The impact of the belgian workers' compensation system on return to work after rotator cuff surgery.
We retrospectively assessed time off work after rotator cuff repair, in relation with the compensation system and the shoulder loading demand at work. The Belgian insurance system distinghuises three main financial compensation systems for time off work. Patients with a work-related accident receive the highest compensation. A second group includes employees suffering a private accident or a chronic rotator cuff tear. Self-employed workers receive the lowest compensation. Work-demand on the shoulder was graded level I to IV according to the Iannotti classification. From a series of 201 young patients who underwent rotator cuff tear surgery, 93 were selected based on specific inclusion criteria; of these 93 patients, 73 could be thoroughly investigated. We found a significantly longer postoperative time off work in the highest compensation group (7 months versus 2.5 months for the lowest compensation group). We found a significantly longer postoperative time to return to work in the higher stages of the Iannoti classification. Based on the results of this study, the probable postoperative absence from work can be roughly estimated for each patient after rotator cuff surgery in relation with the particular compensation system and particular occupational demand level.


[Pathophysiology of infectious diseases in immunosuppressive therapy (author's transl)].
The frequency and the nature of infections due to immunosuppressive therapy is well established now, but the pathophysiology of these infections is not very well known. Immunosuppressive effect itself, other secondary effects, and frequently the preexisting disease, decrease host resistance to infection. With some examples, it is attempted to link the nature of infectious diseases observed in the immunosuppressive therapy, to the effect of these drugs on host resistance to infections. The decrease of antiinfectious cellular immunity is one of the more important factors which may explain the frequency and severity of infectious diseases in these conditions.


A critical assessment of two real-time PCR assays targeting the (SSU) rRNA and gdh genes for the molecular identification of Giardia intestinalis in a clinical laboratory.
Giardiasis is an intestinal diarrhoeal illness caused by the flagellate protozoan parasite Giardia intestinalis. Molecular techniques for the identification of G. intestinalis have generally been shown to offer a better detection rate of the parasite than the traditional faecal concentration and microscopy techniques. The aim of this study was to critically assess the performance of a commercial and a published real-time PCR assay for their potential use as frontline tests for the diagnosis of giardiasis. A composite reference standard of enzyme immunoassay and rapid membrane test was used in a diagnostic accuracy study to assess the performance of Primerdesign's, and Verweij et al G. intestinalis real-time PCR assays, comparing them with the traditional ova, cysts and parasite microscopy test (OCP-M). The Verweij real-time PCR used primers for the (SSU) rRNA gene, and produced a diagnostic sensitivity of 93.4% (95% CI 88.30% to 98.50%) and an efficiency of 100%. Primerdesign's real-time PCR used primers for the glutamate dehydrogenase gene and produced a diagnostic sensitivity of 61.5% (95% CI 51.50% to 71.50%) and an efficiency of 203%. The OCP-M sensitivity was 83.5% (95% CI 75.87% to 91.13%). The Verweij real-time PCR was robust and the most sensitive assay suited for use as a first-line diagnostic test for giardiasis.


The utilisation of vascular limb salvage services in the assessment and management of chronic limb-threatening ischaemia and diabetic foot ulceration: A systematic review.
Specialist vascular limb salvage services have gained prominence as a new model of care to help overcome barriers which exist in the management of patients with chronic limb-threatening ischaemia (CLTI) and/or diabetic foot ulceration (DFU). This systematic review aims to explore the nature of reported services, investigate their outcome in the management of CLTI/DFU, and assess the scope and quality of the evidence base to help make recommendations for future practice and research. A systematic search of MEDLINE, Embase, The Cochrane Library, Scopus and CINAHL, from 1st January 1995 to 18th January 2019, was performed. Specialist vascular limb salvage services were defined as those services conforming to the definition of "centres of excellence" within the 2019 Global Vascular Guidelines. A study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019123325). In total, 2260 articles were screened, with 12 articles (describing 11 services) included in a narrative synthesis. All services ran akin to the "toe-and-flow" model, with a number of services having additional core input from diabetology, microbiology, allied health professionals and/or internal/vascular medicine. Methodological weaknesses were identified within the design of the included articles and only one was deemed of high quality. The inception of services was associated with improved rates of major amputation; however, no significant changes in minor amputation or mortality rates were identified. Further research should adopt more a standardised study design and outcomes measures in order to improve the quality of evidence within the literature.


Enzyme-catalyzed in situ forming gelatin hydrogels as bioactive wound dressings: effects of fibroblast delivery on wound healing efficacy.
In this study, in situ forming gelatin hydrogels via horseradish peroxidase (HRP)-catalyzed cross-linking were developed to serve as bioactive wound dressings with suitable tissue adhesive properties to deliver dermal fibroblasts (DFBs). The DFB-encapsulated gelatin hydrogels with different stiffnesses, GH-soft (1.1 kPa) and GH-hard (6.2 kPa), were prepared by controlling the hydrogen peroxide (H2O2) concentrations. The GH-soft hydrogel was capable of facilitating the proliferation of DFBs and the synthesis of extracellular components, as compared to GH-hard hydrogels. In addition, the subcutaneously injected GH-soft hydrogel with bioluminescent reporter cells provided enhanced cell survival and local retention over 14 days. In vivo transplantation of DFB-encapsulated GH-soft hydrogels accelerated wound contraction, and promoted collagen deposition and neovascularization within the incisions performed on mice skin. Therefore, we expect that HRP-catalyzed in situ forming gelatin hydrogels can be useful for local delivery of cells with high viability in wounds, which holds great promise for advancing wound healing technologies and other tissue engineering applications.


Benchmarking Farm Animal Welfare-A Novel Tool for Cross-Country Comparison Applied to Pig Production and Pork Consumption.
A pluralist approach to farm animal welfare, combining animal welfare legislation with market-driven initiatives, has developed in many countries. To enable cross-country comparisons of pig welfare, a number of welfare dimensions, covering the features typically modified in legislative and market-driven welfare initiatives aimed at pig production, were defined. Five academic welfare experts valued the different welfare states within each dimension on a 0-10 scale, then assessed the relative contribution of each dimension to overall welfare on a 1-5 scale. By combining these values and weights with an inventory of pig welfare initiatives in five countries, the additional welfare generated by each initiative was calculated. Together with information on the national coverage of each initiative, the Benchmark value for each country's production and consumption of pork could be calculated on a scale from 0 to 100. Two (Sweden and the UK) had a much higher Benchmark value than the rest. However, there was a drop in the Benchmark for consumption in Sweden and the UK (indicating imports from countries with lower-Benchmark values for production). Even though the experts differed in the values and weights ascribed to different initiatives, they were largely in agreement in their ranking of the countries.


Catalytically active nanomaterials: a promising candidate for artificial enzymes.
Natural enzymes, exquisite biocatalysts mediating every biological process in living organisms, are able to accelerate the rate of chemical reactions up to 10(19) times for specific substrates and reactions. However, the practical application of enzymes is often hampered by their intrinsic drawbacks, such as low operational stability, sensitivity of catalytic activity to environmental conditions, and high costs in preparation and purification. Therefore, the discovery and development of artificial enzymes is highly desired. Recently, the merging of nanotechnology with biology has ignited extensive research efforts for designing functional nanomaterials that exhibit various properties intrinsic to enzymes. As a promising candidate for artificial enzymes, catalytically active nanomaterials (nanozymes) show several advantages over natural enzymes, such as controlled synthesis in low cost, tunability in catalytic activities, as well as high stability against stringent conditions. In this Account, we focus on our recent progress in exploring and constructing such nanoparticulate artificial enzymes, including graphene oxide, graphene-hemin nanocomposites, carbon nanotubes, carbon nanodots, mesoporous silica-encapsulated gold nanoparticles, gold nanoclusters, and nanoceria. According to their structural characteristics, these enzyme mimics are categorized into three classes: carbon-, metal-, and metal-oxide-based nanomaterials. We aim to highlight the important role of catalytic nanomaterials in the fields of biomimetics. First, we provide a practical introduction to the identification of these nanozymes, the source of the enzyme-like activities, and the enhancement of activities via rational design and engineering. Then we briefly describe new or enhanced applications of certain nanozymes in biomedical diagnosis, environmental monitoring, and therapeutics. For instance, we have successfully used these biomimetic catalysts as colorimetric probes for the detection of cancer cells, nucleic acids, proteins, metal ions, and other small molecules. In addition, we also introduce three exciting advances in the use of efficient modulators on artificial enzyme systems to improve the catalytic performance of existing nanozymes. For example, we report that graphene oxide could serve as a modulator to greatly improve the catalytic activity of lysozyme-stabilized gold nanoclusters at neutral pH, which will have great potential for applications in biological systems. We show that, through the incorporation of modulator into artificial enzymes, we can offer a facile but highly effective way to improve their overall catalytic performance or realize the catalytic reactions that were not possible in the past. We expect that nanozymes with unique properties and functions will attract increasing research interest and lead to new opportunities in various fields of research.


