12.5+/-2.6% and 59.8+/-2.4% of the initial value. The greatest loss of the toxin (up to 100%) was observed in the non-sterile seawater incubated with non-sterile wet sediment. These results indicate an important role of benthic microbial community in nodularin removal. Two biodegradation products with similar spectral characteristics to NOD were detected; one of which was identified as Adda amino acid.


Assessment of needle guidance devices for their potential to reduce fluoroscopy time and operator hand dose during C-arm cone-beam computed tomography-guided needle interventions.
To assess whether the use of needle guidance devices can reduce fluoroscopy time and operator hand dose during cone-beam computed tomography-guided needle interventions. The freehand technique was compared with techniques employing two distinct needle holders and a ceiling-mounted laser guidance technique. Laser guidance was used either alone or in combination with needle holders. Four interventional radiologists were instructed to reach predetermined targets in an abdominal phantom using these techniques. Each operator used all six techniques three times. Fluoroscopy time, procedure time, operator hand dose, and needle tip deviation were obtained for all simulated needle interventions. All data are presented as median (ranges). All procedures were successfully completed within 2-4 minutes, resulting in a deviation from target of 0.8 mm (0-4.7). In freehand procedures, the fluoroscopy time to reach the target was 50 seconds (31-98 s). Laser guidance, used alone or in combination with needle holders, reduced fluoroscopy time to 31 seconds (14-68 s) (P<.02). The operator hand dose in freehand procedures was 275 μSv (20-603 μSv). Laser guidance alone or in combination with needle holders resulted in a reduction of the hand dose to<36 μSv (5-82 μSv) per procedure (P<.001). There were no statistically significant effects on hand dose levels or fluoroscopy time when the needle holders were employed alone. Compared with the freehand technique, all three tested needle guidance devices performed with equivalent efficiency in terms of accuracy and procedure time. Only the addition of laser guidance was found to reduce both fluoroscopy time and operator hand dose.


In vitro localization of the protein synthesis defect associated with experimental phenylketonuria.
We have used a cell-free system derived from hamster brain to investigate protein synthesis during experimental phenylketonuria. In such a system the elongation inhibitor emetine impeded translation in extracts derived from both treated and control animals. On the other hand the initiation inhibitor aurintricarboxylic acid showed no effects on protein synthesis activity of treated hamsters, although it was severely inhibiting in controls. This suggests that initiation is the altered step in brain protein synthesis failure consecutive to phenylketonuria.


Tocilizumab in the Management of COVID-19: A Preliminary Report.
Pneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness. To evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab. Retrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab. Confirmed COVID-19 pneumonia. Outcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed. The average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p < 0.0001), progression to requiring mechanical ventilation (OR = 6.6, p < 0.0001), and increased length of stay (OR = 16.2, p < 0.0001). Our retrospective analysis revealed an association between Tocilizumab administration and increased mortality, ICU admission, mechanical ventilation, and length of stay in subjects with COVID-19. Prospective trials are needed to evaluate the true effect of Tocilizumab in this condition.


Serological characterization of dengue virus infections observed among dengue hemorrhagic fever/dengue shock syndrome cases in upper Myanmar.
In Myanmar, dengue fever (DF)/dengue hemorrhagic fever (DHF) is one of the leading causes of morbidity and mortality among children. From Pyinmana Hospital in 2004 and Mandalay Children Hospital in 2006, 160 patients diagnosed clinically to have DHF/dengue shock syndrome (DSS) were examined for immunoglobulin M (IgM) and IgG levels. A focus reduction neutralization test was also used to determine primary or secondary dengue virus (DENV) infection. By using IgM-capture ELISA, 139 cases were confirmed as DENV infections. Of these IgM-positives, 94 samples were collected 7-24 days from the onset of illness, to which 13 (14%) and 81 (86%) were determined to be primary and secondary DENV infections, respectively. The 13 primary DENV infection cases were spread among the various severity groups (DHF grade I-IV and DSS) and represented age groups ranging from <1 year of age to 9 years of age. The patients in these primary infection cases showed a remarkably high IgM with a low IgG titer response compared with the secondary infection cases. No significant differences were observed in IgG titers with clinical severity. The data obtained in this study suggest that primary DENV infection cases exist certainly among DHF/DSS cases in Myanmar, and that additional mechanism(s) aside from the antibody-dependent enhancement mechanism could have influenced the clinical severity in DHF/DSS cases.


A review of vaccine research and development: tuberculosis.
Substantial progress has been made during the past 15 years towards the development of improved vaccines for tuberculosis. This is due to advances in the characterization of genes and antigens of Mycobacterium tuberculosis (M. tb), aided by the availability of genome sequences of different mycobacterial species and M. tb isolates and to greater understanding of protective immune responses to the pathogen in both animals and humans. More than one hundred candidate vaccines have been tested in animal models, representing all of the major vaccine design strategies, and some have now moved into clinical trials. This review summarizes recent advances in tuberculosis vaccine development.


Hepatitis B virus infection among institutionalized mentally ill patients in Brazil.
The main objective was to evaluate HBV infection and occult HBV infection (OBI) cases in mentally ill patients based on serological and molecular profiles. Serum samples of 333 long-stay mentally ill patients were tested for the prevalence of HBV markers by serological (ELISA) and molecular (PCR) assays. The PCR products were sequenced to determine viral genotypes. It was observed a global prevalence of 12.9% (43/333) for HBV infection markers, considering HBsAg and/or anti-HBc positivity. Fourteen samples tested positive for anti-HBs alone. All samples positive (n=57) for any HBV serological markers were tested for HBV-DNA and six were positive: HBsAg/anti-HBc (n=1), anti-HBc/anti-HBs (n=1), anti-HBs alone (n=1), and anti-HBc alone (n=3). The rate of OBI was 9.2% (5/54) from samples that were anti-HBc and/or anti-HBs positive. All sequenced samples were characterized as genotype A. The high rate of HBV infections found in this study suggests the possibility of HBV transmission due to risk factors displayed by some patients, and highlights the importance of vaccination of susceptible patients and the staff of that institution.


Relationship of political ideology of US federal and state elected officials and key COVID pandemic outcomes following vaccine rollout to adults: April 2021-March 2022.
Scant research, including in the United States, has quantified relationships between the political ideologies of elected representatives and COVID-19 outcomes among their constituents. We analyzed observational cross-sectional data on COVID-19 mortality rates (age-standardized) and stress on hospital intensive care unit (ICU) capacity for all 435 US Congressional Districts (CDs) in a period of adult vaccine availability (April 2021-March 2022). Political metrics comprised: (1) ideological scores based on each US Representative's and Senator's concurrent overall voting record and their specific COVID-19 votes, and (2) state trifectas (Governor, State House, and State Senate under the same political party control). Analyses controlled for CD social metrics, population density, vaccination rates, the prevalence of diabetes and obesity, and voter political lean. During the study period, the higher the exposure to conservatism across several political metrics, the higher the COVID-19 age-standardized mortality rates, even after taking into account the CD's social characteristics; similar patterns occurred for stress on hospital ICU capacity for Republican trifectas and US Senator political ideology scores. For example, in models mutually adjusting for CD political and social metrics and vaccination rates, Republican trifecta and conservative voter political lean independently remained significantly associated with an 11%-26% higher COVID-19 mortality rate. Associations between the political ideologies of US federal elected officials and state concentrations of political party power with population health warrant greater consideration in public health analyses and monitoring dashboards. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.


ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.
AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo-EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small-angle X-ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head-to-head arrangement of two heptameric rings. Biochemical activity assays with site-directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non-conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.


Larval distribution, migratory pattern and histological effects of Toxocara canis in Rattus norvegicus.
The common dog roundworm Toxocara canis can infect other animals and humans which may act as their paratenic and accidental hosts, respectively. Larvae do not further develop to adult worms in these hosts. Instead, they undergo migration to various body organs, causing the neglected parasitic disease known as toxocariasis. Although rats are considered as potential paratenic hosts of the parasite, there are only few studies which utilized Rattus norvegicus (Sprague-Dawley strain) for experimental infections involving toxocariasis. This study aimed to determine whether T. canis could establish in Sprague-Dawley rats artificially infected with 500 T. canis embryonated eggs and if the animals can be used as animal models for toxocariasis. Following squash method and tissue digestion, larvae were recovered from the lungs, liver and brain of the infected rats. Furthermore, gross examination of organs revealed macroscopic lesions and hemorrhages in the lungs and brain. Microscopically, accumulation of inflammatory cells, thickening of alveoli lining and destruction of bronchial walls and hepatic necrosis were observed. This study showed that T. canis has established in Sprague-Dawley rats and could serve as a model for Toxocara infection studies.


Evaluation of dislocation position in patients with recurrent anterior shoulder dislocation.
The usual mechanism of anterior shoulder dislocation is widely believed to be a combination of glenohumeral joint abduction, extension, and external rotation forces, even though no published reports to date have investigated the arm position of anterior shoulder dislocation in detail. Understanding the exact position of anterior shoulder dislocations is important for the management of anterior shoulder instability. The study included 40 shoulders of 38 patients (32 males, 6 females), aged 28.0 (range, 13-73) years with symptomatic post-traumatic recurrent anterior shoulder instability. While patients were under general anesthesia, but before shoulder-stabilizing surgery, we evaluated the angle of external rotation with 90° elevation in the scapular plane at which the humeral head showed anterior translations over the glenoid rim. The center of anterior instability at 90° elevation in the scapular plane was at 25.9° of external rotation. Anterior translations were detected in the range of 3.4° of internal rotation to 55.1° of external rotation, and no shoulders (except one) showed anterior translation at maximal external rotation. Gross anterior translation was seen in the middle range of rotation at approximately 25° of external rotation, and anterior translation decreased close to the end of external and internal rotation. Shoulders with grade III translation showed anterior translation in a wider range of rotation, especially in external rotation. These data will help to further our understanding of the management and the prevention of anterior shoulder dislocations.


Chronic upper airway and systemic inflammation from copier emitted particles in healthy operators at six Singaporean workplaces.
Toner-based printing equipment (TPE), including laser printers and photocopiers, utilize several engineered nanomaterials (ENMs) to improve toner performance. Operation of TPE, which rarely employ any exposure controls, generates high exposures to nanoparticles that contain ENMs and complex organics. Epidemiological literature in copier operators documents respiratory effects, including nasal blockage, cough, excessive sputum, and breathing difficulties, cardiovascular effects, oxidative stress, and inflammation. However, epidemiological studies in humans with adequate exposure assessment and dose-response analysis are lacking. We present herein the analysis of the upper airway and systemic inflammation in plasma of 19 healthy copier operators at six Singapore workplaces. We employed a repeated panel design (four biomarker measurements over two weeks) combined with a multi-marker approach (14 inflammatory cytokines in plasma and nasal lavage (NL)), and comprehensive exposure assessment using four distinct exposure metrics. We investigated spatial and temporal patterns of markers of upper airway and systemic inflammation and their association with various exposure metrics. Several inflammatory markers, namely fractalkine, IL-1β, and IL-1α in NL, and fractalkine, IL-1β, TNF-α, and IFN-γ in plasma, were strongly and positively associated with at least one exposure metric, whereas GM-CSF was negatively associated. The inflammation score was also strongly associated with TPE nanoparticle exposures. Exposure to TPE emissions induced moderate upper airway inflammation and stronger systemic inflammation in these healthy operators, characterized by upregulation of at least IL-1β, fractalkine, TNF-α and IFN-γ. Proinflammatory cytokines TNF-α, IFN-γ and IL-1β play an important role in orchestrating inflammatory responses in various clinical conditions, including cardiovascular and autoimmune disease, and likely trigger activation of endothelial cells, leading to overexpression of fractalkine, a chemokine that is involved in and associated with multiple disorders, including atherosclerosis and vascular disease. Future larger-scale epidemiological studies in these workers and consumers exposed chronically to TPE nanoparticle emissions and proactive interventions to reduce or eliminate TPE exposures are recommended.


The prospects of African yam bean: past and future importance.
African yam bean (AYB) is an underutilised legume indigenous to West and East Africa with nutritional content comparable to other commonly consumed legumes. The nutrient density of the crop makes it a viable food crop for ameliorating the challenges of malnutrition faced in many developing countries, via direct consumption or fortification and enrichment of less nutritious staples. This review summarises the current body of knowledge on the use of African yam bean as a viable enrichment and fortification crop. Proximate composition and nutritional quality of foods (breakfast diets, traditional foods, snacks and instant noodles) fortified, enriched and complemented with AYB were discussed. The phytochemical and antioxidant potential of the crop were also discussed. Future studies should focus more on awareness towards the deliberate commercialisation of the crop and elevation of its status into a widely - consumed food in all households across developing countries. Adequate experimental design for optimum quantity to be used in the enrichment and fortification of many staples to improve their acceptance among consumers should be put in place. Phytochemical extracts of the bean are also proposed for use in the development of functional foods to mitigate against many lifestyle diseases.


Effects of secondary structures in RNA on interlocking probabilities.
In 1967 Wang and Schwartz reported on the formation of interlocked rings between linear or circular DNA molecules by the enzyme topoisomerase. We propose viewing the secondary structured loop in RNA (or single stranded DNA) as analogous to a circular DNA molecule. Formation of a catenane between such an RNA loop with a DNA molecule may constitute a probe of the secondary and general three dimensional structure of the RNA molecule. The experimental results may be compared with the theoretical calculation. We suggest here a method for estimating linkage probabilities and calculate them for several cases for which secondary structures of the RNA have been proposed.


Chemical probes for profiling fatty acid-associated proteins in living cells.
Chemical probes appended with reactive electrophiles afford powerful tools for profiling discrete protein families in living cells. Herein, we have synthesized cell-permeable chemical probes that target fatty acid-associated proteins. These fatty acid-based chemical probes contain acyloxymethylketone or fluorophosphonate functional groups and an alkyne click chemistry tag for visualization of covalently modified proteins by in-gel fluorescence scanning. Our fatty acid-based chemical probe affords new tools to evaluate the activity/expression of lipid-associated proteins that should facilitate their functional characterization and inhibitor discovery.


