Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.
Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.


Information needs and the related characteristics of Japanese family caregivers of newly diagnosed patients with cancer.
In Japan, family caregivers of newly diagnosed patients with cancer usually receive information on the patient from healthcare professionals before patients are told the truth. Efforts to provide suitable information to these caregivers may be crucial to improving the quality of life in patients as well as in family caregivers. A descriptive correlational study explored and assessed the informational needs of family caregivers of newly diagnosed patients with cancer. Data were obtained by a semistructured interview with a questionnaire administered to 66 caregivers. Information needs were assessed on disease, treatment, prognosis, and patient and family care. In addition, the demographic and situational characteristics related to individual information needs were investigated by logistic regression analyses. More than 70% of caregivers wanted the disease-related information and about one third of those wanted the care-related information for the patient and family. The disease-related information needs had significant correlations only with the demographic variables. The care-related information needs were correlated both with the demographic variables and with the situational variables such as the presence of pain in the patient and the presence of other family caregivers. Our results may help healthcare professionals to plan the appropriate provision of information to newly diagnosed patients with cancer and their family caregivers.


Spatiotemporal analysis of 3D kinematic asymmetry in professional cycling during an incremental test to exhaustion.
This study investigated the influence of an incremental exercise on bilateral asymmetry through the spatio-temporal evolution of 3D joint angular displacement, using the Normalized Symmetry Index ([Formula: see text]) and cross-correlation methods. Twelve professional cyclists performed an incremental test to exhaustion, during which motion capture was used. Results revealed a decrease in range of motion between the first and last stages for twelve of the eighteen joint rotations, with the highest impact observed for right hip flexion/extension (61.8 ± 4.7° to 58.8 ± 4.1°, p < 0.05, ES = 0.68). For both stages, significant bilateral differences greater than 10° were observed for hip and knee flexion/extension (p < 0.05, ES>0.90) and ankle and hip internal/external rotation (p < 0.05, ES>0.25). Cross-correlation displayed the lowest pattern similarities for hip abduction/adduction and the highest similarities for knee flexion/extension, ankle plantarflexion/dorsiflexion and hip internal/external rotation. The cross-correlation method showed that the right leg was mostly ahead of time with respect to the left leg, a trend that was accentuated with power output increase. Instantaneous [Formula: see text] fluctuated up to 18% throughout the pedalling cycle, with different behaviour between the power and recovery phases. This study demonstrated the workload effects on side-to-side joint angular pattern similarity.


The Whiteness pandemic behind the racism pandemic: Familial Whiteness socialization in Minneapolis following #GeorgeFloyd's murder.
Family socialization into the centuries-old culture of Whiteness-involving colorblindness, passivity, and fragility-perpetrates and perpetuates U.S. racism, reflecting an insidious Whiteness pandemic. As a poignant case study, this mixed methods study examined Whiteness socialization among White mothers (N = 392, M = 37.99 years, SD = 4.34) in Minneapolis, Minnesota in the month following the May 2020 police killing of unarmed Black resident, George Floyd. Using Helms' (1984, 2017) White racial identity development theory (WRID), content analyses of qualitative responses classified participants into lower versus higher levels of WRID, after which thematic analyses compared their Whiteness socialization beliefs/values, attitudes, practices, and emotions, and analyses of variance compared their demographics, multiculturalism, and psychological distress. There was strong convergence across qualitative and quantitative findings and results aligned with the WRID model. Racially silent participants (i.e., no mention of Floyd's murder or subsequent events on open-ended questions: 53%) had lower multiculturalism scores and lower psychological distress. Among mothers who were racially responsive (i.e., mentioned Floyd's murder or subsequent events: 47%), those with more advanced WRID (17%) had higher multiculturalism scores; lower ethnic group protectiveness scores; a more effective coping style featuring empathy, moral outrage, and hope; more color- and power-conscious socialization beliefs/values; and more purposeful racial socialization practices than their less advanced peers (30%). Collectively, color-evasion and power-evasion-pathogens of the Whiteness pandemic-are inexorably transmitted within families, with White parents serving as carriers to their children unless they take active preventive measures rooted in antiracism and equity-promotion. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Fatal pulmonary involvement in dermatomyositis.
A 12-year-old boy with classic dermatomyositis developed a rapidly progressive pulmonary process that led to his death a month later. Physiologically, there was interference with the oxygenation of the blood even when 100% oxygen was delivered to the lungs under pressure. Microscopic examination of the lungs disclosed diffuse interstitial pulmonary fibrosis. We conclude that these pulmonary changes were a component of the basic disease.


Recommending Hartree-Fock theory with London-dispersion and basis-set-superposition corrections for the optimization or quantum refinement of protein structures.
We demonstrate the importance of properly accounting for London dispersion and basis-set-superposition error (BSSE) in quantum-chemical optimizations of protein structures, factors that are often still neglected in contemporary applications. We optimize a portion of an ensemble of conformationally flexible lysozyme structures obtained from highly accurate X-ray crystallography data that serve as a reliable benchmark. We not only analyze root-mean-square deviations from the experimental Cartesian coordinates, but also, for the first time, demonstrate how London dispersion and BSSE influence crystallographic R factors. Our conclusions parallel recent recommendations for the optimization of small gas-phase peptide structures made by some of the present authors: Hartree-Fock theory extended with Grimme's recent dispersion and BSSE corrections (HF-D3-gCP) is superior to popular density functional theory (DFT) approaches. Not only are statistical errors on average lower with HF-D3-gCP, but also the convergence behavior is much better. In particular, we show that the BP86/6-31G* approach should not be relied upon as a black-box method, despite its widespread use, as its success is based on an unpredictable cancellation of errors. Using HF-D3-gCP is technically straightforward, and we therefore encourage users of quantum-chemical methods to adopt this approach in future applications.


Listeria monocytogenes engineered to activate the Nlrc4 inflammasome are severely attenuated and are poor inducers of protective immunity.
Inflammasomes are intracellular multiprotein signaling complexes that activate Caspase-1, leading to the cleavage and secretion of IL-1β and IL-18, and ultimately host cell death. Inflammasome activation is a common cellular response to infection; however, the consequences of inflammasome activation during acute infection and in the development of long-term protective immunity is not well understood. To investigate the role of the inflammasome in vivo, we engineered a strain of Listeria monocytogenes that ectopically expresses Legionella pneumophila flagellin, a potent activator of the Nlrc4 inflammasome. Compared with wild-type L. monocytogenes, strains that ectopically secreted flagellin induced robust host cell death and IL-1β secretion. These strains were highly attenuated both in bone marrow-derived macrophages and in vivo compared with wild-type L. monocytogenes. Attenuation in vivo was dependent on Nlrc4, but independent of IL-1β/IL-18 or neutrophil activity. L. monocytogenes strains that activated the inflammasome generated significantly less protective immunity, a phenotype that correlated with decreased induction of antigen-specific T cells. Our data suggest that avoidance of inflammasome activation is a critical virulence strategy for intracellular pathogens, and that activation of the inflammasome leads to decreased long-term protective immunity and diminished T-cell responses.


Short-term evaluation of tegumentary changes of the nose in oral breathers undergoing rapid maxillary expansion.
Rapid maxillary expansion is an orthodontic and orthopedic procedure that can change the form and function of the nose. The soft tissue of the nose and its changes can influence the esthetics and the stability of the results obtained by this procedure. The objective of this study was to assess the changes in nose dimensions after rapid maxillary expansion in oral breathers with maxillary atresia, using a reliable and reproducible methodology through computed tomography. A total of 30 mouth-breathing patients with maxillary atresia were analyzed and divided into a treatment group who underwent rapid maxillary expansion (20 patients, 10 of which were male and 10 female, with a MA of 8.9 years and a SD of 2.16, ranging from 6.5 to 12.5 years) and a Control Group (10 patients, 5 of which were male and 5 female, with a MA of 9.2 years, SD of 2.17, ranging from 6.11 to 13.7 years). In the treatment group, multislice computed tomography scans were obtained at the start of the treatment (T1) and 3 months after expansion (T2). The patients of the control group were submitted to the same exams at the same intervals of time. Four variables related to soft tissue structures of the nose were analyzed (alar base width, alar width, height of soft tissue of the nose and length of soft tissue of the nose), and the outcomes between T1 and T2 were compared using Osirix MD software. In the TG, the soft tissues of the nose exhibited significant increases in all variables studied (p<0.05), whereas, changes did not occur in the control group (p>0.05). In the treatment group, mean alar base width increased by 4.87% (p=0.004), mean alar width increased by 4.04% (p=0.004), mean height of the soft tissues of the nose increased by 4.84% (p=0.003) and mean length of the soft tissues of the nose increased by 4.29% (p=0.012). In short-term, rapid maxillary expansion provided a statistically significant increase in the dimensions of the soft tissues of the nose.


