Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.
Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.


Remote Monitoring of Hypertension Diseases in Pregnancy: A Pilot Study.
Although remote monitoring (RM) has proven its added value in various health care domains, little is known about the remote follow-up of pregnant women diagnosed with a gestational hypertensive disorders (GHD). The aim of this study was to evaluate the added value of a remote follow-up program for pregnant women diagnosed with GHD. A 1-year retrospective study was performed in the outpatient clinic of a 2nd level prenatal center where pregnant women with GHD received RM or conventional care (CC). Primary study endpoints include number of prenatal visits and admissions to the prenatal observation ward. Secondary outcomes include gestational outcome, mode of delivery, neonatal outcome, and admission to neonatal intensive care (NIC). Differences in continuous and categorical variables in maternal demographics and characteristics were tested using Unpaired Student's two sampled t test or Mann-Whitney U test and the chi-square test. Both a univariate and multivariate analysis were performed for analyzing prenatal follow-up and gestational outcomes. All statistical analyses were done at nominal level, Cronbach alpha=.05. Of the 166 patients diagnosed with GHD, 53 received RM and 113 CC. After excluding 5 patients in the RM group and 15 in the CC group because of the missing data, 48 patients in RM group and 98 in CC group were taken into final analysis. The RM group had more women diagnosed with gestational hypertension, but less with preeclampsia when compared with CC (81.25% vs 42.86% and 14.58% vs 43.87%). Compared with CC, univariate analysis in RM showed less induction, more spontaneous labors, and less maternal and neonatal hospitalizations (48.98% vs 25.00%; 31.63% vs 60.42%; 74.49% vs 56.25%; and 27.55% vs 10.42%). This was also true in multivariate analysis, except for hospitalizations. An RM follow-up of women with GHD is a promising tool in the prenatal care. It opens the perspectives to reverse the current evolution of antenatal interventions leading to more interventions and as such to ever increasing medicalized antenatal care.


[Growth inhibition of the emulsion from to Brucea javanica cultured human carcinoma cells].
We studied the growth inhibitory activity of the emulsion from Brucea javanica fruit of B. javanica to human squamous cell carcinoma cells. The dose of 250 micrograms/ml at 96 hrs after drug exposure, it showed 42% growth inhibition, and at 500 micrograms/ml inhibited 56% of the cell growth. The effect of more than 50% of the growth inhibition was evident at more than 7 hrs after drug exposure. In the analysis of mechanism of the drug using a flow cytometry, the arrest in G1 phase of cell cycle was found during incubation of cancer cells with drug. These results suggested that the oil of B. javanica is useful as an anticancer drug.


Effect of total flavonoid in rabdosia rubescens on tolerant mice models under cerebral anoxia.
To study the protective effect of total flavonoid in rabdosia rubescens on BIT model by brain ischemic tolerance (hereinafter BIT) model of mice. BIT model is used to block bilateral common carotid arteries and to copy BIT model of mice. After 10 min of transient ischemia for rats in preconditioning group, the mice in the nimodipine group and naoluotong capsule group were given the total flavonoid in rabdosia rubescens (300 mg/kg, 150 mg/kg, 75 mg/kg) for gavage, sham operation group, ischemia/reperfusion injury (hereinafter IRI) group and BIT group were fed with the same volume of 0.5% sodium carboxymethyl cellulose (CMC) once a day for 5 days. After administration for 1 h on day 5 (120 h), the rats in the other groups except for the sham operation group were treated with blood flow block for 30 min and reperfusion for 22 h. The serum NSE level were measured and the brain NO content and NOS activity changes was measured to observe the histopathological changes of brain tissue. BIT models of mice and in rats were both successfully replicated. The total flavonoid in rabdosia rubescens can decrease the mortality of mice, decrease serum NSE level, increase the content of NO and the activity of NOS in the brain tissue of mice, and improve the pathological damage of cortex and hippocampus of mice. The total flavonoid in rabdosia rubescens can stimulate an endogenous protective mechanism by inducing the release of low levels of cytokines NO and NOS, which reduces the release of serum NSE, relieves the brain tissue ischemia-reperfusion injury, and further improves the protection effect of ischemic preconditioning on brain injury. The damage of brain tissue ischemia and reperfusion, and further improve the ischemia Protective effect of preconditioning on brain injury.


How to Fight an Infodemic: The Four Pillars of Infodemic Management.
In this issue of the Journal of Medical Internet Research, the World Health Organization (WHO) is presenting a framework for managing the coronavirus disease (COVID-19) infodemic. Infodemiology is now acknowledged by public health organizations and the WHO as an important emerging scientific field and critical area of practice during a pandemic. From the perspective of being the first "infodemiologist" who originally coined the term almost two decades ago, I am positing four pillars of infodemic management: (1) information monitoring (infoveillance); (2) building eHealth Literacy and science literacy capacity; (3) encouraging knowledge refinement and quality improvement processes such as fact checking and peer-review; and (4) accurate and timely knowledge translation, minimizing distorting factors such as political or commercial influences. In the current COVID-19 pandemic, the United Nations has advocated that facts and science should be promoted and that these constitute the antidote to the current infodemic. This is in stark contrast to the realities of infodemic mismanagement and misguided upstream filtering, where social media platforms such as Twitter have advertising policies that sideline science organizations and science publishers, treating peer-reviewed science as "inappropriate content."


Administration of acetylcholine to the spermatic nerve plexus inhibits testosterone secretion in an in vitro isolated rat testis-nerve plexus system.
Strong evidence indicated that spermatic nerves are involved in the regulation of testosterone secretion. Our previous work showed that the inferior spermatic nerves play a more significant role than the superior ones in the regulation of testosterone secretion. However, it is unknown whether traditional neurotransmitters are involved in this regulation. In order to evaluate this point, the present experiments were carried out in an in vitro system where an isolated testis-spermatic nerve plexus preparation was incubated in two separate containers, one for the testis and the other for the nerve plexus and both interconnected by the inferior spermatic nerves. Both tissues were maintained in the same environmental conditions except for the neurotransmitter treatment, applied only to the nerve plexus. Acetylcholine can significantly inhibit the secretion of testosterone until the end of incubation. The present experiments suggest that the secretion of testosterone could be regulated, at least in part, by acetylcholine through the inferior spermatic nerves.


Pen and Pal are nucleotide-sugar dehydratases that convert UDP-GlcNAc to UDP-6-deoxy-D-GlcNAc-5,6-ene and then to UDP-4-keto-6-deoxy-L-AltNAc for CMP-pseudaminic acid synthesis in Bacillus thuringiensis.
CMP-pseudaminic acid is a precursor required for the O-glycosylation of flagellin in some pathogenic Gram-negative bacteria, a process known to be critical in bacterial motility and infection. However, little is known about flagellin glycosylation in Gram-positive bacteria. Here, we identified and functionally characterized an operon, named Bti_pse, in Bacillus thuringiensis israelensis ATCC 35646, which encodes seven different enzymes that together convert UDP-GlcNAc to CMP-pseudaminic acid. In contrast, Gram-negative bacteria complete this reaction with six enzymes. The first enzyme, which we named Pen, converts UDP-d-GlcNAc to an uncommon UDP-sugar, UDP-6-deoxy-D-GlcNAc-5,6-ene. Pen contains strongly bound NADP(+) and has distinct UDP-GlcNAc 4-oxidase, 5,6-dehydratase, and 4-reductase activities. The second enzyme, which we named Pal, converts UDP-6-deoxy-D-GlcNAc-5,6-ene to UDP-4-keto-6-deoxy-L-AltNAc. Pal is NAD(+)-dependent and has distinct UDP-6-deoxy-d-GlcNAc-5,6-ene 4-oxidase, 5,6-reductase, and 5-epimerase activities. We also show here using NMR spectroscopy and mass spectrometry that in B. thuringiensis, the enzymatic product of Pen and Pal, UDP-4-keto-6-deoxy-L-AltNAc, is converted to CMP-pseudaminic acid by the sequential activities of a C4″-transaminase (Pam), a 4-N-acetyltransferase (Pdi), a UDP-hydrolase (Phy), an enzyme (Ppa) that adds phosphoenolpyruvate to form pseudaminic acid, and finally a cytidylyltransferase that condenses CTP to generate CMP-pseudaminic acid. Knowledge of the distinct dehydratase-like enzymes Pen and Pal and their role in CMP-pseudaminic acid biosynthesis in Gram-positive bacteria provides a foundation to investigate the role of pseudaminic acid and flagellin glycosylation in Bacillus and their involvement in bacterial motility and pathogenicity.


[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].
The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland requires the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, including development, implementation and monitoring of the implementation of procedures into practice, aiming at limiting the dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staff with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include reporting all of the recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as an occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides principles of financing of individual benefits available for the insured TB patients as well as those not insured.


Lessons Learned From GWAS of Asthma.
Asthma is a common complex disease of the airways. Genome-wide association studies (GWASs) of asthma have identified many risk alleles and loci that have been replicated in worldwide populations. Although the risk alleles identified by GWAS have small effects and explain only a small portion of prevalence, the discovery of asthma loci can provide an understanding of its genetic architecture and the molecular pathways involved in disease pathogenesis. These discoveries can translate into advances in clinical care by identifying therapeutic targets, preventive strategies and ultimately approaches for personalized medicine. In this review, we summarize results from GWAS of asthma from the past 10 years and the insights gleaned from these discoveries.


