Oral pristinamycin for the treatment of resistant Gram-positive infections in patients with cancer: Evaluation of clinical outcomes.
Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal/pelvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.


Can Children Catch up from the Consequences of Undernourishment? Evidence from Child Linear Growth, Developmental Epigenetics, and Brain and Neurocognitive Development.
Recovery from nutritionally induced height deficits continues to garner attention. The current literature on catch-up growth, however, has 2 important limitations: wide-ranging definitions of catch-up growth are used, and it remains unclear whether children can recover from the broader consequences of undernutrition. We addressed these shortcomings by reviewing the literature on the criteria for catch-up in linear growth and on the potential to recover from undernutrition early in life in 3 domains: linear growth, developmental epigenetics, and child brain and neurocognitive development. Four criteria must be met to demonstrate catch-up growth in height: after a period in which a growth-inhibiting condition (criterion 1) causes a reduction in linear growth velocity (criterion 2), alleviation of the inhibiting condition (criterion 3) leads to higher-than-normal velocity (criterion 4). Accordingly, studies that are observational, do not use absolute height, or have no alleviation of an inhibiting condition cannot be used to establish catch-up growth. Adoption and foster care, which provide dramatic improvements in children's living conditions not typically attained in nutrition interventions, led to some (but incomplete) recovery in linear growth and brain and neurocognitive development. Maternal nutrition around the time of conception was shown to have long-term (potentially permanent) effects on DNA methylation in the offspring. Undernourishment early in life may thus have profound irreversible effects. Scientific, program, and policy efforts should focus on preventing maternal and child undernutrition rather than on correcting its consequences or attempting to prove they can be corrected.


Grading Gangliogliomas: a Short Case Series With Clinico-Imagistic and Immunohistopathological Correlations.
Ganglioglioma (GG) represents an extremely rare tumor of the central nervous system, which is composed of two different cellular populations: a glial cell population and a neuronal cell population, the former being the one which will establish the histologic grade of the tumor. The current World Health Organization (WHO) Classification of Tumors of the Central Nervous System divides gangliogliomas into benign (WHO grade I) and malignant (WHO grade III). Several scientific studies acknowledge that some tumors are difficult to grade but, due to the scarcity of cases as well as the lack of multicentric epidemiological data, there are no extensive studies regarding this matter in the neuropathology literature. We report a short case series of three patients with ganglioglioma who were admitted and treated at the Neurosurgery Department of "Bagdasar Arseni" Emergency Hospital. The patients had different clinical presentations, varying from migraines and epileptic seizures to development of a large, slowly growing tumor. Tissue fragments were obtained through surgical resection and sent to the Pathology Department for microscopic investigation. Histopathologic examination revealed both components of the tumor, supporting the diagnosis of ganglioglioma, albeit the glial component featured different histologic grade in each tumor. The tumor diagnosed as grade II lacked mitoses, but showed conspicuous atypia and numerous multinucleated cells. Immunohistochemistry revealed immunoreactivity for synaptophysin, chromogranin A and neurofilament in the neuronal component and GFAP positivity in the glial component of the tumor. Neurofilament showed an unusual pattern of staining, in which areas with benign features showed patchy positivity, while areas with malignant features and striking nuclear pleomorphism were completely negative. Due to the completely different clinical outcome, we strongly believe that a grade II ganglioglioma should be differentiated from a grade III GG, based on the lack of mitoses, necrosis and microvascular proliferation. The differentiation between grade II GG and grade I GG should be made on the cellular pleomorphism of both components (glial and neuronal). Based on our experience, we conclude that immunohistochemistry could aid in this differentiation through markers like: Ki67, neurofilament, CD34 and chromogranin A. We strongly believe that further immunohistochemical research on larger study groups will eventually lead to a consensus regarding definitive criteria for grade II gangliogliomas.


The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.
Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.


[To the problem of remote control of physiological function of organism].
We studied the influence of the synchronized signals of action (SSA) that were formed in human organism by natural biological antioxidants from sea-buckthorn (Prielbrusie) on indices of the blood and cardiovascular system. We have shown that the use of the natural biological antioxidants during 10 days normalized SaO2 fluctuation, pulse waves and blood distribution in tissues. SSA that they formed influence in the same way on recipients that were at the large distance from donor, influences were registered through the short time--6 min. We suggested a hypothesis about the distant control of physiological functions and organism adaptation processes through SSA, that were formed at the cell energetic and informational level by natural factors (biological antioxidants, adaptation to high mountains). We suppose that successes in this direction of science will have not fundamental importance only but social and practical as well.


Naturally Segregating Variation at Ugt86Dd Contributes to Nicotine Resistance in Drosophila melanogaster.
Identifying the sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing the precise causative molecular events allows insight into the pathways governing trait variation. Genetic analysis of complex traits in model systems regularly starts by constructing QTL maps, but generally fails to identify causative sequence polymorphisms. Previously we mapped a series of QTL contributing to resistance to nicotine in a Drosophila melanogaster multiparental mapping resource and here use a battery of functional tests to resolve QTL to the molecular level. One large-effect QTL resided over a cluster of UDP-glucuronosyltransferases, and quantitative complementation tests using deficiencies eliminating subsets of these detoxification genes revealed allelic variation impacting resistance. RNAseq showed that Ugt86Dd had significantly higher expression in genotypes that are more resistant to nicotine, and anterior midgut-specific RNA interference (RNAi) of this gene reduced resistance. We discovered a segregating 22-bp frameshift deletion in Ugt86Dd, and accounting for the InDel during mapping largely eliminates the QTL, implying the event explains the bulk of the effect of the mapped locus. CRISPR/Cas9 editing of a relatively resistant genotype to generate lesions in Ugt86Dd that recapitulate the naturally occurring putative loss-of-function allele, leads to a large reduction in resistance. Despite this major effect of the deletion, the allele appears to be very rare in wild-caught populations and likely explains only a small fraction of the natural variation for the trait. Nonetheless, this putatively causative coding InDel can be a launchpad for future mechanistic exploration of xenobiotic detoxification.


GPCR-Mediated Signaling of Metabolites.
In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals in adipose tissue, the liver, and the endocrine pancreas. Importantly, distinct metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets.


Prevalence and correlates of vitamin D status in African American men.
Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia. Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96-10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D >or= 15 ng/mL. Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D <15 ng/mL). Even among men with vitamin D intake >or= 400 IU/day, 55% had 25(OH)D concentrations <15 ng/mL. In multivariate models, 25(OH)D concentrations were significantly associated with supplemental vitamin D intake (OR 4.3, 95% confidence interval (CI) 1.5, 12.4) for >400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for >or= 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection. The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population.


An optimised spectrophotometric assay for convenient and accurate quantitation of intracellular iron from iron oxide nanoparticles.
We report the development and optimisation of an assay for quantitating iron from iron oxide nanoparticles in biological matrices by using ferene-s, a chromogenic compound. The method is accurate, reliable and can be performed with basic equipment common to many laboratories making it convenient and inexpensive. The assay we have developed is suited for quantitation of iron in cell culture studies with iron oxide nanoparticles, which tend to manifest low levels of iron. The assay was validated with standard reference materials and with inductively coupled plasma-mass spectrometry (ICP-MS) to accurately measure iron concentrations ∼1 × 10-6 g in about 1 × 106 cells (∼1 × 10-12 g Fe per cell). The assay requires preparation and use of a working solution to which samples can be directly added without further processing. After overnight incubation, the absorbance can be measured with a standard UV/Vis spectrophotometer to provide iron concentration. Alternatively, for expedited processing, samples can be digested with concentrated nitric acid before addition to the working solution. Optimization studies demonstrated significant deviations accompany variable digestion times, highlighting the importance to ensure complete iron ion liberation from the nanoparticle or sample matrix to avoid underestimating iron concentration. When performed correctly, this method yields reliable iron ion concentration measurements to ∼2 × 10-6 M (1 × 10-7 g/ml sample).


Charged-Particle Bound States in Periodic Boxes.
We consider the binding energy of a two-body system with a repulsive Coulomb interaction in a finite periodic volume. We define the finite-volume Coulomb potential as the usual Coulomb potential, except that the distance is defined as the shortest separation between the two bodies in the periodic volume. We investigate this problem in one and three-dimensional periodic boxes and derive the asymptotic behavior of the volume dependence for bound states with zero angular momentum in terms of Whittaker functions. We benchmark our results against numerical calculations and show how the method can be used to extract asymptotic normalization coefficients for charged-particle bound states. The results we derive here have immediate applications for calculations of atomic nuclei in finite periodic volumes for the case where the leading finite-volume correction is associated with two charged clusters.