Effect of antiretroviral therapy on changes in the fertility intentions of human immunodeficiency virus-positive women in Addis Ababa, Ethiopia: a prospective follow-up study.
With access to antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) are able to consider childbearing to a greater extent than previously. In many cases, ART has transformed their intentions to have children. The present study aimed to assess changes in fertility intentions 12 months after ART initiation among HIV-positive women in Addis Ababa, Ethiopia. An institution-based follow-up study was conducted among 360 HIV-positive women in Addis Ababa. A logistic regression model was used to assess the influence of socio-demographic, reproductive health, and clinical characteristics on changes in the fertility intentions of women. Overall, 40.8% (147 of 360) of the women reported that they desired to have a child in the future at the baseline visit, while 48.3% (174 of 360) did so at the 12-month follow-up. The proportion of women who reported that they desired to have a child 12 months after ART initiation was higher among ART-initiated women (55.8%, 106 of 190) than ART-naïve women (40.0%, 68 of 170). The adjusted analysis indicated that a change in fertility intentions between baseline and the follow-up visit was significantly associated with ART use (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.20 to 5.20) and marital status, with single (aOR, 5.33; 95% CI, 1.10 to 25.92) and married (aOR, 6.35; 95% CI, 1.44 to 27.99) women being more likely to report fertility intentions than divorced/widowed women. ART use was a significant predictor of change in fertility intentions between the baseline and follow-up visit, which suggests that additional efforts are necessary to integrate family planning and HIV services to address the safe fertility goals of women in the study area.


First experience with the deltastream(R) DP3 in venovenous extracorporeal membrane oxygenation and air-supported inter-hospital transport.
Based on continuous technical innovations and recent research, extracorporeal membrane oxygenation (ECMO) has become a promising tool in the treatment of patients with acute (cardio)pulmonary failure. Nevertheless, any extracorporeal technique requires a high degree of experience and knowledge, so that a restriction to specialized centres seems to be reasonable. As a consequence of this demand, the need for inter-hospital transfer of patients with severely impaired (cardio)pulmonary function is rising. Unfortunately, most of the ECMO devices used in the clinical setting are not suitable for inter-hospital transport because of their size, weight or complexity. In this article, we describe our first experiences with the airborne transport of 6 patients on a new portable, miniaturized and lightweight extracorporeal circulation system, the Medos deltastream® DP3. Six patients suffering acute respiratory failure were taken on venovenous ECMO (DP3) out-of-centre and transferred to the University Medical Center Regensburg by helicopter. All cardiorespiratory-relevant parameters of the patients and the technical functioning of the device were continuously monitored and documented. Implantation of the device and air-supported transport were performed without any technical complications. The patients were transported from a distance of 66-178 km, requiring a time of 40-120 min. With the help of the new deltastream® DP3 ECMO device, a prompt stabilization of the cardiopulmonary function could be achieved in all patients. One patient was under ongoing cardiopulmonary resuscitation by the time our ECMO team arrived at the peripheral hospital and died shortly after arrival in the central emergency ward. Our experience shows that the deltastream® DP3 is an absolutely reliable and safe ECMO device that could gain growing importance in the field of airborne transportation of patients on ECMO due to its unsophisticated, miniaturized and lightweight characteristics.


Risk factors associated with intestinal parasitic infections among inmates of Kisii prison, Kisii county, Kenya.
Intestinal parasitic infections are a major health problem worldwide. In Kenya intestinal parasitic infections are highly prevalent especially in prisons due to poor and/or inadequate infrastructure. The aim of this study was to establish the risk factors associated with intestinal parasites infection among inmates of Kisii prison, Kisii county, Kenya. Fresh stool samples of 384 inmates in Kisii prison aged 20 years and above, were screened for intestinal parasitic infections between February and August 2015. Stool samples were processed using direct fecal smear and formol-ether sedimentation techniques for confirmation then they were examined microscopically. Multiple logistic regression analysis was used to establish the relationship of various factors and practices with the occurrence of intestinal parasites. The differences were considered statistically significant at P < 0.05. Of the 384 inmates screened, 95 (24.7 %) were infected with one or more intestinal parasites. Of the positive inmates, 58 (15.1 %) were infected with one species of protozoa while 24 (5.2 %) were infected with at least one species of helminthes and 13 (3.5 %) had mixed infections of species of intestinal parasites. Washing of hands before meals and after visiting toilets significantly reduced risk of infections (P < 0.05). The level of education was inversely related to the risk of intestinal parasites infection where by inmates at post primary education were least infected with intestinal parasites infection as compared to unschooled inmates (P < 0.05). Wearing of shoes was seen to significantly reduce parasitic infections (P ≤ 0.05). Duties assigned to inmates did not significantly determine the risk of intestinal parasitic infection (P > 0.05). Male inmates had significantly more intestinal parasites infections 57 (21.8 %) compared to females 28 (8.1 %) (P < 0.05). Inmates within ages 20-29 years were more infected (11.3 %) compared to the age group of >60 years (0.6 %) (P < 0.05). There was no statistical significant difference between the number of infections among the length of the jail terms (P < 0.05). Prevalence of intestinal parasites was high among inmates in the study area than the general population. Practices like wearing of shoes, washing of hands before meals after visiting a toilet and level of education affect the spread of the infections.


Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease and its associated morbidities.
Ageing is a nonmodifiable risk factor that is linked to increased likelihood of cardiovascular morbidities. Whilst many pharmacological interventions currently exist to treat many of these disorders such as statins for hypercholesterolemia or beta-blockers for hypertension, the elderly appear to present a greater likelihood of suffering non-related side effects such as increased risk of developing new onset type 2 diabetes (NODM). In some cases, lower efficacy in the elderly have also been reported. Alternative forms of treatment have been sought to address these issues, and there has been a growing interest in looking at herbal remedies or plant-based natural compounds. Oxidative stress and inflammation are implicated in the manifestation of ageing-related cardiovascular disease. Thus, it is natural that a compound that possesses both antioxidative and anti-inflammatory bioactivities would be considered. This review article examines the potential of tocotrienols, a class of Vitamin E compounds with proven superior antioxidative and anti-inflammatory activity compared to tocopherols (the other class of Vitamin E compounds), in ameliorating ageing-related cardiovascular diseases and its associated morbidities. In particular, the potential of tocotrienols in improving inflammaging, dyslipidemia and mitochondrial dysfunction in ageing-related cardiovascular diseases are discussed.


Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology.
Glucocorticoid overexposure in utero may underlie the association between low birth weight and subsequent development of common cardiovascular and metabolic pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure in rat reduces birth weight and programs the hypothalamic-pituitary axis and fasting and postprandial hyperglycemia in adult males and hypertension in adult males and females. This study aimed to determine 1) whether there were gender differences in prenatal DEX-programmed offspring, and 2) whether the renin-angiotensin system (RAS) plays a role in the programming of hypertension. Rats exposed to DEX in utero (100 microg.kg(-1).day(-1) from embryonic days 14-21) were of lower birth weight (by 12%, P < 0.01) and displayed full catch-up growth within the first month of postnatal life. DEX-treated male offspring in adulthood selectively displayed elevated plasma adrenocorticotropic hormone (by 221%) and corticosterone (by 188%, P < 0.05), postprandial insulin-glucose ratios (by 100%, P < 0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (by 38%, P < 0.05). Conversely, DEX-programmed females were hypertensive (by 11%, P < 0.05), with elevated hepatic angiotensinogen mRNA expression (by 9%, P < 0.05), plasma angiotensinogen (by 61%, P < 0.05), and renin activity (by 88%, P < 0.05). These findings demonstrate that prenatal glucocorticoids program adulthood cardiovascular and metabolic physiology in a gender-specific pattern, and that an activated RAS may in part underlie the hypertension associated with prenatal DEX programming.


Bones benefits gained by jump training are preserved after detraining in young and adult rats.
We investigated the osteogenic responses to jump training and subsequent detraining in young and adult male rats to test the following hypotheses: 1) jump training has skeletal benefits; 2) these skeletal benefits are preserved with subsequent detraining throughout bone morphometric changes; and 3) there are no differences between young and adult rats during detraining in terms of the maintenance of exercise-induced changes. Twelve-week-old (young) and 44-wk-old (adult) rats were divided into the following four groups: young-sedentary, young-exercised, adult-sedentary, and adult-exercised. The exercised groups performed jump training (height = 40 cm, 10 jumps/day, 5 days/wk) for 8 wk followed by 24 wk of being sedentary. Tibial bone mineral content and bone mineral density in vivo significantly increased with jump training, and the effects were maintained after detraining in both the young and adult exercised groups, although the benefits of training became somewhat diminished. After 24 wk of detraining, the beneficial effects of training on bone mass and strength were preserved and associated with morphometric changes, such as periosteal perimeter, cortical area, and moment of inertia. There were no significant age-exercise interactions in such parameters, except for the periosteal perimeter. These results suggest that there are few differences in bone accommodation and maintenance by training and detraining between young and adult rats.


Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development.
The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.


