Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer.
Centromeres are specialized chromatin domains specified by the centromere-specific CENP-A nucleosome. The stable inheritance of vertebrate centromeres is an epigenetic process requiring deposition of new CENP-A nucleosomes by HJURP. We show HJURP is recruited to centromeres through a direct interaction between the HJURP centromere targeting domain and the Mis18α-β C-terminal coiled-coil domains. We demonstrate Mis18α and Mis18β form a heterotetramer through their C-terminal coiled-coil domains. Mis18α-β heterotetramer formation is required for Mis18BP1 binding and centromere recognition. S. pombe contains a single Mis18 isoform that forms a homotetramer, showing tetrameric Mis18 is conserved from fission yeast to humans. HJURP binding disrupts the Mis18α-β heterotetramer and removes Mis18α from centromeres. We propose stable binding of Mis18 to centromeres in telophase licenses them for CENP-A deposition. Binding of HJURP deposits CENP-A at centromeres and facilitates the removal of Mis18, restricting CENP-A deposition to a single event per cell cycle.


Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA.
The antiproliferative action of human interferon (HuIFN)-gamma on human cells and the inhibition of intracellular pathogens, e.g. Toxoplasma gondii and Chlamydia psittaci, is at least in part due to an induction of indoleamine 2,3-dioxygenase (IDO) enzyme which degrades tryptophan, an essential amino acid. A cDNA clone (called C42) was isolated from a cDNA library made from poly(A)+ RNA obtained from HuIFN-gamma-treated human fibroblasts. Its nucleotide sequence revealed an open reading frame coding for a polypeptide of 403 amino acids, but no homology with any known gene in GenBank database was found. Evidence was obtained indicating that this cDNA codes for IDO: (i) Hybrid selected C42 specific poly(A)+ RNA from IFN-gamma-treated human cells coded for a polypeptide in vitro of approximately 42 kD (reported size of IDO, approximately 40 kD) which was immunoprecipitated by monoclonal anti-IDO antibody but not by a control antibody; and (ii) transfection of human fibroblasts with an expression plasmid containing C42 cDNA transcribed from chicken beta-actin promoter led to constitutive expression of C42 specific RNA as well as IDO activity. This cDNA clone will be useful in studying the role of IDO in the biological effects of IFN-gamma, and the regulation of IDO gene by IFN-gamma.


Study on the reference dose level in radiotherapy treatment planning.
The reference dose level of the dose distribution in the tumor volume is studied. The study is performed using a formula based on the Linear Quadratic (LQ) model. The calculated reference dose level to which the prescribed dose must be referred, for the eradication of a homogeneous tumor, is investigated by varying the dose distribution, that is, the dose volume histogram shape, its range, the prescribed total dose, the fraction size and the linear quadratic model parameters, alpha and beta. For all the simulated dose volume histograms the calculated reference dose level is lower than the mean dose level, depending on the range of dose variation and the considered tumor sensitivity. When the dose nonuniformity is not too great the reference dose level is very near to the mean dose level; when the inhomogeneity of dose distribution is high the reference level is clearly lower than the mean level but not necessarily equal to the minimum level in the tumor. For the dose volume histograms derived from the actual dose distributions obtained from a two tangential beams technique, a four beams technique and a moving beam technique, the reference levels are calculated and compared with the ICRU 29 reference point dose level. In two cases the reference levels are lower than the level at the ICRU 29 reference point. In the case of the four beams technique, the two levels are equal. These theoretical results show the possibility of administering the prescribed dose to a dose level higher than the minimum in the tumor, with the same value of Tumor Control Probability (TCP) as the one corresponding to a uniform tumor irradiation. The application of the proposed study can offer a general support to the choice of the reference dose level, based on the actual dose distribution in the tumor volume.


An umbrella review of systematic reviews of the evidence of a causal relationship between periodontal disease and cardiovascular diseases: Position paper from the Canadian Dental Hygienists Association.
Previous position papers have confirmed associations between periodontal disease and cardiovascular disease. Causal associations have not been confirmed and have been the source of much confusion for oral health professionals and the public. To investigate whether sufficient evidence exists for a causal relationship between periodontal disease and cardiovascular disease. The PICO question was "For adults in good general health who are diagnosed with periodontal disease, will receiving non-surgical periodontal therapy (NSPT), as compared to not receiving NSPT, lower their risk for cardiovascular diseases?" Only systematic reviews (SRs) with or without meta-analyses (MAs) of randomized controlled trials published in the English language between 2007 and 2019 were included. Databases searched included PubMed, MEDLINE, EbscoHost, CINAHL, Scopus, Cochrane Registry of Systematic Reviews, and Clinical Trials Registry. Quality assessments were conducted by both authors using the PRISMA checklist. The Bradford Hill criteria were used to determine evidence for causality. Of 53 cardiovascular disease studies retrieved, 7 met the inclusion criteria, of which 6 contained MAs. Results were mixed for various periodontal interventions lowering the risk for cardiovascular outcomes. Only one SR used cardiovascular events as a direct outcome; the other 6 used various surrogate measures. Bradford Hill criteria analysis failed to support a causal relationship between periodontal disease and cardiovascular disease.


A likelihood model that accounts for censoring due to fetal loss can accurately test the effects of maternal and fetal genotype on the probability of miscarriage.
Heritable maternal and fetal thrombophilia and/or hypofibrinolysis are important causes of miscarriage. Under the constraint that fetal genotype is observed only after a live birth, estimating risk is complicated. Censoring prevents use of published statistical methodology. We propose techniques to determine whether increases in miscarriage are due to the fetal genotype, maternal genotype, or both. We propose a study to estimate the risk of miscarriage contributed by an allele, expressed in either dominant or recessive fashion. Using a multinomial likelihood, we derive maximum likelihood estimates of risk for different genotype groups. We describe likelihood ratio tests and a planned hypothesis testing strategy. Parameter estimation is accurate (bias <0.0011, root mean squared error <0.0780, n = 500). We used simulation to estimate power for studies of three gene mutations: the 4G hypofibrinolytic mutation in the plasminogen activator inhibitor gene (PAI-1), the prothrombin G20210A mutation, and the Factor V Leiden mutation. With 500 families, our methods have approximately 90% power to detect an increase in the miscarriage rate of 0.2, above a background rate of 0.2. Our statistical method can determine whether increases in miscarriage are due to fetal genotype, maternal genotype, or both despite censoring.


New galactolipids from the marine bacillariophycean microalga Nitzschia sp.
Two new galactopyranosyldiacylglycerols have been isolated from the marine bacillariophycean microalga Nitzschia sp. and their structures were determined as (2S)-3-O-beta-D-galactopyranosyl-1,2-di-O-(9Z-hexadecenoyl)glycerol (1) and (2S)-3-O-beta-D-galactopyranosyl-1-O-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-O-(9Z-hexadecenoyl)glycerol (2) by physicochemical evidence.


Total antioxidant capacity and total oxidant status of synovial fluids in patients with temporomandibular joint pain and dysfunction.
The objective of this study was to investigate whether a relationship exists between total antioxidant capacity (TAC) and total oxidant status (TOS) of synovial fluids (SFs) of temporomandibular joint (TMJ) pain patients with pain and dysfunction. Forty-two patients with TMJ pain were included in this study. TAC and TOS values of SFs were measured with a novel colorimetric method. Independent t test and correlations were used to analyze the data. TAC of SFs in patients with TMJ pain and limited mouth opening (LMO; n = 21) were significantly lower (P = 0.03) than patients without LMO (n = 21). TOS of SF was negatively correlated with duration of the disease. There was no correlation between TAC, TOS, and VAS scores of the patients as well as age and maximum mouth opening values. Antioxidant response to oxidative changes (TAC and TOS) in SF decreased as the stage of dysfunction increased. Local administration of antioxidant agents might be considered in management of TMJ pain and dysfunction to prevent possible increased oxidative stress.


Application of MALDI-TOF MS for enumerating bacterial constituents of defined consortia.
Characterization of live biotherapeutic product (LBP) batches typically includes a measurement of viability, such as colony forming units (CFU). However, strain-specific CFU enumeration assays can be complicated by the presence of multiple organisms in a single product with similar growth requirements. To overcome specific challenges associated with obtaining strain-specific CFU values from multi-strain mixtures, we developed a method combining mass spectrometry-based colony identification with a traditional CFU assay. This method was assessed using defined consortia made from up to eight bacterial strains. Among four replicate batches of an eight-strain mixture, observed values differed from expected values by less than 0.4 log10 CFU among all strains measured (range of differences, -0.318 to + 0.267). The average difference between observed and expected values was + 0.0308 log10 CFU, with 95% limits of agreement from -0.347 to 0.408 (Bland-Altman analysis). To estimate precision, a single batch of eight-strain mixture was assayed in triplicate by three different users, for a total of nine measurements. Pooled standard deviation values ranged from 0.067 to 0.195 log10 CFU for the eight strains measured, and user averages did not differ significantly. Leveraging emerging mass-spectrometry-based colony identification tools, a novel method for simultaneous enumeration and identification of viable bacteria from mixed-strain consortia was developed and tested. This study demonstrates the potential for this approach to generate accurate and consistent measurements of up to eight bacterial strains simultaneously and may provide a flexible platform for future refinements and modifications. KEY POINTS: • Enumeration of live biotherapeutics is essential for product quality and safety. • Conventional CFU counting may not differentiate between strains in microbial products. • This approach was developed for direct enumeration of mixed bacterial strains simultaneously.


Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity.
Despite the recent reports describing the benefits of the intravitreal injection of bevacizumab (IVB) to treat ocular neovascular disorders, including retinopathy of prematurity (ROP), the possible adverse effects of this therapy must also be described. We report here a case of advanced ROP which showed an acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab. A female infant born at 23 weeks of gestation with a birth weight of 598 g was referred to the ophthalmologist at 4 weeks of age. With funduscopic examinations, broad avascular retinas were found in both eyes. Since the ROP had progressed to stage 3, zone 1 with plus disease in both eyes, retinal photocoagulation was performed at 10 weeks of age. Despite the adequate photocoagulation therapy, the proliferation progressed further, and partial tractional retinal detachment (TRD) occurred in the right eye, classified as stage 4A with plus disease. After extensive discussion with the parents about the risks and benefits of IVB as an alternative therapy, they consented to the treatment. Under general anesthesia, an intravitreal injection of 0.4 mg bevacizumab was performed at 14 weeks of age. The following day, the vascular component of the fibrovascular membrane (FVM) regressed, and acute fibrosis occurred. However, the ring-shaped FVM contracted centripetally, which caused a deterioration of the TRD. The contraction of the FVM progressed until 7 days after IVB, and resulted in a funnel-like retinal detachment at the posterior retina. The other eye also showed TRD at 19 weeks of age classified as stage 4B, which necessitated a vitrectomy. No systemic complications were noted before and after the treatment. IVB is a useful therapy to maintain aggressive ROP. However, IVB might cause TRD progression in some specific cases.


Clinical analysis of multiple organ failure in burned patients.
Severely burned patients often show various degrees of organ failures, and when several vital organs are involved mortality becomes extremely high. A study was undertaken to elucidate the aetiology and clinical significance of multiple organ failure (MOF) in burned patients. One hundred and fifty-eight burned patients were analysed for organ failures in five vital organs or systems, the heart, lung, liver, kidney and blood clotting system. There were 91 organ failures observed in 34 patients, of which 26 had MOF. The most frequently affected organ was the lung, followed by the heart, kidney, liver and the blood clotting system. The mortality rate was 76.9 per cent in MOF and 1.5 per cent in non-MOF patients. Septicaemia was closely associated with the development of MOF. Also, inhalation injury and 'shock' were contributing factors to the morbidity. Five extensively burned patients had an early development of MOF without infectious foci and this type of early MOF was attributed to endotoxaemia possibly originating from the patient's own intestinal flora.


Morphology and pathology of radiation-induced esophagitis. Double-blind study of naproxen vs placebo for prevention of radiation injury.
Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40-50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)


Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents.
Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. A population-based, self-reported cross-sectional study conducted in Västmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Västmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.


Rapid prediction of moisture content of dehydrated prawns using online hyperspectral imaging system.
Because the shape of prawn is not round, spectroscopy instruments cannot measure the spectra of the whole prawn without containing background information. In this study, an online hyperspectral imaging system in the spectral region of 380-1100 nm was developed to determine the moisture content of prawns at different dehydrated levels. Hyperspectral images of prawns were acquired at different dehydration periods. The spectra of prawns then were extracted from hyperspectral images based on 'Manual Prawn Mask' and 'Automatic Prawn Mask', respectively. Spectral data were analyzed using partial least squares regression (PLSR) and least-squares support vector machines (LS-SVM) to establish the calibration models, respectively. Successive projections algorithm (SPA) was first applied for the optimal wavelength selection in the hyperspectral image analysis. Out of 482 wavelengths, only twelve wavelengths (428, 445, 544, 569, 629, 672, 697, 760, 827, 917, 958, and 999 nm) were selected by SPA as the optimum wavelengths for moisture prediction. Based on these optimum wavelengths, a multiple linear regression (MLR) calibration model was established and used to obtain the moisture distribution of each prawn. The overall results of this study revealed the potentiality of hyperspectral imaging as an objective and non-destructive method to obtain the content and distribution of moisture of prawns whose shapes are not round.


["Fast-track" rehabilitation in thoracic surgery. First experiences with a multimodal, interdisciplinary, and proven perioperative treatment course].
"Fast-track" rehabilitation is a multimodal perioperative treatment concept for accelerating postoperative recovery which has been already used successfully in visceral surgery. Of its use in thoracic surgery however, almost no data exist and the relevance of this concept for pulmonary operations is unknown. In this prospective study we examined a new perioperative fast-track treatment concept for thoracic surgery and evaluated the results. This program employs detailed information of patients, intensive perioperative respiratory therapy, thoracic peridural analgesia, forced mobilization, and an early start of postoperative normal food intake. Fifty consecutive patients with benign or malignant diseases of the lung aged an average of 64 years (range 22-78) were operated on thoracoscopically (n=15) or with thoracotomy (n=35) and treated perioperatively using the fast-track program. All patients were mobilized beginning 4 h postoperatively and had normal food. The incidence of general postoperative complications was 0% in this study. Postoperative stay lasted 4.5 days (range 1.5-28.5). There was no increase in surgical complications, and 6% of the patients were readmitted. The patients' acceptance of this concept was high. Fast-track rehabilitation resulted in a decreased rate of general complications and accelerated rehabilitation in thoracic surgery.


CD4⁺CD25⁺Foxp3⁺ regulatory T cells promote Th17 responses and genital tract inflammation upon intracellular Chlamydia muridarum infection.
The functional role of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in host responses to intracellular bacterial infection was investigated in an in vitro coculturing system and a murine model of Chlamydia muridarum genital tract infection. Remarkably, C. muridarum infection subverted the immune suppressive role of CD4⁺CD25⁺Foxp3⁺ Tregs; instead of hampering immune responses, Tregs not only promoted Th17 differentiation from conventional CD4⁺ T cells but also themselves converted into proinflammatory Th17 cells in both in vitro and in vivo settings. Anti-CD25 mAb PC61 treatment to deplete ∼50% of pre-existing Tregs prior to C. muridarum genital tract infection markedly reduced the frequency and the total number of Th17 but not Th1 CD4⁺ cells at both immune induction and memory phases. Most importantly, Treg-depleted mice displayed significantly attenuated inflammation, neutrophil infiltration, and reduced severity of oviduct pathology upon C. muridarum genital infection. To our knowledge, this is the first report demonstrating that the level of pre-existing CD4⁺CD25⁺Foxp3⁺ Tregs in Chlamydia-infected hosts has a major impact on the development Chlamydia-associated diseases.


Toward systematic integration between self-determination theory and motivational interviewing as examples of top-down and bottom-up intervention development: autonomy or volition as a fundamental theoretical principle.
Clinical interventions can be developed through two distinct pathways. In the first, which we call top-down, a well-articulated theory drives the development of the intervention, whereas in the case of a bottom-up approach, clinical experience, more so than a dedicated theoretical perspective, drives the intervention. Using this dialectic, this paper discusses Self-Determination Theory (SDT) 12 and Motivational Interviewing (MI) 3 as prototypical examples of a top-down and bottom-up approaches, respectively. We sketch the different starting points, foci and developmental processes of SDT and MI, but equally note the complementary character and the potential for systematic integration between both approaches. Nevertheless, for a deeper integration to take place, we contend that MI researchers might want to embrace autonomy as a fundamental basic process underlying therapeutic change and we discuss the advantages of doing so.


Relationships Between Preoperative Mental Health and Improvements in Patient-Reported Outcomes After Total Hip and Knee Arthroplasty.
Poor preoperative mental health has been associated with worse outcomes after total hip (THA) and total knee arthroplasty (TKA). To fully understand these relationships, we assessed post-THA and post-TKA improvements in patient-reported mental and joint health by preoperative mental health groups. Elective cases (367 THA, 462 TKA) were subgrouped by low (<25th percentile), middle (25th-74th), and high (≥75th) preoperative mental health, using Veterans RAND 12-Item Health Survey Mental Component Summary (MCS) scores. In each subgroup, we assessed the relationship between preoperative MCS and 1-year postoperative change in mental and joint health. Pairwise comparisons and multivariable regression models were applied for THA and TKA separately. Median postoperative mental health change was +14.0 points for the low-MCS THA group, +11.1 low-TKA, +2.0 middle-THA and TKA, -4.0 high-THA, and -4.9 high-TKA (between-group differences P < .001). All MCS groups had improved median joint health scores, without significant between-group differences. Preoperative mental health was negatively associated with mental health improvements in all groups (B = -0.94 - -0.68, P < .001-P = .01) but with improvements in joint health only in the low-THA group (B = -0.74, P = .02). Improvements in mental and joint health were positively associated for low and middle (B = 0.61-0.87, P < .001), but not for high-MCS groups, with this relationship differing for the low versus high group. Patients who have low preoperative mental health experienced greater postoperative mental health improvement and similar joint health improvement compared to patients who have high preoperative mental health. Findings can guide subgroup-targeted surgical decision-making and preoperative counseling.


Interaction of retinal image and eye velocity in motion perception.
When we move our eyes, why does the world look stable even as its image flows across our retinas, and why do afterimages, which are stationary on the retinas, appear to move? Current theories say this is because we perceive motion by summation: if an object slips across the retina at r degrees/s while the eye turns at e degrees/s, the object's perceived velocity in space should be r + e. We show that activity in MT+, the visual-motion complex in human cortex, does reflect a mix of r and e rather than r alone. But we show also that, for optimal perception, r and e should not summate; rather, the signals coding e interact multiplicatively with the spatial gradient of illumination.