Clinical-study of multiple-myeloma in the elderly.
From January 1989 until December 1992, 120 elderly patients over 65 years old with multiple myeloma (MM) were enrolled with the Elderly Hematology Study Group (EHSG) with 14 institutions participating. Several courses of chemotherapy were conducted in 103 of the 120 patients, 33 patients with alpha-interferon (IFN) and 70 patients without IFN. The response rate (CR+PR) was 24.0% of all 120 cases, 24.2% of the group treated with IFN and 25.7% of those treated without IFN. Similarly, the efficacy rate (CR+PR+MR) of these groups were 78.8%, 81.8% and 78.8%, respectively. The 50% survival time was 31 months in the 120 cases as a whole, 44 months in the group treated with IFN and 38 months in the group treated without IFN. No significant difference was observed either in response rate (p=0.243) or survival time (p=0.262) in the groups treated with or without IFN.


Relationship Between Quality of Life Indicators and Cardiac Status Indicators in Chemotherapy Patients.
With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients. In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value. Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management.


The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue.
Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.


Dosimetry comparison and characterisation of an Al K ultrasoft x-ray beam from an MRC cold-cathode source.
Ultrasoft x-rays of 0.3-5 keV have provided a unique tool for the investigation of intracellular mechanisms of radiation action in biological organisms, including mammalian cells. However, their use presents unique practical problems in dosimetry and experimental design. Detailed interpretation of the biological results requires reliable dosimetry and well characterised monoenergetic beams. This paper presents a comparison between two fundamentally different dosimetric techniques, namely the ionisation current in an extrapolation chamber and photon counts in a proportional counter. Agreement within 7% was obtained when these two methods were applied to an Al K x-ray beam (1.5 keV) from an MRC cold-cathode transmission target discharge tube as previously used in many biological experiments. Photographic film was calibrated as a relative dosimetric technique and used for investigation of the intensity uniformity of the radiation field. These techniques provide a comprehensive characterisation of the beam in the position of the biological cells, including photon flux (or absorbed dose rate), spectral purity (showing much less than 1% bremsstrahlung relative to characteristic Al x-rays) and uniformity over the irradiation area (within about 5% for mammalian cell irradiations).


[Lymphatic filariasis in Haiti: historical sequel or future public health problem in this geographic region?].
Wuchereria bancrofti persists in Haiti in localized foci, discontinuously distributed. The parasite, transmitted by Culex quinquefasciatus, develops in mesoendemic or hyperendemic fashion in urban and suburban areas, on the coastal plains sheltered from the prevailing winds, predominantly in the Nord department and around the gulf of La Gonave. Lymphatic filariasis is a major public health problem. Its impact is more evident in males on account of the genital repercussion of the disease. The acute lesions appear from early infancy and are related to microfilarial density. The chronic lesions begin with adolescence, and occur with high frequency in adults. Lymphatic filariasis has retreated in the countries where socioeconomic or sanitary conditions have improved: Puerto Rico, French West Indies, Cuba. In countries confronted by underdevelopment, overpopulation and uncontrolled urbanization, the disease is prevalent: Haiti, Dominican Republic, Trinidad. It is essential to carry out epidemiological investigations in order to identify the extend of the lymphatic filariasis problem in the Caribbean, particularly as population migration in both directions is becoming intensified: the native people looking for work in the industrialized countries, and tourists seeking the attractions of the tropics.


[Pregnancy management in women with thalassemia].
Thanks to the improvement of the techniques of assisted fecundation, of the obstetric management and of the fetal and neonatal monitoring now it's possible for a woman suffering from beta-thalassemia to have a child. Our purpose is to stress the importance to control the high maternal and fetal risk through the monitoring of several scales. The problems, connected with pregnancy of beta-thalassemic women are discussed, emphasizing the connection between pregnancy management and gestational and neonatal outcome. A variety of problems should be considered such as the informed consent about maternal and fetal risks, the problems caused by infectious agents or due to the use of some antiviral; the difficulties connected with heart and endocrine diseases are also discussed. Personal experience, from 1995 to 1999, on 4 beta-thalassemic pregnant women (three with the intermediate type and one with the major type) is reported.


Homology between the female paraurethral (Skene's) glands and the prostate. Immunohistochemical demonstration.
Homology between female paraurethral glands and the prostate has often been suggested. A means was developed that would lend histochemical support to this hypothesis. Female urethra from autopsy and surgical material was serially sectioned and studied in 19 patients ranging in age from newborn to 86 years. Paraurethral glands were identified in 18 of these. The tissue was stained with antibodies to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAcPh) using the peroxidase-antiperoxidase method. Of those cases in which paraurethral glands were seen, 83% were positive for PSA and 67% for PSAcPh. Intensity of staining was semi-quantitatively evaluated. In addition, intraluminal secretions and urethral columnar epithelium showed positive enzyme and antigen staining. There was no discernible variation of glandular development or pattern of staining with patient age. This study demonstrates the homologous nature of the female paraurethral glands and the prostate and supports speculations about functional similarity.


CD56brightCD16- NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation.
Recent studies suggested that human CD56(bright)CD16(-) NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56(dim)CD16(+) and CD56(bright)CD16(-) NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56(bright)CD16(-) than in CD56(dim)CD16(+) NK cells. CD57 was mostly expressed by CD56(dim)CD16(+) NK cells. CD203a/PC-1 expression was restricted to CD56(bright)CD16(-) NK cells. CD56(bright)CD16(-) NK cells produce ADO and inhibit autologous CD4(+) T cell proliferation. Such inhibition was 1) reverted pretreating CD56(bright)CD16(-) NK cells with a CD38 inhibitor and 2) increased pretreating CD56(bright)CD16(-) NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56(bright)CD16(-) NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4(+) T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56(bright)CD16(-) NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56(bright)CD16(-) NK cells act as "regulatory cells" through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune/inflammatory diseases.


Distinct mechanisms for synchronization and temporal patterning of odor-encoding neural assemblies.
Stimulus-evoked oscillatory synchronization of neural assemblies and temporal patterns of neuronal activity have been observed in many sensory systems, such as the visual and auditory cortices of mammals or the olfactory system of insects. In the locust olfactory system, single odor puffs cause the immediate formation of odor-specific neural assemblies, defined both by their transient synchronized firing and their progressive transformation over the course of a response. The application of an antagonist of ionotropic gamma-aminobutyric acid (GABA) receptors to the first olfactory relay neuropil selectively blocked the fast inhibitory synapse between local and projection neurons. This manipulation abolished the synchronization of the odor-coding neural ensembles but did not affect each neuron's temporal response patterns to odors, even when these patterns contained periods of inhibition. Fast GABA-mediated inhibition, therefore, appears to underlie neuronal synchronization but not response tuning in this olfactory system. The selective desynchronization of stimulus-evoked oscillating neural assemblies in vivo is now possible, enabling direct functional tests of their significance for sensation and perception.


Tree species traits but not diversity mitigate stem breakage in a subtropical forest following a rare and extreme ice storm.
Future climates are likely to include extreme events, which in turn have great impacts on ecological systems. In this study, we investigated possible effects that could mitigate stem breakage caused by a rare and extreme ice storm in a Chinese subtropical forest across a gradient of forest diversity. We used Bayesian modeling to correct stem breakage for tree size and variance components analysis to quantify the influence of taxon, leaf and wood functional traits, and stand level properties on the probability of stem breakage. We show that the taxon explained four times more variance in individual stem breakage than did stand level properties; trees with higher specific leaf area (SLA) were less susceptible to breakage. However, a large part of the variation at the taxon scale remained unexplained, implying that unmeasured or undefined traits could be used to predict damage caused by ice storms. When aggregated at the plot level, functional diversity and wood density increased after the ice storm. We suggest that for the adaption of forest management to climate change, much can still be learned from looking at functional traits at the taxon level.


Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in medulloblastomas determined with single and double immunohistochemical staining methods.
We examined the growth potential of 17 medulloblastomas by single and double immunohistochemical staining with bromodeoxyuridine (BUdR) and MIB 1, a monoclonal antibody for Ki-67 protein, in serial sections of ethanol-fixed, paraffin-embedded tissues; we also assessed the heterogeneity of the immunoreactivity in the tumors. In the most active areas, the BUdR labeling index (LI) was 6.8 to 26.9% (HCl hydrolysis) and 7.5 to 28.8% (microwave heating), and the MIB 1 proliferating cell index (PCl) was 14.9 to 56.5%. Linear regression analysis showed that the BUdR LI correlated with the MIB 1 PCI (p < 0.001). The ratio of MIB 1-positive to BUdR-positive cells was 2.2 +/- 0.4 by both single and double staining. BUdR-positive nuclei were heterogeneously distributed in all cases, especially in areas with scattered foci of necrosis. Three tumors had areas with many MIB 1-positive but few BUdR-positive nuclei; these areas were associated with recent tumor necrosis. However, in most of the tumors, the densities of BUdR-positive and MIB 1-positive cells changed concomitantly from area to area. These changes were clearly shown by double immunostaining. Thus, transcapillary passage of BUdR does not appear to be impeded in most medulloblastomas. This study suggests that MIB 1 immunostaining provides essentially the same data as BUdR labeling for assessing the proliferative potential of medulloblastomas.


Adrenal-testicular-pituitary relationships in the cheetah subjected to anesthesia/electroejaculation.
The influence of electroejaculation on the acute response in serum cortisol, testosterone and luteinizing hormone (LH) was studied in the South African cheetah . Males were either anesthetized with CT-1341 and 1) serially bled only (controls, n = 7) or 2) serially bled during and following a regimented protocol of rectal probe electroejaculation (n = 14). In the control cheetahs , mean cortisol concentrations declined over time (P less than 0.05) and neither testosterone nor LH varied over the 145-min sampling interval. Serum cortisol rose immediately in electroejaculated cheetahs , peaked at the end of electroejaculation in 13 of 14 males and then declined during the next 90 min. Temporal profiles and serum levels of testosterone and LH were similar in the electroejaculated and control groups (P greater than 0.05). Within individual cheetahs , serum levels of LH and testosterone were highly correlated (r = 0.77, P less than 0.01). Awake (n = 2) and CT-1341 anesthetized (n = 2) cheetahs also were bled and then challenged with an i.m. injection of 25 IU adrenocorticotropic hormone (ACTH, Cortrosyn). Serial blood samples were collected during the next 2 h and assayed. Cortisol concentrations prior to ACTH administration were greater in awake than in anesthetized males. In all animals, cortisol rose immediately and peaked within 30-60 min of injection. Whereas all 4 ACTH-treated cheetahs produced cortisol titers in excess of 200 ng/ml, only 4 of 14 electroejaculated males produced cortisol levels comparable to this concentration range. Neither testosterone nor LH profiles were affected by ACTH-induced elevations in cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)


Black-box tests for algorithmic stability.
Algorithmic stability is a concept from learning theory that expresses the degree to which changes to the input data (e.g. removal of a single data point) may affect the outputs of a regression algorithm. Knowing an algorithm's stability properties is often useful for many downstream applications-for example, stability is known to lead to desirable generalization properties and predictive inference guarantees. However, many modern algorithms currently used in practice are too complex for a theoretical analysis of their stability properties, and thus we can only attempt to establish these properties through an empirical exploration of the algorithm's behaviour on various datasets. In this work, we lay out a formal statistical framework for this kind of black-box testing without any assumptions on the algorithm or the data distribution, and establish fundamental bounds on the ability of any black-box test to identify algorithmic stability.


Dietary intake of fiber, whole grains and risk of colorectal cancer: An updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts.
Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses' Health Study (1980-2012) and 47,924 men from the Health Professionals Follow-up Study (1986-2012), who completed a validated food frequency questionnaire every 4 years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit and vegetable fiber and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person-years of follow-up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (hazard ratio [HR] comparing extreme deciles, 1.17; 95% CI, 0.92-1.48, ptrend = 0.55) or men (HR, 0.90; 95% CI, 0.67-1.21, ptrend = 0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57-1.00) and 0.72 (95% CI, 0.54-0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (pheterogeneity > 0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce CRC risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.


AAEM case report #30: multifocal motor neuropathy.
A 73-year-old man with a 16-year history of fasciculations and 15 years of weakness in his right arm was diagnosed with focal motor neuron disease. After 10 years of purely motor symptoms, he developed mild parasthesias although his sensory examination remained normal. Reflexes were reduced or absent in the weak muscles but were normal elsewhere. Nerve conduction was studied in nerves innervating weak muscles and showed severe motor conduction block. Sensory nerve conduction studies were minimally abnormal, showing reduced amplitudes with normal velocities. Based on the clinical picture and the presence of severe motor conduction block, the patient was diagnosed as multifocal motor neuropathy. Treatment with high-dose intravenous immunoglobulin was given with significant improvement in strength and partial resolution of the conduction block. As this case demonstrates, this treatable disorder may occasionally be mistaken for motor neuron disease although the resemblance is only superficial, and it should never be mistaken for amyotrophic lateral sclerosis. Multifocal motor neuropathy is an inflammatory, demyelinating neuropathy which, like chronic inflammatory demyelinating polyneuropathy (CIDP), is probably immune-mediated. It differs from typical CIDP by virtue of a marked predilection for motor axons, a strikingly restricted distribution, and a protracted course. Treatment with high-dose intravenous immunoglobulin is frequently helpful, but other forms of immune manipulation are less effective.


[Preflight assessment by hypoxic inhalation test in cardiopulmonary patients].
Flying may expose passengers to hypoxic conditions, which may induce hypoxemia, particularly in those with chronic heart and/or lung disease. Onset of dyspnea, wheezing, chest pain, cyanosis and right heart failure can lead to urgent need for oxygen during flight. The hypoxia inhalation test (HIT) provides a safe and simple means of identifying those who may develop hypoxemia during flight. We report our experience with 48 self-reporting patients who underwent HIT prior to pre-planned air travel. They inhaled for 15-minute periods a reduced oxygen concentration (F1O2 15%) under normobaric conditions, during which O2 saturation was monitored by pulse oximeter; electrocardiogram, blood pressure and symptoms were also monitored. O2 saturation of < 85% (PaO2 50 mm Hg) was considered a positive test. In the 8 cases (17%) with a positive test, 5 had chronic obstructive pulmonary disease and 3 had cardiovascular and/or combined heart-lung disease. We calculated predicted O2 partial pressure in altitude (PaO2ALT) and compared it to actual results in the 8 patients with a positive HIT. In 5, use of the predicted formula would have under-diagnosed the hypoxemia that developed during the HIT. Thus, the results of the HIT changed treatment strategy in these patients. We recommend that patients with positive tests use O2 (2LPM or 4LPM) during flight. HIT is practical and of potential benefit in the objective assessment of patients with various degrees of heart, lung or combined heart-lung disease. Clinicians should be aware of the relative risk of hypoxia during flight in such patients, and of the value of HIT in identifying them, leading to increase in its use.


Measurement model exploring a syndemic in emerging adult gay and bisexual men.
The current study was designed to develop a better understanding of the nature of the relationships between mental health burden, drug use, and unprotected sexual behavior within a sample of emerging adult gay and bisexual men, ages 18-19 (N = 598) and to test a theory of syndemics using structural equation modeling. Participants were actively recruited from community-based settings and the Internet for participation in a seven-wave cohort study. Data for participant characteristics and mental health were collected via computer-assisted survey, while drug use and unprotected sex behaviors for the month prior to assessment were collected via a calendar-based technique. Using the baseline data, we developed and tested structural equation models for mental health burden, drug use, and unprotected sex and also tested a second-order model for a single syndemic. First-order measurement models for each of the three epidemics were successfully identified using observed data. Tests of a second-order model seeking to explain the three epidemics as a single syndemic fit poorly. However, a second-order construct comprised of mental health burden and drug use fit the data well and was highly associated with the first-order construct of unprotected sex. The findings advance a theory of syndemics and suggest that in order to be maximally effective both HIV prevention and HIV care must be delivered holistically such that sexual risk behaviors are addressed in relation to, and in sync with, the drug use and mental health of the individual.


Investigating Antibody Reactivity to the Intestinal Microbiome in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Feasibility Study.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals. To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory immunoglobulin (Ig) A and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG, we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome. We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.


Long term operation of high concentration powdered activated carbon membrane bio-reactor for advanced water treatment.
A pilot scale experiment was conducted to evaluate the performance of a membrane bioreactor filled with high concentration powdered activated carbon. This hybrid system has great potential to substitute for existing GAC or O3/BAC processes in the drinking water treatment train. The system was installed at a water treatment plant located downstream of the Nakdong river basin, Korea. Effluent of rapid sand filter was used as influent of the system which consists of PAC bio-reactor, submerged MF membrane module and air supply facility. PAC concentration of 20 g/L was maintained at the beginning of the experiment and it was increased to 40 g/L. The PAC has not been changed during the operational periods. The membrane was a hollow fiber type with pore sizes of 0.1 and 0.4 microm. It was apparent that the high PAC concentration could prevent membrane fouling. 40 g/L PAC was more effective to reduce the filtration resistance than 20 g/L. At the flux of 0.36 m/d, TMP was maintained less than 40 kPa for about 3 months by intermittent suction type operation (12 min suction/3 min idling). Adsorption was the dominant role to remove DOC at the initial operational period. However the biological effect was gradually increased after around 3 months operation. Constant DOC removal could be maintained at about 40% without any trouble and then a tremendous reduction of DBPs (HAA5 and THM) higher than 85% was achieved. Full nitrification was observed at the controlled influent ammonia nitrogen concentration of 3 and 7 mg/L. pH was an important parameter to keep stable ammonia oxidation. From almost two years of operation, it is clear that the PAC membrane bioreactor is highly applicable for advanced water treatment under the recent situation of more stringent DBPs regulation in Korea.