Coping with Stress and Body Image in Patients with Ankylosing Spondylitis.
The aim of this study was to determine coping with stress and body image in patients with ankylosing spondylitis (AS) and to investigate the correlation between these two characteristics together and also between them and disease activity/functional capacity. Fourty healthy controls and 40 patients with AS who were diagnosed on the basis of Modified New York Criteria were included in the study. The exclusion criteria were another medical disease or comorbid psychiatric disorder. All participants were administered the Coping Orientations to Problems Experienced (COPE) questionnaire in order to evaluate attitudes to coping with stress and the Multidimensional Body-Self Relations Questionnaire (MBSRQ) to evaluate body image. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate AS patients' disease activities and functional capacities. There was no difference between the two groups in terms of COPE scores. The MBSRQ 'health evaluation' subscale scores were lower and the 'fitness orientation' scores higher in the AS group. The COPE active coping subscale had a weak, positive correlation with MBSRQ total score and a weak, negative correlation with BASFI score. MBRSQ total score had a moderate, negative correlation with BASFI score, and a weak, negative correlation with BASDAI score. The attitudes to coping with stress in AS patients with no accompanying medical disease or psychiatric disorder may not differ from that in healthy controls. Negative health evaluation and fitness orientation must be characteristics considered in psychotherapeutic interventions applied to these patients. In addition, psychotherapeutic interventions directed toward coping with stress and body image may be especially useful in active stages of the disease and in patients with limited functional capacity.


The HEMO study - where do we go from here?
The HEMO study is a randomized clinical trial using a 2x2 factorial design to assign patients to a standard or high dose of dialysis and to a low flux or a high flux dialyzer. This study is the largest, most comprehensive, randomized clinical trial ever performed in the maintenance hemodialysis population. This review analyzes the results of the study and discusses how the HEMO study results affect efforts to lower morbidity and mortality in the hemodialysis population. The primary outcome of the HEMO study was death from any cause. This outcome was not significantly influenced by treatment assignment for the dose of dialysis or for the flux of the dialysis membranes used. The main secondary outcomes also did not differ significantly in either the dose groups or the flux groups. The results of the HEMO study support current clinical practice guidelines for the delivery of thrice-weekly dialysis, but the results do not support conventional attempts to lower the high morbidity and mortality in hemodialysis patients. Current efforts are being focused on increasing dialysis time and/or frequency, improving phosphate control, and lowering traditional and nontraditional risk factors for adverse cardiovascular events in this patient population.


Endoscopic Ear Surgery for External Auditory Canal Cholesteatoma.
Treatment of external auditory canal cholesteatoma (EACC) has been a question of debate. To our knowledge and according to a systematic review of endoscopic ear surgery (EES) in 2015, this study describes for the first time the technique and outcome by solely transcanal EES for EACC. Retrospective case series, level of evidence IV. Between October 2014 and December 2016, nine patients with unilateral EACC have been treated by EES. Using a bimanual technique, canaloplasty has been performed using tragal perichondrium, cartilage, or artificial bone. Symptoms, signs, and reconstruction technique have been assessed and the primary endpoint: healing time was compared with benchmark values in the literature. During the 26 months study period all of our nine Naim stage III EACCs were successfully treated by EES with median healing time of 23.8 days. EACC limited to the external auditory canal (Naim stage III) represented an ideal target for EES minimizing tissue damage and thus median healing time compared with retroauricular (42-56 d) or endaural (59 d) surgical techniques. Shorter healing time helped to reduce skepticism toward a surgical treatment of EACC from the patient's perspective. Moreover, EES relied on reduced bulky equipment, dressing time, and complex maintenance compared with microscopic techniques. Transcanal endoscopic surgery is a valid treatment option for EACC up to Naim stage III. Moreover, the described procedure fosters in our eyes the teaching of our residence to get familiar with the basic steps of EES.


Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.
Recent evidence shows that long non-coding RNAs (lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma (HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival (OS) of HCC, but the results varied. Thus, more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC. To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC. Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival (RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator (LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas (TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed. The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2J4, EIF3J-AS1, SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio (HR) being 1.807 (95%CI [confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples (P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification. We have constructed a six-lncRNA signature for prognosis prediction of HCC. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.


Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain.
Vagus nerve stimulation therapy, effective for treatment-resistant epilepsy, has recently been approved also for treatment-resistant depression; nevertheless, the molecular mechanism(s) underlying its therapeutic action remains unclear. Given that neurotrophic factors and monoamines could play a crucial role in the pathophysiology of depression, we tested whether vagus nerve stimulation increases the expression of brain-derived neurotrophic factor, fibroblast growth factor, and nerve growth factor as well as the concentration of norepinephrine in the rat brain. Rats were implanted with a vagus nerve stimulator device and the effects of acute stimulation were evaluated on the growth factors mRNA levels and norepinephrine concentration by ribonuclease protection assay and microdialysis, respectively. We found that acute vagus nerve stimulation increased the expression of brain-derived neurotrophic factor and fibroblast growth factor in the hippocampus and cerebral cortex, decreased the abundance of nerve growth factor mRNA in the hippocampus, and, similar to the antidepressant drug venlafaxine, increased the norepinephrine concentration in the prefrontal cortex. This study demonstrates that acute vagus nerve stimulation triggers neurochemical and molecular changes in the rat brain involving neurotransmitters and growth factors known to play a crucial role in neuronal trophism. These new findings contribute to the elucidation of the molecular mechanisms underlying the therapeutic actions of vagus nerve stimulation in both treatment-resistant depression and epilepsy.


Inhibin B as a potential biomarker of testicular toxicity.
Inhibin B is a glycoprotein produced predominantly by Sertoli cells which regulates pituitary FSH release by a negative feedback loop. The regulation of inhibin B is complex with changes in the pattern of secretion occurring during development, and many factors such as FSH, testosterone, Sertoli cell proliferation and germ cell complement likely to contribute to overall production. Systemic inhibin B concentrations seem to reflect the extreme ends of spermatogenic status with high levels of inhibin B observed in normal, fertile individuals and lower levels of inhibin B in individuals with severe damage to the testis as a result of germ cell depletion. Inhibin B has proved valuable in epidemiological studies exploring male infertility with data showing that inhibin B combined with FSH measurements has a higher positive predictive value for detecting male infertility than either alone. Inhibin B is proposed as a potential biomarker of testicular toxicity in rodent toxicity studies to compliment traditional endpoints. In pharmaceutical development, inhibin B might allow better linkage between animal study results and subsequent monitoring of testicular function in clinical trials. An international, intercompany project has been initiated to evaluate the overall suitability and limitations of inhibin B as a biomarker of testicular toxicity.


Foliar Spraying of NaHS Alleviates Cucumber Salt Stress by Maintaining N+/K+ Balance and Activating Salt Tolerance Signaling Pathways.
Hydrogen sulfide (H2S) is involved in the regulation of plant salt stress as a potential signaling molecule. This work investigated the effect of H2S on cucumber growth, photosynthesis, antioxidation, ion balance, and other salt tolerance pathways. The plant height, stem diameter, leaf area and photosynthesis of cucumber seedlings were significantly inhibited by 50 mmol·L-1 NaCl. Moreover, NaCl treatment induced superoxide anion (O2·-) and Na+ accumulation and affected the absorption of other mineral ions. On the contrary, exogenous spraying of 200 μmol·L-1 sodium hydrosulfide (NaHS) maintained the growth of cucumber seedlings, increased photosynthesis, enhanced the ascorbate-glutathione cycle (AsA-GSH), and promoted the absorption of mineral ions under salt stress. Meanwhile, NaHS upregulated SOS1, SOS2, SOS3, NHX1, and AKT1 genes to maintain Na+/K+ balance and increased the relative expression of MAPK3, MAPK4, MAPK6, and MAPK9 genes to enhance salt tolerance. These positive effects of H2S could be reversed by 150 mmol·L-1 propargylglycine (PAG, a specific inhibitor of H2S biosynthesis). These results indicated that H2S could mitigate salt damage in cucumber, mainly by improving photosynthesis, enhancing the AsA-GSH cycle, reducing the Na+/K+ ratio, and inducing the SOS pathway and MAPK pathway.


Pediatric Minimum Speech Test Battery.
Assessment of patient outcomes and documentation of treatment efficacy serves as an essential component of (re)habilitative audiology; however, no standardized protocol exists for the assessment of speech perception abilities for children with hearing loss. This presents a significant challenge in tracking performance of children who utilize various hearing technologies for within-subjects assessment, between-subjects assessment, and even across different facilities. The adoption and adherence to a standardized assessment protocol could help facilitate continuity of care, assist in clinical decision making, allow clinicians and researchers to define benchmarks for an aggregate clinical population, and in time, aid with patient counseling regarding expectations and predictions regarding longitudinal outcomes. The Pediatric Minimum Speech Test Battery (PMSTB) working group-comprised of clinicians, scientists, and industry representatives-commenced in 2012 and has worked collaboratively to construct the first PMSTB, which is described here. Implementation of the PMSTB in clinical practice and dissemination of associated data are both critical for achieving the next level of success for children with hearing loss and for elevating pediatric hearing health care ensuring evidence-based practice for (re)habilitative audiology.


