Benzene Diffusion and Partitioning in Contaminated Drinking Water Pipes under Stagnant Conditions.
Benzene contamination in drinking water systems affected by wildfires is a problem of emerging concern. Polyethylene pipes used in service lines and premise plumbing are vulnerable to permeation by benzene and can potentially cause challenges in sampling and remediation of contaminated systems. However, the kinetics and equilibria of the uptake of benzene by and release of benzene from pipes of differing polyethylene types and manufacturers are not well studied, leading to additional uncertainty when interpreting sampling data and selecting remediation options. This work addresses this data gap by providing diffusion and partitioning data for benzene and several varieties of polyethylene pipes, including field samples from water distribution systems. All polyethylene pipes that were studied exhibited similar partitioning behavior during benzene uptake and release, but some differences in kinetics were observed among pipes. However, these differences were of minor practical importance in the pipe contamination scenario examined in this work. The results of this study can be used in conjunction with diffusion modeling to inform remediation decisions for benzene-contaminated, polyethylene service lines, and premise plumbing.


Classification of coagulase-negative staphylococci of human origin.
A total of 191 coagulase-negative staphylococci isolated from man were identified as Staphylococcus epidermidis on the basis of their biochemical properties. When classified according to the classification scheme suggested by BAIRD-PARKER (1972), 144 of the strains were found to belong to biotype 1, one strain was biotype 2, and four were biotype 3; the remaining 42 strains could not be classified within any of the 4 biotypes of this scheme. Using the classification scheme suggested by PELZER et al. (1973), 158 strains were found to belong to subgroup IIb, one was subgroup IIIb, four were subgroup IV, and 28 were subgroup V, with no strains remaining unclassified. The biochemical properties of the strains were not related to the site of isolation except that urease was produced by only 15 per cent of strains isolated from pus but by 81-92 per cent of strains isolated from a variety of other sources. The majority of the strains (64 per cent) were resistant to penicillin, while 72 per cent were sensitive to streptomycin.


Staged Treatment in Early Psychosis: A sequential multiple assignment randomised trial of interventions for ultra high risk of psychosis patients.
Previous research indicates that preventive intervention is likely to benefit patients "at risk" of psychosis, in terms of functional improvement, symptom reduction and delay or prevention of onset of threshold psychotic disorder. The primary aim of the current study is to test outcomes of ultra high risk (UHR) patients, primarily functional outcome, in response to a sequential intervention strategy consisting of support and problem solving (SPS), cognitive-behavioural case management and antidepressant medication. A secondary aim is to test biological and psychological variables that moderate and mediate response to this sequential treatment strategy. This is a sequential multiple assignment randomised trial (SMART) consisting of three steps: Step 1: SPS (1.5 months); Step 2: SPS vs Cognitive Behavioural Case Management (4.5 months); Step 3: Cognitive Behavioural Case Management + Antidepressant Medication vs Cognitive Behavioural Case Management + Placebo (6 months). The intervention is of 12 months duration in total and participants will be followed up at 18 months and 24 months post baseline. This paper reports on the rationale and protocol of the Staged Treatment in Early Psychosis (STEP) study. With a large sample of 500 UHR participants this study will investigate the most effective type and sequence of treatments for improving functioning and reducing the risk of developing psychotic disorder in this clinical population.


Stable heat-resistant variants in populations of Chinese hamster cells.
Sublines with increased survival at elevated temperatures were obtained by repeated exposure of V79 Chinese hamster lung cells to 44.5 degrees C followed by regrowth of survivors to mass populations at 37 degrees C. After three cycles, the time at 44.5 degrees C required to reduce cell survival to 37% (D0 value) increased from 4.6 to 26.3 minutes. Clonal isolates retained their resistance to thermal stress for at least 3 months in culture at 37 degrees C and showed distinctive differences from precursor cells in growth rate and colonial morphology. These differences disappeared in hybrids constructed between resistant and sensitive cells. In assays of 44.5 degrees C, hybrid survival was only slightly increased over levels obtained with sensitive cells. Heat resistance and associated marker characteristics thus appear to be recessive or weakly codominant. Cytohybrids were also constructed by fusing cytoplasts from sensitive cells to nucleated heat-resistant cells. No cytoplasmic transfer of marker characteristics was detected in these combinations, which suggests that controls for heat resistance are nuclear in origin.


T cell clones reactive with sperm whale myoglobin. Isolation of clones with specificity for individual determinants on myoglobin.
We have been able to isolate clones of sperm whale muscle myoglobin (Mb)-reactive T cells from (C57BL/6 x A/J)F1 [(B6A)F1] mice. Four types of clones were isolated, distinguished by their patterns of recognition of Mb cyanogen bromide (CNBr) fragments and antigen presenting cell (APC) requirements. Individual T cell clones proliferated in response to one of three CNBr fragments of Mb. Dose-response curves of all clones were identical for native Mb and the appropriate fragment. T cell clones reactive to fragment 1-55 did not proliferate in response to peptide 15-22 (a peptide that binds to serum antibody directed against 1-55). These data support previous findings suggesting differences between antigen recognition by T and B cells, i.e., T cells may not recognize antigen in its native conformation and/or T and B cells may recognize distinct epitopes on the same antigen. Using T cell clones to analyze genetic control of responsiveness to Mb, we found that certain (B6A)F1 T cells recognize Mb presented by low responder strain APC. Thus, genetically determined low responsiveness in this case is probably not due to failure of APC function. We also found that responsiveness to certain Mb epitopes mapped to the I-A subregion whereas others mapped, via gene complementation, to the I-A and I-E subregions. We found no examples of responsiveness mapping to the I-C subregion and suggest an alternative explanation for previous reports mapping genetic control of responsiveness to certain Mb determinants to I-C.


Cardiac arrest despite optimal preloading of patient using ultrasonography-guided inferior vena cava indices under subarachnoid neuraxial blockade: A report of two cases.
Spinal anesthesia (SA) is utilized as an effective means of anesthesia and has an impressive safety record but it is not devoid of complications, and sometimes, the complications are as fatal as cardiac arrest. Although many factors are involved in etiology of cardiac arrest under SA, the vagal responses to the decreased preload are the most common culprits. We report two cases of cardiac arrest under SA; which happened despite our patient being adequately preloaded utilizing the ultrasonography-guided targeted volume therapy. The patients were successfully resuscitated with no neurological deficit.


[Treatment of trigeminal neuralgia with radiosurgery].
Idiopathic trigeminal neuralgia is defined as brief paroxysms of pain limited to the facial distribution of the trigeminal nerve. Drug therapy is considered to be the first-line of treatment for trigeminal neuralgia. Unfortunately, medical treatment does not always provide satisfactory pain relief for 25% of the patients. Moreover, the relief provided by drug therapy generally decreases over time, and increased dosages of these medications are limited because of side effects. In this case, patients can be offered several surgical approaches, such as percutaneous techniques (thermocoagulation, microcompression, glycerol injection) or microvascular decompression in the cerebello-pontine angle (Gardner-Jannetta's technique). In this indication, stereotactic radiosurgery, driven by teams using Gamma Knife(®), has shown promising efficacy and tolerance to allow this treatment being truly part of trigeminal neuralgia treatment. Technological progresses now allow performing radiosurgery with ballistic and dosimetric processes optimized with stereotactic radiosurgery dedicated linear accelerators. This procedure supports frame implantation to guarantee targeting accuracy in accordance of elevated dose distribution. This article on trigeminal neuralgia treatment will review the different medical and surgical therapeutic options and specify the contemporary place of stereotactic radiosurgery in the light of its clinical results and tolerance aspects.


Individual Aircraft Noise Exposure Assessment for a Case-Crossover Study in Switzerland.
Accurate exposure assessment is essential in environmental epidemiological studies. This is especially true for aircraft noise, which is characterized by a high spatial and temporal variation. We propose a method to assess individual aircraft noise exposure for a case-crossover study investigating the acute effects of aircraft noise on cardiovascular deaths. We identified all cases of cardiovascular death (24,886) occurring near Zürich airport, Switzerland, over fifteen years from the Swiss National Cohort. Outdoor noise exposure at the home address was calculated for the night preceding death and control nights using flight operations information from Zürich airport and noise footprints calculated for major aircraft types and air routes. We estimated three different noise metrics: mean sound pressure level (LAeq), maximum sound pressure level (LAmax), and number above threshold 55 dB (NAT55) for different nighttime windows. Average nighttime aircraft noise levels were 45.2 dB, 64.6 dB, and 18.5 for LAeq, LAmax, and NAT55 respectively. In this paper, we present a method to estimate individual aircraft noise exposure with high spatio-temporal resolution and a flexible choice of exposure events and metrics. This exposure assessment will be used in a case-crossover study investigating the acute effects of noise on health.


Use of cone beam computed tomography and a laser intraoral scanner in virtual dental implant surgery: part 1.
To describe a new procedure capable of coupling 2 data sets from cone beam computed tomography (CBCT) and an intraoral laser digital scanner to produce a stereolithographic model and surgical guide. Use of DICOM (digital imaging and communications in medicine) format data obtained from CBCT scan images merged with standard triangulation language (STL) file data obtained from digital impressions using an intraoral laser scanner. The 2 data sets were electronically sent to a 3-dimensional imaging and technology software company over the Internet to fabricate a stereolithographic model of the jaws and surgical guide without the use of stone or plaster models obtained from traditional dental impressions. STL file data are able to accurately fabricate a stereolithographic model and surgical guide for implant surgery.