Immunoperoxidase localization of papillomavirus antigen in cutaneous warts and bowenoid papulosis.
Using the immunoperoxidase technique and a broadly cross-reactive antiserum which detects infection with any papillomavirus, papillomavirus capsid antigen was demonstrated in 25 of 48 cutaneous papillomas and in two of 38 cutaneous dysplasias. Both positive dysplastic lesions were diagnosed on histopathologic examination as bowenoid papulosis. Antigen-positive cutaneous warts were scattered in all age categories and at all body sites. In addition, there was little variation in antigen expression by morphologic type of wart. Antigen was localized in the nucleus of superficial epithelial cells. The amount of staining was variable, with some warts showing large numbers of stained nuclei. In other warts only isolated cells stained. In both cases of bowenoid papulosis, small foci of positively stained cells were observed. The finding of papillomavirus antigen in two of 21 cases of bowenoid papulosis is suggestive of an etiologic relationship between this lesion and a papillomavirus. An examination of antigen-negative cases of bowenoid papulosis for a papillomavirus genome will be necessary to confirm these results.


Prospective evaluation of vesicourethral anastomosis outcomes in robotic radical prostatectomy during early experience in a university hospital.
Robotic assisted radical prostatectomy (RARP) presents challenges for the surgeon, especially during the initial learning curve. We aimed to evaluate early and mid-term functional outcomes and complications related to vesicourethral anastomosis (VUA), in patients who underwent RARP, during the initial experience in an academic hospital. We also assessed possible predictors of postoperative incontinence and compared these results with the literature. We prospectively collected data from consecutive patients that underwent RARP. Patients with at least 6 months of follow-up were included in the analysis for the following outcomes: time to complete VUA, continence and complications related to anastomosis. Nerve-sparing status, age, BMI, EBL, pathological tumor staging, and prostate size were evaluated as possible factors predicting early and midterm continence. Results were compared with current literature. Data from 60 patients was assessed. Mean time to complete VUA was 34 minutes, and console time was 247 minutes. Continence in 6 months was 90%. Incidence of urinary leakage was 3.3%, no patients developed bladder neck contracture or postoperative urinary retention. On multivariate analysis, age and pathological staging was associated to 3-month continence status. Our data show that, during early experience with RARP in a public university hospital, it is possible to achieve good results regarding continence and other outcomes related to VUA. We also found that age and pathological staging was associated to early continence status.


Thirty-Minute Psychiatric Management Visits in Academic Medical Centers: Framing and Exploring Distinct Clinical-Educational Social Processes.
To address high clinical demand and manage workflow, some university-based practice settings are tending to replace traditional hour-long outpatient appointments with 30-minute psychiatric management visits, which must comply with multiple regulatory requirements for documentation and billing. This care model can significantly shape the culture of psychiatric treatment and education. Based on the limited published literature on this topic and pooled experiences of faculty, residents, and administrators, this article offers observations and raises questions concerning 1) clinical, educational and administrative benefits, limitations, and challenges for conducting 30-minute psychiatric visits in training contexts; 2) how administrative impositions affecting resident and faculty time and attention impact clinical encounters; 3) how various teaching settings manage regulatory requirements differently; and 4) considerations for education needs and opportunities, research gaps, and policy implications. Quality of care and education could be improved by judicious overhaul of administrative requirements to minimize burdens offering little clinical or educational value.


Clinical and pharmacokinetic effects of regional or general anaesthesia on intravenous regional limb perfusion with amikacin in horses.
Antimicrobial i.v. regional limb perfusion (IV-RLP) is clinically performed on anaesthetised or sedated horses with or without regional anaesthesia. To date, no scientific data are available on the clinical and pharmacokinetic effects of these anaesthetic protocols on antimicrobial IV-RLP, which is believed to result in better tourniquet efficiency due to decreased movement. To determine the effects of regional or general anaesthesia on the clinical and synovial pharmacokinetic parameters of amikacin administered by IV-RLP to horses. Experimental crossover study. Eight healthy horses received 4 treatments of amikacin IV-RLP in a randomised, blinded, crossover design: standing sedation without regional anaesthesia (CNT); standing sedation with i.v. regional anaesthesia; standing sedation with perineural regional anaesthesia (PNA); or general anaesthesia. Synovial fluid amikacin concentrations were measured over 24 h and regional pharmacokinetic parameters calculated. Heart and respiratory rates, visual analogue scale of discomfort, number of times the limb was lifted and number of additional sedations administered were recorded. Analysis of variance crossover analysis was applied with significance level at P < 0.05. Amikacin concentrations and regional pharmacokinetic parameters did not differ significantly among treatments. Visual analogue scores (mean ± s.d.) were significantly lower with PNA (19 ± 15) vs. i.v. regional anaesthesia (69 ± 36) or CNT (81 ± 13; P < 0.001). Significantly less lifting of the limb (mean ± s.d.) occurred with PNA (20 ± 20) vs. CNT (54 ± 22; P < 0.04). Perineural regional anaesthesia before IV-RLP was most effective in providing comfort to standing, sedated horses without significantly affecting the regional pharmacokinetic parameters of amikacin. High variability of synovial amikacin concentrations was present. The use of general anaesthesia for IV-RLP is not justified based on this study.


Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility.
At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-beta. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-beta both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoter-reporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness.


Stimulation of RNA and protein synthesis by intracellular insulin.
Like insulin-sensitive somatic cells, stage IV oocytes from Xenopus laevis increase their synthesis of RNA, protein, and glycogen in response to extracellular insulin. Synthesis of RNA and protein are also increased when oocytes are maintained under paraffin oil and insulin is microinjected into the cytoplasm. The effects of external and intracellular insulin are additive, suggesting separate mechanisms of action. Experiments with nuclei isolated under oil show that RNA synthesis can be stimulated by applying insulin to the nucleus directly. Thus, the nucleus appears to be one intracellular site of hormone action.


Differences in the antigenic expression of immunomodulatory mannoprotein constituents on yeast and mycelial forms of Candida albicans.
The expression of a strongly immunomodulatory mannoprotein complex (GMP) in the different forms of growth of the human commensal and opportunistic pathogen Candida albicans was studied using a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope of GMP. Immunofluorescence revealed that the surface of the yeast cells was highly reactive with mAb AF1, but that the reactivity was greatly reduced or disappeared during mycelial conversion. This modulation was shared by a number of strains of C. albicans, and was not solely a temperature- or nutrition-dependent phenomenon. Hypha-deficient strains (A12 and CA2) did not show variations of surface fluorescence under environmental conditions which were permissive for hyphal conversion (incubation in N-acetylglucosamine or Lee's medium, at 37 degrees C). GMP extracts from yeast and mycelial forms of the fungus were separated into three chromatographically distinct, high molecular mass mannoprotein fractions (F1, F2 and F3), which were tested individually by indirect ELISA for mAb AF1 recognition. All yeast-derived constituents and two (F2 and F3) of the hyphal mannoproteins were recognized by the mAb. The low or absent reactivity of the F1 constituent from hyphal cells was confirmed by immunoblots. Irrespective of their source (yeast or mycelial), all fractions reacted to a similar extent with a polyclonal anti-Candida serum. Overall, the data suggest changes in epitope specificity and/or confinement of reactive constituents in the inner wall layers as possible mechanisms of modulated expression of mAb AF1-reactive epitope during mycelial conversion.