Incidence of para-aortic and pelvic lymph node metastases in epithelial carcinoma of the ovary.
In patients with ovarian carcinoma, the presence of metastatic disease in a retroperitoneal lymph node is indicative of a poor prognosis. Although a "staging laparotomy" is required for proper treatment, definitive information concerning para-aortic and pelvic lymph node metastasis often is not available. To determine the incidence of retroperitoneal lymph node metastases in untreated cases of ovarian carcinoma, a prospective study by selective nodal biopsy was undertaken in 61 unselected patients with the following distribution: Stage I, 11; Stage II, 10; Stage III, 31; and Stage IV, 9. The incidence of para-aortic node metastasis overall was 37.7% and of pelvic node metastasis, 14.8%. Of 23 patients with positive para-aortic nodes, 30.4% had no concomitant pelvic node involvement. Direct relationships between nodal metastasis and clinical stage, tumor grade, and histologic type of tumor were demonstrated. The incidence of positive para-aortic nodes in Stage I disease was 18.2%; in Stage II, 20.0%; in Stage III, 41.9%; and in Stage IV, 66.7%. The corresponding incidence of pelvic node metastasis was 9.1% in Stage I, 10.0% in Stage II, 12.9% in Stage III, and 33.3% in Stage IV. Grade 3 tumors were associated most frequently with nodal involvement, with an incidence of positive para-aortic nodes of 52.5% and of positive pelvic nodes of 15.5%. In patients with a serous type of malignancy, the frequencies of positive para-aortic/pelvic nodes were 44.4%/16.7%, respectively; in the undifferentiated type, 50.0%/10.0%; in the clear cell type, 25.0%/25.0%; and in the mucinous type, 14.3%/14.3%. In this small series, 32 patients (52.5%) had positive retroperitoneal nodal involvement. It is concluded that selective biopsies of the para-aortic and pelvic lymph nodes should be part of any "staging laparotomy" for ovarian carcinoma, and that the true incidence of nodal involvement in these patients awaits further investigation.


Granular cells in the connective tissue of Helix pomatia L. (gastropoda, pulmonata). Histochemistry, ultrastructure, and results of polyacrylamide electrophoretic investigations.
Granular cells (cells crowded with colourless granules staining with paraldehyde fuchsin according to Gomori-Gabe and not containing calcium) are independent cells in the connective tissue of Helix pomatia. Histochemical data suggest that the granules are rich in sulfhydryl-containing proteins, but lack biogenic monoamines. Electron microscopic investigations confirm the supposed secretory activity of the granular cells. Secretory proteins are presumed to be synthetized in the endoplasmic reticulum and condensed in the Golgi apparatus giving rise to the granules. Extrusion occurs by exocytosis. Electrophoresis of homogenates, prepared from tissues containing numerous granular cells, results in the separation and identification of a secretory protein from the granular cells. An electrophoretically homologous protein is recognized in the hemolymph, but in very small quantities. Our findings and the work of others suggest the involvement of granular cells in neuroendocrine events.


A community-based lung cancer rapid tissue donation protocol provides high-quality drug-resistant specimens for proteogenomic analyses.
For the advancement of cancer research, the collection of tissue specimens from drug-resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post-therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment-resistant lung cancers. Consent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non-tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin-fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD-L1) clones. Next-generation sequencing was performed on 13 specimens from 5 patients. Postmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD-L1 IHC revealed heterogeneity within and between tumors. An AGK-BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule-associated protein-like 4 to anaplastic lymphoma kinase (EML4-ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells. Post-therapy specimens demonstrated PD-L1 heterogeneity and an acyl glycerol kinase to B-rapidly accelerated fibrosarcoma (AGK-BRAF) fusion in a patient with an EML4-ALK-positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance.


Responses of substantia nigra pars reticulata neurons to GABA and SKF 38393 in 6-hydroxydopamine-lesioned rats are differentially affected by continuous and intermittent levodopa administration.
Systemic administration of the selective D1 agonist, SKF 38393, to rats with unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine pathway induces contralateral turning and reduces firing rates of substantia nigra pars reticulata neurons. Previous studies have shown that chronically administered levodopa diminishes the contralateral turning induced by SKF 38393 in these animals. The present study demonstrates that twice daily injections (45-50 mg/kg, i.p.) of levodopa for 19 days also diminishes the effects of SKF 38393 on substantia nigra pars reticulata activity. Concomitant with this change, chronic levodopa injections reversed the lesion-induced supersensitivity of substantia nigra pars reticulata neurons to iontophoresed GABA. Neither of these effects were produced by the continuous infusion of levodopa (90-100 mg/kg/day, i.p. by osmotic pump) for 19 days, a treatment that produces average daily blood levodopa levels similar to those produced by chronic levodopa injection. These results suggest that large variations in circulating levodopa levels in 6-hydroxydopamine lesioned rats may desensitize the behavioral responses to D1 dopamine agonist administration by down-regulating D1 and GABA receptor-mediated mechanisms of basal ganglia output through the substantia nigra pars reticulata.


Abnormal cognitive network interactions in Lennox-Gastaut syndrome: A potential mechanism of epileptic encephalopathy.
In patients with Lennox-Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI), we recently showed that epileptiform discharges in LGS recruit large-scale networks that normally support key cognitive processes. In LGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions in LGS are persistently abnormal. We studied 15 LGS patients (mean age ± 1 standard deviation [SD] = 28.7 ± 10.6 years) and 17 healthy controls (mean age ± 1 SD = 27.6 ± 6.6 years) using task-free EEG-fMRI. Four networks of interest (default-mode, dorsal attention, executive control, and anterior salience) were defined using group-level independent components analysis (ICA). Functional connectivity within and between networks was determined for each subject, and then LGS network interactions were compared to network behavior in the control group. To test whether group differences were present in periods without scalp-detectable epileptiform discharges (i.e., persistent), we separately assessed discharge-affected and discharge-unaffected epochs in six patients with sufficient data for this analysis. In LGS, cognitive networks showed (1) reduced within-network integration, including weaker connectivity within the default-mode network, and (2) impaired between-network segregation, including stronger connectivity between the default-mode and dorsal attention networks. Abnormal interactions were present during fMRI periods with and without discharges, indicating that impaired network behavior may endure during periods without scalp-detectable epileptic activity. In LGS, cognitive network interactions are persistently abnormal. Given that cognition typically worsens with the onset of LGS, and may improve after seizure control, our findings are consistent with the hypothesis that the epileptic process in LGS may initiate and perhaps sustain abnormal network behavior. We propose that epileptic encephalopathy may be a consequence of persistently disrupted cognitive network interactions.


Expression of ER stress markers (GRP78/BiP and PERK) in adenoid cystic carcinoma.
A high GRP78/BiP expression was proved to be a significant marker for predicting poor outcome after surgery. GRP78/BiP may be a promising molecular target for treatment of ACC. The glucose-regulated protein GRP78/BiP plays a crucial role in the endoplasmic reticulum (ER) stress. The level of GRP78 is highly elevated in various human cancers, but the clinicopathological significance of GRP78/BiP remains controversial in patients with adenoid cystic carcinoma (ACC). A total of 26 ACC patients were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP, PERK, Ki-67, and microvessel density (MVD) determined by CD34. GRP78/BiP and PERK were highly expressed in 58% (15/26) and 35% (9/26), respectively. The high expression of GRP78/BiP was significantly associated with PERK, cell proliferation and angiogenesis.