Food-based dietary guidelines: a comparative analysis between the Dietary Guidelines for the Brazilian Population 2006 and 2014.
In 2014, the Brazilian Ministry of Health launched the second edition of the Dietary Guidelines for the Brazilian Population (DGBP), which deploys the new food classification NOVA. It esteems that the second DGBP overcomes the limitations in the previous food guide, reformulating the diet concepts, food pattern, culture and system. The present paper analyses the advances and limits established in the second edition, contrasting with its first edition. The study employs a discourse analysis. The corpus was established through four stages: (i) floating reading of the empirical materials; (ii) deepening readings; (iii) selected discursive sequences; and (iv) organization of the discursive sequences into a matrix for analysis. The data analysis used three steps: (i) identification of similar texts in external materials; (ii) elucidation of linguistic effect through deepening readings of the external materials; and (iii) systematic analysis to identify sequences that expressed equivalence or disparities. Brazil. DGBP 2006 and 2014. Adoption of the NOVA food classification, based on food processing level, enabled the development of dietary guidelines that consider the limitations of the nutritional discourse and may incorporate the sociocultural and social-environmental discourses, evoking pleasure in food, diversity of feeding habits and stimulating culinary practices as promoters of healthy eating practices. The second DGBP enables a new way of thinking about meals and foods, on the strengthening of socio-cultural dimensions of feeding, and on addressing food and nutritional guidelines on culinary practices, eating and edibility.


Fractures in children and adolescents living with perinatally acquired HIV.
Across numerous settings, bone mineral density for age and sex is lower in children/adolescents living with perinatally-acquired HIV (PHIV) compared to uninfected peers. We assessed incidences of any fracture/any long bone fracture, and osteoporosis prevalence in PHIV and HIV-exposed uninfected (PHEU) participants in the Pediatric HIV/AIDS Cohort Study (PHACS). Lifetime history of fracture events from birth up to age 20 years was obtained by chart review and/or interview, including age at fracture, mechanism, and bone(s) fractured. Poisson regression models were fit comparing fracture incidence by HIV status adjusted for age, sex, and race, with effect modification by age (<6, ≥6 yr). PHIV (N = 412) were older (median 17.5 vs 16.7 yr) and more frequently reported black race (72% vs 61%) than PHEU children/adolescents (N = 206). 17% of PHIV and 12% of PHEU ever reported a fracture. Among children <6 yr, the adjusted incidence rate ratio of ≥1 fracture was higher (7.23; 95% CI 0.98, 53.51) in PHIV than PHEU, but similar among children/adolescents ≥6 years (1.20; 95% CI: 0.77, 1.87). Results were similar for long bone fracture. The most common fracture mechanisms were falling to the ground from a standing height (23.6% PHIV vs 8.8% PHEU) and sports injuries (21.3% vs 32.4%), and the most commonly fractured sites were the forearm and small bones of the wrist/hands. None of the children had osteoporosis. Among children/adolescents ≥6 yr of age, fractures were similar by perinatal HIV status. Prospective, targeted collection of fracture history will be necessary to determine rates of fracture as PHIV and PHEU age into adulthood. Lifetime fracture history was collected in children/adolescents living with perinatally-acquired HIV (PHIV) and HIV-exposed uninfected (PHEU) children from birth up to age 20 years. Fracture incidence was higher in PHIV compared to PHEU among children <6 years old, but not among older children/adolescents.


Estimation of invasive Group B Streptococcus disease risk in young infants from case-control serological studies.
Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable use of efficient clinical trial designs for vaccine development and licensure, without needing to undertake efficacy trials in prohibitively large number of mother-infant dyads. The association of maternal naturally acquired serotype-specific anti-capsular antibodies (IgG) against serotype-specific IGbsD in their infants has been studied in case-control studies. The statistical models used so far to estimate IGbsD risk from these case-control studies assumed that the antibody concentrations measured sharing the same disease status are sampled from the same population, not allowing for differences between mothers colonised by GBS and mothers also potentially infected (e.g urinary tract infection or chorioamnionitis) by GBS during pregnancy. This distinction is relevant as infants born from infected mothers with occult medical illness may be exposed to GBS prior to the mother developing antibodies measured in maternal or infant sera. Unsupervised mixture model averaging (MMA) is proposed and applied here to accurately estimate infant IGbsD risk from case-control study data in presence or absence of antibody concentration subgroups potentially associated to maternal GBS carriage or infection. MMA estimators are compared to non-parametric disease risk estimators in simulation studies and by analysis of two published GBS case-control studies. MMA provides more accurate relative risk estimates under a broad range of data simulation scenarios and more accurate absolute disease risk estimates when the proportion of IGbsD cases with high antibody levels is not ignorable. MMA estimates of the relative and absolute disease risk curves are more amenable to clinical interpretation compared to non-parametric estimates with no detectable overfitting of the data. Antibody concentration thresholds predictive of protection from infant IGbsD estimated by MMA from maternal and infant sera are consistent with non-parametric estimates. MMA is a flexible and robust method for design, accurate analysis and clinical interpretation of case-control studies estimating relative and absolute IGbsD risk from antibody concentrations measured at or after birth.


TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level.
Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine N-acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied. Several experiments were undertaken to verify the adequate time to reach the maximal effect by using the TRPV4 agonist GSK1016790A, together with a dose-response study. An increase of 2.4 folds in AANAT was seen after 18 h of incubation with 10 nM of GSK1016790A (p < 0.001, n = 6). This increment was verified by antagonist assays. In summary, AANAT levels and therefore melatonin synthesis change after TRPV4 channel stimulation. Using this cell model together with human ciliary body tissue it is possible to suggest that AANAT plays an important role in pathologies related to intraocular pressure.


Endothelin-like immunoreactivity in hippocampus following transient global cerebral ischemia. I. Neuronal and glial cells.
The effect of transient, global ischemia on endothelin (ET) localization in CA1 area of hippocampus of the rats was investigated using post-embedding immunogold method. This paper provides immunocytochemical evidence that cerebral ischemia is accompanied by the increase of production of endothelin in CA1 area of the rat. This study focuses on the analysis ET-like immunoreactive neurons and glial cells in hippocampal CA1 area after long-term survival after ischemia: 1 week-12 months. One and two weeks after ischemia appearance of shrunken neurons and significant increase in ET-like immunoreactivity in astroglial cells as well as their proliferation was observed. Six and twelve months--marked immunoreactivity of endothelin in shrunken neurons and in perineuronal microglial macrophages was observed. The data suggest the possibility that the increased intracellular content of endothelin has a role in the development of neuronal death even following a long-term period after ischemia.


[Control of milk composition and quality on the farm].
Milk and milk products have a reputation for quality among consumers. Yet the raw material--milk collected on the farm--varies widely in its composition and quality depending on the farming conditions, animal genetics, feed, and environmental determinants. The micronutrient content of milk and milk products, their organoleptic qualities, and the factors that influence these characteristics are now better known. Thus, the dairy industry is better able to develop foods meeting modern demands for taste, safety and health-promoting qualities.


Influence of Tasking During Vestibular Testing.
Purpose The purpose of this study was to investigate the effectiveness of different types of tasking on the measurement of peak slow phase velocity (SPV) for caloric testing and rotary chair testing. Method This study evaluated the peak SPV response for caloric testing and rotary chair across five conditions. Three verbal, one tactile, and one condition without tasking were used for both caloric testing and rotary chair. The subjects consisted of 20 young adults (age range: 22-33 years, M = 26.65, SD = 3.72; seven male, 13 female) with normal vestibular function and no history of ear surgery or vestibular disorder. Study participation consisted of two visits with 24 hr minimum between each, one for caloric testing and one for rotary chair testing. The test completed at each visit was counterbalanced. Caloric Testing: The caloric irrigations were performed 5 times, with the ears randomized and tasking conditions randomized. Rotary Chair Testing: Rotary chair sinusoidal harmonic acceleration testing was performed 5 times at 0.08 Hz with the tasking conditions randomized. Results Tasking of any kind resulted in significantly larger peak SPV responses when compared to the no tasking condition for rotary chair testing. When comparing each type of tasking, no significant differences were noted. No significant difference was noted when comparing the conditions with tasking to the no tasking condition for caloric testing. Conclusions Clinically, either mental or tactile tasking can be utilized as a method to reduce VOR suppression during rotary chair testing. As no difference was found when comparing different verbal tasks to each other, the type of tasking can be catered to the patient. If verbal tasking cannot be completed, the braiding tactile task is a valid substitution. Caloric results varied widely across subjects and did not reach statistical significance, so conclusions on the need for tasking cannot be drawn.


Do not miss rifampicin-induced thrombocytopenic purpura.
Drug-induced immune thrombocytopenia (DITP) can be triggered by a wide range of medications. Although many cases of DITP are mild, some are characterised by life-threatening bleeding symptoms. In the treatment of tuberculosis there are special therapeutic problems related to adverse effects of drugs, compliance to treatment and microbial resistance. Thrombocytopenia is an uncommon but potentially fatal adverse effect of certain antituberculous drugs when the incriminating drug is taken by a susceptible individual. Here the authors report a case of rifampicin-induced thrombocytopenia, which although rare, needs attention.


Pulmonary tuberculosis after lung transplantation.
During a 5-year study period, we diagnosed pulmonary tuberculosis in two (2%) of 94 lung and heart-lung transplant recipients. Each infection occurred 3 months after bilateral lung transplantation in the presence of evidence implicating donor-to-recipient transmission of the pathogen. The radiographic patterns of pulmonary tuberculosis were subtle: narrowing of the middle lobe bronchus of the right lung caused by an endobronchial granulomatous mass (n = 1) and a focal cluster of small nodules in the upper lobe of the left lung and small bilateral pleural effusions (n = 1). Each patient achieved complete clinical and radiographic response after antituberculous therapy. We conclude that Mycobacterium tuberculosis may be transmitted directly by a donor lung and may involve bronchial mucosa, pulmonary parenchyma, and pleura.