Surgical management of stage T1 renal tumours at Canadian academic centres.
The proportion of patients with stage 1 renal tumours receiving partial nephrectomy is considered a quality of care indicator. The objective of this study was to characterize surgical practice patterns at Canadian academic institutions for the treatment of these tumours. The Canadian Kidney Cancer Information System (CKCis) is a multicentre collaboration of 13 academic institutions in Canada. All patients with pathologic stage T1 renal tumours in CKCis were identified. Descriptive statistics were performed to characterize practice patterns over time. Associations between patient, tumour, and treatment factors with the use of partial nephrectomy were determined. From 1988 to April 2014, 1453 patients with pathologic stage 1 renal tumours were entered in the CKCis database. Of these, 977 (67%) patients had pT1a tumours; of these, 765 (78%) received partial nephrectomy. Of the total number of patients (1453), 476 (33%) had pT1b tumours; of these, 204 (43%) received partial nephrectomy. The use of partial nephrectomy increased over time from 60% to 90% for pT1a tumours and 20% to 60% for pT1b tumours. Stage pT1b (relative risk [RR] 0.56, 95% confidence interval [CI] 0.50-0.63) and minimally invasive surgical approach (RR 0.78, 95% CI 0.73-0.84 for pT1a and RR 0.23, 95% CI 0.17-0.30 for pT1b) were associated with decreased use of partial nephrectomy. Most patient factors including age, gender, body mass index, hypertension, and renal function were not significantly associated with use of partial nephrectomy (p > 0.05). Almost all pT1a and most pT1b renal tumours managed surgically at academic centres in Canada receive partial nephrectomy. The use of partial versus radical nephrectomy appears to occur independently of patient age and comorbid status, which may indicate that urologists are performing partial nephrectomy whenever technically feasible based on tumour factors. Although the ideal proportion patients receiving partial nephrectomy cannot be determined, treatment distribution observed in this cohort may indicate an achievable case distribution among experienced surgeons.


A friendships and dating program for adults with intellectual and developmental disabilities: a formative evaluation.
Meaningful relationships with others are often elusive for people with intellectual and developmental disabilities, but no less desired for their full inclusion and participation in society. It is well documented that people with disabilities are victims of interpersonal violence at higher rates than peers without disabilities. This article presents a formative evaluation of the Friendships and Dating Program (FDP). The FDP was designed to teach the social skills needed to develop healthy, meaningful relationships and to prevent violence in dating and partnered relationships. Thirty-one adults were recruited by 5 community agencies in Alaska to participate. The results showed the size of the participants' social networks increased and the number of incidents of interpersonal violence was reduced for participants who completed the FDP, and outcomes were maintained 10 weeks later.


Wax Secretion and Color Phases of the Desert Tenebrionid Beetle Cryptoglossa verrucosa (LeConte).
The desert beetle Cryptoglossa verrucosa(LeConte) exhibits distinct color phases that range from light blue to jet black when subjected to extremes of low and high humidity, respectively. The color phases are created by "wax filaments" that spread from the tips of miniature tubercles that cover the cuticle surface. The meshwork that accumulates at low humidity reduces transcuticular water loss and may lower the rate at which body temperature rises under a radiation load by increasing reflectance.


The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer.
A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma-infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.


Castration promotes welfare in group-housed male Swiss outbred mice maintained in educational institutions.
Educational institutions maintain group-housed mice of both sexes for training veterinarians and technicians in husbandry, medication, and sampling procedures. Mice kept in all-male groups may experience poor welfare due to fighting. Castrated mice may be used to replace gonadally intact males for such training programs. In this prospective cohort study, 80 castrated and 80 control (intact) male mice were studied over 3 mo to monitor aggression frequency and injury levels. Behavioral observations were performed twice weekly by using an all-occurrences sampling method to quantify behavioral events and the number and severity of bite wounds. Under these housing conditions, group-housed male mice castrated postpubertally exhibited significantly less aggression than did intact male mice. Castration therefore improves welfare in group-housed male mice and thus provides a husbandry alternative to individually housing animals in nonstudy situations.


Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: roles of cyclic AMP and p38 mitogen-activated protein kinase.
Fatty acid-CoA ligase 4 (FACL4) is an arachidonate-preferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigate the role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process. We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines. In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver tissues. In addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overexpression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8-bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression. FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.


Growth modelling of non-functioning pituitary adenomas in patients referred for surgery.
Recent observational studies have established progression and recurrence rates of pituitary adenomas. However, it is still unknown how individual pituitary adenomas grow over years and whether growth kinetics follow a distinct growth model. The objective of this study was to define a growth model for non-functioning pituitary adenomas. Fifteen patients who had five or more serial high-quality examinations with magnetic resonance images or computerized tomography scans were identified among 216 patients with non-functioning pituitary adenomas. Tumour volumes were assessed using a stereological method based on the Cavalieri principle. Tumour growth during the observation period was analysed and different growth models were fitted to the data. Fifteen pituitary adenomas (12 recurrent tumours and 3 newly diagnosed tumours) were longitudinally observed during a median observation period of 7.4 years (range: 2.3-11.9 years). Growth kinetics could be described either by an exponential growth model (nine patients) or by a logistic model (five patients) with initial exponential growth followed by deceleration of growth. One tumour remained unchanged in size during the observation period. None of the adenomas showed accelerated growth during the observation period. Overall, the linear growth model was not suitable to describe the growth kinetics of non-functioning pituitary adenomas. Our study shows that growth of pituitary adenomas can be described by distinct growth models. Knowledge of growth dynamics has implications for clinical practice and helps to adjust scanning protocols for follow-up investigations.


PET Reconstruction With an Anatomical MRI Prior Using Parallel Level Sets.
The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) offers unique possibilities. In this paper we aim to exploit the high spatial resolution of MRI to enhance the reconstruction of simultaneously acquired PET data. We propose a new prior to incorporate structural side information into a maximum a posteriori reconstruction. The new prior combines the strengths of previously proposed priors for the same problem: it is very efficient in guiding the reconstruction at edges available from the side information and it reduces locally to edge-preserving total variation in the degenerate case when no structural information is available. In addition, this prior is segmentation-free, convex and no a priori assumptions are made on the correlation of edge directions of the PET and MRI images. We present results for a simulated brain phantom and for real data acquired by the Siemens Biograph mMR for a hardware phantom and a clinical scan. The results from simulations show that the new prior has a better trade-off between enhancing common anatomical boundaries and preserving unique features than several other priors. Moreover, it has a better mean absolute bias-to-mean standard deviation trade-off and yields reconstructions with superior relative l2-error and structural similarity index. These findings are underpinned by the real data results from a hardware phantom and a clinical patient confirming that the new prior is capable of promoting well-defined anatomical boundaries.


LINE-1 hypomethylation is associated with the risk of coronary heart disease in Chinese population.
Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD. To examine whether global methylation is associated with the risk of CHD in Chinese population. A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing. In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (Ptrend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (<median) LINE-1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (Pinteraction = 0.042) and those with diagnosis of hypertension (Pinteraction = 0.012). LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk.


Immunization Against Staphylococcus aureus Infections.
Background: Infections caused by Staphylococcus aureus continue to plague surgical patients, whether as surgical site infections or other nosocomial infections that complicate surgical care. The only meaningful methods available to decrease the risk of developing such infections are topical skin antisepsis (pre-operative skin preparation) and peri-operative antibiotic prophylaxis, neither of which offer a panacea. Alternatives to the latter are sought so as to minimize antibiotic selection pressure as a factor in the increasing problem of antimicrobial drug resistance. This review considers the possibility that immunization against S. aureus may offer a viable alternative for prophylaxis. Methods: Review and synthesis of pertinent English-language medical literature. Results: Vaccination against viral pathogens has been in successful clinical use for more than two centuries and was instrumental in the eradication of smallpox and the near-elimination of diseases such as poliomyelitis. Vaccinations against a limited number of bacterial pathogens (e.g., Bordetella pertussis, Clostridium tetanii, Corynebacterium diphtheriae, Haemophilus influenzae type b, Neisseria meningiditis, Streptococcus pneumoniae) have also been introduced with success, whereas others against bacteria are in development (C. difficile, Pseudomonas aeruginosa, S. aureus). Vaccination against S. aureus infection is in current veterinary use (e.g., to prevent mastitis among dairy cattle) but has not been successful to date in human beings despite multiple attempts, although development continues. Conclusions: Because of its complex microbiology, including multiple virulence factors and the ability to evade host immune surveillance, S. aureus presents numerous antigenic targets for vaccine development. Failure of two prior single-antigen vaccines in clinical trials has led to the consensus that future vaccine candidates must be directed against multiple antigens. Two distinct four-antigen vaccines are in clinical trials, but efficacy is yet to be determined.


Reporter-based synthetic genetic array analysis: a functional genomics approach for investigating the cell cycle in Saccharomyces cerevisiae.
Temporal control of gene expression is a widespread feature of cell cycles, with clear transcriptional programs in bacteria, yeast, and metazoans. In budding yeast, approximately 1,000 genes are transcribed during a specific interval of the cell cycle. Although a number of factors that contribute to this periodic pattern of gene expression have been studied in Saccharomyces cerevisiae, pathways of cell cycle-regulated transcription remain largely undefined. To identify regulators of genes exhibiting cell cycle periodicity, we have developed a functional genomics approach termed reporter-based synthetic genetic array (R-SGA) analysis. Based on synthetic genetic array (SGA) analysis, R-SGA allows rapid and easily automated incorporation of a cell cycle reporter gene into the array of viable haploid yeast gene-deletion mutants. Scoring of reporter activity in mutant strains compared to wild type identifies candidate regulators of the cell cycle gene of interest. In contrast to microarrays, which generally provide information about the expression of all genes under a particular condition (for example, a single gene deletion), R-SGA analysis facilitates the study of the expression of a single gene in all deletion mutants. Our system can be adapted to examine the expression of any gene not only in the context of haploid deletion mutants but also using other array-based strain collections available to the yeast community.