Is social engagement linked to body image and depression among aging women?
Maintaining an active and engaged social life is a critical component of aging well, and women are generally more socially active than men. However, as women age their self-perceptions of their bodies may reduce social behaviors and consequently, increase depressive symptoms. Because little is known about how body image is associated with social engagement and depressive symptoms among aging women, four aspects of body image: satisfaction with cosmetic features, body function, physical appearance, and weight were assessed among women aged 65 and older (n = 123). Regression analyses indicated that cosmetic appearance, body function, and physical appearance were associated with depressive symptoms, whereas satisfaction with weight was unrelated. Further, both greater satisfaction with cosmetic features and body function were associated with higher levels of social engagement, and social engagement mediated the association between these aspects of body satisfaction and depressive symptoms. The findings indicate that specific age-relevant aspects of body satisfaction are linked to social behavior and depression among aging women, and reduced body satisfaction may lead to lower social engagement, and consequently aging women's health and well-being may be diminished.


Mastering the Best Practices: A Comprehensive Look at the European Guidelines for Cardiopulmonary Bypass in Adult Cardiac Surgery.
The successful outcome of a cardiac surgery procedure is significantly dependent on the management of cardiopulmonary bypass (CPB). Even if a cardiac operation is technically well-conducted, a patient may suffer CPB-related complications that could result in severe comorbidities, reduced quality of life, or even death. However, the role of clinical perfusionists in perioperative patient care, which is critical, is often overlooked. Therefore, the European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Cardiothoracic Anaesthesiology (EACTA), and the European Board of Cardiovascular Perfusion (EBCP) have agreed to develop joint clinical practice guidelines (CPGs) for CPB due to its significant impact on patient care and significant variations in practice patterns between countries. The European guidelines, based on the EACTS standardized framework for the development of CPGs, cover the entire spectrum of CPB management in adult cardiac surgery. This includes training and education of clinical perfusionists, machine hardware, disposables, preparation for initiation of CPB, a complete set of procedures during CPB to help maintain end-organ function and anticoagulation, weaning from CPB, and the gaps in evidence and future research directions. This comprehensive coverage ensures that all aspects of CPB management are addressed, providing clinicians with a standardized approach to CPB management based on the latest evidence and best practices. To ensure better integration of these evidence-based recommendations into daily practice, this review aims to provide a general understanding of guideline development and an overview of essential treatment recommendations for CPB management.


High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome.
The objective of this study was to report the dramatic improvement of patients with systemic capillary leak syndrome obtained with high-dose intravenous immunoglobulins. Systemic capillary leak syndrome is a rare and life-threatening disorder characterized by hypotension that can lead to shock, weight gain, hypoalbuminemia, and elevated hematocrit secondary to unexplained episodic capillary fluid extravasation into the interstitial space. Because its cause is unknown, systemic capillary leak syndrome treatment has remained largely supportive. Intravenous immunoglobulins administration to a patient with refractory systemic capillary leak syndrome yielded dramatic improvement. The patient is still alive 11 yrs after systemic capillary leak syndrome diagnosis and receives intravenous immunoglobulins monthly. Later, based on that result, intravenous immunoglobulins were successfully given to two other patients during the acute phase of systemic capillary leak syndrome. Both are still alive 8 and 1.5 yrs after receiving intravenous immunoglobulins at the onset of each flare. Intravenous immunoglobulins were effective against systemic capillary leak syndrome symptoms in three patients, but their exact mechanism remains unknown. Their immunomodulatory effect merits further investigation.


MicroRNAs and cancer.
The Nobel Prize in Medicine and Physiology was awarded to the RNA interference (RNAi) field in 2006 because of the huge therapeutic potential this technique harbours. However, the RNAi technology is based on a natural mechanism that utilizes short noncoding RNA molecules (microRNAs) to regulate gene expression. This paper reviews our current knowledge about microRNAs focusing on their involvement in cancer and their potential as diagnostics and therapeutics.


Influence of pulsed magnetic field on soybean (Glycine max L.) seed germination, seedling growth and soil microbial population.
The effects of pulsed magnetic field (PMF) treatment of soybean (Glycine max L. cv CO3) seeds were investigated on rate of seed germination, seedling growth, physico-chemical properties of seed leachates and soil microbial population under laboratory conditions. Seeds were exposed to PMF of 1500 nT at 0.1, 1.0 10.0 and 100.0 Hz for 5 h per day for 20 days, induced by enclosure coil systems. Non-treated seeds were considered as controls. All PMF treatments significantly increased the rate of seed germination, while 10 and 100 Hz PMFs showed the most effective response. The 1.0 and 10 Hz PMFs remarkably improved the fresh weight of shoots and roots, leaf area and plant height from seedlings from magnetically-exposed seeds compared to the control, while 10 Hz PMF increased the total soluble sugar, total protein and phenol contents. The leaf chlorophyll a, b and total chlorophyll were higher in PMF (10 and 100 Hz) pretreated plants, as compared to other treatments. In addition, activities of alpha-amylase, acid phosphatase, alkaline phosphatase, nitrate reductase, peroxidase and polyphenoloxidase were increased, while beta-amylase and protease activities were declined in PMF (10 Hz)-exposed soybean plants. Similarly, the capacity of absorbance of water by seeds and electrical conductivity of seed leachates were significantly enhanced by 10 Hz PMF exposure, whereas PMF (10 Hz) pretreated plants did not affect the microbial population in rhizosphere soil. The results suggested the potential of 10 Hz PMF treatment to enhance the germination and seedling growth of soybean.


HBV prevalence in Sub-continental countries: A systematic review and meta-analysis.
Hepatitis B virus (HBV) is a major source of disease burden worldwide, with an estimated 296 million individuals living with infections worldwide. Although vaccine programs exist to control infections, certain sub-populations around the world continue to have very high prevalence of HBV infection. A systematic search of studies of HBV published after 2010 was conducted for India, Pakistan, Bangladesh, Nepal, Sri Lanka and Bhutan. Each paper was independently screened for risk of bias and inclusion. Data were extracted from included studies before being analysed to estimate pooled prevalence, and to conduct sub-group analyses. Random-effects models were used for estimating summary prevalence due to a high level of heterogeneity between studies, and funnel plots were combined with Egger's test to assess publication bias. Meta-regression was conducted to investigate sources of between-study heterogeneity. The pooled prevalence of HBV across all studies was 3% (95% CI 0.02, 0.05). For countries with multiple studies, the pooled prevalence in India was 3% (95% CI 0.02, 0.04), in Pakistan 6% (95% CI 0.03, 0.09), in Bangladesh 5% (95% CI of 0.02, 0.12), and in Nepal 1% (95% CI 0.00, 0.08). There was some evidence of publication bias, and a high level of heterogeneity across studies. Risk of bias analysis found most studies to be of fair or moderate quality. The prevalence of HBV among countries in the sub-continent was higher than the global average, but was not as high as some other regions. Countries with greater numbers of displaced persons had higher prevalence of HBV, with a wide range of prevalence between subpopulations likely reflecting differential uptake, and implementation, of vaccination programs.


CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease.
Primary intestinal lymphangiectasia (PIL) or Waldmann's disease was described in 1961 as an important cause of protein-losing enteropathy (PLE). PIL can be the sole finding in rare individuals or occur as part of a multisystemic genetic syndrome. Although genetic etiologies of many lymphatic dysplasia syndromes associated with PIL have been identified, the pathogenesis of isolated PIL (with no associated syndromic features) remains unknown. Familial cases and occurrence at birth suggest genetic etiologies in certain cases. Recently, CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and PLE (the CHAPLE syndrome) has been identified as a monogenic form of PIL. Surprisingly, loss of CD55, a key regulator of complement system leads to a predominantly gut condition. Similarly to other complement disorders, namely paroxysmal nocturnal and hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), CHAPLE disease involves pathogenic cross-activation of the coagulation system, predisposing individuals to severe thrombosis. The observation that complement system is overly active in CHAPLE disease introduced a novel concept into the management of PLE; anti-complement therapy. While CD55 deficiency constitutes a treatable subgroup in the larger pool of patients with isolated PIL, the etiology remains to be identified in the remaining patients with intact CD55.


[Anti-inflammatory effect of anesthesiological support of intervention for infected pancreonecrosis].
The protocols of conventional (total intravenous narcosis) and innovation antinociceptive anesthesiological support of interventions, made for an acute destructive pancreatitis and infected pancreonecrosis, are adduced. There was estimated the antiinflammatory capacity of the anesthesiological method proposed and of perioperative intensive therapy.


The butanol-soluble proteins of Klebsiella aerogenes.
Membranes of Klebsiella aerogenes were extracted with acid butanol at pH 4.2 and the solubilized proteins were fractionated by precipitation at 0 degrees C and -20 degrees C. The -20 degrees C precipitate was examined by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. Several enzyme activities associated with polysaccharide biosynthesis have been identified in the crude -20 degrees C precipitate and an attempt was made to separate the enzymes from other protein. The role of certain of these enzymes in a control mechanism for polysaccharide synthesis in K. aerogenes has been postulated.