[Er:YAG laser in periodontics and implication in the orthodontic treatment plan].
The Er:YAG laser is used in periodontal surgery to remove excess tissue formations and to clean periodontal pockets. Combined with ultrasonic procedures lasers have significantly advanced the parameters of periodontal surgery. The goal of this article is to review the working mechanisms of the Er:YAG laser in the wide variety of its applications in complex treatment situations in both periodontics and orthodontics.


The geography of talent development.
Geography (i.e., birthplace) is one of many factors that influence talent development. When one's birthplace leads to advantages in sport participation or performance, it is called a birthplace effect. Nearly two decades of committed research has revealed that birthplace effects are pervasive across sports and countries. Recently, researchers have attempted to better understand birthplace effects by considering various metrics that serve as proxies for birth advantages; for instance, population size, population density, and proximity to sport clubs. Underlying mechanisms that explain birthplace effects include infrastructure (e.g., environment and facilities) and social structure (e.g., family and safety), though contextual differences across existing research (e.g., sports and countries) make it difficult to fully explain the effects. Herein, we provide more depth regarding these elements of birthplace effects, while also presenting new data on "talent hotspots"; that is, communities with optimal population and density for talent development.


Effects of Ca antagonists on the norepinephrine release and contractile responses of isolated canine saphenous veins to transmural nerve stimulation.
Effects of verapamil, diltiazem and nicardipine on tritium overflow and contraction evoked by transmural nerve stimulation (TNS) were evaluated using canine saphenous vein strips preincubated with [3H]norepinephrine. External Ca2+ was required for both tritium overflow and contraction evoked by TNS. All the Ca antagonists tested significantly increased the spontaneous overflow of tritium in a concentration-dependent manner with no changes in basal tension. Verapamil in concentrations lower than 10(-5) M significantly enhanced the TNS-evoked tritium overflow, but reduced it at 3 X 10(-5) M, while this drug at 3 X 10(-6)-3 X 10(-5) M concentration-dependently inhibited the TNS-evoked contraction. Verapamil, 3 X 10(-5) M, inhibited the TNS-evoked contraction more strongly than the evoked tritium overflow. On the other hand, diltiazem and nicardipine in concentrations higher than 10(-5) M significantly inhibited both tritium overflow and contraction evoked by TNS. There was no significant difference between inhibitions of the TNS-evoked tritium overflow and contraction by either diltiazem or nicardipine. Neither increase in the spontaneous tritium overflow nor inhibitions of the TNS-evoked tritium overflow and contraction by nicardipine appeared to be related to its phosphodiesterase inhibiting activity. These results suggest that diltiazem and nicardipine may inhibit the TNS-evoked contraction mainly by inhibiting Ca2+-dependent transmitter release from the adrenergic nerve endings, whereas verapamil may inhibit it by restricting the availability of Ca2+ at the postsynaptic sites and in the highest concentration used, by additional inhibition of transmitter release.


Diagnostics and Resistance Profiling of Bacterial Pathogens.
Worldwide infectious disease is one of the leading causes of death. Despite improvements in technology and healthcare services, morbidity and mortality due to infections have remained unchanged over the past few decades. The high and increasing rate of antibiotic resistance is further aggravating the situation. Growing resistance hampers the use of conventional antibiotics, and substantial higher mortality rates are reported in patients given ineffective empiric therapy mainly due to resistance to the agents used. These infections cause suffering, incapacity, and death and impose an enormous financial burden on both healthcare systems and on society in general. The accelerating development of multidrug resistance is one of the greatest diagnostic and therapeutic challenges to modern medicine. The lack of new antibiotic options underscores the need for optimization of current diagnostics, therapies, and prevention of the spread of multidrug-resistant organisms. The so-called -omics technologies (genomics, transcriptomics, proteomics, and metabolomics) have yielded large-scale datasets that advanced the search for biomarkers of infectious diseases in the last decade. One can imagine that in the future the implementation of biomarker-driven molecular test systems will transform diagnostics of infectious diseases and will significantly accelerate the identification of the bacterial pathogens at the infected host site. Furthermore, molecular tests based on the identification of markers of antibiotic resistance will dramatically change resistance profiling. The replacement of culturing methods by molecular test systems for early diagnosis will provide the basis not only for a prompt and targeted therapy, but also for a much more effective stewardship of antibiotic agents and a reduction of the spread of multidrug resistance as well as the appearance of new antibiotic resistances.


Visual, Vestibular, and Proprioceptive Dependency of the Control of Posture in Chronic Neck Pain Patients.
Sensory reweighting of postural control was compared in participants with and without neck pain. Center of pressure variables of 60 volunteers, the same in each group, were calculated under four standing conditions: (a) eyes open, neutral head posture; (b) foam interface, eyes open; (c) cervical extension, eyes open; and (d) cervical extension, eyes closed. All center of pressure variables except anterior posterior range/velocity increased significantly in Condition 2 compared with Conditions 1 and 3 (p < .001) and in Condition 4 compared with Conditions 1 and 3. The mediolateral range/velocity and path length in both groups, anterior posterior range in patients, and center of pressure area in the control group were significantly different between Conditions 2 and 4 (p < .001). No overweighting was observed on the vestibular or visual afferents in patients. Compensatory strategies seem to lie within the proprioceptive system.


The "Wallstent": a new stent for the treatment of urethral strictures.
Ten patients have been reviewed in whom urethral stents were implanted for treatment of urethral stricture. Their urethral strictures had been treated with a median of 4.2 endoscopic urethrotomies under direct vision without success. The patients were first treated with optical urethrotomy, and dilatation to 30 F--after which the stents were inserted under direct endoscopic control. A total of 12 stents were inserted. All patients had a 30 mm stent inserted first, and two patients had an additional 20 mm stent inserted because of recurrent stricture at the distal or proximal end of the first stent. One patient had a urethrotomy 12 months after insertion of the stent because of a short recurrent stricture at its distal end. The median length of follow up was 24 months. The median preoperative maximum flow rate was 6.5 ml/s, and the median postoperative maximum flow rate was 20.3 ml/s. Half the patients had postmicturition dribbling postoperatively. The stents were covered with epithelium after 6-18 months, most between 12 and 18 months.


Intrapartum management associated with obesity in nulliparous women.
The objective of this systematic review was to determine the current state of knowledge about intrapartum management associated with obesity in healthy nulliparous women. Nulliparous obese women are at higher risk for unplanned cesarean birth when compared with their normal-weight counterparts, and much of this increased risk is associated with labor management differences. There is a need to better understand the differences in intrapartum management of nulliparous women who are obese. The PubMed, CINAHL, EBSCO, Google Scholar, and MEDLINE databases were searched in August 2012, with identified studies then assessed for applicability and quality. Eight studies were retained for the review. Intrapartum interventions used significantly more often for healthy, obese nulliparous women when compared with normal-weight women were induction of labor, augmentation of labor, and cesarean birth. It is unclear if assisted vaginal birth occurs more frequently among obese women. Epidural anesthesia, artificial rupture of membranes prior to 6 cm of cervical dilation, and early hospital admission were shown in separate studies to be used more often in obese women. Intrapartum interventions were used more frequently in obese women in a dose-dependent manner by body mass index. Future studies examining the intrapartum management of obese nulliparous women are needed with: 1) samples defined by standardized obesity classifications; 2) further analysis of diverse intrapartum interventions; and 3) prospective, randomized designs to allow for causality conclusions linking intrapartum intervention use to an obese woman's risk for cesarean birth. Implications for clinical practice from this systematic review are that healthy, nulliparous obese women are exposed to common intrapartum interventions more often than normal-weight women. In the absence of evidence on the use of appropriate use of intrapartum interventions in this population, health care providers should carefully monitor management choices when working with healthy, nulliparous obese women.


BK polyomavirus in kidney transplant recipients: screening, monitoring and clinical management.
BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.


Theoretical Bases for the Role of Red Blood Cell Shape in the Regulation of Its Volume.
The red blood cell (RBC) membrane contains a mechanosensitive cation channel Piezo1 that is involved in RBC volume homeostasis. In a recent model of the mechanism of its action it was proposed that Piezo1 cation permeability responds to changes of the RBC shape. The aim here is to review in a descriptive manner different previous studies of RBC behavior that formed the basis for this proposal. These studies include the interpretation of RBC and vesicle shapes based on the minimization of membrane bending energy, the analyses of various consequences of compositional and structural features of RBC membrane, in particular of its membrane skeleton and its integral membrane proteins, and the modeling of the establishment of RBC volume. The proposed model of Piezo1 action is critically evaluated, and a perspective presented for solving some remaining experimental and theoretical problems. Part of the discussion is devoted to the usefulness of theoretical modeling in studies of the behavior of cell systems in general.


Genomic signatures of local adaptation in the Drosophila immune response.
As environments and pathogen landscapes shift, host defenses must evolve to remain effective. Due to this selection pressure, among-species comparisons of genetic sequence data often find immune genes to be among the fastest evolving genes across the genome. The full extent and nature of these immune adaptations, however, remain largely unexplored. In a recent study, we analyzed patterns of selection within distinct components of the Drosophila melanogaster immune pathway. While we found evidence of positive selection within some immune processes, immune genes were not universally characterized by signatures of strong selection. On the contrary, we even found that some immune functions show greater than expected constraint. Overall these results highlight 2 major factors that appear to play an outsize role in determining a gene's evolutionary rate: the type of pathogen the gene targets and the gene's position within the immune network. These results join a growing body of literature that highlight the complexity of immune adaptation. Rather than there being uniformly strong selection across all immune genes, a combination of pathogen-specificity and host genetic constraints appear to play key roles in determining each immune gene's individual evolutionary trajectory.


