Potentiation of the human GABA(A) receptor as a novel mode of action of lower-chlorinated non-dioxin-like PCBs.
PCBs are still ubiquitous pollutants despite the ban on their industrial and commercial use. To date, risk characterization and assessment of non-dioxin-like PCBs (NDL-PCBs), especially with respect to neurotoxicity, is hampered by a lack of data. Therefore, the effects of six common NDL congeners (PCB28, 52, 101, 138, 153 and 180) on human GABA(A) receptors, expressed in Xenopus oocytes, were investigated using the two-electrode voltage-clamp technique. When coapplied with GABA (at EC(20)), PCB28 and PCB52 concentration-dependently potentiate the GABA(A) receptor-mediated ion current. Though the LOEC for both PCB28 and PCB52 is 0.3 microM, PCB28 is more potent than PCB52 (maximum potentiation at 10 muM amounting to 98.3 +/- 12.5% and 25.5 +/- 1.4%, respectively). Importantly, coapplication of PCB28 (0.3 microM) and PCB52 (10 microM) resulted in an apparently additive potentiation of the GABA(A) response, whereas coapplication of PCB28 (0.3 microM) and PCB153 (10 microM) attenuated the PCB28-induced potentiation. The present results suggest that the potentiation of human GABA(A) receptor function is specific for lower-chlorinated NDL-PCBs and that higher molecular weight PCBs may attenuate this potentiation as a result of competitive binding to human GABA(A) receptors. Nonetheless, this novel mode of action could (partly) underlie the previously recognized NDL-PCB-induced neurobehavioral alterations.


A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates.
Azinphosmethyl (APM) is one of the most common insecticides used in fruit farming. The object of this paper is to develop a quick and practical test for assessing the risk for humans coming into contact with APM. It has been shown that the principal component of occupational and/or accidental exposure is through the skin (C. A. Franklin et al., 1981, J. Toxicol. Environ. Health 7, 715-731), but our approach is applicable to exposures via any route or a combination of routes. The method proposed in the present paper can accommodate a single-event exposure or repeated exposures over long periods. Urinary alkylphosphate (AP) metabolites are reliable bioindicators of the presence of APM in the body; they are easily accessible and can be used to estimate APM body burden. We developed a simple toxicokinetic model to link the time varying APM body burden to absorbed doses and to rates of elimination in the form of AP urinary metabolites. Using this model and data available in the literature, we are able to propose a "no observed adverse effect level" (NOAEL) for APM body levels and for corresponding absorbed doses. We have established that after a single exposure, the safe limit corresponding to the NOAEL is reached at a cumulative 0.215 mumoles AP/kg bw eliminated in urine in the first 24 hours following the beginning of exposure. For repeated daily exposures at steady state, the corresponding urinary AP metabolite level is equal to a cumulative 0.266 mumoles AP/kg bw eliminated per 24 hours.


Cognitive Outcome of Pediatric Moyamoya Disease.
Quality of life is the current trend and issue for the most of human diseases. In moyamoya disease (MMD), surgical revascularization has been recognized as the possible assistance to reduce the neurological insult. However, the progressive nature of the disease has been invincible so far. To improve the quality of life of MMD patients not only the protection from the neurological insult but also the maintenance or improvement of cognitive function is inevitable. For pediatric MMD patients, younger age or longer duration of disease is the key factor among the prognostic factors for bad neurological outcomes. Hence, 'the earlier, the better' is the most precious rule for treatment. Protection from neurological insult is very critical and foremost important to improve cognitive outcome. Clinicians need to know the neuropsychological profile of MMD patients for the care of whole person and make an effort to protect the patients from neurological insults to maintain or improve it.


Discerning temporal expectancy effects in script processing: evidence from pupillary and eye movement recordings.
Accessing the temporal position of events (early or late in the event sequence) can influence the generation of predictions about upcoming events. However, it is unclear how the temporal position is processed strategically. To investigate this, we presented event pairs to 23 healthy volunteers manipulating temporal order (chronological, inverse) and temporal position (early, late). Pupil dilation, eye movements, and behavioral data, showed that chronological and early event pairs are processed with more ease than inverse and late event pairs. Indexed by the pupillary response late events and inversely presented event pairs elicited greater cognitive processing demands than early events and chronologically presented event pairs. Regarding eye movements, fixation duration was less sensitive to temporal position than to temporal order. Looking at each item of the event sequence only once was behaviorally more effective than looking multiple times at each event regardless of whether temporal position or temporal order was processed. These results emphasize that accessing temporal position and temporal order information results in dissociable behavioral patterns. While more cognitive resources are necessary for processing late and inverse items, change of information acquisition strategies turns out to be most effective when temporal order processing is required.


An in-plane solid-liquid-solid growth mode for self-avoiding lateral silicon nanowires.
We report an in-plane solid-liquid-solid (IPSLS) mode for obtaining self-avoiding lateral silicon nanowires (SiNW) in a reacting-gas-free annealing process, where the growth of SiNWs is guided by liquid indium drops that transform the surrounding a-SiratioH matrix into crystalline SiNWs. The SiNWs can be approximately mm long, with the smallest diameter down to approximately 22 nm. A high growth rate of >10(2) nm/s and rich evolution dynamics are revealed in a real-time in situ scanning electron microscopy observation. A qualitative growth model is proposed to account for the major features of this IPSLS SiNW growth mode.


Alpha-adrenergic receptors in human blood vessels.
The evidence for the presence of postjunctional alpha 1- and alpha 2-adrenoceptor subtypes in human blood vessels is reviewed. Experiments in healthy subjects are described that show that alpha 1- as well as alpha 2-adrenoceptor mediated vasoconstriction contribute to vascular smooth muscle tone and that adrenaline and noradrenaline have similar affinities for each subtype. In addition, evidence is presented for a preferential intrajunctional location of alpha 1-adrenoceptors and a preferential extrajunctional location of alpha 2-adrenoceptors in human blood vessels. It is concluded that at present postjunctional alpha-adrenoceptors in human blood vessels can be classified as alpha 1 and alpha 2. Despite the fact that both subtypes mediate vasoconstriction, these receptors are likely to subserve different physiological functions.


Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions.
Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells.


A Novel Immune-Related ceRNA Network and Relative Potential Therapeutic Drug Prediction in ccRCC.
Renal cell carcinoma (RCC) is the third common solid tumor in the urinary system with a high distant metastasis rate. The five-year survival rate of RCC has reached 75%, benefiting from the emergence and update of multiple treatments, while its pathogenesis and prognostic markers are still unclear. In this study, we committed to explore a prognostic ceRNA network that could participate in the development of RCC and had not been studied yet. We screened nine immune-related hub genes (AGER, HAMP, LAT, LTB4R, NR3C2, SEMA3D, SEMA3G, SLC11A1, and VAV3) using data of The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA-KIRC) through survival analysis and the cox proportional hazard model. Next, we successfully constructed a ceRNA network of two mRNA (NR3C2 and VAV3), miRNA (hsa-miR-186-5p), and lncRNA (NNT-AS1) for ccRCC based on numerous online bioinformatics tools and Cytoscape. Finally, we predicted five potential drugs (clemizole, pentolonium, dioxybenzone, Prestwick-691, and metoprolol) based on the above results.


Atomically Resolved Structural and Chemical Investigation of Single MXene Sheets.
The properties of two-dimensional (2D) materials depend strongly on the chemical and electrochemical activity of their surfaces. MXene, one of the most recent additions to 2D materials, shows great promise as an energy storage material. In the present investigation, the chemical and structural properties of individual Ti3C2 MXene sheets with associated surface groups are investigated at the atomic level by aberration corrected STEM-EELS. The MXene sheets are shown to exhibit a nonuniform coverage of O-based surface groups which locally affect the chemistry. Additionally, native point defects which are proposed to affect the local surface chemistry, such as oxidized titanium adatoms (TiOx), are identified and found to be mobile.


Stress, Anxiety, Depression and Their Associated Factors among Health Care Workers During COVID -19 Pandemic in Nepal.
Frontline Health Care Workers are at risk of developing mental and psychological distress during Corona virus disease 2019 pandemic. This study aimed to assess level of stress, anxiety, depression and their associated factors among health care workers during Corona virus disease 2019 pandemic in Nepal. This is a web based cross-sectional survey conducted among 404 Health Care Workers during early phase of Corona virus disease 2019 pandemic. The participants were selected using convenience sampling technique and were invited to participate via various online networks. Depression, anxiety and stress were assessed using the Depression Anxiety Stress Scale-21 (DASS-21) and their associated factors were measured using structured questionnaires. Multivariable logistic regression was carried out to determine the associated factors. The symptoms of stress, anxiety and depression among health care workers were found to be 28.9%, 35.6% and 17.0% respectively. Females were found to be 2 fold more likely to have anxiety and depression than male. Nurses were found to be two times more likely to have anxiety than doctors. Laboratory personnel were almost three folds more likely to have anxiety than doctors. Health care workers with insufficient/ no PPE were almost three fold more likely to have depression. health care workers working in high-risk areas had almost 2 fold higher odds of having depression. Health care workers experienced symptoms of stress, anxiety and depression in varied level of severity. This experience was higher among the nurses and laboratory workers than doctors. Pandemic preparedness assuring PPE and appropriate psychological interventions may be beneficial to promote mental health and well-being of health care workers.


