The Blunt Abdominal Trauma Bedside Ultrasonography Comparison with Trauma Severity Scores and Computerized Tomography.
To investigate the accuracy of focussed assessment sonography for trauma (FAST) bedside ultrasonography application in patients with blunt abdominal trauma and patient management, clinical outcome, and trauma severity scores. Cross-sectional descriptive study. Department of Emergency Medicine, Ondokuz Mayis University, Faculty of Medicine, Samsun, Turkey, from April 2013 to June 2017. The presence of intraperitoneal free fluid (FF) was investigated by FAST application by emergency physicians. Abdominal computed tomography (CT), which was considered the gold standard, was made use of for evaluating intraperitoneal FF presence. Patients were evaluated for urgent surgical intervention, requirement of blood transfusion, and mortality status. The relationship between the FF presence / absence in FAST practice and revised trauma score (RTS), injury severity score (ISS) and trauma injury severity score (TRISS) was statistically analysed. All 28 FAST (+) patients also had intraperitoneal FF in gold standart CT. Although the gold standart CT detected intraperitoneal FF in 6 (4.2%) of 140 FAST (-) patients, the compatibility between FAST and CT in the detection of intraperitoneal FF in patients with blunt abdominal trauma was statistically significant (k: 0.882, p<0.001). RTS and ISS scores were 6.24 ± 1.74 and 44.0 ± 15.7 in eleven (3.5%) dead patients. The sensitivity, specificity, positive predictive value, and negative predictive value were found to be 82.3% (95% CI: 65.4-93.2), 100% (95% CI: 97.2-100), 100% and 95.7% (95% CI: 91.5-97.8), respectively. FAST had a high accuracy compared to gold standard CT in detecting FF. Low RTS and high ISS are associated with impaired hemodynamic parameters and detected FF [FAST (+)].


Identification of Protein Recognition Elements within Heparin Chains Using Enzymatic Foot-Printing in Solution and Online SEC/MS.
Understanding molecular mechanisms governing interactions of glycosaminoglycans (such as heparin) with proteins remains challenging due to their enormous structural heterogeneity. Commonly accepted approaches seek to reduce the structural complexity by searching for "binding epitopes" within the limited subsets of short heparin oligomers produced either enzymatically or synthetically. A top-down approach presented in this work seeks to preserve the chemical diversity displayed by heparin by allowing the longer and structurally diverse chains to interact with the client protein. Enzymatic lysis of the protein-bound heparin chains followed by the product analysis using size exclusion chromatography with online mass spectrometry detection (SEC/MS) reveals the oligomers that are protected from lysis due to their tight association with the protein, and enables their characterization (both the oligomer length, and the number of incorporated sulfate and acetyl groups). When applied to a paradigmatic heparin/antithrombin system, the new method generates a series of oligomers with surprisingly distinct sulfation levels. The extent of sulfation of the minimal-length binder (hexamer) is relatively modest yet persistent, consistent with the notion of six sulfate groups being both essential and sufficient for antithrombin binding. However, the masses of longer surviving chains indicate complete sulfation of disaccharides beyond the hexasaccharide core. Molecular dynamics simulations confirm the existence of favorable electrostatic interactions between the high charge-density saccharide residues flanking the "canonical" antithrombin-binding hexasaccharide and the positive patch on the surface of the overall negatively charged protein. Furthermore, electrostatics may rescue the heparin/protein interaction in the absence of the canonical binding element.


TWO-WAY Bridge between Muscular Dysfunction and Cognitive Impairment: Secondary Analyses of SABE - Bogota Study.
Muscular dysfunction and cognitive impairment are both disabling states, affecting especially the elderly. Thus, are important subjects of research. Our goal is to describe the association between these two entities in the elderly. This is a secondary analysis from the SABE 2012 Bogota survey, which is a cross-sectional study. We define muscular dysfunction as an abnormal result in gait speed and/or handgrip strength tasks. Cognitive impairment was defined as an abnormal result in Mini Mental State Examination. Other independent variables were measured. A total of 1,564 older adults were included in the analysis. Cognitive impairment showed statistically significant association with both low handgrip strength (OR: 2.25; CI 1.52 - 3.33) and low gait speed (OR: 2.76; CI 1.83 - 4.15) in the adjusted model. In older adults, muscular dysfunction is associated with cognitive impairment. New studies should address the causality and temporality of this relationship.


The TGFβ-SMAD3 pathway inhibits IL-1α induced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration.
The most abundant cells in the extensive desmoplastic stroma of pancreatic adenocarcinomas are the pancreatic stellate cells, which interact with the carcinoma cells and strongly influence the progression of the cancer. Tumor stroma interactions induced by IL-1α/IL-1R1 signaling have been shown to be involved in pancreatic cancer cell migration. TGFβ and its receptors are overexpressed in pancreatic adenocarcinomas. We aimed at exploring TGFβ and IL-1α signaling and cross-talk in the stellate cell cancer cell interactions regulating pancreatic adenocarcinoma cell migration. Human pancreatic stellate cells were isolated from surgically resected pancreatic adenocarcinomas and cultured in the presence of TGFβ or pancreatic adenocarcinoma cell lines. The effects of TGFβ were blocked by inhibitors or amplified by silencing the endogenous inhibitor of SMAD signaling, SMAD7. Pancreatic stellate cell responses to IL-1α or to IL-1α-expressing pancreatic adenocarcinoma cells (BxPC-3) were characterized by their ability to stimulate migration of cancer cells in a 2D migration model. In pancreatic stellate cells, IL-1R1 expression was found to be down-regulated by TGFβ and blocking of TGFβ signaling re-established the expression. Endogenous inhibition of TGFβ signaling by SMAD7 was found to correlate with the levels of IL-1R1, indicating a regulatory role of SMAD7 in IL-1R1 expression. Pancreatic stellate cells cultured in the presence of IL-1α or in co-cultures with BxPC-3 cells enhanced the migration of cancer cells. This effect was blocked after treatment of the pancreatic stellate cells with TGFβ. Silencing of stellate cell expression of SMAD7 was found to suppress the levels of IL-1R1 and reduce the stimulatory effects of IL-1α, thus inhibiting the capacity of pancreatic stellate cells to induce cancer cell migration. TGFβ signaling suppressed IL-1α mediated pancreatic stellate cell induced carcinoma cell migration. Depletion of SMAD7 upregulated the effects of TGFβ and reduced the expression of IL-1R1, leading to inhibition of IL-1α induced stellate cell enhancement of carcinoma cell migration. SMAD7 might represent a target for inhibition of IL-1α induced tumor stroma interactions.


Deferoxamine-conjugated AgInS2 nanoparticles as new nanodrug for synergistic therapy for hepatocellular carcinoma.
Herein, a new nanodrug that exhibits multi-therapeutic modalities for synergistic treatment of hepatocellular carcinoma is reported. The nanodrug is composed of carboxymethyl cellulose modified silver indium sulfide nanoparticle (CMC-AgInS2 NP, served as a source of reactive oxygen species) covalently linked with deferoxamine (DFO, served as iron chelating agent). The DFO/CMC-AgInS2 nanodrug was taken up by the HepG2 cell and accumulated within the cytosol as well as the nucleus, leading to induction of cell arrest in the G2/M phase and subsequent apoptosis cell death. Compared to DFO, the DFO/CMC-AgInS2 nanodrug demonstrated better anti-proliferative activity against the HepG2 cell. As they were cultured in a medium supplemented with ferric ions, the HepG2 cells were induced to grow faster as compared to the cells without the addition of ferric ions. Fortunately, our nanodrug was found to inhibit the cell growth induced by ferric ions. Our results indicate that the nanodrug has synergistic effect for treatment of HepG2 cells via the intrinsic therapeutic property of CMC-AgInS2 NP and the iron chelating capability of DFO.


[Transfusion risk related to female/male plasma use. Analysis and debate].
Transfusion-related acute lung injury (TRALI) is a syndrome characterized by acute respiratory distress following the transfusion of blood components. The pathophysiological hallmark of TRALI is increased pulmonary microvascular permeability. Several reports demonstrate that the majority of TRALI cases are precipitated by transfusion of donor antibodies directed against HLA (human leukocyte antigens) or HNA (human neutrophil antigens) expressed on the neutrophils' surface of the recipient. This antibody-antigen interaction is thought to directly cause neutrophils activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Following plasma transfusion is an important and underreported adverse event. Some blood centers have limited the collection of plasma from female donors due to their propensity for developing anti HLA antibodies after pregnancy.


Scattering of a Bessel beam by a sphere: II. Helicoidal case and spherical shell example.
In prior work [P. L. Marston, "Scattering of a Bessel beam by a sphere," J. Acoust. Soc. Am. 121, 753-758 (2007)] the partial wave series for the scattering by a sphere centered on a zero-order Bessel beam was derived. The present work extends the analysis of the far-field scattering to the case of a Bessel beam having an angular dependence on phase. The beam considered is an example of a helicoidal beam where "helicoidal" refers to a type of beam that possesses an axial null and has an azimuthal phase gradient. This type of beam is sometimes also referred to as an acoustic vortex. The beam considered here has a phase ramp equal to the azimuthal angle. In agreement with symmetry arguments given previously, the backward scattering and forward scattering vanish for all frequencies. Some of the resulting modifications of the scattering are illustrated for a rigid sphere and an evacuated steel shell in water. For some directions and choices for the frequency, the calculated scattering by the shell increases when shifting to a helicoidal beam illumination.


