Interleukin-8 promotes cell migration via CXCR1 and CXCR2 in liver cancer.
Liver cancer (LC), which is one of the most common types of cancer worldwide, is notorious for its high morbidity and mortality rates. Interleukin-8 (IL-8), an important member of the CXC chemokine family that was originally classified as a potent neutrophil chemoattractant, has been shown to serve an important role in inflammation, tumor growth, invasion and metastasis through interactions with its receptors. However, the expression and functional roles of IL-8 and its receptors, CXC chemokine receptor (CXCR) 1 and CXCR2 in the progression of liver cancer remain to be fully elucidated. In the present study, it was shown that the mRNA levels of IL-8, CXCR1 and CXCR2 were increased in peripheral blood mononuclear cells from patients with liver cancer compared with those from patients with cirrhosis or normal controls (P<0.05). Higher levels of CXCR1, CXCR2 and IL-8 were associated with advanced tumor stage and increased risk of lymph node or distant metastasis. Immunohistochemistry showed that the IL-8, CXCR1 and CXCR2 proteins were expressed in the cytoplasm of hepatoma cells at higher intensities than those of normal controls (P<0.05). The semi-quantitative analysis revealed that the relative mean density of hepatic IL-8, CXCR1 and CXCR2 staining in liver cancer was significantly increased compared with that in normal liver tissues (P<0.05). The analysis revealed that the mRNA expression of IL-8 was positively associated with that of CXCR1 (r=0.618; P<0.05) and CXCR2 (r=0.569; P<0.05). The mRNA levels of CXCR1 and CXCR2 gradually increased with elevated expression of IL-8 in liver cancer. Experiments were performed using human Huh-7 and HepG2 cell lines, incubating cells with IL-8 and conducting in vitro migration and invasion assays. The results showed that the wound healing activity and migration of Huh-7 and HepG2 cells were increased by IL-8. Pretreatment of the cells with anti-CXCR1 or anti-CXCR2 (5 µM) for 30 min markedly inhibited IL-8-directed cell migration. Taken together, these results indicated that IL-8 promotes liver cancer cell migration via CXCR1 and CXCR2 and that targeting the CXCR1/2 may be a potential strategy for liver cancer treatment.


Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area.
Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency. Particulate matter (PM<0.1, PM0.1-0.5, PM0.5-2.5, PM2.5-10, PM>10) samples collected at sites within Windsor, Ontario, were screened for biological potency in human A549 lung epithelial and murine J774A.1 macrophage-like cells using cytotoxicity bioassays (cellular ATP, resazurin reduction, lactate dehydrogenase (LDH) release), cytokine production, and transcript profiles. Potency was determined from the slope of each dose-effect relationship. Cytotoxic potency varied across size fractions and within a fraction across sites and sampling periods, suggesting that particle composition, in addition to size and mass, affected particle toxicity. While ATP and LDH profiles showed some similarity, resazurin reduction (a measure of metabolic activity) exhibited a unique pattern of response, indicating that the cytotoxicity assays were sensitive to distinct particle characteristics. Chemical speciation varied in relation to prevailing winds, consistent with enrichment of source emissions (e.g. higher metal and polycyclic aromatic hydrocarbon content downwind of the industrial site). Notwithstanding this variability, site-dependent differences in particle toxicity were evident, including greater potency of coarse fractions at the industrial site and of ultrafine particles at the traffic site (Site × Size interactions, p < 0.05). Regression of potency against particle constituents revealed correlations between resazurin reduction, induction of metal-responsive genes, and metal content, which were particularly strong for the coarse fraction, and between cytokine release and endotoxin, suggesting that these factors were important drivers of biological effects that explain, at least in part, the contrasting potencies of particles compared on an equivalent mass basis. The data show that 1) particle potency and composition can exhibit significant temporal variation in relation to source contributions; 2) sources may differentially impact the potency of specific size fractions; and 3) particle constituents, notably metals and endotoxin, may elicit distinct biological responses. Together, the data are consistent with the notion that sources and composition, in addition to size and mass concentration, are relevant to particle toxicity.


Delay in diagnosis of cancer. Possible effects on the stage of disease and survival.
A total of 2299 new cancer patients were referred to the Northern Israel Oncology Center in 1974 and in 1980. The stage of disease, delay in diagnosis, the responsibility for the delay, and the survival of those referred in 1974 were investigated. At the time of diagnosis, 39% of the patients had localized disease, 34% had locally advanced disease, and 23% had metastatic disease. In 52% of the patients there was no delay in diagnosis. No correlation was found in the group as a whole between the stage of disease and delay in diagnosis. Only in the breast cancer group without delay in diagnosis, however, were there significantly more patients at an early stage than at an advanced stage of disease. At each stage of disease, responsibility for the delay was shared about equally between the patients and the physicians, except in advanced breast cancer, where the patients were more often responsible for the delay. The survival rate was higher in patients in whom the disease was diagnosed earlier. It was also higher at each clinical stage (Stages I and II) in patients who had no delay than in those with delay in diagnosis. The survival rate was higher in patients who were themselves responsible for the delay in diagnosis than in patients whose physicians were responsible for the delay. In 1980, less diagnosis were delayed in fewer patients than in 1974 (42% versus 65%). Responsibility for the delay in 1980 lay equally with the patients and with the physicians, but when compared to 1974, the physicians' responsibility and administrative delay were less. Campaigns for early diagnosis are advocated.


Inhibition of in vitro cell adherence of Clostridium difficile by Saccharomyces boulardii.
The influence on the adherence of Clostridium difficile to Vero cells of the yeast Saccharomyces boulardii, the yeast fractions (cytoplasm and cell wall) and the culture supernatant was investigated in vitro. C. difficile adherence was significantly inhibited when bacteria were pre-incubated with the whole yeast and the cell wall fraction; this adherence inhibition was dose-dependent. The cell wall fraction also acts upon the target cultured cells inasmuch as the level of adherence was significantly decreased when Vero cells were preincubated with it. The same experiments carried out in the presence of an inhibitor of serine proteases resulted in no inhibition of bacterial adherence. These results suggest that the yeast could inhibit adherence of C. difficile to cells thanks to its proteolytic activity but also through steric hindrance.


Early-Age Performance Analysis of Sludge Water Incorporation in High-Temperature Steam Cured Green High-Performance Concrete.
Sludge water (SW) with abundant sulfate ions (SO42-) was utilized in this work to replace freshwater (FW) to prepare green high performance concrete (GHPC). A comprehensive investigation was conducted to evaluate the early-age performance of GHPC specimen mixed with SW incorporation (GHPC-SW). High temperature steam curing (HTS) has been presented to prepare GHPC-SW specimens. The compressive strength of the GHPC-SW specimen cured by HTS curing for 2 days is 85.2 MPa, which is 34% higher than the compressive strength of the GHPC-SW specimen cured by 3 days standard curing as the reference. The mechanical property results reveal that the incorporation of SW makes no harmful effects on the strength formation of HPC specimens, compared with FW added specimens under the same curing methods. Moreover, XRD and TG analyses indicate that HTS curing can effectively improve the hydration degree of GHPC-SW specimens. MIP analysis has been conducted and the specimens cured by HTS curing exhibit a more refined pore structure with fewer harmful pores. This work lays a solid foundation for the utilization of SW in the concrete construction industry, which is resource saving and environmentally friendly.


Organopalladium(IV) chemistry.
Although the chemistry of Pd(0), Pd(I) and Pd(II) is well established, high oxidation state Pd(IV) complexes are less well-known. This situation has highly changed in recent years. Many well-defined Pd(IV) complexes has been isolated and characterized, providing evidence for a series of proposed Pd(II)/Pd(IV) catalytic reactions. A deep understanding of the behavior of Pd(IV) complexes could lead to the design and development of novel reactions that could not be accessed by traditional Pd(0)/Pd(II) chemistry. This critical review describes the stoichiometric reactions of Pd(IV) complexes and discusses their potential mechanism in catalytic reactions (137 references).


Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells.
Apoptosis and underlying mechanisms were evaluated in human umbilical vein endothelial cells (HUVECs), in target tissues of late diabetic vascular complications [human aortic endothelial cells (HAECs) and human retinal endothelial cells (HRECs)], and in endothelial progenitor cells (EPCs) exposed to FFAs, which are elevated in obesity and diabetes. Saturated stearic acid concentration dependently induced apoptosis that could be mediated via reduced membrane fluidity, because both apoptosis and membrane rigidity are counteracted by eicosapentaenoic acid. PUFAs triggered apoptosis at a concentration of 300 micromol/l in HUVECs, HAECs, and EPCs, but not HRECs, and, in contrast to stearic acid, involved caspase-8 activation. PUFA-induced apoptosis, but not stearic acid-induced apoptosis, strictly correlated (P < 0.01) with protein expression of E2F-1 (r = 0.878) and c-myc (r = 0.966). Lack of c-myc expression and activity owing to quiescence or transfection with dominant negative In373-Myc, respectively, renders HUVECs resistant to PUFA-induced apoptosis. Because c-myc is abundant in growing cells only, apoptosis triggered by PUFAs, but not by saturated stearic acid, obviously depends on the growth/proliferation status of the cells. Finally, this study shows that FFA-induced apoptosis depends on the vascular origin and growth/proliferation status of endothelial cells, and that saturated stearic acid-induced apoptosis and PUFA-induced apoptosis are mediated via different mechanisms.