Proteome analysis of cytoplasmatic and plastidic β-carotene lipid droplets in Dunaliella bardawil.
The halotolerant green alga Dunaliella bardawil is unique in that it accumulates under stress two types of lipid droplets: cytoplasmatic lipid droplets (CLD) and β-carotene-rich (βC) plastoglobuli. Recently, we isolated and analyzed the lipid and pigment compositions of these lipid droplets. Here, we describe their proteome analysis. A contamination filter and an enrichment filter were utilized to define core proteins. A proteome database of Dunaliella salina/D. bardawil was constructed to aid the identification of lipid droplet proteins. A total of 124 and 42 core proteins were identified in βC-plastoglobuli and CLD, respectively, with only eight common proteins. Dunaliella spp. CLD resemble cytoplasmic droplets from Chlamydomonas reinhardtii and contain major lipid droplet-associated protein and enzymes involved in lipid and sterol metabolism. The βC-plastoglobuli proteome resembles the C. reinhardtii eyespot and Arabidopsis (Arabidopsis thaliana) plastoglobule proteomes and contains carotene-globule-associated protein, plastid-lipid-associated protein-fibrillins, SOUL heme-binding proteins, phytyl ester synthases, β-carotene biosynthesis enzymes, and proteins involved in membrane remodeling/lipid droplet biogenesis: VESICLE-INDUCING PLASTID PROTEIN1, synaptotagmin, and the eyespot assembly proteins EYE3 and SOUL3. Based on these and previous results, we propose models for the biogenesis of βC-plastoglobuli and the biosynthesis of β-carotene within βC-plastoglobuli and hypothesize that βC-plastoglobuli evolved from eyespot lipid droplets.


Rehabilitation of shoulder impingement syndrome and rotator cuff injuries: an evidence-based review.
Rehabilitation of the patient with glenohumeral impingement requires a complete understanding of the structures involved and the underlying mechanism creating the impingement response. A detailed clinical examination and comprehensive treatment programme including specific interventions to address pain, scapular dysfunction and rotator cuff weakness are recommended. The inclusion of objective testing to quantify range of motion and both muscular strength and balance in addition to the manual orthopaedic clinical tests allows clinicians to design evidence-based rehabilitation programmes as well as measure progression and patient improvement.


Matrix confinement plays a pivotal role in regulating neutrophil-generated tractions, speed, and integrin utilization.
Neutrophils are capable of switching from integrin-dependent motility on two-dimensional substrata to integrin-independent motion following entry into the confined three-dimensional matrix of an afflicted tissue. However, whether integrins still maintain a regulatory role for cell traction generation and cell locomotion under the physical confinement of the three-dimensional matrix is unknown, and this is challenging to deduce from motility studies alone. Using three-dimensional traction force microscopy and a double hydrogel sandwich system, we determined the three-dimensional spatiotemporal traction forces of motile neutrophils at unprecedented resolution and show, for the first time, that entry into a highly confined space (2.5D) is a sufficient trigger to convert to integrin-independent migration. We find that integrins exert a significant regulatory role in determining the magnitude and spatial distribution of tractions and cell speed on confined cells. We also find that 90% of neutrophil tractions are in the out-of-plane axis, and this may be a fundamental element of neutrophil traction force generation.


Neurogenesis in the embryonic and adult brain: same regulators, different roles.
Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region.


[Videofluoroscopic Examination of Swallowing Using the AsR Score for Postoperative Swallowing Function in Oral Cancer Patients].
To evaluate the postoperative swallowing function in head and neck cancer patients, videofluoroscopic examination of swallowing (VF) proved useful as a qualitative evaluation, but was complex as a quantitative evaluation. We made use of the AsR score which consisted of a 10-point scale as a quantitative evaluation of VF. To identify the usefulness of the AsR score, 146 patients who had undergone extensive resection and reconstruction with free flaps or pedicle grafts were reviewed. The AsR score of VF for the first time after surgery was defined as "first score", and at the last time in the hospital was defined as "last score". The correlations between the first score and continuity of direct therapy, and between the last score and way of nutrition at the time of discharge were examined. Using the ROC (receiver operator characteristic) analysis and the AUC (area under the curve) the cut-off values of the AsR score were estimated. One hundred and thirty one patients could continue direct therapy after the first time of VF. The first score detected continuity of direct therapy with high accuracy (AUC = 0.946), furthermore using a cut-off of 5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were about 96.2%, 86.6%, 98.4%, and 72.2%, respectively. At the time of discharge, 138 patients had no limitation of oral intake and 8 patients had a limitation e.g. PEG (n = 7) and a total laryngectomy for preventing aspiration (n = 1). The last score detected oral intake ability with no limitation with high accuracy (AUC = 0.925). Using a cut-off of 6, the sensitivity, specificity, PPV and NPV were about 82.6%, 87.5%, 99.1% and 22.6%, respectively. The AsR score is useful as a quantitative evaluation of postoperative swallowing function in oral cancer patients.


Functional distinction of rat liver natural killer cells from spleen natural killer cells under normal and acidic conditions in vitro.
The microenvironment within solid tumors has often been shown to exhibit an acidic extracellular pH. Although the morphologic and functional differences in natural killer (NK) cells of the liver and spleen have been reported previously under physiological conditions, the difference under acidic conditions is still unclear. This study was to investigate the differences in the morphological and functional characteristics between rat liver and spleen NK cells under normal and acidic conditions in vitro. Liver and spleen NK cells were isolated and purified from Sprague-Dawley rats by density gradient centrifugation and the Dynabeads(®) FlowComp(TM) Flexi system, and stimulated for 4 days with or without IL-2 or treated with low pH or control for different times. Morphology was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cell death and proliferation assays were performed by flow cytometry, IFN-gamma production was tested by ELISA, and cytotoxic activity was evaluated by lactate dehydrogenase (LDH) release assay. Liver NK cells had significantly higher levels of cytotoxic activity than spleen NK cells under normal and acidic conditions, and the maximum difference was observed at pH 5.6. Further analysis revealed that the cytotoxic activity of NK cells was correlated with morphology, cell death, proliferative activity and IFN-gamma production. By TEM, liver NK cells contained a greater number of electron-dense granules per cell at pH 5.6. Moreover, a modest elevation of cell death and reduction of proliferation of liver NK cells occurred within a range of 5.6-7.2. Interestingly, an acidic extracellular pH only marginally, and not significantly, suppressed IFN-gamma production by liver NK cells. The sharp morphological and functional differences shown by the two types of NK cells in vitro indicate that liver NK cells are unexpectedly resistant to pH shock.


Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease.
As a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as well as in obesity, mood disorders and cancer. Thus, several hY1R-preferring NPY analogs have been developed as versatile tools to unravel the complex NPY/hY1R signaling in health and disease. Further, these peptides provide basic lead structures for the development of innovative drugs. Here, the current research is summarized focusing on the development of differently sized hY1R-preferring NPY analogs as well as their advances with respect to hY1R profiling, potential therapeutic applications and targeted cancer imaging and therapy. Finally, major limitations and innovative strategies for next generation hY1R-preferring NPY analogs are addressed.


Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study.
No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae. We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality. Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060-0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation. Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.


[Possible long-term prognosis in epidemiologically significant virus infections].
The long-range prognosis of viral diseases must be assessed differently according to their geographical occurrence. The genetic disposition, environmental factors and additional infectious diseases play a decisive part here. Vaccinations are the most important measures in the prevention of these infections. The spectrum of possible chemotherapeutic intervention for viral infectious diseases is very small, which usually makes specific treatment impossible. The most important infective viruses epidemiologically, which lead to persistent complications, are discussed in detail as follows: influenza virus, measles virus, human T-cell leukaemia virus, human immuno-deficiency virus, hepatitis B and C virus. In a discussion conclusions are drawn from the virologist's point of view for a possible long-range prognosis, which depends on the one hand on the infective agent and on the other on individual reactivity. The last chapter talks about insurance medical aspects of the most important infective viruses, which have already been discussed virologically. Some scientific developments are shown which could be future solutions of problems in diagnosis and prognosis. Such new developments could help insurance medical officers to important decision parameters for long-range prognosis, which are still largely missing at present.


A prototypic mathematical model of the human hair cycle.
The human hair cycle is a complex, dynamic organ-transformation process during which the hair follicle repetitively progresses from a growth phase (anagen) to a rapid apoptosis-driven involution (catagen) and finally a relative quiescent phase (telogen) before returning to anagen. At present no theory satisfactorily explains the origin of the hair cycle rhythm. Based on experimental evidence we propose a prototypic model that focuses on the dynamics of hair matrix keratinocytes. We argue that a plausible feedback-control structure between two key compartments (matrix keratinocytes and dermal papilla) leads to dynamic instabilities in the population dynamics resulting in rhythmic hair growth. The underlying oscillation consists of an autonomous switching between two quasi-steady states. Additional features of the model, namely bistability and excitability, lead to new hypotheses about the impact of interventions on hair growth. We show how in silico testing may facilitate testing of candidate hair growth modulatory agents in human HF organ culture or in clinical trials.