Diesel exhaust is not a pulmonary carcinogen in CD-1 mice exposed under conditions carcinogenic to F344 rats.
Differences among laboratory animal species in the pulmonary carcinogenicity of chronic inhalation exposure to diesel exhaust have raised several important interpretive issues. Under similar heavy exposure conditions, it is clear that diesel exhaust is a pulmonary carcinogen in rats, but not in Syrian hamsters. Previous reports give conflicting views of the response of mice, which is presently considered equivocal. This report describes carcinogenicity results from a bioassay of CD-1 mice conducted in parallel with a previously reported bioassay of F344 rats (Mauderly et al. (1987) Fundam. Appl. Toxicol. 9, 208-221). Exposure to whole diesel exhaust 7 hr/day, 5 days/week for 24 months at soot concentrations of 0.35, 3.5, or 7.1 mg/m3 caused accumulations of soot in mouse lungs similar to those in lungs of rats and, like the results from rats, did not significantly affect survival or body weight. In contrast to the dose-related neoplastic response of rats, however, the exposures of mice did not increase the incidence of lung neoplasms. This finding is consistent with other data showing that mice, as well as Syrian hamsters, differ from rats in their lung neoplastic and nonneoplastic responses to heavy, chronic inhalation exposure to diesel exhaust soot and several other particles. Although rodents serve as useful indicators of potential human carcinogenic hazards, it is not yet clear which, if any, rodent species have lung neoplastic responses that are useful for quantitative predictions of human lung cancer risk from chronic inhalation of poorly soluble, respirable particles.


Is S3 a Viable Osseous Fixation Pathway?
To report the incidence of patients with a third sacral segment (S3) osseous fixation pathway (OFP) that could accommodate a transiliac-transsacral screw. Retrospective case series. Regional Level 1 Trauma Center. A total of 250 patients without pelvic trauma from January 2017 to February 2017 were included. The axial and sagittal reconstruction images of each patient's computed abdomen and pelvis tomography (CT) scans were reviewed. Each CT was evaluated for the presence of sacral dysmorphism and whether an S3 OFP that could accommodate an intraosseous transiliac-transsacral screw exists. There were 130 of the 250 patients (52%) with sacral dysmorphism. Overall, 38 of the 250 patients (15.2%) had an S3 OFP that could accommodate a 7.0-mm transiliac-transsacral style screw. When narrowed to patients who had an S3 OFP, 38 of 153 patients (24.8%) could accommodate a 7.0-mm transiliac-transsacral screw. Specific to the 38 patients with an adequate S3 OFP, 34 of 38 patients (89.5%) were noted to have sacral dysmorphism. Our study demonstrates that 15.2% of patients have an S3 OFP large enough to accommodate an intraosseous implant. Patients who have sacral dysmorphism are more likely to have an adequate S3 OFP. Additional studies are needed to quantify the S3 OFP, understand the bone quality of the S3 segment and accompanying biomechanical implications, and investigate the anatomical concerns associated with S3 screw placement. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assessment of dietary exposure to heterocyclic amines based on the Korean total diet study.
Heterocyclic amines (HCAs) are contaminants in proteinaceous foods produced by cooking at high temperatures. This study was the first assessment of exposure to HCAs using the Korean total diet study. Twelve HCAs were analysed in 1,232 pooled samples using six isotope-labelled internal standards and HPLC-MS/MS. The daily intake of HCAs in the Korean population was estimated based on the concentration of HCAs in the total diet study samples and individual food consumption data from the Korean National Health and Nutrition Examination Survey. Among HCAs, the intake of β-carbolines, such as harman and norharman, was the highest, followed by the intake of PhIP. The primary sources of HCA intake were meat, fish, shellfish, and beverages, including alcohol. The margin of exposure to PhIP was 2,349,000 at the average level and 373,000 at the 95th percentile in the Korean population. The estimated daily intake of all HCAs in the Korean population was considered safe.


[Constrained ICA and its application to removing artifacts in EEG].
Independent component analysis (ICA) is a statistic technique which extracts independent components from a set of standard signals. Since Electroencephalogram (EEG) signals are the mixture of several relatively independent sources, ICA has attracted extensive attention in the field of EEG processing. In this paper, a new Constrained ICA (cICA) algorithm is introduced, it would solve the problem of orderless output when FastICA algorithm is used. The experiment results testify that the cICA algorithm can reduce the effect of different individual when the artifacts of EEG are removed manually. The results also show that the cICA algorithm is robust and performs faster convergence.


Effect of nitric oxide generators on ischemia-reperfusion injury and histamine release in isolated perfused guinea pig heart.
In an ischemia-reperfusion model obtained in isolated perfused guinea pig heart by means of a double ligature of the left anterior descending coronary artery, the reperfusion of the ischemic myocardium leads to a release of lactate dehydrogenase and histamine, related to a decrease in the microdensitometry of cardiac mast cells and to a tissue calcium overload. The perfusion of the heart with L-arginine and with nitric oxide donors significantly reduces the release of histamine, the loss of mast cell metachromasia and calcium overload. These effects were potentiated by superoxide dismutase.


[The characteristic analysis of several mineral contents in Chinese orange juice].
A study was carried out on the contents of mineral elements such as K, Ca, Na, and Mg in seven different orange varieties, namely Pineapple orange, Hamlin, Trovita, Jincheng, 1,232 Tangor, Olinda Valencia and Delta Valencia, by flame atomic absorption spectrometry. The results indicated that the content sequence of different nutritional elements was K > Mg > Ca > Na, with a range of 1,233.75-1,866.23, 77.51-167.15, 49.32-125.29 and 1.22-9.26 mg x L(-1) respectively. The range scale of the four elements was largely consistent with the reference value of AIJN (Association of the Industry of Juices and Nectars from Fruits and Vegetables of the European Union). The samples can be clustered into 2 groups by factor analysis, and lower Na content would be the characteristic of the Valencia varieties. All these data would offer important information for orange juice adulteration determination and quality evaluation.


Understanding Students' Instrumental Goals, Motivation Deficits and Achievement: Through the Lens of a Latent Profile Analysis.
Building on the future oriented and regulated nature of instrumental goals, Lens and colleagues developed a 2 (proximal-distal) x 2 (internal-external) motivational framework. The current study aimed to test this framework from a person-centred perspective, while equally taking into account students' lack of motivation as to extend the empirical and theoretical borders of the model. Latent Profile Analyses were used to test the viability of two to five motivational profiles among Japanese second-year students (N = 781). A solution with three latent subgroups fitted the sample best, explaining 6% to 62% of the variance in the measured variables. The profiles were labelled "low future oriented motivational profile", "average motivated profile", and "highly motivated profile". The highly motivated subgroup reported the most adaptive pattern of motivation and highest levels of deep level learning, while few differences were found for surface learning and GPA. Theoretical and practical implications are discussed.


Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats.
In the present study, Nigella sativa oil (NSO), nigellone (polythymoquinone) and derived thymoquinone were studied to evaluate their effect on the formation of 5-lipoxygenase (5-LO) products from polymorphonuclear leukocytes (PMNL).NSO produced a concentration dependent inhibition of 5-LO products and 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) production with half maximal effects (IC(50)) at 25+/-1 micro g/ml, respectively 24+/-1 micro g/ml. Nigellone caused a concentration-related inhibition of 5-HETE production (IC(50): 11.9+/-0.3 micro g/ml). Moreover thymoquinone, the active principle of NSO inhibited the production of 5-LO products (IC(50): 0.26+/-0.02 micro g/ml) and 5-HETE production (IC(50): 0.36+/-0.02 micro g/ml) in a similar way. The effects are probably due to an antioxidative action. The data may in part explain the effect of the oil, its derived thymoquinone and nigellone in ameliorating inflammatory diseases.


Results of treatment in amblyopia associated with unilateral high myopia without strabismus.
Fifty-five patients with amblyopia in unilateral high myopia without strabismus were treated. Thirty-two (58%) had a visual improvement by two lines or more on the Snellen chart and 17 (31%) attained a final visual acuity of 6/12 or better. In patients with pretreatment corrected vision of 6/60 or better in the amblyopic eye treatment consisted of full-time occlusion of the good eye, in some cases supplemented by the after-image method of pleoptic exercises in the amblyopic eye. Overall improvement of vision in this group was 72.7%. Occlusion of the good eye combined with pleoptic exercises in the amblyopic eye had no advantage over simple occlusion of the good eye. In patients with pretreatment corrected vision worse than 6/60 in the amblyopic eye occlusion of the amblyopic eye was done and the after-image method of pleoptic exercises was instituted. Improvement of vision in this group was 36.3%. The study showed that it is worth the trouble to treat this disorder even after the age of 14 years and stresses the utility of pleoptic therapy in older patients with severe amblyopia.


Impact of pollution and place of residence on atopic diseases among schoolchildren in Telemark County, Norway.
For estimation of the prevalence, degree of severity, and association with outdoor pollution, a questionnaire on asthma and other atopic diseases was distributed to the parents of 4666 7-13-year-olds, comprising all the children in 36 schools in Telemark County, Norway, including 37% of the schoolchildren in the county. The response rate was 94%. In a validity study employing clinical evaluations, the questionnaire-based diagnosis of asthma was found to have a sensitivity of 0.96 and a specificity of 0.88. The lifetime prevalence of asthma in Telemark was 9% (boys 11.3%, girls 6.6%; p < 0.001). There was no significant difference in the lifetime prevalence of asthma by pollution zone; 8.3% in heavily, 9.3% in moderately, and 9.2% in minimally polluted zones. The asthma prevalence was significantly higher (14.2%; p < 0.05) among boys in the coastal area of the county than in the mountainous area (8.9%). Both of these areas were in the minimal pollution zone. Of asthma cases, 67% were categorized as mild, 29% as moderate, and 4% as severe. The lifetime prevalence was 17.8% (boys 21.3%, girls 14.2%; p < 0.001) for allergic rhinitis, 13.2% (boys 11.4%, girls 15.2%; p < 0.001) for atopic eczema, and 29.6% (boys 31.7%, girls 27.4%; p < 0.01) for overall atopic disease (asthma, allergic rhinitis, eczema). These findings are not compatible with the hypothesis that outdoor pollution is associated with the lifetime prevalence of asthma in school-age children. The results also show that less than 0.5% of schoolchildren suffer from severe asthma.


[Chyluria treated with stripping of the renal pedicle: a case report].
A 54-year-old male was referred to our outpatient clinic because of milky urine. He had lived in Kumamoto, an area of endemic filariasis. There were no microfilaria found in his blood smear. Lymphangiography showed dilation of the retroperitoneal lymphatics and bilateral renal refluxes. The thoracic duct was obvious. The initial treatment consisted of irrigating the bilateral renal pelvis with silver nitrate solution, but was not successful and recurrent acute urinary retention developed. Therefore, we performed stripping and ligation of the bilateral renal lymphatics. Chyluria disappeared immediately after surgery. The etiology and various treatments for chyluria are discussed.