Modelling the effects of alcohol ethoxylates on diffusion of pesticides in the cuticular wax of Chenopodium album leaves.
Cuticular waxes represent the first and, in most cases, the limiting barrier for foliar uptake of pesticides from solution. Sorption of pesticides in reconstituted cuticular wax (wax/water partition coefficients) of Chenopodium album L. and in isolated cuticular membranes (cuticle/water partition coefficients) of Prunus laurocerasus L. was determined. Diffusion coefficients of pesticides in reconstituted cuticular wax of C. album leaves were size-dependent, increasing with increasing molar volume. In the presence of alcohol ethoxylates, diffusion coefficients were enhanced by up to two orders of magnitude, and size selectivity was significantly decreased. The accelerating effect and the decrease in size selectivity were attributed to plasticisation of the cuticular wax by the alcohol ethoxylates increasing the fluidity in the wax. A free volume model adopted from polymer science was successfully applied to predict diffusion coefficients of pesticides on the basis of the transport properties of the wax (size selectivity and crystallinity), the molar volume of the diffusing compound and the accelerator concentration in the wax.


[New possibilities for structural analysis of bone biopsies using microcomputer tomography (muCT)].
The combined histological and microcomputed analysis of human iliac crest biopsies leads to major advances in our understanding of three-dimensional bone architecture. Microcomputed tomography avoids the time-consuming reconstruction and artifacts of serial sections. Furthermore, its high resolution allows the recording of structural differences as low as 10 microns. Thus, three-dimensional analysis in combination with histological evaluation of cellular dynamics facilitates earlier and easier recording of changes of cancellous bone.


Probing the structural dependency of photoinduced properties of colloidal quantum dots using metal-oxide photo-active substrates.
We used photoactive substrates consisting of about 1 nm coating of a metal oxide on glass substrates to investigate the impact of the structures of colloidal quantum dots on their photophysical and photochemical properties. We showed during irradiation these substrates can interact uniquely with such quantum dots, inducing distinct forms of photo-induced processes when they have different cores, shells, or ligands. In particular, our results showed that for certain types of core-shell quantum dot structures an ultrathin layer of a metal oxide can reduce suppression of quantum efficiency of the quantum dots happening when they undergo extensive photo-oxidation. This suggests the possibility of shrinking the sizes of quantum dots without significant enhancement of their non-radiative decay rates. We show that such quantum dots are not influenced significantly by Coulomb blockade or photoionization, while those without a shell can undergo a large amount of photo-induced fluorescence enhancement via such blockade when they are in touch with the metal oxide.


Interaction between drought and chronic high temperature during kernel filling in wheat in a controlled environment.
Wheat plants (Triticum aestivum L. 'Lyallpur'), limited to a single culm, were grown at day/night temperatures of either 18/13 degrees C (moderate temperature), or 27/22 degrees C (chronic high temperature) from the time of anthesis. Plants were either non-droughted or subjected to two post-anthesis water stresses by withholding water from plants grown in different volumes of potting mix. In selected plants the demand for assimilates by the ear was reduced by removal of all but the five central spikelets. In non-droughted plants, it was confirmed that shading following anthesis (source limitation) reduced kernel dry weight at maturity, with a compensating increase in the dry weight of the remaining kernels when the total number of kernels was reduced (small sink). Reducing kernel number did not alter the effect of high temperature following anthesis on the dry weight of the remaining kernels at maturity, but reducing the number of kernels did result in a greater dry weight of the remaining kernels of droughted plants. However, the relationship between the response to drought and kernel number was confounded by a reduction in the extent of water stress associated with kernel removal. Data on the effect of water stress on kernel dry weight at maturity of plants with either the full complement or reduced numbers of kernels, and subjected to low and high temperatures following anthesis, indicate that the effect of drought on kernel dry weight may be reduced, in both absolute and relative terms, rather than enhanced, at high temperature. It is suggested that where high temperature and drought occur concurrently after anthesis there may be a degree of drought escape associated with chronic high temperature due to the reduction in the duration of kernel filling, even though the rate of water use may be enhanced by high temperature.


[Experimental study of circulatory dynamics following inhalation injury in dogs].
Early changes in respiratory and circulatory dynamics before and after steam-inhalation injury were made in a dog model were studied. The results showed that the resistance of the respiratory system was significantly higher 3 hours and 4 hours post injury than that before injury (P < 0.05), the compliances of both the lung 4 hours post-injury and the respiratory system 3 hours psot-injury significantly decreased (P < 0.05), and the heart rate markedly lowered (P < 0.01), and the cardiac output also decreased (P < 0.05) 2 hours after injury. It is suggested that the early changes in the respiratory and circulatory dynamics may be used as markers for the diagnosis and treatment of the inhalation injury.


Effects of non-medicated and copper IUDs on sperm migration.
35 women of proven fertility who were scheduled for surgical sterilization by salpingectomy were selected for this study; 15 control patients, 10 patients using the Multiload (ML) Cu 250 IUD, and 10 fitted with nonmedicated IUDs. Increased copper concentration did not affect sperm receptivity by the cervical mucus, but did significantly affect sperm motility and survival. Nonmedicated IUDs did not interfere with sperm transport in the oviduct. ML Cu IUDs inhibited sperm transport in the oviduct. The effects of the ML Cu IUD on sperm migration were more evident at the tubal level than at the cervical level.


Source separation with an acoustic vector sensor for terrestrial bioacoustics.
Passive acoustic monitoring is emerging as a low-cost, non-invasive methodology for automated species-level population surveys. However, systems for automating the detection and classification of vocalizations in complex soundscapes are significantly hindered by the overlap of calls and environmental noise. We propose addressing this challenge by utilizing an acoustic vector sensor to separate contributions from different sound sources. More specifically, we describe and implement an analytical pipeline consisting of (1) calculating direction-of-arrival, (2) decomposing the azimuth estimates into angular distributions for individual sources, and (3) numerically reconstructing source signals. Using both simulation and experimental recordings, we evaluate the accuracy of direction-of-arrival estimation through the active intensity method (AIM) against the baselines of white noise gain constraint beamforming (WNC) and multiple signal classification (MUSIC). Additionally, we demonstrate and compare source signal reconstruction with simple angular thresholding and a wrapped Gaussian mixture model. Overall, we show that AIM achieves higher performance than WNC and MUSIC, with a mean angular error of about 5°, robustness to environmental noise, flexible representation of multiple sources, and high fidelity in source signal reconstructions.


Effects of Prosthetic Mismatch and Subscapularis Tear on Glenohumeral Contact Patterns in Total Shoulder Arthroplasty: A Numerical Musculoskeletal Analysis.
Prosthetic components' mismatch and subscapularis (SC) tear are determining factors for glenoid failure complication in nonconforming total shoulder arthroplasty (NC-TSA). Risk factors are linked to glenoid prosthetic loading. However, the mechanisms underlying the clinical observations remain unclear. This study assessed the combined impact of mismatch and subscapularis tear on glenoid loading. It was assumed that adequate glenoid loading was associated with minimal, but non-null, humeral head translations and contact pressure, as well as with maximal glenoid contact area, and that the center of pressure (COP) on the glenoid would have a centered displacement pattern. A numerical model was used to achieve two objectives. The first was to verify whether an optimum mismatch existed, for which failure risk would be minimal. The second was to explore the effect of subscapularis tear on the position of applied forces on the glenoid. A shoulder AnyBody musculoskeletal model was adapted to the arthroplasty context by introducing humeral head translations and contact between implants. Ten simulations were computed to compare combinations of varying mismatches (1.4 mm, 3.4 mm, 6.4 mm, 8.6 mm, and 9 mm) with two shoulder conditions (intact-muscle or subscapularis tear). Humeral head translations, center-of-pressure, contact area, contact pressure, and glenohumeral joint contact forces were numerically estimated. Mismatches between 3.4 mm and 6.4 mm were associated with the most minimal humeral translations and contact pressure, as well as with maximal contact area. Center of pressure displacement pattern differed according to shoulder condition, with an outward anterior tendency in presence of tear.