Neuromast topography in anuran amphibians.
Generalized anuran tadpoles across families exhibit a similar neuromast morphology on their heads, as follows: (1) all neuromast lines known for anurans are present; (2) within these lines total neuromast number ranges from about 250 to 320; (3) neuromasts form linear stitches composed of two to three, but sometimes up to five, neuromasts; (4) neuromast linear dimensions are ⩽ 10 μm; and (5) neuromasts contain ⩽ 15 hair cells. Compared with generalized forms, stream, arboreal, carnivorous, and desert-pond forms have fewer neuromasts but they contain more hair cells. They do not, however, form stitches. Obligate midwater suspension-feeding forms, including Xenopus (Pipidae), Rhinophrynus (Rhinophyrnidae), and Phrynomerus (Microhylidae), form stitches that contain > six, but potentially up to 18 or more, loosely aggregated neuromasts. Xenopus and Rhinophrynus have large neuromasts (up to 40 μm across). Chiasmocleis (Microhylidae) tadpoles form stiches that are linearly arranged with up to ten neuromasts. Whereas urodeles can have more than one neuromast row per line and may form both linear and transverse stitches, anurans have only one row of neuromasts per line and form only transverse stitches. Neuromasts in anurans tend to be smaller and more circular than in urodeles and positioned flush with the epidermal surface. A greater percentage of anurans form stitches, and anurans have greater intrafamilial variation in stitch formation than do urodeles.


Nodal marginal zone B-cell lymphoma: Analysis of 36 cases. Clinical presentation and treatment outcomes of nodal marginal zone B-cell lymphoma.
Nodal marginal zone B-cell lymphoma (NMZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and the optimal treatment modality have not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of NMZL. Thirty-six patients who were histologically diagnosed as NMZL were included in the analysis. Fifty-three percent of the patients had localized disease (stages I and II), and 21.2% (7/33) had bone marrow involvement at presentation. B symptom was present in only three patients (8.3%). Most patients were categorized as low or low-intermediate risk group by international prognostic index (IPI) (77.1%). Majority (94.4%) of the patients with localized disease achieved complete remission (CR) after the initial treatment. Of the seven patients with disseminated disease, who were treated with anthracycline-based chemotherapy, four patients achieved CR. Of the seven patients who received nonanthracycline-based chemotherapy, no patient achieved CR. After the median follow-up duration of 36 months, the median progression-free survival (PFS) was 3.9 (95% CI; 2.9-5.6) years, and the estimated 5-year PFS and overall survival rates were 47.2 and 82.7%, respectively. The significant predictive factors for PFS were performance status, advanced stage, and follicular lymphoma IPI (FLIPI) in this study. This clinical feature is similar to FL rather than to MZL-MALT type.


Study of vancomycin and high-level aminoglycoside-resistant Enterococcus species and evaluation of a rapid spot test for enterococci from Central Referral Hospital, Sikkim, India.
Enterococcus is an important pathogen, and with its emergence of resistance to multiple antimicrobials, the management of infection is becoming increasingly difficult. The aim of the study is to determine the prevalence, antibiotic resistance, and risk factors associated with enterococcal infection or colonization. In this prospective study, samples from inpatients were screened for resistant enterococci. Antibiotic susceptibility testing was performed using the disc diffusion method and minimum inhibitory concentration by the agar dilution method. A modification of a test tube method of sodium chloride-esculin hydrolysis to a spot test was evaluated for its rapidity and reliability in the presumptive diagnosis of enterococci. Fisher's exact test was used for continuous (Student's t-test) and categorical variables. Multivariate analysis was performed with logistic regression using IBM SPSS 20.0 software (Armonk, NY, USA). Enterococcus species were isolated from 182 samples: Enterococcus faecalis (68.7%), Enterococcus faecium (20.9%), Enterococcus gallinarum (6%), and Enterococcus durans (4.4%). Maximum resistance was to ciprofloxacin (59.3%) and least to linezolid (0.5%). The isolation rate of vancomycin-resistant enterococci (VRE) was 13.7%; 30.2% and 20.9% were of high-level gentamicin and streptomycin, respectively. All 182 Enterococcus species gave positive results within 30-60 min by the rapid spot test. Overall, high-level aminoglycoside resistance (HLAR) was observed more than glycopeptide resistance. Surveillance strategies need to be upgraded and implemented in order to prevent the emergence and further spread of not only VRE but also HLAR enterococci in the hospital. The spot test gave reliable and rapid results in presumptive identification of enterococci.


[Progressive human viral encephalitis associated to a bat bite].
Human rabies is a rapidly progressive encephalitis that is transmitted by the bites of an infected mammal. In June 2004, a male patient was admitted to a hospital emergency department after a 5-days history of progressive right arm pain, paresthesias and muscle weakness. He reported contact with a sick bat 5 weeks before admission. He suffered steady neurologic decline with fever, confusion, disorientation, hydrophobia and aerophobia the following day. The patient died two days later. Postmortem histopathology showed perivascular mononuclear infiltration and extensive neuronolysis. When the fluorescent antibody technique was applied, most residual neurons were infected by the rabies virus. Lyssavirus isolation was achieved in a murine neuroblastoma cell culture. A nested reverse transcription polymerase chain reaction was positive in the patient's cerebrospinal fluid as well as the tissues of the bat Lasionycteris noctivagans. Clinicians should suspect rabies when unexplained progressive encephalitis is observed.


[Characteristics of RNA isolated from the nuclear RNA-synthesizing complex of influenza virus].
When Ehrlich ascitic carcinoma cells infected with classical fowl plague virus and treated with actinomycin D were pulse labeled for 10 min with 3H-uridine, it was mainly incorporated into nucleoplasm structures sedimenting in sucrose gradients at 120S. At 2-hr exposure of the infected cells to 3H-uridine radioactivity was found in nucleoplasm in the area of 65S and in the cytoplasm in 30-40S zone. The analysis of RNA isolated from these structures gave the following results. The RNA isolated from 120S structures sedimented in two zones of sucrose gradient: 11S and 16-23S. The 11S RNA was resistant to RNA-ase, while 16-23S RNA was sensitive to RNA-ase. A similar (16-23S) RNA was isolated from virus-specific structures 65S and 30-40S.


[Expression of NKG2A and NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients].
To investigatethe expressions of NKG2A, NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients. Decidua tissues were collected from 30 patients with mild preeclampsia, 42 patients with severe preeclampsia and 46 normal pregnancy as contrast. The expressions of NKG2A, NKG2C protein were detected by immunohistochemitry and mRNAs of NKG2A, NKG2C and HLA-E genes were detected by RT-PCR. The expression of HLA-E mRNA was significantly decreased in preeclampsia, especially in severe preeclampsia patients (P < 0.05); The mRNA and protein expression of NKG2A, NKG2C in severe preeclampsia group were significantly higher than that in normal pregnancy group (P < 0.05); In the severe preeclampsia group, the ratio of expression level of NKG2A and NKG2C was significantly lower than that of normal group and the mRNA and protein expression of NKG2C receptor were both significantly higher than that of NKG2A (P < 0.05); The mRNA expression level of HLA-E, NKG2A and NKG2C were closely related with clinical and biochemical indexes,such as blood pressure of late pregnancy and 24-hour proteinuria. The decreased expression of HLA-E and the unevenly increase of NKG2A and NKG2C may involve in the pathogenesis of preeclampsia.


Dolutegravir, a second-generation integrase inhibitor for the treatment of HIV-1 infection.
To review the pharmacology, safety, and efficacy of dolutegravir, an integrase strand-transfer inhibitor (INSTI), and to discuss its role in the treatment of HIV-1-infected patients. PubMed articles indexed through August 2013 were identified using the search terms S/GSK1349572, dolutegravir, and integrase inhibitor. Information was also identified from the package insert, cited publication references, professional meeting abstracts, and the ClinicalTrials.gov registry. English language articleswere selected for evaluation, with preference given to safety, efficacy, and pharmacokinetic studies conducted in HIV-1-infected patients. Dolutegravir is a new INSTI approved for combination treatment in HIV-1-infected adults and adolescent children. Four phase 3 studies provide the basis for current labeling in antiretroviral-naïve and antiretroviral-experienced adults. Results from these studies demonstrate that dolutegravir is noninferior in efficacy to raltegravir in antiretroviral-naïve patients and superior in antiretroviral-experienced patients. Superiority to efavirenz and darunavir/ritonavir was also demonstrated in antiretroviral-naïve patients. Dolutegravir is well tolerated, exhibits low potential for drug-drug interactions, and has a long serum half-life, allowing it to be administered once-daily in patients without preexisting INSTI resistance. Twice-daily administration is recommended in patients with known or suspected resistance mutations to first-generation INSTIs. Mild elevations in serum creatinine occur following dolutegravir initiation from inhibition of renal organic cation transporter 2 but do not reflect changes in glomerular filtration. Dolutegravir is the first second-generation INSTI and exhibits several advantages over current integrase inhibitors and other preferred antiretrovirals. Long-term efficacy and safety are needed to define dolutegravir's role in treatment.