Palliative Care for the Interstitial Lung Disease Patient a Must and Not Just a Need.
Patients with interstitial lung disease (ILD) have many unmet palliative care needs. The majority of patients with chronic ILD have poor access to a specialist in palliative medicine and that is due to several barriers. The mortality for the ILD patient is high and reaches up to 80% if admitted to the ICU with respiratory failure. Palliative care addresses symptoms in diseases where cure is unlikely or impossible. Palliative care consultation also ensures communication among patients, caregivers and providers regarding treatments, prognosis, and end of life planning. Methods: We performed a literature review on palliative care and ILD, accessing articles published since 2002. We found 71 articles related to the topic. We chose 37 that were most relevant and with no redundancy of information to include in this review. Objectives: Summarize the palliative care needs of patients with ILD, discuss the barriers to receiving palliative care, and summarize clinical practice for providing palliative care to this patient population.


Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania.
The effect of depression on HIV disease progression was examined among 996 HIV-positive Tanzanian women participating in a trial on micronutrients and pregnancy outcomes, vertical transmission, and disease progression. Depression and social support were measured 2 months after HIV screening and every 6 to 12 months thereafter. Depression measures from pregnancy and more than 12 months postpartum were included in this analysis. Participants' clinical condition and access to supportive individual or group counseling was assessed throughout the 6 to 8 years of follow-up. Cox proportional hazard models were used to estimate the time-varying effect of depression on progression to HIV clinical stage III/IV (World Health Organization) and all-cause mortality. Participation in group or individual counseling and baseline social support were also examined. More than half (57%) of the study sample had symptoms comparable with depression at least once during the follow-up period. Controlling for sociodemographic variables, psychosocial support, and clinical condition at enrollment, depression was associated with an increased risk of disease progression (HIV clinical stage III/IV [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.28 to 2.03] and mortality [HR = 2.65, 95% CI: 1.89 to 3.71]). Depression is common among HIV-infected Tanzanian women and increases the risk of disease progression. Screening for depression and providing psychosocial interventions should be considered part of comprehensive HIV care.


Development of the ICD-10 simplified version and field test.
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) has been used in various Asia-Pacific countries for more than 20 years. Although ICD-10 is a powerful tool, clinical coding processes are complex; therefore, many developing countries have not been able to implement ICD-10-based health statistics (WHO-FIC APN, 2007). This study aimed to simplify ICD-10 clinical coding processes, to modify index terms to facilitate computer searching and to provide a simplified version of ICD-10 for use in developing countries. The World Health Organization Family of International Classifications Asia-Pacific Network (APN) developed a simplified version of the ICD-10 and conducted field testing in Cambodia during February and March 2016. Ten hospitals were selected to participate. Each hospital sent a team to join a training workshop before using the ICD-10 simplified version to code 100 cases. All hospitals subsequently sent their coded records to the researchers. Overall, there were 1038 coded records with a total of 1099 ICD clinical codes assigned. The average accuracy rate was calculated as 80.71% (66.67-93.41%). Three types of clinical coding errors were found. These related to errors relating to the coder (14.56%), those resulting from the physician documentation (1.27%) and those considered system errors (3.46%). The field trial results demonstrated that the APN ICD-10 simplified version is feasible for implementation as an effective tool to implement ICD-10 clinical coding for hospitals. Developing countries may consider adopting the APN ICD-10 simplified version for ICD-10 code assignment in hospitals and health care centres. The simplified version can be viewed as an introductory tool which leads to the implementation of the full ICD-10 and may support subsequent ICD-11 adoption.


Epidemiology in the courtroom: an evidence-based paradigm for the determination of causation in compensation environments.
Identify an evidence-based paradigm for the determination of causation of occupational injury and illness litigation. The Westlaw and LexisNexis databases were used to identify legal principles governing the admissibility of scientific evidence in legal proceedings. The Medline database was referenced to identify evidence-based methods for the determination of causation complying with legal precepts for the admissibility of scientific testimony. Expert witness testimony must be relevant and reliable. Testimony must be sufficiently based on reliable facts and data. Testimony must be the product of reliable principles or methods. The witness must have reliably applied the principles and methods to the facts of the case. Conscientious application of the National Institute for Occupational Safety and Health Guide for the Determination of Work-Relatedness of Disease, as adapted, comforts with legal prerequisites for the admissibility of scientific evidence in medicolegal proceedings.


Learning objectives in resident training. Objectives in clinical chemistry.
The use of learning objectives has recently found extensive application in the evolution of medical school curricula; however, they have not been utilized systematically in the education of pathology residents. In attempting to define the end-point behavior or objectives of a resident during a rotation in clinical biochemistry, 567 midwestern pathologists, clinical chemists and medical technologists working in chemistry sections rated proposed objectives as essentail, desirable but not essential, or not needed. Twenty-four of 52 objectives were considered essential for the resident to achieve by 75% or more of the respondents. These included 10 of 33 related to technical knowledge, 5 to 10 related to business and supervisory skills, 5 of 5 related to investigative problem solving, and 4 of 4 related to communicating with persons outside of the laboratory. In general, respondents considered knowledge of principles more important than technical skills. Management, business and communicative skills were highly rated.


Medicinal plants of the genus Anthocleista--A review of their ethnobotany, phytochemistry and pharmacology.
The genus Anthocleista of the Gentianaceae family contains 14 species of trees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. They serve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the first time a repository of ethnopharmacological information while critically evaluating the relation between the traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleista species so as to unveil opportunities for future research. A search for relevant information on Anthocleista species was performed on scientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertations for un-published resources. Out of the 14 species of Anthocleista, 6 have been reported in literature to be widely used in traditional medicine for the treatment of various ailments. The six species include: A. djalonensis, A. vogelii, A. nobilis, A. grandiflora, A. schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from Anthocleista species fall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of which majority of the compounds were isolated from A. djalonensis and A. vogelii. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Anthocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity, antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic and laxative activities which supports most of their uses in traditional medicine. However, the bulk of the studies where centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, although the evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the in vitro and in vivo results. A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterial potency relates to infections or diseases caused by E. coli, S. typhi and S. aureus such as urinary tract infections, typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite elementary and limited, thus, more advanced research is necessary to isolate and determine the activities of bioactive compounds in vitro and in vivo, establish their mechanisms of action and commence the process of clinical research.


[Mycosis fungoides and Sézary syndrome : a systematic review].
The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF presents as cutaneous patches and can progress to plaques, tumors and erythroderma. SS is characterized by the presence of erythroderma, generalized lymphadenopathy and clonal T cells in the peripheral blood, consistent with a poorer prognosis. Histologically, early CTCL lesions are sometimes indistinguishable from more common inflammatory skin diseases and a clinico-pathological correlation is essential for an accurate diagnosis. Except for allogenic stem-cell transplantation, therapy is generally palliative and aims to improve patient quality of life.


Oxidative stress in tumor angiogenesis- therapeutic targets.
Historically, oxidative stress was recognized to contribute to cancer development uniquely by induction of genomic instability. However, recent research has provided multiple evidence that reactive oxygen species and other free radicals, such as nitric oxide, often produced at elevated levels within tumor tissue, may function as signaling molecules that initiate and/or modulate the different regulatory pathways involved in tumorigenesis and metastasis. This review will focus on the complex role of oxidative stress and redox signaling in cancer neovascularization, a process without which the tumor is unable to grow beyond few millimeters in size. Reactive oxygen species and nitric oxide affect cell responses to hypoxia, a major trigger of angiogenic switch in tumors and are important upstream regulators as well as downstream mediators of action of the most potent proangiogenic factor - vascular endothelial growth factor. We will discuss targeting the redox-regulated mechanisms for antiangiogenic anticancer therapy and focus on recent developments in small-molecule agents that have either completed clinical trials or show a great promise to be subjected to them. Modulation of redox species production, signaling and metabolism and/or manipulating cellular antioxidant responses represents a multitargeted therapeutic approach which may possibly overcome the limitations of single-agent antiangiogenic treatments and potentiate effects of standard methods.


The prevalence of internet gaming disorders and the associated psychosocial risk factors among adolescents in Malaysian secondary schools.
Internet Gaming Disorder (IGD) has been placed under the conditions for further study segment in DSM-5. The purpose of the current study was to develop a preliminary psychosocial model as a reference for providing appropriate intervention, particularly for adolescents with IGD. A total of 5290 adolescents from secondary schools in seven states in Malaysia were recruited by using proportionate random sampling. A standardized set of validated questionnaires such as DASS-21, BIS-11, and IGDS9-SF were distributed to participants that fulfilled the inclusion criteria. The prevalence of IGD among Malaysian adolescents was 3.5%. The bivariate analysis summarized that factors such as stress, impulsivity, gender, time spent using the internet, and relationship with parents and friends; have statistically significant associations with IGD. The logistic regression model revealed that adolescents with IGD were 9 times more likely to experience extremely severe stress (p < 0.001). Several psychosocial factors were associated strongly with IGD in the current study, however, mental health shows the most significant issues among adolescents with IGD. Immediate intervention through a psychological approach to internet gaming is needed from parents, schools, and also respective stakeholders. IGD may become one of the addictions diseases that cause deterioration in many aspects of an adolescent's future life without serious intervention.