The contribution of the contralateral labyrinth to second order vestibular neuronal activity in the cat.
Vestibular brain stem units of the horizontal canal in the awake C1 transected cat were examined in acute experiments before and after the contralateral vestibular nerve was cut. The latter procedure resulted in an immediate increase in mean resting rate from 19 to 45 spikes/sec and greater spontaneous fluctuations in firing rate. Mean sensitivity to constant accelerations from 2 to 16 degrees/sec2 was significantly reduced. In the 4-6 degrees/sec2 range, for example, mean sensitivity fell from 5.7 +/- 3.2 spike/sec/deg/sec2 (range 0.7-13.6, n = 107) to 2.8 +/- 1.4 (range 0.2-5.5, n = 29). Mean sensitivity to 4-6 degrees/sec2 deceleration was reduced from about 4.5 to 3.0. On the other hand, time constants and the ratio of adapting to non-adapting units was unchanged. Removal of the midline cerebellum, including the vermis and fastigial nuclei in a portion of the animals, did not materially alter the above results. It is concluded that the contralateral labyrinth, acting via the vestibular brain stem commissural pathway, not only exerts a powerful effect on the resting activity of brain stem canal vestibular neurons, but also on their response to acceleration.


Irregular patterns of actin and myosin filaments in human skeletal muscle cells.
The ultrastructural study of cross sections of normal skeletal muscle cells showed the existence of irregular patterns of actin filaments in connection with the hexagonal pattern of the myosin filaments. The actin filaments surrounding each myosin filament vary in number from 6 to 11. The most frequent relationship is 9 to 1, followed by 10 to 1 and 8 to 1. The hexagonal pattern of actin filaments was observed only in the 6 to 1 arrays; as the actin filaments increase in number, they tend to form different polygons or circles around the myosin filaments. All described patterns may occur in each sarcomere. The actin to myosin filament ratio varies from 3 to 4 within each individual myofibril. The described variability of the actin filaments arrays leads to several difficulties in an explanation of the mechanism of muscular contraction.


Obesity Determines the Immunophenotypic Profile and Functional Characteristics of Human Mesenchymal Stem Cells From Adipose Tissue.
Adipose tissue is a major source of mesenchymal stem cells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs. We also hypothesized that persistent hypoxia treatment of cultured hASCs may be necessary but not sufficient to drive significant changes in mature adipocytes. hASCs were obtained from subcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n=8; body mass index [BMI]: 23±1 kg/m2) and obese (n=8; BMI: 35±5 kg/m2). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor's BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Therefore, obesity is an important determinant of stem cell function independent of oxygen tension. The obesity-related hypoxic environment may have latent effects on human adipose tissue-derived mesenchymal stem cells (hASCs) with potential consequences in mature cells. This study explores the immunophenotypic profile of hASCs obtained from lean and obese individuals and its potential relationship with the altered plasticity of hASCs observed in obesity. In this context, an altered pattern of cell surface marker expression in obese-derived hASCs in both undifferentiated and differentiated stages is demonstrated. Differences in proliferation, migration, and differentiation capacity of hASCs from obese adipose tissue correlated with alterations in cell surface expression. Remarkably, altered plasticity observed in obese-derived hASCs was maintained in the absence of hypoxia, suggesting that these cells might be obesity conditioned.


Pyrene-conjugated hyaluronan facilitated exfoliation and stabilisation of low dimensional nanomaterials in water.
Pyrene-conjugated hyaluronan (Py-HA) facilitates the exfoliation of low-dimensional nanomaterials including graphite, hexagonal boron nitride (h-BN) and molybdenum disulfide (MoS2), and the dispersion of carbon nanotubes (CNTs) and carbon nano-onions (CNOs) in water (and PBS solutions), with the assistance of sonication.


Normocalcaemic pseudohypoparathyroidism with unusual phenotype.
We describe a boy who presented at 4 years of age with radiological hyperparathyroidism, osteosclerosis, and necrosis of the femoral heads. Plasma biochemistry was normal but the parathyroid hormone (PTH) level was very high. He was deaf and had an unusual facies but did not have the phenotype of Albright's hereditary osteodystrophy. Plasma and urine cyclic AMP reponses to bovine PTH were markedly subnormal. Vitamin D produced sustained hypercalcaemia and a fall in plasma phosphorus. After four hyperplastic parathyroid glands were removed he became hypocalcaemic and plasma phosphorus rose. After operation he remained unresponsive to exogenous PTH; We suggest that he had a form of pseudohypoparathyroidism without the phenotype of Albright's hereditary osteodystrophy and with some residual skeletal and renal responsiveness to PTH.


Validity of ocular trauma score in open globe injury patients from Turkey.
To determine the efficacy of ocular trauma score (OTS) in determining the prognosis in patients with open globe injury who admitted to our clinic. Data of patients with open globe injury who were admitted to our clinic between 2014 and 2016 were retrospectively analyzed. The OTS raw score of each patient was determined and translated into OTS categories according to OTS study. Prognostic results of OTS study and current study was compared with chi square analysis. In our study, 101 eyes of 101 patients were examined. The mean age of the patients was 27.08±15.36 years. The mean follow-up period was 12.84±9.04 months. In total, 86 of the cases were male (85.1%). In our study, the mean initial visual acuity of the patients was 0.10±0.23. In 64.3% of the cases, IVA was at hand movement level or lower. IVA was found to be≥20/40 in 10.9%. The mean FVA was 0.38±0.37. In total, 41.6% of the cases had a FVA≥20/40. In 28.7% of these cases, FVA was at hand movement level or lower. While no significant difference was found in patients with OTS3, OTS 4 and OTS 5 (P>0.05), prognosis of patients with OTS 1 and OTS 2 was better than OTS study (P<0.001) CONCLUSION: Although OTS can be effective and safe data in terms of prognosis, it can be improved with more comprehensive studies.


Ionic liquids in soils: effects of different anion species of imidazolium based ionic liquids on wheat (Triticum aestivum) as affected by different clay minerals and clay concentrations.
This study contributes to a prospective hazard assessment of ionic liquids, focusing on the terrestrial environment. The influence of differently composed soils-varying contents of the clay minerals smectite and kaolinite-on the toxicity of different anion species of imidazolium based ionic liquids was studied for growth inhibition of wheat (Triticum aestivum). IM14 (CF(3)SO(2))(2)N appeared the most toxic, independently of the investigated soil type. The toxicity of IM14 Cl, IM14 BF(4) and IM14 HSO(4) was mainly dominated by the cationic moiety. The observed effects varied in dependence of the added clay type and clay concentration. An increase of clay content resulted in less pronounced effects of these substances. In contrast, for IM14 (CF(3)SO(2))(2)N the addition of clay minerals caused higher toxic effects in comparison to the reference soil. Our results give first hints for the assumption, that ionic liquids whose toxic action is based on the anionic moiety are especially hazardous for soils, particular for soils with high clay contents.