Alcohol-related sexual assault: a common problem among college students.
This article summarizes research on the role of alcohol in college students' sexual assault experiences. Sexual assault is extremely common among college students. At least half of these sexual assaults involve alcohol consumption by the perpetrator, the victim or both. Two research literatures were reviewed: the sexual assault literature and the literature that examines alcohol's effects on aggressive and sexual behavior. Research suggests that alcohol consumption by the perpetrator and/or the victim increases the likelihood of acquaintance sexual assault occurring through multiple pathways. Alcohol's psychological, cognitive and motor effects contribute to sexual assault. Although existing research addresses some important questions, there are many gaps. Methodological limitations of past research are noted, and suggestions are made for future research. In addition, recommendations are made for college prevention programs and policy initiatives.


Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells.
Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.


Emerging drugs for endometriosis.
Endometriosis is a benign, common gynecological disorder affecting mostly women of reproductive age. It is associated with dysmenorrhea, pelvic pain, and subfertility. The current non-surgical medical treatment is not satisfactory and there is a pressing need for novel therapeutics with better efficacy, tolerability and safety profiles. To investigate the development of new therapies for endometriosis. The PubMed database has been extensively searched for all compounds tested preclinically and clinically. Besides the three main classes of drugs, i.e., GnRH agonists, progestins, and androgenic agents, there are several classes of compounds that have been tested preclinically and clinically. Surprisingly, a considerable proportion of officially registered Phase II/III clinical trials are listed as completed yet no information on their outcomes is available. Three completed and published Phase II trials found the tested compound disappointing. Another two Phase II clinical trials have been suspended. This apparent gap between the generally promising preclinical findings and the clinical trial outcomes reflects our current woefully inadequate understanding of the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis; questions the adequacy and value of animal models of endometriosis that are still in use; highlights the difficulty in developing new therapeutics for endometriosis; and calls for more research in the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis.


Mechanical effects of intramedullary acrylic cement on fracture healing in rats.
In one group of rats, the medullary cavity was reamed and bone cement was injected. In a control group, only reaming was performed. A closed fracture was then produced in the middle of the femur. At 40,60 and 90 days following operation the torsional moment, the elastic stiffness, the volume and the density of the callus tissue were evaluated. No differences were found between the two groups. It is concluded that acrylic bone cement in the medullary cavity does not impair the healing of non-immobilized fractures in young rats.


Combined gas chromatographic-mass spectrometric procedure for the measurement of captopril and sulfur-conjugated metabolites of captopril in plasma and urine.
A gas chromatographic-mass spectrometric method is described for the simultaneous measurement of the novel anti-hypertensive drug captopril, and the following metabolites: captopril disulfide dimer, S-methyl captopril, and S-methyl captopril sulfone. With this method all derivatives can be chromatographed using conventional gas chromatography of hexafluoroisopropyl esters in one temperature-programmed run and these can then be quantitated using selected-ion monitoring techniques. Using urine or plasma, captopril, S-methyl captopril and the disulfide dimer of captopril in concentrations as low as 1 ng/ml, 10 ng/ml and 25 ng/ml, respectively can be detected. The reproducibility of the method is satisfactory both within-assay and inter-assay. This technique has demonstrated that the pattern of urinary excretion of these compounds in both man and rat was similar. Excretion of unchanged captopril, S-methyl captopril and the disulfide dimer over 6 h in man given captopril (50 or 100 mg) chronically was 18.3%, 0.97% and 3.06%, respectively. Corresponding excretion of these three compounds in the rat following a single 10 mg/kg dose was 18.3%, 2.69% and 1.8%, respectively. A possible sulfone oxidation product of S-methyl captopril was not detected in the urine of either man or rat.


Immersive interactive virtual walking reduces neuropathic pain in spinal cord injury: findings from a preliminary investigation of feasibility and clinical efficacy.
Chronic neuropathic pain (NP) is a common and often debilitating secondary condition for persons with spinal cord injury (SCI) and is minimally responsive to existing pharmacological and nonpharmacological treatments. The current preliminary investigation describes the feasibility and initial comparative efficacy of an interactive virtual reality walking intervention, which is a novel extension of visual feedback/illusory walking therapies shown to reduce SCI NP. Virtual reality walking intervention builds on previous research by, for the first time, allowing individuals with SCI NP to volitionally control virtual gait to interact with a fully immersive virtual environment. The current pilot study compared this interactive, virtual walking intervention to a passive, noninteractive virtual walking condition (analogous to previous illusory walking interventions) in 27 individuals with complete paraplegia (interactive condition, n = 17; passive condition, n = 10; nonrandomized design). The intervention was delivered over 2 weeks in individuals' homes. Participants in the interactive condition endorsed significantly greater reductions in NP intensity and NP-related activity interference preintervention to postintervention. Notable improvements in mood and affect were also observed both within individual sessions and in response to the full intervention. These results, although preliminary, highlight the potentially potent effects of an interactive virtual walking intervention for SCI NP. The current study results require replication in a larger, randomized clinical trial and may form a valuable basis for future inquiry regarding the mechanisms and clinical applications of virtual walking therapies.


An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.
Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement. Most of these cells have rearranged their heavy-chain locus but not their light chain genes, suggesting that an active v-abl protein interferes with this differentiation step. To test this hypothesis, light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene. Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes. These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs. These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase. As documented in the accompanying paper (Klug et al., this issue), an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer. Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression.


Effect of subthreshold up and down states on the whisker-evoked response in somatosensory cortex.
Changes in spontaneous activity within the cortex recognized by subthreshold fluctuations of the membrane potential of cortical neurons modified the response of cortical neurons to sensory stimuli. Sensory stimuli occurring in the hyperpolarized "down" state evoked a larger depolarization and were more effective in evoking action potentials than stimuli occurring in the depolarized "up" state. Direct electrical stimulation of the thalamus showed the same dependence on the cell's state at the time of the stimulus, ruling out a strictly thalamic mechanism. Stimuli were more effective at triggering action potentials in the down state even during moderate de- or hyperpolarization of the somatic membrane potential. The postsynaptic potential (PSP) evoked from the down state was larger than the up state PSP but achieved about the same peak membrane potential, which was also near the reversal potential of the PSP (about -51 mV). Chloride loading shifted the reversal potentials of both the up state and the whisker-evoked PSP toward a more depolarized membrane potential. In addition, the threshold for action potentials evoked from the down state was lower than for spikes evoked in the up state. Thus the larger PSP from the down state may be caused by its larger driving force, and the state dependence of action potential generation in response to whisker stimulation may in part be related to a shift in threshold. Different mechanisms are therefore responsible for the state-dependence of PSP amplitude and the spike frequency response to the whisker stimulus.


Medically unexplained symptoms in family medicine: defining a research agenda. Proceedings from WONCA 2007.
Medically unexplained symptoms (MUSs) are frequently presented in primary care. Unfortunately, knowledge of these patients and/or symptoms in primary care is still limited. Available research comes mainly from Europe and North America, while the perspectives of cultures such as Africa, Asia and South America are relatively unknown. To bring cultural perspectives together, a symposium and workshop on MUS in primary care was held at the WONCA World Conference 2007 in Singapore. Main goals of this symposium and workshop-apart from presenting ongoing research and bringing together experts in MUS-were to detect knowledge gaps in MUS and to establish priorities in MUS research. This publication focuses on the proposed research agenda. Using a nominal group technique, we generated research topics and set priorities. Research topics were grouped into research themes. Participants' (66 researchers and GPs from 29 nationalities) most important research topics were 'formulating a broadly accepted definition of MUS', 'finding a strategy to recognize MUS better and at an earlier stage', 'studying the value of self-management and empowerment in patients with MUS' and 'finding predictors to decide which strategy will best help the individual patient with MUS'. Priorities in research themes of MUS are as follows: (i) therapeutic options for patients with MUS and (ii) problems in consultations with these patients. More research on MUS in primary care is needed to improve the consultations with and management of these patients. Internationally primary care conferences are excellent for exchanging ideas and formulating central issues of research.


Survival of patients with KRAS wild-type metastatic colorectal cancer is identical after sequential treatment with cetuximab and bevacizumab regardless of the sequence - A retrospective single-center study.
To investigate the overall survival of patients with KRAS wild-type metastatic colorectal cancer (mCRC) after sequentially receiving both bevacizumab and cetuximab during the course of treatment. Twenty-six mCRC patients who received both bevacizumab and cetuximab at the Sun Yat-sen University Gastrointestinal Hospital were retrospectively analyzed. Group A (n = 8) comprised patients who received bevacizumab first, and group B (n = 18) comprised those who received cetuximab first. The objective response rate, progression-free survival, and overall survival were compared. Baseline characteristics between the two groups were statistically similar. The objective response in groups A and B patients was 62.5% and 66.6%, respectively (P = 0.132). The median progression-free survival for groups A and B patients was 13 and 10 months, respectively (P = 0.798). The median overall survival for the entire cohort was 42 months, 44 months for group A and 39 months for group p B (P = 0.862) patients, respectively. Patients aged <40 years had worse survival than those aged ≥40 years (22 vs 44 months; P = 0.029). Patients with synchronous metastasis had worse survival than those with metachronous metastasis (unreached and 36 months, respectively). In multivariate analyses, synchronous metastasis and age remained statistically significant. The hazard ratio for synchronous metastasis was 4.548, and the HR for patients aged ≥40 years was 0.237. A longer median survival time was observed in patients regardless of the targeted therapy sequence, which warrants further investigation.