Application of a water quality model in the White Cart water catchment, Glasgow, UK.
Water quality models of urban systems have previously focused on point source (sewerage system) inputs. Little attention has been given to diffuse inputs and research into diffuse pollution has been largely confined to agriculture sources. This paper reports on new research that is aimed at integrating diffuse inputs into an urban water quality model. An integrated model is introduced that is made up of four modules: hydrology, contaminant point sources, nutrient cycling and leaching. The hydrology module, T&T consists of a TOPMODEL (a TOPography-based hydrological MODEL), which simulates runoff from pervious areas and a two-tank model, which simulates runoff from impervious urban areas. Linked into the two-tank model, the contaminant point source module simulates the overflow from the sewerage system in heavy rain. The widely known SOILN (SOIL Nitrate model) is the basis of nitrogen cycle module. Finally, the leaching module consists of two functions: the production function and the transfer function. The production function is based on SLIM (Solute Leaching Intermediate Model) while the transfer function is based on the 'flushing hypothesis' which postulates a relationship between contaminant concentrations in the receiving water course and the extent to which the catchment is saturated. This paper outlines the modelling methodology and the model structures that have been developed. An application of this model in the White Cart catchment (Glasgow) is also included.


Visible Light Induced Brønsted Acid Assisted Pd-Catalyzed Alkyl Heck Reaction of Diazo Compounds and N-Tosylhydrazones.
A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. A broad range of vinyl arenes and heteroarenes with high functional group tolerance, as well as a range of different diazo compounds, can efficiently undergo this transformation. This method features Brønsted acid-assisted generation of hybrid palladium C(sp3 )-centered radical intermediate, which allowed for new selective C-H functionalization protocol.


MALDI-TOF mass spectrometry as a potential tool for Trichomonas vaginalis identification.
Trichomonas vaginalis is a flagellated protozoan causing trichomoniasis, a sexually transmitted human infection, with around 276.4 million new cases estimated by World Health Organization. Culture is the gold standard method for the diagnosis of T. vaginalis infection. Recently, immunochromatographic assays as well as PCR assays for the detection of T. vaginalis antigen or DNA, respectively, have been also available. Although the well-known genome sequence of T. vaginalis has made possible the application of proteomic studies, few data are available about the overall proteomic expression profiling of T. vaginalis. The aim of this study was to investigate the potential application of MALDI-TOF MS as a new tool for the identification of T. vaginalis. Twenty-one isolates were analysed by MALDI-TOF MS after the creation of a Main Spectrum Profile (MSP) from a T. vaginalis reference strain (G3) and its subsequent supplementation in the Bruker Daltonics database, not including any profile of protozoa. This was achieved after the development of a new identification method created by modifying the range setting (6-10 kDa) for the MALDI-TOF MS analysis in order to exclude the overlapping of peaks derived from the culture media used in this study. Two MSP reference spectra were created in 2 different range: 3-15 kDa (standard range setting) and 6-10 kDa (new range setting). Both MSP spectra were deposited in the MALDI BioTyper database for further identification of additional T. vaginalis strains. All the 21 strains analysed in this study were correctly identified by using the new identification method. In this study it was demonstrated that changes in the MALDI-TOF MS standard parameters usually used to identify bacteria and fungi allowed the identification of the protozoan T. vaginalis. This study shows the usefulness of MALDI-TOF MS in the reliable identification of microorganism grown on complex liquid media such as the protozoan T. vaginalis, on the basis of the proteic profile and not on the basis of single markers, by using a "new range setting" different from that developed for bacteria and fungi.


Overnight variation in tidal expiratory flow limitation in COPD patients and its correction: an observational study.
Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known. COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use. Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36-100% for naïve users with most users rating therapy as comfortable. Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients. The trial was retrospectively registered at CT.gov NCT04725500.


[Isolation and some properties of exoribonuclease from the cell nuclei of the rat liver].
Exoribonuclease from rat liver cell nuclei was isolated and purified using selective extraction at pH 8.0, salting out with ammonium sulfate (30-50% saturation) and chromatography on DEAE-Sephadex A-50. The enzyme has the pH optimum 7.4-7.6, it requires Mg-2+. It catalyses the gradual removal of ribonucleoside-5'-monophosphates from synthetic polynucleotides and RNA; it preferably attacks single-stranded polynucleotides and is less efficient when hydrolysing poly-stranded helical polymers. It is supposed that exoribonuclease can participate in the destruction of non-informative regions in new-formed hyper-molecular RNA of cell nuclei.


Ultrasound measurement of gallbladder wall thickening as a diagnostic test and prognostic indicator for severe dengue in pediatric patients.
Gallbladder wall thickening measured by ultrasound was significantly associated with severe dengue, as well as with hallmark features of thrombocytopenia and elevated hematocrit/hemoconcentration, in children with suspected dengue in Nicaragua. We demonstrate that gallbladder wall thickening serves as a clinically relevant diagnostic test and prognostic indicator of severe dengue in pediatric populations.


Critical appraisal of implant impression accuracies: A systematic review.
Different assessment methods have been used to measure the accuracy of implant impression techniques; therefore, the readers should understand the benefits and limitations of each assessment method used. The purpose of this systematic review was to classify the implant impression studies by the assessment methods and techniques used and to understand the characteristics of each assessment method. The results of published studies were also analyzed to draw meaningful conclusions about the accuracy of the implant impressions. An electronic search of the MEDLINE/PubMed database was performed in February 2013 using specific search terms and predetermined criteria to identify and assess laboratory studies of the accuracy of implant impression techniques. A final list of articles deemed to be of interest was comprehensively reviewed by 2 reviewers to ensure that these were suitable for the purpose of this review. The results of the current review were also compared with results from a previous systematic review. A total of 56 studies met the inclusion criteria for this review. Thirty-seven studies measured the amount of linear distortion, and 17 studies compared the angular change to assess the accuracy. Most linear or angular distortions were only measured in 2 dimensions, and 3-dimensional analysis was rare. More than 80% of the studies compared nonsplinting versus splinting, direct versus indirect techniques, and different impression materials. In recent publications, the direct or splint technique showed more accurate results than the indirect or nonsplinted technique. In contrast to external connection implants, inconsistent results were reported for internal connection implants.


Factors influencing willingness to participate in new drug trial studies: a study among parents whose children were recruited into these trials in northern Ghana.
During the last decade, the number of clinical trials conducted in sub-Saharan Africa has increased significantly which has helped to address priority health problems in the region. Navrongo health research centre since it was established in 1989, has conducted several trial studies including rectal artesunate trial in the Kassena-Nankana districts. However, there is little evidence-based for assessing the impact of new drug trials. This study explored factors that motivate parents to allow their children to participate in new drug trials in northern Ghana. The study used both quantitative and qualitative methods. The participants were randomly selected from among parents whose children were enrolled in a new drug trial conducted in the Kassena-Nankana districts between 2000 and 2003. QSR Nvivo 9 software was used to code the qualitative data into themes before analysis while STATA software Version 11.2© was used to analyze the quantitative data. The results showed that majority (95.9%) of the parents were willing to allow their children to be enrolled in future new drug trials. The main factors motivating their willingness to allow their children to be enrolled in these trials were quality of health care services offered to trial participants (92.9%), detail medical examination (90.8%), promptness of care provided (94.4%) and quality of drugs (91.9%). Other factors mentioned included disease prevention (99.5%) and improved living standard (96.1%). Parents reported that the conduct of these trials had reduced the frequency of disease occurrences in the communities because of the quality of health care services provided to the children recruited into these trial studies. Though the implementation of clinical trials in the study area is believed to have positive impact on health status of people particularly trial participants, measures should however be taken to address safety and likely side effects of new drugs given to trial participants during these trial studies.


Marine Drug Discovery through Computer-Aided Approaches.
Besides the importance of our oceans as oxygen factories, food providers, shipping pathways, and tourism enablers, oceans hide an unprecedented wealth of opportunities [...].


Association of increased QT dispersion with coronary atherosclerosis in patients with aortic stenosis.
To evaluate correlates between electrocardiographic QT dispersion and coronary atherosclerosis in patients with aortic stenosis before aortic valve replacement, 39 consecutive patients >40 years old with symptomatic aortic stenosis and coronary diameter narrowing > or =50% measured by digital angiographic study were included. An additional matched group with insignificant coronary lesions (<50%) consisted of 39 patients for comparisons. Matching by age, sex heart rate and incidence of chest pain resulted in two comparable groups with identical baseline characteristics. Preoperative transthoracic echocardiography and electrocardiograms were performed in all subjects. QT dispersion was defined as the difference between maximal and minimal QT interval measurements occurring among any of the 12 leads on a standard electrocardiogram. No subject had fewer than nine measurable leads. There were no significant differences of risk factors of coronary artery disease between the two groups. From a conditional multivariate logistic regression analysis, independent predictors of development of coronary artery disease in aortic stenosis were only QTc dispersion (odds ratio= 1.255, P=0.01). A wide QTc dispersion > or =70 ins) correlated with the presence of angiographically significant coronary artery disease with a sensitivity and specificity of 72% and 79%. The positive accuracy of having significant coronary artery disease in the presence of QTc dispersion > or =70 ms was 78%. The negative predictive value was 74%. In conclusion, electrocardiographic QTc dispersion may provide important clinical information. A wide QTc dispersion in patients with aortic stenosis is associated with a high incidence of coronary artery disease. These findings warrant further investigation in a large trial.