Mitochondria-targeting therapeutic strategies for overcoming chemoresistance and progression of cancer.
The cytotoxic effects of many anticancer drugs are mediated via the apoptotic pathways. Chemoresistant tumor cells have acquired the ability to evade the action of multiple classes of anti-cancer drugs. One mechanism by which tumor cells survive in the presence of chemotherapy is by increasing anti-apoptotic activities. Since mitochondria are critical 'gatekeepers' to the apoptosis process, development of cytotoxic drugs that target mitochondria may provide a new strategy to induce apoptosis in tumor cells. Mitochondrial permeability transition pore complex (PTPC) controls mitochondrial membrane permeabilization, which is a critical event in the process leading to chemotherapy-induced apoptosis. Therefore, targeting of PTPC components may overcome chemoresistance in tumor cells. Moreover, alterations in mitochondrial DNA such as mutation and the subsequent dysfunction of mitochondrial respiratory enzyme have been reported in various types of cancer, and their functional consequences are associated cancer development, chemoresistance, and therapeutic implications. In this mini-review, we aim to provide a brief review on several mitochondria-targeting strategies to overcome chemoresistance in cancer.


Couplepause: A New Paradigm in Treating Sexual Dysfunction During Menopause and Andropause.
At midlife and beyond, both men and women face organic changes that can affect sexual functioning. For women, ovarian exhaustion causes estrogen deficiency, leading to genitourinary syndrome of menopause, which may include vaginal dryness, irritation/itching, inadequate lubrication, and dyspareunia. Hypoactive sexual desire disorder also can result from biopsychosocial factors. For men, erectile dysfunction prevalence increases with age, and some men develop testosterone deficiency. In this narrative review, we summarize the literature on how menopause and andropause can affect the sexual health of both the patient and partner and describe a new paradigm ("couplepause") for addressing the sexual health needs of the aging couple as a whole. We combined a literature review conducted using PubMed with insights garnered from our own clinical experiences. We reviewed publications relating to couples-based approaches to sexual dysfunction, male perceptions of female sexual dysfunction, female perceptions of male sexual dysfunction, interactions between male and female sexual dysfunctions, sexual dysfunction and midlife changes in homosexual couples, and impact of pharmacologic treatments for sexual dysfunctions on the couple's sexual health. Both members of a couple may experience age-related changes concurrently and interdependently. In such cases, it is unhelpful, and sometimes detrimental, to treat the symptoms for only one member of the couple without also treating the other. Therefore, as an evolution of the couple-oriented approaches of Masters and Johnson and others, we introduce the concept of couplepause and the need for a new diagnostic and therapeutic paradigm that addresses the sexual health needs of the aging couple as a whole rather than treating the individual patient in isolation. Taking a couple-oriented approach to evaluate and manage couplepause in the latter half of life can dramatically and simultaneously help both members of the couple to improve sexual satisfaction and intimacy. Jannini EA, Nappi RE. Couplepause: A New Paradigm in Treating Sexual Dysfunction During Menopause and Andropause. Sex Med Rev 2018;6:384-395.


Proteomic profiling of perturbed protein sulfenation in renal medulla of the spontaneously hypertensive rat.
Protein sulfenic acids have been proposed as potential biochemical switches for redox signaling. This post-translational modification (PTM) is readily reversible, in contrast to some other types of oxidative PTM. Enhanced oxidative stress has been reported as a feature of hypertension, and renal function has been implicated in the development and progression of the disease in animal models such as the spontaneously hypertensive rat (SHR). However, reactive oxygen species (ROS) are also signaling molecules and may play a role in vascular function. To investigate protein sulfenation under hypertensive conditions, we examined protein extracts of SHR kidney medulla in comparison to medulla from normotensive Wistar rats. Total free thiol content of the SHR medulla was significantly lower than that of Wistar medulla, indicating enhanced oxidation of sulfhydryls. Protein sulfenation was also significantly greater in the medulla of hypertensive animals. Thioredoxin reductase activity was also reduced in SHR medulla and this may account, in part, for enhanced protein sulfenation. Purification of sulfenated proteins from SHR medulla revealed several proteins involved in processes such as metabolism, antioxidant defense, and regulation of nitric oxide synthase. Enhanced sulfenation may represent perturbed redox signaling in SHR medulla, or simply enhanced ROS generation.


Postictal mania versus postictal psychosis: differences in clinical features, epileptogenic zone, and brain functional changes during postictal period.
To clarify the differences between postictal mania (PIM) and postictal psychosis (PIP). Five patients with PIM were compared to 17 patients with PIP, with respect to clinical, epileptological, electrophysiological, and neuroimaging features. PIM was distinguished from PIP by the symptoms observed in the postictal period based on the ICD-10 criteria. Postictal manic episodes lasted for a longer period than postictal psychotic episodes. Patients with PIM had more recurrent postictal episodes than patients with PIP. The age at onset of epilepsy in patients with PIM was older than that in patients with PIP. PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP was associated with temporal lobe epilepsy. The estimated epileptogenic zone was on the language dominant side in PIM, whereas there was no predominant hemispheric laterality in PIP. Electroencephalography (EEG) performed during the early period of postictal manic and psychotic episodes showed decreased frequency of interictal epileptiform discharges in both PIM and PIP. Single-photon emission computed tomography (SPECT) during postictal manic and psychotic episodes showed increased perfusion in the temporal and/or frontal lobes in both PIM and PIP. Three patients with PIM showed increased perfusion during postictal episodes on bilateral or the language nondominant side, which were contralateral to the estimated epileptogenic zone, whereas three patients with PIP showed increased perfusion on the areas, which were ipsilateral to the estimated epileptogenic zone. PIM has a distinct position among the mental disorders observed in the postictal period.


Inter-instrumental variation of skin capacitance measured with the Corneometer.
Measurement of skin surface and stratum corneum (SC) hydration during clinical and/or experimental trials needs devices with acceptable reproducibility and sensitivity under conditions ranging from increased and normal to low hydration. A previous study comparing Corneometer instruments (European group for Efficacy Measurement of Cosmetics and Other products--EEMCO) used for measurement of electrical capacitance of skin indicated a major difference among Corneometer instruments. The aim of this study was to assess three inter-instrumental similar Corneometer instruments (two pieces of CM820 and one CM810) in normal skin. We named them CM-A(CM820), CM-B(CM820), and CM-C(CM810). The hydration state of SC measured as electrical capacitance of six body sites were measured in 53 subjects with three Corneometer instruments. We found that the Corneometer instruments displayed close capacitance levels. When one Corneometer was plotted against another the regression line indicated a good correlation among instruments albeit a major and random disagreement could appear in individual sites as an exception. Three Corneometer instruments evaluated in this study gave close measurements and correlated well. Nevertheless, pretest validation of instruments should be undertaken in multicenter studies where capacitance data are compared or pooled, and concordance among instruments should be documented prior to study.


'Fat but powerful' paradox: association of muscle power and adiposity markers with all-cause mortality in older adults from the EXERNET multicentre study.
To assess the influence of muscle power and adiposity on all-cause mortality risk and to evaluate the 'fat but powerful' (F+P) (or 'fat but fit') paradox in older adults. A total of 2563 older adults (65‒91 years old) from the EXERNET multicentre study were included. Adiposity (body mass index (BMI), waist circumference, body fat percentage (BF%) and fat index), allometric and relative power (sit-to-stand muscle power test) and various covariates (age, sex, hypertension, smoking status and walking and sitting times per day) were registered at baseline. All-cause mortality was recorded during a median follow-up of 8.9 years. Participants were classified into four groups: lean and powerful (L+P), F+P, lean but weak and fat and weak (F+W). Cox proportional hazard regression models and adjusted HRs were calculated. According to BMI and waist circumference, all-cause mortality risk was reduced in the F+P (HR=0.55 and 0.63, p=0.044 and 0.049, respectively) and L+P (HR=0.57 and 0.58, p=0.043 and 0.025, respectively) groups. According to BF%, all-cause mortality decreased in the L+P group (HR=0.53; p=0.021), and a trend for a reduction was reported in the F+P group (HR=0.57; p=0.060). According to fat index, a survival benefit was only noted in the L+P group (HR=0.50; p=0.049). Higher levels of relative power reduced all-cause mortality risk among older people (HR=0.63 and 0.53, p=0.006 and 0.011, respectively). Powerful older people exhibited a reduced 9-year all-cause mortality regardless of BMI, waist circumference and BF%. Obesity according to fat index blunted the survival benefits of being powerful.


Nuclease protection analysis of ribonucleoprotein complexes: use of the cytotoxic ribonuclease alpha-sarcin to determine the binding sites for Escherichia coli ribosomal proteins L5, L18, and L25 on 5S rRNA.
A rapid and convenient method has been devised to determine the binding sites for proteins on RNA. The procedure is an adaptation of one used to map DNA-protein complexes by protection against nuclease digestion. The method uses the cytotoxic ribonuclease alpha-sarcin, which hydrolyzes purines in both single- and double-stranded regions of RNA. It has been authenticated by confirming the binding sites for the Escherichia coli ribosomal proteins L18 and L25 on 5S rRNA and its value has been established by identifying the attachment site for protein L5. The procedure should be useful for the analysis of other ribonucleoprotein complexes.


The properties of reticular thalamic neuron GABA(A) IPSCs of absence epilepsy rats lead to enhanced network excitability.
Both human investigations and studies in animal models have suggested that abnormalities in GABA(A) receptor function have a potential role in the pathophysiology of absence seizures. Recently we showed that, prior to seizure onset, GABA(A) IPSCs in thalamic reticular (NRT) neurons of genetic absence epilepsy rats from Strasbourg (GAERS) had a 25% larger amplitude, a 40% faster decay and a 45% smaller paired-pulse depression than those of nonepileptic control (NEC) rats. By means of a novel mathematical description, the properties of both GAERS and NEC GABAergic synapses can be mimicked. These model synapses were then used in an NRT network model in order to investigate their potential impact on the neuronal firing patterns. Compared to NEC, GAERS NRT neurons show an overall increase in excitability and a higher frequency and regularity of firing in response to periodic input signals. Moreover, in response to randomly distributed stimuli, the GAERS but not the NEC model produces resonance between 7 and 9 Hz, the frequency range of spike-wave discharges in GAERS. The implications of these results for the epileptogenesis of absence seizures are discussed.