Behaviour Change and e-Health - Looking Broadly: A Scoping Narrative Review.
Behaviour change can refer to any transformation or modification of human behaviour. Within healthcare it refers to a broad range of activities and approaches that focus on the individual, community, or environmental influences on health-related behaviour. For e-Health (or digital health) it refers to behavioural impacts mediated through a specific e-Health intervention. However, there are also other health-related behaviour changes being quietly imposed upon both the populace and the healthcare professions broadly, by use of information and communications technologies for health. To better understand these deliberate or incidental impacts on the behaviour of healthcare consumers and providers alike, a scoping narrative review was performed using peer-reviewed and grey literature resources. Qualitative information was charted from the selected literature. This created an objective analysis of both contemporary and less commonly appreciated aspects of behaviour change in our 'digital' age. Many contemporary examples exist. The Internet and www brought alternate approaches moving from face-to-face or paper-based to websites, electronic diaries, and now mobile phones (particularly smartphones) to personalize health-related behaviour change in a myriad of diseases and conditions. Segments of the population have also exhibited health-related behaviour change through their growing www-based health-information seeking. More recent examples include 'spontaneous telemedicine' where physicians have changed the behaviour of themselves and colleagues through use of Instant Messaging, e.g., WhatsApp. Patients are also changing their behaviour spontaneously through taking and providing 'medical selfies'. However, the recent and rapid growth in accessibility and popularity of social media has markedly impacted behaviour change through the speed with which information can be spread, by both legitimate users and socialbots. Insidious examples include spread of health-related 'misinformation' (e.g., vaginal cleansing,), and now 'disinformation' (e.g., the 'anti-vaccination' movement, now resulting in recurrence of once eradicated diseases). These, and other examples, represent the broader, sometimes incidental, impact of some current e-health approaches on health-related behaviour change and should be identified and acknowledged as such. Doing so may fundamentally change opinion and efforts to redirect elements of behaviour change and aspects of behaviour change theory in unexpected ways.


A study of a decade of road traffic accidents in Benghazi-Libya: 2001 to 2010.
This paper aims to observe and to study the trends of road traffic accidents (RTA's) for the past ten years in Benghazi-Libya. A retrospective analysis was done using the patient records of Al-Jalaa hospital (the main trauma center in Benghazi) from over 21,753 RTA cases. The annual data were compared to each other and changes of trends were observed. RTA's represented an increasing percentage of Al-Jalaa's case load across the years. Around 41% of these cases needed to undergo surgery. The younger age group (20-29 years of age) formed the majority of cases while there was a trend towards an increasing average age of patients involved in an accident. Male patients were found to be younger than their female counterparts. Males comprised 81.5% while females formed 18.5% of RTA patients. In terms of inpatient duration, most patients stayed in the hospital for less than 1 week. Vehicle occupants (drivers and passengers) were admitted more often than pedestrians. There was a trend across the years towards an increased involvement of vehicle occupants and decrease in the proportion of pedestrians that had to be hospitalized. Additionally, there was a decrease in the fatalities of pedestrians. Overall, most RTA patients were discharged and made to follow-up in outpatient clinics however there was a startling trend towards increased LAMA and absconded patients. There were both encouraging findings as well as points that needed further emphasis and action. Public education, life support training and diversification of transport (apart from the use of the roads) should be looked into, as possible means of improving the current situation.


Evolution in hip resurfacing design and contemporary experience with an uncemented device.
The concepts of surface replacement of the hip and metal-on-metal articulation date back to the 1930s, and recent hip resurfacing designs have been more successful than their predecessors. Experience with the Cormet device followed initial collaboration with Mr. Derek McMinn. Both hybrid implants (a cementless cup and a cemented head) and entirely cementless implants, inserted with use of a variety of surgical approaches, yielded good results, with the cementless option increasing in popularity. The indications for hip resurfacing have become better understood, with the procedure considered most suitable for young and middle-aged males with a high activity profile. In addition, revision surgery, if necessary, has been associated in most cases with bone and soft-tissue conservation. Caution should be exercised when treating small individuals (especially females) and individuals with accompanying diagnoses other than osteoarthritis (such as hip dysplasia), for whom other bone-conserving options may be more appropriate to avoid an adverse reaction to metal debris. Correct implant placement during hip resurfacing is of critical importance.


Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) and IgA: their parallel distribution in the human gastrointestinal tract.
Using a combined immunoperoxidase (PAP)/direct immunofluorescence (IF) staining technique, pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) has been shown to be present in the majority of IgA-producing plasma cells in the lamina propria of both the jejunum and the colon. Both proteins have also been detected on the apical surface of columnar epithelial cells, particularly in the colon, and it is suggested that alpha 2-PAG, like IgA, may be secreted into the lumen of the gastrointestinal (GI) tract by an active transport mechanism. The concentration of alpha 2-PAG in the jejunal fluid of most subjects was found to be less than 20 micrograms/liter, although a number of subjects showed substantially elevated levels. The significance of the association between IgA and alpha 2-PAG, which is known to have immunosuppressive properties, is discussed in relation to the requirement for an efficient immunologic barrier within the GI tract.


Large-quantity production of chicken embryo tracheal organ cultures and use in virus and mycoplasma studies.
Chicken tracheal organ cultures were made from embryos which were 19 to 20 days old. Transversely cut rings of trachea were placed in screw-capped tissue-culture tubes with Eagle's-N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) medium and incubated in roller drums. The method had advantages over other organ culture systems in that these cultures were prepared in numbers similar to conventional tissue cultures, ciliary activity was quickly and accurately evaluated, and contamination occurred less frequently than with organ cultures in petri dishes. Ciliary activity persisted for at least 1 month when the medium was changed at 5-to 7-day intervals and for 10 to 15 days without a change. Infectious bronchitis virus stopped ciliary movement, and this effect was used as a basis for titrating the virus and for determining the neutralizing capacity of immune mouse ascitic fluid. Twenty-four Mycoplasma strains were tested. Organisms of 17 strains, both avian and mammalian, multiplied in the organ cultures, and 7 strains, belonging to the species M. gallisepticum and M. mycoides var. capri, inhibited ciliary activity.


Skill acquisition in the implementation of functional analysis methodology.
Functional analysis methodology is a powerful assessment tool for identifying contingencies that maintain a wide range of behavior disorders and for developing effective treatment programs. Nevertheless, concerns have been raised about the feasibility of conducting functional analyses in typical service settings. In this study, we examined the issue of skill acquisition in implementing functional analyses by evaluating an instructional program designed to establish a basic set of competencies. Eleven undergraduate students enrolled in a laboratory course in applied behavior analysis served as participants. Their performance was assessed during scripted simulations in which they played the roles of "therapists" who conducted functional analyses and trained graduate students played the roles of "clients" who emitted self-injurious and destructive behaviors. To approximate conditions under which an individual might conduct an assessment with limited prior training, participants read a brief set of materials prior to conducting baseline sessions. A multiple baseline design was used to assess the effects of training, which consisted of reading additional materials, watching a videotaped simulation demonstrating correct procedural implementation, passing a written quiz, and receiving feedback on performance during sessions. Results showed that participants scored a relatively high percentage of correct therapist responses during baseline, and that all achieved an accuracy level of 95% or higher following training that lasted about 2 hr. These results suggest that basic skills for conducting functional analyses can be acquired quickly by individuals who have relatively little clinical experience.


Non-Mono-Exponential Analysis of Diffusion-Weighted Imaging for Treatment Monitoring in Prostate Cancer Bone Metastases.
Diffusion-weighted imaging quantified using the mono-exponential model has shown great promise for monitoring treatment response in prostate cancer bone metastases. The aim of this prospective study is to evaluate whether non-mono-exponential diffusion models better describe the water diffusion properties and may improve treatment response assessment. Diffusion-weighted imaging data of 12 treatment-naïve patients with 34 metastases acquired before and at one, two, and three months after initiation of antiandrogen treatment are analysed using the mono-exponential, the intravoxel incoherent motion, the stretched exponential, and the statistical model. Repeatability of the fitted parameters and changes under therapy are quantified. Model preference is assessed and correlation coefficients across times are calculated to delineate the relationship between the prostate-specific antigen levels and the diffusion parameters as well as between the diffusion parameters within each model. There is a clear preference for non-mono-exponential diffusion models at all time points. Particularly the stretched exponential is favoured in approximately 60% of the lesions. Its parameters increase significantly in response to treatment and are highly repeatable. Thus, the stretched exponential may be utilized as a potential optimal model for monitoring treatment response. Compared with the mono-exponential model, it may provide complementary information on tissue properties and improve response assessment.