Ultraviolet laser ablation of skin: healing studies and a thermal model.
We have followed the course of healing of incisions made with the krypton-fluoride excimer laser. Incisions were made in guinea pig skin, in vivo, under identical conditions of irradiation. The progressive healing of these incisions was followed over the course of 3 weeks. We noted excellent healing with re-epithelialization, and the re-formation of collagen fibers with minimal fibrosis. We present a simple thermal model for ablation of tissue by a short pulse of strongly absorbed laser radiation.


In vitro gene transfer by electrosonoporation.
Among the nonviral methods for gene delivery in vitro, electroporation is simple, inexpensive and safe. To upregulate the expression level of transfected gene, we investigated the applicability of electrosonoporation. This approach consists of a combination of electric pulses and ultrasound assisted with gas microbubbles. Cells were first electroporated with plasmid DNA encoding-enhanced green fluorescent protein and then sonoporated in presence of contrast microbubbles. Twenty-four hours later, cells that received electrosonoporation demonstrated a four-fold increase in transfection level and a six-fold increase in transfection efficiency compared with cells having undergone electroporation alone. Although electroporation induced the formation of DNA aggregates into the cell membrane, sonoporation induced its direct propulsion into the cytoplasm. Sonoporation can improve the transfer of electro-induced DNA aggregates by allowing its free and rapid entrance into the cells. These results demonstrated that in vitro gene transfer by electrosonoporation could provide a new potent method for gene transfer.


Quantitative real time PCR detection of Saboya virus: A flavivirus member of yellow fever genetic group.
The genus Flavivirus in the Flaviridae contains arthropod born viruses associated with high public health burdens like Zika, Dengue or Yellow fever. Saboya virus (SABV) is an understudied flavivirus grouping in the same genetic sub-group as Yellow Fever Virus (YFV) together with Sepik virus (SEPV) and Wesselbron virus (WSLV). Flavivirus infections are characterized by non-specific clinical presentations resulting in a high risk of misdiagnosis. SABV virus has been shown to circulate in the Sahelian zone and in central Africa. To study this virus we a qRT-PCR system based on TaqMan chemistry was developed to allow rapid and specific detection of SABV. The SABV assay was evaluated on available SABV isolates and others flaviviruses (DENV, ZIKV, YFV, WNV, KEDV). The system reliably detected all used SABV strains without cross amplification of other flaviviruses. In term of sensitivity the SABV assay detect up to 40.25 copies of SABV standard DNA molecule per ul. This system can be easily added to the available panel of arboviruses detection assays as a reliable tool to study virus prevalence in human, vertebrate and insect-vector samples.


In vitro inhibition of RecA-mediated homologous pairing by UmuD'C proteins.
The process of SOS mutagenesis in Escherichia coli requires: i) the replisome enzymes; ii) RecA protein; and iii) the formation of the UmuD'C protein complex which appears to help the replisome to resume DNA synthesis across a lesion. It has recently been shown that the UmuD'C complex, if overproduced, inhibits recombinational repair of a UV-damaged plasmid DNA as well as homologous recombination in an Hfr x F- cross. Since UmuD'C proteins might inhibit an early recombination step by interacting with a RecA nucleo-protein filament, we checked whether UmuD'C proteins will inhibit RecA promoted homologous pairing in vitro. We tested the inhibitory action of UmuD'C proteins in a crude bacterial extract containing possible cofactors such as chaperone proteins that ensure the proper folding of UmuC and the assembly of the UmuD'C complex in vivo. We used a novel recombination assay in which RecA protein promotes the formation of a stable plectonemic joint between a circular single-stranded DNA immobilized onto a membrane and an incoming homologous linear duplex DNA. Under these conditions we show that UmuD'C proteins inhibit the formation of joint molecules.


Prevalence of mental distress and associated factors among caregivers of patients with severe mental illness in the outpatient unit of Amanuel Hospital, Addis Ababa, Ethiopia, 2013: Cross-sectional study.
Caregivers like family members or other relatives are central and provide not only practical help and personal care but also give emotional support, and they are suffering from plenty of challengeable tasks. These, eventually, cast out family caregivers into multidimensional problems prominently for mental distress like depression, anxiety, sleep problem and somatic disorder which are followed by physiologic changes and impaired health habits that ultimately lead to illness and possibly to death. Numerous studies demonstrate that mental distress of caregivers are two times compared to general populations. Despite it was not uncommon to observe manifestations of caregivers' mental distress, yet there was no study on this area. Therefore, this study was intended to assess the prevalence of mental distress and associated factors among the caregivers of persons with severe mental illness in the out patients unit of Amanuel Hospital, Ethiopia. Institutional based cross sectional study was conducted from May 1 to 31, 2013 at Amanuel Hospital, Addis Ababa, Ethiopia. Systematic random sampling technique with "k" interval of 13 was employed to withdraw a total of 423 participants from study population. Five psychiatric nurses carried out interview by using standardized and validated Self Reported Questionnaire (SRQ 20). Descriptive statistics, binary and multivariate logistic regression analysis were conducted. This study revealed that the overall prevalence of mental distress was found to be 221(56.7 %). The factors like missed social support, two or more times admission of patient, care giving for psychotic patient, being farmer and being female were found to be predictors for mental distress of caregivers with this [AOR 95 % CI = 9.523(5.002, 18.132)], 3.293(1.474, 3.3560), 2.007(1.109, 3.634), 2.245(1.129, 4.463) and 3.170(1.843, 5.454)] respectively. In this respect the study observed that there was a higher level of mental distress experienced by caregivers of patients with severe mental illness in Amanuel Hospital, and social support are strongly associated with mental distress besides to other variables. Effectively planned interventions have to be targeted at alleviating mental distress and actions like on-going psycho-education and mutual support that could expand social support should be implemented in Amanuel hospital health service delivery system.


Considerations on chemical composition of psammoma bodies: Automated detection strategy by infrared microspectroscopy in ovarian and thyroid cancer tissues.
Ectopic calcifications are observed in many soft tissues and are associated with several diseases, including cancer. The mechanism of their formation and the correlation with disease progression are often unclear. Detailed knowledge of the chemical composition of these inorganic formations can be very helpful in better understanding their relationship with unhealthy tissue. In addition, information on microcalcifications can be very useful for early diagnosis and provide insight into prognosis. In this work the chemical composition of psammoma bodies (PBs) found in tissues of human ovarian serous tumors was examined. The analysis using Micro Fourier Transform Infrared Spectroscopy (micro-FTIR) revealed that these microcalcifications contain amorphous calcium carbonate phosphate. Moreover, some PB grains showed the presence of phospholipids. This interesting result corroborates the proposed formation mechanism reported in many studies according to which ovarian cancer cells switch to a calcifying phenotype by inducing the deposition of calcifications. In addition, other techniques as X-ray Fluorescence Spectroscopy (XRF), Inductively Coupled Plasma Optical Emission Spectroscopy(ICP-OES) and Scanning electron microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDX) were performed on the PBs from ovary tissues to determine the elements present. The PBs found in ovarian serous cancer showed a composition comparable to PBs isolated from papillary thyroid. Based on the chemical similarity of IR spectra, using micro-FTIR spectroscopy combined with multivariate analysis, an automatic recognition method was constructed. With this prediction model it was possible to identify PBs microcalcifications in tissues of both ovarian cancers, regardless of tumor grade, and thyroid cancer with high sensitivity. Such approach could become a valuable tool for routine macrocalcification detection because it eliminates sample staining, and the subjectivity of conventional histopathological analysis.