Structural details of a calcium-induced molecular switch: X-ray crystallographic analysis of the calcium-saturated N-terminal domain of troponin C at 1.75 A resolution.
We have solved and refined the crystal and molecular structures of the calcium-saturated N-terminal domain of troponin C (TnC) to 1.75 A resolution. This has allowed for the first detailed analysis of the calcium binding sites of this molecular switch in the calcium-loaded state. The results provide support for the proposed binding order and qualitatively, for the affinity of calcium in the two regulatory calcium binding sites. Based on a comparison with the high-resolution apo-form of TnC we propose a possible mechanism for the calcium-mediated exposure of a large hydrophobic surface that is central to the initiation of muscle contraction within the cell.


Porous ZnO nanosheet arrays constructed on weaved metal wire for flexible dye-sensitized solar cells.
Porous zinc oxide (ZnO) nanosheet (NS) arrays constructed by connected nanocrystallites were built on weaved metal wire (WMW) via hydrothermal treatment followed by calcination, and used as photoanodes for flexible dye-sensitized solar cells (DSSCs). An overall light-to-electricity conversion efficiency (η) of 2.70% was achieved for the DSSC under 100 mW cm(-2) illumination, and this η was found to be much higher than that of the DSSC with ZnO nanowire (NW) as the photoanode (0.71%). The far superior performance of the DSSC with ZnO-NS is essentially attributed to: (i) the film consisting of nanosheets with interconnected nanocrystallites can allow relatively direct pathways for the transportation of electrons as the nanosheets have a regular structure with the sheets being oriented to the electrode; (ii) the nanocrystallites assembly and porous character of the nanosheets can provide a large surface area for dye adsorption, which is in favor of enhancing the light absorption and the light propagation; (iii) the nanopores embedded in the nanosheet can act as "branch lines" for more efficient electrolyte diffusion into the interstice of the densely packed nanosheets in the array. A further improvement in the efficiency of the DSSC with ZnO-NS was achieved through the atomic layer deposition (ALD) of an ultrathin titanium oxide (TiO2) layer onto the ZnO-NS layer. The larger charge transfer resistance along with the introduction of a TiO2 shell is thought to reduce the surface recombination and thus contribute to the increase in the open circuit voltage (Voc) of the DSCs and higher conversion efficiency (3.09%).


Combination effects of baicalin with levofloxacin against biofilm-related infections.
It is important to improve the existing techniques and develop new strategies to prevent bacterial biofilm formation. In this in vitro study, biofilms were established by a clinically isolated strain of Staphylococcus aureus 17546 (t037). Different concentrations of baicalin were added to 3- and 7-day biofilms. Based on colony counts and quantitative analysis of the biomass, sub-minimum inhibitory concentrations (sub-MICs) (1024, 512 or 256 μg/mL) of baicalin clearly decreased the number of bacterial colonies and biomass in vitro. Fluorescence microscopy revealed that sub-MICs (1024, 512, or 256 μg/mL) of baicalin inhibited bacterial adherence to the carrier surface and decreased polysaccharide production. Moreover, baicalin disrupted biofilms and exhibited synergistic effects with levofloxacin. Virulence factors were assessed by western blotting and real-time quantitative polymerase chain reaction, confirming that staphylococcal enterotoxin A, α-haemolysin and coagulase production decreased after baicalin treatment. Additionally, baicalin increased production of thermonuclease in S. aureus, and baicalin at 1024 and 512 μg/mL downregulated agrA expression. Based on these findings, the combination of baicalin with levofloxacin might be a new, feasible strategy for treating S. aureus biofilm-related infections. Baicalin may serve as a new inhibitor that modulates S. aureus virulence factors.


Facile Approach to Fabricating Stretchable Organic Transistors with Laser-Patterned Ag Nanowire Electrodes.
Stretchable electronics are poised to revolutionize personal healthcare and robotics, where they enable distributed and conformal sensors. Transistors are fundamental building blocks of electronics, and there is a need to produce stretchable transistors using low-cost and scalable fabrication techniques. Here, we introduce a facile fabrication approach using laser patterning and transfer printing to achieve high-performance, solution-processed intrinsically stretchable organic thin-film transistors (OTFTs). The device consists of Ag nanowire (NW) electrodes, where the source and drain electrodes are patterned using laser ablation. The Ag NWs are then partially embedded in a poly(dimethylsiloxane) (PDMS) matrix. The electrodes are combined with a PDMS dielectric and polymer semiconductor, where the layers are individually transfer printed to complete the OTFT. Two polymer semiconductors, DPP-DTT and DPP-4T, are considered and show stable operation under the cyclic strain of 20 and 40%, respectively. The OTFTs maintain electrical performance by adopting a buckled structure after the first stretch-release cycle. The conformability and stretchability of the OTFT is also demonstrated by operating the transistor while adhered to a finger being flexed. The ability to pattern highly conductive Ag NW networks using laser ablation to pattern electrodes as well as interconnects provides a simple strategy to produce complex stretchable OTFT-based circuits.


Endogenous formation of protein adducts with carcinogenic aldehydes: implications for oxidative stress.
In the present study, we characterize the covalent modification of a protein by crotonaldehyde, a representative carcinogenic aldehyde, and describe the endogenous production of this aldehyde in vivo. The crotonaldehyde preferentially reacted with the lysine and histidine residues of bovine serum albumin and generated a protein-linked carbonyl derivative. Upon incubation with the histidine and lysine derivatives, crotonaldehyde predominantly generated beta-substituted butanal adducts of histidine and lysine and N(epsilon)-(2,5-dimethyl-3-formyl-3,4-dehydropiperidino)lysine (dimethyl-FDP-lysine) as the putative carbonyl derivatives generated in the crotonaldehyde-modified protein. To verify the endogenous formation of crotonaldehyde in vivo, we raised the monoclonal antibody (mAb82D3) against the crotonaldehyde-modified protein and found that it cross-reacted with the protein-bound 2-alkenals, such as crotonaldehyde, 2-pentenal, and 2-hexenal. The anti-2-alkenal antibody recognized multiple crotonaldehyde-lysine adducts, including dimethyl-FDP-lysine and an unknown product, which showed the greatest immunoreactivity with the antibody. On the basis of the chemical and spectroscopic evidence, the major antigenic product was determined to be a novel Schiff base-derived crotonaldehyde-lysine adduct, N(epsilon)-(5-ethyl-2-methylpyridinium)lysine (EMP-lysine). It was found that the lysine residues that had disappeared in the protein treated with crotonaldehyde were partially recovered by EMP-lysine. The presence of immunoreactive materials with mAb82D3 in vivo was demonstrated in the kidney of rats exposed to the renal carcinogen, ferric nitrilotriacetate. In addition, the observations that the metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of proteins resulted in an increase in the antigenicity of the protein indicated that lipid peroxidation represents a potential pathway for the formation of crotonaldehyde/2-alkenals in vivo. These data suggest that the formation of carcinogenic aldehydes during lipid peroxidation may be causally involved in the pathophysiological effects associated with oxidative stress.


Orbital metastasis as the primary manifestation of pancreatic carcinoma: a case report and literature review.
Orbital metastasis from pancreatic tumors is extremely rare, and its clinical characteristics are still unclear. Our case was a 73-year-old female who noticed diplopia on right gaze 3 months before referral to us. Imaging studies demonstrated a mass involving the lateral rectus muscle in the right orbit. The results of pathological examination of an excised specimen corresponded to poorly differentiated adenocarcinoma. Systemic work-up revealed pancreatic carcinoma with peritoneal metastasis. The patient underwent chemotherapy. We reviewed literature on similar cases and found 19 reported cases of pancreatic tumors metastasizing to the orbit. The results of our review indicate a tendency for formation of solitary mass without bony erosion, delayed detection of the primary pancreatic carcinoma, and poorer prognosis of such tumors, compared to metastatic orbital tumors from other lesions. We report a rare case of metastatic orbital tumor from an unknown primary pancreatic carcinoma. Clinical characteristics of cases with metastatic pancreatic tumors seem to be different from those with metastatic tumors from the other lesions. Pancreatic tumors are frequently asymptomatic in an early stage, leading to delayed detection of the primary pancreatic carcinoma and poorer prognosis.


Injury risk is altered by previous injury: a systematic review of the literature and presentation of causative neuromuscular factors.
Active adults commonly present with lower extremity (LE) injuries from a variety of professional and amateur sports activities. Decreased LE function significantly alters daily life and subsequent injuries increase this impact. The purpose of this systematic review was to examine the association between previous injury and the risk of re-injury, and to describe the changes in kinematics and motor programming that may contribute to this relationship. A preliminary search was conducted to determine the four most common LE injuries on PubMed, CINAHL and Web of Science. These injuries, in a healthy active adult population, were hamstring strain (HS), anterior cruciate ligament injury (ACL), achilles tendon pathology, and ankle sprain. After these injuries were established, the search for this systematic review found evidence relating these injuries to re-injury. Articles related to degenerative changes were excluded. Twenty-six articles were included in the systematic review detailing the risk of re-injury from a previous injury and were graded for quality. ACL injury was linked to a successive injury of the same ACL, and other injuries in the LE. HS was associated with subsequent ipsilateral HS and knee injuries. Previous achilles tendon rupture increased the risk of an analogous injury on the contralateral side. An ankle sprain was associated with a re-injury of either the ipsilateral or the contralateral ankle. Post-injury changes were present in strength, proprioception, and kinematics, which may have led to overall changes in motor control and function. This review provides insight into the changes occurring following common LE injuries, how these changes potentially affect risk for future injury, and address the needs of the active adult population in rehabilitation. Current research on previous injury and re-injury is of high quality, but scarce quantity. Deficits following an injury are known, but how these deficits correlate or lead to re-injury requires further exploration. 1.