An IS900-like sequence found in a Mycobacterium sp. other than Mycobacterium avium subsp. paratuberculosis.
The insertion sequence IS900 has been considered specific for Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) and has, therefore, been used as the target gene for diagnostic PCR of M. paratuberculosis. From a healthy dairy cow we have isolated and characterised a mycobacterium harbouring one copy of a sequence with 94% identity to IS900 at the nucleic acid level. The isolate was shown to be related to Mycobacterium cookii, as assessed by 16S rRNA sequencing. Strong amplifications were obtained with several PCR primers described for detection of IS900. This finding shows the need of alternative PCR systems based on other genes than IS900 to confirm the presence of M. paratuberculosis.


Group B streptococci during pregnancy and infancy.
Group B streptococcus (Streptococcus agalactiae) is still of great relevance in the perinatal period, although maternal antimicrobial prophylaxis has significantly reduced the rate of culture-confirmed invasive infection in neonates. This strategy, however, raises considerable concern because preterm delivery or late-onset sepsis cannot be prevented, and antibiotic resistance is increasing worldwide. Several advances in the development of conjugate vaccines and in research on virulence factors and pathways involved in the immune response to group B streptococcus have been accomplished, some of which might reach clinical practice in the near future.


An ethanolic phosphotungstic acid (EPTA) analysis of photoreceptor and synaptic ultrastructure in the guinea pig retina.
Ethanolic phosphotungstic acid (EPTA) has been used to elucidate the structure of certain organelles contained within retinal cells not clearly discernible using conventional preparations. Both synaptic and nonsynaptic components of the guinea pig neural retina have been analyzed. Within the photoreceptor (PR) cell EPTA-stained components include the connecting cilia, their basal bodies, and the root filament system. Cross-striated fibrillar organelles, similar in appearance to the root filaments, are also observed in the nuclear region, the synaptic terminal and other parts of the PR cell. The possible structural continuity and significance of these structures are discussed. Within retinal synapses of both the inner and outer plexiform layers, ribbons and associated paramembranous specializations are stained. The photoreceptor ribbons have a trialaminar structure with filamentous, tufted borders. Synaptic cleft material and postsynaptic densities are also stained. Bipolar cell synapses in the inner plexiform layer contain stained short ribbons as well as closely associated peg-like densities extending towards the presynaptic membrane.


Antihypertensive 1-acyl-4-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethylamino]pip eridines.
Several 1-acyl-4-[2-(1,4-benzodioxan-2-yl)-2-hydroxy-ethylamino]piperidine s were prepared and a number of the compounds showed antihypertensive activity in the spontaneously hypertensive rat (SHR). This activity was specific for the (2S, 2R) enantiomers. General pharmacological evaluation and ligand binding data on selected compounds indicated a moderate degree of alpha 1- and beta-antagonistic activity. The alpha 1 antagonism was probably not of sufficient magnitude to explain the blood pressure lowering activity in the SHR.


Aortic Dissection in a Young Patient With Unsuspected Aortopathy.
Aortic dissection is often a fatal condition if not recognized and treated emergently. Fortunately, it is extremely rare in children and adolescents. We report a case of an adolescent boy who survived an aortic dissection due to severe aortic root dilation. A comprehensive history and physical examination, including family history, can facilitate an early diagnosis of connective tissue diseases, such as Loeys-Dietz syndrome (LDS).


The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers.
Signaling through the B cell antigen receptor promotes activation and survival of mature B cells. B cell-activating factor belonging to the tumor necrosis factor family (BAFF) is another critical survival factor for B cells, and is also necessary for B cell maturation. Abnormal production of BAFF disturbs immune tolerance by allowing the survival of autoreactive B cells, thus triggering autoimmune disorders. BAFF can also have an important impact on B cell malignancies. In contrast to normal B cells, malignant B cells show uncontrolled cell proliferation. BAFF levels are elevated in the serum of patients with systemic autoimmune diseases, and, importantly, in patients with B-lymphoid malignancies. Furthermore, BAFF is produced by malignant B cells and acts as an essential autocrine survival factor. The strong dependence of certain lymphoid cancer cells on BAFF might be a point of vulnerability, which offers exciting new therapeutic possibilities.


Catabolism of plasma enzymes, as studied with 125I-labeled lactate dehydrogenase-1 in the rabbit.
Circulating enzymes may be inactivated in the plasma and the inactive breakdown products may be hydrolyzed in the lumen of the small intestine. Evidence for this mechanism was based upon previous studies with 125I-labeled lactate dehydrogenase-5, and here similar studies with radioiodinated lactate dehydrogenase-1 are reported, to determine whether this isoenzyme is similarly catabolized. The pure rabbit enzyme was labeled with 125I by use of lactoperoxidase and hydrogen peroxide (the labeled enzyme had 80-85% of the original catalytic activity). After its intravenous injection into rabbits, plasma enzyme activity and radioactivity disappeared during the first 4 h at similar fast rates, apparently because of distribution of the injected enzyme throughout the extracellular fluid. During a second phase (30-h), catalytic activity disappeared significantly faster than radioactivity, suggesting inactivation of the enzyme in either the plasma or a compartment in close proximity to it, or both. Enzyme activity then remained constant while plasma radioactivity continued to decrease at a slower, exponential rate, apparently owing to removal of breakdown products. In no case did tissue radioactivity, studied 6 h after injection, approach that of plasma. We therefore conclude that removal of the enzyme protein or its breakdown products is a passive process. Appreciable radioactivity was detected in the intestinal contents, a finding which suggests that removal via the small intestine is an important route for the removal of inactivated enzyme products from the circulation. Less than 3% of the injected radioactivity appeared in the feces during the first three days; urinary excretion accounted for about 67% during the same period, about 60% of which consisted of radio-iodinated amino-acids, the remainder of iodide. Free mono- and di-iodotyrosines were among the products excreted. These appear to originate from absorption of the products of further breakdown of the enzyme molecule in the intestine.


Trans-dimer D, a novel dimeric sesquiterpene with a bis-bisabolene skeleton from a Hainan sponge Axinyssa variabilis.
A novel bisabolene sesquiterpene dimer named trans-dimer D (1) and its diastereoisomer trans-dimer C (2) reported in our previous work have been isolated as an inseparable mixture in a ratio of 1.5:1 from the South China Sea sponge Axinyssa variabilis. The structure of 1 was determined on the basis of extensive spectroscopic analysis and by comparison of its NMR spectral data with those of structurally related compounds. Compound 1 represents the fourth example of a sesquiterpene dimer with a bis-bisabolene skeleton.


Propofol--contrasting effects in movement disorders.
We report two patients presenting for thalamotomy in whom tremor was abolished for 8 h after propofol anaesthesia. Propofol has two contrasting actions. It may have an anti-Parkinsonion effect, abolishing abnormal limb movements. On other occasions, propofol is known to induce spontaneous abnormal limb movements, as well as epileptiform activity. Propofol is probably best avoided for stereotactic procedures. It is difficult to reconcile these two opposing actions.


Structural stabilization of tissue for embryo phenotyping using micro-CT with iodine staining.
The International Mouse Phenotyping Consortium has been established to conduct large-scale phenotyping of the approximately 23,000 single-gene knockout mice generated by the International Knockout Mouse Consortium to investigate the role of each gene in the mouse genome. Of the generated mouse lines, 30% are predicted to be embryonic lethal, requiring the implementation of imaging techniques and analysis tools specific to late gestation mouse embryo phenotyping. A well-adopted technique combines the use of iodinated contrast solutions and micro-computed tomography imaging. This simple iodine immersion technique provides superior soft-tissue contrast enhancement, however, the hypertonic nature of iodine promotes dehydration causing moderate to severe tissue deformation. Here, we combine the stabilizing properties of a hydrogel mesh with the enhanced contrast properties of iodine. The protocol promotes cross linking of tissue through formaldehyde fixation and the linking of hydrogel monomers to biomolecules. As a result, the hydrogel supports tissue structure and preserves its conformation taking advantage of iodine-enhanced soft tissue contrast to produce high quality mouse embryo images with minimal tissue distortion. Hydrogel stabilization substantially reduces intersample anatomical variation of mature mouse embryos subjected to iodine preparation protocols. A 20% and 50% reduction in intersample variation of normalized brain and lung volume is achieved through hydrogel stabilization, as well as a 20% reduction in variation in overall embryo anatomy as measured through image registration methods. This increases the sensitivity of computer automated analysis to reveal significant anatomical differences between mutant and wild-type mice.