Amino acid sequence and three-dimensional structure of cytosolic adenylate kinase from carp muscle.
The amino acid sequence of cytosolic adenylate kinase from carp muscle has been determined. For the analysis of the blocked amino terminus an N-acylaminoacyl peptidase has been isolated and applied successfully. The resulting sequence is homologous to those of other adenylate kinases. It has 76% and 74% identical amino acids when compared with the enzymes from chicken and pig, respectively. The carp enzyme forms X-ray-grade crystals, the structure of which has been solved at 0.58-nm resolution. The observed chain fold is very similar to the known fold of the porcine enzyme in crystal form-A, whereas the molecular packing arrangements are quite different. This finding confirms that the observed porcine enzyme structure is intrinsically stable and has not been enforced during the crystallization process. The sequence of cytosolic adenylate kinase from carp muscle is: (table; see text)


Ventral Windowed Total Contact Casts Safely Offload Diabetic Feet and Allow Access to the Foot.
Irremovable total contact casts (TCCs) are the gold standard to offload diabetic foot ulcers (DFUs) and to immobilize feet with active Charcot neuro-osteoarthropathy (CN). They do not allow checks of the foot and are contraindicated in people with peripheral arterial disease (PAD). Frequently, removable TCCs and other removable devices are used because they allow wound care, modifications of the inner surface of the cast, and checks of the foot. The authors propose TCCs with ventral windows (VW-TCCs) whenever patients with high-risk conditions show poor adherence to wearing a removable cast all the time and access to the foot is necessary. This retrospective study compares treatments with bivalved, removable TCCs applied prior to the introduction of the novel design (from 1 January 2016 to 1 July 2017, "c") to treatments in the following period (t) with both bivalved removable TCCs and VW-TCCs in use. Forty-five treatments after introduction (17 with the VW-TCC) showed a 52.8% lower median time to reach remission of the DFS than 41 controls (128/267 days, log-rank test P = .013). Reasons given for not using the novel design were: sufficient offloading with a removable TCC (16), patient preference (six), anatomical conditions (two), casts applied as a service for other facilities (three), and calf ulcers (one). Adverse effects from both designs were uncommon and not severe. VW-TCCs combine advantages of both removable and irremovable TCCs. Complications do not limit the use, even in patients with PAD.


Anomalous origin of left internal mammary artery from the lateral junction of the left subclavian artery and aorta.
We describe the first reported case of an internal mammary artery originating from the junction of the left subclavian artery and aorta. Noting this, along with other reported anomalies and various pathologic conditions, it appears warranted to perform routine preoperative internal mammary artery angiography before coronary artery bypass surgery.


Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique.
The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell--nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell--nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.


APPRIS 2017: principal isoforms for multiple gene sets.
The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the 'principal' isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants.


[Clinical phase III study on TAP-144-SR, an LH-RH agonist depot formulation, in patients with prostatic cancer].
A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.


[Clinical practice guidelines: Summary of recommendations for first surgical treatment of female pelvic organ prolapse by 5 French academic societies: AFU, CNGOF, SIFUD-PP, SNFCP, and SCGP].
Providing clinical practice guidelines for first surgical treatment of female pelvic organ prolapse. Systematic literature review, level of evidence rating, external proofreading, and grading of recommendations by 5 French academic societies: Association française d'urologie, Collège national des gynécologues et obstétriciens français, Société interdisciplinaire d'urodynamique et de pelvi-périnéologie, Société nationale française de coloproctologie, and Société de chirurgie gynécologique et pelvienne. It is useful to evaluate symptoms, their impact, women's expectations, and to describe the prolapse prior to surgery (Grade C). In the absence of any spontaneous or occult urinary sign, there is no reason to perform urodynamics (Grade C). When a sacrocolpopexy is indicated, laparoscopy is recommended (Grade B). A bowel preparation before vaginal (Grade B) or abdominal surgery (Grade C) is not recommended. There is no argument to systematically use a rectovaginal mesh to prevent rectocele (Grade C). The use of a vesicovaginal mesh by vaginal route should be discussed taking into account an uncertain long-term risk-benefit ratio (Grade B). Levator myorrhaphy is not recommended as a first-line rectocele treatment (Grade C). There is no indication for a vaginal mesh as a first-line rectocele treatment (Grade C). There is no reason to systematically perform a hysterectomy during prolapse repair (Grade C). It is possible to not treat stress incontinence at the time of prolapse repair, if the woman is advised of the possibility of a 2-step surgical treatment (Grade C). Clinical practice guidelines. © 2016 Published by Elsevier Masson SAS.


Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats.
The present study was aimed to study the effects of different doses of atorvastatin on Co Q10 content in the myocardium tissue in rats. A subcutaneous injection of isoproterenol (5 mg/kg/day) for 10 days was used for the induction of heart failure. Rats were randomly assigned to control, treatment with atorvastatin (5, 10, 20 mg/kg/day) and treatment with atorvastatin plus coenzyme Q10 (10 mg/kg/day). Coenzyme Q10 content of myocardium was measured using HPLC method with UV detector after hemodynamic parameters measurements. The malondialdehyde (MDA) content of the myocardium was evaluated in order to determine coenzyme Q10 antioxidative effect. A high dose of atorvastatin (20 mg/kg/day) was significantly reduced the myocardium content of coenzyme Q10 as compared with isoproterenol treated group (p<0.001). Compared with atorvastatin alone treated animals, co-administration of coenzyme Q10 with atorvastatin was improved the level of coenzyme Q10 in the myocardium (p<0.05, p<0.001). Increasing the dose of atorvastatin also led to increase in MDA content of the myocardium (p<0.01). Serum lipid profile showed no changes in atorvastatin treated groups. The results of this study demonstrate that high doses of atorvastatin reduce coenzyme Q10 content of the myocardium and increase lipid peroxidation in myocardium which is reversed by coenzyme Q10 co-administration.


Apical membrane antigen-1 (AMA-1) gene sequences of re-emerging Plasmodium vivax in South Korea.
Plasmodium vivax malaria re-emerged in South Korea in 1993, and epidemics continue since then. We examined genetic variation in the region encompassing the apical membrane antigen-1 (PvAMA-1) of the parasites by DNA sequencing of the 22 re-emerging P. vivax isolates. The genotype of the PvAMA-1, which was based on sequence data previously reported for the polymorphic regions, showed that two haplotypes were present at one polymorphic site. Compared with reported data, the two types, SKOR type I and type II, were similar to Chinese CH-10A and CH-05A isolates, respectively. Thus, the present study showed that two genotypes of AMA-1 genes coexist in the re-emerging Korean P. vivax.


Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity.
A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone. The percentages of infected mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749), and correlate positively with transmission intensity. We also estimated exposure to malaria vectors through genetic matching of blood from 1094 wild-caught bloodfed mosquitoes with that of humans resident in the same houses. Although adults transmitted fewer parasites to mosquitoes than children, they received more mosquito bites, thus balancing their contribution to the infectious reservoir.


Direct and indirect pathogenicity of anaerobic bacteria in respiratory tract infections in children.
Bacteroides sp (Bacteroides melaninogenicus, Bacteroides oralis, and Bacteroides fragilis), peptostreptococci, and fusobacteria are important pathogens in respiratory tract infections (RTI). These organisms are often recovered mixed with other aerobic, facultative, and anaerobic bacteria. Evidence supporting their virulence is provided by studies showing their synergistic potentials in mixed infections and their increased virulence when encapsulated. A recent increase in numbers of beta-lactamase producing strains of anaerobic gram-negative bacteria in RTI has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis, and lung abscesses. The pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin susceptible pathogens from that drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. The synergy that exists between different aerobic and anaerobic organisms in the respiratory tract is due to several pathogenic mechanisms. These mechanisms include the production of a capsule, which protects organisms from phagocytosis, and the production of beta-lactamase, which inactivates penicillins and first-generation cephalosporins. Both of these mechanisms enhance infection and induce complications. However, more work is necessary to prevent encapsulation and the production of enzymes. Data, thus far, indicate that there are therapeutic modalities that can be used to prevent these occurrences and eliminate many mixed RTI.


Utility of a novel simulator paradigm in the assessment of driving ability in individuals with and without attention-deficit hyperactivity disorder.
This study aimed to evaluate the utility of a novel, more cost-effective driving simulator, Assetto Corsa (AC), in detecting differences in driving performance between individuals with and without ADHD. Driving simulators are a useful means of assessing driving performance in those with attention-deficit hyperactivity disorder (ADHD); however, they are frequently expensive and thus unavailable to many researchers. A total of 87 participants (16 with ADHD, 71 without) completed an AC driving simulator task. They also completed computerized measures of attention and executive functioning and a questionnaire assessing self-reported driving behaviors and anger, ADHD and related symptoms, and mind wandering. Relative to those without ADHD, participants with ADHD reached higher average ground speeds and more greatly utilized the throttle. They also applied higher maximum pressure to the throttle and brake pedals. Within the full sample, greater mind wandering was associated with average and maximum throttle pressure and maximum ground speed. Findings confirm prior works indicative of a deleterious effect of ADHD diagnosis on simulator performance and may be attributed to a combination of impulsivity and mind wandering.


Effect of temporal focus on the recall of expectancy-consistent and expectancy-inconsistent information.
This research examined the impact of temporal focus on the recall of information that is consistent or inconsistent with an expectation. A consistent pattern of results across 4 experiments indicates that when Ss' expectations are temporally unfocused, better memory for consistent information is observed. In contrast, when expectations are focused in time--that is, Ss know when the relevant events are likely to occur--recall for consistent and inconsistent information is more balanced. Experiment 4 tied these recall findings to the amount of processing devoted to consistent and inconsistent events. When expectations were temporally unfocused, processing time and recall was greater for the confirmatory information. When expectations were temporally focused, more equivalent processing time and recall of consistent and inconsistent information was observed. Discussion centers on the role of temporal focus as a determinant of whether an event is one-sided or two-sided.