Meniscus transplantation.
Understanding the structure and function of the meniscus is critical to understanding its role in overall knee joint function. Injury to, or removal of, meniscal tissue may be associated with articular cartilage wear, knee instability, and, ultimately, the progression of osteoarthritis. While every effort is made for preserving and/or repairing damaged meniscal tissue, in some cases, the meniscus is not amenable to repair after injury. For appropriately indicated patients with symptomatic meniscal deficiency, meniscus allograft transplantation is an excellent surgical solution aimed at reducing pain and improving function. Indications for meniscus allograft transplantation are limited, and concomitant procedures such as osteotomy for malalignment, ligamentous, and/or articular cartilage restoration may be necessary in order to ensure an optimal result following meniscus allograft transplantation. Surgical techniques for meniscus allograft transplantation are variable and include soft-tissue fixation versus bone plug fixation versus bone bridge fixation. Outcomes following meniscus allograft transplantation are generally good to excellent, though reoperation rates are relatively high. The purpose of this article is to provide a concise review of recently published data on meniscus allograft transplantation, with a focus on recent outcomes studies.


Update on mitochondria and muscle aging: all wrong roads lead to sarcopenia.
Sarcopenia is a well-known geriatric syndrome that has been endorsed over the years as a biomarker allowing for the discrimination, at a clinical level, of biological from chronological age. Multiple candidate mechanisms have been linked to muscle degeneration during sarcopenia. Among them, there is wide consensus on the central role played by the loss of mitochondrial integrity in myocytes, secondary to dysfunctional quality control mechanisms. Indeed, mitochondria establish direct or indirect contacts with other cellular components (e.g. endoplasmic reticulum, peroxisomes, lysosomes/vacuoles) as well as the extracellular environment through the release of several biomolecules. The functional implications of these interactions in the context of muscle physiology and sarcopenia are not yet fully appreciated and represent a promising area of investigation. Here, we present an overview of recent findings concerning the interrelation between mitochondrial quality control processes, inflammation and the metabolic regulation of muscle mass in the pathogenesis of sarcopenia highlighting those pathways that may be exploited for developing preventive and therapeutic interventions against muscle aging.


Quality assurance in neuropathology: Experiences from the round robin trials on IDH mutation and MGMT promoter methylation testing launched by the Quality Assurance Initiative Pathology (QuIP) in 2018 and 2019.
We here report on the first neuropathological round robin trials initiated by the Quality Assurance Initiative Pathology (QuIP) in Germany in the years 2018 and 2019. Testing services as external laboratory controls were offered for IDH1-R132H immunohistochemistry in 2018 followed by a molecular trial for IDH1 and IDH2 mutations in 2019 including the rare mutational variants. Also in 2019, a trial on MGMT promoter methylation testing was offered. On a national scale, trial offers were well received with around 40 participating institutions. The international announcement of the molecular IDH1/IDH2 mutational trial achieved only moderate European outspread. Success rates in all three trials were excellent (IDH1-R132H immunohistochemistry 2018: 94%, 18 out of 20 possible points required; IDH1/IDH2 mutational status 2019: 100%, 19 out of 20 possible points required; MGMT promoter methylation 2019: 94%, 19 out of 20 possible points required) indicating that quality standards are high in the broad majority of the institutions. Trial participation also involved filling in a questionnaire asking for background information on local testing procedures. We here present a first assessment of the information collected providing unique insights in the landscape of molecular testing in neuropathology. Derived from this information we identify future challenges and provide an outlook on the development of quality assurance in the field of neuropathology.


Thymoma and cellular immune deficiency in an adolescent.
Thymoma has been associated with both humoral immunodeficiency and cellular immunodeficiency, but the latter association has never been described in the pediatric age group. We report a 15-year-old female with thymoma, recalcitrant oropharyngeal candidiasis, recurrent generalized cutaneous herpes simplex virus type 2 infection, recurrent pneumonia and myasthenia gravis. Pathology of the thymic lesion showed a 10x5x6 cm extensively hyalinized mass with residual regions of spindle cell predominant and lymphocyte-rich thymoma. There was no evidence of humoral immunodeficiency but there was clinical and laboratory evidence of cellular immunodeficiency with cutaneous anergy and absence of T cell proliferation to Candida antigen. Six weeks after the thymoma was resected, she was no longer anergic and Candida proliferation was normal, although she continued to experience infections. This is the first reported pediatric patient with an association of cellular immunodeficiency with thymoma.


New approach to diagnosis and treatment of Acanthamoeba keratitis--systematic review of literature.
To present new methods of diagnosis and treatment of Acanthamoeba keratitis. Searching Medline base for articles in English publicated since 2006 till the beginning of 2011, describing the way and results of diagnosis and treatment Acanthamoeba keratitis. Publications include studies, reviews as well as case reports concerning discussed subject. 14 publications were found and used to present miscellaneous methods utilized nowadays to identify the reason of Acanthamoeba keratitis with simultaneous evaluations of its' sensitivity and specificity. The review comprises improvements of laboratory diagnosis as well as corneal imaging systems helpful to diagnose infectious keratitis. 17 publications were quoted to elaborate results of pharmacological protocols as well as surgical procedures of Acanthamoeba keratitis treatment. Outcomes of experimental investigations were also cited. As none of presented methods of diagnosis and treatment of Acanthamoeba keratitis have become a standardized guideline jet, still there is a great need to look for new ones.


Heme-induced biomarkers associated with red meat promotion of colon cancer are not modulated by the intake of nitrite.
Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer. We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats.


Naming Faces and Objects Without Comprehension A Case Study.
The case of a 74-year-old woman with Alzheimer's dementia is presented. Her ability to identify objects and faces was investigated, and it was shown that an item's name could sometimes be recalled in the absence of any appropriate semantic information. Performance on multiple-choice tests of semantic knowledge for items that were named was not above chance levels, even though the semantic test immediately followed the naming response. These data appear problematic for current models of face and object processing, where access to a name is dependent upon prior access to information about the identity of the item. However, in the trials where the patient named faces without category information, she appeared to know that the people were celebrities, which suggests that this limited information may allow access to the name and that the degree of semantic access required when naming faces is lower than previously thought.


The Program Evaluation and Monitoring System: a key source of data for monitoring evidence-based HIV prevention program processes and outcomes.
The Centers for Disease Control and Prevention (CDC) Division of HIV/AIDS Prevention (DHAP) has responded to the need for accurate and timely data to monitor and evaluate federally funded HIV prevention programs by designing and implementing the Program Evaluation and Monitoring System (PEMS). PEMS is a national data reporting system that includes a standardized set of HIV prevention data variables, Web-based software for data entry and management, data collection and evaluation guidance and training, and software implementation support services. This article discusses the purposes of evaluation and the need for and development of PEMS and also describes how PEMS strengthens the monitoring and evaluation of HIV prevention services nationally and program planning, management, and monitoring locally. PEMS data may be used by prevention stakeholders at all levels to examine program fidelity, adaptation and tailoring, and key program health service utilization and behavioral outcomes. PEMS provides a strong foundation to bring a program closer to its intended goals and to serve the needs of the clients and the community, provides a means for agencies to fulfill their reporting mandates and funding obligations, and enables the CDC to monitor HIV prevention efforts in a consistent, efficient, and effective manner across the United States.


Post-traumatic pulmonary insufficiency following chest trauma: identification and prophylaxis.
Post-traumatic pulmonary insufficiency is a syndrome characterized by tachypnea, increasing respiratory effort, progressive pulmonary infiltrates and relentless progressive hypoxemia. Prophylaxis of this syndrome currently comprises adequate treatment and depends upon its early recognition by frequent monitoring of blood gases, chest radiograph, and determination of values of circulatory variables. Once the syndrome is recognized in its early stages, artificial ventilation, with the possible addition of positive end-expiratory pressure, meticulous fluid therapy properly monitored, and prevention of infection constitute the hallmark of treatment.


The formation of CuCl2-specific metallogels of pyridyloxalamide derivatives in alcohols.
Isomeric pyridyloxalamide derivatives 1-3, which differed in the position of the nitrogen atom on the pyridyl ring, showed remarkably different gel-forming aptitudes in the presence of CuCl2 salt in alcohols. Whilst derivatives 1 and 3 formed a soluble complex and a solid precipitate, respectively, ligand 2 generated a remarkably metal- and anion-specific metallogel.


Hemoglobin adsorption to silica monitored with polarization-dependent evanescent-wave cavity ring-down spectroscopy.
Evanescent-wave cavity ring-down spectroscopy was used to monitor the adsorption of human hemoglobin to a fused-silica surface from aqueous solution. An uncoated dove prism was situated in a ring-down cavity such that the beam entered and exited with a normal-incidence geometry. This afforded ring-down times as high as 5 mus and values of sigma(tau)/tau as low as 0.3%. Normal-incidence geometry permits the detection of both S- and P-polarized light, yielding some information of the orientation of adsorbates. The orientation of the adsorbed hemoglobin molecules is found to change as adsorption progresses, but with a different time profile than adsorption itself. The adsorption kinetics from a quiescent solution is consistent with a reaction-diffusion model that includes both reversible and irreversible adsorption operating in parallel. Systems behaving according to this model also seem to display adsorption isotherms, although the increased adsorption from more concentrated solutions is only a consequence of the system being under kinetic control. In some cases, this may be sufficient to explain the paradox of protein adsorption systems which seem to be both irreversible and consistent with isotherm models as well.