Labile iron pool correlates with iron content in the nucleus and the formation of oxidative DNA damage in mouse lymphoma L5178Y cell lines.
Labile iron pool (LIP) constitutes a crossroad of metabolic pathways of iron-containing compounds and is midway between the cellular need for iron, its uptake and storage. In this study we investigated oxidative DNA damage in relation to the labile iron pool in a pair of mouse lymphoma L5178Y (LY) sublines (LY-R and LY-S) differing in sensitivity to hydrogen peroxide. The LY-R cells, which are hydrogen peroxide-sensitive, contain 3 times more labile iron than the hydrogen peroxide-resistant LY-S cells. Using the comet assay, we compared total DNA breakage in the studied cell lines treated with hydrogen peroxide (25 microM for 30 min at 4 degrees C). More DNA damage was found in LY-R cells than in LY-S cells. We also compared the levels of DNA lesions sensitive to specific DNA repair enzymes in both cell lines treated with H(2)O(2). The levels of endonuclease III-sensitive sites and Fapy-DNA glycosylase-sensitive sites were found to be higher in LY-R cells than in LY-S cells. Our data suggest that the sensitivity of LY-R cells to H(2)O(2) is partially caused by the higher yield of oxidative DNA damage, as compared to that in LY-S cells. The critical factor appears to be the availability of transition metal ions that take part in the OH radical-generating Fenton reaction (very likely in the form of LIP).


MiR-486-5p inhibits IL-22-induced epithelial-mesenchymal transition of breast cancer cell by repressing Dock1.
Epithelial-mesenchymal transition (EMT) is one of important steps that lead to cancer metastasis. Interleukin-22 (IL-22) is a T helper 17 (Th17) cells-secreted cytokine, it can promote invasion and metastasis of many cancers. MiR-486-5p is a microRNA that known to function as a tumor suppressor, and bioinformatics analysis predicts that Dock-1 has a binding site of miR-486-5p. In current research, we examined the relative expression levels of miR-486-5p and Dock-1 in 80 pairs of breast cancer tissues and corresponding adjacent normal tissues, also the effects of modifying their levels in cultured cells. We illustrated that IL-22 and Dock1 promote the invasion, metastasis, and EMT of breast cancer using Transwell invasion assay, western blot and immunofluorescence. MiR-486-5p directly bound the Dock1 mRNA 3' untranslated region and inhibited IL-22-induced EMT of breast cancer cells via the Dock1/NF-κB/Snail signaling pathway. Dock1 overexpression reversed the effect caused by the overexpression of miR-486-5p. Overexpression of miR-486-5p or downregulation of Dock1 reduced pulmonary metastasis in mice. This study provided insight into a potential mechanism where miRNAs regulate breast cancer metastasis and provided a novel therapeutic target for breast cancer treatment.


Patients readmitted to ICUs* : a systematic review of risk factors and outcomes.
To evaluate the causes, risk factors, and mortality rates associated with unexpected readmission to medical and surgical ICUs. MEDLINE citation review of primary articles focusing on ICU readmission or ICU outcomes from January 1966 to June 1999, and contact with authors of primary studies. Eight primary studies of ICU readmission and eight multi-institutional ICU outcome studies that reported ICU readmission rates were included. We abstracted data on the methodology and design of the primary studies, overall rates, causes, predictors, outcomes, and measures of quality of care associated with ICU readmission. The average ICU readmission rate of 7% (range, 4 to 14%) has remained relatively unchanged in both North America and Europe. Respiratory and cardiac conditions were the most common (30 to 70%) precipitating cause of ICU readmission. Patients readmitted to ICUs had average hospital stays at least twice as long as nonreadmitted patients. Hospital death rates were 2- to 10-times higher for readmitted patients than for those who survived an ICU admission and were never readmitted. Predictors of ICU readmission have been neither well studied nor reproducible. Unstable vital signs, especially respiratory and heart rate abnormalities, and the presence of poor pulmonary function at time of ICU discharge appear to be the most consistent predictors of ICU readmission. There were no consistent data supporting the use of readmission rates as a measure of quality of care. ICU readmission is associated with dramatically higher hospital mortality. Unstable vital signs at the time of ICU discharge are the most consistent predictor of ICU readmission. Further studies focusing on processes of ICU and hospital care are needed to determine if ICU readmission rates are a measure of quality of care.


[Are extra costs generated by patients justifiable? Methodology and results from a study carried out in a Belgian general hospital].
Cost outliers account for 6 to 8% of hospital inpatient stays and concentrate 22 to 30% of inpatient costs. Explanatory factors were highlighted in various studies. They are the lenght of stay, an intensive care unit stay, the severity of illness index related to DRG and social factors. Patients are not always explained by these factors. The objective of this study is to analyse cases not explained by those factors, through a detailed analysis of medical files. In the studied hospital, there are 6,3% high cost outliers and 1,1% low cost outliers. These stays were isolated on the basis of a rule based on percentiles. Extra costs generated by high cost outliers are 6.999 euro per stay. The extra lenght of stay for these patients is 20,42 days. Among the 454 patients high cost outliers, 334 patients are explained by factors extracted from a statistical analysis based on a logistic regression (intensive care unit stay, severity of illness index, lenght of stay and social factors). The analysis of medical files of the 120 not explained inpatient stays highlights new explanatory factors (coding errors, heterogeneity of DRGs, etc.). At the end of this study, the conclusion is that a statistical analysis combined with a precise analysis of medical files allowed to explain the majority of cost outliers. An explanation is however not necessarily synonymous with medical justification.


Extracorporeal membrane oxygenation for acute life-threatening neurogenic pulmonary edema following rupture of an intracranial aneurysm.
Neurogenic pulmonary edema (NPE) leading to cardiopulmonary dysfunction is a potentially life-threatening complication in patients with central nervous system lesions. This case report describes a 28-yr woman with life-threatening fulminant NPE, which was refractory to conventional respiratory treatment, following the rupture of an aneurysm. She was treated successfully with extracorporeal membrane oxygenation (ECMO), although ECMO therapy is generally contraindicated in neurological injuries such as brain trauma and diseases that are likely to require surgical intervention. The success of this treatment suggests that ECMO therapy should not be withheld from patients with life-threatening fulminant NPE after subarachnoid hemorrhage.


Budget model can aid group practice planning.
A medical practice can enhance its planning by developing a budgetary model to test effects of planning assumptions on its profitability and cash requirements. A model focusing on patient visits, payment mix, patient mix, and fee and payment schedules can help assess effects of proposed decisions. A planning model is not a substitute for planning but should complement a plan that includes mission, goals, values, strategic issues, and different outcomes.


[Enterovirus pollution of seawater in a health resort area].
Virological examinations of sea water specimens from the littoral zone were carried out for 5 years. The specimens studied had been collected in the areas of municipal and therapeutic beaches, port, and rivers falling into the sea. Examinations of 603 specimens demonstrated enterovirus strains in 166 (27.5%) and untypable agents in 6.4% of the specimens. Enteroviruses were most frequently isolated from unpurified sewage discharged into the sea (59.4% of the specimens). The serological spectrum of the isolates was variable, yielding 28 virus serotypes. Introduction of the deepwater discharge of sewage resulted in a decrease of contamination with enteric microflora by 95%, enterophages by 73.7%, enteroviruses by 41.3%.


Aggressiveness and size: a model and two tests.
Individual variation in aggressive behavior in animals might be caused by adaptive covariation with body size. We developed a model that predicts the benefits of aggressiveness as a function of body size. The model indicated that individuals of intermediate sizes would derive the greatest benefits from being aggressive. If we assume that the cost of aggression is approximately uniform with respect to body size, selection should favor higher aggression in intermediate-sized individuals than in large or small individuals. This prediction was tested by stimulating male Madagascar hissing cockroaches, Gromphadorhina portentosa, with disembodied antennae and recording the males' aggressive responses. Antennae from larger males evoked weaker responses in subjects, suggesting that males obtained information about their opponents' size from the opponents' antennae alone. After accounting for this effect, we found support for the key prediction of our model: aggressiveness peaked at intermediate sizes. Data from actual male-male interactions validated that the antenna assay accurately measured aggressiveness. Analysis of an independent data set generated by staging male-male interactions also supported the prediction that intermediate-sized males were most aggressive. We conclude that adaptive covariation between body size and aggressiveness explains some interindividual variation in aggressiveness.