MicroRNA Isolation by Trizol-Based Method and Its Stability in Stored Serum and cDNA Derivatives.
MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Since aberrant expression of miRNAs has been proposed as usage for blood-based biomarkers, hence reliable techniques for miRNA isolation as well as stability of miRNAs in various stored conditions needs to be explored. This present study aimed to investigate the efficacy of the Trizol-based isolation technique and the stability of miRNAs in stored serum and cDNA derivatives. Total RNA, including miRNAs, was isolated from human serum and a comparison of the efficiency of the Trizol®LS reagent isolation method against the miRNeasy®mini kit was conducted. Expression of RNU6, miR-145, and miR-20a was determined by quantitative real-time polymerase chain reaction (qRT-PCR). We showed that Trizol®LS isolation yielded significantly lower RNA concentrations than that of the miRNeasy®mini kit by approximately 35%. Purity of the isolated RNAs by both methods was similar. RNU6, miR-145, and miR-20a degraded at room temperature, but all genes were stable at 4ºC, -20ºC and -80ºC for a 72-hrs period, in both serum and cDNA storage conditions. In the stored cDNA derivatives, we observed the stability of RNU6, miR-145, and miR-20a for 3 months at -20ºC, and all genes also resisted 4 repeated freeze-thaw cycles at -20ºC. In conclusion, the Trizol-based method is efficient as well as economical to use for quantification of circulating miRNAs. In addition, we proposed that the storage of miRNA-derived cDNAs may be an alternative choice to avoid the stability effect.


Maximum Proton Energy above 85 MeV from the Relativistic Interaction of Laser Pulses with Micrometer Thick CH_{2} Targets.
We present a study of laser-driven ion acceleration with micrometer and submicrometer thick plastic targets. Using laser pulses with high temporal contrast and an intensity of the order of 10^{20} W/cm^{2} we observe proton beams with cutoff energies in excess of 85 MeV and particle numbers of 10^{9} in an energy bin of 1 MeV around this maximum. We show that applying the target normal sheath acceleration mechanism with submicrometer thick targets is a very robust way to achieve such high ion energies and particle fluxes. Our results are backed with 2D particle in cell simulations furthermore predicting cutoff energies above 200 MeV for acceleration based on relativistic transparency. This predicted regime can be probed after a few technically feasible adjustments of the laser and target parameters.


Satellite data based estimation of methane emissions from rice paddies in the Sanjiang Plain in northeast China.
The Sanjiang Plain (SJP), one of the major rice producing regions in China, is an important source of methane (CH4) emissions. However, there have been large uncertainties in the estimates of CH4 emissions from this area during the past few years. In this study, we estimated CH4 emissions using a process-based model derived by rice area, CH4 flux, land surface temperature (LST), and the ratio of precipitation (P) and evapotranspiration (ET) in rice paddies in the SJP during the rice growing seasons in 2000, 2006, and 2010, respectively. The results showed that the total area of rice fields was 1.64 million ha in 2010, which was approximately 35 and 13% higher than in 2000 and 2006, respectively. The average LST was 22.1°C in 2000 which was higher than in 2006 (21.6°C) and 2010 (21.5°C). Monthly ET and P displayed similar seasonal and annual variability. The monthly ET was 61.7, 66.5, and 63.0 mm month-1 and P was 85.1, 80.6 and 85.9 mm month-1 during the rice growing seasons in 2000, 2006, and 2010, respectively. The averaged CH4 flux rates were 24.83, 24.63, and 24.59 ton km-2, and the estimated mean annual CH4 emissions from rice paddies were 0.30, 0.36, and 0. 40 Tg yr-1 in 2000, 2006, and 2010, respectively. The CH4 emissions displayed obvious spatial variations that decreased from east to west in the SJP, and were mainly affected by temperature. The results will improve our understanding of the inter-annual and spatial variations of CH4 emissions and provide a more accurate regional budget of CH4 emissions from rice paddies in the Sanjiang Plain.


Protecting kidneys in liver transplant patients: A pathway to preventive interventions.
Acute kidney injury (AKI) is a frequent postoperative complication after liver transplantation. The etiology is multifactorial, including perioperative renal status, surgery related events, and postoperative immunosuppression therapy. The role of renal hypoperfusion and hepatic ischemia-reperfusion injury as causes of early AKI are now being increasingly recognized. Further studies should focus on therapies that would attenuate this injury.


Undergraduate orthodontics in Belfast: 12 years on.
The British and European Community recommendations for teaching orthodontics in the undergraduate curriculum from 1963 up to the present day are reviewed. 12 years experience of the course introduced in Belfast in 1984 is reviewed and some of the difficulties are identified. Modifications in the course to meet these difficulties are described.


Influence of radiographic contrast media on myocardial tissue oxygen tension: NaCl-controlled, randomised, comparative study of iohexol versus iopromide in an animal model.
It was tested whether a bolus injection of 10 ml radiographic contrast medium (iopromide vs. iohexol), compared to a 10 ml NaCl bolus and administered into the left anterior descending artery (LAD) of farm pigs, influenced the tissue pO2 in the territory of this artery. The radiographic contrast media and the NaCl bolus were given in randomised order. The mean pO2 LAD fell from initially 40.3+/-10.9 mmHg to a minimal value of 22.5+/-8.9 mmHg 241+/-44 sec after injecting the iopromide bolus, with this result representing a mean decrease of 44.2% (p=0.0003). The initial pO2 (baseline) was reached again after approximately 10 minutes. The mean pO2 LAD fell from the initial value of 34.5+/-14.6 mmHg to a minimal value of 29.4+/-13.9 mmHg 171.7+/-11.9 sec after injection of the iohexol bolus, with this result representing a mean decrease of 14.8% (p=0.0003). The baseline pO2 was reached again after approx. 5 minutes. The drop in the pO2 after iopromide administration was significantly larger than that after iohexol (p=0.0001), and also the time after which the baseline pO2 is reached again was considerably shorter for iohexol (p=0.001). The two radiographic contrast media did not influence the tissue pO2 in either the territory of the right coronary artery or in skeletal muscle. Injection of a NaCl bolus into the LAD influenced neither the tissue pO2 of the territory of the LAD nor that of the RCA or of the skeletal muscle. The tissue temperature, heart rate and the systolic and diastolic blood pressure were not affected during the three injections. Injection of radiographic contrast media into a coronary artery can lead to a distinct, local microcirculatory impairment in the myocardial territory supplied by this artery. In this case, the extent of the microcirculation impairment seems to depend not only on the viscosity of the contrast media but rather also on its chemotoxicity.


Depletion of regulatory T cells in a hapten-induced inflammation model results in prolonged and increased inflammation driven by T cells.
Regulatory T cells (Tregs ) are known to play an immunosuppressive role in the response of contact hypersensitivity (CHS), but neither the dynamics of Tregs during the CHS response nor the exaggerated inflammatory response after depletion of Tregs has been characterized in detail. In this study we show that the number of Tregs in the challenged tissue peak at the same time as the ear-swelling reaches its maximum on day 1 after challenge, whereas the number of Tregs in the draining lymph nodes peaks at day 2. As expected, depletion of Tregs by injection of a monoclonal antibody to CD25 prior to sensitization led to a prolonged and sustained inflammatory response which was dependent upon CD8 T cells, and co-stimulatory blockade with cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) suppressed the exaggerated inflammation. In contrast, blockade of the interleukin (IL)-10-receptor (IL-10R) did not further increase the exaggerated inflammatory response in the Treg -depleted mice. In the absence of Tregs , the response changed from a mainly acute reaction with heavy infiltration of neutrophils to a sustained response with more chronic characteristics (fewer neutrophils and dominated by macrophages). Furthermore, depletion of Tregs enhanced the release of cytokines and chemokines locally in the inflamed ear and augmented serum levels of the systemic inflammatory mediators serum amyloid (SAP) and haptoglobin early in the response.


Reduced expression of NDUFS3 and its clinical significance in serous ovarian cancer.
Expression of the mitochondrial protein, nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), down-regulates in some cancers including breast and kidney. This study evaluates NDUFS3 expression and its clinical significance in human serous ovarian adenocarcinoma. 30 ovarian normal epithelium, 30 benign serous adenoma, and 100 serous carcinoma tissues were collected, and the expression of NDUFS3 protein and messenger RNA was evaluated by immunohistochemistry, Western blot, and real-time reverse transcription-polymerase chain reaction, respectively. Relationships between NDUFS3 protein expression and clinicopathologic parameters and disease-free and overall survival were also studied. The expression of NDUFS3 messenger RNA and protein was significantly decreased in serous ovarian adenocarcinoma compared with normal ovarian epithelium and benign serous adenoma (both P < 0.001). Reduced NDUFS3 immunostaining correlated with advanced Federation of Gynecology and Obstetrics stage (P = 0.002) and suboptimal residual disease after primary surgery (P = 0.021). Reduced NDUFS3 expression also correlated with shorter disease-free (P = 0.002) and overall survival (P = 0.004). NDUFS3 expression is down-regulated in serous ovarian adenocarcinoma, suggesting that NDUFS3 may contribute to the development of serous ovarian cancer.