Water-dispersible, multifunctional, magnetic, luminescent silica-encapsulated composite nanotubes.
A multifunctional one-dimensional nanostructure incorporating both CdSe quantum dots (QDs) and Fe(3)O(4) nanoparticles (NPs) within a SiO(2)-nanotube matrix is successfully synthesized based on the self-assembly of preformed functional NPs, allowing for control over the size and amount of NPs contained within the composite nanostructures. This specific nanostructure is distinctive because both the favorable photoluminescent and magnetic properties of QD and NP building blocks are incorporated and retained within the final silica-based composite, thus rendering it susceptible to both magnetic guidance and optical tracking. Moreover, the resulting hydrophilic nanocomposites are found to easily enter into the interiors of HeLa cells without damage, thereby highlighting their capability not only as fluorescent probes but also as possible drug-delivery vehicles of interest in nanobiotechnology.


Automatic continous frequency calibration for super-regenerative oscillators used in nuclear quadrupole resonance.
A new and improved method for continuous frequency calibration of the super-regenerative oscillator spectrum is described. The arrangement employs a Hewlett-Packard Model HP5345A reciprocal frequency counter capable of measuring the carrier frequency of rf pulses. The counter gate time is externally controlled via the quench pulses. High-resolution measurements are obtained through the use of the frequency-averaging mode provided by the counter. Three successive digits are displayed on a two-channel recorder using a digital-to-analog converter along with the lock-in output. This method provides automatic and continous high-accuracy frequency calibration of the spectrum which is independent of the rf level, quench frequency, and FM amplitude.


Characterization of human prodynorphin gene transcripts.
Prodynorphin gene transcripts have been characterized in human tissues with cRNA probes covering parts of the non-coding exon 1 and the main coding exon 4 using Northern blot and RNase protection experiments. A 2.8-kb signal was observed in human brain RNA with both the exon 1 and exon 4 probes. An RNase protection assay with the exon 1 probe, performed to map the 5' end of this transcript, produced protected fragments in the range of 0.11 to 0.15 kb indicating that exon 1 is 1.2 kb shorter than previously proposed. 5'-RACE-PCR and sequencing of amplified cDNA fragments confirmed this assignment. In adrenal gland, testis and the human small cell lung carcinoma cell line, U1690, several prodynorphin-like mRNAs structurally different from the brain prodynorphin mRNA species were observed.


Auditory brain stem response--interwave measurements in acoustic neuromas.
Auditory brain stem responses (ABR) of 61 patients with tumors of the VIIIth nerve or cerebellopontine angle were analyzed for latency of the I-III, III-V, and I-V interwave intervals. Of the 61 patients, 16 yielded ABR records with repeated waves I, III, and V so that interwave intervals could be measured. Results indicate that not only is the I-III interval often abnormal, but in almost 50% of the cases the III-V interval is also extended. Additional analysis included comparing a group of subjects with cochlear lesions with the 16 patients with VIIIth nerve tumors. These findings indicated a higher degree of specificity than sensitivity for the ABR interwave measurement. These findings, as well as additional analyses, are discussed.


How should psychology interventions be reported?
Psychology requires new heuristics for intervention research and reporting. There are problems with evidence-based practice (EBP) and with publications reporting intervention studies in Psychology. These issues are connected. EBP is associated with unsustainable levels of Waste, Inertia, Invalidity, Simplisticity and Opacity. Eleven domains of behaviour change are defined which encompass a vast array of programmes, interventions and techniques. These procedures are delivered in a multitude of combinations enabling millions of different interventions in Psychology. Reporting an intervention study in Psychology is a complex operation. A taxonomy for intervention reports is described.


Efficacy of new leukocyte parameters versus serum C-reactive protein, procalcitonin, and interleukin-6 in the diagnosis of neonatal sepsis.
The aim of this study was to investigate and compare the efficacy of the new leukocyte parameters mean neutrophil and monocyte volume (MNV, MMV), conductivity (MNC, MMC), scattering (MNS, MMS) and volume distribution width (NDW, MDW) with serum C-reactive protein (CRP), procalcitonin (PC) and interleukin (IL)-6 in the diagnosis of neonatal sepsis. A total of 227 newborns (132 boys, 95 girls) were analyzed. There were 116 infants in the sepsis group (proven sepsis, n = 40; clinical sepsis, n = 76) and 111 in the control group. Venous blood samples were collected from infants at the time of diagnosis and complete blood count, peripheral blood smear, blood cultures, CRP, PC, IL-6 and MNV, MMV, MNC, MMC, MNS, MMS, NDW, and MDW were analyzed. MNV, NDW, MMV and, MDW were higher in infants with sepsis than in controls (P < 0.05 for all). MNS was lower in the patients with sepsis (P = 0.002). There was no significant difference between the sepsis and control groups in terms of MNC, MMC and MMS. Although the predictive value of leukocyte parameters including neutrophil and monocyte volume, conductivity, scattering and volume distribution width in the diagnosis of neonatal sepsis was lower than that of CRP, PC and IL-6, some of these new parameters may be useful in the differential diagnosis of newborn sepsis, along with the other screening tools. In particular, MNV seems to be the most useful parameter with the highest specificity; also, the importance of PC in the diagnosis of early onset sepsis was confirmed.


Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk.
Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-β can be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.


JAK3, STAT3 and CD3-zeta signaling proteins status in regard to the lymphocytes function in patients with ovarian cancer.
Several groups of author have published that, in most cases of carcinoma, circulating lymphocytes are unable to carry out immune functions successfully. A molecular mechanism responsible for T lymphocytes defective reactivity in cancer patients is not completely defined. We evaluated whether the impaired function of peripheral blood lymphocytes (PBLs) from ovarian cancer patients could be associated with signaling elements such as JAK3, STAT3 and CD3-zeta chain. The study addressed to the simultaneous expression and phosphorylation status of mentioned molecules evaluation in regard to lymphocyte function in patients with advanced ovarian cancer has not yet been demonstrated by others. We found that PBLs of cancer patients showed lower JAK3, CD3-zeta molecules expression levels, as well as lower STAT3 and CD3-zeta phosphorylation levels than cells of control. The lower proliferative response and IL-2 production capacity of cancer patients PBLs in comparison with that of the control group cells were the functional consequences of reported in this study signaling abnormalities.


Multisystem inflammatory syndrome in children (MIS-C): Report of the clinical and epidemiological characteristics of cases in Santiago de Chile during the SARS-CoV-2 pandemic.
To describe the clinical and epidemiological characteristics of hospitalized children with multisystem inflammatory syndrome in children (MIS-C) in Santiago, Chile. This was an observational study of children with MIS-C (May 1 to June 24, 2020), in three pediatric hospitals in Santiago. Demographic characteristics and epidemiological data, medical history, laboratory tests, cardiology evaluations, treatment, and clinical outcomes were analyzed. Twenty-seven patients were admitted (median age 6, range 0-14 years). Sixteen of the 27 (59%) required intensive care unit admission; there were no deaths. Seventy-four percent had no comorbidities, and the median number of days of symptoms before admission was 4 (range 2-9 days). Gastrointestinal symptoms were the most frequent, and inflammatory markers were increased at admission. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in 82% of cases. The severe group showed significantly lower hemoglobin and albumin levels, decreased platelet counts, and higher d-dimer during disease evolution. Echocardiography showed abnormalities (myocardial, pericardial, or coronary) in 12 patients (46%) during their hospital stay. Anti-inflammatory treatment (immunoglobulin and/or corticosteroids) was prescribed in 24 patients. MIS-C appeared in clusters weeks after the peak of SARS-CoV-2 cases, especially in the most vulnerable areas of Santiago. This study describes the first series (n = 27) of children with MIS-C in a Latin American country, showing favorable clinical outcomes. Education and alerts are required for clinical teams to establish an early diagnosis and prompt treatment.


Pregnancies averted among U.S. teenagers by the use of contraceptives.
The personal and social costs associated with teenage pregnancy in the United States concern many policymakers and researchers, yet the role of contraception in preventing these pregnancies has not been adequately quantified. Published estimates of contraceptive effectiveness were applied to 1995 National Survey of Family Growth data on sexual and contraceptive practices in order to estimate the number of pregnancies averted through the use of contraceptives by U.S. teenagers. Four scenarios of contraceptives access--from current levels of access to highly restricted access--and teenagers' sexual and contraceptive practices in response to such restrictions are used to project the potential impact on pregnancies among teenagers. Current levels of contraceptive use averted an estimated 1.65 million pregnancies among 15-19-year-old women in the United States during 1995. If these young women had been denied access to both prescription and over-the-counter contraceptive methods, an estimated one million additional pregnancies (ranging from 750,000 to 1.25 million) would have occurred, assuming some decrease in sexual activity. These pregnancies would have led to 480,000 live births, 390,000 abortions, 120,000 miscarriages, 10,000 ectopic pregnancies and 37 maternal deaths. Contraceptive use by teenage women prevents pregnancies and negative pregnancy-related health consequences that can disrupt the lives of adolescent women and that have substantial societal costs. Continued and expanded access to contraceptives for adolescents is a critically important public health strategy.