DNA methylation signatures of early life adversity are exposure-dependent in wild baboons.
The early life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits.


[Doctor Google: use of Internet during pregnancy in France in 2009].
To determine the profile of pregnant women who use Internet during pregnancy as well as their motivations. We conducted a transversal prospective survey with questionnaires distributed to women during pregnancy and in the postpartum period in a regional hospital in the Yvelines from July 13th to November 28th, 2009. The same questionnaire was posted for pregnant women on Internet websites and forums dedicated to pregnancy from October 1st, 2009 to January 6th, 2010. Qualitative variables were compared by Chi(2) or Fisher tests. We obtained 791 answers, with 83 and 97% using Internet during pregnancy in the hospital and on-line population respectively. Their motivations to use Internet are the easy access (85% of the population, n=606) and the anonymity afforded by this media (49.1%, n=351). The profile of the patient using Internet was: primiparous, less than 35 years, higher education and having a profession. The most popular information searched was on the delivery (49.1%). The population using Internet during pregnancy seems homogeneous and represented by young, educated, and working women.


Application values of prenatal screening and non-invasive gene sequencing in fetal birth defects.
To investigate effects of prenatal screening and non-invasive gene sequencing on the clinical diagnosis of fetal birth defects and the outcome of pregnancy. Totally 2520 pregnant women who received prenatal screening in our hospital were selected as the research subjects. The high-risk pregnant women were further tested by the non-invasive gene sequencing technology. Pregnant women with positive results were diagnosed by amniocentesis and fetal chromosome karyotype analysis, and the pregnancy outcome was followed up for one year. 870 out of the 2520 pregnant women was tested by non-invasive gene sequencing technology; 26 of the 870 women was 13-trisomy-positive and was diagnosed by amniocentesis and fetal chromosome karyotype analysis, 22 of which was diagnosed as 47, XN, +13 and four of which was normal; the diagnosis accuracy of non-invasive prenatal testing (NIPT) was 84.6%. 18 out of the 22 confirmed cases underwent abortion, three cases had termination of embryonic development, and one case had postnatal anomaly. Thirty four out of the 2520 pregnant women was 18-trisomy-positive and was diagnosed by amniocentesis and fetal chromosome karyotype analysis, 31 of which was diagnosed as 47, XN, +18 and three cases were normal; the diagnosis accuracy of NIPT was 91.2%. 29 out of the 31 confirmed cases underwent abortion and two cases had termination of embryonic development. Forty out of the 2520 pregnant women was 21-trisomy-positive and was diagnosed by amniocentesis and fetal chromosome karyotype analysis, 39 of which was diagnosed as 47, XN, +21 and one case was normal; the diagnosis accuracy of NIPT was 97.5%. Thirty four out of the 39 confirmed cases underwent abortion, three cases had termination of embryonic development, and two cases had postnatal anomaly. Twenty eight cases were tested as sex chromosome-positive and were diagnosed by amniocentesis and fetal chromosome karyotype analysis, 25 out of which was diagnosed as abnormal and three cases were normal; the diagnosis accuracy of NIPT was 89.3%. 24 out of the 25 confirmed cases underwent abortion, and one case had termination of embryonic development. Prenatal screening and non-invasive gene sequencing technology have a high accuracy in the diagnosis of fetal birth defects, which can reduce the maternal abortion injury as much as possible and relieve the psychological pressure. The promotion of the mode can be strengthened in clinics.


A case of a vaginal Brenner tumor without a gland mimicking a borderline tumor: unusual morphology and diagnostic pitfalls.
Brenner tumor is a rare neoplasm of the vagina. This tumor is diagnosed according to the criteria of ovarian tumors. We report here a 64-year-old postmenopausal woman with a 2.0-cm sessile vaginal polyp for 9 years. Microscopic examination showed unusual features of no gland appearing in the tumor, but the other two characteristic components of transitional islands and dense fibrous stroma were observed. The tumor was diagnosed as a vaginal Brenner tumor on the basis of the definition proposed by the World Health Organization classification of female reproductive organ tumors. In our case, part of the epithelial nests of the Brenner tumor showed basaloid cell differentiation with peripheral palisading, and irregular papillary hyperplasia was observed around the epithelial nests similar to a borderline tumor. However, no mitotic activity or nuclear atypia was present in either the epithelial or stromal components. The presence of epithelial nests requires attention in the medical history of the patient. Our patient did not have a history of primary urothelial carcinoma. Our patient's benign vaginal Brenner tumor with different morphological characteristics supports the current notion that Walthard nests might act as possible precursor lesions.


Rapid Adaptation to the Timbre of Natural Sounds.
Timbre, the unique quality of a sound that points to its source, allows us to quickly identify a loved one's voice in a crowd and distinguish a buzzy, bright trumpet from a warm cello. Despite its importance for perceiving the richness of auditory objects, timbre is a relatively poorly understood feature of sounds. Here we demonstrate for the first time that listeners adapt to the timbre of a wide variety of natural sounds. For each of several sound classes, participants were repeatedly exposed to two sounds (e.g., clarinet and oboe, male and female voice) that formed the endpoints of a morphed continuum. Adaptation to timbre resulted in consistent perceptual aftereffects, such that hearing sound A significantly altered perception of a neutral morph between A and B, making it sound more like B. Furthermore, these aftereffects were robust to moderate pitch changes, suggesting that adaptation to timbral features used for object identification drives these effects, analogous to face adaptation in vision.


The emergence of a collective sensory response threshold in ant colonies.
SignificanceIn this study, we ask how ant colonies integrate information about the external environment with internal state parameters to produce adaptive, system-level responses. First, we show that colonies collectively evacuate the nest when the ground temperature becomes too warm. The threshold temperature for this response is a function of colony size, with larger colonies evacuating the nest at higher temperatures. The underlying dynamics can thus be interpreted as a decision-making process that takes both temperature (external environment) and colony size (internal state) into account. Using mathematical modeling, we show that these dynamics can emerge from a balance between local excitatory and global inhibitory forces acting between the ants. Our findings in ants parallel other complex biological systems like neural circuits.


Using game format in small group classes for pharmacotherapeutics case studies.
To incorporate games in classroom teaching to encourage student interest and participation in a small group pharmacy therapeutics case studies class. Using a television quiz show and classic board game format, students and the instructor developed games to discuss patient care plans. At the end of the course, a questionnaire was administered to assess students' attitudes and perception of using game format in the class and whether this teaching method was useful in reinforcing therapeutic knowledge. The majority of the students felt that games were beneficial in their learning process. The game format also resulted in higher student participation scores. The game-format approach to learning aroused student interest, enhanced participation, and improved their participation grades. Although the game format of leaning is an effective way of actively engaging students in higher leaning, determining how these games improve test scores will require further assessment.