Two exo-beta-D-glucosaminidases/exochitosanases from actinomycetes define a new subfamily within family 2 of glycoside hydrolases.
A GlcNase (exo-beta-D-glucosaminidase) was purified from culture supernatant of Amycolatopsis orientalis subsp. orientalis grown in medium with chitosan. The enzyme hydrolysed the terminal GlcN (glucosamine) residues in oligomers of GlcN with transglycosylation observed at late reaction stages. 1H-NMR spectroscopy revealed that the enzyme is a retaining glycoside hydrolase. The GlcNase also behaved as an exochitosanase against high-molecular-mass chitosan with K(m) and kcat values of 0.16 mg/ml and 2832 min(-1). On the basis of partial amino acid sequences, PCR primers were designed and used to amplify a DNA fragment which then allowed the cloning of the GlcNase gene (csxA) associated with an open reading frame of 1032 residues. The GlcNase has been classified as a member of glycoside hydrolase family 2 (GH2). Sequence alignments identified a group of CsxA-related protein sequences forming a distinct GH2 subfamily. Most of them have been annotated in databases as putative beta-mannosidases. Among these, the SAV1223 protein from Streptomyces avermitilis has been purified following gene cloning and expression in a heterologous host and shown to be a GlcNase with no detectable beta-mannosidase activity. In CsxA and all relatives, a serine-aspartate doublet replaces an asparagine residue and a glutamate residue, which were strictly conserved in previously studied GH2 members with beta-galactosidase, beta-glucuronidase or beta-mannosidase activity and shown to be directly involved in various steps of the catalytic mechanism. Alignments of several other GH2 members allowed the identification of yet another putative subfamily, characterized by a novel, serine-glutamate doublet at these positions.


Altitudinal biodiversity patterns of seed plants along Gongga Mountain in the southeastern Qinghai-Tibetan Plateau.
The mechanisms underlying elevation patterns in species and phylogenetic diversity remain a central issue in ecology and are vital for effective biodiversity conservation in the mountains. Gongga Mountain, located in the southeastern Qinghai-Tibetan Plateau, represents one of the longest elevational gradients (ca. 6,500 m, from ca. 1,000 to 7,556 m) in the world for studying species diversity patterns. However, the elevational gradient and conservation of plant species diversity and phylogenetic diversity in this mountain remain poorly studied. Here, we compiled the elevational distributions of 2,667 native seed plant species occurring in Gongga Mountain, and estimated the species diversity, phylogenetic diversity, species density, and phylogenetic relatedness across ten elevation belts and five vegetation zones. The results indicated that species diversity and phylogenetic diversity of all seed plants showed a hump-shaped pattern, peaking at 1,800-2,200 m. Species diversity was significantly correlated with phylogenetic diversity and species density. The floras in temperate coniferous broad-leaved mixed forests, subalpine coniferous forests, and alpine shrublands and meadows were significantly phylogenetically clustered, whereas the floras in evergreen broad-leaved forests had phylogenetically random structure. Both climate and human pressure had strong correlation with species diversity, phylogenetic diversity, and phylogenetic structure of seed plants. Our results suggest that the evergreen broad-leaved forests and coniferous broad-leaved mixed forests at low to mid elevations deserve more conservation efforts. This study improves our understanding on the elevational gradients of species and phylogenetic diversity and their determinants and provides support for improvement of seed plant conservation in Gongga Mountain.


Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population.
Osteosarcoma, a malignant primary bone tumor most commonly diagnosed in children and adolescents, has a poorly understood genetic etiology. Genome-wide association studies (GWAS) and candidate-gene analyses have identified putative risk variants in subjects of European ancestry. However, despite higher incidence among African-American and Hispanic children, little is known regarding common heritable variation that contributes to osteosarcoma incidence and clinical presentation across racial/ethnic groups. In a multi-ethnic sample of non-Hispanic white, Hispanic, African-American and Asian/Pacific Islander children (537 cases, 2165 controls), we performed association analyses assessing previously-reported loci for osteosarcoma risk and metastasis, including meta-analysis across racial/ethnic groups. We also assessed a previously described association between genetic predisposition to longer leukocyte telomere length (LTL) and osteosarcoma risk in this independent multi-ethnic dataset. In our sample, we were unable to replicate previously-reported loci for osteosarcoma risk or metastasis detected in GWAS of European-ancestry individuals in either ethnicity-stratified analyses or meta-analysis across ethnic groups. Our analyses did confirm that genetic predisposition to longer LTL is a risk factor for osteosarcoma (ORmeta: 1.22; 95% CI: 1.09-1.36; P = 3.8 × 10-4), and the strongest effect was seen in Hispanic subjects (OR: 1.32; 95% CI: 1.12-1.54, P = 6.2 × 10-4). Our findings shed light on the replicability of osteosarcoma risk loci across ethnicities and motivate further characterization of these genetic factors in diverse clinical cohorts.


Fabrication and luminescence of designer surface patterns with beta-cyclodextrin functionalized quantum dots via multivalent supramolecular coupling.
Supramolecular microcontact printing was used to obtain controlled patterns consisting of quantum dots (QDs) functionalized at their periphery with beta-cyclodextrin (beta-CD) in combination with adamantyl terminated dendrimeric "glues". Functionalization of core--shell CdSe/ZnS QDs was achieved by surface ligation. Immobilization of the QDs from solution onto glass substrates printed with (a) adamantyl-terminated poly(propylene imine) dendrimers and (b) via direct microcontact printing of QDs onto the dendrimer layer both yielded stable and robust multilayer structures. The stability of the patterns was primarily due to multivalent supramolecular host--guest interactions between beta-CD located at the QD surface and adamantyl groups at the dendrimer periphery as the dendrimers acted as a "supramolecular glue". The surface-immobilized QDs were capable of forming host--guest complexes with other molecules of interest at binding cavities not occupied by adamantyl groups. Complex formation with ferrocene-functionalized molecules at these sites led to partial quenching of the luminescence emission of QDs demonstrating the principle for sensing using the QD multilayer structures.


Independent contrasts and regression through the origin.
Following the pioneering work of Felsenstein and Garland, phylogeneticists have been using regression through the origin to analyze comparative data using independent contrasts. The reason why regression through the origin must be used with such data was revisited. The demonstration led to the formulation of a permutation test for the coefficient of determination and the regression coefficient estimates in regression through the origin. Simulations were carried out to measure type I error and power of the parametric and permutation tests under two models of data generation: regression models I and II (correlation model). Although regression through the origin assumes model I data, in independent contrast data error is present in the explanatory as well as the response variables. Two forms of permutations were investigated to test the regression coefficients: permutation of the values of the response variable y, and permutation of the residuals of the regression model. The simulations showed that the parametric tests or any of the permutation tests can be used when the error is normal, which is the usual assumption in independent contrast studies; only the test by permutation of y should be used when the error is highly asymmetric; and the parametric tests should be used when extreme values are present in covariables. Two examples are presented. The first one concerns non-specificity in fish parasites of the genus Lamellodiscus, the second the richness in parasites in 78 species of mammals.


Update on the supply of tetanus and diphtheria toxoids and of diphtheria and tetanus toxoids and acellular pertussis vaccine.
During the last quarter of 2000, the U.S. Public Health Service learned of a shortage of tetanus and diphtheria toxoids (Td) and tetanus toxoid (TT) resulting from decreased production of these vaccines by the two U.S. manufacturers. Previously published recommendations outlined priorities for use of the limited supply of Td and TT. The shortage was expected to be resolved by early 2001; however, on January 10, 2001, Wyeth Lederle (Pearl River, New York) announced it had stopped production of tetanus toxoid-containing products. Although a small amount of Td is produced by the University of Massachusetts for local distribution, Aventis Pasteur (Swiftwater, Pennsylvania) is now the sole nationwide distributor of Td and TT. Aventis Pasteur is shipping limited quantities of vaccine to assure a wide distribution of available doses.


Total anthelmintic failure to control nematode parasites of small ruminants on government breeding farms in Sabah, East Malaysia.
Government-owned small-ruminant breeding farms in Malaysia provide the source of sheep and goats to smallholder farmers in the country. In the eastern Malaysian state of Sabah, high-level stock losses have been recorded on these farms for several years, frequently accompanied by clinical signs indicating pathogenic levels of infections with the nematode parasite Haemonchus contortus. This suggests that their dependence on chemotherapy to control parasite infections had failed. Accordingly, tests for anthelmintic efficacy using the faecal egg count reduction test (FECRT) on the range of drugs used to control nematode parasites were carried out on the five government small-ruminant breeding farms in Sabah. These tests showed a total failure of the benzimidazole, imidothiazole, macrocyclic lactone and salicylanilide groups of anthelmintics to control H. contortus infections of sheep and goats on all farms. Drastic changes in animal management need to be made in an attempt to deal with this situation, for which suggestions are made.


Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.


Drug-analysis technology: overview and state of the art.
Analytical techniques are available to reliably detect and, if necessary, quantify drugs of abuse and their metabolites in urine. A variety of different immunoassays are likely to remain at the heart of initial screening methods but with an increasing emphasis on confirmation of positive findings by GC-MS. The quality of work in laboratories (which may make considerable financial gain through increased volume of samples) must be guarded by both internal quality assurance and external proficiency testing, but most of all by ensuring that staff are truly forensic toxicologists with adequate credentials and experience. Laboratories must be credible to the courts and to their clients, which is simply not the case today. For the past 20 years, the toxicologist has played an increasingly important role as an ombudsman of public-health issues; this new dimension of professional responsibility has almost frightening proportions. The alarm that is rightly felt in the profession can only be assuaged and brought into perspective by increasing the knowledge base from which toxicological opinions are rendered, and by recognizing that, however critical, the analytical laboratory report is only a part, and never the whole case. Just a few areas of immediate needs have been mentioned, but they are critical, they cannot be avoided, and they must receive appropriate attention very soon.