Identification of common themes from after-hour telephone calls made to urology residents.
To characterize the content and sources of after-hour telephone calls from a general urology practice so that common themes can be identified and incorporated into the education of urology residents. After-hour telephone calls were prospectively assessed for 6 months by a single senior urology resident. Calls occurring on weekends/holidays and between 5 PM and 8 AM on weekdays were directly referred to the on-call resident. The day of week, time, source, initiating event, and required action from each call was recorded. Exclusion criteria included calls regarding established hospital urology in-patients and duplicate calls from individual patients calling more than once within 24 hours. Eighty-seven calls were collected. Seventy percent occurred on weekends, primarily between 8 AM and 5 PM. The most common source was from outpatients (56%) followed by emergency room physicians (30%). In general, 61% and 26% of all calls regarded new urologic symptoms and postoperative issues, respectively. Urinary calculi were the most common specific reason for a call, followed by lower urinary tract symptoms and hematuria. An acute urologic evaluation was required for 27% of all telephone calls. Nine patients (10%) required admission within 48 hours of calling. The education of urology residents should emphasize telephone evaluations of patients who present with urinary calculi and common postoperative issues. The number of after-hour calls may be able to be reduced if patients and nonurologist physicians are also educated in the management of nonacute urologic problems.


How can transforming representation of mathematical entities help us employ more cognitive resources?
This article discusses the cognitive process of transforming one representation of mathematical entities into another representation. This process, which has been called mathematical metaphor, allows us to understand and embody a difficult-to-understand mathematical entity in terms of an easy-to-understand entity. When one representation of a mathematical entity is transformed into another representation, more cognitive resources such as the visual and motor systems can come into play to understand the target entity. Because of their nature, some curves, which are one group of visual representations, may have a great motor strength. It is suggested that directedness, straightness, length, and thinness are some possible features that determine degree of motor strength of a curve. Another possible factor that can determine motor strength of a curve is the strength of association between shape of the curve and past experiences of the observer (and her/his prior knowledge). If an individual has had the repetitive experience of observing objects moving along a certain curve, the shape of the curve may have a great motor strength for her/him. In fact, it can be said that some kind of metonymic relationship may be formed between the shapes of some curves and movement experiences.


Elastic phases of Ge(x)Sb(x)Se(100-2x) ternary glasses driven by topology.
Topology offers a practical set of computational tools to accurately predict certain physical and chemical properties of materials including transformations under deformation. In network glasses with increased cross-linking three generic elastic phases are observed. We examine ternary Ge(x)Sb(x)Se(100-2x) glasses in Raman scattering, modulated DSC and volumetric measurements, and observe the rigidity transition, x = x(c)(1) = 14.9% that separates the flexible phase from the Intermediate phase, and the stress transition, x = x(c)(2) = 17.5% that separate the intermediate phase from the stressed rigid one. Raman scattering provides evidence of the structural motifs populated in these networks. Using size increasing cluster agglomeration, we have calculated the rigidity and stress transitions to occur near x(c)(1)(t) = 15.2% and x(c)(2)(t) = 17.5%, respectively. Theory predicts and experiments confirm that these two transitions will coalesce if edge-sharing Ge-tetrahedral motifs were absent in the structure, a circumstance that prevails in the Ge-deficient Ge7Sb(x)Se(93-x) ternary, underscoring the central role played by topology in network glasses. We have constructed a global elastic phase diagram of the Ge-Sb-Se ternary that provides a roadmap to network functionality. In this diagram, regions labeled A, B, and C comprise networks that are flexible, rigid but unstressed, and stressed-rigid, respectively.


Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood.
Adversity exposures in the prenatal and postnatal period are associated with an increased risk for psychopathology, which can be perpetuated across generations. Nonhuman animal research highlights the gut microbiome as a putative biological mechanism underlying such generational risks. In a sample of 450 mother-child dyads living in Singapore, we examined associations between three distinct adversity exposures experienced across two generations-maternal childhood maltreatment, maternal prenatal anxiety, and second-generation children's exposure to stressful life events-and the gut microbiome composition of second-generation children at 2 y of age. We found distinct differences in gut microbiome profiles linked to each adversity exposure, as well as some nonaffected microbiome features (e.g., beta diversity). Remarkably, some of the microbial taxa associated with concurrent and prospective child socioemotional functioning shared overlapping putative functions with those affected by adversity, suggesting that the intergenerational transmission of adversity may have a lasting impact on children's mental health via alterations to gut microbiome functions. Our findings open up a new avenue of research into the underlying mechanisms of intergenerational transmission of mental health risks and the potential of the gut microbiome as a target for intervention.


An epidemiological study of road traffic accident cases attending emergency department of teaching hospital.
Several studies have shown that road traffic injuries are a major cause of death and disability globally, with a disproportionate number occurring in developing countries. The growth in numbers of motor vehicles is a major contributing factor in the rising toll of fatalities and injuries from road traffic crashes in poor countries. In this study, we reviewed medical records of all the victims of road traffic accidents attending the emergency department of Kathmandu Medical College Teaching Hospital within a year. A total of 757 road traffic victims were reported which accounted for 6.66% of all the cases attending the emergency. 49.93% cases belonged to 21-40 years age group. The most common victim group comprised the pedestrians (56.54%) with motorcycle (55.09%) being the most commonly involved vehicle. 44.65% accidents occurred in evening (12-6 pm). The lower limbs (in 42.0% cases) were the most common body region injured with superficial injuries (bruise/abrasion) accounting for the most common injury pattern followed by soft tissue injuries, incised/lacerated wounds and fractures and dislocations. Most accidents occurred in the April-June trimester.


Synthesis and assignment of absolute configuration of (-)-oleocanthal: a potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from extra virgin olive oils.
[structure: see text] Effective total syntheses and the assignment of absolute configurations of both the (+)- and (-)-enantiomers of oleocanthal 1 (a.k.a. deacetoxy ligstroside aglycon), the latter derived from extra virgin olive oils and known to be responsible for the back of the throat irritant properties of olive oils, have been achieved. The absolute and relative stereochemistry of the naturally occurring enantiomer (-)-1 proved to be 3S,4E. Both syntheses begin with d-(-)-ribose, proceed in 12 steps, and are achieved with an overall yield of 7%. Both enantiomers proved to be non-steroidal anti-inflammatory and anti-oxidant agents.


Developmental changes in distribution of the mucous gel layer in rat small intestine.
The intraluminal mucous gel layer across the small intestine of rats aged 3 days, 1, 2, 4 and 6 weeks (n=10x5) was studied to investigate its postnatal development. Celloidin stabilisation of dried cryostat sections of small intestine, with the luminal contents, preserved the intraluminal mucous gel layer for staining by the periodic acid-Schiff reaction. Morphological differences in the mucous gel, between the villi of the small intestine, in rats of several postnatal ages were observed, most notably after the age of 2 weeks. The adhesive mucous gel layer, covering the intestinal epithelium in the small intestine, appears to undergo rapid development after weaning.


Primary papillary mucinous adenocarcinoma of the ureter mimicking genitourinary tuberculosis.
Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome.


The immunomodulatory role of sulfated chitosan in BMP-2-mediated bone regeneration.
The immunomodulatory property of biomaterials is vital in determining the in vivo fate of implants and tissue regeneration. Bone morphogenetic protein-2 (BMP-2) has been identified as an effective inducer of osteogenic differentiation for bone repair. But it is still unclear how the immunomodulatory effects of materials impact on BMP-2-mediated osteogenesis. Herein, this study aims to investigate the immunoregulatory role of 2-N,6-O-sulfated chitosan (26SCS), a sulfated polysaccharide, in the osteogenetic capacity of BMP-2 and the subsequent effects on bone regeneration. It was noted that 26SCS can robustly activate a moderate pro-inflammatory macrophage response initially, followed by transitioning towards an anti-inflammatory response later on. The immune microenvironment caused by 26SCS could facilitate bone marrow stromal cell (BMSC) chemoattraction. Furthermore, 26SCS significantly up-regulated the expression of BMPR-IA as well as amplified BMP-2-activated BMP/Smad signaling. In addition, the 26SCS-triggered immune microenvironment had a positive effect on proangiogenesis by BMSCs. Our findings suggest that 26SCS may be involved in the induction of a favorable immune microenvironment enhancing crosstalk between immune cells and stem cells undergoing osteogenic differentiation. This relationship is likely responsible for the enhanced bone tissue development observed with 26SCS in an ectopic ossification model.


The evolution of Jen3 proteins and their role in dicarboxylic acid transport in Yarrowia.
Jen proteins in yeast are involved in the uptake of mono/dicarboxylic acids. The Jen1 subfamily transports lactate and pyruvate, while the Jen2 subfamily transports fumarate, malate, and succinate. Yarrowia lipolytica has six JEN genes: YALI0B19470g, YALI0C15488g, YALI0C21406g, YALI0D20108g, YALI0D24607g, and YALI0E32901g. Through phylogenetic analyses, we found that these genes represent a new subfamily, Jen3 and that these three Jen subfamilies derivate from three putative ancestral genes. Reverse transcription-PCR. revealed that only four YLJEN genes are expressed and they are upregulated in the presence of lactate, pyruvate, fumarate, malate, and/or succinate, suggesting that they are able to transport these substrates. Analysis of deletion mutant strains revealed that Jen3 subfamily proteins transport fumarate, malate, and succinate. We found evidence that YALI0C15488 encodes the main transporter because its deletion was sufficient to strongly reduce or suppress growth in media containing fumarate, malate, or succinate. It appears that the other YLJEN genes play a minor role, with the exception of YALI0E32901g, which is important for malate uptake. However, the overexpression of each YLJEN gene in the sextuple-deletion mutant strain ΔYLjen1-6 revealed that all six genes are functional and have evolved to transport different substrates with varying degrees of efficacy. In addition, we found that YALI0E32901p transported succinate more efficiently in the presence of lactate or fumarate.


Why study mechanisms of cell death?
Cell death plays a variety of important roles in biology, both physiological and pathological. Physiological cell death is an important part of development, cell turnover and various aspects of immunological defenses. Pathological cell death is an element of some of the most important diseases plaguing modern society. Recent studies on the mechanisms of calcium-mediated cell death, thought to be important for both physiological and pathological cell death, have indicated that it is a multi-step process in which the cells are active participants, triggering their own self-destruction. Such mechanisms suggest the potential for pharmacological intervention, either to prevent disease-induced tissue death or to remove unwanted tissues.


Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro.
The preparation of suspensions of porcine adrenocortical cells is described. Within the conditions adopted, the cell suspension responded to various agents as expected. It was possible to screen drugs (standard range 0.3-100 microM, incubation period 1 h) for actions on the production/release of aldosterone by the cortical cells using 1 microM deoxycorticosterone as substrate. Progesterone, pregnenolone or corticosterone were also used as substrates. Feed additives of the quinoxaline type induced a slowly developing inhibition of aldosterone production/release by the cell suspension, which was virtually irreversible. During the standard 1 h incubation period inhibitions of up to 22 +/- 2% of control were observed, which increased upon prolongation of the incubation by 2 h. With 100 microM cyadox the inhibition increased from 19 +/- 2% to 35 +/- 2% with prolonged incubation. Ten nitrofuran compounds exerted a more rapidly developing inhibition (by up to 79 +/- 1% of control) of aldosterone production/release, which was reversible. A submaximal inhibition with 10 microM furazolidone of 21 +/- 5% increased to 40 +/- 1% with longer incubation. The concentrations at which these compounds exerted this effect in vitro were well below the peak blood plasma concentrations encountered after administration of the drugs in therapeutic doses. Polyether-antibacterials/ionophores rapidly inhibited aldosterone production/release (to 26 +/- 1% of control) and this effect was completely reversible. The nitroimidazole compounds tested did not affect aldosterone production/release when deoxycorticosterone or progesterone were used as substrates. With use of corticosterone and to a lesser extent with pregnenolone as substrates a clear inhibition (to 73 +/- 3% of control) of aldosterone production was obtained. Amprolium in concentrations up to 100 microM, with deoxycorticosterone as substrate, did not induce a significant change in aldosterone production/release by the suspension of adrenocortical cells. In the same dose range tylosin and roxarsone induced a small but significant inhibition (by up to 10 +/- 3% of control) of aldosterone production/release, which was not dose-dependent. It is concluded that a wide range of growth-promoting drugs may be able to change aldosterone production/release in the animal.


[Intoxication with beta-receptor blockers (author's transl)].
Beta-blockers are increasingly often used with suicidal intent, but are also sometimes swallowed accidentally by small children. Beta-blockers available in the Federal Republic of Germany differ in their pharmacodynamics and pharmacokinetics. After analysing 49 cases of intoxication, no certain relationship was found between the different substances and specific symptoms. Cardiovascular signs such as sinus bradycardia, arrhythmia, hypotension (30 cases), as well as dizziness and drowziness (17) were the most frequent ones. Loss of consciousness and hallucination (13), as well as seizures (3), also occurred frequently. Hypoglycaemia or symptoms due to it (12) were noted especially in young children. In addition to primary removal of the drug, repeated administration of charcoal and sodium sulphate are recommended with most of the drugs for interrupting the enterohepatic circulation. Administration of atropine for bradycardia and hypotension was usually not effective. Dopamine is recommended; glucagon for definite signs of shock. Haemodialysis is indicated only in exceptional instances and is effective for only a few of the drugs. Forced diuresis should not be practised.


The significance of intraoperative monitoring of muscle motor evoked potentials during unruptured large and giant cerebral aneurysm surgery.
The goal of this study was to characterize the utility of muscle motor evoked potentials (MMEPs) elicited by direct cortical stimulation as a means of monitoring during unruptured large and giant cerebral aneurysm surgery. This analysis focused on intraoperative changes in MMEPs and their relationship to postoperative motor function. The study population consisted of 50 patients who underwent surgery for large (n = 31) or giant (n = 19) cerebral aneurysms. Intraoperative MMEPs were continuously and successfully obtained in muscles belonging to the vascular territory of interest. There was no postoperative motor paresis in 31 (62%) patients in whom intraoperative MMEPs remained unchanged. Transient MMEP change occurred in 15 (30%) of the 50 patients, but 9 of those patients had no postoperative motor deficits, 5 had transient motor deficits, and 1 suffered permanent motor deficits resulting from postoperative delayed blood flow insufficiency due to arteriosclerosis of the parent artery. Permanent MMEP loss occurred in 4 (8%) of 50 patients, all of whom developed severe and permanent postoperative motor deficits. MMEP is a useful monitoring modality in patients undergoing surgery for large or giant cerebral aneurysms. This strategy can help predict functional prognosis or guide the neurosurgeon intraoperatively in an effort to promote better outcomes.


[Study of characteristics of monoclonal antibody against substance P].
Cross-reaction of a rat monoclonal antibody (BTP-1) against seventeen substance P analogues was studied. The antibody was of IgG type and related to the carboxyl terminal of substance P, especially methionyl in the terminal, but did not depend on the strength of antagonistic effects of these analogues. It did not show cross-reaction with the following nine peptides: glucagon, endorphin, angiotensin I, II, leucine-enkephalin, methionine-enkephalin, bradykinin, oxytocin and dernorthin, indicating its high specificity to substance P. By means of immuno-enzyme histochemical method, it was shown that stained nerve fibers were located in the gelaliternous substance of Rolando, interpeduncular nucleus, substantia nigra and nerve cell bodies in the vestibular nucleus, lateral tegmental nucleus of mesencephalon and ventral region of third ventricle.


Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, B0AT2 and y+LAT1 functional cooperation.
In the CNS, amino acid (AA) neurotransmitters and neurotransmitter precursors are subject to tight homeostatic control mediated by blood-brain barrier (BBB) solute carrier amino acid transporters (AATs). Since the BBB is composed of multiple closely apposed cell types and opportunities for human in vivo studies are limited, we used in vitro and computational approaches to investigate human BBB AAT activity and regulation. Quantitative real-time PCR (qPCR) of the human BBB endothelial cell model hCMEC/D3 (D3) was used to determine expression of selected AAT, tight junction (TJ), and signal transduction (ST) genes under various culture conditions. L-leucine uptake data were interrogated with a computational model developed by our group for calculating AAT activity in complex cell cultures. This approach is potentially applicable to in vitro cell culture drug studies where multiple "receptors" may mediate observed responses. Of 7 Leu AAT genes expressed by D3 only the activity of SLC7A5-SLC3A2/LAT1-4F2HC (LAT1), SLC43A2/LAT4 (LAT4) and sodium-dependent AATs, SLC6A15/B0AT2 (B0AT2), and SLC7A7/y+LAT1 (y+LAT1) were calculated to be required for Leu uptake. Therefore, D3 Leu transport may be mediated by a potentially physiologically relevant functional cooperation between the known BBB AAT, LAT1 and obligatory exchange (y+LAT1), facilitative diffusion (LAT4), and sodium symporter (B0AT2) transporters.


The enhancing effect of ethanol on the mutagenic activation of N-nitrosomethylbenzylamine by cytochrome P450 2A in the rat oesophagus.
Alcohol consumption is frequently associated with various cancers and the enhancement of the metabolic activation of carcinogens has been proposed as a mechanism underlying this relationship. The ethanol-induced enhancement of N-nitrosodiethylamine (DEN)-mediated carcinogenesis can be attributed to an increase in hepatic activity. However, the mechanism of elevation of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis remains unclear. To elucidate the mechanism underlying the role of ethanol in the enhancement of NMBA-induced oesophageal carcinogenesis, we evaluated the hepatic and extrahepatic levels of the cytochrome P450 (CYP) and mutagenic activation of environmental carcinogens by immunoblot analyses and Ames preincubation test, respectively, in F344 rats treated with ethanol. Five weeks of treatment with 10% ethanol added to the drinking water or two intragastric treatments with 50% ethanol, both resulted in elevated levels of CYP2E1 (1.5- to 2.3-fold) and mutagenic activities of DEN, N-nitrosodimethylamine and N-nitrosopyrrolidine in the presence of rat liver S9 (1.5- to 2.4-fold). This was not the case with CYP1A1/2, CYP2A1/2, CYP2B1/2 or CYP3A2, nor with the activities of 2-amino-3-methylimidazo[4,5-f]quinoline, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, aflatoxin B(1) or other N-nitroso compounds (NOCs), including NMBA. Ethanol-induced elevations of CYP2A and CYP2E1 were observed in the oesophagus (up to 1.7- and 2.3-fold) and kidney (up to 1.5- and 1.8-fold), but not in the lung or colon. In oesophagus and kidney, the mutagenic activities of NMBA and four NOCs were markedly increased (1.3- to 2.4-fold) in treated rats. The application of several CYP inhibitors revealed that CYP2A were likely to contribute to the enhancing effect of ethanol on NMBA activation in the rat oesophagus and kidney, but that CYP2E1 failed to do so. These results showed that the enhancing effect of ethanol on NMBA-induced oesophageal carcinogenesis could be attributed to an increase in the metabolic activation of NMBA by oesophageal CYP2A during the initiation phase, and that this occurred independently of CYP2E1.