Sediment and porewater geochemistry in a metal contaminated estuary, Dulas Bay, Anglesey.
Remobilisation of contaminant metals from sediments can occur by chemical, biological or physical changes. This in turn can lead to contaminant fluxes to the porewaters and ultimately the water column. The aim of the research presented here is to document post-depositional controls on metal mobility and fluxes in a heavily metal-contaminated estuary. This will allow for an improved understanding of the impact of contaminated sediments on water quality from both a short-term and long-term perspective. Dulas Bay is situated on the east coast of Anglesey, North Wales, and receives polluted waters from Parys Mountain. Metals within Dulas Bay sediments show surface enrichment and variations in mineralogical form. Diagenesis clearly plays a role in post-depositional behaviour of the metals, forming sulphides and potentially carbonates. The presence of a dominant exchangeable/carbonate fraction, and elevated porewater metals, in this sulphidic system is significant and could indicate the presence of freshwater diagenesis, or, reflect the high levels of metals in the sediment.


Anatomic abnormalities are common potential explanations of manometric esophagogastric junction outflow obstruction.
Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility diagnosis associated with a myriad of conditions. The frequency of EGJOO attributed to anatomic causes compared to idiopathic causes is uncertain. Our study aims to identify the frequency of EGJOO and to compare these two groups. We conducted a case-control study of high-resolution manometry (HRM) studies with a diagnosis of EGJOO performed at a single academic center. EGJOO cases were classified as anatomic (if any potential anatomic cause was identified) or idiopathic. Clinical and manometric characteristics of idiopathic EGJOO were compared with anatomic EGJOO cases. Criteria for EGJOO were met in 11% of HRM studies. Ancillary studies revealed 21/32 EGJOO cases had potential anatomic causes with a hiatal hernia noted in 15/21 cases of anatomic EGJOO. Idiopathic EGJOO cases met Chicago Classification criteria for hypercontractile esophagus with greater frequency than anatomic cases (p = 0.01). The mean distal contractile integral was significantly greater for idiopathic cases compared to anatomic cases (p = 0.003). Treatments used for EGJOO were varied and usually successful in alleviating symptoms. Patients with anatomic EGJOO related to a hiatal hernia who underwent an antireflux operation did not develop dysphagia postoperatively. EGJOO is a frequently encountered manometric diagnosis, commonly associated with anatomic abnormalities potentially explaining the EGJOO. These findings support current recommendations to pursue ancillary diagnostics to investigate cases of unexplained EGJOO. Cases of idiopathic EGJOO are more likely to have hypercontractility on HRM, possibly suggesting a primary esophageal motility disorder.


Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Structure and function of isolated components.
Four major components of the hemoglobin of the bullfrog tadpole, Rana catesbeiana, have been isolated and characterized structurally and functionally. These components fall into two clear functional classes. Components I and II have substantially higher affinities for oxygen than do components III and IV. Components I and II predominate in very young tadpoles and are largely replaced by components III and IV in older tadpoles. The data (Broyles, R.H., and Frieden, E. (1973) Nature New Biol. 241, 207-209) indicate that component I arises in the kidney and components III and IV in the liver. The synchrony of appearance and functional similarity o components I and II suggest that component II probably also arises in the kidney. Thus the development of the tadpole is associated with the successive proliferation of three distinct populations of red cells, first from the kidney, then from the liver, and finally, after metamorphosis, from bone marrow...


Regional homogeneity, functional connectivity and imaging markers of Alzheimer's disease: a review of resting-state fMRI studies.
Resting-state functional magnetic resonance imaging (fMRI), a promising technique for measuring brain activities during rest, has attracted much attention in the past few years. In this paper, we review recent progress on the study of Alzheimer's disease (AD) based on resting-state fMRI. First, we briefly introduce some AD-related studies from other groups. Then we describe our AD-related work in detail from three aspects: (1) alterations in regional homogeneity (ReHo) of the fMRI signal in the resting state, (2) altered patterns of functional connectivity from regions of interest and whole brain analyses, and (3) discriminative analyses based on classification features from resting-state fMRI data for differentiating AD patients from healthy elders. Finally, we summarize the main results and some prospects for future work.


The development and testing of a nurse-led smartphone-based self-management programme for diabetes patients with poor glycaemic control.
To describe a systematic process for the development of a nurse-led smartphone-based self-management programme for type 2 diabetes patients with poor glycaemic control in Singapore. A three-step process involving the application of a theoretical framework, evidence from literature, content validity, and pilot tests were conducted for the content and technical development of the programme. Content experts and lay patients evaluated the appropriateness, relevance, and comprehensibility of the newly developed Care4Diabetes application. A pilot randomized controlled trial was conducted with 40 patients recruited in Singapore. Twenty patients each were randomly allocated to the control and intervention groups. The study outcomes were collected at baseline and at 3 months thereafter. The nurse-led smartphone-based self-management programme was developed with integration of the Care4Diabetes application and the web-portal system. The pilot results indicated that the effects of this smartphone-based programme on patient's health-related outcomes were comparable with those of the currently available nurse-led diabetes service. The smartphone-based self-management intervention was deemed effective, yet full-scale randomized controlled trials are still ongoing and the results of these may provide strong evidence of the effectiveness of such an approach in improving patient care. The uniqueness of this study lies in the integrated system used, which offers a clinical platform for diabetes nurses to provide personalized coaching and care to patients remotely, while monitoring patients' progress closely. By adopting such an approach, it would free up more time for nurses to cater to patients who are more critically in need of their direct attention.


Stretch-inactivated cationic channels in single smooth muscle cells.
Stretch-inactivated channels (SICs) were identified in single smooth muscle cells freshly dissociated from the stomach of the toad, Bufo marinus. In both cell-attached and excised inside-out patches, negative pressure applied to the extracellular surface of the membrane patch suppressed the activity of SICs. These channels were permeable to cations and were not significantly permeable to Cl-. The current-voltage relationship showed outward rectification in cell-attached patches with high NaCl in the pipette solution (2 mM MgCl2), and the slope conductance at negative potentials was approximately 8 pS under these conditions. When divalent cations were eliminated from the pipette solution, the slope conductance at negative potentials increased to approximately 30 pS. No significant voltage dependence of SIC gating could be observed between -100 mV and 60 mV.


Hypoxia increases thrombospondin-1 transcript and protein in cultured endothelial cells.
The exposure of endothelial cells to hypoxic environments regulates the expression of a number of genes with products that are vasoactive or mitogenic for vascular tissue, including platelet-derived growth factor, endothelin-1, and endothelial nitric oxide synthase. Hypoxia is also known to alter the adhesive properties of endothelium toward a variety of blood cell types. Thrombospondin-1 (TSP-1) is a glycoprotein with major roles in cellular adhesion and vascular smooth muscle proliferation and migration. We report here that hypoxia induces TSP-1 gene and protein expression. Oxygen tensions of < or =30 torr resulted in TSP-1 transcript induction initially apparent at 1 to 6 hours, with maximal induction (6.5-fold+/-1.2-fold) within 24 to 48 hours in both human and bovine endothelial cells. TSP-1 protein levels remain elevated after 72 hours of continuous hypoxic exposure. The induction of TSP-1 steady-state transcript levels is caused in large part, if not entirely, by post-transcriptional stabilization of the TSP-1 mRNA. The TSP-1 induction by hypoxia is a graded and reversible physiologic response and can be mimicked by the use of cobalt chloride or the inhibition of nitric oxide production, suggesting both the involvement of a heme-containing oxygen sensor and a role for the endogenous production of nitric oxide in TSP-1 regulation. The effects of hypoxia both on the stabilization of the TSP-1 transcript and the stimulation of TSP-1 protein production are completely inhibited by arginine butyrate.


Determination of the hydraulic conductivity function of grey Vertosol with soil column test.
Expansive soils exhibit swell-shrink behaviour in wet-dry periods resulting in distresses on light-weight structures founded on/in them. Therefore, it is essential to investigate the climate-ground interaction when designing structures on expansive soils. Laboratory-based models are preferred to investigate the climatic-ground interaction of expansive soils due to the uncontrollability of the boundary conditions and expenses associated with field monitoring. More flexibility in analysing the climatic-induced hydraulic responses in expansive soils can be achieved by finite element modelling of data from physical model tests. However, these laboratory-based models regularly encounter the effects of boundary flaw, preferential flow paths and entrapped air that needs to be accounted for when numerically simulated. In this study, the authors aim to numerically model the hydraulic responses in an instrumented Vertosol soil column (ISC) under controlled laboratory conditions. The effects of the preferential flow paths and boundary flaws were incorporated into a modified hydraulic conductivity as a practical approach to model the hydraulic responses in ISC. Influence of the entrapped air was rectified by a suitable correction factor. These findings present a practical method for geotechnical practitioners to accurately estimate the suction and volumetric water content profiles in laboratory-based expansive soil model tests.


A case study of neurodevelopmental risks from combined exposures to lead, methyl-mercury, inorganic arsenic, polychlorinated biphenyls, polybrominated diphenyl ethers and fluoride.
We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18-45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.