Effect of sequential treatment as a first-line therapy for Helicobacter pylori eradication in patients with diabetes mellitus.
The Maastricht III Consensus agreed that effective treatment for Helicobacter pylori (HP) should achieve an intention-to-treat (ITT) eradication rate above 80%, which is still lacking in patients with type 2 diabetes mellitus (DM). This pilot study was designed to confirm the efficacy of a 14-day sequential treatment regimen in patients with type 2 DM. This is a prospective, open-label, single-center pilot study. All patients included in this study underwent upper gastrointestinal endoscopy. HP status was evaluated in each patient by a rapid urease test and histopathologic examination. For seven days, all patients received pantoprazole 40 mg twice daily (b.i.d.) and amoxicillin 1000 mg b.i.d., followed by pantoprazole 40 mg b.i.d., metronidazole 500 mg b.i.d., and tetracycline 500 mg four times per day (q.i.d.) [DOSAGE ERROR CORRECTED] for the remaining seven days. The study population consisted of 38 consecutive patients with type 2 DM (18 female, 20 male; mean age 48.0 ± 12.2 years), 30 of whom had non-ulcer dyspepsia, four had gastritis, one had gastric ulcer, and three had duodenal ulcer disease. Eradication was defined as the absence of HP as assessed with the 14C-urea breath test. Thirty-seven of 38 patients completed the study. All side effects were observed in eight patients (21.1%). None of the patients discontinued treatment because of side effects. The eradication rate in the DM group was 22/38 (57.9%) for the ITT analysis and 22/37 (59.5%) for the per-protocol (PP) analysis. The results of 14-day sequential therapy for the first-line treatment of HP in patients with type 2 DM were disappointing. Further studies with new antibiotic combinations are needed to find better methods of eradicating HP in patients with type 2 DM.


Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.
Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.


Genomics, Computational Biology and Drug Discovery for Mycobacterial Infections: Fighting the Emergence of Resistance.
Tuberculosis (TB) and leprosy are mycobacterial infections caused by Mycobacterium tuberculosis and Mycobacterium leprae respectively. These diseases continue to be endemic in developing countries where the cost of new medicines presents major challenges. The situation is further exacerbated by the emergence of resistance to many front-line antibiotics. A priority now is to design new antimycobacterials that are not only effective in combatting the diseases but are also less likely to give rise to resistance. In both these respects understanding the structure of drug targets in M. tuberculosis and M. leprae is crucial. In this review we describe structure-guided approaches to understanding the impacts of mutations that give rise to antimycobacterial resistance and the use of this information in the design of new medicines.


A practical approach to the clinical evaluation and management of children with ambiguous genitalia.
A plea is made for an immediate and multidisciplinary approach in children with ambiguous genitalia. The manner of working of the team in the Sophia Children's Hospital, Rotterdam, is presented. Four examples are given and a review of the literature completes the paper.


Uniportal video-assisted thoracoscopic surgery (VATS) for the treatment of early-stage lung cancer with whole pleural adhesion.
Uniportal video-assisted thoracoscopic surgery (VATS) is considered a challenging procedure in cases of lung cancer where the entire pleura and lung are attached (whole pleural adhesion). The purpose of this study was to evaluate the surgical results of uniportal VATS for the treatment of lung cancer with whole pleural adhesion. For all patients who underwent VATS lung cancer surgery at a single hospital in Korea, multiportal VATS was performed before 2017 and uniportal VATS was performed after January 2017 by the same surgeons. The surgical results of multiportal VATS and uniportal VATS for the treatment of lung cancer with whole pleural adhesion were compared retrospectively. There were 16 eligible uniportal VATS cases and 57 multiportal VATS cases. There were no significant differences of clinicopathologic characteristics between the two groups. There were 5 conversions to open thoracotomy in the multiportal VATS group and no conversion to open thoracotomy in the uniportal group (P=0.579). The perioperative and postoperative outcomes were not different between the two groups. There was no mortality in all patients. For patients undergoing VATS lobectomy, the perioperative and postoperative outcomes were similar after uniportal and multiportal VATS lobectomy. For all patients, the 3-year recurrence-free survival (RFS) was 80.0% after uniportal VATS and 79.5% after multiportal VATS (P=0.951) and for patients with stage I non-small cell lung cancer (NSCLC), the 3-year RFS after uniportal VATS was 91.7% and the 3-year RFS after multiportal VATS was 89.3% (P=0.999). Uniportal VATS was not a significant risk factor for recurrence in the multivariate analysis. Uniportal VATS was not inferior to multiportal VATS in surgical outcome or short-term prognosis in resection of lung cancer with whole pleural adhesion. Whole pleural adhesion is not a contraindication to uniportal VATS, which has been safe and feasible in cases of lung cancer with whole pleural adhesion.


Relationship Between Cerebrovascular Diseases and Vasculitis: A Cross-Sectional Nationwide Inpatient Study.
Objectives To evaluate the risk factors and hospitalization outcomes for cerebrovascular diseases (CVD) in patients with vasculitis. Methods We conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS), 2019. We included 26,855 adults (aged 18 to 65 years, average age 48.57 ± 12.79 years) with a co-diagnosis of vasculitis, and the sample was divided by the primary diagnosis of CVD (N = 670, 2.5%). A demographic-adjusted logistic regression model was used to evaluate the odds ratio (OR) of association with CVD in patients with vasculitis by comparing it to the non-CVD cohort. Results The majority of the vasculitis patients with CVD were elders (51 to 65 years, 46%), females (62%), and whites (52%). There was a significant difference in the geographic distribution of CVD with vasculitis with the highest prevalence in the South Atlantic (23%) and Middle Atlantic (16%), and the lowest in the Mountain (4%) and New England (2%). Vasculitis patients with comorbid lymphoma (OR 2.46, P<0.001), peripheral vascular diseases (PVD (OR 1.54, P<0.001)), and complicated hypertension (OR 1.31, P<0.001) were associated with increasing the likelihood for CVD-related hospitalization. The mean length of stay was 13 days and the mean cost was $169,440 per CVD-related hospitalization in vasculitis patients. Cerebrovascular diseases in patients with vasculitis resulted in a major loss of body functioning (80%) leading to adverse disposition including transfer to a skilled nursing facility/intermediate care facility (22%) and requiring home health care (13%). Conclusion The prevalence of CVD-related hospitalization in vasculitis patients was 2.5% and females were observed to be at higher risk. Comorbid lymphoma, PVD, and hypertension further increase the risk for CVD with vasculitis. They have a higher loss of functioning that affects patient quality of life and require increased care after hospital discharge.


An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome.
Congenital central hypoventilation syndrome is a rare genetic disorder affecting ventilatory response to hypercapnia and/or hypoxemia. We describe a case of diaphragm pacing (DP) failure in a 38-year-old woman with congenital central hypoventilation syndrome who used DP as ventilatory support only during sleep for 24 years. Diagnostic evaluation began with examination of external DP equipment, but adjustment did not elicit adequate diaphragm contractions. Clinical evaluation and transtelephonic monitoring showed absent function of the right pacer and diminished function of the left pacer. The patient had surgical exploration of her internal DP components. The operation revealed that the right pacer receiver had significant circumferential calcium accumulation. After replacement of the receivers in subcutaneous pockets closer to the skin surface, robust diaphragm contractions bilaterally occurred with stimulation. This case suggests DP failure can result from development of calcification and increased distance from the skin surface to the receivers due to weight gain. Kwon A, Lodge M, McComb JG, et al. An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome. J Clin Sleep Med. 2022;18(3):949-952.


Induction of Sca-1 in the duct cells of the mouse submandibular gland by obstruction of the main excretory duct.
The effect of ligation of the main excretory duct (MED) of the mouse submandibular gland (SMG) on the expression of Sca-1, a stem cell antigen, was examined by Western blotting and immunohistochemistry. By Western blotting, the expression of Sca-1 with a molecular weight of 18 kDa was identified in the normal gland. At 1 day post-ligation, the expression level of Sca-1 was strongly increased in the experimental gland and weakly in the contralateral gland, and such expression in both glands decreased at 6 days. By immunohistochemistry, Sca-1 was detected weakly in the apical membrane of excretory duct (ED) cells of the SMG under the normal condition. By duct ligation, Sca-1 became expressed strongly in most cells of the two major duct systems, i.e., the striated duct (SD) and granular convoluted tubules (GCT), but was not detected in the acinar (Ac) cells. By fluorescence-activated cell sorter (FACS) analysis, the number of side population (SP) cells in this gland was found to be increased by ligation. These results imply that Sca-1-positive cells may have a role in the duct cell proliferation in the regeneration step elicited by MED ligation-induced injury.


Job stressors and coping in health professions.
In spite of their knowledge about stressors, health hazards and coping, health professionals are in general not aware of their own health risks. In an attempt to clarify the issue results of our own studies are compared to the relevant literature. A survey on 1,248 Swiss nurses confirmed the major stressors known: ethical conflicts about appropriate patient care, team conflicts, role ambiguity, workload and organizational deficits. In doctors workload and shortage of time, combined with specific responsibility in decision making, are most prominent. Nevertheless, job satisfaction is still high in both professions. Health hazards in doctors are considerable, although life expectancy has improved and is comparable to the general public, but still lower as compared to other professionals. Depression and substance abuse are related to higher suicide rates. The specific role strain of female doctors is responsible for health risks with an alarming 10 years lower life expectancy than in the general population. Little is known about specific health hazards in nurses, except for burnout. A lack of coping research in the field makes conclusions difficult. Our own studies show limited coping skills in nurses, but good buffering effect in 1,700 Swiss dentists.


[Cyclin-dependent kinase 4 inhibitor a and tumor].
INK4a/ARF locus encodes at least two products, P16(INK4a) and P19(ARF), which are very important in controlling cell-cycle arrest and apoptosis. Many human cancers have been found to be highly related to the mutations at this locus. Here is a review of its structure, function and role in tumor suppression.