High precision micro-impulse measurements for micro-thrusters based on torsional pendulum and sympathetic resonance techniques.
A sympathetic resonance theory is analyzed and applied in a newly developed torsional pendulum to measure the micro-impulse produced by a μN s-class ablative pulsed plasma thruster. According to theoretical analysis on the dynamical behaviors of a torsional pendulum, the resonance amplification effect of micro-signals is presented. In addition, a new micro-impulse measurement method based on sympathetic resonance theory is proposed as an improvement of the original single pulse measurement method. In contrast with the single pulse measurement method, the advantages of sympathetic resonance method are significant. First, because of the magnification of vibration signals due to resonance processes, measurement precision for the sympathetic resonance method becomes higher especially in reducing reading error. With an increase in peak number, the relative errors induced by readout of voltage signals decrease to approximately ±1.9% for the sympathetic resonance mode, whereas the relative error in single pulse mode is estimated as ±13.4%. Besides, by using the resonance amplification effect the sympathetic resonance method makes it possible to measure an extremely low-impulse beyond the resolution of a thrust stand without redesigning or purchasing a new one. Moreover, because of the simple operational principle and structure the sympathetic resonance method is much more convenient and inexpensive to be implemented than other high-precision methods. Finally, the sympathetic resonance measurement method can also be applied in other thrust stands to improve further the ability to measure the low-impulse bits.


Castration of the Vietnamese pot-bellied boar: 8 cases.
Surgical techniques for castration of the Vietnamese pot-bellied boar and outcome are described. Vietnamese pot-bellied pig (VPBP) boars (n = 8) were admitted for castration. Data retrieved from medical records (2002-2011) for these pigs included signalment, history, reason for castration, perioperative management, surgical technique, and complications. Follow-up information was obtained from owners. A scrotal approach with closed technique was used for 6 boars with normally descended testes. A scrotal approach and open technique was used in 1 inguinal cryptorchid boar. In a hemicastrated abdominal cryptorchid boar an ipsilateral parainguinal approach was used. No complications occurred. Castration of the Vietnamese pot-bellied boar is associated with minimal complications and a satisfactory cosmetic outcome. We recommend the routine closure of the external inguinal rings, a simple and fast procedure that may prevent post-castration inguinal herniation. Surgical techniques for castration of the Vietnamese pot-bellied boar and outcome are described. Vietnamese pot-bellied pig (VPBP) boars (n = 8) were admitted for castration. Data retrieved from medical records (2002–2011) for these pigs included signalment, history, reason for castration, perioperative management, surgical technique, and complications. Follow-up information was obtained from owners. A scrotal approach with closed technique was used for 6 boars with normally descended testes. A scrotal approach and open technique was used in 1 inguinal cryptorchid boar. In a hemicastrated abdominal cryptorchid boar an ipsilateral parainguinal approach was used. No complications occurred. Castration of the Vietnamese pot-bellied boar is associated with minimal complications and a satisfactory cosmetic outcome. We recommend the routine closure of the external inguinal rings, a simple and fast procedure that may prevent post-castration inguinal herniation.


Culture, stress and substance use in Cambodian refugee women.
Initial data were generated on the use of alcohol and other drugs by Cambodian refugee women and their families (N = 120) in two sites: Massachusetts and California. Information on frequency and situations surrounding use, and culturally specific use, was elicited. In those families where alcohol was perceived as a problem, the majority of problem drinkers were husbands. About 45% of the East Coast women, however, said they used alcohol for nervousness, stress, headaches, insomnia and pain. In addition, about 15% of the East Coast women reported that a family member used street drugs and was having dependency problems. While use of alcohol or street drugs was not perceived as problematic on the West Coast, over 58% reported using prescription drugs for self-treatment of illnesses other than those targeted by the prescription. When prescription drugs were misused by women, it was most frequently to get an altered state, or "street drug effect". Numerous stressors influence Cambodian women during the pressures of acculturation to the U.S. lifestyle. Some may turn to self-medication in the form of alcohol, prescription sleeping pills, or other drugs. A better understanding of how and why these women make coping choices is needed.


Identification of ETS domain proteins in murine T lymphocytes that interact with the Moloney murine leukemia virus enhancer.
The enhancer of Moloney murine leukemia virus (Mo-MuLV) contains an array of transcriptional control elements that direct viral gene expression in diverse cell types. The murine transcription factor Ets-1 was shown to bind to the LVb and LVc elements of the enhancer by DNase I protection and methylation interference assays. Enhancers containing disrupted Ets-1 binding sites were tested in transient expression assays in the murine T-cell line EL4.E1; alterations in the LVb element affected constitutive enhancer activity, while mutation of either the LVb or LVc element disrupted phorbol ester-induced enhancer activity. Members of the ets gene family of proteins display similar DNA-binding properties; therefore, we speculated that ets proteins other than Ets-1 also might bind these elements. Crude nuclear extracts of EL4.E1 cells were assayed to identify the protein(s) that potentially functions at the LVb element. The predominant binding activity was not Ets-1 but rather two independent DNA-protein complexes that comigrated in mobility shift assays. UV cross-linking and denaturing gel electrophoresis sized the two DNA-binding species, which we denoted p55 and p100. Immunoprecipitation combined with UV cross-linking identified p55 as the alpha subunit of GA-binding protein. The DNA-binding properties of p100 and several ets proteins were compared. Similarities suggested that p100 is also an ETS domain protein, possibly Elf-1. This strategy could be used to identify other ETS domain proteins in crude nuclear extracts. These findings suggest multiple ETS domain proteins could regulate gene expression of Mo-MuLV.


[Professional management of death--sociocultural aspects].
During recent decades, treatment of death has been removed from the family and placed in the hands of experts and specialized institutions. More and more people die outside their homes. Our statistical analysis shows that in Switzerland between 1969 and 1986 the old people's home has replaced the private home. However the proportion of people dying in the hospital (55%) has not changed. Proceeding from these facts, we conducted a sociological research project with participant observation that explored attitudes, strategies and practices of professionals who deal closely with death and dying. Our case studies involved people working on the wards of a hospital, in a hospital mortuary, in an old people's home, in an autopsy department, in a funeral home and in a cemetery. The analysis showed that in the context of preservation of life (hospital), the consciously maintained attitude is ambivalence and an openness to various outcomes. In the context of applied science (autopsy department), the attitude is search for unequivocal exactness. In the context of loss (funeral home, cemetery), we find two different orientations among two different groups of actors. Those who deal with the practical side of death, such as the crematorium attendant, show a technical orientation, while those who deal with death's non-practical side, such as the minister, show a social and a symbolic orientation. At the points of intersection between these contexts, the actors develop complex strategies: maintenance of the past, negation of the present and anticipation of the future. (1.) The fight against death in the university hospital is being more and more replaced by the development of a strategy of openness.(ABSTRACT TRUNCATED AT 250 WORDS)


Echographic verification of radioactive plaque position in the treatment of melanomas.
Visualization of the position of an episcleral plaque in relation to the underlying choroidal melanoma during the early radiation treatment period reconfirms accurate plaque location and may help assure optimal treatment. We used high-resolution B-scan echography to confirm the position of the episcleral plaque in 16 consecutive cases of choroidal melanoma. The technique is most useful for well-defined tumors as small as 3 mm in height whose anterior border does not extend beyond the ora serrata.


Role of monitoring in management of acute ischemic stroke patients.
Although several studies have demonstrated the effectiveness of specialist Stroke Unit (SU) care of stroke patients, there is still disagreement over how these units are best organized. We sought to clarify the role of continuous monitoring of physiological parameters in acute ischemic stroke. We conducted a prospective study of 268 first-ever ischemic stroke patients admitted to our Cerebrovascular Department and allocated, according to the availability of beds, to the SU or Cerebrovascular Unit (CU). Statistical analysis compared mortality and outcome at discharge, medical and neurological complications, and length of hospitalization in the 2 care settings. Two hundred sixty-eight patients were enrolled. A good outcome at discharge, observed in 114 SU patients (85%) and 78 CU patients (58%) (odds ratio, 2.63; 95% CI, 1.4 to 4.8; P<0.02), was found, on multivariate analysis, to be significantly related to type of care (SU versus CU). A significantly greater proportion of SU patients showed adverse changes in monitored parameters, which required acute medical treatment (SU: 64%; CU: 19%; P<0.0001). The mean duration of these complications was significantly shorter in the SU patients (SU: 1.0 day; CU: 2.4 days; P<0.02), and the outcome in patients experiencing complications covered by the monitoring protocol was significantly better in the SU (66%) than in the CU (35%) group (P<0.0001). Admission of acute stroke patients to a monitoring SU may positively influence their outcome at discharge. Confirmation of our findings in larger trials will indicate the need for a revision of the minimum requirements of SUs, with the addition of monitoring as a new requirement.


Personalized Prediction Model to Risk Stratify Patients With Myelodysplastic Syndromes.
Patients with myelodysplastic syndromes (MDS) have a survival that can range from months to decades. Prognostic systems that incorporate advanced analytics of clinical, pathologic, and molecular data have the potential to more accurately and dynamically predict survival in patients receiving various therapies. A total of 1,471 MDS patients with comprehensively annotated clinical and molecular data were included in a training cohort and analyzed using machine learning techniques. A random survival algorithm was used to build a prognostic model, which was then validated in external cohorts. The accuracy of the proposed model, compared with other established models, was assessed using a concordance (c)index. The median age for the training cohort was 71 years. Commonly mutated genes included SF3B1, TET2, and ASXL1. The algorithm identified chromosomal karyotype, platelet, hemoglobin levels, bone marrow blast percentage, age, other clinical variables, seven discrete gene mutations, and mutation number as having prognostic impact on overall and leukemia-free survivals. The model was validated in an independent external cohort of 465 patients, a cohort of patients with MDS treated in a prospective clinical trial, a cohort of patients with paired samples at different time points during the disease course, and a cohort of patients who underwent hematopoietic stem-cell transplantation. A personalized prediction model on the basis of clinical and genomic data outperformed established prognostic models in MDS. The new model was dynamic, predicting survival and leukemia transformation probabilities at different time points that are unique for a given patient, and can upstage and downstage patients into more appropriate risk categories.