Bovine pituitary folliculo-stellate cells have beta-adrenergic receptors positively coupled to adenosine 3',5'-cyclic monophosphate production.
The specific beta-adrenergic radioligand [125I]iodocyanopindolol (ICYP) was used to identify and characterize beta-adrenergic receptors in bovine pituitary folliculo-stellate cells (bFSC) grown in culture. Saturation analysis demonstrated the binding of ICYP to bFSC particulate fractions to be of high affinity (apparent Kd = 80 pM) and low capacity (Bmax = 37 fmol/mg protein). The specific beta-adrenergic radioligand [3H] dihydroalprenolol also bound to bFSC particulate preparations with parameters compatible with binding to the beta-adrenergic receptor (Kd = 3.0 nM; Bmax = 52 fmol/mg protein). No specific binding was observed with either the dopamine receptor radioligand [3H]spiperone or the alpha-adrenergic radioligand [3H]dihydro-alpha-ergocryptine. The bFSC beta-adrenergic receptors were further characterized by computer modeling of competition studies with a variety of agonists and antagonists selective for beta-adrenergic subtypes. The pharmacological profiles of ICYP binding obtained from these studies indicated that approximately equal proportions of both beta 1- and beta 2-adrenergic subtypes are expressed in cultured bFSC. Bovine FSC beta-adrenergic receptors are functionally coupled to activation of cAMP. The beta-adrenergic agonists isoproterenol, epinephrine, and norepinephrine provoked a rapid and marked stimulation of intracellular cAMP accumulation. The approximately equipotent effect of epinephrine and norepinephrine indicated that the beta-adrenergic effect on cAMP production is principally mediated via the beta 1-adrenergic receptor. The identification of beta-adrenergic receptors on bFSC positively coupled to adenylate cyclase provides a possible regulatory control pathway for the proposed role of pituitary FSC in the modulation of anterior pituitary hormone secretion.


Management of varus or valgus ankle deformity with ankle replacement.
Ankle replacements are probably here to stay. Improved designs and surgical technique led to much better mid-term and longer term outcomes than the first-generation replacements in the 1970s. Multiple recent papers also have discussed the many potential complications with total ankle replacement surgery. As we proceed in the future, one should be cognizant of all the pitfalls and know how to deal with the difficult ankles, especially varus and valgus deformities. There should be a clear understanding that the greater the varus or valgus, the harder the procedure and the less predictable the outcome of ankle replacement.


Operating Room Noise and Team Communication during Facial Plastic and Reconstructive Surgery: A Multicenter Study.
Operating room (OR) noise contributes to team miscommunication. In facial plastic and reconstructive surgery (FPRS), many cases are completed under sedation. This creates a unique environment wherein patients are aware of OR noise. The objectives of this study were to quantify noise and evaluate team members' perspectives on communication inside of FPRS ORs. This study was completed across three surgical institutions. Objective noise measurements were recorded with SoundMeter X. A communication questionnaire was delivered to OR team members following each case. Four hundred and twenty-three noise measurements were recorded during facelift/neck, eye/brow, rhinoplasty, and fat transfer/lip surgeries. The mean and maximum noise levels were 66.1 dB (dB) and 87.6 dB, respectively. Measurements during cases with general anesthetic (221/423, 52.2%) had higher noise measurements (70.3 dB) compared with those with sedation (202/423, 47.8%) (69.7 dB) (p = 0.04). The OR was louder with suction on (72.3 dB) versus off (69.3 dB) (p <0.00). Suction (34.5%) and music (22.4%) were the largest noise contributors according to questionnaire replies. Intraoperative noise, awake patients, and suctions/music may negatively impact FPRS OR communication. Innovation to improve FPRS intraoperative communication should be considered for effective patient care.


Big Data to Knowledge: Application of Machine Learning to Predictive Modeling of Therapeutic Response in Cancer.
In recent years, the availability of high throughput technologies, establishment of large molecular patient data repositories, and advancement in computing power and storage have allowed elucidation of complex mechanisms implicated in therapeutic response in cancer patients. The breadth and depth of such data, alongside experimental noise and missing values, requires a sophisticated human-machine interaction that would allow effective learning from complex data and accurate forecasting of future outcomes, ideally embedded in the core of machine learning design. In this review, we will discuss machine learning techniques utilized for modeling of treatment response in cancer, including Random Forests, support vector machines, neural networks, and linear and logistic regression. We will overview their mathematical foundations and discuss their limitations and alternative approaches in light of their application to therapeutic response modeling in cancer. We hypothesize that the increase in the number of patient profiles and potential temporal monitoring of patient data will define even more complex techniques, such as deep learning and causal analysis, as central players in therapeutic response modeling.


Associated Pyoderma Gangrenosum, Erythema Elevatum Diutinum, and Chronic Recurrent Annular Dermatosis: The Neutrophilic Disease Spectrum.
Neutrophilic dermatoses (ND) refer to a group of skin diseases characterized histologically by a cutaneous infiltrate of mature polymorphonuclear cells without an identifiable cause. Previously described as autonomous, these clinically distinct entities are included in the spectrum of neutrophilic disease due to the existence of overlapping forms, as described in our observation. Erythema elevatum diutinum (EED) is a rare dermatosis characterized by reddish-violaceous to browning papulonodular and plaques and belongs to the spectrum of cutaneous leukocytoclastic vasculitis. Chronic recurrent annular neutrophilic dermatosis (CRAND) is an exceptional neutrophilic dermatosis characterized by chronic annular lesions and the absence of generalized signs or hematological abnormalities. Histological features are similar to those seen in Sweet's syndrome. A 55-year-old woman with a history of pyoderma gangrenosum (PG) presented successively with two rare forms of ND, namely, EED and CRAND. There were no clinical or paraclinical arguments for any underlying systemic disease. Treatment with azathioprine 100 mg/day and topical steroids led to a total regression of lesions after a nine-month follow-up. Our observation is important because it reports two rare entities, CRAND and EED. Their occurrence in a single patient with a history of PG illustrates the concept of "neutrophilic disease" reported in the 1990s.


A structure-based virtual screening and molecular docking by using potent inhibitors against nucleoprotein of Crimean-Congo hemorrhagic fever virus.
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a vector borne pathogen, well-known for causing endemic hemorrhagic fever in Asia, Europe and Africa. There is no specific drug or vaccine available against CCHFV. The recent upsurge of Crimean-Congo Hemorrhagic Fever around the globe has made it a major health issue and this demands investigation for specific inhibitors to viral proteins. The objective of this study was to assess inhibitors that may have the potential to dock CCHFV nucleoprotein which plays an important role in viral assembly. We performed structure-based virtual screening and molecular docking by using potent inhibitors against nucleoprotein of CCHFV. Screening was performed by a webserver, MtiOpenScreen which gave 1000 drug-like molecules from PubChem. PyRx Autodock vina was utilized to dock the protein. The docking poses were observed for interaction analysis by LigPlot+. This study provided ten potential candidates capable of binding to the active site of NP of CCHFV. The selected hits were then subjected to toxicity prediction by ProTox-II. Four hits were identified that specifically dock nucleoprotein at the presumed binding site. Furthermore, these compounds have less binding energy i.e., 9.7 kcal/mol, 9.8 kcal/mol and 10.4 kcal/mol and with equal toxicity measures when compared to an FDA approved drug. This study illustrates that virtual screening is an efficient in silico approach to identify target-specific inhibitors. Researchers in this area who investigate drugs or synthesize agents against CCHFV with better efficacy could utilize reported inhibitors rather than trying random compounds ambivalently.


Predictors of gestational diabetes mellitus in a high-parity community in Saudi Arabia.
A study in Riyadh, Saudi Arabia investigated the prevalence of gestational diabetes mellitus (GDM) and its predictors in a high-parity group of pregnant women (n = 633, 50.1% grand multiparas). The prevalence of GDM was 12.5% and 3.8% by World Health Organization and American Diabetes Association criteria respectively. Multiparous women were 8.29 times more likely to have GDM than nulliparous women. However, after adjustment for maternal age and history of abortion, nulliparous women were 2.95 times more likely to develop GDM than parous women. The probability of GDM for a parous woman increased from 2% to 21% when age increased from 20 to 40 years. The high rate of GDM among grand multiparas may be due to the confounding effect of maternal age.


Family origins of distinct forms of children's involvement in interparental conflict.
Previous research has highlighted the value in parsing unidimensional assessments of children's involvement in interparental conflict into distinct forms for advancing an understanding of children's development; however, little is known about the underlying antecedents of distinct forms of involvement. The present study provides the first systematic analysis of the interparental conflict and parenting predictors of residualized change in maternal reports of three forms of children's involvement in interparental conflict (i.e., cautious, caregiving, coercive). Participants in this multimethod, multi-informant longitudinal study included 243 preschool children (Mage = 4.60 years), mothers, and their partners from racially, ethnically, and socioeconomically diverse backgrounds. Multivariate analyses demonstrated selectivity in links between interparental conflict and parenting and children's involvement in interparental conflict. Findings from the interparental conflict analyses revealed that Wave 1 constructive conflict uniquely predicted lower Wave 2 cautious involvement, and Wave 1 hostile conflict uniquely predicted greater Wave 2 coercive involvement. Findings from the parenting analyses indicated that Wave 1 maternal responsiveness uniquely predicted lower Wave 2 cautious involvement and Wave 1 maternal vulnerability uniquely predicted greater Wave 2 coercive involvement. Although interparental conflict and parenting antecedents did not predict caregiving involvement, a series of follow-up analyses individually examining each form of interparental conflict and parenting as a predictor of children's involvement revealed that greater Wave 2 caregiving involvement was predicted by higher levels of Wave 1 disengaged conflict and lower levels of Wave 1 constructive conflict. Findings are interpreted in the context of developmental psychopathology models that emphasize children's response patterns to family adversity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential.
Convalescing coronavirus disease 2019 (COVID-19) patients mount robust T cell responses against SARS-CoV-2, suggesting an important role of T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells and predominantly Tcm cells with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can proliferate homeostatically, and can persist for over 2 months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection and support an important role of SARS-CoV-2-specific T cells in host control of COVID-19.


Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. Two-hundred and eighty-eight patients were included. There was no association between typical sphingolipids and NAFLD and its different entities. There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis.


Liquid chromatography in open tubes.
Liquid chromatography in open tubes is evaluated for applicability to clinical analysis. The principal advantages of this technique include high separation power, reduced solvent consumption, and small sample volume requirements. Technology for the production of columns as small as 8 micron (i.d.) is described. Preliminary results are encouraging and, with further development in column and detector technology, the technique should find wide applicability in clinical analysis.


Laboratory surveillance for wild and vaccine-derived polioviruses, January 2003-June 2004.
In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by 2000. Progress toward achieving this goal has been reported from countries where polio is endemic, and three World Health Organization (WHO) regions (Americas, Europe, and Western Pacific) appear to be free of indigenous wild poliovirus (WPV) transmission. One key strategy for eradicating polio is establishing sensitive polio surveillance systems by investigating acute flaccid paralysis (AFP) cases. To ensure that specimens from persons with AFP undergo appropriate processing for viral isolation, WHO established a global polio laboratory network in 1988. This report updates previous publications, summarizes the laboratory network's performance, and describes the location and characterization of WPV and vaccine-derived poliovirus (VDPV) during January 2003-June 2004.


Genetic mapping and phenotypic analysis of shotH.3.2 in Drosophila melanogaster.
Genetic screens are used to identify genes involved in specific biological processes. An EMS mutagenesis screen in Drosophila melanogaster identified growth control phenotypes in the developing eye. One mutant line from this screen, H.3.2, was phenotypically characterized using the FLP/FRT system and genetically mapped by complementation analysis and genomic sequencing by undergraduate students participating in the multi-institution Fly-CURE consortium. H.3.2 was found to have a nonsense mutation in short stop (shot), anortholog of the mammalian spectraplakin dystonin (DST). shot and DST are involved in cytoskeletal organization and play roles during cell growth and proliferation.


Circumscribed choroidal hemangioma.
Circumscribed or solitary choroidal hemangioma is a relatively rare, benign vascular tumor. Because its appearance may mimic more serious intraocular lesions, eye care practitioners should be familiar with differential diagnosis and treatment options. A patient presented with an asymptomatic, elevated, red-orange lesion above the macula in the right eye and a history of longstanding unexplained visual acuity loss in the eye. Intraocular lesions such as amelanotic melanoma, metastatic tumor, choroidal osteoma, disciform scar, serous detachment, and central serous chorioretinopathy can appear similar to circumscribed choroidal hemangioma (CCH) on ophthalmoscopy, but may be differentially diagnosed with fluorescein angiography, ultrasonography, and periodic observation. CCH requires various therapeutic options. Until the patient becomes symptomatic from visual loss secondary to serous macular detachment or subretinal neovascular membrane formation, no treatment is necessary. Laser photocoagulation is the preferred therapeutic intervention, and most patients will require a minimum of two sessions. A small percentage of individuals will progress to complete retinal detachment with profound visual loss regardless of therapy. Most CCHs remain stable in size and do not undergo malignant transformation. CCHs may be overlooked because of their initial subtle clinical appearance with no associated cutaneous or systemic anomaly. Even though CCH is a benign tumor, it may mimic more serious intraocular lesions and require a combination of ancillary tests for proper diagnosis. Depending on visual symptoms or potential threat to vision, management options include periodic observation, laser photocoagulation, cryotherapy, microwave therapy, and possible enucleation. CCH has little or no growth potential, but visual prognosis remains guarded due to significant secondary retinal changes that can occur over the tumor's surface. CCH must be considered in the differential diagnosis of an elevated intraocular lesion.


A genetically defined animal model of anembryonic pregnancy.
Mutant mouse conceptuses, homozygous for a defect in the gene encoding the glycolytic enzyme, glucose phosphate isomerase (GPI) died in utero by 9 1/2 days post coitum. By this stage there was no normal embryo, but trophoblast and some extra-embryonic membranes usually survived. The morphology of these genetically determined, anembryonic conceptuses was similar to some of the sporadic cases of anembryonic conceptuses that occurred in control crosses. These similarities suggest that an understanding of the cause of death of the homozygous mutant embryos might shed light on the aetiology of some of the cases of sporadic anembryonic conceptuses in both mouse and man. At implantation, the conceptus depends on anaerobic glycolysis for its energy production and any shortage of substrates would compromise development. It is argued that, in the absence of efficient glycolysis, a homozygous null embryo would be unable to produce sufficient energy to develop normally beyond the egg cylinder stage. However, the outer part of the conceptus might survive if nutrients and oxygen were available from the surrounding maternal tissue to produce energy by the aerobic tricarboxylic acid cycle. The homozygous GPI-null conceptuses may provide a useful animal model for some types of human anembryonic pregnancy.


A serological survey for human immunodeficiency virus types 1 and 2 of individuals who visited health centers in Tokyo.
The serum antibodies to human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) were examined for among individuals who visited health centers in Tokyo. Of 8,198 sera screened, one was true-positive and 37 false-positive for HIV-1 antibodies. These 37 false-positives and 305 sera from the population groups at risk for HIV-2 (42 sojourners in Africa, 251 homo- and bisexuals, and 19 prostitutes) were further examined for HIV-2 antibodies by indirect immunofluorescence and Western blotting. No antibodies reactive with HIV-2 were detected in the sera examined. Serological cross-reactivity between HIV-1 and HIV-2 was examined by use of rabbit antisera.


Evaluation of surgical margins in anatomic pathology: technical, conceptual, and clinical considerations.
Virtually all anatomic pathologists are involved in the assessment of tissue margins in surgical procedures that are performed for malignant diseases. The natural tendency to view this process as uncomplicated has, in recent years, been countered by a body of literature on the biological milieu of the marginal zone. Moreover, empirical clinical information has shown that "negative" and "positive" marginal status has an imperfect correlation with risk of recurrent disease in several organ systems and in reference to various tumor types. Problems also remain regarding the optimal techniques for pathologic sampling of margins; the possible roles, if any, of adjuvant (eg, immunohistologic and "molecular") procedures for margin evaluation, and reporting motifs for selected surgical resections. This review considers conceptual data now available on surgical margins, provides a working approach to the generic assessment of marginal surfaces, and presents organ- and tumor- specific information pertaining to this area of practice.


Screening of antibacterial activity of mucus extract of snakehead fish, Channa striatus (Bloch).
The objective of this study is to gain a better understanding of the antimicrobial properties of the mucus extract of snakehead fish, Channa striatus against selected human and fish pathogenic microbes. The fish mucus samples were extracted with crude, acidic and aqueous solvents to identify potential antimicrobial agents including aqueous and acid soluble compounds. The study also determined the protein content of the three different mucus extracts. The highest protein content (0.589 mg/ml) was noticed in the crude extract followed by aqueous mucus extract (0.291 mg/ml) and acidic extract (0.267 mg/ml). Preliminary screening for antimicrobial activity of all three mucus extracts were tested against 5 human pathogens (Bacillus subtilis, Klebsiella pneumoniae, Salmonella enteritidis, Proteus vulgaris and Pseudomonas aeruginosa) and fish pathogen (Aeromonas hydrophila) using the British Society for Antimicrobial Chemotherapy (BSAC) standardized disc susceptibility test method. The activity was measured in terms of zone of inhibition in mm. The acidic mucus extracts exhibited a bactericidal activity and inhibited the growth of Klebsiella pneumoniae, Pseudomonas aeruginosa and Bacillus subtilis while aqueous and crude extract showed no bactericidal activity for any of the human pathogens tested. Further test against fish pathogen Aeromonas hydrophila showed that the aqueous and crude extracts are capable of inhibiting the growth of the pathogen, demonstrating the presence of antimicrobial agents and the role of fish mucus in antimicrobial protection. The present results suggest that the mucus extracts of snakehead fish Channa striatus may be a potential source of antimicrobial agents for human and fish pathogens.


Alkali Cation/Sucrose Co-transport in the Root Sink of Sugar Beet.
The mechanism of sucrose transport into the vacuole of root parenchyma cells of sugar beet was investigated using discs of intact tissue. Active sucrose uptake was evident only at the tonoplast. Sucrose caused a transient 8.3 millivolts depolarization of the membrane potential, suggesting an ion co-transport mechanism. Sucrose also stimulated net proton efflux. Active (net) uptake of sucrose was strongly affected by factors that influence the alkali cation and proton gradients across biological membranes. Alkali cations (Na(+) and K(+)) at 95 millimolar activity stimulated active uptake of sucrose 2.1- to 4-fold, whereas membrane-permeating anions inhibited active sucrose uptake. The pH optima for uptake was between 6.5 and 7.0, pH values slightly higher than those of the vacuole. The ionophores valinomycin, gramicidin D, and carbonyl cyanide m-chlorophenylhydrazone at 10 micromolar concentrations strongly inhibited active sucrose uptake. These data are consistent with the hypothesis that an alkali cation influx/proton efflux reaction is coupled to the active uptake of sucrose into the vacuole of parenchyma cells in the root sink of sugar beets.