Knockdown of circular RNA tousled-like kinase 1 relieves ischemic stroke in middle cerebral artery occlusion mice and oxygen-glucose deprivation and reoxygenation-induced N2a cell damage.
Ischemic stroke (IS) is an essential contributor to the neurological morbidity and mortality throughout the world. The significance of circular RNA tousled-like kinase 1 (circTLK1) in IS has been documented. This study set out to explore the mechanism of circTLK1 in IS. Middle cerebral artery occlusion (MCAO) mouse models in vivo and oxygen-glucose deprivation and reoxygenation (OGD/R) cell models in vitro were first established, followed by evaluation of infarct volume and neurological impairment, and cell viability and apoptosis. The expression patterns of circTLK1, miR-26a-5p, phosphatase and tensin homolog (PTEN), insulin-like growth factor type 1 receptor (IGF-1 R), and glucose transporter type 1 (GLUT1) were detected by RT-qPCR and Western blotting. Co-localization of circTLK1 and miR-26a-5p in N2a cells was tested by fluorescence in situ hybridization assay. The binding relationships among circTLK1, PTEN, and miR-26a-5p were verified by dual-luciferase assay and RNA pull-down. circTLK1 and PTEN were highly expressed while miR-26a-5p was under-expressed in IS models. circTLK1 knockdown decreased infarct volume and neurological impairment in MCAO mouse models and relieved OGD/R-induced neuronal injury in vitro. circTLK1 and miR-26a-5p were co-located in the N2a cell cytoplasm. circTLK1 regulated PTEN as a sponge of miR-26a-5p. PTEN positively regulated IGF-1 R and GLUT1 expressions. miR-26a-5p inhibitor annulled the repressive effects of circTLK1 silencing on OGD/R-induced neuronal injury. sh-PTEN partially annulled the effects of the miR-26a-5p inhibitor on OGD/R-induced neuronal injury. In conclusion, circTLK1 knockdown relieved IS via the miR-26a-5p/PTEN/IGF-1 R/GLUT1 axis. These results may provide a new direction to IS potential therapeutic targets.


TRAF6 autophagic degradation by avibirnavirus VP3 inhibits antiviral innate immunity via blocking NFKB/NF-κB activation.
Ubiquitination is an important reversible post-translational modification. Many viruses hijack the host ubiquitin system to enhance self-replication. In the present study, we found that Avibirnavirus VP3 protein was ubiquitinated during infection and supported virus replication by ubiquitination. Mass spectrometry and mutation analysis showed that VP3 was ubiquitinated at residues K73, K135, K158, K193, and K219. Virus rescue showed that ubiquitination at sites K73, K193, and K219 on VP3 could enhance the replication abilities of infectious bursal disease virus (IBDV), and that K135 was essential for virus survival. Binding of the zinc finger domain of TRAF6 (TNF receptor associated factor 6) to VP3 mediated K11- and K33-linked ubiquitination of VP3, which promoted its nuclear accumulation to facilitate virus replication. Additionally, VP3 could inhibit TRAF6-mediated NFKB/NF-κB (nuclear factor kappa B) activation and IFNB/IFN-β (interferon beta) production to evade host innate immunity by inducing TRAF6 autophagic degradation in an SQSTM1/p62 (sequestosome 1)-dependent manner. Our findings demonstrated a macroautophagic/autophagic mechanism by which Avibirnavirus protein VP3 blocked NFKB-mediated IFNB production by targeting TRAF6 during virus infection, and provided a potential drug target for virus infection control.Abbreviations: ATG: autophagy related; BafA1: bafilomycin A1; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; Cas9: CRISPR-associated protein 9; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GST: glutathione S-transferase; IBDV: infectious bursal disease virus; IF: indirect immunofluorescence; IFNB/IFN-β: interferon beta; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MS: mass spectrometry; NFKB/NF-κB: nuclear factor kappa B; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; pAb: polyclonal antibody; PRRs: pattern recognition receptors; RNF125: ring finger protein 125; RNF135/Riplet: ring finger protein 135; SQSTM1/p62: sequestosome 1; TAX1BP1: tax1 binding protein1; TCID50: 50% tissue culture infective dose; TRAF3: TNF receptor associated factor 3; TRAF6: TNF receptor associated factor 6; TRIM25: tripartite motif containing 25; Ub: ubiquitin; Wort: wortmannin; WT: wild type.


"Writing biochips": high-resolution droplet-to-droplet manufacturing of analytical platforms.
The development of high-resolution molecular printing allows the engineering of analytical platforms enabling applications at the interface between chemistry and biology, i.e. in biosensing, electronics, single-cell biology, and point-of-care diagnostics. Their successful implementation stems from the combination of large area printing at resolutions from sub-100 nm up to macroscale, whilst controlling the composition and volume of the ink, and reconfiguring the deposition features in due course. Similar to handwriting pens, the engineering of continuous writing systems tackles the issue of the tedious ink replenishment between different printing steps. To this aim, this review article provides an unprecedented analysis of the latest continuous printing methods for bioanalytical chemistry, focusing on ink deposition systems based on specific sets of technologies that have been developed to this aim, namely nanofountain probes, microcantilever spotting, capillary-based polymer pens and continuous 3D printing. Each approach will be discussed revealing the most important applications in the fields of biosensors, lab-on-chips and diagnostics.


Isolation and expression of Lea gene in desiccation-tolerant microspore-derived embryos in Brassica spp.
Desiccation tolerance can be induced in microspore-derived embryos of Brassica spp. by application of abscisic acid (ABA). As part of our effort to elucidate the molecular mechanism in induction of desiccation tolerance of embryos, we have isolated Lea genes and examined their expression in microspore-derived embryos of B. napus and B. campestris. The cDNA clones of Lea genes were isolated from desiccation-tolerant microspore-derived embryos of both species. Two cDNA clones of B. napus and B. campestris shared a similar homology of 92.9% identity between the two deduced proteins. These proteins also had high homology with Lea 76 which was isolated from zygotic embryos of B. napus, but were 54 amino acids shorter than Lea 76. Acquisition of desiccation tolerance of the microspore-derived embryos and accumulation of mRNA and its transcripts of the Lea genes began within 12 h of ABA treatment. The embryos treated with ABA for 48-168 h showed a high desiccation tolerance and accumulation of Lea proteins at high levels. The close relationships between the induction of desiccation tolerance of embryos and the expression level of Lea genes suggest an important function of Lea proteins for desiccation tolerance in embryos.


The Mechanics of Injury to Isolated Protoplasts following Osmotic Contraction and Expansion.
Micro-osmotic manipulation was used to determine the influence of osmotic contraction on the expansion potential of individual protoplasts isolated from rye (Secale cereale L. cv Puma) leaves. For protoplasts isolated from leaves of nonacclimated plants (NA protoplasts), osmotic contraction in sufficiently hypertonic solutions (>1.53 osmolal) predisposed the protoplasts to lysis during osmotic expansion when they were returned to isotonic conditions (0.53 osmolal). In contrast, for protoplasts isolated from leaves of cold acclimated plants (ACC protoplasts), osmotic contraction in either 2.6 or 4.0 osmolal solutions was readily reversible. Following osmotic contraction, the resting tension (gamma(r)) of NA protoplasts was similar to that determined for protoplasts in isotonic solutions (i.e. 110 +/- 22 micronewtons per meter). In contrast, gamma(r) of ACC protoplasts decreased from 164 +/- 27 micronewtons per meter in isotonic solutions to values close to zero in hypertonic solutions. Following expansion in hypotonic solutions, gamma(r)'s of both NA and ACC protoplasts were similar for area expansions over the range of 1.3 to 1.6. Following osmotic contraction and reexpansion of NA protoplasts, hysteresis was observed in the relationship between gamma(r) and surface area-with higher values of gamma(r) at a given surface area. In contrast, no hysteresis was observed in this relationship for ACC protoplasts. Direct measurements of plasma membrane tension (gamma) during osmotic expansion of NA protoplasts from hypertonic solutions (1.53 osmolal) revealed that gamma increased rapidly after small increments in surface area, and lysis occurred over a range of 1.2 to 8 millinewtons per meter. During osmotic expansion of ACC protoplasts from hypertonic solutions (2.6 osmolal), there was little increase in gamma until after the isotonic surface area was exceeded. These results are discussed in relation to the differences in the behavior of the plasma membrane of NA and ACC protoplasts during osmotic contraction (i.e. endocytotic vesiculation versus exocytotic extrusion) and provide a mechanistic interpretation to account for the differential sensitivity of NA and ACC protoplasts to osmotic expansion from hypertonic solutions.


Diagnosis and treatment of gastroesophageal reflux disease: recommendations of the Asociación Mexicana de Gastroenterología.
Emerging concepts in the pathophysiology of gastroesophageal reflux disease (GERD) and the constant technologic advances in the diagnosis and treatment of this clinical condition make it necessary to frequently review and update the clinical guidelines, recommendations, and official statements from the leading academic groups worldwide. The Asociación Mexicana de Gastroenterología (AMG), aware of this responsibility, brought together national experts in this field to analyze the most recent scientific evidence and formulate a series of practical recommendations to guide and facilitate the diagnostic process and efficacious treatment of these patients. The document includes algorithms, figures, and tables for convenient consultation, along with opinions on GERD management in sensitive populations, such as pregnant women and older adults.


Perceptual interaction between real and synesthetic colors.
People with color-graphemic synesthesia experience vivid, reliable color upon viewing achromatic alphanumeric characters. Recent evidence indicates that synesthetic color experiences are as perceptually real as actual colors are for non-synesthetic observers. To investigate possible interactions between real and synesthetic colors, we tested two adult color-graphemic synesthetes on a pair of perceptual grouping tasks. In Experiment 1, we employed a well-known phenomenon of motion perception, bistable apparent motion, to explore whether synesthetic colors interact with real colors in grouping over time. Two-frame apparent motion sequences were presented with both path lengths and colors systematically manipulated. Results showed that synesthetic colors of motion tokens interacted with matching real colors of the corresponding motion tokens, which could subsequently bias perceived direction of motion. In Experiment 2, we exploited binocular rivalry, a condition under which two dissimilar monocular images compete with each other and result in perceptual switches, to explore whether synesthetic colors interact with real colors in grouping over space. Pairs of rival images with two different characters were presented dichoptically with colors of characters manipulated. Results showed that synesthetic and real colors of characters tended to group together, which, in turn, promoted the perceived global dominance during binocular rivalry. Therefore, the present results identify substantial interaction between synesthetic colors and real colors in perceptual grouping.