Effect of the vascular endothelium on contractions induced by noradrenaline and phenylephrine in perforating branch of the human internal mammary artery.
The effects of noradrenaline (Nor) and phenylephrine (Phe) on the isolated, non-precontracted perforating branch of the human internal mammary artery (HIMA) were investigated. Nor and Phe induced concentration-dependent contractions of intact and endothelium-denuded arterial rings with no statistically significant differences between the pEC(30) and maximal response values. The pretreatment of arterial rings with indomethacin had no effect on Nor- and Phe-induced contractions of both, intact and endothelium-denuded preparations. The pre-addition of L-NMMA did not affect contractions of perforating branch of the HIMA evoked by Nor, but provoked significant potentiation of Phe-induced contractions of perforating branch of the HIMA both intact and denuded of endothelium only at Phe concentration higher than 3 x 10(-6)M. The effects of selective alpha1-adrenoceptor antagonist, prazosin and selective alpha2-adrenoceptor antagonist, rauwolscine were concentration-dependent, and they induced a significant shift to the right (for both studied antagonists) of the concentration-response curves for Nor in both preparations with or without endothelium. The effects of prazosin and rauwolscine on the concentration-response curves for Phe were similar. In conclusion, this study has shown that Nor and Phe induce concentration-dependent contractions of the perforating branch of the HIMA. Removal of the endothelium did not modify this effect. Products of cyclooxygenase pathway had no influence on Nor and Phe action. Endothelium derived nitric oxide (NO) had no modulatory effect of Nor-induced contractions, but inhibition of NO synthesis provoked potentiation of Phe-induced contractions either in intact or endothelium-denuded preparations. The mechanism of this effect remains still unclear. On the basis of differential affinity of the antagonists and affinities of Nor and Phe themselves, we suggest that alpha1-adrenoceptor subtype is probably involved in the Nor- and Phe-induced contraction of the perforating branch of the HIMA both intact or denuded of endothelium.


BayesFold: rational 2 degrees folds that combine thermodynamic, covariation, and chemical data for aligned RNA sequences.
BayesFold is a Web application that folds an alignment of closely related sequences and evaluates hypotheses about their shared structure. It uses Bayes's Theorem to combine information from several sources, including chemical mapping (if available), thermodynamic folding, and observed sequence variations. Its method provides a rational basis for integrating results, even when these methods conflict. On a gapped alignment of 86 tRNAPhe sequences each 77 bases long, BayesFold takes 31 sec to perform the calculations; the best structure contained 95% of the base pairs in the true structure, and the true structure was ranked second. Notably, similar results come from random samples of only 10 sequences from the alignment (running time 3 sec), suggesting that remarkably few sequences are required for good results. In contrast, folding single sequences with BayesFold produced structures 9.6 bp different, or with the Vienna package, 13.4 bp different, from the true structure. Similar results were obtained for other families of tRNAs. We especially recommend BayesFold for alignments of 3-50 closely related sequences, such as the sequence families frequently found in SELEX. In addition to providing a convenient way to explore the effects of each of the criteria on the plausibility of different structures, BayesFold also makes it easy to produce publication-quality secondary-structure graphics. The Web interface, available at http://bayes.colorado.edu/fold/, includes the flexibility to thread any of the sequences (or the consensus sequence) through any of the structures, including the one judged most probable.


Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred and forty knees.
A prospective, randomized study was conducted to evaluate the efficacy of cefuroxime-impregnated cement in the prevention of deep infection after primary total knee arthroplasties performed without so-called clean-air measures, such as laminar flow and body-exhaust suits. Three hundred and forty primary total knee arthroplasties were performed with cementless fixation of the femoral component and cement fixation of the patellar and tibial components. The knees were randomly divided into two groups. In Group 1 (178 knees), cefuroxime-impregnated cement was used for fixation, whereas in Group 2 (162 knees), the cement did not contain cefuroxime. There was no significant difference between the two groups regarding demographic variables, the preoperative or postoperative knee score, the duration of the operation or of the use of the tourniquet, or the amount of blood transfused perioperatively. The average duration of follow-up was forty-nine months (range, twenty-six to eighty months). No deep infection developed in the 178 knees in Group 1, whereas a deep infection developed in five (3.1%) of the 162 knees in Group 2 (p = 0.0238). Two superficial wound infections developed in each group. Cefuroxime-impregnated cement was shown to be effective in the prevention of early to intermediate deep infection after primary total knee arthroplasty performed with use of perioperative systemic antibiotic prophylaxis but no so-called clean-air measures.


Sustained renal inflammation following 2 weeks of inhalation of occupationally relevant levels of zinc oxide nanoparticles in Sprague Dawley rats.
Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m3 (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure. A significant increase in microscopic inflammatory foci with pronounced periglomerular inflammation and interstitial lymphocytic infiltration was found in rats exposed to low and high doses of ZnONPs compared with rats exposed to HEPA-FA at the three time points following 2 weeks of exposure. Tubulitis featuring lymphocytic infiltrate within the tubular epithelium was found after 24 hours but had disappeared at 7 and 30 days in both the low- and high-dose exposure groups. Our findings demonstrate that inhaled ZnONPs cause sustained renal periglomerular and interstitial inflammation through lymphocytic infiltration. These findings provide histopathological evidence regarding sustained renal inflammation of nanoparticle exposure in rats and may provide some insight into the occupational health effects of ZnONPs on exposed workers.


Stimulation of V(D)J cleavage by high mobility group proteins.
V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex.


Engagement in Health Risk Behaviours before and during the COVID-19 Pandemic in German University Students: Results of a Cross-Sectional Study.
Tobacco and cannabis use, alcohol consumption and inactivity are health risk behaviors (HRB) of crucial importance for health and wellbeing. The impact of the COVID-19 pandemic on university students' engagement in HRB has yet received limited attention. We investigated whether HRB changed during the COVID-19 pandemic, assessed factors associated with change and profiles of HRB changes in university students. A web-based survey was conducted in May 2020, including 5021 students of four German universities (69% female, the mean age of 24.4 years (SD = 5.1)). Sixty-one percent of students reported consuming alcohol, 45.8% binge drinking, 44% inactivity, 19.4% smoking and 10.8% cannabis use. While smoking and cannabis use remained unchanged during the COVID-19 pandemic, 24.4% reported a decrease in binge drinking while 5.4% reported an increase. Changes to physical activity were most frequently reported, with 30.6% reporting an increase and 19.3% reporting a decrease in vigorous physical activity. Being female, younger age, being bored, not having a trusted person and depressive symptoms were factors associated with a change in HRB. Five substance use behavior profiles were identified, which also remained fairly unchanged. Efforts to promote student health and wellbeing continue to be required, also in times of the COVID-19 pandemic.


[Leukoencephalopathy with swelling, megalencephalopathy and surprisingly mild course. A case report].
Leukoencephalopathy with swelling and a discrepantly mild clinical course is a recently identified syndrome described by van der Knaap et al. It is characterised by macrocephaly occurring during the first year of life, initially normal or nearly normal development, slowly progressive ataxia and spasticity with initial preservation of intellectual functions. MRI shows diffuse abnormality of signal intensity in the hemisphere white matter with subcortical cyst-like spaces in the fronto-parietal and anterior temporal areas. The case of a 5-year-old boy whose clinical and neuroimaging findings are consistent with this syndrome is reported. The clinical and neuroimaging findings of this case may provide further information about this new syndrome which could possibly be useful also for genetic counselling.


[Mechanisms of psychophysiological choice in schoolchildren and humanitarian students].
Described in the paper is a case study targeted at detecting the age-related dynamics of some indices and psychophysiological mechanisms of decision-making in senior schoolchildren and humanitarian students; the study was based on computer-aided test systems. The research methods are presented and its results are analyzed.


A quantitative interresponse-time analysis of DRL performance differentiates similar effects of the antidepressant desipramine and the novel anxiolytic gepirone.
We describe an interresponse-time analysis of performance on a differential-reinforcement-of-low-rate 72-s schedule. This analysis compares the obtained interresponse-time distribution of individual rats to a corresponding random interresponse-time distribution. The random interresponse-time distribution is a negative exponential probability function; it predicts the relative distribution of interresponse times if the rat emitted the same number of responses randomly (i.e., with a constant probability) with respect to time. The analysis provides quantitative measures of peak location and dispersion of the interresponse times toward random performance. In Experiment 1, an unexpected outcome of this analysis was that the rats would have obtained more reinforcers had they responded at the same rate but randomly. Based on the interresponse-time analysis in Experiment 1, it was shown that rats trained on the differential-reinforcement-of-low-rate 72-s schedule could increase the number of reinforcers obtained in two ways: first, by a coherent shift of the interresponse-time distribution toward longer durations and, second, by dispersal of the interresponse times toward a random interresponse-time distribution. Experiment 2 applied the analysis described in Experiment 1 to the effects of desipramine and gepirone. Both drugs decreased response rate and increased reinforcement rate, but their effects on the distribution of interresponse times were different. The increase in reinforcement rate observed with desipramine was accompanied by a coherent shift of the reinforcement rate observed with gepirone was accompanied by dispersal of the interresponse-time distribution toward the random negative exponential prediction.