Exploration of the form factors of turbulence kinetic energy transfer for shear exfoliation of graphene.
Mass production of defect-free and large-lateral-size 2D materials via cost-effective methods is very important. Recently, shear exfoliation has shown great promise for large-scale production due to its simple operation, environmental-benignity and wide adaptability. However, a long-standing challenge is that with the production of more nanosheets, a ceiling yield and shattered products are encountered, which significantly limits their wider application. The method and efficiency of energy transfer in fluid is undoubtedly the key point in determining exfoliation efficiency, yet its in-depth mechanism has not yet been described. Thus, a thorough investigation of turbulence energy transfer is critically necessary. Herein, we identify two main factors that critically determine the exfoliation yield and provide a statistical analysis of the relationship between these factors and the exfoliation yield. In the initial shearing process, the coexistence of the 2D nanosheets and raw particles is the dominant factor; as time passes, the dimensional change of raw materials gradually has a greater influence on the energy transfer. These factors together lead to attenuated efficiency and a power function relationship between yield and exfoliation time. This investigation gives a statistical explanation of shear exfoliation technology for 2D material preparation and provides valuable insights for mechanical exfoliating high-quality 2D materials.


Characterization of an immunodeficient mouse model of mucopolysaccharidosis type I suitable for preclinical testing of human stem cell and gene therapy.
Mucopolysaccharidosis type I (MPS-I or Hurler syndrome) is an inherited deficiency of the lysosomal glycosaminoglycan (GAG)-degrading enzyme alpha-l-iduronidase (IDUA) in which GAG accumulation causes progressive multi-system dysfunction and death. Early allogeneic hematopoietic stem cell transplantation (HSCT) ameliorates clinical features and extends life but is not available to all patients, and inadequately corrects its most devastating features including mental retardation and skeletal deformities. To test novel therapies, we characterized an immunodeficient MPS-I mouse model less likely to develop immune reactions to transplanted human or gene-corrected cells or secreted IDUA. In the liver, spleen, heart, lung, kidney and brain of NOD/SCID/MPS-I mice IDUA was undetectable, and reduced to half in heterozygotes. MPS-I mice developed marked GAG accumulation (3-38-fold) in these organs. Neuropathological examination showed GM(3) ganglioside accumulation in the striatum, cerebral peduncles, cerebellum and ventral brainstem of MPS-I mice. Urinary GAG excretion (6.5-fold higher in MPS-I mice) provided a non-invasive and reliable method suitable for serially following the biochemical efficacy of therapeutic interventions. We identified and validated using rigorous biostatistical methods, a highly reproducible method for evaluating sensorimotor function and motor skills development. This Rotarod test revealed marked abnormalities in sensorimotor integration involving the cerebellum, striatum, proprioceptive pathways, motor cortex, and in acquisition of motor coordination. NOD/SCID/MPS-I mice exhibit many of the clinical, skeletal, pathological and behavioral abnormalities of human MPS-I, and provide an extremely suitable animal model for assessing the systemic and neurological effects of human stem cell transplantation and gene therapeutic approaches, using the above techniques to measure efficacy.


Incontinence in a child with a duplex kidney: case report.
Persistent incontinence after toilet training in young girls and urinary tract infections or epididymitis in prepubertal boys should raise suspicion of an ectopic ureter. This often occurs in the context of duplication of kidney structures or other parenchymal abnormalities. The presence or absence of reflux affects surgical treatment, which may consist of ureteral reimplantation, ureteroureterostomy, and/or upper pole nephrectomy.


Clinical assessment and management of patients with multimorbidity.
Internal medicine specialists, also known as general internal medicine specialists are specialist physicians trained to manage particularly complex or multisystem disease conditions that single-organ-disease specialists may not be trained to deal with. The management of multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience in appropriate diagnostic and therapeutic procedures. Multimorbidity is associated with a decline in many aspects of health and in consequence with an increase in hospital admissions, polypharmacy, and use of health care and social resouces. When prescribing medicine to patients with multimorbidity, all the risks and benefits, as well as possible interactions should be carefully considered. The prescription appropriateness can be assessed by validated tools like STOPP-START criteria. Beneficial part of good prescribing is deprescribing - planned and supervised process of dose reduction or withdrawal of medications that are no longer needed in the circumstances of the patient.


[Value of reoperation after local resection of thyroid cancer].
To evaluate the rate of residual disease in the thyroid gland and rate of cervical lymph node metastasis after preliminary local resections in thyroid cancer. From 1994 - 1999, 160 thyroid cancer patients who had previously been treated with nodulectomy or subtotal lobectomy in other hospitals were reoperated. The rate of residual disease at the primary site was 42.5%. The lymph node metastatic rate at level VI was 28.1%. The rate of lymph node metastasis in those with enlarged lymph nodes in the ipsilateral internal jugular chain was 35.4%. The rate of laryngeal recurrent nerve injury was 12.5% at the first operation which is much higher than that of the second operation (1.9%). Because of the high rate of local residual disease, nodulectomy or subtotal lobectomy alone is not indicated for thyroid cancer. The exploration to level VI is needed for thyroid cancer. It is of utmost importance to be familiar with laryngeal recurrent nerve anatomy in thyroid surgery.


Chromium supplementation can alleviate negative effects of heat stress on egg production, egg quality and some serum metabolites of laying Japanese quail.
This study was conducted to determine the effects of Cr (chromium picolinate, CrPic) supplementation at various levels (0, 200, 400, 800 or 1200 microg/kg of diet) on egg production, egg quality and serum concentrations of insulin, corticosterone and glucose in laying Japanese quail (Coturnix coturnix japanica) reared under conditions of heat stress (32.5 degrees C). Laying Japanese quail (n = 150; 45 d old) were divided into five groups of 30 birds. The quail were fed either a control diet containing 965 microg Cr/kg diet or the control diet supplemented with 200, 400, 800 or 1200 microg of Cr/kg diet. Increased supplemental chromium increased body weight (P = 0.05, linear), feed intake (P = 0.05, linear), egg production (P = 0.01, linear) and also improved feed efficiency (P = 0.01, linear). Increased supplemental chromium linearly increased egg weight (P = 0.01), eggshell thickness, egg specific gravity (P = 0.05) and Haugh unit (P = 0.01). Serum insulin concentration increased linearly (P = 0.01), whereas corticosterone and glucose concentration decreased linearly (P = 0.05) as dietary chromium increased. The best results were obtained with 1200 microg Cr/kg diet, and chromium supplementation at such a level can be considered to be protective management practice in a quail diet, reducing the negative effects of heat stress.


Intramolecular hole-transfer in protonated anthracene.
Excitation spectra of protonated and deuteronated anthracene are obtained by triple-resonance dissociation spectroscopy. Very cold cations, protonated/deuteronated exclusively at the 9-position, are generated from two-colour two-photon threshold ionisation of 9-dihydroanthracenyl radicals (C14H11). The excitation spectra reveal rich structure, not resolved in previous studies, that is assigned based on anharmonic and Herzberg-Teller coupling calculations. This work reveals that the excitation of protonated anthracene induces a symmetry-breaking intramolecular charge-transfer process along a Marcus-Hush coordinate, where the positively charged hole hops from the central bridging sp2 carbon, onto one of the aromatic rings. Signatures of this charge-transfer event are observed in the excitation spectrum, through active Herzberg-Teller progressions.


Combined experimental and theoretical study on photoionization cross sections of benzonitrile and o/m/p-cyanotoluene.
Photoionization cross sections (PICSs) for the products of the reaction from CN with toluene, including benzonitrile and o/m/p-cyanotoluene, were obtained at photon energies ranging from ionization thresholds to 14 eV by tunable synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS). Theoretical calculations based on the frozen-core Hartree-Fock approximation and Franck-Condon simulations were carried out to cross-verify the measured PICS. The results show that the photoionization cross sections of benzonitrile and cyanotoluene isomers are similar. The generalized charge decomposition analysis was used to investigate the components of the highest occupied molecular orbital (HOMO) and HOMO-1. It was found that the HOMO and HOMO-1 of benzonitrile and cyanotoluene isomers are dominated by the features of the benzene ring, indicating that the substitution of CN and methyl has a minor influence on the PICS of the studied molecules. The reported PICS on benzonitrile and cyanotoluene isomers in the present work could contribute to the near-threshold PIMS experiments and determine the ionization and dissociation rates in interstellar space for these crucial species. The theoretical analysis on characteristics of molecular orbitals provides clues to estimating the PICS of similar substituted aromatic compounds.


A pure uterine lipoma: a rare, benign entity.
A 71-year-old woman presented with a history of left loin pain and where renal calculi were clinically suspected. As part of her initial investigations, she had an ultrasound and an unenhanced CT of her abdomen. Within the body of the uterus, there was a 2.5 cm well demarcated, hyperechoic mass. The CT demonstrated a well-defined, round lesion within the uterus, of fat attenuation. The overall appearances were in keeping with a benign uterine lipoma. Uterine lipomas are rare, benign tumours that are part of a spectrum of uterine fatty tumours. Although they have characteristic imaging findings, they can be misdiagnosed and confused with more sinister neoplasms. The authors present a case of a pure uterine lipoma and discuss the imaging features on ultrasound, CT and MRI. The authors hope that highlighting the radiological characteristics of this benign entity will aid confident diagnosis and avoid unnecessary investigations or surgery in this patient population.


Are flexible designs sound?
Flexible designs allow large modifications of a design during an experiment. In particular, the sample size can be modified in response to interim data or external information. A standard flexible methodology combines such design modifications with a weighted test, which guarantees the type I error level. However, this inference violates basic inference principles. In an example with independent N(mu, 1) observations, the test rejects the null hypothesis of mu < or = 0 while the average of the observations is negative. We conclude that flexible design in its most general form with the corresponding weighted test is not valid. Several possible modifications of the flexible design methodology are discussed with a focus on alternative hypothesis tests.