Carbonic Anhydrase Glycoinhibitors belonging to the Aminoxysulfonamide Series.
A general approach for the synthesis of carbonic anhydrases glycoinhibitors belonging to an aminoxysulfonamide series is presented using a Ferrier sulfonamidoglycosylation reaction on glycals. All the compounds showed good in vitro inhibitory activity against four human carbonic anhydrase isoforms, with selectivity against the cytosolic (hCA II) vs the tumor associated (hCA IX and XII) enzymes.


Influence of dose and infusion duration on pharmacokinetics of ifosfamide and metabolites.
The anticancer drug ifosfamide is a prodrug requiring activation through 4-hydroxyifosfamide to ifosforamide mustard, to exert cytotoxicity. Deactivation of ifosfamide leads to 2- and 3-dechloroethylifosfamide and the release of potentially neurotoxic chloracetaldehyde. The aim of this study was to quantify and to compare the pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide, 4-hydroxyifosfamide, and ifosforamide mustard in short (1-4 h), medium (24-72 h), and long infusion durations (96-240 h) of ifosfamide. An integrated population pharmacokinetic model was used to describe the autoinducible pharmacokinetics of ifosfamide and its four metabolites in 56 patients. The rate by which autoinduction of the metabolism of ifosfamide developed was found to be significantly dependent on the infusion schedule. The rate was 52% lower with long infusion durations compared with short infusion durations. This difference was, however, comparable with its interindividual variability (22%) and was, therefore, considered to be of minor clinical importance. Autoinduction caused a less than proportional increase in the area under the ifosfamide plasma concentration-time curve (AUC) and more than proportional increase in metabolite exposure with increasing ifosfamide dose. During long infusion durations dose-corrected exposures (AUC/D) were significantly decreased for ifosfamide and increased for 3-dechloroethylifosfamide compared with short infusion durations. No differences in dose-normalized exposure to ifosfamide and metabolites were observed between short and medium infusion durations. This study demonstrates that the duration of ifosfamide infusion influences the exposure to the parent and its metabolite 3-dechloroethylifosfamide. The observed dose and infusion duration dependence should be taken into account when modeling ifosfamide metabolism.


Measuring Binding Constants of His-Tagged Proteins Using Affinity Chromatography and Ni-NTA Immobilized Enzymes.
Affinity chromatography is one way to measure the binding constants of a protein-ligand interaction. Here, we describe a method of measuring a binding constant using Ni-NTA resin to immobilize a His-tagged enzyme and the method of frontal analysis. While other methods of immobilization are possible, using the strong affinity interaction between His-tagged proteins and Ni-NTA supports results in a fast, easy, and gentle method of immobilization. Once the affinity support is created, frontal analysis can be used to measure the binding constant between the protein and various analytes.


Broadband form birefringent quarter-wave plate for the mid-infrared wavelength region.
We discuss the design, fabrication and optical performance of a broadband form-birefringent quarter-wave plate for the 3.5 to 5 aem wave-length region. Rigorous coupled wave analysis (RCWA) was used to design the requisite subwavelength grating for silicon substrates in ambient air. Fabricated samples yield a measured phase retardation of 89ø to 102ø over the desired wavelength range.


Controlled formation of model homo- and heterodimer coiled coil polypeptides.
Sequence-simplified coiled coil polypeptides were synthesized and their folding properties characterized in order to define the role of charged border residues at the coiled coil interface for the controlled formation of homodimer and heterodimer structures. Three peptides were designed to form parallel coiled coils with valine and leucine occupying the hydrophobic interface positions a and d, respectively, of the heptad repeat abcdefg. The polypeptide designated E/K42, with the heptad repeat sequence VSSLESK, contained glutamate and lysine in the interface border positions e and g, respectively, and was designed to form a coiled coil homodimer at neutral pH. Two other polypeptides, designated E/E35 and K/K35, have the heptad repeats VSSLESE and VSSLKSK, respectively. E/E35 contains only glutamic acid at both e and g positions; K/K35, only lysine, E/E35 and K/K35 were designed to form a stable coiled coil heterodimer when combined at neutral pH. All three polypeptides were prepared by solid-phase synthesis and purified by reverse-phase high-performance liquid chromatography followed by size-exclusion chromatography. E/K42 formed a stable dimeric coiled coil structure as determined by circular dichroism and size-exclusion chromatography. The alpha-helical content of E/K42 was highest at neutral pH and decreased at extremes of pH. The alpha-helical structure of E/K42 at micromolar concentrations had a Tm of 62-65 degrees C and exhibited a concentration dependence of thermal denaturation consistent with dimer formation. In contrast to results with E/K42, a mixture of E/E35 and K/K35, but neither alone, forms alpha-helix at neutral pH.(ABSTRACT TRUNCATED AT 250 WORDS)


Social insurance for health service.
Implementation of social insurance for financing health services has yielded different patterns depending on a country's economic level and its government's political ideology. By the late 19th century, thousands of small sickness funds operated in Europe, and in 1883 Germany's Chancellor Bismarck led the enactment of a law mandating enrollment by low-income workers. Other countries followed, with France completing Western European coverage in 1928. The Russian Revolution in 1917 led to a National Health Service covering everyone from general revenues by 1937. New Zealand legislated universal population coverage in 1939. After World War II, Scandinavian countries extended coverage to everyone and Britain introduced its National Health Service covering everyone with comprehensive care and financed by general revenues in 1948. Outside of Europe Japan adopted health insurance in 1922, covering everyone in 1946. Chile was the first developing country to enact statutory health insurance in 1924 for industrial workers, with extension to all low-income people with its "Servicio Nacional de Salud" in 1952. India covered 3.5 percent of its large population with the Employees' State Insurance Corporation in 1948, and China after its 1949 revolution developed four types of health insurance for designated groups of workers and dependents. Sub-Saharan African countries took limited health insurance actions in the late 1960s and 1970s. By 1980, some 85 countries had enacted social security programs to finance or deliver health services or both.


Selection of anticoagulant-preservatives for canine and feline blood storage.
Blood or blood component transfusions have become a well recognized, lifesaving form of therapy in veterinary medicine. Blood used for small animal transfusions may be collected and prepared with a variety of anticoagulants, anticoagulant-preservatives, or additive solutions. Selection of the most appropriate of these collection or storage solutions requires a knowledge of their formulations and of the shelf-lives previously established for storage of canine or feline red blood cells. Other factors that should be considered in the selection process are based on the specific transfusion needs of a clinic and its patients, including whether the blood will be used fresh or stored, the length of storage time desired, and whether components will be prepared. New products and techniques for blood storage continue to be developed, offering exciting new possibilities for the future practice of veterinary transfusion medicine.


Structural effects of the local anesthetic bupivacaine hydrochloride on the human erythrocyte membrane and molecular models.
The interaction of the local anesthetic bupivacaine with the human erythrocyte membrane and molecular models is described. The latter consisted of isolated unsealed human erythrocyte membranes (IUM), large unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC), and phospholipid multilayers built-up of DMPC and dimyristoylphosphatidylethanolamine (DMPE), representatives of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. Optical and scanning electron microscopy revealed that bupivacaine induced erythrocyte spheroechinocytosis. According to the bilayer couple hypothesis, this result implied that bupivacaine inserted in the outer monolayer of the erythrocyte membrane. Experiments performed on IUM and DMPC LUV by fluorescence spectroscopy and X-ray diffraction on DMPC and DMPE multilayers confirmed this result. Changes in the molecular organization of membranes alter lipid-protein interactions and induce functional perturbation of membrane proteins such as Na(+) channels. Since local anesthetics may control the influx of Na(+) into the human erythrocyte, in order to relate the structural perturbations induced by bupivacaine in these systems to Na(+) transport, the interaction of this anesthetic with isolated toad skin was also studied. Electrophysiological measurements indicated a significant decrease in the potential difference and in the short-circuit current of the skin after the application of the anesthetic, reflecting inhibition of the active transport of ions. These results suggest that bupivacaine-induced conformational changes of the lipid molecules alter the lipid-protein boundaries of the outer moiety of the erythrocyte membrane, thus interfering with the function of neighboring sodium channels.


[Role of transesophageal echocardiography in the diagnosis of cardiac disorders].
Transesophageal echocardiography provides a new window for ultrasound examination of the heart. The approach allows ultrasonic access to the heart in patients with transthoracic images of inadequate quality. Furthermore, transesophageal examination may provide information additional to that from the conventional transthoracic approach in the search for lesions including complications of endocarditis, mitral prosthesis dysfunction, aortic dissection, embolism of cardiac origin and selected cardiac malformations.


Neuraxial anesthesia versus general anesthesia for urological surgery: systematic review.
CONTEXT AND OBJECTIVE Choosing the best anesthetic technique for urological surgery with the aim of mortality reduction remains controversial. The objective here was to compare the effectiveness and safety of neuraxial anesthesia versus general anesthesia for urological surgery. DESIGN AND SETTING Systematic review, Universidade Federal de Alagoas. METHODS We searched the Cochrane Central Register of Controlled Trials in the Cochrane Library (Issue 10, 2012), Medline via PubMed (1966 to October 2012), Lilacs (1982 to October 2012), SciELO and EMBASE (1974 to October 2012). The reference lists of the studies included and of one systematic review in the same field were also analyzed. The studies included were randomized controlled trials (RCT) that analyzed neuraxial anesthesia and general anesthesia for urological surgery. RESULTS The titles and abstracts of 2720 articles were analyzed. Among these, 16 studies were identified and 11 fulfilled the inclusion criteria. One RCT was published twice. The study validity was: Jadad score > 3 in one RCT; seven RCTs with unclear risk of bias as the most common response; and five RCTs not fulfilling half of the Delphi list items. The frequency of mortality was not significant between study groups in three RCTs. Meta-analysis was not performed. CONCLUSION At the moment, the evidence available cannot prove that neuraxial anesthesia is more effective and safer than general anesthesia for urological surgery. There were insufficient data to pool the results relating to mortality, stroke, myocardial infarction, length of hospitalization, quality of life, degree of satisfaction, postoperative cognitive dysfunction and blood transfusion requirements.


Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of aggressiveness.
The biological factors responsible for the increased aggressiveness in atypical meningiomas are not well known. The aim of this study is to evaluate the discriminatory value of a number of biological markers (S100 proteins and galectin-3 and its ligand profile) with respect to benign and atypical meningiomas. Using 63 meningiomas (39 benign and 24 atypical), we performed a semi-quantitative histochemical analysis of both the expression of galectin-3 and its ligand profile and the Ca2+-binding proteins S100A5, S100A6 and S100B. Three features were considered for each marker, namely the labeling index (LI), the staining intensity (SI) and the global score (LI + SI). A low S100A6 labeling index was observed in 51% of the benign and 25% of the atypical meningiomas (P=0.035). Furthermore, high S100B scores were observed in 46% of the benign and in only 8% of the atypical meningiomas (P=0.001). Seventy-one percent of the atypical meningiomas exhibited a low level of staining intensity for the galectin-3-binding sites as compared to only 36% of the benign meningiomas (P=0.007). The combination of these three markers (by means of a decision tree) enabled an improved discriminatory criterion to be established between the benign and the atypical meningiomas. Our results thus suggest that the galectin-3-binding sites and S100B (and S100A6 to a lesser extent) could play a role in the aggressiveness characterizing atypical meningiomas.


Automatic quality assessment protocol for MRI equipment.
The authors have developed a protocol and software for the quality assessment of MRI equipment with a commercial test object. Automatic image analysis consists of detecting surfaces and objects, defining regions of interest, acquiring reference point coordinates and establishing gray level profiles. Signal-to-noise ratio, image uniformity, geometrical distortion, slice thickness, slice profile, and spatial resolution are checked. The results are periodically analyzed to evaluate possible drifts with time. The measurements are performed weekly on three MRI scanners made by the Siemens Company (VISION 1.5T, EXPERT 1.0T, and OPEN 0.2T). The results obtained for the three scanners over approximately 3.5 years are presented, analyzed, and compared.


The Role of Chemokines in Cervical Cancers.
Both clinical-pathological and experimental studies have shown that chemokines play a key role in activating the immune checkpoint modulator in cervical cancer progression and are associated with prognosis in tumor cell proliferation, invasion, angiogenesis, chemoresistance, and immunosuppression. Therefore, a clear understanding of chemokines and immune checkpoint modulators is essential for the treatment of this disease. This review discusses the origins and categories of chemokines and the mechanisms that are responsible for activating immune checkpoints in cervical dysplasia and cancer, chemokines as biomarkers, and therapy development that targets immune checkpoints in cervical cancer research.


Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews.
We have shown previously that repeated laboratory restraint stress or daily corticosterone administration affects the structure of CA3 hippocampal neurons in rats. In the present study, we investigated the effect of repeated daily psychosocial stress on the structure of hippocampal CA3 pyramidal neurons in male tree shrews (Tupaia belangeri). Male tree shrews develop social hierarchies in which subordinates show characteristic changes in physiological and behavioral parameters when confronted with a dominant. In the present experiments, subordinate animals lost body weight soon after starting the daily social conflict, and urinary excretion of cortisol was elevated throughout the experiment as compared with the control period. Golgi-impregnated brain tissue from subordinates exposed to 28 d (1 hr/d) of social confrontations was compared with that from control nonstressed animals. The apical dendrites of the CA3 pyramidal cells from subordinates had a decreased number of branch points and total dendritic length as compared with controls. No differences were observed in apical dendritic spine density or in the basal dendritic tree morphology. The stress-induced CA3 apical dendritic atrophy in subordinates was prevented by administering daily oral doses of the antiepileptic drug phenytoin (Dilantin, Sigma, St. Louis, MO) (200 mg/kg), which interferes with excitatory amino acid (EAA) action. These results suggest that the naturalistic stressor psychosocial stress induces specific structural changes in hippocampal neurons of subordinate male tree shrews. These changes, like those in the rat after glucocorticoid treatment or restraint stress, probably are mediated by activation of the hypothalamo-pituitary-adrenal-axis acting in concert with endogenous EAAs from mossy fiber input.


Developmental and environmental regulation of tissue- and cell-specific expression for a pea protein farnesyltransferase gene in transgenic plants.
Farnesylation mediates membrane targeting and in vivo activities of several key regulatory proteins such as Ras and Ras-related GTPases and protein kinases in yeast and mammals, and is implicated in cell cycle control and abscisic acid (ABA) signaling in plants. In this study, the developmental expression of a pea protein farnesyltransferase (FTase) gene was examined using transgenic expression of the beta-glucuronidase (GUS) gene fused to a 3.2 kb 5' upstream sequence of the gene encoding the pea FTase beta subunit. Coordinate expression of the GUS transgene and endogenous tobacco FTase beta subunit gene in tobacco cell lines suggests that the 3.2 kb region contains the key FTase promoter elements. In transgenic tobacco plants, GUS expression is most prominent in meristematic tissues such as root tips, lateral root primordia and the shoot apex, supporting a role for FTase in the control of the cell cycle in plants. GUS activity was also detected in mature embryos and imbibed embryos, in accordance with a role for FTase in ABA signaling that modulates seed dormancy and germination. In addition, GUS activity was detected in regions that border two organs, e.g. junctions between stems and leaf petioles, cotyledons and hypocotyls, roots and hypocotyls, and primary and secondary roots. GUS is expressed in phloem complexes that are adjacent to actively growing tissues such as young leaves, roots of light-grown seedlings, and hypocotyls of dark-grown seedlings. Both light and sugar (e.g. sucrose) treatments repressed GUS expression in dark-grown seedlings. These expression patterns suggest a potential involvement of FTase in the regulation of nutrient allocation into actively growing tissues.


Variability of the reproductive system of Piscicola fasciata (Kollar, 1842 (Hirudinea, Piscicolidae).
The studies on the reproductive system of P. fasciata were based on 43 specimens. Two main types of the reproductive system can be distinguished in the studied population. Two types of reproductive system were the most frequent (20.93% each): with symmetrical ejaculatory ducts without a loop and symmetrical seminal vesicles reaching the end of the first pair of testes, situated next to the testes (adult individuals) (fig. 23) and with symmetrical ejaculatory ducts without a loop (fig. 21) and symmetrical poorly developed seminal vesicles situated asymmetrically anterior to the first pair of testes (juvenile individuals). The structure of the reproductive system corresponding with the description of the type specimen (BRUMPT, 1900) was not observed in the studied population.


Distraction First Metatarsophalangeal Arthrodesis With Tricortical Calcaneus Autograft: Technique Tips.
First metatarsophalangeal joint arthritis can stem from a biomechanical imbalance as in hallux abducto valgus, metabolic arthritidies such as rheumatoid or gout, and even in posttraumatic cases. Advanced arthritis in the foot and ankle can often become debilitating. Surgical intervention is often necessary. Revision of failed first metatarsophalangeal joint arthroplasty is often in the setting of bony erosion and lysis, cystic changes, and loss of bone stock. In this article, we describe first metatarsophalangeal distraction arthrodesis technique using tricortical calcaneus autograft with the aim of simplifying donor site graft harvesting and decreasing donor site morbidity while attaining successful osseous union. Level V.


Health-related quality of life among adolescents with polycystic ovary syndrome.
To explore health-related quality of life (HRQoL) among adolescents with polycystic ovary syndrome (PCOS). Qualitative study. Two out-patient gynecology clinics in Yorkshire, England. Fifteen young women diagnosed with PCOS were recruited. Semistructured interviews were carried out, transcribed verbatim, and subjected to thematic analysis using NVivo software version 2.0. A few areas were identified where PCOS had a positive impact upon HRQoL (e.g., improved relationships). However, overall the condition had a negative impact upon HRQoL. Weight problems (in particular the difficulties associated with managing/maintaining weight) and body perceptions appeared to be the most significant contributors to a reduced HRQoL. Menstrual dysfunction, fertility issues, and hirsutism also had adverse affects on emotional well-being, self-perception (including poor body image, self-consciousness, & low self-esteem), social functioning, and sexual behavior. A number of participants described receiving insufficient information from health care professionals (HCPs) and negative experiences in relation to the diagnosis and management of their condition. Overall, PCOS has a negative impact on the HR QoL of adolescent girls with the condition. Emotional and social functioning appeared to be most affected rather than areas of physical functioning. Future research is needed to identify ways to improve communication between adolescents with PCOS and their HCPs, particularly around the diagnosis and potential for infertility. Finally, HCPs need to be more aware of the emotional impact of PCOS upon adolescents' HRQoL and of the potential for poor sexual health through risk-taking behaviors that may occur due to the potential loss of fertility.


Utilization of a National Writing Challenge to Promote Scholarly Work: A Pilot Study.
Background Hospitalists value mentorship and scholarly work, yet often struggle to find time and mentors amid busy clinical workloads. Objective To help catalyze writing for hospitalists nationally, we created a Writing Challenge, where we asked hospitalists to commit to the goal of writing 400 words a day, four days a week, for four weeks. Methods Prospective, programmatic evaluation with daily logs followed by a survey at the completion of the project. The four-week Writing Challenge occurred between June 7 and July 5, 2021. Email invitations to participate in the challenge were disseminated to peer networks, and the challenge was promoted using social media. Participants agreed to attempt to write 400 words per day, four days per week, for four weeks. Results Seventy-four individuals from 28 institutions registered for the Writing Challenge, with 36 (49%) participating in the challenge by logging their writing. Participants wrote an average of 4,372 +/- 4,324 words during the challenge. Sixty-eight percent of the participants reported that their amount of writing increased during the challenge and 50% of the participants stated they planned to publish their work, though many participants (46%) reported struggling to write each day. Conclusions The Writing Challenge is one way to generate increased writing and may result in increased scholarly output for academic hospitalists.