A migratory abscess pointing intraorally and extraorally. Case report.
A case of migratory abscess pointing both intraorally and extraorally at a considerable distance from the causative site is reported. The anatomy of the area leading to the formation of such an abscess is described.


Role of cell cycle-associated proteins in microglial proliferation in the axotomized rat facial nucleus.
We analyzed cell cycle-associated proteins, including cyclins, cyclin-dependent protein kinases (Cdks), and Cdk inhibitors (CdkIs) in the axotomized rat facial nucleus. Immunoblotting revealed that cyclin A and cyclin D are induced 3-5 days after transection. The induced cyclin A was immunohistochemically recognized in microglia. Cdk2 and Cdk4 were also detected in the facial nucleus. The CdkI p21 was elevated 5 days after axotomy. Inhibition experiments in vitro using a cFms (receptor for macrophage-colony stimulating factor, M-CSF) inhibitor indicated that M-CSF-cFms signaling leads to upregulation of the levels of cyclin A, cyclin D, proliferating cell nuclear antigen (PCNA), and cFms in microglia. The role of cyclin A/Cdk2 activity in M-CSF-dependent microglial proliferation was ascertained using the specific inhibitor purvalanol A. Experiments using specific mitogen-activated protein kinase inhibitors suggested that c-Jun N-terminal kinase (JNK) is associated with M-CSF-dependent induction of cyclins and PCNA, whereas p38 is associated with cFms induction. Both JNK and p38 were proved to be phosphorylated by stimulation with M-CSF. Our results indicated that cyclin A, cyclin D, Cdk2, Cdk4, and p21 are involved in microglial proliferation in the transected facial nucleus, and that the M-CSF-dependent upregulations of cyclins/PCNA and cFms in microglia are differentially regulated by JNK and p38.


Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations.
To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology. Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed. No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P=0.006) and benign testicular lesions (P=0.006). FA was significantly higher both in malignancies (P=0.001) and benign lesions (P<0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P=0.221) CONCLUSIONS: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation.


Structure and function of the human platelet thrombin receptor. Studies using monoclonal antibodies directed against a defined domain within the receptor N terminus.
Based upon its recently cloned nucleotide sequence, the human platelet thrombin receptor is thought to be formed by a single polypeptide chain with seven transmembrane domains and an extracellular N terminus that can be cleaved by thrombin. As yet, however, little is known from studies of the receptor protein itself. To obtain such information, we have prepared monoclonal antibodies against a peptide corresponding to receptor residues Ser42 through Phe55, the domain immediately distal to the site of cleavage by thrombin. By flow cytometry, all of the antibodies reacted with the thrombin-responsive megakaryoblastic CHRF-288 and HEL cell lines, but not with the T-lymphoid Sup-T1 cell line. Functionally, the antibodies inhibited platelet responses to alpha-thrombin, gamma-thrombin, and trypsin, but had no effect on platelet activation by ADP, epinephrine, or the thromboxane analog U46619. Radioiodinated antibody bound to approximately 1,800 sites/platelet, a value similar to the reported number of moderate affinity thrombin binding sites per platelet. On Western blots, the antibodies recognized a 66-kDa protein in platelet, HEL, and CHRF-288 membranes. The discrepancy between this apparent size and the predicted mass of the receptor suggests that, as with other G protein-coupled receptors, one or more of the potential sites for N-linked glycosylation have been utilized. Therefore, these results suggest that: 1) the cloned thrombin receptor is involved in a broad range of platelet responses to thrombin, as well as gamma-thrombin and trypsin; 2) as predicted, the N terminus of the receptor is accessible on the platelet surface; 3) the moderate affinity thrombin binding site noted in earlier studies may be the receptor; 4) potentially as much as one third of the mass of the receptor is carbohydrate.


The effect of probiotic and synbiotic use on glycemic control in women with gestational diabetes: A systematic review and meta-analysis.
To investigate the impact of probiotic/synbiotic use on glycemic control in women with gestational diabetes. We searched the PubMed, Medline, Scopus, ScienceDirect, Web of Science, Cochrane Central Register of Controlled Trials, Dergipark, and Council of Higher Education Thesis Center databases through March 2022. Screening was performed according to the population, intervention, comparison, outcome and study type. This systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Review and meta-analyses (PRISMA-2020) statement. Eight RCTs involving 551 patients were included in the meta-analysis. Probiotic use in women with gestational diabetes significantly decreased fasting blood glucose (mean difference: -1.43; 95 % CI: -2.78 to -0.09, p: 0.04) and serum insulin (mean difference: -3.66; 95 % CI: -5.04 to -2.27, p < 0.001). Moreover, the use of probiotics and synbiotics significantly reduced the HOMA-IR level compared to the control group (probiotic group: mean difference: -0.74; 95 % CI: -1.05 to -0.44, p < 0.001; synbiotic group: mean difference: -0.68; 95 % CI: -1.26 to -0.09, p: 0.02). The use of probiotics in women with GDM reduced fasting plasma glucose, fasting serum insulin, and HOMA-IR levels. In addition, the use of synbiotics decreased HOMA-IR. Probiotic/synbiotic use is promising as a potential therapy to assist in glycemic control in gestational diabetes. Further high-quality studies are required to determine their safety.


Metabolomic profiling to identify early urinary biomarkers and metabolic pathway alterations in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of numerous fluid-filled cysts that lead to progressive loss of functional nephrons. Currently, there is an unmet need for diagnostic and prognostic indicators of early stages of the disease. Metabolites were extracted from the urine of patients with early-stage ADPKD (n = 48 study participants) and age- and sex-matched normal controls (n = 47) and analyzed by liquid chromatography-mass spectrometry. Orthogonal partial least squares-discriminant analysis was used to generate a global metabolomic profile of early ADPKD for the identification of metabolic pathway alterations and discriminatory metabolites as candidates of diagnostic and prognostic biomarkers. The global metabolomic profile exhibited alterations in steroid hormone biosynthesis and metabolism, fatty acid metabolism, pyruvate metabolism, amino acid metabolism, and the urea cycle. A panel of 46 metabolite features was identified as candidate diagnostic biomarkers. Notable putative identities of candidate diagnostic biomarkers for early detection include creatinine, cAMP, deoxycytidine monophosphate, various androgens (testosterone; 5-α-androstane-3,17,dione; trans-dehydroandrosterone), betaine aldehyde, phosphoric acid, choline, 18-hydroxycorticosterone, and cortisol. Metabolic pathways associated with variable rates of disease progression included steroid hormone biosynthesis and metabolism, vitamin D3 metabolism, fatty acid metabolism, the pentose phosphate pathway, tricarboxylic acid cycle, amino acid metabolism, sialic acid metabolism, and chondroitin sulfate and heparin sulfate degradation. A panel of 41 metabolite features was identified as candidate prognostic biomarkers. Notable putative identities of candidate prognostic biomarkers include ethanolamine, C20:4 anandamide phosphate, progesterone, various androgens (5-α-dihydrotestosterone, androsterone, etiocholanolone, and epiandrosterone), betaine aldehyde, inflammatory lipids (eicosapentaenoic acid, linoleic acid, and stearolic acid), and choline. Our exploratory data support metabolic reprogramming in early ADPKD and demonstrate the ability of liquid chromatography-mass spectrometry-based global metabolomic profiling to detect metabolic pathway alterations as new therapeutic targets and biomarkers for early diagnosis and tracking disease progression of ADPKD.NEW & NOTEWORTHY To our knowledge, this study is the first to generate urinary global metabolomic profiles from individuals with early-stage ADPKD with preserved renal function for biomarker discovery. The exploratory dataset reveals metabolic pathway alterations that may be responsible for early cystogenesis and rapid disease progression and may be potential therapeutic targets and pathway sources for candidate biomarkers. From these results, we generated a panel of candidate diagnostic and prognostic biomarkers of early-stage ADPKD for future validation.


Improvements in health-related quality of life following a group intervention for coping with AIDS-bereavement among HIV-infected men and women.
AIDS-related bereavement is a severe life stressor that may be particularly distressing to persons themselves infected with HIV. Increasing evidence suggests that psychological health is associated with disease progression, HIV-related symptoms, and mortality. This study assessed change in health-related quality of life among HIV + persons following a group intervention for coping with AIDS-related loss. The sample included 235 HIV + men and women of diverse ethnicities and sexual orientations who had experienced an AIDS-related loss within the previous 2 years. Participants were randomly assigned to a 12-week cognitive-behavioral bereavement coping group intervention or offered individual psychotherapy upon request. Quality of life was assessed at baseline and 2 weeks after the intervention. Participants in the group intervention demonstrated improvements in general health-related and HIV-specific quality of life, while those in the comparison remained the same or deteriorated. Effect sizes indicated that the majority of change occurred in women. This bereavement group aimed at improving coping with grief also had a positive impact on health-related quality of life among HIV + men and women, and suggests that cognitive-behavioral interventions may have a broad impact on both emotional and physical health.