A family of dioxo-molybdenum(VI) complexes of N2X heteroscorpionate ligands of relevance to molybdoenzymes.
Four new Mo(VI)-dioxo complexes of a family of N2X heteroscorpionate ligands are reported which, together with data already available for (TpR)-, provide a unique example of a comprehensive set of isostructural, isoelectronic complexes differing only in one biologically relevant donor atom. A study of these complexes allows for a direct comparison of structural, spectroscopic, and oxygen atom transfer reactivity properties of the Mo(VI)-dioxo center (of relevance to various families of molybdoenzymes) as a function of donor atom identity.


Stabilization of boron carbide via silicon doping.
Boron carbide is one of the lightest and hardest ceramics, but its applications are limited by its poor stability against a partial phase separation into separate boron and carbon. Phase separation is observed under high non-hydrostatic stress (both static and dynamic), resulting in amorphization. The phase separation is thought to occur in just one of the many naturally occurring polytypes in the material, and this raises the possibility of doping the boron carbide to eliminate this polytype. In this work, we have synthesized boron carbide doped with silicon. We have conducted a series of characterizations (transmission electron microscopy, scanning electron microscopy, Raman spectroscopy and x-ray diffraction) on pure and silicon-doped boron carbide following static compression to 50 GPa non-hydrostatic pressure. We find that the level of amorphization under static non-hydrostatic pressure is drastically reduced by the silicon doping.


Differential Dynamics at Glycosidic Linkages of an Oligosaccharide as Revealed by 13C NMR Spin Relaxation and Stochastic Modeling.
Among biomolecules, carbohydrates are unique in that not only can linkages be formed through different positions, but the structures may also be branched. The trisaccharide β-d-Glcp-(1→3)[β-d-Glcp-(1→2)]-α-d-Manp-OMe represents a model of a branched vicinally disubstituted structure. A 13C site-specific isotopologue, with labeling in each of the two terminal glucosyl residues, enabled the acquisition of high-quality 13C NMR relaxation parameters, T1 and T2, and heteronuclear NOE, with standard deviations of ≤0.5%. For interpretation of the experimental NMR data, a diffusive chain model was used, in which the dynamics of the glycosidic linkages is coupled to the global reorientation motion of the trisaccharide. Brownian dynamics simulations relying on the potential of mean force at the glycosidic linkages were employed to evaluate spectral densities of the spin probes. Calculated NMR relaxation parameters showed a very good agreement with experimental data, deviating <3%. The resulting dynamics are described by correlation times of 196 and 174 ps for the β-(1→2)- and β-(1→3)-linked glucosyl residues, respectively, i.e., different and linkage dependent. Notably, the devised computational protocol was performed without any fitting of parameters.


Deuterium nuclear magnetic resonance measurements of blood flow and tissue perfusion employing 2H2O as a freely diffusible tracer.
The use of deuterium oxide (2H2O) is proposed as a freely diffusible nuclear magnetic resonance (NMR) blood flow and tissue perfusion tracer of potential clinical utility. Deuterium is a stable, nonradiative isotope commercially available as 2H2O at enrichment levels of essentially 100%--i.e., 110 molar equivalent deuterium. This high concentration, together with the short relaxation time of the spin 1 (quadrupole) deuterium nuclide, provides substantial sensitivity for NMR spectroscopy. As a result, when 2H2O is administered in a bolus fashion to a specific tissue or organ in vivo, the deuterium NMR intensity time course can be analyzed, using mathematical models developed by others for radiolabeled tracers, to measure the rate of blood flow and tissue perfusion. Such an application is demonstrated herein at a static magnetic field of 8.5 tesla. Using single-compartment flow modeling, hepatic blood flow and tissue perfusion in fasted (18 hr) male Sprague-Dawley rats was determined to be 61 +/- 17 (mean +/- SD) ml/100 g per min (n = 5).


MEASURING NATURAL SELECTION ON PHENOTYPIC PLASTICITY.
To understand natural selection we need to integrate its measure across environments. We present a method for measuring phenotypic selection that combines the potential for both environmental variation and phenotypic plasticity. The method uses path analysis and a measure of selection that is analogous to selection on breeding values. For individuals growing in alternative environments, paths are created that represent potential changes in the environment. The probabilities for these changes are then multiplied by the path coefficients to calculate selection coefficients. Selection on plasticity is measured as the difference in selection within each environment. We illustrate these methods using data on selection in an experimental population of Arabidopsis thaliana. Individuals from 36 families were grown in one of four environments, a factorial combination of shaded/open and early/late shading. For final height of the inflorescence, there was positive selection in both the open and shaded environments and negative selection on plasticity of height. For bolting time, there was also positive selection in both environments, but no selection on plasticity. We show how to use this information to examine how selection would change with changes in environmental frequencies and their transition probabilities. These methods can be expanded to encompass continuous traits and continuous environments as well as other complexities of natural selection.


[What is the role of Epstein-Barr virus in the pathogenesis of connective tissue diseases?].
In rheumatoid arthritis (RA) abnormalities of T suppressive/cytotoxic responses to Epstein-Barr virus (EBV) have been reported: lack of inhibition of spontaneous proliferation of autologous B lymphocytes infected by EBV, lack of late suppression of immunoglobulin secretion induced in vitro by EBV. Moreover, a cross-reaction between EBNA antigen (Epstein Barr Nuclear Antigen) and a cytoplasmic protein of 62 KD present in the rheumatoid synovitis has been described. In primary Sjögren's syndrome, EBV genome has been observed in the parotid of some patients. The abnormalities of T suppressive/cytotoxic responses observed in rheumatoid arthritis are inconstant and non specific; they are noted in some cases of systemic scleroderma and lupus; they remain for a given patient and could be the marker of a particular subset of connective tissue diseases. The pathophysiological role of EBV infection, especially in rheumatoid arthritis and Sjögren's syndrome, remains to be determined.


Recognizing translation initiation sites of eukaryotic genes based on the cooperatively scanning model.
Translation initiation sites (TISs) of genes are the key points of protein synthesis. Exact recognition of TISs in eukaryotic genes is one of the most important tasks in gene-finding algorithms. However, the task has not been satisfactorily fulfilled up to the present. Here, we propose a cooperatively scanning model for recognizing TISs and the first exons of eukaryotic genes on the basis of the structural characteristics of multi-exon genes. The model was employed to cooperatively scan the TISs and 3' splicing sites in eukaryotic genes, and the TISs and the first exons of 132 mammalian gene sequences are identified to evaluate the model. Accuracy of exactly recognizing the TISs and the first exons has been found to amount respectively to 64.4 and 51.5%. We believe that the model will be a useful tool for genome annotation and that it can be easily incorporated into other algorithms to achieve higher accuracy in recognizing TISs and the first exons. The program is available upon request.


Veno-occlusive disease of the small bowel. An entity in search of identity.
Veno-occlusive disease of the bowel is a rare entity, and, to our knowledge, only two studies have been reported in the literature; these reports describe 11 patients with veno-occlusive disease of the small and large bowels. We describe a patient who developed veno-occlusive disease of the small bowel, whose histologic findings were somewhat different from those previously reported.


Structural diversity of CuZn2InSe4 quaternary chalcogenides: electronic and phonon properties from first principles.
First principles simulations are utilized to calculate the electronic and vibrational properties of several metastable structural phases of the CuZn2InSe4 quaternary chalcogenide, including stanite, kesterite, primitive mixed CuAu, wurtzite-stanite, and wurtzite-kesterite lattices. We find that although each phase is formed by nearest cation-chalcogen bonds, the structural diversity due to cation and polyhedral arrangements has direct consequences in the electronic structure. The simulations further indicate that hybrid functionals are needed to account for the s-p and p-d orbital hybridization that is found around the Fermi level, which leads to much enhanced energy band gaps when compared with standard exchange-correlation approaches. We also find that the thermal conductivities for all phases are relatively low, and the main scattering channel comes from a low frequency optical band hybridized with acoustic phonons. Given that CuZn2InSe4 is a material from a larger class of quaternary chalcogenides, other materials may exhibit similar electronic and vibrational properties, which may be useful for electronic and thermal management applications.


Effect of surface area to weight ratio of egg masses on the hatchability of Boophilus microplus eggs.
On global basis, ticks transmit a number of pathogens than any other arthropod vector, and are among the most important vectors of diseases affecting humans, livestock and companion animals. Control of the vector has been focused on integrated management involving strategic use of insecticides, use of vaccines, use of herbal acaricides and breed resistance. It has been established that tick vaccine is working on limiting the egg laying potentiality and subsequent hatchability of the ticks fed on immunized animals. To generate entomological data following immunization of animals against ticks an experiment was conducted to establish the role of water content in egg masses for successful hatching into larvae. Different size and shape of egg masses of Boophilus microplus, Izatnagar isolate were obtained by manipulating the egg laying process. The weight of the egg masses was measured, keeping their integrity and surface areas of respective egg masses were calculated with the aid of computer software. Larvae hatched from the respective egg masses were counted individually. It is clear that, with an increase in the exposed surface area of the cylindrical egg mass per unit weight, there is a reduction in the number of larvae hatched out. Also, the spherical egg masses significantly (0.026 at 95% confidence level) yielded more larvae per unit weight in comparison to the cylindrical egg masses. It has been established that the larval count yielded from an egg mass is more or less dependent on the surface area : weight ratio of the respective egg masses rather than on either the surface area alone or weight of the egg mass alone.