Daily tympanometry in children during the cold season: association of otitis media with upper respiratory tract infections.
The causal association between otitis media and viral upper respiratory tract infections (URI) suggests that early intervention during the course of a viral URI could prevent many episodes of otitis media. However, the feasibility of this approach can not be assessed at present since many aspects of the epidemiology and natural history of URI-associated otitis media are undefined. To address this deficiency, daily monitoring of middle ear status (tympanometry) and cold symptoms and weekly pneumatic otoscopy were done on a pilot cohort of 20 children. These children, between the ages of 2 and 6, were followed from November 1996 to April 1997. Compliance with symptom diaries was 85%, with tympanograms was 90%, and with weekly physician visits was 70%. During the study period, there were 53 'colds' (average 2.65 per child) and 28 new episodes of middle ear effusion (10 unilateral and 9 bilateral). Overall, 47.3% of the tympanograms were Type A, 17.2% Type C1, 9.4% Type C2, and 21.8% Type B. Children who developed MEE during the study spent more time with abnormal MEP (either MEP < -150 or flat) during both cold and healthy days than children who did not develop MEE. Temporally, during colds, high negative pressures preceded the development of Type B tympanograms in children who developed middle ear effusions. Children who did not develop effusions still had high negative pressures during colds, but recovered to a normal pressure within days. These observations document the feasibility of this investigational format for study of the sequential changes in middle ear status before, during and after a URI.


Interankle systolic blood pressure difference and renal outcomes in patients with chronic kidney disease.
Interankle blood pressure (BP) difference has been associated with peripheral artery disease and adverse cardiovascular outcomes. However, the relationship between interankle BP difference and renal outcomes in chronic kidney disease (CKD) has never been evaluated. The purpose of this study was to determine whether interankle BP difference is associated with the rate of renal function decline and progression to renal end points in patients with stage 3-5 CKD. We enrolled 144 patients with CKD from one regional hospital. The BP in four limbs was simultaneously measured using an ABI-form device. The decline in renal function was evaluated using an estimated glomerular filtration rate (eGFR) slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min per 1.73 m(2) per year. The renal end points were defined as ≥ 25% decline in eGFR or commencement of dialysis during the follow-up period. During a mean follow-up period of 3.1 years, 90 patients (62.5%) reached renal end points. Multivariate analysis showed that an increased interankle systolic BP difference (per 5 mmHg) was associated with a worse eGFR slope (regression β, -0.292; 95% confidence interval [CI], -0.482 to -0.102; P = 0.003), rapid renal progression (odds ratio, 1.189; 95% CI, 1.015-1.394; P = 0.032), and an increased risk of progression to renal end points (hazard ratio, 1.126; 95% CI, 1.052-1.204, P = 0.001). Interankle systolic BP difference was associated with rapid renal progression and progression to renal end points in patients with stage 3-5 CKD in our study.


Triage body temperature and its influence on patients with acute myocardial infarction.
Fever can occur after acute myocardial infarction (MI). The influence of body temperature (BT) after hospital arrival on patients with acute MI has rarely been investigated. Patients who were diagnosed with acute MI in the emergency department (ED) of a tertiary teaching hospital between 1 January 2020 and 31 December 2020 were enrolled. Based on the tympanic temperature obtained at the ED triage, patients were categorized into normothermic (35.5°C-37.5°C), hypothermic (< 35.5°C), or hyperthermic (> 37.5°C) groups. The primary outcome was in-hospital cardiac arrest (IHCA), while the secondary outcomes were adverse events. Statistical significance was set at p < 0.05. There were 440 enrollees; significant differences were found among the normothermic (n = 369, 83.9%), hypothermic (n = 27, 6.1%), and hyperthermic (n = 44, 10.0%) groups in the triage respiratory rate (median [IQR]) (20.0 [4.0] cycles/min versus 20.0 [4.0] versus 20.0 [7.5], p = 0.009), triage heart rate (88.0 [29.0] beats/min versus 82.0 [28.0] versus 102.5 [30.5], p < 0.001), presence of ST-elevation MI (42.0% versus 66.7% versus 31.8%, p = 0.014), need for cardiac catheterization (87.3% versus 85.2% versus 72.7%, p = 0.034), initial troponin T level (165.9 [565.2] ng/L versus 49.1 [202.0] versus 318.8 [2002.0], p = 0.002), peak troponin T level (343.8 [1405.9] ng/L versus 218.7 [2318.2] versus 832.0 [2640.8], p = 0.003), length of ICU stay (2.0 [3.0] days versus 3.0 [8.0] versus 3.0 [9.5], p = 0.006), length of hospital stay (4.0 [4.5] days versus 6.0 [15.0] versus 10.5 [10.8], p < 0.001), and infection during hospitalization (19.8% versus 29.6% versus 63.6%, p < 0.001) but not in IHCA (7.6% versus 14.8% versus 11.4%, p = 0.323) or any adverse events (50.9% versus 48.1% versus 63.6%, p = 0.258). Multivariable analysis showed no significant association of triage BT with IHCA or any major complication. Triage BT did not show a significant association with IHCA or adverse events in patients with acute MI. However, triage BT could be associated with different clinical presentations and should warrant further investigation.


Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population.
We conducted a case-control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer's disease in Chinese Southern Han population. PCR-restriction fragment length polymorphism assay was performed to genotype rs75932628 in 279 cases with late onset Alzheimer's diseases patients and 346 control subjects in Shanghai and Nanjing. There was no rs75932628-T variant detected in our sample. However, APOEϵ4 was shown closely associated with the risk of Alzheimer's disease (Chi-square = 60·288, P = 0·000). Our study suggested that TREM2 (rs75932628-T) was rare in Chinese Han population. Further association studies with large samples are needed to further study the association of TREM2 with late-onset Alzheimer's disease.


FEMALE SEXUALITY, NATIONALISM AND LARGE GROUP IDENTITY.
Nationalist movements are emerging today everywhere in the world. Many of them display a high level of aggression and a negative attitude toward sexuality and especially female sexuality. Along with this, erotic fiction with a sadomasochistic orientation has achieved great success and has hundreds of millions of readers in the world. This collective fantasy allows some integration of aggression in sexual life while questioning liberal morality and its equality in gender roles and conservative morality and its idea of control over passion. Both phenomena may represent different responses to the appearance of a new female sexuality threatening the social structure we know.


Phobic dimensions--II. Cross-national confirmation of the multidimensional structure underlying the Mobility Inventory (MI).
In a previous study (Cox, Swinson, Kuch & Reichman, Behaviour Research and Therapy, 31, 427-431, 1993), factor analyses of the responses of 177 Canadian panic disorder with agoraphobia patients to the 'When Accompanied' and 'When Alone' scales of the Mobility Inventory (Chambless, Caputo, Jasin, Gracely & Williams, Behaviour Research and Therapy, 23, 35-44, 1985) revealed three factors in each case: Fears of (1) Public places; (2) Enclosed spaces; and (3) Open spaces. Using two distinct methods of factorial analysis, evidence was found for the cross-national generalizability of the factor model when the responses of Dutch members of a society for individuals suffering from an anxiety disorder (N = 213) were contrasted with the original Canadian findings. Inventory items were distributed in a non-overlapping fashion across the corresponding three subscales. Psychometric properties of the subscales were encouraging, although some difficulties emerged when attempts were made at distinguishing Fears of Enclosed spaces from Fears of Open spaces. This was because of their correlational configurations with other measures. Scores on all scales varied with socioeconomic status (SES); Ss in lower SES groups had significantly higher agoraphobic avoidance scores than their equivalents in higher SES groups. Results of higher-order analysis, which included several state and trait measures of psychological functioning in addition to the Mobility Inventory, revealed two orthogonal, second-order factors which were interpreted as Agoraphobia and Neuroticism/Negative Affect vs Positive Affect. Implications for further studies are briefly outlined.