Diagnosis and management of ischemic cardiomyopathy: Role of cardiovascular magnetic resonance imaging.
Coronary artery disease (CAD) represents an important cause of mortality. Cardiovascular magnetic resonance (CMR) imaging evolved as an imaging modality that allows the assessment of myocardial function, perfusion, contractile reserve and extent of fibrosis in a single comprehensive exam. This review highlights the role of CMR in the differential diagnosis of acute chest pain by detecting the location of obstructive CAD or necrosis and identifying other conditions like stress cardiomyopathy or myocarditis that can present with acute chest pain. Besides, it underlines the prognostic implication of perfusion abnormalities in the setting of acute chest pain. Furthermore, the review addresses the role of CMR to detect significant CAD in patients with stable CAD. It elucidates the accuracy and clinical utility of CMR with respect to other imaging modalities like single-photon emission computed tomography and positron emission tomography. Besides, the prognostic value of CMR stress testing is discussed. Additionally, it summarizes the available CMR techniques to assess myocardial viability and describes algorithm to identify those patient who might profit from revascularization those who should be treated medically. Finally, future promising imaging techniques that will provide further insights into the fundamental disease processes in ischemic cardiomyopathy are discussed.


Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.
The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment. Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability. Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals. These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.


Creating local estimates from a population health survey: practical application of small area estimation methods.
Regular health surveys can produce reliable estimates at higher geographic levels but not for small areas. Alternatives are to aggregate data over several years or use model-based methods. We created and evaluated model-based estimates for four health-related outcomes by gender, for 153 Local Government Areas using data from the New South Wales Population Health Survey. The evaluation examined evidence on bias and determined the covariates available and appropriate for each outcome variable. The evaluation considered the likely precision of the resulting estimates. The bias and precision of results for single years (2006-2008) for each outcome variable using six covariate specifications were compared with direct survey estimates based on a single year's data and those obtained by aggregating over seven years. A practical issue is how to choose covariates to include in the models as the best covariate specification varies between outcome variables. Model-based results had median root mean squared errors between 3.3% and 5.5% (max 5.2% and 11.3% respectively) and median relative root mean squared errors between 6.8% and 24.5% (max 11.7% and 41.5% respectively). The model-based estimates were unbiased compared with direct estimates based on one or seven years of data and when aggregated to a point where direct estimates were reliable. The bias and reliability assessment process provides a way for policymakers to have confidence in model-based estimates.


Protein interference applications in cellular and developmental biology using DARPins that recognize GFP and mCherry.
Protein-protein interactions are crucial for cellular homeostasis and play important roles in the dynamic execution of biological processes. While antibodies represent a well-established tool to study protein interactions of extracellular domains and secreted proteins, as well as in fixed and permeabilized cells, they usually cannot be functionally expressed in the cytoplasm of living cells. Non-immunoglobulin protein-binding scaffolds have been identified that also function intracellularly and are now being engineered for synthetic biology applications. Here we used the Designed Ankyrin Repeat Protein (DARPin) scaffold to generate binders to fluorescent proteins and used them to modify biological systems directly at the protein level. DARPins binding to GFP or mCherry were selected by ribosome display. For GFP, binders with KD as low as 160 pM were obtained, while for mCherry the best affinity was 6 nM. We then verified in cell culture their specific binding in a complex cellular environment and found an affinity cut-off in the mid-nanomolar region, above which binding is no longer detectable in the cell. Next, their binding properties were employed to change the localization of the respective fluorescent proteins within cells. Finally, we performed experiments in Drosophila melanogaster and Danio rerio and utilized these DARPins to either degrade or delocalize fluorescently tagged fusion proteins in developing organisms, and to phenocopy loss-of-function mutations. Specific protein binders can thus be selected in vitro and used to reprogram developmental systems in vivo directly at the protein level, thereby bypassing some limitations of approaches that function at the DNA or the RNA level.


The assessment of child sexual abuse allegations: using research to guide clinical decision making.
As reports of child sexual abuse (CSA) have risen, greater attention has been focused on how clinicians evaluate allegations of abuse. A common theme in the CSA assessment literature is to encourage comprehensive, multimodal assessments. This recommendation, however, is rarely accompanied by suggestions regarding how clinicians might integrate and differentially weight the information gathered. The present article is designed to address the issue of which sources of information clinicians should rely upon when conducting CSA assessments. Specifically, the commonly used indicators and procedures for assessing allegations of abuse are identified and then examined in light of their respective empirical literatures. It is concluded that medical examinations and the child's report are among the best sources of information, and should therefore be most heavily relied upon to arrive at accurate decisions. Clinicians are encouraged to adopt the mind set of a scientist conducting an a priori, hypothesis-driven research investigation. This approach should help clinicians avoid the temptation of post hoc analyses that reflect personal biases more than the actual data.


Methodological quality and risk-of-bias assessments in systematic reviews of treatments for peri-implantitis.
The purpose of the present study was to evaluate the methodological quality and risk of bias in systematic reviews (SRs) on the effectiveness of peri-implantitis treatments. We searched four electronic databases: MEDLINE, Web of Science, Cochrane Database of Systematic Reviews, and EMBASE. Previous SRs focusing on peri-implantitis treatment published between 2010 and 2017 were identified. After literature screening, eligible SRs were qualitatively assessed using two validated instruments: Assessing the Methodological Quality of Systematic Reviews (AMSTAR2) and Risk Of Bias In Systematic reviews (ROBIS). The characteristics and findings of SRs are also reported. A total of 23 SRs formed the basis of this study. Of the 23, six included randomized controlled trials (RCTs) only. Overall, the AMSTAR2 assessment revealed three studies with high and six studies with low methodological quality, and all the other SRs were judged as having critically low methodological quality. ROBIS revealed only one Cochrane review with a low risk of bias and the others with a high risk of bias. In particular, the assessment of non-randomized studies (NRSIs), appropriateness of ROB assessment, and meta-analysis did not satisfy the criteria in AMSTAR2 assessment. Furthermore, there were a few SRs that interpreted and discussed the results of risk of bias (ROB) and heterogeneity assessment, together with the impact of treatment. Due to the lack of head-to-head comparisons conducted in RCTs, review authors need to use other sources of evidence, such as clinical control trials (CCTs), cohort studies (CS), clinical research (CR), and animal studies. The end result is the presentation of low-quality evidence, with high ROB. Several SRs conducted network meta-analysis as an alternative to head-to-head conventional meta-analysis of RCTs. We suggest that the best methods to generate, access, and assess evidence in situations where RCT evidence is lacking should be discussed on an urgent basis.


Strong anisotropy of Sc2X2Se2 (X = Cl, Br, I) monolayers contributes to high thermoelectric performance.
As a novel type of anisotropic two-dimensional material, extensive attention has been paid to the thermoelectric (TE) properties of FeOCl-type monolayers, such as Al2X2Se2 (X = Cl, Br, I), Sc2I2S2, and Ir2Cl2O2. Recently, theoretical works based on first-principles calculations have been powerful driving forces in field of TE research. In this work, we perform an investigation into the TE properties of Sc2X2Se2 (X = Cl, Br, I) monolayers based on density functional theory (DFT). A study on the stability, including AIMD simulation and phonon calculation, shows the stable structure of Sc2Cl2Se2, Sc2Br2Se2, and Sc2I2Se2 monolayers. Additionally, the electronic and thermal transport properties of Sc2X2Se2 monolayers are anisotropic along the x and y directions. Moreover, the combination of excellent Seebeck coefficient and ultralow lattice thermal conductivity contributes to outstanding ZT values, and the ZT values follow the order: Sc2I2Se2 > Sc2Br2Se2 > Sc2Cl2Se2. At 300 K, we obtained maximum ZT of 0.34, 0.77, and 1.97 for Sc2Cl2Se2, Sc2Br2Se2, and Sc2I2Se2, respectively, by n-type doping in the x direction. These results demonstrate that monolayer Sc2X2Se2 (X = Cl, Br, I) materials are promising thermoelectric materials, Sc2I2Se2 has more desirable properties along the x direction, and n-type doping can significantly enhance the ZT values. Our work lays a foundation for exploring the TE transport properties of FeOCl-type monolayers.


Preparation of Barbed ZnO Fibers and the Selective Adsorption Behavior for BSA.
ZnO electrospun nanofibers can act as seed fibers to fabricate multidentate barbed fibers perpendicular to the growth of the fibers using the chemical bath deposition (CBD) method. Fibers with a multirod morphology have a porous grid structure. The sample is easy to recover, and the nonpolar surface in the sample is sufficiently exposed. In the research of barbed fiber fabrication and adsorption on bovine serum albumin (BSA), the effects of different chemical bath conditions on the growth of ZnO nanorods were discussed. Barbed fibers with large slenderness ratios were obtained at a water content of 60 mL at 75 °C. Each milligram of barbed fibers can quickly adsorb about 162 μg of protein within 30 min. The adsorption activity of BSA between polar and nonpolar ZnO surfaces was also studied. The selective adsorption behavior of BSA on the nonpolar surface was revealed.


Fatty acid transport proteins in disease: New insights from invertebrate models.
The dysregulation of lipid metabolism has been implicated in various diseases, including diabetes, cardiopathies, dermopathies, retinal and neurodegenerative diseases. Mouse models have provided insights into lipid metabolism. However, progress in the understanding of these pathologies is hampered by the multiplicity of essential cellular processes and genes that modulate lipid metabolism. Drosophila and Caenorhabditis elegans have emerged as simple genetic models to improve our understanding of these metabolic diseases. Recent studies have characterized fatty acid transport protein (fatp) mutants in Drosophila and C. elegans, establishing new models of cardiomyopathy, retinal degeneration, fat storage disease and dermopathies. These models have generated novel insights into the physiological role of the Fatp protein family in vivo in multicellular organisms, and are likely to contribute substantially to progress in understanding the etiology of various metabolic disorders. Here, we describe and discuss the mechanisms underlying invertebrate fatp mutant models in the light of the current knowledge relating to FATPs and lipid disorders in vertebrates.