Deciphering the atomic-scale structural origin for large dynamic electromechanical response in lead-free Bi0.5Na0.5TiO3-based relaxor ferroelectrics.
Despite the extraordinary electromechanical properties of relaxor ferroelectrics, correlating their properties to underlying atomic-scale structures remains a decisive challenge for these "mess" systems. Here, taking the lead-free relaxor ferroelectric Bi0.5Na0.5TiO3-based system as an example, we decipher the atomic-scale structure and its relationship to the polar structure evolution and large dynamic electromechanical response, using the direct atomic-scale point-by-point correlation analysis. With judicious chemical modification, we demonstrate the increased defect concentration is the main driving force for deviating polarizations with high-angle walls, leading to the increased random field. Meanwhile, the main driving force for deviating polarizations with low-angle walls changes from the anti-phase oxygen octahedral tilting to the multidirectional A-O displacement, leading to the decreased anisotropy field. Benefiting from the competitive and synergetic equilibrium of anisotropic field versus random field, the facilitated polarization rotation and extension versus facilitated domain switching are identified to be responsible for the giant electromechanical response. These observations lay a foundation for understanding the "composition-structure-property" relationships in relaxor ferroelectric systems, guiding the design of functional materials for electromechanical applications.


Ammonium nitrate and iron nutrition effects on some nitrogen assimilation enzymes and metabolites in Spirulina platensis.
The effect of various concentrations of ammonium nitrate (5-60 mM), an economical nitrogen source, on the growth, nitrate-ammonium uptake rates, production of some pigments and metabolites, and some nitrogen assimilation enzymes such as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamate synthase (GOGAT) in Spirulina platensis (Gamont) Geitler was investigated. Ten millimolars of ammonium nitrate stimulated the growth, production of pigments and the other metabolites, and enzyme activities, whereas 30 and 60 mM ammonium nitrate caused inhibition. In the presence of 10 mM ammonium nitrate, different concentrations of iron were tried in the growth media of S. platensis. After achieving the best growth, levels of metabolite and pigment production, and enzyme activities in the presence of 10 mM ammonium nitrate as a nitrogen source, different iron concentrations (10-100 µM) were tried in the growth medium of S. platensis. The highest growth, pigment and metabolite levels, and enzyme activities were determined in the medium containing 50 µM iron and 10 mM ammonium nitrate. In this optimum condition, the highest dry biomass level, chlorophyll a, and pyruvate contents were obtained as 55.42 ± 3.8 mg mL(-1) , 93.114 ± 7.9 µg g(-1) , and 212.5 ± 18.7 µg g(-1) , respectively. The highest NR, NiR, GS, and GOGAT activities were 67.16 ± 5.1, 777.92 ± 52, 0.141 ± 0.01, and 44.45 ± 3.6, respectively. Additionally, 10 mM ammonium nitrate is an economical and efficient nitrogen source for nitrogen assimilation of S. platensis, and 50 µM iron is optimum for the growth of S. platensis.


Biological variation of β-sitosterol, campesterol, and lathosterol as cholesterol absorption and synthesis biomarkers.
The analysis of blood for β-sitosterol and campesterol is the measures of cholesterol absorption while lathosterol is a measure of cholesterol synthesis. The biological variability of β-sitosterol, campesterol, and lathosterol was measured using liquid-chromatography tandem mass spectrometry from a cohort of 25 apparently healthy subjects, where blood was taken once every weeks for 6 weeks. The analytical, intra-individual, and group inter-individual variations (CVA, CV(I), and CV(G), respectively) were calculated. Using absolute values, the CVI for β-sitosterol, campesterol, and lathosterol was 11.8%, 11.8%, and 22.5%, respectively, and the CV(G) was 28.5%, 28.8%, and 52.0%, respectively. This produced reference change values of about 24-36% for declining values and 32-47% for increasing values. The index of individuality was between 0.41 and 0.58, indicating that population based reference values are of little use for these biomarkers. The number of points needed for a homeostatic setpoint was 5 samples for β-sitosterol and campesterol, and 19 samples for lathosterol. Similar findings were observed for values when normalized to total cholesterol. These results were higher than the biological variation for total, low density and high density cholesterol obtained from the literature. Results were essentially identical when sterol values were corrected to their respective total cholesterol concentration. The establishment of the biological variation for these biomarkers enables their use in the interpretation of results from clinical trials and lipid lowering treatment of patients at risk for cardiovascular disease in clinical practice.


Different proteins associated with 10-nanometer filaments in cultured chick neurons and nonneuronal cells.
A protein of molecular size 180 kilodaltons is associated with 10-nanometer filaments in neurons and is immunologically distinct from smaller putative neurofilament subunits and from 10-nanometer filament proteins in nonneuronal cells, such as myotubes and fibroblasts. Neurons do not contain vimentin, the major filament protein in many other cells, including the nonneuronal cells in cultures of neural tissue.


Advances in ulcerative colitis.
Ulcerative colitis is one of the two common chronic inflammatory bowel diseases which affect the colon of children. The disease can occur at any time during infancy and childhood and is far commoner than Crohn's disease of the colon in children less than 6 years old. The Jewish population outside of Israel is at far greater risk of developing the condition than any other ethnic group. The reason for this is unknown. The chances of a family member developing the condition is 2-3 times as great as in the general population. The etiology of the condition remains unknown; however, recent advances in the understanding of the immune mechanisms in the bowel and circulation indicate there are major immunological differences between ulcerative colitis and Crohn's disease. Intestinal B cells secrete enormously increased amounts of IgG1 and a lesser increase in IgG3 in ulcerative colitis whereas in Crohn's disease, all IgG subclasses are increased, but especially IgG2. Failure of the gut immune system to control antigen crossing the colonic mucosa may be the basis for the condition. The disease is classified as moderate to severe two thirds of children as opposed to less than one third of adults. Diagnostic testing must include 3 stool cultures negative for bacterial and viral pathogens, 3 stools negative for amebiasis, trichuriasis and other intestinal parasites and absence of clostridium difficile and its toxin in the stool. Flexible proctosigmoidoscopy and/or colonoscopy should be done in every case with biopsies. Barium enema is contraindicated in the severely ill patient. Major improvements in medical treatment being tested involve the development of nonabsorbable corticosteroid enemas and sulfapyridene-free forms of salicylazosulfapyridene for use in enema and oral form. Surgery for ulcerative colitis has made major advances with the development of the Koch pouch (internal ileostomy) and ileoproctostomy. Both procedures although associated with relatively high complication rates, are esthetically and psychologically better than standard ileostomy because in neither procedure must the patient wear an ileostomy appliance. However these advanced surgical procedures are typically not done until adolescence is reached.


Neutrophilia as prognostic biomarker in locally advanced stage III lung cancer.
To study the prognostic value of baseline leukocytosis or neutrophiliain two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients. Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively. We identified 238 patients, displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p<0.05). Neutrophilia independently decreased Locoregional Control (LRC) (HR = 2.5, p<0.001) and Distant Metastasis Control (DMC) (HR = 2.1, p<0.001). Neutrophilia was significantly associated with worse brain metastasis control (p = 0.004), mostly in adenocarcinoma patients (p<0.001). In stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia were associated with worse OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.


The novel herbicide oxaziclomefone inhibits cell expansion in maize cell cultures without affecting turgor pressure or wall acidification.
Oxaziclomefone [OAC; IUPAC name 3-(1-(3,5-dichlorophenyl)-1-methylethyl)-3,4-dihydro-6-methyl-5-phenyl-2H-1,3-oxazin-4-one] is a new herbicide that inhibits cell expansion in grass roots. Its effects on cell cultures and mode of action were unknown. In principle, cell expansion could be inhibited by a decrease in either turgor pressure or wall extensibility. Cell expansion was estimated as settled cell volume; cell division was estimated by cell counting. Membrane permeability to water was measured by a novel method involving simultaneous assay of the efflux of (3)H(2)O and [(14)C]mannitol from a 'bed' of cultured cells. Osmotic potential was measured by depression of freezing point. OAC inhibited cell expansion in cultures of maize (Zea mays), spinach (Spinacia oleracea) and rose (Rosa sp.), with an ID(50) of 5, 30 and 250 nm, respectively. In maize cultures, OAC did not affect cell division for the first 40 h. It did not affect the osmotic potential of cell sap or culture medium, nor did it impede water transport across cell membranes. It did not affect cells' ability to acidify the apoplast (medium), which may be necessary for 'acid growth'. As OAC did not diminish turgor pressure, its ability to inhibit cell expansion must depend on changes in wall extensibility. It could be a valuable tool for studies on cell expansion.