Mesenchymal stem cells might be used to induce tolerance in heart transplantation.
Heart transplantation is the last treatment selection for end-stage heart diseases, but the side-effects of immunosuppressive agents and morbidity brought by lifelong immunosuppression still remains unavoidable. Mesenchymal stem cell (MSC) is one kind of adult pluripotent cell that not only can differentiate into cardiomyocytes but also maintain some unique immunomodulatory function. There were reports that MSCs could both in vitro and in vivo suppress alloreactive CD4(+) T cell which is mainly responsible for chronic rejection that leads to progressive graft vascular stenosis. We based our hypothesis on that MSC could escape recognition of alloreactive cells and would interact with important immune cells such as T cells, dendritic cells after cardiac transplantation to induce a cytokine profile shift in the Th1/Th2 balance toward the anti-inflammatory phenotype Th2. And then tolerance may be induced. Also it is conceivable that MSCs may differentiate toward cardiomyocyte in the specific microenvironment. Further work are necessary to verify if MSCs can protect heart graft from chronic rejection and its potential to be used as substitutes for classic immunosuppressants.


Determination of flunitrazepam in plasma by liquid chromatography.
A reversed-phase liquid chromatographic method has been used to determine flunitrazepam in plasma. Extraction was simple and there was no need to hydrolyse the drug. Separation was achieved on a 150 x 3.9 mm i.d. column packed with 4-microns Nova Pack C18 using a mobile phase of water-acetonitrile-triethylamine (700:300:4, v/v/v) (adjusted to pH 7.5 with orthophosphoric acid). The method was shown to be rapid and reliable with a lower limit of detection of 5 ng ml-1. Results are reported of simple experiments on the effects of temperature and light on the stability of flunitrazepam in plasma kept on the laboratory bench.


Left atrial function and scar after catheter ablation of atrial fibrillation.
Catheter ablation of atrial fibrillation (AF) involves extensive radiofrequency ablation (RFA) of the left atrium (LA) around the pulmonary veins. The effect of this therapy on LA function is not fully characterized. The purpose of this study was to determine whether catheter ablation of AF is associated with a change in LA function. LA and right atrial (RA) systolic function was assessed in 33 consecutive patients with paroxysmal or persistent AF referred for ablation using cardiovascular magnetic resonance (CMR) imaging. Steady-state free precession ECG cine CMR imaging was performed before and after (mean 48 days) AF ablation. All patients underwent circumferential pulmonary vein isolation using an 8-mm tip RFA catheter. High spatial resolution late gadolinium enhancement CMR images of LA scar were obtained in 16 patients. Maximum LA volume decreased by 15% (P <.001), and LA ejection fraction decreased by 14% (P <.001) after AF ablation. Maximum RA volume decreased by 13% (P = .018), but RA ejection fraction increased by 5% (P = .008). Mean LA scar volume was 8.1 +/- 3.7 mL. A linear correlation was observed between change in LA ejection fraction and scar volume (r = -0.75, P <.001). Catheter ablation of AF is associated with decreased LA size and reduced atrial systolic function. This change strongly correlates with the volume of LA scar. This finding may have implications for postprocedural thromboembolic risk and for procedures involving more extensive RFA.


Effect of isoprinosine on interleukin 1 and 2 production and on suppressor cell activity in pokeweed mitogen stimulated cultures of B and T cells.
Isoprinosine appeared to potentiate the production of interleukin 1 and interleukin 2 in cultures of lipopolysaccharide stimulated human monocytes and phytohemagglutinin stimulated cultures of blood mononuclear cells respectively at pharmacological drug levels. Administration of the drug in vivo was associated with increased activity of radiation sensitive suppressor T cell activity against immunoglobulin production in pokeweed mitogen stimulated cultures of B and T cells. Addition of isoprinosine to the latter cultures in vitro appeared to enhance immunoglobulin production consistent with inhibition of suppressor cell activity or stimulation of helper activity. It is not clear from these studies whether the contrasting effects of the drug in vitro and in vivo represent different actions of metabolites or alteration of the proportion of lymphocyte subsets in the circulation. Further studies are required to answer these questions and to determine whether the changes persist with long term administration of the drug.


Metallothionein isoform expression by breast cancer cells.
Expression of metallothionein (MT) isoforms by a human breast cancer cell line, PMC42, which retains many characteristics of normal breast epithelial cells and expresses functional estrogen receptors, was examined because it has been proposed that human breast cancer cells which are estrogen receptor positive can be differentiated from those which are estrogen receptor negative, by failure to express MT-1E [J.A. Friedline, S.H. Garrett, S. Somji, J.H. Todd, D. A. Sens, Differential expression of the MT-1E gene in estrogen-receptor positive and -negative breast cancer cell lines, Am. J. Pathol. 152 (1998) 23-27]. Using RT-PCR, PMC42 cells were found to transcribe genes for the MT isoforms IE, IX and 2A but not 1A or 1H. In order to examine which of the expressed isoforms might protect against metal toxicity, the cells were challenged with high concentrations of zinc and copper. Using competitive RT-PCR, cells resistant to 500 microM zinc showed 7+/-2 fold (SD, n=3) increases in expression of MT-1X and 6+/-3 fold increases in expression of MT-2A compared to control cells in normal media. For cells resistant to 250 microM copper the corresponding increases were 37+/-13 and 60+/-20 fold, whilst for control cells treated with 250 microM copper for only 6 h, increases were 10+/-3 and 6+/-3 fold. There was only a low level of expression of MT-1E in untreated cells and but a >120 fold increase in copper- resistant cells. Thus estrogen receptor positive cells cannot, in general, be differentiated from estrogen receptor negative cells by failure to express MT-1E, as suggested by Friedline et al. (1998). Increased expression of MT-1E, as well as MT-1X and MT-2A, protects against metal toxicity in PMC42 breast cancer cells.


Enterohepatic Migration of Fish Bone Resulting in Liver Abscess.
Liver abscess formation due to enterohepatic migration of a foreign body is extremely rare. Foreign body ingestion is generally an unconscious and painless event, thus complicating preoperative diagnosis in most patients. We report the case of a 61-year-old man who presented with secondary peritonitis from a ruptured hepatic abscess after an ingested fish bone migrated into the liver.


Stereoselective synthesis of functionalized gamma-amino esters: azetidinium salts and epoxy esters.
Addition of several lithium ester enolates to chiral 1-aminoalkyl chloromethyl ketones 1 affords enantiomerically pure 3-hydroxyazetidinium salts 3 or 3-(1'-aminoalkyl)-3,4-epoxy esters 4, depending on the reaction conditions. [reaction: see text]