Association between REDUCE-IT criteria, coronary artery disease severity, and cardiovascular events: the Western Denmark Heart Registry.
The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) trial demonstrated that icosapent ethyl lowered the risk of atherosclerotic cardiovascular disease (ASCVD) among patients with elevated triglycerides. However, how to appropriately implement its use in clinical practice is not well-defined. We aimed to determine whether plaque burden as assessed by coronary artery calcium (CAC) could stratify ASCVD risk among patients eligible for icosapent ethyl. Among 23 759 patients who underwent computed tomography angiography (CTA) in the Western Denmark Heart Registry, we identified eligibility for the REDUCE-IT trial. A total of 2146 participants (9%) met enrolment criteria for REDUCE-IT. During a median of 4.3 years of follow-up, 146 ASCVD events occurred. Overall, there was a stepwise increase in ASCVD event rates per 1000 person-years with increasing CAC (CAC = 0: 10.5, CAC 1-299: 18.7, CAC ≥300: 49.8). REDUCE-IT-eligible patients with CAC ≥300 had a multivariable-adjusted hazard ratio of 3.1 compared with CAC = 0 (95% confidence interval: 1.9-4.9). Coronary artery calcium differentiated risk similarly in patients with and without obstructive coronary artery disease (CAD). Overall, the 5-year estimated number needed to treat to prevent one event with icosapent ethyl was 45 and ranged from 87 in those with CAC = 0 to 17 in those with CAC ≥300. Some patients with non-obstructive CAD had lower estimated number needed to treat than patients with obstructive CAD when their plaque burden was higher. Atherosclerotic plaque burden as assessed by CAC can identify REDUCE-IT-eligible patients who are expected to derive most, and least, absolute benefit from treatment with icosapent ethyl regardless of obstructive versus non-obstructive CAD status.


Energy- and Weight-Loss Functions for Decomposing Foliage in Birch and Aspen Forests in Interior Alaska.
Linear relationships were established for energy loss as a function of weight loss for birch, aspen, and alder foliage. Half times for weight loss ranged from 555 days to 651 days. Half times for energy loss ranged from 604 to 720 days.


Evolutionary conservation of the vertebrate Ah (dioxin) receptor: amplification and sequencing of the PAS domain of a teleost Ah receptor cDNA.
The PAS domain of a teleost Ah receptor was amplified using reverse transcription-PCR with degenerate primers containing inosine. The deduced amino acid sequence of the amplified cDNA fragment was 62-64% identical with the PAS domains of mammalian Ah receptors. These data demonstrate the homology of Ah receptors in mammals and fish, and reveal regions of this protein that are highly conserved between these diverse vertebrate groups.


Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio.
Pretreatment hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. In this study, we evaluated the prognostic significance of various hematologic parameters in patients with nasopharyngeal carcinoma (NPC). Clinical data from 251 patients with NPC were retrospectively collected. Neutrophil counts, lymphocyte counts, platelet counts, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were adopted as potential prognostic biomarkers. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the progression-free survival (PFS) and overall survival (OS) rates. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. NLR ≥2.7 (hazard ratio [HR] = 2.01; 95% confidence interval [CI] = 1.23-3.29; p = .005) and PLR ≥167.2 (HR = 2.12; 95% CI = 1.35-3.33; p = .001) were significantly associated with shorter PFS, whereas PLR ≥163.4 (HR = 2.64; 95% CI = 1.25-5.60; p = .011) was correlated with poor OS. Pretreatment NLR and PLR can be independent prognostic factors for patients with NPC. © 2015 Wiley Periodicals, Head Neck 38: E1332-E1340, 2016.


Enhancement of the efficiency of photodynamic therapy of tumours by t-butyl-4-hydroxyanisole.
The effects of photodynamic therapy (PDT) alone and in combination with 3(2)-t-butyl-4-hydroxyanisole (BHA) on Ehrlich ascites carcinoma (EAC) cells have been investigated. BHA, a widely used food antioxidant, administered to the cells prior to light exposure is found to cause concentration-dependent alterations of the haematoporphyrin derivative (HpD)-based PDT. BHA (0.15 mM) causes a small (about 10%) inhibition in the rate of HpD-photosensitized injury of EAC cells. In contrast, upon increasing the concentration of BHA from 0.15 to 0.5 mM, a 1.3-fold enhancement in HpD-PDT efficiency is achieved. The cytotoxic effect on the cells treated with HpD-PDT and a higher concentration of BHA (0.5 mM) is additive. When BHA (0.5 mM) is given immediately after HpD-PDT, the combination is found to be three to four times more effective than when BHA is added to EAC cells before phototherapy. In this treatment regimen BHA acts synergistically with HpD-PDT. Such a difference in the action of BHA on the efficiency of HpD-PDT might be explained by the ability of BHA to inhibit the HpD-photosensitized destruction of some biomolecules. An enhancing action of BHA on the intensity of HpD-photosensitized death of tumour cells is also observed in vivo. Even a single dose of BHA (0.6 mM kg-1, 15 min after irradiation) causes (in an additive manner) an approximately two-fold increase in the efficiency of HpD-PDT of mice bearing Ehrlich ascites tumour (intraperitoneal transplantation). The results obtained indicate that the potentiating effect of BHA on the HpD-PDT could be caused by the impairment of the mitochondrial respiration, since there is a good correspondence between the concentration of BHA that increases the efficiency of PDT and the concentration that inhibits the oxygen consumption and dehydrogenase activity of EAC cells. The influence of BHA on the efficiency of PDT does not depend on the nature of the photosensitizer used; the effects with chlorin-e6 trimethyl ester are similar to that seen for HpD.


TOB1 modulates the decidualization of human endometrial stromal cells via the Notch pathway.
Decidualization is critical for embryo implantation and the success of pregnancy; however, the mechanisms underlying this process remain largely unknown. In the present study, RNA sequencing was used to detect the expression levels of transducer of ERBB2/1(TOB1) in endometrial samples derived from proliferative and secretory phases. A decidualization model was induced using the combination of estrogen (E2) and progestin (P4) in human endometrial stromal cells (HESCs). The cell counting kit-8 assay was used to detect the viability of HESCs. Related proteins were detected by qPCR and western blot. The results indicated that TOB1 expression was upregulated in the secretory endometrial samples compared with the corresponding expression observed in the proliferative samples. The expression levels of TOB1 and Notch1 were markedly increased in E2P4-treated HESCs compared with those in the control cells. Treatment with E2P4 strongly suppressed the proliferation of HESCs and induced a G1-phase cell cycle arrest. These effects were abolished by knockdown of TOB1 or treatment with of the cells with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester. Therefore, these findings highlighted an important role for TOB1/Notch signaling in E2P4-induced decidualization in HESCs, which may provide novel targets for improving the endometrial receptivity.


[Factors associated with the risk of developing eating disorders among medical students in Casablanca, Morocco].
eating disorders (EDs) are particularly common among young adults, including students. The purpose of this study is to determine eating disorder prevalence among medical students in Casablanca and to assess the risk of developing EDs on the bases of associated factors including socioeconomic factors, clinical features, anxiety and depression. we conducted a cross-sectional, descriptive and analytical study at the Ibn Rochd University Hospital and at the Faculty of Medicine and Pharmacy of Casablanca, Morocco, during the academic year 2016-2017. The survey involved a sample of 506 students. We used the SCOFF-F (Sick, Control, One Stone, Fat, Food, French version) questionnaire, a validated tool for eating disorders and the hospital anxiety and depression scale (HAD) for anxiety and depression. the SCOFF questionnaire found that 127 people out of 506 (25.09%) were likely to suffer from eating disorders. Age, educational level, weight-management tools, anxiety and depression were significantly associated with the risk of developing eating disorders among medical students. our results are in agreement with data from the literature concerning eating disorder rates in the student population and, more specifically, among medical students. Further, studies of a more heterogeneous population are needed to have a more global vision of the situation in Morocco.


Morphological Changes Caused by Streptozotocin-Induced Diabetes in the Healthy Gingiva of Rats.
Epidemiologic and clinical studies have indicated that diabetes is a risk factor for periodontal disease progression. The aim of the present study was to evaluate the morphological changes of gingiva in streptozotocin diabetic rats. 30 male Wistar rats that weighed 250-300 g were used in this study. The animals were randomly divided into 2 groups, one with streptozotocin-induced diabetes and another one with healthy (non-diabetic) animals. All rats were sacrificed after 21 days, and their maxillary first molars with surrounding tissues were observed morphological analyses. In this study, it was observed that the epithelial thickness was greater in the diabetes group, compared to the control group. The statistical comparison of the diabetes and control groups for the thickness of each of the layers of the epithelium demonstrated that the thickness of the keratinized (corneum), granular and basal layers had significantly increased in the diabetic animals. Furthermore, the diabetes group displayed a decrease in the height of the connective tissue papillae, which was found to be statistically insignificant. Another important finding detected in the diabetes group was the congestion of the gingival capillaries, which showed that blood circulation is impaired in diabetes cases. On the basis of the results obtained in this study, it was concluded that streptozotocin-induced diabetes may increase predisposition to periodontal disease by causing morphological changes in the periodontal tissues.