Functional magnetic resonance studies of the reorganization of the human hand sensorimotor area after unilateral brain injury in the perinatal period.
Functional magnetic resonance imaging was used to map the hand sensorimotor area of hemiparetic adolescents and young adults who had suffered unilateral brain damage in the perinatal period. Unlike normal subjects, who exhibit cortical activation primarily contralateral to voluntary finger movements, the hemiparetic patients' intact hemispheres were equally activated by contralateral and ipsilateral finger movements. Our findings are consistent with previous clinical observations and animal experiments which suggest that the immature brain is able to reorganize in response to focal injury.


Role of fibrinolysis in sepsis.
Sepsis, defined as infection-induced systemic inflammatory response syndrome, invariably leads to hemostatic abnormalities ranging from insignificant coagulopathy to disseminated intravascular coagulation (DIC). The inflammation-induced activation of coagulation, the downregulation of physiologic anticoagulant pathways, and impairment of fibrinolysis play a pivotal role in the pathogenesis of microvascular fibrin thrombosis and multiple organ dysfunction syndrome (MODS) in DIC associated with sepsis. The balance between tissue plasminogen activator and plasminogen activator inhibitor-1 mainly regulates fibrinolytic activity. Thrombin-activatable fibrinolysis inhibitor and neutrophil elastase also modulate fibrinolysis. Dynamic changes in these molecules are deeply involved in the pathomechanisms of the impairment of fibrinolysis, leading to MODS in DIC associated with sepsis. Evidence indicates that physical entrapment of bacteria by fibrin at the site of infection may limit their capacity to disseminate into nearby tissues, organs, and systemic circulation. Under this circumstance, impairment of fibrinolysis has protective role in the host defense. Given the protective and pathologic potential of fibrinolysis during sepsis, therapeutics that control DIC as a systemic syndrome, while maintaining the host defense at the infectious foci, are required for the protection against both the development of MODS and for the host defense mechanisms.


NHC Core Phosphonium Ylide-based Palladium(II) Pincer Complexes: The Second Ylide Extremity Makes the Difference.
The coordinating properties of N-heterocyclic carbene (NHC) (A), phenolate (B), and phosphonium ylide (C) moieties were investigated systematically through the preparation of a family of NHC, phosphonium ylide-based pincer ligands, where the third donor extremity can be either an NHC, a phenolate, or a phosphonium ylide. The overall donor character of such ligands [NHC(AaBbCc)] (a + b + c = 2) was analyzed by comparison of the molecular orbitals (energy and shape), oxidation potentials (Epox), and IR νCO and νCN stretching frequencies of their isostructural pincer Pd(II) complexes [NHC(AaBbCc)PdL][OTf] (L = NCCH3, CO, or CNtBu). The three categories of pincer complexes based on phosphonium ylides were easily obtained by acidic treatment of their highly stable ortho-metalated Pd(II) precursors prepared in a single step from readily available N-phosphonio-substituted imidazolium salts. Analysis of IR data indicated that NHC and phenolate ligands have a similar donor character but which remains lower than that of the phosphonium ylide. The impact on catalytic performance of the incorporation of a second strongly donating phosphonium ylide into the ligand architecture was illustrated in the Pd-catalyzed allylation of aldehydes.


Polystyrene thin films in CO(2).
In air, or vacuum environments, liquid polystyrene (PS) thin films (thickness, h<100 nm ) supported by SiOx /Si substrates are structurally metastable or unstable, depending on film thickness. They rupture and eventually form droplets on the SiOx /Si substrates (dewet) due to the influence of destabilizing long-ranged van der Waals dispersion forces. We used scanning force microscopy to examine the structural stability of liquid PS films in the thickness range 5 nm<h<100 nm in liquid and in supercritical carbon dioxide ( CO2 ) environments. All films in this thickness range were metastable; holes developed throughout the films and over time these holes grew, impinged, and eventually formed droplets. The rate of destabilization is controlled by three factors: film thickness, temperature, and CO2 pressure (which dictates CO2 volume fraction in the films). Calculations of the effective interface potentials suggest that the energy barrier for nucleation and growth of holes in CO2 is larger than that in air, and in the limit of vanishingly low PS volume fraction the films should be stable.


Positron Emission Tomography of Neuroimmune Responses in Humans: Insights and Intricacies.
The brain's immune system plays a critical role in responding to immune challenges and maintaining homeostasis. However, dysregulated neuroimmune function contributes to neurodegenerative disease and neuropsychiatric conditions. In vivo positron emission tomography (PET) imaging of the neuroimmune system has facilitated a greater understanding of its physiology and the pathology of some neuropsychiatric conditions. This review presents an in-depth look at PET findings from human neuroimmune function studies, highlighting their importance in current neuropsychiatric research. Although the majority of human PET studies feature radiotracers targeting the translocator protein 18 kDa (TSPO), this review also considers studies with other neuroimmune targets, including monoamine oxidase B, cyclooxygenase-1 and cyclooxygenase-2, nitric oxide synthase, and the purinergic P2X7 receptor. Promising new targets, such as colony-stimulating factor 1, Sphingosine-1-phosphate receptor 1, and the purinergic P2Y12 receptor, are also discussed. The significance of validating neuroimmune targets and understanding their function and expression is emphasized in this review to better identify and interpret PET results.


Enhancing safety and quality of shrimp by nanoparticles of sodium alginate-based edible coating containing grapefruit seed extract.
Edible coatings are safe and effective in extending the shelf life of foods. In this study, a nanoparticle-based edible coating solution was prepared, containing alginate as a coating agent and grapefruit seed extract as an antibacterial agent to improve the safety and quality of shrimp during storage. Shrimp coated with this formulation were maintained at 4°C for 8 days, and periodically analyzed for changes in sensory, chemical [total volatile basic nitrogen (TVB-N) and pH] and microbial parameters. The uncoated shrimp exceeded the microbiological limits at 7.87 log CFU/g on Day 4 of storage, whereas the nanoparticle-based coated shrimp did not exceed the limit by Day 8 of storage. In addition, uncoated shrimp tended to maintain their quality, while uncoated shrimp deteriorated due to increased TVB-N values, pH values, and off-flavors. Nanoparticles are easily dispersed in food to minimize flavor impact and enhance diffusion and bioactivity. We concluded that the nanoparticles coating extended the shelf life of shrimp by more than 5 days. Therefore, the use of nanoparticle-based coatings could be a new and effective way to maintain shrimp quality.


Alcohols as Surface Disinfectants in Healthcare Settings.
Isopropyl alcohol and ethyl alcohol have been used as low-level disinfectants in healthcare settings for many years. Recent studies have found that ethyl alcohol inhibits protein synthesis in Escherichia coli by direct effects on ribosomes and RNA polymerase and that 60%-70% solutions have in vitro efficacy against murine norovirus, Ebola virus, and several coronaviruses. Alcohol prep pads or towelettes containing isopropyl or ethyl alcohol and water have been used primarily for disinfection of small noncritical items due to a concern regarding their rapid evaporation rates and associated short contact times. Sterile alcohol solutions are used mostly for disinfection of compounding pharmacies and controlled areas. One new Environmental Protection Agency (EPA)-registered cleaner/disinfectant formulation differs from other alcohol-based disinfectants by virtue of having a 30-second contact time for multiple pathogens and a toxicity rating of category IV. Multiple disinfectants containing ethyl alcohol and/or isopropyl alcohol combined with other active agents such as quaternary ammonium or phenolic compounds are widely used for disinfecting environmental surfaces in healthcare facilities. Infect Control Hosp Epidemiol 2018;39:323-328.


Vibration of a Liquid Crystal Elastomer Spring Oscillator under Periodic Electrothermal Drive.
The oscillations of electrically actuated thermally-responsive liquid crystal elastomer (LCE) microfibers under cyclic electric actuation have been discovered in recent experiments. Periodic electric actuation is a common method of active control with potential applications in the fields of micro-actuators. In this paper, the vibration behavior of LCE spring oscillator under periodic electrothermal drive is studied theoretically. Based on the dynamic LCE model, the dynamic governing equation of the LCE spring oscillator is established, and the time history curves of the vibration are obtained by numerical calculations. The results show that the periodic electrothermal drive can cause periodic vibration of the LCE spring oscillator. With the increase of time rate, the vibration amplitude increases first and then decreases. In a small damping system, there exist optimal sets of electrothermal drive period and electrothermal drive time rate to maximize the system amplitude. For the optimum periodic mode, the vibration amplitude of the spring oscillator is affected by the current heat, damping coefficient, gravital acceleration, spring constant and shrinkage coefficient, but not by the initial velocity. The application examples of LCE materials show that periodic electrothermally driven LCEs have promising applications. The results of this study are instructive for the design of soft robots and LCE-based electric locomotives.