Cardiac stimulation with high voltage discharge from stun guns.
The ability of an electrical discharge to stimulate the heart depends on the duration of the pulse, the voltage and the current density that reaches the heart. Stun guns deliver very short electrical pulses with minimal amount of current at high voltages. We discuss external stimulation of the heart by high voltage discharges and review studies that have evaluated the potential of stun guns to stimulate cardiac muscle. Despite theoretical analyses and animal studies which suggest that stun guns cannot and do not affect the heart, 3 independent investigators have shown cardiac stimulation by stun guns. Additional research studies involving people are needed to resolve the conflicting theoretical and experimental findings and to aid in the design of stun guns that are unable to stimulate the heart.


Aging drives cerebrovascular network remodeling and functional changes in the mouse brain.
Aging is the largest risk factor for neurodegenerative disorders, and commonly associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts the vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods (serial two-photon tomography and light sheet microscopy) and in vivo imaging (wide field optical spectroscopy and two-photon imaging) to determine detailed changes in aged cerebrovascular networks. Whole-brain vascular tracing showed an overall ~10% decrease in vascular length and branching density, and light sheet imaging with 3D immunolabeling revealed increased arteriole tortuosity in aged brains. Vasculature and pericyte densities showed significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. Moreover, in vivo imaging in awake mice identified delays in neurovascular coupling and disrupted blood oxygenation. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.


Influence of estrogen and polyamines on mifepristone-induced apoptosis in prostate cancer cells.
Although androgens are the main steroids controlling the growth of prostate glands, estrogens are also important in the regulation of its growth. Prostate cancer cells, like other cancer cells, maintain high levels of polyamines. In LNCaP cells, apoptosis is induced by mifepristone. During the process of cell death, the regulation of ROS production, caspase-3 activation and poly (ADP-ribose) polymerase cleavage were investigated in the presence of estrogen and polyamines to identify their possible roles. The cell growth was assessed using the MTT assay, and the intracellular ROS production by the DCFH-DA assay. The p53 protein expression, activation of caspase-3 and PARP cleavage were checked by Western blotting, with specific antibodies to each. The growth and viability of the cells were significantly inhibited, in a dose- and time-dependent manners, by mifepristone (MIF) treatment. The production of ROS were dependent on the MIF dosage. The activation of caspase-3 and cleavage of PARPalso increased with the duration of MIF treatment. The expression of p53 protein also increased with increases in the MIF incubation time. E(2) severely inhibited the ROS production, caspase-3 activation and PARP cleavage. However, polyamines only inhibited the ROS production, without influencing the caspase-3 activation or PARP cleavage. In LNCaP cells, MIF induces apoptosis through ROS production. The expression of p53 protein, caspase-3 activation and PARP cleavage accompanied the process of apoptosis. The apoptotic processes were inhibited by E(2), but polyamines only inhibited the ROS production, implying the multifunctional role of E(2), in addition to its role as a free radical scavenger.


Dosing monitoring system using iMec and ubiquitous sensors.
Recently, the number of senior citizens who are living alone and taking medicine is increasing due to population aging. Since these people have many risks of incorrect dosing, their caretakers living at a distance are concerned about their health. Therefore, we developed iMec (intelligent medicine case) and propose iMec system that is composed of iMec and ubiquitous sensors. The system can support correct dosing of recipient and dosing monitoring of their caretakers. The iMec is a medicine case that not only detects medicine in the medicine case by image processing but also notifies about dosing timing and dosage by touch display and speaker. The ubiquitous sensors assist the iMec to decide dosing timing. We have confirmed the validity of the image processing methods by experiments.


Oxygen affinity and electrolyte distribution of human blood: changes induced by propranolol.
Propranolol causes a massive leakage of potassium ions from red cells, which results in an alteration of the Gibbs-Donnan equilibrium across the red cell membrane. According to such a mechanism, the presence of propranolol significantly increases the hydrogen ion activity of the interior of the red cell, causing a decreased oxygen affinity of hemoglobin according to the classical Bohr effect. No release of 2,3-diphosphoglycerate which may be bound to the membrane is thus necessary to explain the effect of propranolol on the oxygen dissociation curve of blood.


The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis.
Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells. GPR56 was upregulated in transgenic mice overexpressing human progastrin. While recombinant human progastrin promoted the growth and survival of wild-type colonic organoids in vitro, colonic organoids cultured from GPR56-/- mice were resistant to progastrin. We found that progastrin directly bound to, and increased the proliferation of, GPR56-expressing colon cancer cells in vitro, and proliferation was increased in cells that expressed both GPR56 and the cholecystokinin-2 receptor (CCK2R). In vivo, deletion of GPR56 in the mouse germline abrogated progastrin-dependent colonic mucosal proliferation and increased apoptosis. Loss of GPR56 also inhibited progastrin-dependent colonic crypt fission and colorectal carcinogenesis in the azoxymethane (AOM) mouse model of colorectal cancer. Overall, we found that progastrin binds to GPR56 expressing colonic stem cells, which in turn promotes their expansion, and that this GPR56-dependent pathway is an important driver and potential new target in colorectal carcinogenesis.


Micropatterned co-culture of cardiac myocytes on fibrous scaffolds for predictive screening of drug cardiotoxicities.
The spatial arrangement of cardiac myocytes (CMs) and other non-myocytes scaffolds, closely resembling native tissue, is essential to control the CM morphology and function for cardiac tissue regeneration. In the current study, micropatterned fibrous scaffolds were developed to establish a CM co-culture system with cardiac fibroblasts (CFs) and endothelial cells (ECs) as a potential in vitro drug screening model. To pursue a biomimetic approach to influence CM behaviors, strip, oval and wave-patterned mats were constructed by deposition of electrospun fibers on lithographic collectors, followed by precise stacking for cell co-cultures. CMs, CFs, and ECs were located on the patterned scaffolds with controlled cellular distribution in the respective regions and no across condition was found. Compared with those after strip and oval-patterned co-culture, CMs co-cultured on wave-patterned scaffolds displayed significantly greater cell viabilities, larger cell elongation ratios, stronger expressions of cardiac-specific Troponin I, connexin 43 and sarcomeric α-actinin and higher beating rates during 15 days of incubation. The responses of co-cultured CMs to quinidine, erythromycin and sotalol show good correlations with clinical observations in the beating rate and the prolongation of the contraction and relaxation time. The in vivo safety data reflected well with the concentrations for 50% of maximal effect (EC50) after drug treatment on co-cultured CMs, which was determined from the changes in the corrected field potential duration (FPDc) against the drug concentrations. During 15 days of patterned co-culture, the interbeat intervals and fluctuations of the CMs indicated quick changes in response to haloperidol treatment and sufficient restoration of the original beating profiles after drug removal. This study demonstrates the capabilities of micropatterned co-culture of CMs to establish the cardiac function as a reproducible and reliable platform for screening cardiac side effects of drugs.


Does occupational exposure to brown coal dust cause a decline in lung function?
To determine if the rate of change in forced expiratory volume in one second (FEV1) in subjects with high exposure to Latrobe Valley brown coal dust was significantly greater than the rate of change among subjects with low exposure. A retrospective dynamic cohort design with variable time windows. This study was conducted over a period of 14 years from 1980 to 1994 and used data collected by the State Electricity Commission (SEC) Lung Function Unit for an asbestos surveillance programme. The subjects were exposed to low, medium, or high levels of coal dust. Basic spirometry with wedge bellows spirometers was used to assess lung function. A general linear model (GLM) was used to assess the effects of smoking and exposure to coal dust upon the change in forced expiratory volume in one second (FEV1) while adjusting for age and height. The mean (95% confidence interval (95% CI) rate of decline in FEV1 was 40 (36 to 44) ml/year. Age was a significant predictor of change. A significant effect was found for smoking (P = 0.02) and for exposure to coal dust (P = 0.008). The only significant difference with exposure to coal dust was between the high and mixed exposure categories. There is no convincing evidence of excessive decline in FEV1 with exposure to coal dust > 0.75 mg/m3. The absence of a dose response relation provides some evidence against a causal relation. On the basis of this study, reduction of the exposure standards currently applied to brown coal dust in the Victorian electricity industry is not warranted to prevent respiratory disease.


Unusual and Unexpected Allergic Reactions Can Be Unraveled by Molecular Allergy Diagnostics.
The fifth class of immunoglobulin, immunoglobulin E (IgE) was discovered in 1967 and has had immense importance for the understanding, diagnosis, and treatment of allergic disease. More than 50 years have passed and efforts to characterize, standardize, and refine allergens with the aim to improve clinical diagnosis and allergen-specific immunotherapy are still ongoing. Another important breakthrough was made in 1999 with the introduction of component-resolved diagnostics (CRD), making it possible to quantify IgE antibodies against individual allergen proteins for diagnostic purposes at a molecular level. The progress and developments made in allergy diagnosis often originate from clinical observations and case studies. Observant physicians and health-care personnel have reported their findings in the medical literature, which in turn has inspired researchers to become involved in clinical research. Allergists continuously encounter new allergies and are often asked by their patients how to prevent new reactions. In the current article, we focus on recent clinical observations that can now be explained by CRD. The examples taken concern allergic reactions toward peanuts, tree nuts, lemon kernels, health drinks, meat, insects, dog dander, cannabis, and semen. We now have an improved understanding of why patients may react in a serious or unexpected way, as illustrated by these examples, yet many other clinical observations remain unexplained. The aim of this review is to highlight the importance of clinical observations among allergic patients, focusing on systemic, or unusual and unexpected allergic reactions, where component-testing has further refined the diagnosis of IgE-mediated allergy.