Prevention of coronary heart disease in clinical practice: a commentary on current treatment patterns in six European countries in relation to published recommendations.
Market research surveys can be a source of up-to-date information about current clinical practices. Data from one such survey, Cholesterol Monitor (made available by Merck & Co., Inc., Whitehouse Station, N.J., USA) was examined to ascertain to what extent management of cholesterol in six European countries conforms with the advice of the joint Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension for prevention of coronary heart disease (CHD). Rates of cholesterol testing in patients with CHD varied from less than 50% in the UK to more than 80% in France and Italy. Across Europe, the average cholesterol levels in surveyed patients was 6 mmol/l, and the average intervention level was 7.5 mmol/l. In all countries, there was evidence of a substantial treatment gap, even among high-risk patients with established CHD. This gap took the form of non-treatment of a proportion of patients whose risk status merited intervention on the basis of expert recommendations and the results of the Scandinavian Simvastatin Survival Study (in which sustained lowering of total and low-density lipoprotein cholesterol reduced total and coronary mortality in patients with baseline total cholesterol as low as 5.5 mmol/l). The findings indicate that a concerted programme of physician education is required if the recommendations of the joint Task Force are to be put into effect, and if the present nontreatment/undertreatment of cholesterol in high-risk patients is to be corrected.


"This is the best fatal illness that you can have": contrasting and comparing the experiences of parenting youth with cystic fibrosis and congenital heart disease.
Despite the important instrumental and emotional role that parents play in the lives of children with cystic fibrosis (CF) and congenital heart disease (CHD), qualitative researchers have not examined the similarities and differences between caregivers' experiences. Informed by thematic analysis, in this qualitative study I explored what it is like to care for a child with a chronic illness from the perspective of CF and CHD parents at a children's hospital in Canada. Pediatric caregiver stress was qualitatively different between CF and CHD parents, whereas temporal dilemmas were unique sources of stress for CF parents only. To alleviate stress, all parents drew on a three-way, interrelated process to comprehend their child's illness and acquire perspective. By opening up the social worlds of parents, I illuminate important similarities and differences in the caregiving experience of parents of youth with CF and CHD, and offer novel contributions to the literature.


Beyond positive a priori bias: reframing community engagement in LMICs.
Showing the causal link between community engagement and improved health outcomes is a 'holy grail' of health policy. This article argues that this 'holy grail' has remained elusive because community engagement in primary health care is under-theorized, having been based on positive a priori assumptions, e.g. that people necessarily want to be engaged in governing their health system. By adopting a theory-driven approach and an agnostic premise, we show that understanding why, how and when community engagement may emerge or function spontaneously is important for informing efforts to support community engagement in primary health care primary health care governance. We draw on empirical research on community engagement in Nigeria and on the literature to identify the 'why' (coalition of service users can emerge in response to under-governance); the 'how' (five modes: through meetings; reaching out within their community; lobbying governments; augmenting government support; and taking control of service delivery) and the 'when' (as geographical, socio-economic and institutional context align, such that the benefits of action outweigh costs). Understanding the broad patterns of mechanisms and of contextual factors that apply across communities is, after all, our 'holy grail'-and this understanding should inform efforts to tailor support for community engagement in governance in different settings.


Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice.
Kiss1 mRNA and its corresponding peptide products, kisspeptins, are expressed in two restricted brain areas of rodents, the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC). The concentration of mature kisspeptins may not directly correlate with Kiss1 mRNA levels, because mRNA translation and/or posttranslational modification, degradation, transportation and release of kisspeptins could be regulated independently of gene expression, and there may thus be differences in kisspeptin expression even in species with similar Kiss1 mRNA profiles. We measured and compared kisspeptin-immunoreactivity in both nuclei and both sexes of rats and mice and quantified kisspeptin-immunoreactive nerve fibers. We also determined Kiss1 mRNA levels and measured kisspeptin-immunoreactivity in colchicine pretreated rats. Overall, we find higher levels of kisspeptin-immunoreactivity in the mouse compared to the rat, independently of brain region and gender. In the female mouse AVPV high numbers of kisspeptin-immunoreactive neurons were present, while in the rat, the female AVPV displays a similar number of kisspeptin-immunoreactive neurons compared to the level of Kiss1 mRNA expressing cells, only after axonal transport inhibition. Interestingly, the density of kisspeptin innervation in the anterior periventricular area was higher in female compared to male in both species. Species differences in the ARC were evident, with the mouse ARC containing dense fibers, while the rat ARC contains clearly discernable cells. In addition, we show a marked sex difference in the ARC, with higher kisspeptin levels in females. These findings show that the translation of Kiss1 mRNA and/or the degradation/transportation/release of kisspeptins are different in mice and rats.


[Residential and living conditions of elderly women and men immigrants in Hamburg].
In 1996 the Public Authority for Employment, Health and Social Welfare of the Free and Hanseatic City of Hamburg did research on the living and health conditions of Hamburg's foreign senior citizens with the intention of providing general assistance in all areas of life including health care planning. The sampling (n = 1034) included six nationalities: Turkish (482), Yugoslavian (153), Italian (119), Portuguese (109), Polish (94), and Iranian (77). The foreigners interviewed said they felt older and considered themselves in worse health than their German counterparts. Their incomes were lower, their flats smaller and their lives less comfortable. Additionally, they had more children with a higher number of people per household. Only 17% wanted to return to their home countries after going into retirement. Most would rather live only part of the year in their home country and the other part in Germany. The results of the study show that it is preferable to integrate foreigners into Hamburg's elderly care system by modifying existing facilities instead of developing completely new ones and by providing information (booklets and videos) on the health care system.


Salter-Harris type III fractures of the distal femur: plain radiographs can be deceptive.
Salter-Harris (SH) III fractures of the distal femur, although rare, can have devastating effects. The purposes of this study were to: (1) compare the intra-articular fracture displacement measured on plain x-ray and magnetic resonance imaging (MRI) or computed tomography (CT) scan and (2) report the outcomes of patients with a SH III fracture of the distal femur. All SH III distal femur fractures treated at a large Children's Hospital with a Level I Pediatric Trauma Center between 1995 and 2006 were retrospectively reviewed. A total of 14 patients (average age: 13 y, 11 mo; range: 7 y, 8 mo to 17 y, 11 mo) with an average follow-up time of 21.50 months (range: 2 to 47 mo) were included in this study. Fracture displacement on plain x-ray was compared with the fracture displacement measured on MRI or CT scan. The average time between the initial plain x-ray and MRI or CT scan was 37.48 days (range: 3 h to 6 mo). Plain x-rays significantly underestimated the displacement of SH III fractures versus MRI or CT scan. Six patients who had both plain x-ray and MRI or CT scan had a measured displacement of 0.42 mm and 2.70 mm, respectively (paired Student t test, P=0.005). Ten of the 14 patients (71%) had no physical limitations and full knee motion at their most recent follow-up visit. The treatment of 4 patients (29%) was changed based on the findings of the additional MRI or CT scan. This study and earlier studies have shown a high rate of poor results with SH III fractures of the distal femur. This type of fracture pattern is extremely unstable and the true displacement is often underestimated by x-rays. Thus, it is strongly recommended that an MRI or CT scan be obtained on every SH III fracture of the distal femur. Moreover, any SH III fracture visible on plain radiographs should be treated with open reduction, internal fixation. Level IV.


Natural history and management of splanchnic artery aneurysms in a single tertiary referral center.
Splanchnic artery aneurysms (SAAs) are rare, and little is known about their natural history and management. We reviewed our single-center experience in managing this population of patients. A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with an SAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Our primary outcomes included aneurysm growth rate and risk of rupture in those patients managed nonoperatively and morbidity and mortality of those SAA patients who underwent operative intervention. There were 122 patients with 138 SAAs identified; 77 were male (62%), with a mean age of 66 years (range, 25-94 years). On computed tomography, 56 (45%) had previously diagnosed or concomitant aneurysms elsewhere. Of the patients managed nonoperatively, 101 patients (79%) had 108 SAAs; in the operative intervention group, 25 (21%) patients had 30 SAAs. The mean overall vessel diameter was 1.76 ± 0.83 cm. The diameter of observed and operatively repaired SAAs was 1.58 ± 0.56 cm and 2.41 ± 1.23 cm, respectively (P = .00001). Mean follow-up was 50 ± 42 months for nonoperative management without any adverse events related to SAA, including 10 patients with SAA >2.0 cm. The mean observed growth rate for SAA was 0.064 ± 0.18 cm/y. All symptomatic patients who presented with severe abdominal pain (n = 11 [44%]) underwent operative intervention. Five patients presented with a ruptured SAA (3.6%; range, 2.3-5.0 cm); all of them except one underwent operative intervention. Other indications for repair included large size in seven, rapid growth in two, other open abdominal surgical procedures in two, multiple aneurysms in one, and desire to pursue fertility treatment in one. Operative repair included 14 (56%) endovascular embolizations and 11 (44%) open abdominal operations. After endovascular embolization, two patients underwent abdominal operation for hemorrhage and splenectomy. Open repairs included bypasses in six, splenectomy in two, resection in two, and plication in one. Two patients had postoperative acute kidney injury that resolved and one died of multisystem organ failure. One bypass occluded without sequelae. On multivariable regression analysis, female sex (P = .02) was associated with faster growth rate, and a history of smoking (P = .04) was associated with slower growth rate. It seems reasonable to observe asymptomatic patients with an SAA <2.0 cm because of the slow growth rate (0.064 ± 0.18 cm/y) and benign behavior. When intervention is needed, both open and endovascular options should be considered.