Characterizations of annexin A1-interacting proteins in apical membrane and cytosolic compartments of renal tubular epithelial cells.
Annexin A1 (ANXA1) is a multifunctional calcium-binding protein that can bind to membrane phospholipids. Under high-calcium condition, ANXA1 expression increases on renal epithelial cell surface, leading to enhanced adhesion of calcium oxalate (CaOx) crystal (stone material) onto the cells. To regulate various cellular processes, ANXA1 interacts with many other intracellular protein partners. However, components of the ANXA1-interacting protein complex remain unclear. Herein, we characterized the interacting complexes of apical membrane (ApANXA1) and cytosolic (cyANXA1) forms of ANXA1 in apical membrane and cytosolic compartments, respectively, of renal epithelial cells under high-calcium condition using proteomic and bioinformatic approaches. After fractionation, the ApANXA1- and CyANXA1-interacting partners were identified by immunoprecipitation followed by nanoLC‑ESI‑Qq-TOF tandem mass spectrometry (IP-MS/MS). The ANXA1-interacting partners that were common in both apical membrane and cytosolic compartments and those unique in each compartment were then analyzed for their physico-chemical properties (molecular weight, isoelectric point, amino acid contents, instability index, aliphatic index, and grand average of hydropathicity), secondary structure (α-helix, β-turn, random coil, and extended strand), molecular functions, biological processes, reactome pathways and KEGG pathways. The data demonstrated that each set of these interacting proteins exhibited common and unique characteristics and properties. The knowledge from this study may lead to better understanding of the ApANXA1 and CyAXNA1 biochemistry and functions as well as the pathophysiology of CaOx kidney stone formation induced by high-calcium condition.


Robust genome and RNA editing via CRISPR nucleases in PiggyBac systems.
CRISPR/Cas-mediated genome editing in human pluripotent stem cells (hPSCs) offers unprecedented opportunities for developing in vitro disease modeling, drug screening and cell-based therapies. To efficiently deliver the CRISPR components, here we developed two all-in-one vectors containing Cas9/gRNA and inducible Cas13d/gRNA cassettes for robust genome editing and RNA interference respectively. These vectors utilized the PiggyBac transposon system, which allows stable expression of CRISPR components in hPSCs. The Cas9 vector PB-CRISPR exhibited high efficiency (up to 99%) of inducing gene knockout in both protein-coding genes and long non-coding RNAs. The other inducible Cas13d vector achieved extremely high efficiency in RNA knockdown (98% knockdown for CD90) with optimized gRNA designs. Taken together, our PiggyBac CRISPR vectors can serve as powerful toolkits for studying gene functions in hPSCs.


A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy.
An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.


Switch from a ritonavir to a cobicistat containing antiretroviral regimen and impact on tacrolimus levels in a kidney transplant recipient.
Solid-organ transplantation due to end-stage organ disease is increasingly performed in people living with HIV. Despite improved transplant outcomes, management of these patients remains challenging due to higher risk for allograft rejection, infection and drug-drug interactions (DDIs). Complex regimens for multi-drug resistant HIV-viruses may cause DDIs particularly if the regimen contains drugs such as ritonavir or cobicistat. Here we report on a case of an HIV-infected renal transplant recipient on long-term immunosuppressive therapy with mycophenolate mofetil and tacrolimus dosed at 0.5 mg every 11 days due to the co-administration of a darunavir/ritonavir containing antiretroviral regimen. In the presented case the pharmacokinetic booster was switched from ritonavir to cobicistat for treatment simplification. A close monitoring of tacrolimus drug levels was performed in order to prevent possible sub- or supratherapeutic tacrolimus trough levels. A progressive decrease in tacrolimus concentrations was observed after switch requiring shortening of tacrolimus dosing interval. This observation was unexpected considering that cobicistat is devoid of inducing properties. This case highlights the fact that the pharmacokinetic boosters ritonavir and cobicistat are not fully interchangeable. Therapeutic drug monitoring of tacrolimus is warranted to maintain levels within the therapeutic range.


Fibroblastic osteosarcoma of the mandible.
Osteosarcoma of the mandible is a rare lesion. We report the case of a 16-year-old male who developed a fibroblastic osteosarcoma at the site of a wisdom tooth extraction. The lesion followed an aggressive course of recurrence and diffuse disseminated osteosarcomatosis. We speculate on the causal factors that resulted in this rapid course.


Molecular packing in the feather keratin filament.
Avian feathers have a filament-matrix texture and X-ray diffraction studies show that the filament has a helical structure with four repeating units per turn. Each repeating unit consists of a pair of twisted beta-sheets related by a perpendicular diad, and the twist in the sheets is of opposite hand to that of the helix. Each sheet is believed to comprise a 32-residue segment of the feather keratin molecule, which contains around 100 residues, the remainder constituting the matrix. In the present contribution, the sequence of emu feather is mapped to the low-resolution model derived earlier from X-ray studies. This shows that the inner surface of the "beta-sandwich" is densely populated by hydrophobic residues and that the charged residues and cysteine residues lie on the outer surface. In addition, the inner residues in the repeating unit mesh neatly together in layers oriented perpendicular to the filament axis. Amino acid sequences from a range of avian and reptilian keratins were collected and a 32-residue segment corresponding to the filament framework could be identified in every case, supporting the notion that there is a common plan for the filament framework in all of these materials. The hairpin turns in the beta-sheet were also identified and shown to be unusually rich in proline residues and also of variable composition. Two variants of the mapping were found which have complimentary conformations of the hairpin turns and these are illustrated and discussed. Since feather keratin yields a fiber rather than a crystalline X-ray pattern refinement of the model is restricted to trial-and-error methods and the assumptions made in its derivation are critically examined and some possible modifications discussed.


Levels of different subtypes of tumour-infiltrating lymphocytes correlate with each other, with matched circulating lymphocytes, and with survival in breast cancer.
Breast cancer tumour-infiltrating lymphocytes associate with clinico-pathological factors, including survival, although the literature includes many conflicting findings. Our aim was to assess these associations for key lymphocyte subtypes and in different tumour compartments, to determine whether these provide differential correlations and could, therefore, explain published inconsistencies. Uniquely, we also examine whether infiltrating levels merely reflect systemic lymphocyte levels or whether local factors are predominant in recruitment. Immunohistochemistry was used to detect tumour-infiltrating CD20+ (B), CD4+ (helper T), CD8+ (cytotoxic T) and FoxP3+ (regulatory T) cells in breast cancers from 62 patients, with quantification in tumour stroma, tumour cell nests, and tumour margins. Levels were analysed with respect to clinico-pathological characteristics and matched circulating levels (determined by flow-cytometry). CD4+ lymphocytes were the most prevalent subtype in tumour stroma and at tumour edge and CD8+ lymphocytes were most prevalent in tumour nests; FoxP3+ lymphocytes were rarest in all compartments. High grade or hormone receptor negative tumours generally had significantly increased lymphocytes, especially in tumour stroma. Only intra-tumoural levels of CD8+ lymphocytes correlated significantly with matched circulating levels (p < 0.03), suggesting that recruitment is mainly unrelated to systemic activity. High levels of stromal CD4+ and CD20+ cells associated with improved survival in hormone receptor negative cases (p < 0.04), while tumour nest CD8+ and FoxP3+ cells associated with poor survival in hormone receptor positives (p < 0.005). Lymphocyte subtype and location define differential impacts on tumour biology, therefore, roles of tumour-infiltrating lymphocytes will only be unravelled through thorough analyses that take this into account.


Age, sex, and ischaemic heart disease as prognostic indicators in long-term cardiac pacing.
The influence of age, sex, and overt ischaemic heart disease on survival after pacing was studied in a population of 427 patients. The median survival for the whole group was 7.75 years. Women between 55 and 74 years and men between 65 and 74 years enjoyed median survivals in excess of 10 years. Patients over 74 years and men with ischaemic heart disease had median survivals of the order of 5 years and 3 1/2 years, respectively. The findings may help to match generator lifetimes to patient-survival prospects.


Staphylococcus aureus (MSSA) and MRSA (CC398) isolated from post-mortem samples from pigs.
There are many reports on the occurrence of Livestock Associated Methicilline resistant Staphylococcus aureus (LA-MRSA, CC398) in healthy pigs. There are however, very few reports of LA-MRSA being associated with pathological lesions in pigs. With this study we try to find the answers to the questions: (1) how often is S. aureus found in post-mortem material from pigs, (2) how many of these isolates are methicillin resistant, (3) are these equally distributed over the years? Here we report the isolation of MRSA and of methicillin sensitive S. aureus (MSSA) from samples derived from post-mortem examinations at the Animal Health Service in The Netherlands in the period from 2003 through October 2008. The MSSA and MRSA described here were isolated from 159 pathological lesions and from 7 submissions of aborted foetuses derived from a total of 116 animals, representing 103 submissions coming from 92 different herds. This is approximately 0.5% of all pigs submitted for post mortem examination in those years. The proportion of pigs from which S. aureus (both MSSA and MRSA) was isolated from, did not increase over the years. MSSA (N=97) and LA-MRSA CC398 (N=18) were present mainly in (peri)arthritis in over 30% of all cases, but were also isolated from internal organs such as lung, brain, spleen, kidneys, heart, indicating septicaemia. Remarkably, one non-CC398 MRSA (ST1) was isolated in a joint and a kidney of one pig. This isolate was resistant to 5 out of 6 antimicrobials tested. There was no significant difference in the type of lesions in which LA-MRSA was found compared to MSSA. The number of antimicrobials these isolates were resistant to, increased rapidly after 2004. LA-MRSA was isolated for the first time in 2005 and then again in 2007 and 2008, suggesting that this is an emerging pathogen. However, due to changes in the panel of antimicrobials used to test S. aureus for antimicrobial susceptibility in 2005 and 2007, the possibility exists that we may have missed some MRSA isolates. LA-MRSA isolates are resistant to at least three but sometimes five out of six antimicrobials tested. All isolates were susceptible to the combination of Trimethoprim/Sulfamethaxol.