Effect of microthreads on coronal bone healing of narrow-diameter implants with reverse-tapered design in beagle dogs.
The objective of this study was to investigate the effect of microthreads on the coronal bone healing of narrow-diameter implants with reverse-tapered design. A total of 52 implants were classified into two groups according to presence or absence of coronal microthreads, the reverse-tapered narrow-diameter implant (RTN) group, and the reverse-tapered narrow-diameter implant with microthreads (RTNM) group. The implants were installed in split-mouth design in the edentulous mandible of six dogs. Three animals were sacrificed at 4 weeks and three at 8 weeks. Resonance frequency analysis, bone measurement using microcomputed tomography (micro-CT), removal torque test, and histometric analysis were performed. No significant differences in implant stability quotient value were observed between the groups at baseline, 4 weeks, or 8 weeks. Bone measurement using micro-CT showed that bone-implant contact volume (BICV) and bone-implant contact volume ratio (BICVR) in the coronal part of RTNM were statistically higher than those in RTN at 4 and 8 weeks. Histometric analysis showed statistically higher bone-implant contact length (BICL) in the coronal part of RTNM than in RTN at 4 weeks; however, bone-implant contact ratio (BICR) was not significantly different between the groups. At 8 weeks, the BICL and BICR did not differ significantly between the groups. Removal torque test showed no significant differences between the groups at 4 and 8 weeks. The microthreads might facilitate more coronal bone-implant contact due to increased surface areas at an early healing phase; however, they did not significantly affect coronal bone healing at 8 weeks.


Immunoglobulin E response during measles.
Serum IgE levels were determined in 41 patients with measles infection. 23 patients (56%) had an increased level (greater than 20%) during the acute phase of the disease in comparison with the recovery phase. 14 showed no change, and decreased levels were observed in 4 patients only. In contrast, both IgG and IgA levels decreased or remained unchanged in the majority of the patients during disease activity. The changes in the pattern of serum immunoglobulins during measles might be attributed to selective depletion of T-cell subpopulations.


Immunomodulatory effect of splenectomy in lung cancer mouse xenograft models receiving radiation therapy.
This study aims to investigate the effect of splenectomy on radiation-mediated growth inhibition and immune modulation in lung cancer xenograft models. Human non-small cell lung cancer H1299 cells and murine Lewis lung carcinoma LL/2-luc cells were injected into the right hind leg of BALB/c-nude mice and C57BL/6 mice, respectively. Splenectomy or sham operation was performed prior to tumor cell injection or before and after irradiation during tumor growth. Irradiation was delivered with 2-3 fractions of 6 Gy X-ray using a linear accelerator. Flow cytometry analysis was performed for immune cell profiling. Splenectomy prior to tumor injection or at early stage inhibited growth of LL/2-luc tumors but not that of H1299 tumors; however, it did not enhance the antitumor effect of radiation regardless of intervention timing. Flow cytometry analysis showed monocytic myeloid-derived suppressor cells (MDSCs) and activated CD8+ T cells increased after irradiation in the tumors of splenectomized mice, compared to those of sham-operated mice. Administration of anti-PD-1 (programmed death-1) antibodies improved the ability of splenectomy to attenuate the growth of irradiated tumors. Splenectomy has paradoxical effects on radiation-induced tumor growth inhibition, depending on tumor types and intervention timing, but it has an immune-modulating effect when combined with radiation.


The Nano-Intestine Interaction: Understanding the Location-Oriented Effects of Engineered Nanomaterials in the Intestine.
Engineered nanomaterials (ENMs) are used in food additives, food packages, and therapeutic purposes owing to their useful properties, Therefore, human beings are orally exposed to exogenous nanomaterials frequently, which means the intestine is one of the primary targets of nanomaterials. Consequently, it is of great importance to understand the interaction between nanomaterials and the intestine. When nanomaterials enter into gut lumen, they inevitably interact with various components and thereby display different effects on the intestine based on their locations; these are known as location-oriented effects (LOE). The intestinal LOE confer a new biological-effect profile for nanomaterials, which is dependent on the involvement of the following biological processes: nano-mucus interaction, nano-intestinal epithelial cells (IECs) interaction, nano-immune interaction, and nano-microbiota interaction. A deep understanding of NM-induced LOE will facilitate the design of safer NMs and the development of more efficient nanomedicine for intestine-related diseases. Herein, recent progress in this field is reviewed in order to better understand the LOE of nanomaterials. The distant effects of nanomaterials coupling with microbiota are also highlighted. Investigation of the interaction of nanomaterials with the intestine will stimulate other new research areas beyond intestinal nanotoxicity.


Normal Reference Values for Left Atrial Strain and Its Determinants from a Large Korean Multicenter Registry.
Left atrial (LA) strain is a novel parameter of LA function. However, its reference value has not been established, and the determining factors for LA strain remain elusive. We aimed to present LA strain with reservoir, conduit, and contractile components and associated parameters in a large-sized group of healthy individuals. The present study was from a prospective multicenter registry in South Korea. Subjects who had no history of cardiovascular disease with adequate images were eligible for inclusion. LA reservoir, conduit, and contractile strains (LASRES, LASCD and LASCT, respectively) were measured. Left ventricular global longitudinal strain (LV GLS) and early and late diastolic strain rates (DSRe and DSRa, respectively) were also evaluated. Among a total of 324 subjects (mean age: 49 ± 16 years, 167 females), the mean LASRES, LASCD, and LASCT values were 35.9% ± 10.6%, 21.9% ± 9.3%, and 13.9% ± 3.6%, respectively. Mean LV GLS was -20.4% ± 2.2%, and mean DSRe and DSRa were 1.6 ± 0.4 s-1 and 0.8 ± 0.3 s-1, respectively. With aging, LASRES and LASCD showed significant decreases. Factors showing independent associations with LASRES were age (B = -0.425, p < 0.001), DSRe (B = 4.706, p = 0.001), and LV GLS (B = -1.081, p < 0.001). Age (B = -0.319, p < 0.001), DSRe (B = 4.140, p = 0.002), DSRa (B = -3.409, p = 0.018), and LV GLS (B = -0.783, p < 0.001) showed associations with LASCD. With LASCT, only DSRa showed a correlation (R = 0.277, p < 0.001). We presented LA strain in a large-sized group of healthy subjects. Age is a significant determinant of LA function. Associations of LA strain with diastolic strain rates and LV GLS reflect cardiac mechanics.


13C-xylose and 14C-xylose breath tests for the diagnosis of coeliac disease.
Xylose absorption testing has traditionally involved measurement of serum xylose and/or measurement of excreted xylose in urine. However, by enriching xylose with a 13C- or 14C-isotope, absorption of an oral xylose load will be reflected in the time-dependent pattern of 13CO2 or 14CO2 exhaled in breath. Our objectives were to evaluate the diagnostic properties of 13C-xylose and 14C-xylose breath tests in coeliac disease, and to develop a diagnostic breath test index. We reviewed data from 41 coeliac patients who underwent the 14C-xylose breath test before and after commencement of a gluten-free diet, and 60 coeliac patients who underwent the 13C-xylose breath test, 37 of whom repeated the test after starting a gluten-free diet. Coeliac patients were compared with healthy control subjects. Coeliac patients exhaled significantly less 13CO2 or 14CO2 than healthy controls during the first hour of the test and more isotope-labelled CO2 than control subjects after 3 h. Diagnostic accuracy was optimal with test duration of 210 min combining gas measurements at 30 min and 210 min in a simple fraction. This gas fraction index (30 min/210 min) distinguished between coeliac patients and healthy control subjects with 84-95% sensitivity and 87-94% specificity. After commencement of a gluten-free diet, the gas fraction index increased in most coeliac patients, but remained lower than that in healthy control subjects. 13C-xylose- and 14C-xylose breath tests discriminate between coeliac patients and healthy control subjects with high sensitivity and specificity. The stable isotope 13C-xylose breath test has comparable diagnostic accuracy to the radioactive isotope 14C-xylose breath test and should be the preferred alternative to traditional xylose absorption tests.


Prevalence and Bacterial Isolates of Mastitis in Dairy Farms in Selected Districts of Eastern Harrarghe Zone, Eastern Ethiopia.
The study was conducted from November 2015 to April 2016 to estimate the prevalence of clinical and subclinical mastitis in lactating cows, to assess the associated risk factors, and to isolate the major bacterial pathogens in dairy farms in selected district of Eastern Harrarghe Zone, Eastern Ethiopia. The study was carried out in 384 dairy cows based on data collection, farm visit, animal examination, California mastitis test (CMT), and isolation bacterial pathogens using standard techniques. In the present study the overall mastitis at cow level was 247 (64.3%). The prevalence of clinical and subclinical mastitis and quarter level prevalence for clinical and subclinical mastitis were 12.5% and 51.8% at cow level and 10.7% and 46.4% at quarter level, respectively. Clinically, 101 (6.6%) quarters which belong to 75 (19.5%) animals were found to be with blind teat. In the present study prevalence of mastitis was significantly associated with parity and age (p < 0.05). Bacteriological examination of milk sample revealed 187 isolates where coagulase negative Staphylococcus species (CNS) (34.2%) was the predominant species while Streptococcus faecalis (2.1%) was identified as the least bacteria. The present study concluded that prevalence of mastitis particularly the subclinical mastitis was major problem of dairy cows in the area and hence warrants serious attention.