Dual relationships in psychotherapy.
A dual relationship in psychotherapy occurs when the therapist engages in another, significantly different relationship with the patient. The two relationships may be concurrent or sequential. For both sexual and nonsexual dual relationships, men are typically the perpetrators and women are typically the victims. This article presents examples of dual relationships, notes the attention that licensing boards and other agencies devote to this topic, reviews the meager research concerning nonsexual dual relationships, and discusses common strategies that promote both sexual and nonsexual dual relationships.


Role of Mean Platelet Volume in the Prognosis of Gallbladder Carcinoma: A Tertiary Centre Experience.
Mean platelet volume (MPV) is an inflammatory marker indicative of platelet activation. There are several studies that suggest an association between the neoplastic process and cancer metastasis. We performed a retrospective analysis to investigate the role of MPV as a prognostic informative marker in gallbladder cancer. This study included 73 patients who underwent treatment for gallbladder cancer with curative or palliative intent. MPV was obtained and statistically analysed to investigate the association between the nodal status (N), the overall stage as per the American Joint Committee on Cancer (AJCC) staging system, perineural invasion, and differentiation of the tumor. The statistical analysis was done using SPSS Statistics, version 23 (IBM Corp., Armonk, NY). We found that the MPV values were significantly high in node-positive cases (OR = 3.623, 95% CI = 7.778-1.687, p value = -0.0001), cases in the advanced stage (OR = 3.623, 95% CI = 7.778-1.687, p value = 0.0001), cases with perineural invasion (OR = 3.396, 95% CI = 8.319-1.387, p value = -0.0001), and poor differentiation (OR = 2.327, 95% CI = 4.651-1.164, p value = -0.002 ). MPV is an inexpensive and convenient inflammatory marker that correlates with nodal positivity in the staging and prognostication of gallbladder cancer. This marker can be used to ascertain the risk status of gallbladder cancer.


Smart Preventive Maintenance of Hybrid Networks and IoT Systems Using Software Sensing and Future State Prediction.
At present, IoT and intelligent applications are developed on a large scale. However, these types of new applications require stable wireless connectivity with sensors, based on several standards of communication, such as ZigBee, LoRA, nRF, Bluetooth, or cellular (LTE, 5G, etc.). The continuous expansion of these networks and services also comes with the requirement of a stable level of service, which makes the task of maintenance operators more difficult. Therefore, in this research, an integrated solution for the management of preventive maintenance is proposed, employing software-defined sensing for hardware components, applications, and client satisfaction. A specific algorithm for monitoring the levels of services was developed, and an integrated instrument to assist the management of preventive maintenance was proposed, which are based on the network of future states prediction. A case study was also investigated for smart city applications to verify the expandability and flexibility of the approach. The purpose of this research is to improve the efficiency and response time of the preventive maintenance, helping to rapidly recover the required levels of service, thus increasing the resilience of complex systems.


Osmotic effects on arginine kinase function in living muscle of the blue crab Callinectes sapidus.
Flux was examined through the reaction catalyzed by arginine kinase in intact blue crab (Callinectes sapidus) muscle during simulated changes in salinity. Isolated dark levator muscles from the swimming leg were superfused with a saline solution that had an osmolarity equivalent to that of the hemolymph under different salinity regimes. Animals were acclimated for 7 days to a salinity of 5, 17 or 35 per thousand, which corresponds to a hemolymph osmolarity of 640, 720 or 960 mosmoll(-1), respectively. Experiments were conducted under control conditions, in which the osmolarity of the superfusion medium matched that of the acclimated hemolymph, as well as under hypo- and hyperosmotic conditions. These latter treatments were meant to simulate a rapid change in environmental salinity. Pseudo-first-order unidirectional rate constants and flux rates were measured for arginine kinase in the forward and reverse directions using a (31)P-nuclear magnetic resonance saturation transfer method. There were no differences in the rate constants or flux rates among the controls, indicating that arginine kinase function is not modulated by salinity if the animal has had sufficient acclimation time. However, the rate constants and flux rates of arginine kinase varied over a modest 1.7-fold range across the three types of osmotic treatments, although the range for the flux data was reduced when cell volume changes were taken into account. The hyperosmotic treatments led to a reduction in arginine kinase flux, while the hypo-osmotic treatments led to an enhanced arginine kinase flux. We propose that this effect is mediated by an increase in the concentration of perturbing inorganic ions under hyperosmotic conditions and a decrease in the concentration of such ions during the hypo-osmotic treatments.


Promoting the Efficiency and Stability of CsPbIBr2-Based All-Inorganic Perovskite Solar Cells through a Functional Cu2+ Doping Strategy.
Although organic-inorganic halide perovskite solar cells (PSCs) have shown dramatically enhanced power conversion efficiencies (PCEs) in the last decade, their long-term stability is still a critical challenge for commercialization. To address this issue, tremendous research efforts have been devoted to exploring all-inorganic PSCs because of their intrinsically high structural stability. Among them, CsPbIBr2-based all-inorganic PSCs have drawn increasing attention owing to their suitable band gap and favorable stability. However, the PCEs of CsPbIBr2-based PSCs are still far from those of their organic-inorganic counterparts, thus inhibiting their practical applications. Herein, we demonstrate that by simply doping an appropriate amount of Cu2+ into a CsPbIBr2 perovskite lattice (0.5 at. % to Pb2+), the perovskite crystallinity and grain size are increased, the perovskite film morphology is improved, the energy level alignment is optimized, and the trap density and charge recombination are reduced. As a consequence, a decent PCE improvement from 7.81 to 10.4% is achieved along with an enhancement ratio of 33% with a CsPbIBr2-based PSC. Furthermore, the long-term stability of CsPbIBr2-based PSCs against moisture and heat also remarkably improved by Cu2+ doping. This work provides a facile and effective route to improve the PCE and long-term stability of CsPbIBr2-based all-inorganic PSCs.


Incident fall risk and physical activity and physical performance among older men: the Osteoporotic Fractures in Men Study.
Physical activity and physical performance have been linked to fall risk in the elderly. The authors examined the relation between physical activity and physical performance with incident falls in the Osteoporotic Fractures in Men Study, a large prospective cohort study of 5,995 community-dwelling men in the United States at least 65 years of age. The authors also examined what types of activities are associated with falling. Incident falls between 2000 and 2005 were captured from up to 17 triannual follow-up questionnaires per participant and analyzed with generalized estimating equations. Follow-up averaged 4.5 years. The average risk of falling in the first 4 months of follow-up was 6.6%. The most active quartile had a significantly greater fall risk than did the least active quartile (relative risk = 1.18, 95% confidence interval (CI): 1.07, 1.29). Men with greater leg power and grip strength had significantly reduced fall risk (for highest leg power quartile vs. lowest: relative risk = 0.82, 95% CI: 0.73, 0.92; for highest grip strength quartile vs. lowest: relative risk = 0.76, 95% CI: 0.69, 0.85). Partitioning components of activity showed no association between fall risk and leisure activities but a positive association with household activities (for highest quartile vs.lowest: relative risk = 1.17, 95% CI: 1.07, 1.28).


Identification and Biochemical Characterization of Pyrrolidinediones as Novel Inhibitors of the Bacterial Enzyme MurA.
To develop novel antibiotics, targeting the early steps of cell wall peptidoglycan biosynthesis seems to be a promising strategy that is still underutilized. MurA, the first enzyme in this pathway, is targeted by the clinically used irreversible inhibitor fosfomycin. However, mutations in its binding site can cause bacterial resistance. We herein report a series of novel reversible pyrrolidinedione-based MurA inhibitors that equally inhibit wild type (WT) MurA and the fosfomycin-resistant MurA C115D mutant, showing an additive effect with fosfomycin for the inhibition of WT MurA. For the most potent inhibitor 46 (IC50 = 4.5 μM), the mode of inhibition was analyzed using native mass spectrometry and protein NMR spectroscopy. The compound class was nontoxic against human cells and highly stable in human S9 fraction, human plasma, and bacterial cell lysate. Taken together, this novel compound class might be further developed toward antibiotic drug candidates that inhibit cell wall synthesis.


Pregnancy during obstetrics and gynecology residency: effect on surgical experience.
This study explored residents' views about pregnancy during residency and the effect leaves of absence had on the quantity of surgical procedures performed. Physicians who graduated from an obstetrics and gynecology residency between 1994 and 2002 were contacted by mail. Respondents completed a questionnaire and consented to use of the program's surgical database to obtain information regarding surgical procedures performed during their training. Thirty-one of the 41 eligible resident physicians returned the questionnaire and consent form (response rate, 75.6%). Among the 14 responding men, 2 had taken a total of three nonvacation, noneducational leaves. Among the 17 women respondents, there were 16 leaves associated with deliveries, and the nonvacation, noneducational leave for women who were pregnant was statistically longer than for other residents (median of 6 weeks compared with 0 weeks, P<.001). Most pregnancies were planned (27/29, 93.1%) and were delivered in the third or fourth year of training (11/16, 68.8%). Former residents listed several ways that the program accommodated pregnancy and were satisfied with the program. The mean number of procedures for women with deliveries compared with other residents were as follows: cesarean section, 315 versus 281 cases (P=.20); abdominal hysterectomy, 116 versus 102 cases (P=.08); laparoscopy, 87 versus 92 cases (P=.72); vaginal hysterectomy, 51 versus. 45 cases (P=.11). Pregnancy and delivery did not decrease surgical experience of four major procedures in this program, and pregnant physicians perceived appropriate support from their colleagues and the program administration.