Atypical Neurological Manifestation in Childhood Microscopic Polyangiitis: A Case Report and Review of Literature.
Microscopic polyangiitis (MPA), a systemic necrotizing vasculitis of small vessels, is primarily associated with necrotizing and crescentic glomerulonephritis and pulmonary capillaritis. Neurological involvement, particularly of the central nervous system (CNS) is scarcely observed. The diversity of CNS symptoms could puzzle the diagnosis causing delays in treatment and potentially having a considerable effect on patient's quality of life or even death. The aim of this case report is to highlight the unusual manifestation of MPA in order to raise awareness of this orphaned disease among pediatricians or even pediatric rheumatologists and neurologists. Herein we report the case of a 13-year-old Thai girl diagnosed with MPA presented with rapidly progressive glomerulonephritis (RPGN). Renal biopsy was performed demonstrated crescentic glomerulonephritis with negative immunofluorescence and positive titer of myeloperoxidase (MPO) antibody. Pulse methylprednisolone (MP) and cyclophosphamide (CYC) as well as plasmapheresis were initiated. Despite treatment with prednisolone (45 mg/day) and monthly CYC for two doses, she experienced a brief generalized tonic-clonic seizure during the follow-up period. The potential differential diagnosis of new-onset neurological manifestation contains infection owing to the immunocompromised status of the patient and CNS vasculitis as a result of the disease itself. Lumbar puncture was performed, and cerebrospinal fluid analysis demonstrated pleocytosis with negative infectious panel. Contrast magnetic resonance imaging studies of the brain showed multifocal patchy T2/FLAIR-hyperintense lesions in the cerebral as well as cerebellum regions, and irregular narrowing along the V4 segment of the right vertebral artery was demonstrated in magnetic resonance angiography. In the presence of CNS vasculitis, pulse MP and CYC were provided. The symptom of nervous system has progressively improved. In our case, MPA revealed RPGN with neurological manifestation. Despite the fact that it is scarcely reported, CNS vasculitis is one of the organ-threatening symptoms. To improve patient morbidity and mortality, multidisciplinary care teams with prompt diagnosis and treatment are highly recommended.


RAD6 inhibition enhances paclitaxel sensitivity of triple negative breast cancer cells by aggravating mitotic spindle damage.
Paclitaxel (PTX), a first-line therapy for triple negative breast cancers (TNBC) induces anti-tumor activity by microtubule stabilization and inhibition of cell division. Its dose-limiting toxicity and short half-life, however, pose clinical challenges underscoring the need for strategies that increase its efficiency. RAD6, a E2 ubiquitin conjugating enzyme, is associated with centrosomes at all phases of cell cycle. Constitutive overexpression of the RAD6B homolog in normal breast cells induces centrosome amplification and multipolar spindle formation, indicating its importance in centrosome regulation. TNBC centrosome numbers were scored by pericentrin immunostaining. PTX sensitivities and interactions with SMI#9, a RAD6-selective small molecule inhibitor, on TNBC cell survival were analyzed by MTT and colony forming assays and an isogenic MDA-MB-468 TNBC model of PTX resistance. The molecular mechanisms underlying PTX and SMI#9 induced cytotoxicity were determined by flow cytometry, immunoblot analysis of cyclin B1 and microtubule associated protein TAU, and dual immunofluorescence staining of TAU and α-tubulin. Our data show aberrant centrosome numbers and that PTX sensitivities are not correlated with TNBC BRCA1 status. Combining PTX with SMI#9 synergistically enhances PTX sensitivities of BRCA1 wild-type and mutant TNBC cells. Whereas SMI#9/PTX combination treatment increased cyclin B1 levels in MDA-MB-468 cells, it induced cyclin B1 loss in HCC1937 cells with accumulation of reproductively dead giant cells, a characteristic of mitotic catastrophe. Cell cycle analysis revealed drug-induced accumulation of tetraploid cells in S and G2/M phases, and robust increases in cells with 4 N DNA content in HCC1937 cells. TAU overexpression is associated with reduced PTX efficacy. Among the six TAU isoforms, both SMI#9 and PTX downregulated 1N3R TAU in MDA-MB-468 and HCC1937 cells, suggesting a common mechanism of 1N3R regulation. Dual TAU and α-tubulin immunostaining showed that SMI#9 induces monopolar mitotic spindles. Using the isogenic model of PTX resistance, we show that SMI#9 treatment restores PTX sensitivity. These data support a common mechanism of microtubule regulation by SMI#9 and PTX and suggest that combining PTX with RAD6 inhibitor may be beneficial for increasing TNBC sensitivities to PTX and alleviating toxicity. This study demonstrates a new role for RAD6 in regulating microtubule dynamics.


An evaluation of pharmacist contribution to an oncology ward in a Swedish hospital.
The aim of this project was to establish the importance of a pharmacist in the health-care team in improving drug use in an oncology ward in the Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. The pharmacist participated in the medical round in the mornings and worked as a member of the health-care team. Drug-related problems (DRPs) were identified by drug chart reviews based on data from medical files, laboratory tests and interviews with patients and/or relatives. A questionnaire to physicians and nurses was used to evaluate their experiences of the pharmacist's contribution to the oncology ward. In total, 114 DRPs were identified in 58 patients. For each DRP, the pharmacist gave proposals for solutions. Sixty-eight suggestions out of 114 (59.6%) were implemented by the physician. Two suggestions (1.8%) were partly followed. For 32 suggestions (28.0%) it was unclear if they had caused any change in medication. Twelve suggestions (10.5%) were not followed. Most of the physicians and nurses acknowledged the pharmacist's contribution to improved drug use in the ward. A pharmacist can improve drug use in an oncology ward as a member of the health-care team. The pharmacist contributes with a systematic focus on the patient from a drug perspective.


The Oral Bioavailability of 8-Prenylnaringenin from Hops (Humulus Lupulus L.) in Healthy Women and Men is Significantly Higher than that of its Positional Isomer 6-Prenylnaringenin in a Randomized Crossover Trial.
Prenylated chalcones and flavonoids from hop (Humulus lupulus L.), such as 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), are investigated for their health beneficial and anticancer activities. We, thus, compare the oral bioavailability and safety of 6-PN and 8-PN in healthy young women and men, and investigated their effects on peripheral blood mononuclear cells (PBMC). A double-blind, placebo-controlled, crossover trial is conducted with 16 healthy volunteers (eight women, eight men) given a single oral dose of 500 mg 6-PN, 8-PN, or placebo in random order. Maximum total concentrations of 6-PN and 8-PN in plasma (Cmax ; 543 and 2834 nmol L-1 ) and their respective area under the plasma concentration-time curve (AUC; 3635 and 15801 nmol L-1 × h) are significantly (5.2- and 4.3-fold) higher for 8-PN than for 6-PN (p ˂ 0.05). PBMC for ex vivo experiments are isolated from blood sampled before and 6 h after intake of 6-PN, 8-PN, or placebo. Despite the single-treatment regime and low blood concentrations, both 6-PN and 8-PN increase the survival of PBMC relative to control. 8-PN is significantly more bioavailable in healthy humans than its isomer 6-PN. Interestingly, 6-PN, despite being less bioavailable, is similarly effective as 8-PN in enhancing PBMC viability.


Interactions between four gene polymorphisms and their association with patients with Parkinson's disease in a Chinese Han population.
The four previously reported Parkinson's disease (PD)-related single-nucleotide polymorphisms (SNPs) - rs1775143, rs823114, rs2071746 and rs62063857 - have rarely been studied in Chinese Han populations. To examine the association between these SNPs and PD, we conducted a case-control study of 158 patients with PD and 210 controls. All participants were Chinese Han from Northern China. With covariate adjustment for clinical characteristics, logistic regression analysis revealed no differences in genotype or allele frequencies for the four SNPs. Stratified by age of disease onset, sex, smoking status, duration of disease, baseline UPDRS, Hoehn-Yahr Stage, PD subtypes, scores of Hamilton anxiety scale, Hamilton depression scale and activity of daily living, all of the p values did not remain significant after Bonferroni correction. However, the haplotype rs1775143T-rs823114G-rs2071746T-rs62063857A was associated with increased risk of developing PD (p = 0.003, OR = 456.88, 95% CI: 27.40-7619.75) in our case-control sample set. The haplotype rs1775143T-rs823114G-rs2071746T was also associated with increased risk of developing PD (p = 0.003, OR = 338.43, 95% CI: 20.68-5538.27). Although the haplotype rs1775143T-rs823114G-rs62063857A was associated with increased risk of PD (p = 0.03), the 95% CI was 0.993-22.469. Our data demonstrate that although specific SNPs were not related with PD patients, certain haplotypes were associated with increased risk for PD in the Chinese Han population. These results provide further evidence that the etiology of PD is multifactorial, although the underling mechanism needs further study.


PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie.
The present study investigated the relationship among PrP deposition, microglial activation, vacuolation, and neuronal death in the hippocampus of the 301V/VM murine scrapie model (mean incubation period 117 +/- 1 days). PrP deposition was first detected after 30 days and microglial activation after 60 days. Vacuolation in the CA1 and CA2 pyramidal layer was present from 90 days onward. Only occasional in situ end labeling (ISEL)-positive neurons were present in the hippocampus of scrapie-infected mice from 75 days postinoculation (d.p.i.), except at 105 d.p.i. when relatively large numbers of apoptotic, ISEL-positive neurons in the CA1 hippocampal region were observed. Terminally ill animals showed almost complete loss of CA1 pyramidal neurons. Electron microscopy of the CA1 region at 105 days confirmed that these neurons were dying by apoptosis. These data suggest that microglial activation in scrapie is a response to abnormal PrP deposition rather than a response to neuronal cell loss.


Height-Adjustable Desks: Energy Expenditure, Liking, and Preference of Sitting and Standing.
Breaking periods of sitting with standing may prevent chronic diseases and increase energy expenditure (EE). Sit-to-stand height adjustable desks may promote workplace standing, but workers have to be willing to stand for portions of the workday. For studies 1 and 2, EE was measured during word processing while sitting in a chair and while standing. Subjects scored their liking of each posture and time they would be willing to work in each posture during an 8-hour workday. Study 2 included an intervention of replacing subjects' sitting desks with a height adjustable desk. Liking of and willingness to work in each posture were measured before and after the 12-month intervention. EE was 7.5 kcal/h greater when standing than when sitting. Subjects liked sitting more than standing in study 1. In study 2, liking of postures did not differ or change across 12 months use of height adjustable desks. Perceived willingness to stand decreased from 4.5 h/d at baseline to 3.4 h/d after 12 months. Standing rather than sitting increased EE by 7.5 kcal/h. Use of a height adjustable desk for 12 months did not alter the hedonic value of standing or sitting, which is promising for long-term increases in standing.