Anticholinergic burden and cognitive function in a large German cohort of hospitalized geriatric patients.
Previous studies suggest an association between use of anticholinergic drugs in elderly patients and cognitive impairment. However, there are still limited data on the association of anticholinergic drug use and cognitive impairment as well as contribution of individual drugs to anticholinergic load using large, well-documented patient cohorts treated in geriatric units from Europe. We investigated 797,440 prescriptions to 89,579 hospitalized patients treated in geriatric units within the GiB-DAT database. Data of all patients discharged between 1 January 2013 and 30 June 2015 was included. The Anticholinergic Cognitive Burden (ACB) scale was used to classify anticholinergic drugs as definite (score 2 or 3) and possible anticholinergics (score 1). Cognitive function was determined using Mini-Mental State Examination (MMSE) and the standardized scale for dementia (4D+S). In two multivariable logistic regression models age, sex, number of drugs and ACB total scores were identified as variables independently associated with cognitive impairment as measured by MMSE (odds ratio per ACB unit 1.114, 95% CI 1.099-1.130) or the diagnosis dementia (odds ratio 1.159 per ACB unit, 95% CI 1.144-1.173, both p < 0.0001). High anticholinergic load was associated with patients with severe cognitive impairment (p < 0.05 for all pairwise comparisons). ACB score 3 anticholinergic drugs contributed 77.9% to the cumulative amount of ACB points in patients with an anticholinergic load of 3 and higher. Using a cross-sectional study design, a significant positive association between anticholinergic drug load and cognitive impairment in European patients treated in specialised geriatric units was found. The most frequently used definitve anticholinergic drugs were quetiapine, amitriptyline and carbamazepine.


An experimentalist's reply to "What is an atom in a molecule?".
Parr, Ayers and Nalewajski have opined in this Journal that the concept of an atom in a molecule "is an object knowable by the mind or intellect, not by the senses." This view is countered by the two hundred years of experimental chemistry underlying the realization that the properties of some total system are the sum of its atomic contributions. This paper concludes that an experimentalist has no doubt but that he or she is measuring the properties of atoms when performing an experiment.


Mammary Paget's Disease of the Male Breast: A Rare Case With an Unusual Immunohistochemical Profile.
Mammary Paget's disease is rare and comprises about 0.62% of all breast cancer cases, only 1.65% of which occur in male patients. This case report involves a 76-year-old man who presented to his primary care physician with an itching, scaly, unilateral lesion involving the nipple skin. He underwent wide local excision of the lesion for a diagnosis of Bowen's disease (squamous cell carcinoma in situ). Histologic examination of the specimen revealed mammary Paget's disease with ductal carcinoma in situ in the underlying breast tissue. A panel of immunohistochemical stains revealed the Paget cells to be positive for cytokeratin 7, MUC1, GATA3, and androgen receptor and negative for cytokeratins 5/6, p63, SOX10, and MART-1/Melan-A. Paget cells were also negative for estrogen receptor and progesterone receptor, and positive for HER2/neu. However, the underlying ductal carcinoma in situ was positive for both estrogen receptor and progesterone receptor and negative for HER2/neu. This discordance, supported by the current literature, suggests an alternative etiology for Paget's disease in certain cases that cannot be explained by the well-established epidermotropic and transformative theories of Paget's disease evolution.


Artemisinin induces selective and potent anticancer effects in drug resistant breast cancer cells by inducing cellular apoptosis and autophagy and G2/M cell cycle arrest.
To investigate the anticancer properties of a well-known naturally occurring sesquiterpene lactone - artemisinin - against cisplatin resistant human breast carcinoma cells along with examining its effects on apoptosis, autophagy as well as cell cycle phase distribution. MTT assay was used to study cytotoxic effects of artemisinin while clonogenic assay analysed its effects on cancer cell colony formation. Fluorescence microscopy using DAPI staining was employed to study apoptotic effects of artemisinin which was followed by annexin V/propidium iodide (PI) assay which quantified the apoptotic effects of artemisinin in cancer cells. Apoptotic effects of artemisinin were finally confirmed by western blot assay by analysing its effects on Bcl-2 and Bax protein expressions. Effects of artemisinin on autophagy were determined by transmission electron microscopy (TEM). Effects on cell cycle were analysed by flow cytometry and western blot. The results indicated that artemisinin led to considerable and dose-dependent antiproliferative effects on MDA-MB-231 cisplatin-resistant breast cancer cells with less toxicity in normal cell line, thus exhibiting selectivity. The colony formation decreased significantly as artemisinin dose increased. DAPI and comet assays revealed that artemisinin induced powerful apoptotic effects, triggering significant dose-dependent DNA damage. TEM indicated that artemisinin induced autophagy in MDA-MB-231 cisplatin-resistant human breast cancer cells by creating autophagosomes and autophagic vacuoles. The molecule also targeted G2/M phase cell cycle along with targeting some key cell cycle related proteins including cyclin-B1, cyclin D1 and cyclin E. The results show that artemisinin showed strong anticancer effects in MDA-MB-231 cisplatin-resistant cancer cells by triggering apoptosis and autophagy and G2/M phase arrest.


Isolation and characterization of infectious Vibrio sinaloensis strains from the Pacific shrimp Litopenaeus vannamei (Decapoda: Penaeidae).
Infectious diseases especially those caused by bacterial and viral pathogens are serious loss factors in shrimp farming. In this study, bacteria were isolated from the gut and hepatopancreas of stressed shrimps obtained from a commercial farm. The isolates were screened on Thiosulfate citrate bile salt sucrose (TCBS) agar plates for the selection of Vibrio species. Presumptive vibrios were characterized through tests for hemolytic and enzymatic activity, hydrophobicity, growth and molecular identification. Three experimental infections were conducted in order to confirm the pathogenicity of selected bacterial strains VHPC18, VHPC23, VHPC24 and VIC30. In the third experimental challenge the LD50 was obtained, it lasted 10 days with 10 shrimp, weighing 6.9+1. Ig, per tank. The treatments in triplicate were: (1) saline solution (control group); (2) 2xl0(5)CFU/shrimp; (3) 4xl05CFU/shrimp; (4) 2x10(6)CFU/shrimp; (5) 4x10(6)CFU/shrimp, and (6) 8x10(6)CFU/shrimp. In all challenges, water parameters measured during the experimental period remained within optimum ranges. Pathogenicity tests confirmed that the mixture of four vibrio isolates, identified as Vibrio sinaloensis, was virulent for L. vannamei. The LD50 value was 1.178x10(5)CFU/g body weight. V sinaloensis may act as opportunistic pathogens for cultured L. vannamei.


Muscle-building therapy in treatment of nasal valve collapse.
The purpose of this paper is to describe the outcome of muscle-building therapy for nasal muscles in cases of nasal valve stenosis or collapse. The present study was performed to investigate the best way to combine transcutaneous and intranasal surface electromyography (sEMG) biofeedback training of muscles involved in nasal valve function with a home exercise program and electric stimulation of nasal muscles. A randomized pilot study of 3 groups of patients (n1=12, n2=12, n3=10; total 34 patients) presenting with symptoms of obstructed nasal breathing was conducted. All selected patients demonstrated nasal valve stenosis with a positive Cottler maneuver and clinically evident nasal valve collapse. Follow-up ranged from 8 to 12 months. Treatment for Group 1 included transcutaneous and intranasal electric stimulation of nasal muscles only. Treatment for Group 2 included biofeedback training and home exercise program of specific nasal movements, and treatment for Group 3 included surface and intranasal EMG biofeedback assisted specific strategies for nasal muscle education, home exercises and electric stimulation. All patients in these groups exhibited subjective improvement. For Group 3, in 80% the improvement was proved objectively; for Group 2, in 75% the improvement was proved objectively; for Group 1, in 58,33% the improvement was proved objectively. We found no significant difference between the results in Groups 3 and 2 and poorer results in Group 1. Relieve of nasal valve stenosis and collapse can be achieved with a complex muscle-building therapy as described. It helps a significant cohort of patients with symptoms of obstructed nasal breathing to avoid surgical intervention. Electric stimulation of the muscles does not contribute significantly in achieving of good results.


Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model.
This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) (n = 8 piglets/group). A control group of healthy pigs (n = 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B(2) (TxB(2)), PGF(2alpha), and 6-keto-PGF(1alpha). Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB(2) and PGF(2alpha) increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen in endotoxemic piglets given INO only. We conclude that the rebound response to INO discontinuation is related to COX products.