Etiology of depression: genetic and environmental factors.
In summary, depressed patients with a history of childhood trauma may have a distinct depression endophenotype characterized by a specific neurobiology and risk genotype that may be responsive to different treatment strategies than depressed patients without childhood adversity. Based on current findings, treatment strategies should be multimodal and include the following: 1. Psychotherapy that addresses a number of domains, such as emotional regulation, cognitive reframing, careful exploration of past traumatic events, attachment, and interpersonal relationships in a safe and trusting therapeutic environment. 2. The therapy should likely be longer term in order to effectively impact those domains. 3. Pharmacotherapy that will be effective in quieting the body's hyperresponsiveness to stress and reverse epigenetic modifications induced by trauma and stress. 4. Environmental interventions that provide a support network (maternal care, a positive family environment, the support of a close friend) have all been shown to attenuate the impact of childhood abuse. In addition, there is great potential in the identification of genomic biomarkers to help guide us in the identification of traumatized individuals who are susceptible to depression. These indices may also help identify those for whom the immediate provision of treatment may have a preventive effect and may someday guide us in the development of novel pharmacologic approaches.


[Knowledge of attitudes and expectations: a prerequisite for effective health education].
Some global results are presented here several studies of psychosociology conducted in Lorraine; they deal with attitudes and expectations of the people about their health and are obtained from a special factor analysis. This method, of a descriptive nature, allows us to understand the pluridimensional universe of some of the representations considered and particularly to determine how each representation is connected with the others and how they are assembled within the whole system so as to establish typologies. The observation is made, notably by means of 2 projections on situational maps, that axis 1 establishes a bi-polarity among the wider tendencies such as medecine, physicians, health which corresponds, roughly speaking, to an opposition between "some collar" workers and "white collar" cadres, fatalists and non-fatalists. Less clearly appears a double splitting within the group of cadres and whtin the group of workers, the latter being less favored in the field of medicine and health. We can thus perceive 4 sectors where constellations of variables are organized and which correspond to typologies of attitudes. In fact, whether we rely on socio-professional stratifications or on mentalities, we must, to be efficient, take into account associations of attitudes as well as expectations, constructed according to this method, before starting selective actions of health education.


Interactions between αCaMKII and calmodulin in living cells: conformational changes arising from CaM-dependent and -independent relationships.
αCaMKII plays central and essential roles in long-term potentiation (LTP), learning and memory. αCaMKII is activated via binding with Ca²⁺/CaM in response to elevated Ca²⁺ concentration. Furthermore, prolonged increase in Ca²⁺ concentration leads to the auto-phosphorylation of αCaMKII at T286, maintaining the activation of αCaMKII even after Ca²⁺/CaM dissociation. Importantly, the active form of αCaMKII is thought to exhibit conformational change. In order to elucidate the relationships between the interaction of αCaMKII with CaM and the conformational change of αCaMKII, we generated molecular probes (YFP-αCaMKII with CFP-CaM and YFP-αCaMKII-CFP) and performed time-lapse imaging of the interaction with CaM and the conformational change, respectively, in living cells using FRET. The interaction of YFP-αCaMKII with CFP-CaM and the conformational change of YFP-αCaMKII-CFP were induced simultaneously in response to increased concentrations of Ca²⁺. Consistent with previous predictions, high levels of Ca²⁺ signaling maintained the conformational change of YFP-αCaMKII-CFP at the time when CFP-CaM was released from YFP-αCaMKII. These observations indicated the transfer of αCaMKII conformational change from CaM-dependence to CaM-independence. Furthermore, analyses using αCaMKII mutants showed that phosphorylation at T286 and T305/306 played positive and negative roles, respectively, during in vivo interaction with CaM and further suggested that CaM-dependent and CaM-independent conformational changed forms displays similar but distinct structures. Importantly, these structual differences between CaM-dependent and -independent forms of αCaMKII may exhibit differential functions for αCaMKII, such as interactions with other molecules required for LTP and memory. Our molecular probes could thus be used to identify therapeutic targets for cognitive disorders that are associated with the misregulation of αCaMKII.


Aberrant, canavanyl protein formation and the ability to tolerate or utilize L-canavanine.
L-Canavanine, 2-amino-4-(guanidinooxy)butyric acid, and L-arginine incorporation into de novo synthesized proteins was compared in six organisms. Utilizing L-[guanidinooxy14C]canavanine and L-[guanidino14C]arginine at substrate saturation, the canavanine to arginine incorporation ratio was determined in de novo synthesized proteins. Caryedes brasiliensis and Sternechus tuberculatus, canavanine utilizing insects; Canavalia ensiformis, a canavanine storing plant; and to a lesser extent Heliothis virescens, a canavanine resistant insect, failed to accumulate significant canavanyl proteins. By contrast, Manduca sexta, a canavanine-sensitive insect, and Glycine max, a canavanine free plant, readily incorporated canavanine into newly synthesized proteins. This study supports the contention that the incorporation of canavanine into proteins in place of arginine contributes significantly to canavanine's antimetabolic properties.


Monitoring the release of anti-inflammatory and analgesic pharmaceuticals in the receiving environment.
The occurrence of anti-inflammatory and analgesic pharmaceuticals (AIAPs) in the effluents of 16 hospitals, influent and effluent of wastewater treatment plant (WWTP), the contribution and mass load of each hospital to WWTP influent, and the removal efficiencies in WWTP were investigated. Environmental risk was also evaluated by toxicity tests using organisms from three different trophic levels. Acetaminophen had the highest concentration in summer and winter samples, followed by ketoprofen, ibuprofen, and naproxen. The total daily load of AIAPs detected in influent of WWTP was 1677 mg/day/1000 inhabitants in summer and 5074 mg/day/1000 inhabitants in winter. The contribution of 16 hospitals to the total AIAP load in influent of WWTP was 11.30% in summer and 7.09% in winter. The highest mass loads were calculated as 203 mg/bed.day in general hospital in summer and 300 mg/bed.day in pediatric hospital in winter. The removal efficiencies of AIAPs in WWTP ranged between 13% and 100% in summer and 0.88% and 99% in winter. WWTP is not sufficient to remove all the AIAPs. Diclofenac (in summer), mefenamic acid, indomethacin, and phenylbutazone exhibited poor removal below 50%. The effluents of the WWTP exhibited a low risk for fish and Daphnia magna and an insignificant risk for algae.


Aggressive Langerhans cell histiocytosis following T-cell acute lymphoblastic leukemia.
A 4-year-old female child developed cutaneous Langerhans cell histiocytosis 6 months following a diagnosis of T-cell acute lymphoblastic leukemia. Imaging revealed no evidence of systemic disease. Seven months later, the first systemic lesion was discovered on laryngoscopy. Restaging Positron Emission Tomography - Computed Tomography at that time revealed new 18-fluorodeoxyglucose-positive lesions in the left apical pleural margin, right lower peri-esophageal region, left ventricular myocardium, pancreas, upper pole of the left kidney, and inguinal and gluteal regions consistent with progressive systemic disease. Genomic testing revealed a low tumor mutational burden as well as mutations in KRAS G12A, ARID1A Q524, CDKN2A/B loss, and an alteration in NOTCH1.


[What's new in the couple thyroid and heart in 2008?].
Beginning in development and extending to adult physiology, a close relationship exists between the thyroid gland and the heart. They migrate together during ontogeny and possess common factors of transcriptions. Among them, Nkx2-5 whose mutations were recently described in patients with congenital hypothyroidism. The genomic impact of triiodothyronine (T3) on cardiac tissue allows the activation of synthesis of proteins belonging to the contractile device. The progress realized in the understanding of the mechanisms of cardiac remodelling strengthens the links between both organs : for example the recent discovery of interactions between some microARNs, activated in case of heart failure and the thyroid hormone receptor. There are numerous parallels between hypothyroidism and heart failure. The low- T3 syndrome are the single most significant predictor of cardiovascular and all-cause mortality in adults with heart disease and the treatment by T3 in these circumstances could allow improvement in cardiac function.


Random amplified polymorphic DNA analysis for differentiation of Leuconostoc mesenteroides subspecies isolated from Tenerife cheese.
In the present study, a RAPD-PCR fingerprinting method was developed to assign Tenerife cheese Leuconostoc mesenteroides strains to its three subspecies (mesenteroides, cremoris and dextranicum). Arbitrarily primed-PCR gave different DNA banding patterns for each type strain of Leuc. mesenteroides subspecies consisting in three major and intense bands of: 1800, 1600 and 1150 bp for subspecies mesenteroides 1800, 1150 and approximately 350 bp for subspecies cremoris; and 1800, 1600 and 1500 bp for subspecies dextranicum. DNA fingerprints of Tenerife cheese Leuc. mesenteroides subspecies were coincident to that of their respective type strain. RAPD profiles were reproducible with DNA template obtained by two different extraction methods. Tenerife cheese Leuc. mesenteroides strains were rapidly and unequivocally assigned to one of the subspecies by comparing their RAPD-PCR fingerprints with those displayed by type strains used as standards. This technique can be applied to complement preliminary identification of Leuc. mesenteroides to the species level by other molecular methods such as protein fingerprinting. RAPD-PCR allows reliable, reproducible and rapid molecular differentiation of Tenerife cheese Leuc. mesenteroides subspecies with no need to use time-consuming and often ambiguous biochemical tests.