Colo-colonic intussusception secondary to a lipomatous lesion in an asymptomatic patient.
Colo-colonic intussusception is a rare clinical condition in adults. The predominant aetiology of intussusception in adults is a pathological lead point, with malignant lesions being the most common type. Lipomas are benign tumours of adipocytes that can sometimes be difficult to diagnose without histopathological confirmation as we highlight with this case report. We report a case of an asymptomatic female patient in her 50s who presented with an intussusception due to a giant colonic lipoma. Her CT imaging showed the possibility of a low-grade liposarcomatous component or atypical lipomatous tumour component. A laparoscopic right hemicolectomy was performed due to intussusception with the possibility of leading to colonic obstruction as well as diagnostic uncertainty of the risk of malignancy. Histopathology confirmed the diagnosis of a lipomatous lesion. In cases such as this, early surgical management is appropriate to rule out malignancy and prevent emergency presentation and surgery.


Volumetric expiratory HRCT of the lung: clinical applications.
Expiratory high-resolution CT (HRCT) of the chest offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. In 2003 a clinical HRCT scan protocol was developed. It has since been used for evaluation of diffuse lung disease with suspected airway abnormalities. It provides volumetric assessment of the entire thorax at end-inspiration and at end-expiration, and allows for detailed analysis of the airway and parenchyma. It offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. This article explores its clinical applications for chronic obstructive pulmonary disease, bronchiectasis, and sarcoidosis. It concludes that standardization of image acquisition and post-processing in CT examinations will be necessary for the real application of quantitative data derived from volumetric expiratory HRCT to daily clinical medical practice.


Cross-sectional analysis of physical activity in 2-4-year-olds in England with paediatric quality of life and family expenditure on physical activity.
Many children do not meet the recommended level of daily physical activity, even with the widely acknowledged health benefits associated with being physically active. There is a need to establish factors related to physical activity in children so that public health interventions may be appropriately designed. We investigated the association between Pediatric Quality of Life Inventory (PedsQL), family expenditure on physical activity and objectively measured daily physical activity in 2-4-year-old children. Cross-sectional study with a sample of 81 UK preschool children taking part in the NAPSACC UK feasibility randomized controlled trial. Descriptive statistics are presented. We undertook Student t-tests to establish differences in physical activity by gender, age, parental education and nursery versus non-nursery days. Mixed effects linear regressions were used to model the association between minutes spent physically activity, minutes spent in moderate-to-vigorous (MVPA) physical activity and PedsQL scores (physical and psychosocial) and family expenditure on physical activity. Most children (88.9%) did not engage in the recommended 180 min daily physical activity. There was mean (SD) of 141.9 (33.1) daily minutes of physically activity and 22.2 min per day (SD = 9.9) of MVPA. Boys and older children were more physically active. Children were more active on nursery days. There was no difference in physical activity by parental education. Half of the sample parents (50.6%) spent less than £9.00 weekly on their pre-schooler's physical activity. Children within the highest tertile of PedsQL physical functioning scores had higher levels of MVPA (3.6, 95% CI: - 1.3-8.4, p-value 0.15), although confidence intervals crossed the null in the adjusted model. We found no evidence of an association between positive PedsQL psychosocial scores, or higher parental expenditure on physical activity, with the physical activity variables. Children in this sample were not meeting the recommended 180 min of daily physical activity. The 2-4-year-olds were most active on nursery days. There is no evidence of an association between better PedsQL physical scores and higher levels of MVPA. There was no evidence of an association between expenditure on physical activity and time spent physically active. Further examination in larger representative datasets is needed.


Neuroprotective effect of zinc chelator DEDTC in a zebrafish (Danio rerio) Model of Hypoxic Brain Injury.
A study was conducted using zebrafish as a model of hypoxic brain injury to investigate the potential neuroprotective effects of zinc (Zn(2+)) chelation. The accumulation of intracellular Zn(2+) is a significant causal factor of the neuronal injury, and has been implicated in cell death followed by ischemic stroke. In this study, the zebrafish was placed in the hypoxia chamber with an extremely low level of dissolved oxygen (less than 0.8 mg/L), which is similar to the conditions in a complete global ischemic stroke. Approximately 50% of zebrafish died after a short period (≈11 min) of hypoxic treatment, suggesting that this is a responsive model system for use in evaluating treatments for hypoxic brain damage. The application of DEDTC reduced intracellular Zn(2+) accumulation and produced a concentration-dependent effect by increasing the survival rate of zebrafish. Zn(2+) chelation also enhanced zebrafish tolerance for hypoxia. When the brain damages were evaluated with TTC staining, the zebrafish that were treated with DEDTC in hypoxic treatment yielded the improvement of TTC staining that was similar to the healthy zebrafish brain. The results support that rising intracellular Zn(2+) plays a critical role in the neuronal damages, and demonstrate the protective effects of Zn(2+) chelation in hypoxic-ischemic brain injury in zebrafish.


Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats.
Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the progression of ischaemic brain damage. In the present study, we investigated the effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin E(2) (PGE(2)) levels, myeloperoxidase (MPO) activity, Evans blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischaemia in the rat. Post-ischaemic treatment with nimesulide markedly reduced the increase in PGE(2) levels in the ischaemic cerebral cortex 24 h after stroke and diminished infarct size by 48% with respect to vehicle-treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischaemic episode. These studies provide the first experimental evidence that COX-2 inhibition with nimesulide is able to limit BBB disruption and leukocyte infiltration following transient focal cerebral ischaemia. Neuroprotection afforded by nimesulide is observed even when the treatment is delayed until 6 h after the onset of ischaemia, confirming a wide therapeutic window of COX-2 inhibitors in experimental stroke. On the contrary, selective inhibition of COX-1 with VAS had no significant effect on the evaluated parameters. These data suggest that COX-2 activity, but not COX-1 activity, contributes to the progression of focal ischaemic brain injury, and that the beneficial effects observed with non-selective COX inhibitors are probably associated to COX-2 rather than to COX-1 inhibition.


In vivo generation of cytotoxic T cells from epitopes displayed on peptide-based delivery vehicles.
The development of nonviral, peptide-based constructs able to elicit protective in vivo CTL responses represents a major challenge in the design of future vaccines. We report the design of branched peptide delivery vehicles, termed loligomers, that facilitate the import, processing, and presentation of CTL epitopes onto nascent MHC class I molecules. These complexes are then effectively displayed on the surface of APCs. The intracellular delivery of CTL epitopes by loligomers prolonged the expression of Ag-MHC class I complexes on the surface of APCs in comparison with free CTL epitope alone. Furthermore, the injection of CTL epitope-containing loligomers into mice led to the generation of in vivo CTL responses and the induction of autoimmune disease in an animal model. Synthetic epitope-carrying, peptide-based delivery vehicles may represent useful components to be included in the formulation of future vaccines.


Effects of digital-based interventions on muscular strength in adults: a systematic review, meta-analysis and meta-regression of randomized controlled trials with quality of evidence assessment.
In the last three decades, both medical and sports science professionals have recognized the considerable potential of digital-based interventions (DBI) to enhance the health-related outcomes of their practitioners. This study aimed to investigate the effectiveness and potential moderators of DBI on measures of muscular strength. Six databases (PubMed/MEDLINE, Web of Science, SportDiscus, Embase, Cochrane Register of Controlled Trials and Google Scholar) were searched for eligible studies up to June 2022. The GRADE, PEDRO, and TIDieR checklists were used to assess the quality of evidence, methodology, and completeness of intervention descriptions, respectively. A total of 56 studies were included in the meta-analysis (n = 2346), and participants were classified as healthy (n = 918), stroke survivors (n = 572), diagnosed with other neurological disorders (n = 683), and frail (n = 173). The DBI showed a small effect (standardized mean difference [SMD] = 0.28, 95% CI 0.21 to 0.31; p < 0.001) on strength, regardless of the type of intervention, control group, or tested body part. More specifically, while splitting the studies into different subgroups, a meta-analysis of 19 studies (n = 918) showed a small effect (SMD = 0.38, 95% CI 0.12 to 0.63; p = 0.003) on strength in the asymptomatic population. Similarly, small but positive effects of DBI were observed for stroke survivors (SMD = 0.34, 95% CI 0.13 to 0.56; p = 0.002), patients diagnosed with other neurological disorders (SMD = 0.17, 95% CI 0.03 to 0.32; p = 0.021), and the frail population (SMD = 0.25, 95% CI 0.0 to 0.5; p = 0.051). Sub-group analysis and meta-regression revealed that neither variable modified the effects of the DBI on measures of strength. Overall, DBI may serve as an effective method to improve measures of strength in adults, regardless of their health status as well as the type of digital device, the presence of human-computer interaction, and the age of participants. In addition, the DBI was found to be more effective than traditional training or rehabilitation methods.KEY MESSAGESDigital-based intervention (DBI) is effective in improving measures of muscular strength in adults regardless of participants' health statusDBIs were equally effective for strength improvements in lower and upper limbsAlthough, DBIs were found to be effective in improving muscular strength, most studies did not follow strength training guidelines when prescribing the interventions.