[Johann Mueller and modern experimental research].
Johann Mueller believes "time of observation" basis of scientific research, to have an almost exclusive function in methodologic reflection and axiomatic construction. Though tolerating some deriving principles from "Philosophy of Nature" - which presents accidental facts only by generic images, without entering causes - he maintains that things of the surrounding world cannot be demonstrated in themselves, but only through the events they generate in affecting our sensory organs. Assuming that studies about morphology and physiology in general serve as an introduction to the specific study of single organs and apparatuses, Mueller points out a new address for physiologic investigation, based upon measurement and comparison criteria independent from various mechanisms involved in the determinism of function.


Obstructive Sleep Apnea and Diabetes: A State of the Art Review.
OSA is a chronic treatable sleep disorder and a frequent comorbidity in patients with type 2 diabetes. Cardinal features of OSA, including intermittent hypoxemia and sleep fragmentation, have been linked to abnormal glucose metabolism in laboratory-based experiments. OSA has also been linked to the development of incident type 2 diabetes. The relationship between OSA and type 2 diabetes may be bidirectional in nature given that diabetic neuropathy can affect central control of respiration and upper airway neural reflexes, promoting sleep-disordered breathing. Despite the strong association between OSA and type 2 diabetes, the effect of treatment with CPAP on markers of glucose metabolism has been conflicting. Variability with CPAP adherence may be one of the key factors behind these conflicting results. Finally, accumulating data suggest an association between OSA and type 1 diabetes as well as gestational diabetes. This review explores the role of OSA in the pathogenesis of type 2 diabetes, glucose metabolism dysregulation, and the impact of OSA treatment on glucose metabolism. The association between OSA and diabetic complications as well as gestational diabetes is also reviewed.


Case Study: How Horses Helped a Teenager with Autism Make Friends and Learn How to Work.
I was born in 1947 and had autism with speech delay until age four. I am now a college professor of animal science. Horse activities enabled me to make friends through a shared interest in horses. This paper describes the benefits that I experienced from working with horses and my friendships and work skills. A close friendship developed with another student through both riding and horse craft projects. Keeping employment is a serious problem for many people with Autism Spectrum Disorder (ASD). The responsibility of caring for horses and cleaning stalls every day taught me good work skills. My experiences suggest that there were valuable outcomes from working with horses. This may be a beneficial intervention to include in programming for youth with ASD.


Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis.
Retinoic acid receptor beta (RAR beta) is a retinoic acid receptor gene that has been shown to play key roles during multiple cancer processes, including cell proliferation, apoptosis, migration and invasion. Numerous studies have found that methylation of the RAR beta promoter contributed to the occurrence and development of malignant tumors. However, the connection between RAR beta promoter methylation and prostate cancer (PCa) remains unknown. This meta-analysis evaluated the clinical significance of RAR beta promoter methylation in PCa. We searched all published records relevant to RAR beta and PCa in a series of databases, including PubMed, Embase, Cochrane Library, ISI Web of Science and CNKI. The rates of RAR beta promoter methylation in the PCa and control groups (including benign prostatic hyperplasia and normal prostate tissues) were summarized. In addition, we evaluated the source region of available samples and the methods used to detect methylation. To compare the incidence and variation in RAR beta promoter methylation in PCa and non-PCa tissues, the odds ratio (OR) and 95% confidence interval (CI) were calculated accordingly. All the data were analyzed with the statistical software STATA 12.0. Based on the inclusion and exclusion criteria, 15 articles assessing 1,339 samples were further analyzed. These data showed that the RAR beta promoter methylation rates in PCa tissues were significantly higher than the rates in the non-PCa group (OR=21.65, 95% CI: 9.27-50.57). Subgroup analysis according to the source region of samples showed that heterogeneity in Asia was small (I2=0.0%, P=0.430). Additional subgroup analysis based on the method used to detect RAR beta promoter methylation showed that the heterogeneity detected by MSP (methylation-specific PCR) was relatively small (I2=11.3%, P=0.343). Although studies reported different rates for RAR beta promoter methylation in PCa tissues, the total analysis demonstrated that RAR beta promoter methylation may be correlated with PCa carcinogenesis and that the RAR beta gene is particularly susceptible. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic utility of RAR beta promoter methylation in PCa.


Prosthodontic treatment of an edentulous epileptic patient with an implant-retained overdenture. A case report.
This report describes the treatment of a completely edentulous, mentally retarded patient with epilepsy with an implant-retained overdenture, anchored by a locator system. The intractable epileptic condition of the patient with frequent grand mal seizures and complex partial seizures required a stable, well retained prosthesis, however the maxilla and the mandible were severely atrophied. The bone volume of the maxilla allowed the placement of only two implants it the region of the canines, compared with the generally required four. On long time recall, after one year, patient's chewing ability was satisfactory.


Salt tolerance in Aster tripolium L. III. Na and K fluxes in intact seedlings.
Uptake and transport of Na and K was studied using the radioactive tracers 22 Na and 42 K in intact Aster tripolium L. seedlings grown at two salinities CS 10 and CS 100, (containing 10mol m-1 and 100 mol m-3 Na, respectively, together with other major ions in the proportions found in sea water). At both salinities a much greater proportion of the Na than K taken up by the plant was subsequently transported to the shoot. Most 42 K fluxes were reduced by about 40% in CS 100 plants relative to CS 10 except root accumulation which increased. Experiments involving changing the salinity from CS 10 to CS 100 showed that 42 K fluxes remained constant for at least 40 h, indicating that competition with Na for uptake sites was not the cause of the reduced flux in CS 100 plants. 22 Na fluxes responded immediately to a change in salinity with all fluxes increasing six-fold when the salinity was raised. When the salinity was lowered, however, root accumulation returned to the level in CS 10 control plants whereas transport to the shoot was inhibited by the previous high salinity treatment, being reduced to only 35% of the rate in CS 10 plants. The time courses of osmotic adjustment and Na accumulation following an increase in salinity were found to be very similar, with sufficient Na being accumulated to account for the observed increase in sap osmotic pressure.


Understanding and Accommodating Patient and Staff Choice When Implementing Video Consultations in Mental Health Services.
During the COVID-19 pandemic, some mental healthcare in the United Kingdom has moved online, with more likely to follow. The current evidence base for video consultations is modest; hence, this study seeks to aid decision-makers by reporting on one large National Health Service mental health trust's video-consultation pilot project. Patients' choices/preferences were gathered via online forms; and staff's views, through a focus group. The typical patient was female, 26 years old, living in a deprived locality. Consultations typically lasted 37 minutes, saving patients 0-30 minutes of travel and £0-£3.00. Satisfaction was high, and the software was intuitive. Audio quality varied, but patients felt able to disclose "as if in person," were willing to use video consultation again, and found them more preferable than home visits and clinic attendance. Staff could foresee benefits but were concerned for their therapeutic relationships and were avoidant without familiarization, training, clinical coaching, and managerial reassurances especially regarding high-risk patients/situations. They argued video consultation would not suit all patients and should be used according to individual need. We found COVID-19 is necessitating staff to adopt video consultation and that patients are satisfied. However, unless staff's concerns are resolved, enabling them to use their full repertoire of interpersonal skills, therapeutic relationships will trump efficiency and video consultations may not remain their treatment modality of choice.


Structural and optical characterization of Eu3+ doped beta-Ga2O3 nanoparticles using a liquid-phase precursor method.
Eu3+ doped beta-Ga2O3 and non-doped beta-Ga2O3 nanoparticles were synthesized at 800 degrees C using a liquid-phase precursor (LPP) method, with different annealing times and Eu3+ ion concentrations. Eu3+ doped beta-Ga2O3 nanoparticles showed broad XRD peaks, revealing a second phase compared with the non-doped beta-Ga2O3 nanoparticles. The cathode luminescence (CL) spectra of beta-Ga2O3 and Eu3+ doped beta-Ga2O3 nanoparticles showed a broad band emission (300-500 nm) of imperfection and two component emissions. The luminescence quenching properties of Eu3+ dopant ion concentration appeared gradually beyond 5 mol% in our investigation.


The results of hypofractionated radiotherapy in 31 patients with high-grade gliomas.
In this prospective study, we investigated the effects of hypofractionated radiotherapy for patients with high-grade gliomas. About 31 patients with glioblastoma multiforme or anaplastic astrocytoma were studied between October 2003 and December 2004. Hypofractionated radiotherapy (3 Gy/fraction/day) was delivered to a total dose of 45 Gy in 15 fractions in 10 patients (32%) who had total excision before radiotherapy and to a total dose of 54 Gy in 18 fractions in 21 patients (68%) who had subtotal excision or biopsy alone. Sex, age, type of surgery, tumor grade, Karnofsky performance status, time between surgery and initiation of radiotherapy, and total radiotherapy dose were analyzed as potential prognostic factors for survival using the univariate log-rank method. The median follow-up was 15 months (4-16 months). A total of 15 patients (48%) died of their illness; 16 patients (52%) were still alive at the last follow-up. The median survival time was 8 months. Actuarial 1-year overall survival was 40%. Type of surgery, timing of radiotherapy after surgery, and initial Karnofsky performance status were significant prognostic factors for survival. No grade 3-4 acute or late neurotoxicity was observed. The tolerance of patients to hypofractionated RT was not different from that for conventional radiotherapy. This treatment schedule can be used for patients with high-grade gliomas. Future investigations are needed to determine the optimal fractionation for high-grade gliomas.