Therapy Management of Metabolic Disorder Comorbidity With Depression.
Depression is a common disease that seriously endangers the physical and mental health of human beings, and it often coexists with other metabolic disorders such as diabetes and cancer. There have been endless reports on the mechanism, prevention, and cure of comorbidity because of its high incidence and poor prognosis and the increased burden on the family and society. There may be a specific comorbid basis and causal relationship between depression and metabolic diseases. Depression in patients with metabolic disorders can be effectively alleviated through psychotherapy and medication. The timely and effective treatment of depression can significantly improve the quality of life of patients with metabolic disorders, reduce their psychological burden, and promote the effective treatment of metabolic diseases. This study reorganized the research progress on the management of metabolic disorder comorbidity with depression.


Factors associated with high-risk human papillomavirus infection and high-grade cervical neoplasia: A population-based study in Paraguay.
Cervical cancer (CC) is one of the leading causes of cancer mortality among women from Paraguay, with high incidence and mortality rates (31.2 and 16 per 100 000 women, respectively). Although the risk factors associated with high-risk human papillomavirus (hrHPV) infection and preneoplastic cervical lesions are widely studied, population-based characteristics of particular settings may influence the feasibility of HPV-based CC screening implementation. This study aimed to explore factors associated with hrHPV infection and high-grade cervical neoplasia in hrHPV-positive (hrHPV+) women from Paraguay. A total of 5677 women aged 30-64 years from the Central Department of Paraguay were screened with HPV test (Hybrid Capture 2) and Pap smear. Sociodemographic and risk factor interviews were conducted. hrHPV+ women were referred to colposcopy and women with an abnormal colposcopy had a biopsy taken. The outcomes recorded were the hrHPV status and the presence of high-grade cervical intraepithelial neoplasia or worse (CIN2+) among hrHPV+ women. Associations were investigated using multivariate logistic regressions. hrHPV prevalence was 13.8% (95%CI 13.0-14.8). This value decreased with the age of women (p-trend<0.001) and increased with the lifetime number of sexual partners (p-trend<0.001) and number of previous female partners of their current male partner if women had had one lifetime sexual partner (p-trend<0.001), increasing from 3.06 (95%CI 0.073-20.9) if partners had had one previous female partner to 9.19 (95%CI 2.36-61.1) if they had had eight or more. In hrHPV+ women, CIN2+ prevalence was 10.7% (95%CI 8.58-13.2) and increased with time since the last Pap smear (p-trend<0.001) and with the increasing number of pregnancies (p-trend = 0.05). In these settings, the sexual behavior of women and their male partners is associated with hrHPV infection. In hrHPV+ women, underscreening practices and multiple pregnancies are associated with CIN2+. This knowledge can contribute to public health policies for CC prevention and control in Paraguay.


Reactive nitrogen restructures and weakens microbial controls of soil N2O emissions.
The global surplus of reactive nitrogen (Nr) in agricultural soils is accelerating nitrous oxide (N2O) emission rates, and may also strongly influence the microbial controls of this greenhouse gas resulting in positive feedbacks that further exacerbate N2O emissions. Yet, the link between legacy effects of Nr on microbial communities and altered regulation of N2O emissions is unclear. By examining soils with legacies of Nr-addition from 14 field experiments with different edaphic backgrounds, we show that increased potential N2O production is associated with specific phylogenetic shifts in communities of frequently occurring soil microbes. Inputs of Nr increased the complexity of microbial co-association networks, and altered the relative importance of biotic and abiotic predictors of potential N2O emissions. Our results provide a link between the microbial legacy of Nr addition and increased N2O emissions by demonstrating that biological controls of N2O emissions were more important in unfertilized soils and that these controls are weakened by increasing resource levels in soil.


Anomalous branching of the axillary artery: a case report.
We present a case regarding the anomalous branching in the third part of the axillary artery on the left side in a 35-year-old male Nepalese cadaver. In the third part the axillary artery divided into superficial brachial and deep brachial arteries. The superficial brachial artery continued in the arm without giving any branches and ended in the cubital fossa dividing into radial and ulnar arteries. The deep brachial artery gave rise to subscapular, profunda brachii, articular branch to the shoulder joint, anterior circumflex humeral artery and posterior circumflex humeral artery. This variation is very rare and incidence is around 0.12-3.2% in the available literature. The normal and abnormal anatomy of the axillary region is having practical importance for the vascular radiologist and surgeon and it should be known for accurate diagnostic interpretation.


[Hemolytic group B streptococcus in cervico-vaginal secretions].
The group B streptococcus can be an etiological agent of newborn's infections and vaginitis. Therefore, we evaluated the statistical incidence of this microorganism in vaginal swabs of 1403 non-selected subjects. We isolated this streptococcus in 12.3% samples and it was present in 26.3% of positive cultures. Our study confirms the elevate incidence of this microorganism and suggests the opportunity of this research in pregnancy monitoring and in gynaecological flogosis.


Our experience in using the brachial venae comitantes as a native vascular access for hemodialysis.
A native arteriovenous fistula is the preferred vascular access for patients on long-term hemodialysis. In the absence of suitable superficial veins, the deep venous system can be used. We intend to present our experience in using the brachial venae comitantes (VC) to create a native arteriovenous fistula. From January 2012 to December 2014, we utilized the brachial vena comitantes to create 12 arteriovenous fistulae. Data from these 12 subjects were analyzed retrospectively to produce this case series. The average age of our subjects was 55.6 years. Forty-two percent of the subjects were women. Fifty percent of the subjects had diabetes mellitus and 58% had hypertension. We achieved a functional patency rate of 58% at 1 month's follow up after maturation. The brachio-brachial vena comitans fistula is a safe and plausible option in patients with no other suitable veins for a native fistula, more so in the hands of experienced surgeons. The longer time to cannulation has to be taken into consideration when creating a VC fistula. In suitable patients with end-stage renal disease, it can delay the use of an arteriovenous graft or a tunneled central venous catheter.


Agenesis of pancreas.
Complete agenesis of pancreas is a rare and lethal condition. Four cases have previously been reported in combination with other malformations, such as severe intrauterine growth retardation, hyperglycaemia and meconium ileus. We report a case of pancreatic agenesis as a single anomaly. The child died when 48 h old with severe metabolic acidosis. The literature is surveyed and the pathogenesis is discussed.


Omniphobic Hollow-Fiber Membranes for Vacuum Membrane Distillation.
Management of produced water from shale gas production is a global challenge. Vacuum membrane distillation (VMD) is considered a promising solution because of its various advantages. However, low-surface-tension species in produced water can easily deposit on the membrane surface and cause severe fouling or wetting problems. To solve the problems, an omniphobic polyvinylidene difluoride (PVDF) hollow-fiber membrane has been developed via silica nanoparticle deposition followed by a Teflon AF 2400 coating in this study. The resultant membrane shows good repellency toward various liquids with different surface tensions and chemistries, including water, ethylene glycol (EG), cooking oil, and ethanol. It also exhibits stable performance in 7 h VMD tests with a feed solution containing up to 0.6 mM of sodium dodecyl sulfate (SDS). In addition, the effects of surface energy and surface morphology as well as nanoparticle size on membrane omniphobicity have been systematically investigated. This work may provide valuable guidance to molecularly design omniphobic VMD membranes for produced water treatment.


Comparing two predictive methods for determining serum vancomycin concentrations at a Veterans Affairs Medical Center.
Two predictive methods for determining serum vancomycin concentrations (SVCs) at a Veterans Affairs medical center were compared. The data for inpatients at the San Francisco Veterans Affairs Medical Center who received i.v. vancomycin and had vancomycin concentrations recorded in 2003 were included in this retrospective study. Creatinine clearance was estimated by the Cockcroft and Gault equation. Volume of distribution and creatinine clearance were calculated for each patient, using the Leonard and Boro method and the Rushing and Ambrose method. The Sheiner and Beal method for determining precision and bias was used to evaluate whether the two methods significantly differed in their ability to predict SVCs. Of the 223 patients identified, 122 patients were included, and 212 SVCs were analyzed. The population was mostly male and had a mean age of 64.1 years. There were no significant differences in 95% confidence intervals for relative precision and relative bias between the two methods. In patients whose weight was within 120% of their ideal body weight (IBW), the Leonard and Boro method was significantly more precise and less biased in predicting SVCs. In patients whose weight exceeded 120% of their IBW, the Rushing and Ambrose method was less biased and tended to be more precise, although the difference in precision was not significant. Both methods yielded similar predictability for SVCs in a veterans population. The Leonard and Boro method better predicted SVCs in patients weighing within 120% of their IBW, while the Rushing and Ambrose method appeared to be more appropriate for calculating vancomycin dosages in patients whose weight exceeded 120% of their IBW.