Degenerative lumbar spondylolisthesis: an epidemiological perspective: the Copenhagen Osteoarthritis Study.
A cross-sectional epidemiological survey of 4151 participants of the Copenhagen Osteoarthritis Study. To identify prevalences and individual risk factors for degenerative lumbar spondylolisthesis. The Copenhagen Osteoarthritis Study has registered health parameters since 1976. In 1993, standardized, lateral radiographs of the lumbar spine were recorded. There were 1533 men and 2618 women. Statistical correlations were made between degenerative spondylolisthesis, and physical, occupational, and general epidemiological data. A total of 254 cases of lumbar slip were found (males 2.7%, females 8.4%). In females, no significant relationship between age at menopause or childbirths and the presence of degenerative spondylolisthesis were found. In women, relationships between body mass index (BMI) in 1976 and L4 olisthesis (P = 0.001), and between BMI in 1993 and both L4 and L5 olisthesis were found (L4: P = 0.003; L5: P = 0.006). Lumbar lordosis was associated with degenerative spondylolisthesis in women. Occupational exposures to daily lifting or smoking were not associated with degenerative spondylolisthesis. Degenerative spondylolisthesis was associated with increased age in both sexes (L4: P < 0.001; L5: P < 0.001). BMI longitudinally and at index evaluations, age, and angle of lordosis were significantly associated with degenerative spondylolisthesis in women. In men, no individual risk factors for degenerative spondylolisthesis were found, save increased age.


Quantification and colonisation dynamics of Escherichia coli O157:H7 inoculation of microgreens species and plant growth substrates.
Microgreens are edible plants used in food preparation for their appealing flavours and colours. They are grown beyond the point of harvest of sprouted seeds, and normally include the cotyledons and first true leaves. Their method of production is similar to sprouted seeds, which is known to be favourable for growth of microbial pathogens, although there is little data on the potential of food-borne pathogens such as Shigatoxigenic Escherichia coli (STEC) to colonise these plants. We found colonisation of nine different species of microgreen plants by STEC (isolate Sakai, stx-), with high levels of growth over five days, of approximately 5 orders of magnitude, for plants propagated at 21 °C. STEC (Sakai) formed extensive colonies on external tissue, with some evidence for internalisation via stomatal pores. Several factors impacted the level of colonisation: (1) plant tissue type such that for broccoli microgreens, the highest levels of STEC (Sakai) occurred on cotyledons compared to the true leaf and hypocotyl; (2) the route of contamination such that higher levels occurred with contaminated irrigation water compared to direct seed contamination; (3) inoculation dose, although only at low levels of inoculation (3 log10) compared to medium (5 log10) or high (7 log10) levels; (4) environmental factors, including to some extent humidity, but also plant growth substrate types. It was also evident that a starvation response was induced in STEC (Sakai) in low-nutrient plant irrigation medium. Together these data show that microgreens represent a potential hazard of contamination by food-borne pathogens, and to mitigate the risk, they should be considered in the same manner as sprouted seeds.


Therapeutic angiography for giant bleeding gastro-duodenal artery pseudoaneurysm.
We present the case of an 18-year-old female transferred to our center from an outside hospital due to persistent gastrointestinal bleeding. Two weeks prior to her transfer she underwent duodenal omentopexy for a perforated duodenal peptic ulcer. The patient underwent a computed tomography angiogram which identified the source of bleeding as a giant gastro-duodenal artery (GDA) pseudoaneurysm. The patient was taken to interventional radiology where successful microcoil embolization was performed. We present this rare case of a giant GDA pseudoaneurysm together with imaging and a review of the medical literature regarding prevalence, etiology and treatment options for visceral arterial aneurysms.


Simultaneous Removal of SO2 and NO Using a Novel Method of Ultraviolet Irradiating Chlorite-Ammonia Complex.
A novel advanced oxidation process (AOP) using ultraviolet/sodium chlorite (UV/NaClO2) is developed for simultaneous removal of SO2 and NO. NH4OH, as an additive, was used to inhibit the generation of ClO2 and NO2. The removal efficiencies of SO2 and NO reached 98.7 and 99.1%. NO removal was enhanced by greater UV light intensity and shorter wavelengths but was insensitive to changes in pH and temperature. SO2 at 500-1000 mg/m3 improved NO removal, especially in the absence of UV. The coexistence of SO2 and O2 facilitated the removal of NO by ClO2-. HCO3-, Cl-, and Br- enhanced NO removal, but their roles were negligible when UV was added. The generation of ClO2 and ClO•/HO• was verified by an UV-vis spectrometer, electron spin resonance (ESR), and radical-quenching tests. The mechanisms responsible for the removal of SO2 and NO were attributed to the synergism between acid-base neutralization and radical-induced oxidation. The ClO2- evolution and product composition were demonstrated by UV-vis and X-ray photoelectron spectroscopy (XPS). Kinetics analyses showed that the Hatta numbers were 329-798 and 747-1000 without and with UV. Thus, the gas-film resistance mainly controlled the mass-transfer process.


Phosphorus-centered ion-molecule reactions: benchmark ab initio characterization of the potential energy surfaces of the X- + PH2Y [X, Y = F, Cl, Br, I] systems.
In the present work we determine the benchmark relative energies and geometries of all the relevant stationary points of the X- + PH2Y [X, Y = F, Cl, Br, I] identity and non-identity reactions using state-of-the-art electronic-structure methods. These phosphorus-centered ion-molecule reactions follow two main reaction routes: bimolecular nucleophilic substitution (SN2), leading to Y- + PH2X, and proton transfer, resulting in HX + PHY- products. The SN2 route can proceed through Walden-inversion, front-side-attack retention, and double-/multiple-inversion pathways. In addition, we also identify the following product channels: H--formation, PH2-- and PH2-formation, 1PH- and 3PH-formation, H2-formation and HY + PHX- formation. The benchmark classical relative energies are obtained by taking into account the core-correlation, scalar relativistic, and post-(T) corrections, which turn out to be necessary to reach subchemical (<1 kcal mol-1) accuracy of the results. Classical relative energies are augmented with zero-point-energy contributions to gain the benchmark adiabatic energies.


Assessment of the Nursing Quality Indicators for Reporting and Evaluation (NQuIRE) database using a data quality index.
A comprehensive data quality assessment is necessary to expand a nursing database that is designed for evaluating the impact of implementing Best Practice Guidelines (BPG) developed by the Registered Nurses' Association of Ontario (RNAO). This case report presents a method to standardize data quality assessments of the Nursing Quality Indicators for Reporting and Evaluation (NQuIRE) database by developing a data quality framework (DQF) and assessing key dimensions of the framework using a data quality index (DQI). The data quality index is a single key performance metric for assessing the quality of the database. The aims of sharing this case report are 2-fold: (1) to promote best practices for assessing data quality by developing and implementing a data quality framework and (2) to demonstrate an unprecedented method of assessing the data quality of a nursing database.


Use of monoclonal antibodies MSN-1 and B72.3 in the prediction of the natural history of endometrial hyperplasia.
Forty patients, originally diagnosed as endometrial hyperplasia, were reviewed histopathologically and evaluated for immunohistochemical staining with antibodies directed against TAG-72 and MSN-1 antigens. All patients had follow-up endometrial biospies or hysterectomies from 1 to 13 years later. The extent of regression to normal of nonhyperplastic endometrium, persistence as any type of endometrial hyperplasia, or progression to endometrial adenocarcinoma was correlated with the histologic hyperplastic subtype and immunohistochemical staining. As expected, cases of complex or atypical hyperplasia more often progressed to carcinoma than cases of simple or no hyperplasia. Interestingly, MSN-1 positivity was more prevalent in cases of higher grades than lower grades of hyperplasia and was associated with the tendency to show persistent hyperplasia or progression to carcinoma. B72.3 positivity was uncommon in the hyperplastic endometrium and was not correlated with clinical regression or progression. Although the tendency for progression of endometrial hyperplasia to endometrial carcinoma is best judged histologically, MSN-1 may add prognostic information in subgroups of hyperplasia.


Studies on the constituents from the aerial part of Baccharis dracunculifolia DC. II.
Ten new glycosides were obtained along with five known compounds from the aerial part of Baccharis dracunculifolia DC. (Compositae). The structures of these glycosides were determined based on spectral and chemical evidence. These new compounds consisted of beta-D-glucopyranose or beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranose, and most possessed an (E)-caffeoyl group the same as dracunculifosides A-J.


[Hospital infection and its countermove].
Actual activities of Infection Control Team (ICT) in Suzuka General Hospital is reported. Surveillance of hospital infection, feedback of actual information of infection to each fields and ward round by ICT with certified Infection Control Nurse (ICN) can lead good confidence between ICT and other departments. Participation of ICN for ICT is important due to its trans-department activities.


In- and out-hospital mortality rate in surgical patients.
Death rates after surgery are increasingly analysed for clinical audit and quality assessment. Many studies commonly provide information only on deaths that occur during hospital stay, known as in-hospital death rates. By using hospital data set linked to death certificate registry, we recorded in- and out-hospital deaths within 30 and 60 post-operative days. The study included all consecutive surgical procedures (denominator) under general or locoregional anaesthesia in adult patients admitted for elective or non-elective inpatient surgery. Patients undergoing planned day-case surgery or obstetrical procedures were excluded. The primary outcome was 30- and 60-day post-operative mortality rate (numerator) whether before or after discharge. The study material consisted of a sample of 36,494 surgical procedures corresponding to 28,202 patients. At 30-day, 384 (crude mortality rate of 1.1%) patients died, 314 (82%) during their hospitalisation and 70 (18%) after discharge. Factors that were associated with in-hospital mortality are ASA scores, emergency, duration of surgery and rate of admission to critical care unit. Within the 30-60 days interval, we recorded 231 supplemental deaths, 103 (45%) after discharge. In-hospital mortality alone is an incomplete measure of mortality even within 30 days of care. To identify the missing deaths, hospital records need to be linked to data from death certificate. This connection with the national death registry will allow obtaining the rate of in-hospital and out-hospital death.