Testing an Integrated Model of Alcohol Norms and Availability, Binge Drinking, and Teen Dating Violence.
This study examined an integrated model that proposes that alcohol availability and alcohol norms will directly and indirectly via binge drinking predict physical, sexual, and emotional teen dating violence (TDV) victimization. These data come from 22,336 high school students (49.6%) from 69 schools who participated in the New Hampshire Youth Risk Behavior Survey in 2017. All teens included in the analyses reported dating in the past year. Perceptions of alcohol availability and peer and parental acceptance of teen drinking related to an increased likelihood of binge drinking, and binge drinking related to an increased risk of physical, sexual, and emotional TDV victimization. Also, alcohol availability and perceived parental and peer norms exerted a direct influence on the increased likelihood of TDV victimization. Lastly, we examined the moderating role of gender on these associations. Only one significant association emerged, such that for boys, but not for girls, perceived parental alcohol norms related to an increased likelihood of emotional TDV victimization. Findings suggest that TDV prevention and risk reduction initiatives need to focus on efforts that reduce binge drinking in teens. Reducing alcohol availability and shifting perceptions of parental alcohol norms and peer alcohol norms could be helpful in reducing both binge drinking and TDV victimization.


A Case Series and Review of Bisphosphonate-associated Orbital Inflammation.
To report the largest series of new cases to date of bisphosphate-associated orbital inflammation. A retrospective case review of patients with orbital inflammation following treatment with systemic bisphosphonate. Six patients over an 18-month period (2 males, 4 females) with an average age of 62.2 years had onset of orbital inflammatory symptoms 1-11 days after intravenous bisphosphonate infusion or, in 1 case, 4 weeks after initiation of oral bisphosphonate therapy. Imaging revealed diffuse orbital involvement in 3 cases, isolated lateral rectus muscle involvement in 2 cases, and superior rectus-levator involvement in 1 case. Two patients' symptoms resolved spontaneously within 2 weeks, and 3 responded rapidly and completely to corticosteroid therapy. The 1 patient on oral bisphosphonate had a slower but complete response to corticosteroid treatment. Clinicians should be aware of the association between acute orbital inflammation and recent treatment with systemic bisphosphonate medication.


Combining passive acoustics and imaging sonar techniques to study sperm whales' foraging strategies.
Sperm whales forage in the deep ocean, hunting for squid. An innovative approach for the study of sperm whale foraging behavior and habitat selection is reported in this letter. A DIDSON imaging sonar mounted on a profiler with a conductivity, temperature, and depth sensor was used to count and measure potential prey in the deep ocean during sperm whales' acoustical foraging encounters in Hawaii. Preliminary results show how this technique can be applied to the study of deep diving whale foraging and habitat selection. Sperm whales foraged where the density of prey decreased with depth and where the size of prey increased with depth.


In Vitro and In Silico Study of Analogs of Plant Product Plastoquinone to Be Effective in Colorectal Cancer Treatment.
Plants have paved the way for the attainment of molecules with a wide-range of biological activities. However, plant products occasionally show low biological activities and/or poor pharmacokinetic properties. In that case, development of their derivatives as drugs from the plant world has been actively performed. As plant products, plastoquinones (PQs) have been of high importance in anticancer drug design and discovery; we have previously evaluated and reported the potential cytotoxic effects of a series of PQ analogs. Among these analogs, PQ2, PQ3 and PQ10 were selected for National Cancer Institute (NCI) for in vitro screening of anticancer activity against a wide range of cancer cell lines. The apparent superior anticancer potency of PQ2 on the HCT-116 colorectal cancer cell line than that of PQ3 and PQ10 compared to other tested cell lines has encouraged us to perform further mechanistic studies to enlighten the mode of anti-colorectal cancer action of PQ2. For this purpose, its apoptotic effects on the HCT-116 cell line, DNA binding capacity and several crucial pharmacokinetic properties were investigated. Initially, MTT assay was conducted for PQ2 at different concentrations against HCT-116 cells. Results indicated that PQ2 exhibited significant cytotoxicity in HCT-116 cells with an IC50 value of 4.97 ± 1.93 μM compared to cisplatin (IC50 = 26.65 ± 7.85 μM). Moreover, apoptotic effects of PQ2 on HCT-116 cells were investigated by the annexin V/ethidium homodimer III staining method and PQ2 significantly induced apoptosis in HCT-116 cells compared to cisplatin. Based on the potent DNA cleavage capacity of PQ2, molecular docking studies were conducted in the minor groove of the double helix of DNA and PQ2 presented a key hydrogen bonding through its methoxy moiety. Overall, both in vitro and in silico studies indicated that effective, orally bioavailable drug-like PQ2 attracted attention for colorectal cancer treatment. The most important point to emerge from this study is that appropriate derivatization of a plant product leads to unique biologically active compounds.


Leucoencephalopathy with brainstem and spinal cord involvement and high lactate: quantitative magnetic resonance imaging.
Leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is a white matter disorder caused by DARS2 mutations. The pathology is unknown. We observed striking discrepancies between improvement on longitudinal conventional magnetic resonance images and clinical deterioration and between large areas of high signal on diffusion-weighted imaging and small areas with low apparent diffusion coefficient values. These observations prompted a longitudinal and quantitative magnetic resonance imaging study. We investigated eight patients (two males, mean age 27 years). Maps of T(2) relaxation times, fractional anisotropy, apparent diffusion coefficients, signal on diffusion-weighted imaging, and axial and radial diffusivities were generated. Brain metabolites, obtained by chemical shift imaging, were quantified. Data analysis focused on: (i) white matter with low apparent diffusion coefficient; (ii) white matter with high T(2) values; (iii) white matter with intermediate T(2) values; and (iv) normal-appearing white matter. The areas were compared with similarly located areas in eight matched controls. In five patients, T(2)-weighted images, spectroscopy, apparent diffusion coefficient maps and diffusion-weighted imaging maps were compared with those obtained 5-7 years ago. In white matter with low apparent diffusion coefficient, axial and radial diffusivities were decreased and fractional anisotropy was high. T(2) values were intermediate. These areas with truly restricted diffusion were small and often observed at the periphery of areas with high T(2) values. In the white matter with high and intermediate T(2) values, apparent diffusion coefficients and axial and radial diffusivities were increased and fractional anisotropy decreased. The signal on diffusion-weighted imaging was highest in white matter with high T(2) values, an effect of T(2) shinethrough. Chemical shift imaging in both white matter types showed increased lactate, increased myo-inositol and decreased N-acetylaspartate, most pronounced in white matter with high T(2) values. Normal-appearing white matter was comparable with white matter of control subjects. Over time, mild decreases in T(2) signal intensities, signal on diffusion-weighted imaging and in extent of the low apparent diffusion coefficient areas were seen. In conclusion, the disease process in leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is extremely slow. We hypothesize that diffusion restriction is the first stage of the disease caused by intramyelinic water accumulation, followed by slow shift and then loss of the surplus of water. On conventional T(2) images this leads to improvement. We hypothesize that it is loss of water rather than structural restoration that causes the change in T(2) signal intensity, which would be in better agreement with the slow clinical deterioration.


A quadrupole ion trap mass spectrometer for dry microparticle analysis.
In this work, we report a new design of a charge detection quadrupole ion trap mass spectrometer (QIT-MS) for the analysis of micro-sized dry inorganic and bioparticles including red blood cells (RBCs) and different sizes of MCF-7 breast cancer cells. The developed method is one of the fastest methods to measure the mass of micro-sized particles. This system allows the online analysis of various micro-sized particles up to 1 × 1017 Da. The calibration of the mass spectrometer has been done by using different sizes of polystyrene (PS) particles (2-15 μm). The measured masses of RBCs were around 1.8 × 1013 Da and MCF-7 cancer cells were between 1 × 1014 and 4 × 1014 Da. The calculated mass distribution profiles of the particles and cells were given as histogram profiles. The statistical data were summarized after Gaussian type fitting to the experimental histogram profiles. The new method gives very promising results for the analysis of particles and has very broad application.