Defining the steps that lead to cancer: replicative telomere erosion, aneuploidy and an epigenetic maturation arrest of tissue stem cells.
Recently, an influential sequencing study found that more than 1700 genes had non-silent mutations in either a breast or colorectal cancer, out of just 11 breast and 11 colorectal tumor samples. This is not surprising given the fact that genomic instability is the hallmark of cancer cells. The plethora of genomic alterations found in every carcinoma does not obey the 'law of genotype-phenotype correlation', since the same histological subtype of cancer harbors different gene mutations and chromosomal aberrations in every patient. In an attempt to make sense out of the observed genetic and chromosomal chaos in cancer, I propose a cascade model. According to this model, tissue regeneration depends on the proliferation and serial activation of stem cells. Replicative telomere erosion limits the proliferative life span of adult stem cells and results in the Hayflick limit (M1). However, local tissue exhaustion or old age might promote the activation of M1-deficient tissue stem cells. Extended proliferation of these cells leads to telomere-driven chromosomal instability and aneuploidy (abnormal balance of chromosomes and/or chromosome material). Several of the aforementioned steps have been already described in the literature. However, in contrast to common theories, it is proposed here that the genomic damage blocks the epigenetic differentiation switch. As a result of aneuploidy, differentiation-specific genes cannot be activated by modification of methylation patterns. Consequently, the phenotype of cancer tissue is largely determined by the epigenetic maturation arrest of tissue stem cells, which in addition enables a fraction of cancer cells to proliferate, invade and metastasize, as normal adult stem cells do. The new model combines genetic and epigenetic alterations of cancer cells in one causative cascade and offers an explanation for why identical histologic cancer types harbor a confusing variety of chromosomal and gene aberrations. The Viennese Cascade, as presented here, may end the debate on if and how 'tumor-unspecific' aneuploidy leads to cancer.


Vertically aligned gold nanorod monolayer on arbitrary substrates: self-assembly and femtomolar detection of food contaminants.
Public attention to the food scandals raises an urgent need to develop effective and reliable methods to detect food contaminants. The current prevailing detections are primarily based upon liquid chromatography, mass spectroscopy, or colorimetric methods, which usually require sophisticated and time-consuming steps or sample preparation. Herein, we develop a facile strategy to assemble the vertically aligned monolayer of Au nanorods with a nominal 0.8 nm gap distance and demonstrate their applications in the rapid detection of plasticizers and melamine contamination at femtomolar level by surface-enhanced Raman scattering spectroscopy (SERS). The SERS signals of plasticizers are sensitive down to 0.9 fM concentrations in orange juices. It is the lowest detection limit reported to date, which is 7 orders of magnitude lower than the standard of United States (6 ppb). The highly organized vertical arrays generate the reproducible "SERS-active sites" and can be achieved on arbitrary substrates, ranging from silicon, gallium nitride, glass to flexible poly(ethylene naphthalate) substrates.


Simultaneous operation of hydatid cyst of the heart and liver: a case report.
Primary echinococcosis of the heart is exceptionally uncommon and is reported 0.5% to 2% of all hydatid cyst sites in comparison with liver (70%) or lung (20%) involvement. Hydatid disease of the heart is caused by the cestode tapeworm echinococcosis granulosis or alveolaris. We present a 29-year-old female with hydatid disease of the liver and heart. She only complained of abdominal pain and palpitation. Echocardiography and multi-slice computed tomography (MSCT) showed a 120×101 mm cyst in the liver and 64 mm in the right ventricular free wall. Both cysts were excised within one procedure successfully.


Transition Metal Dichalcogenides (TMDC)-Based Nanozymes for Biosensing and Therapeutic Applications.
Nanozymes, a type of nanomaterial with enzyme-like properties, are a promising alternative to natural enzymes. In particular, transition metal dichalcogenides (TMDCs, with the general formula MX2, where M represents a transition metal and X is a chalcogen element)-based nanozymes have demonstrated exceptional potential in the healthcare and diagnostic sectors. TMDCs have different enzymatic properties due to their unique nano-architecture, high surface area, and semiconducting properties with tunable band gaps. Furthermore, the compatibility of TMDCs with various chemical or physical modification strategies provide a simple and scalable way to engineer and control their enzymatic activity. Here, we discuss recent advances made with TMDC-based nanozymes for biosensing and therapeutic applications. We also discuss their synthesis strategies, various enzymatic properties, current challenges, and the outlook for future developments in this field.


Kefir in the Prevention and Treatment of Obesity and Metabolic Disorders.
This review summarizes recent animal and human trials examining the potential for kefir to improve obesity, type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). Evidence for pathways affected and suggestions of possible mechanisms of action are also considered. Human trials examining the ability of kefir to recapitulate metabolic health benefits previously observed in rodent models have found mixed results. Kefir has long been associated with improvements in health including obesity, diabetes, NAFLD, and dyslipidemia in preventative animal trials. While recent evidence from human trials supports a positive role of kefir in modulating diabetes-related markers, the impact of kefir consumption on markers of dyslipidemia, NAFLD, and body composition has been for the most part contradictory to animal findings. Variability in organisms for kefir fermentation poses a significant challenge in making meaningful comparisons. Recommendations for future well-controlled animal and human research are provided.


Endovascular occlusion of intracranial vessels for curative treatment of unclippable aneurysms: report of 16 cases.
Among 121 intracerebral aneurysms presenting at one institution between 1984 and 1989, 16 were treated by endovascular means. All 16 lesions were intradural and intracranial, and had failed either surgical or endovascular attempts at selective exclusion with parent vessel preservation. The lesions included four giant middle cerebral artery (MCA) aneurysms, one giant anterior communicating artery aneurysm, six giant posterior cerebral artery aneurysms, one posterior inferior cerebellar artery aneurysm, one giant mid-basilar artery aneurysm, two giant fusiform basilar artery aneurysms, and one dissecting vertebral artery aneurysm. One of the 16 patients failed an MCA test occlusion and was approached surgically after attempted endovascular selective occlusion. Treatment involved pretreatment evaluation of cerebral blood flow followed by a preliminary parent vessel test occlusion under neuroleptic analgesia with vigilant neurological monitoring. If the test occlusion was tolerated, it was immediately followed by permanent occlusion of the parent vessel with either detachable or nondetachable balloon or coils. The follow-up period ranged from 1 to 8 years. Excellent outcomes were obtained in 12 cases with complete angiographic obliteration of the aneurysm and no new neurological deficits and/or improvement of the preembolization symptoms. Four patients died: two related to the procedure, one secondary to rupture of another untreated aneurysm, and the fourth from a postoperative MCA thrombosis after having failed endovascular test occlusion. The angiographic, clinical, and cerebral blood flow criteria for occlusion tolerance are discussed.


Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission.
RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.


Stat5a sobers up inTOXicated T cells.
Exhausted T cells are largely hampered by epigenetically enforced mechanisms that limit their effector potential. In this issue of Immunity, Beltra et al. found that Stat5 can alter these epigenetic profiles when T cells transition from the Tpex precursor stage into differentiated cells. At this stage, enforced Stat5 expression increases the number of intermediate exhausted T cells and induces durable effector cells with superior anti-tumor activity.


SIDS-CDF Hypothesis Revisited: Cause vs. Contributing Factors.
The sudden infant death syndrome (SIDS)-critical diaphragm failure (CDF) hypothesis was first published by Siren and Siren in 2011 (1). Since its publication, the hypothesis has continued to generate interest and several colleagues have contributed perspectives and insights to it (2-5). The basic premise of the hypothesis is that the diaphragm is a vital organ that must continuously generate adequate force to maintain ventilation, and that CDF is a terminal event and the cause of death in SIDS. I have argued in two follow-up articles that all SIDS factors either increase the workload of the respiratory muscles, the diaphragm being the primary muscle affected, or reduce its force generating capacity (6, 7). The SIDS-CDF hypothesis posits that SIDS has many contributing factors but only one cause, namely, the failure of the vital respiratory pump. There are several known SIDS factors, such as the prone sleeping position, non-lethal infections, deep sleep, gestational prematurity, low birth weight, cigarette smoke, male gender, and altitude, but of these, some such as the prone sleeping position more significantly both impact diaphragm function and correlate with SIDS. However, SIDS cases are multifactorial and as such can be caused by different combinations of factors. An infection combined with a prone sleeping position and elevated room temperature could lead to SIDS, whereas in other circumstances, low birth weight, cigarette smoke, prone sleeping position, and altitude could result in CDF and SIDS. The SIDS-CDF hypothesis also posits that SIDS does not have a congenital or genetic origin, and that efforts to identify significant genetic anomalies in SIDS victims are unlikely to be successful (8-11).