Frequent hereditable shutdown of murine retrovirus gene expression in murine cell lines.
Friend spleen focus-forming virus shuts down its gene expression frequently (ca. 10(-3) per generation) in a cis-dominant hereditable fashion in various murine cells but much less frequently in rat cells (less than 10(-6) per generation). Thus, nonexpresser variants were isolated at high frequency from murine cell lines by immunoselection directed against virus-encoded cell surface glycoproteins and also simply by subcloning cells from lines which had been cultured for many generations. Studies of independently infected cell clones indicate that shutdown is a property of the cell line rather than of the specific proviral site. Nucleic acid blot analyses suggest that shutdown correlates with decreased transcription. Moreover, preliminary evidence indicates that other murine retroviruses also shut down frequently in murine but not in rat cells and that shutdown of replication-competent murine leukemia viruses with accompanying loss in interference to superinfection may be the rate-limiting reaction enabling cells to acquire multiple proviruses in their chromosomes. High-frequency shutdown in vivo would have important pathological consequences.


An assessment of fetal loss among currently married women in India.
The present paper assesses fetal loss among currently married women in India. In addition, the effects of social, economic, demographic and health factors on fetal loss are studied. The study uses data from the second National Family Health Survey conducted in India during 1998-2000. The results show wide variations in fetal loss (induced abortion, spontaneous abortion and still-birth) measures across the country. The importance of mother's nutritional status, birth spacing, risky behaviours such as smoking, drinking and chewing tobacco and age at marriage for pregnancy outcomes in India is also discussed. The study results imply a broad understanding of reproductive health in India, and emphasize the importance of widening the scope of community-based reproductive health education programmes to improve the reproductive health of women.


Intermolecular interactions in weak donor-acceptor complexes from symmetry-adapted perturbation and coupled-cluster theory: tetracyanoethylene-benzene and tetracyanoethylene-p-xylene.
The interactions in the complexes of tetracyanothylene (TCNE) with benzene and p-xylene, often classified as weak electron donor-acceptor (EDA) complexes, are investigated by a range of quantum chemical methods including intermolecular perturbation theory at the DFT-SAPT (symmetry-adapted perturbation theory combined with density functional theory) level and explicitly correlated coupled-cluster theory at the CCSD(T)-F12 level. The DFT-SAPT interaction energies for TCNE-benzene and TCNE-p-xylene are estimated to be -35.7 and -44.9 kJ mol(-1), respectively, at the complete basis set limit. The best estimates for the CCSD(T) interaction energy are -37.5 and -46.0 kJ mol(-1), respectively. It is shown that the second-order dispersion term provides the most important attractive contribution to the interaction energy, followed by the first-order electrostatic term. The sum of second- and higher-order induction and exchange-induction energies is found to provide nearly 40 % of the total interaction energy. After addition of vibrational, rigid-rotor, and translational contributions, the computed internal energy changes on complex formation approach results from gas-phase spectrophotometry at elevated temperatures within experimental uncertainties, while the corresponding entropy changes differ substantially.


Diverticular Disease and Colorectal Neoplasms: Association between Left Sided Diverticular Disease with Colorectal Cancers and Right Sided with Colonic Polyps.
Both colorectal cancer (CRC) and diverticular disease (DD) are common in the affluent West, and their prevalence is also increasing in the rest of the world with economic development. Both diseases have common epidemiologic characteristics; increasing incidence, more common with advancing age and related to specific dietary changes. However, studies of associations between the two have generated mixed results with some showing positive correlations, whilst others have shown no or negative links. Most of these studies have been from the West with study populations that were predominantly Caucasians. Here the focus was on DD and colorectal neoplasms, including CRC, in Brunei. All patients who had undergone complete colonoscopy between 2011 and 2014 were identified and retrospectively reviewed. Patients under the age of 18 years old or had previous colonic surgeries (including previous CRC resection) were excluded. The total number of colonoscopies included in the study was 2,766 (mean age 53.2±14.8 years old, male 51.8%), of which DD, CRC and colonic polyps were detected in 17.3%, 4.7% and 28.2% respectively. The proportions of DD, polyps and CRC increased proportionally with age (<30 years, 30-49, 50-69 and ≥70). Overall, there was no association between the presence of DD and CRC (3.6% vs. 5.0%, p=0.179) but there was a significant association between CRC and left sided DD (p=0.034 by trend). There were also a significant association between presence of DD and polyps (36.1% vs. 28.2%, p=0.001), in particular with right-sided and pan-DD (p=0.001 for trend). Our study showed that the prevalence of DD, CRC and polyps increases with age. There were significant associations between presence of left-sided DD with CRC and right-sided or pan-DD with colonic polyps. This suggests shared risk factors. Further studies are required to assess links in other countries of the Asian Pacific region.


An Efficient Greedy Search Algorithm for High-dimensional Linear Discriminant Analysis.
High-dimensional classification is an important statistical problem that has applications in many areas. One widely used classifier is the Linear Discriminant Analysis (LDA). In recent years, many regularized LDA classifiers have been proposed to solve the problem of high-dimensional classification. However, these methods rely on inverting a large matrix or solving large-scale optimization problems to render classification rules-methods that are computationally prohibitive when the dimension is ultra-high. With the emergence of big data, it is increasingly important to develop more efficient algorithms to solve the high-dimensional LDA problem. In this paper, we propose an efficient greedy search algorithm that depends solely on closed-form formulae to learn a high-dimensional LDA rule. We establish theoretical guarantee of its statistical properties in terms of variable selection and error rate consistency; in addition, we provide an explicit interpretation of the extra information brought by an additional feature in a LDA problem under some mild distributional assumptions. We demonstrate that this new algorithm drastically improves computational speed compared with other high-dimensional LDA methods, while maintaining comparable or even better classification performance.


Hippocampal serotonin responses in short and long attack latency mice.
Short and long attack latency mice, which are selected based on their offensive behaviour in a resident-intruder model, differ in their neuroendocrine regulation as well as in aspects of their brain serotonin system. Previous studies showed that the binding capacity and expression of serotonin-1A receptors in the hippocampal CA1 field of long attack latency mice are significantly lower than that found in short attack latency mice. We tested whether the functional responses of CA1 hippocampal cells to serotonin are also reduced in long attack latency mice. To this end, serotonin-induced changes in the membrane potential and input resistance were recorded in vitro with microelectrodes in CA1 pyramidal neurones of long and short attack latency mice. The data show that in long attack latency mice, along with a reduction of the serotonin-1A receptor mRNA expression, the serotonin-induced membrane hyperpolarization and decrease in resistance are attenuated. Basal membrane properties of CA1 neurones in the two.mice lines were comparable. Plasma corticosterone levels in response to a novelty stress were elevated in long compared to short attack latency mice and inversely related to the serotonin-induced responses. We tentatively conclude that long attack latency mice show attenuated functional responses to serotonin in the hippocampus, possibly linked to a chronic perturbation of hormonal levels.


Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection.
The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log10 IU/mL (DBS) and 0.3 log10 IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values. IMPORTANCE Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.


Tissue metabolic profiling shows that saccharopine accumulates during renal ischemic-reperfusion injury, while kynurenine and itaconate accumulate in renal allograft rejection.
To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 min warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.


[Determination of myelin basic protein in the cerebrospinal fluid in neurologic diseases].
Myelin basic protein (BP) is a specific constituent of the myelin sheath. This structural protein cannot be detected in the cerebrospinal fluid (CSF) unless myelin is acutely degraded. In order to detect active demyelinating diseases, BP was measured in CSF samples of radioimmunoassay. The assay is specific and sensitive to as little as 1.5 to 2.5 ng/ml BP. A moderate non-parallelism between the standard curve and various dilutions of CSF samples indicates that in CSF BP is present in an altered state. Over 1000 CSF samples have been measured in a double-blind study, in which 100 patients were selected and their clinical records evaluated. Twenty-eight patients without demyelinating disease had BP levels lower than 2.5 ng/ml. 72 patients had values higher than 2.5 ng/ml. Among them, the most frequent causes of demyelination were multiple sclerosis (19 cases), brain tumors (22 cases) and cerebral or spinal vascular accidents (12 cases). During a single acute demyelinating episode, BP levels revert to background levels within a few days. In contrast to immunological anomalies observed in the CSF, the presence of BP is concomitant with the breakdown of myelin. The size and location of the lesion influence the level of BP in the CSF. Thus, the assay is useful for the detection of active demyelination in the central nervous system and in following the course of the disease, although normal values do not rule out the presence of demyelinating lesions. For the time being, therefore, this assay should be restricted to specialized neurological centers and selected patients.


ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice.
Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins affects Salmonella pathogenesis. Here we leveraged a candidate cellular GWAS screen to identify natural genetic variation in the ARHGEF26 (Rho Guanine Nucleotide Exchange Factor 26) gene that renders lymphoblastoid cells susceptible to Salmonella Typhi and Typhimurium invasion. Experimental follow-up redefined ARHGEF26's role in Salmonella epithelial cell infection. Specifically, we identified complex serovar-by-host interactions whereby ARHGEF26 stimulation of S. Typhi and S. Typhimurium invasion into host cells varied in magnitude and effector-dependence based on host cell type. While ARHGEF26 regulated SopB- and SopE-mediated S. Typhi (but not S. Typhimurium) infection of HeLa cells, the largest effect of ARHGEF26 was observed with S. Typhimurium in polarized MDCK cells through a SopB- and SopE2-independent mechanism. In both cell types, knockdown of the ARHGEF26-associated protein DLG1 resulted in a similar phenotype and serovar specificity. Importantly, we show that ARHGEF26 plays a critical role in S. Typhimurium pathogenesis by contributing to bacterial burden in the enteric fever murine model, as well as inflammation in the colitis infection model. In the enteric fever model, SopB and SopE2 are required for the effects of Arhgef26 deletion on bacterial burden, and the impact of sopB and sopE2 deletion in turn required ARHGEF26. In contrast, SopB and SopE2 were not required for the impacts of Arhgef26 deletion on colitis. A role for ARHGEF26 on inflammation was also seen in cells, as knockdown reduced IL-8 production in HeLa cells. Together, these data reveal pleiotropic roles for ARHGEF26 during infection and highlight that many of the interactions that occur during infection that are thought to be well understood likely have underappreciated complexity.