Soft-tissue tension during total hip arthroplasty measured in four patients and predicted using a musculoskeletal model.
Soft-tissue tension around the hip joint is related to the incidence of dislocation after total hip arthroplasty (THA), but it remains difficult to quantify the soft-tissue tension during surgery. In this study, a three-dimensional force sensor-instrumented modular femoral head was developed and used to quantify soft-tissue tension during THA. The forces at the hip joint were also calculated using a three-dimensional musculoskeletal computer model to validate the measured forces. Soft-tissue tension was investigated by measuring the hip joint forces and directions during intraoperative trialing in four patients through passive range of motion (ROM) from 0° extension to 90° flexion. A musculoskeletal model with THA, which was scaled to one of four patients, was developed. The hip joint forces were calculated under the same motion. Through the passive ROM, the magnitude of soft-tissue tension was greatest when the hip was extended, decreased with flexion to 34°, and progressively increased to flexion at 90°. The mediolateral force component was relatively constant, but the supero-inferior and anterior-posterior force components changed significantly. Within-individual variations were small during three repeated cycles of measurement, but magnitudes varied significantly among patients. Similar force patterns and magnitudes were calculated by the musculoskeletal model. This study demonstrates that it is possible to quantify soft-tissue tension and direction during THA with an instrumented head. There was general agreement between the calculated and measured forces in both pattern and magnitude. Including additional subject-specific details would further enhance agreement between the model and measured hip forces.


How do German veterinarians use social networks? A study, using the example of the 'NOVICE' veterinary medicine network.
NOVICE (Network Of Veterinary ICT in Education, http://www.noviceproject.eu/), is a professional online social network for veterinarians, lecturers and students of veterinary medicine as well as for e-Learning advisers and others working in establishments that teach veterinary medicine. This study sets out to investigate to what extent German veterinarians, lecturers, students of veterinary medicine and e-Learning representatives would accept a specialist network, what requirements would have to be met by an online social network, how to use web 2.0 tools [21], [30] and what advantages a specialist network could offer. The investigation was carried out by analysing data from the Elgg platform database as well as using Google Analytics. Annual focus group surveys and individual interviews were carried out in order to perform an analysis of acceptance among network users. 1961 users from 73 different countries registered on the NOVICE site between 1 September 2010 and 21 March 2012. Germany represents the biggest user group, with 565 users (28.81%). During this period, most individual hits on the website came from Germany too. In total, 24.83% of all members are active, while 19.22% of German members participate actively. In terms of gender, there are significantly more female members than male members, both in the NOVICE network as a whole as well as in Germany. The most used web 2.0 tools are chat and email messaging services as well as writing wikis and contributing to forum discussions. The focus group surveys showed that respondents generally make use of other online communities too. Active members generally use more web 2.0 tools than in other networks, while passive members are generally more reluctant in all networks. All participants of the survey welcomed the idea of having a network specifically set up for the profession and believe that it could be very useful for veterinary medicine. The network and its membership figures developed very positively during the assessed time period. Until now, the focus of the content of contributions in NOVICE (Network of Veterinary ICT in Education) has been on veterinary medicine teaching supported by e-Learning. An increase in the number of members would, however, be beneficial in order to further develop the network so that valuable exchange of information and informal learning can also take place in other specialist areas of veterinary medicine.


The utility of p16INK4a and Ki-67 staining on cell blocks prepared from residual thin-layer cervicovaginal material.
Cell blocks can be prepared from residual thin-layer cervicovaginal (ThinPrep) material and can be used in immunohistochemical staining assays for p16INK4a and Ki-67, which are surrogate markers related to human papillomavirus infection and cell proliferation, respectively. The objectives of the current study were 1) to investigate the feasibility and the role of cell block preparations in identifying significant neoplastic and preneoplastic lesions of the uterine cervix and 2) to assess the feasibility of using p16INK4a and Ki-67 immunohistochemical staining patterns on cell blocks to identify significant preneoplastic cervical lesions. Cervicovaginal cytology specimens from 85 patients were analyzed. Cytologic diagnoses based on ThinPrep Papanicolaou test results were as follows: squamous cell carcinoma was diagnosed in 3 specimens, high-grade squamous intraepithelial lesions (HSIL) were diagnosed in 27 specimens, low-grade squamous intraepithelial lesions (LSIL) were diagnosed in 20 specimens, and atypical squamous cells of uncertain significance (ASCUS) were diagnosed in 11 specimens. Diagnoses of negativity for intraepithelial lesions or malignancy (NILM) were made in 24 specimens. Cell block sections were stained with hematoxylin and eosin and were immunostained with antibodies against p16INK4a protein and Ki-67 antigen. The cytomorphologic diagnoses made using cell block preparations were as follows: SCC in 2 specimens, HSIL in 20 specimens, LSIL in 30 specimens, NILM in 32 specimens, and no diagnosis in 1 specimen. In 62 cases (73%), the diagnoses made using cell block preparations were in agreement with the ThinPrep diagnoses. Immunostaining of cell blocks for p16INK4a and Ki-67 exhibited a statistically significant association (P < 0.05) with the presence of significant lesions on either cell block or ThinPrep analysis. To the authors' knowledge, p16INK4a has not been analyzed previously in ThinPrep cell blocks, and the correlation between Ki-67 expression and cell block diagnoses also has not been reported previously. The current results indicate that cell blocks prepared from residual ThinPrep material represent an additional reliable diagnostic tool in the evaluation of cervical samples. Furthermore, immunohistochemical studies may be helpful in differentiating significant preneoplastic changes from other cervical lesions, such as atrophy.


A scoping review of simulation-based dental education.
This article was migrated. The article was marked as recommended. In order to meet the needs of student learning within a competency-based pedagogy, it is necessary to understand the current philosophies and modalities being used in dental and oral health simulation-based education. The aim of this literature review is to identify the existing research relating to the educational structure of dental and oral health simulation activities. The review is presented as a scoping review, formulated and conducted using a modified five stage methodological framework. Despite evidence showing that the healthcare simulation model is ideal for learning and assessments of non-clinical and clinical tasks such as psychomotor skills, there is a paucity of published literature relating to simulation in dental and oral health education. Out of 72 initial articles only six papers related to dental preclinical psychomotor skills in an educational setting, none of which were deemed high-quality. Deficiencies in these papers included no statements defining underpinning educational theory, limited acknowledgement of evidence-based simulation activities including preparation, briefing, simulation, feedback, debriefing, reflection and evaluation. Given the widespread use of simulation in dentistry, academics should be encouraged to publish their scholarly activities in simulation-based dental education in order so that all dental faculties can work towards developing contemporary simulation curriculum to provide optimum teaching and learning opportunities for students.


Visual search elicits the electrophysiological marker of visual working memory.
Although limited in capacity, visual working memory (VWM) plays an important role in many aspects of visually-guided behavior. Recent experiments have demonstrated an electrophysiological marker of VWM encoding and maintenance, the contralateral delay activity (CDA), which has been shown in multiple tasks that have both explicit and implicit memory demands. Here, we investigate whether the CDA is evident during visual search, a thoroughly-researched task that is a hallmark of visual attention but has no explicit memory requirements. The results demonstrate that the CDA is present during a lateralized search task, and that it is similar in amplitude to the CDA observed in a change-detection task, but peaks slightly later. The changes in CDA amplitude during search were strongly correlated with VWM capacity, as well as with search efficiency. These results were paralleled by behavioral findings showing a strong correlation between VWM capacity and search efficiency. We conclude that the activity observed during visual search was generated by the same neural resources that subserve VWM, and that this activity reflects the maintenance of previously searched distractors.


Risk and protective factors of dementia among adults with post-traumatic stress disorder: a systematic review protocol.
Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia. Individual epidemiological studies have controlled for several confounders of the relationship between PTSD and increased dementia risk, yet particular risk factors underlying this relationship have not been determined. This systematic review protocol aims to identify risk and protective factors of dementia among adults with PTSD. We will conduct an electronic search of the databases: PubMed, CINAHL, PsychINFO, The Cochrane Library, Scopus and ProQuest Dissertation and Theses Global. After screening the studies, quantitative synthesis will be performed, if possible. Otherwise, a narrative synthesis will be performed. We will include randomised controlled trials and other types of research evidence including longitudinal cohort studies. Strength of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations method. Examples of variables that will be extracted are: year of PTSD diagnosis, comorbid conditions, health behaviours, pharmacological treatments and year of mild cognitive impairment or dementia diagnosis. We developed this systematic review protocol according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. The proposed study will not collect individual-level data and, therefore, does not require ethical approval. Results of this study will provide current evidence on risk and protective factors of dementia in adults with PTSD. Findings will be disseminated in peer-reviewed publications and conference presentations. CRD42019128553.


Joint effects of birth outcomes and childhood body mass index on respiratory symptoms.
Thinness in infancy and higher childhood body mass index (BMI) are risk factors for poor respiratory health. However, few studies have examined the joint effects of birth outcomes and childhood BMI on the occurrence of respiratory symptoms. A total of 78,011 Taiwanese middle-school children were investigated between 1995 and 1996 in a nationwide International Study of Asthma and Allergies in Childhood (ISAAC) survey, with standardised height/weight measurement. Their survey data was compared successfully with the birth registration dataset. Childhood BMI was positively associated with all respiratory symptoms, with greater effects and significant risks associated with serious phenotypes in the video questionnaire. Children with a history of low birth weight (LBW), those who were born prematurely (pre-term), or those who were small for gestational age (SGA) were also more likely to have allergic respiratory symptoms. As birthweight and gestational age were not positively associated with childhood BMI, we proposed that LBW, pre-term birth and childhood BMI were independent factors for respiratory symptoms. LBW, pre-term birth and childhood BMI are all independent risk factors for respiratory symptoms in children. Children with a history of LBW, pre-term birth or SGA and a higher current BMI might have larger respiratory burden.


[Corneal biomechanics].
To review the corneal biomechanic concepts and to analyse, clarify and understand their relevance in refractive surgery. A literature review has been done using different databases. Corneal biomechanic concepts are not new and are applied implicitly in numerous surgical procedures. Their origin is related to tonometry studies, but they gained in popularity when they were linked to the treatment of keratoconus, a pathology in which the mechanical properties of the cornea are altered. Factors determining corneal stability were thus defined. Corneal biomechanics have also been used following refractive surgery to study post-operative keratectasia and to improve ablation patterns, which ignores the corneal response. The new ablation systems need to include the biomechanical factors, which motivate research conducted in physical-mathematical models and in corneal wound healing, improving our knowledge about the corneal biomechanical response. The corneal biomechanic concepts have gained in popularity with the advent of refractive surgery, although they did exist previously. Their relevance is linked to improvements in the ablation systems used in an attempt to obtain more accurate and reliable results.


Failure analysis of explanted sternal wires.
To classify and understand the mechanisms of surface damages and fracture mechanisms of sternal wires, explanted stainless steel sternal wires were collected from patients with sternal dehiscence following open-heart surgery. Surface alterations and fractured ends of sternal wires were examined and analyzed. Eighty fractured wires extracted from 25 patients from January 1999 to December 2003, with mean implantation interval of 55+/-149 days (range 5-729 days) after cardiac surgery, were studied by various techniques. The extracted wires were cleaned and the fibrotic tissues were removed. Irregularities and fractured ends were assayed by a scanning electron microscopy. After stereomicroscopy and documentation, the explants were cleaned with 1% sodium hypochlorite to remove the blood and tissues and was followed by cleaned with deionized water and alcohol. The explants were examined by stereomicroscopy, and irregularities on surface and fracture surfaces of sternal wires were assayed by scanning electron microscopy, energy dispersive X-ray analysis (EDAX) and X-ray mapping. The explants with surrounding fibrotic tissue were stained and examined with stereomicroscopy and transmission electronic microscopy. Corrosion pits were found on the surface of explanted sternal wires. EDAX and X-ray mapping examinations revealed diminution of nickel concentration in the severely corroded pits on sternal wires. A feature of transgranular cracking was observed for stress corrosion cracking and striation character for typical corrosion fatigue was also identified. TEM examination of tissue showed the metallic particles in phagolysosomes of macrophages inside the surrounding sternal tissue. The synergic effect of hostile environment and the stress could be the precursors of failures for sternal wires.


Characterization of Theiler's murine encephalomyelitis virus RNA.
Theiler's murine encephalomyelitis viruses are usually included in the enterovirus genus of the family Picornaviridae, although there is little physicochemical evidence to support this classification. In this report, the size of the RNA of highly virulent and less virulent representatives of the Theiler's group of viruses has been determined by sucrose gradient centrifugation and electrophoresis in agarose to be the same as that of other enteroviruses. The absence of a poly(C) residue provides evidence that these viruses are not cardioviruses or aphthoviruses. The base composition of the two members are similar to each other but differ from those of other enteroviruses. However the one- and two-dimensional maps of the ribonuclease T1 hydrolysates of the two virus RNAs show considerable differences despite their close serological similarity. Virus-specified RNA synthesis in cells infected with the more virulent strain of the virus was almost 10 times greater than that induced by the less virulent strain, in accord with the yields of virus particles.


Diabetic severity and oncological outcomes of colorectal cancer following curative resection: A population-based cohort study in Taiwan diabetes and colorectal cancer prognosis.
Although diabetes is a poor prognostic factor for colorectal cancer (CRC), whether diabetes severity provides an additional predictive value for CRC prognosis remains unclear. The study aimed to investigate the prognostic differences after curative CRC resection among patients with different diabetic severities. This population-based retrospective cohort study analyzed data registered between 2007 and 2015 in the Cancer Registry Database, which is linked to the National Health Insurance Research Database and National Death Registry. Patients with CRC who underwent curative radical resection for stage I-III disease were evaluated, with their diabetic status subdivided into no diabetes, diabetes without complication, and diabetes with complications. Cox regressions were applied to determine the association between diabetes severity and CRC survival, including overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS). A total of 59,202 patients with CRC were included. Compared with the no diabetes group, the diabetes without complication group has insignificantly worse OS (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09), DFS (HR, 1.08; 95% CI, 1.04-1.12), and CSS (HR, 0.98; 95% CI, 0.93-1.03), whereas those with complicated diabetes had a significantly higher risk of poor survival (OS: HR, 1.85; 95% CI, 1.78-1.92; DFS: HR, 1.75; 95% CI, 1.69-1.82; CSS: HR, 1.41; 95% CI, 1.33-1.49). Patients with CRC and diabetes also had a higher risk of recurrence than did those without diabetes. Sex and TNM staging were important effect modifiers. Among patients with CRC who undergo curative resection, the severity of the diabetes is inversely correlated with long-term outcomes, especially in women and patients in the earlier stages of CRC. The prognostic impact of diabetes severity in colorectal cancer (CRC) is yet to be clarified. In this cohort study of 59,202 patients with CRC, compared with patients with CRC and without diabetes, those with uncomplicated diabetes had an insignificantly worse CRC survival, whereas those with complicated diabetes had a significantly higher risk of poor survival. Multidisciplinary medical care to prevent progression into diabetes with complications is needed to improve survival among patients with CRC and diabetes.


A perception correlated comparison method for dynamic meshes.
There are multiple areas of computer graphics where triangular meshes are being altered in order to reduce their size or complexity, while attempting to preserve the original shape of the mesh as closely as possible. Recently, this area of research has been extended to cover even a dynamic case, i.e., surface animations which are compressed and simplified. However, to date very little effort has been made to develop methods for evaluating the results, namely the amount of distortion introduced by the processing. Even the most sophisticated compression methods use distortion evaluation by some kind of mean squared error while the actual relevance of such measure has not been verified so far. In this paper, we point out some serious drawbacks of the existing error measures. We present results of the subjective testing that we have performed, and we derive a new measure called Spatiotemporal edge difference (STED) which is shown to provide much better correlation with subjective opinions on mesh distortion.


Streptococcus agalactiae septicemia in a patient with diabetes and hepatic cirrhosis.
Streptococcus agalactiae is a well-known pathogen during pregnancy and in neonates. Among non-pregnant adults, invasive infection, although rare, is showing increasing frequency, especially in chronically ill, immunosuppressed, or older patients. Although rare, the clinical features of meningeal infection caused by S. agalactiae are similar to other bacterial meningitis. The authors report the case of a middle-aged man previously diagnosed with hypertension, diabetes mellitus, and alcoholic liver cirrhosis, who was admitted at the emergency department with a Glasgow Coma Scale of 11/12, generalized spasticity, bilateral Babinski sign, and hypertension. The clinical outcome was bad, with refractory shock and death within 24 hours of hospitalization. The bacteriological work-up isolated S. agalactiae in the cerebral spinal fluid (CSF), blood, and urine. An autopsy revealed meningoencephalitis, acute myocardial infarction, and pyelonephritis due to septic emboli. The authors point out the atypical CSF findings, the rapid fatal outcome, and the importance of including this pathogen among the etiologic possibilities of invasive infections in this group of patients.


Menopause and sexual desire: the role of testosterone.
The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of women's sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 µg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.


An evaluation of a thicker versus a standard condom with gay men.
Although thicker (stronger) condoms are advocated in western Europe for anal intercourse between men, empirical evidence supporting their greater efficacy is lacking. The present study aimed to determine whether a thicker condom is less likely to fail (break or slip off) than a standard (regular thickness) condom, and to establish factors associated with condom failure among gay men. A total of 283 homosexual couples participated in a double-blind, randomized, controlled trial of a standard and a thicker condom. Each couple was allocated nine of either condom type. Data were collected on user characteristics, and a questionnaire completed immediately after the use of each condom. The thicker and the standard condoms were used by 142 and 141 couples, respectively. No significant differences were found between the two condom types with respect to either clinical or non-clinical definitions of failure (breakage and slippage). With instances of inappropriate use removed, failure rates for the standard and the thicker condom were low at 2.5 and 2.3%, respectively. User characteristics associated with breakage were lower educational achievement, lack of confidence in condom use, and a history of condom breakage. Behaviours associated with breakage were unrolling the condom before fitting to the penis, longer penis length, absence of additional lubricant, the use of inappropriate lubricant, and longer duration of intercourse. Breakage and slippage rates were low for both condom types. There is no evidence from the present investigation to support the use of stronger (thicker) condoms over standard strength condoms among gay men. The appropriate use of additional lubricant should be encouraged.