[Effectiveness of olopatadine therapy in seasonal allergic conjunctivitis].
The study shows the antihistaminic and anti-inflammatory efficient treatment with olopatadina 0.1%. The study group consisting of 30 patients evaluated in the ophthalmological ambulatory between the period of april-august 2007 were diagnosed with acute seasonal allergic conjunctivites. Ig E and seric eosinofiles were quantified for all patients and the severity of conjunctivitis was evaluated by summing up the scores of the cardinal signs of allergic conjunctivitis: itching, conjunctival hyperemia and tearing. For a month every patients was treated with olopatadina 0.1% 2x1 drop/day. They were evaluated in day 1, day 8 and day 30. The tolerance of the treatment was judged by the reduced symptoms after olopatadine instilation. The score in day 1 was higher in children under 16 years of age who presented itching and tearing. After day 8 of treatment the scores droped significantly and after a month the scores decreased highly to a percentage from 60-85%. Choosing the best therapy in allergic conjunctivitis involves studying the mechanism implicated in triggering the allergy Olopatadina 0.1% with its double mechanism has proven to be efficient in moderate seasonal allergic conjunctivitis.


Changes of glycolipids dependent on cell density of Ehrlich ascites carcinoma cells.
The glycolipid composition of Ehrlich ascites carcinoma cells was found to depend strongly on the cell density of the suspension. The general trend observed upon dilution of the cell suspension was a reduction of the less complex gangliosides GM3 and GM2 with concomitant increase of the more complex gangliosides, especially GM1. The increase of the content of ganglioside GM1 upon dilution was accompanied by a comparable decrease of the content of its immediate precursor, asialo-GM1, whereas the content of other neutral glycosphingolipids did not change very much. When the cell suspension was diluted with medium conditioned by dense cells the ganglioside profile of the diluted suspension remained similar to that of the dense cell suspension. It is postulated that the medium conditioned with dense cells contains a transferable factor inhibiting sialylation of asialo-GM1.


White Cord Syndrome After Cervical Laminoplasty in an 81-Year-Old Man.
White cord syndrome (WCS) shows high intramedullary signaling in T2-weighted MRI with worsening motor nerve symptoms after cervical spinal decompression surgery. It has been reported in only 13 cases. An 81-year-old man had numbness, weakness, and impaired fine motor control in both upper limbs for the previous five years. C3, C4, C6, open-door laminoplasty, and C5 laminectomy were performed. Intraoperative transcranial motor evoked potential normalization by compound muscle action potential showed an 80% reduction in amplitude in the right abductor pollicis brevis and a 96% reduction in the right abductor hallucis. Tetraplegia occurred immediately after the operation. Magnetic resonance imaging (MRI) on the day after the operation showed intramedullary T2 high signals at the C4 and C5 levels. According to Brunnstrom's staging, the upper and lower right limbs and the lower left limb were at stage two, and the upper left limb was at stage three, six months after the operation. Thirteen cases of WCS have been reported in the literature. These were thought to be caused by reperfusion due to decompression.


The Impact of Antibiotic Stewardship Programs in Combating Quinolone Resistance: A Systematic Review and Recommendations for More Efficient Interventions.
Quinolones are among the most commonly prescribed antibiotics worldwide. A clear relationship has been demonstrated between excessive quinolone use and the steady increase in the incidence of quinolone-resistant bacterial pathogens, both in hospital and community sites. In addition, exposure to quinolones has been associated with colonization and infection with healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus and Clostridium difficile in hospitalized patients. Therefore, the management of quinolone prescribing in hospitals through antibiotic stewardship programs is considered crucial. Although suggestions have been made by previous studies on the positive impact of stewardship programs concerning the emergence and spread of multidrug-resistant bacteria at hospital level, the association of quinolone-targeted interventions with reduction of quinolone resistance is vague. The purpose of this article was to evaluate the impact of stewardship interventions on quinolone resistance rates and healthcare-associated infections, through a literature review using systematic methods to identify and select the appropriate studies. Recommendations for improvements in quinolone-targeted stewardship programs are also proposed. Efforts in battling quinolone resistance should combine various interventions such as restriction formulary policies, prospective audits with feedback to prescribers, infection prevention and control measures, prompt detection of low-level resistance, educational programs, and guidelines for optimal quinolone usage. However, the effectiveness of such strategies should be assessed by properly designed and conducted clinical trials. Finally, novel approaches in diagnostic stewardship for rapidly detecting bacterial resistance, including PCR-based techniques, mass spectrometry, microarrays, and whole-genome sequencing as well as the prompt investigation on the clonality of quinolone-resistant strains, will strengthen our ability to personalize quinolone prescribing to individual patients.


Biology of extracellular vesicles secreted from senescent cells as senescence-associated secretory phenotype factors.
The increase of the morbidity rate in age-related diseases, such as cancer, Alzheimer's disease, arteriosclerosis and pulmonary fibrosis, has become a profound social problem. Recent reports have pointed out that senescent cells accumulated in the body with aging might cause these aged-related pathologies. Cellular senescence is known as an irreversible cell cycle arrest induced by various stresses, and can function as an important tumor suppression mechanism to exclude the premalignant cells. In contrast, senescent cells provoke the phenomenon, termed the senescence-associated secretory phenotype, which causes the secretion of various inflammatory proteins, and it is at risk of facilitating chronic inflammation and oncogenic transformation to surrounding cells. We have previously reported that senescent cells secrete not only inflammatory proteins, but also extracellular vesicles (EV). EV include various cellular components, such as proteins, lipids and nucleic acids, which are proven to be important factors for cell-to-cell communication. Recent evidence suggests that EV secreted from senescent cells might contribute to tumorigenesis and age-associated pathologies as new senescence-associated secretory phenotype factors. In addition, we also showed that the EV secretion pathway is one of the essential defense mechanisms to maintain cellular homeostasis by excretion of intercellular toxic substances into extracellular space. Herein, this review shows the biological functions of EV secreted from senescent cells. Geriatr Gerontol Int 2020; ••: ••-••.


Herbal intoxication. Psychoactive effects from herbal cigarettes, tea, and capsules.
Herbal preparations, designed to be smoked or ingested for "health and happiness", are promoted as legal hallucinogens, euphoriants, and marihuana substitutes. A total of 25 psychoactive substances have been identified in these products, and a number of intoxications have resulted from their short- or long-term use. Physicians should be alerted to the nature of these effects when taking drug histories, and their possible role in the causation of medical complaints should be considered.


Acquired resistance to monepantel in C. elegans: What about parasitic nematodes?
In 2008, Novartis Animal Health developed a new class of anthelmintics, the amino-acetonitrile derivatives (AAD) of which monepantel is the most prominent compound. Monepantel was designed for the treatment of sheep against the parasitic nematode Haemonchus contortus. Because monepantel acts through a different mechanism, it is effective against nematodes that have acquired resistance to long-standing anthelmintics. In order to benefit from a maximum lifespan and efficacy of this new compound, the mode of action of monepantel needs to be understood. Studies on the model nematode Caenorhabditis elegans led to the identification of at least one target of monepantel: the monovalent cation channel ACR-23. Here we comment on the effects of monepantel on C. elegans and on the development of resistant parasitic nematode strains.


Abscisic acid-type sesquiterpenes and ansamycins from Amycolatopsis alba DSM 44262.
Two new abscisic acid-type sesquiterpenes (1, 2), and one new ansamycin (3), together with four known ansamycins, namely ansacarbamitocins 4-7, were isolated from the fermentation extract of Amycolatopsis alba DSM 44262. The structures of the new compounds were elucidated to be (E)-3-methyl-5-(2,6,6-trimethyl-3-oxocyclohex-1-enyl)pent-2-enoic acid (1) and (E)-3-methyl-5-(2,6,6-trimethyl-4-oxocyclohex-2-enyl)pent-2-enoic acid (2), and 9-O-methylansacarbamitocin A1 (3), on the basis of comprehensive analysis of spectroscopic data, respectively. The antimicrobial activities were also evaluated for all seven compounds.


Hypofractionated radiotherapy for early glottic cancer: a retrospective interim analysis of a single institution.
To evaluate the results of hypofractionated radiotherapy (HFX) for early glottic cancer. Eighty-five patients with cT1-2N0M0 squamous cell carcinoma of the glottis who had undergone HFX, performed using intensity-modulated radiotherapy (IMRT, n = 66) and three-dimensional conformal radiotherapy (3D CRT, n = 19) were analyzed. For all patients, radiotherapy was administered at 60.75 Gy in 27 fractions. Forty-three patients received a simultaneous integrated boost (SIB) of 2.3-2.5 Gy per tumor fraction. The median follow-up duration was 29.9 months (range, 5.5 to 76.5 months). All patients achieved complete remission at a median of 50 days after the end of radiotherapy (range, 14 to 206 days). The 5-year rates for locoregional recurrence-free survival was 88.1%, and the 5-year overall survival rate was 86.2%. T2 stage was a prognostic factor for locoregional recurrencefree survival after radiotherapy (p = 0.002). SIB for the tumor did not affect disease control and survival (p = 0.191 and p = 0.387, respectively). No patients experienced acute or chronic toxicities of ≥grade 3. IMRT significantly decreased the dose administered to the carotid artery as opposed to 3D CRT (V35, p < 0.001; V50, p < 0.001). Patients treated with HFX achieved acceptable locoregional disease control rates and overall survival rates compared with previous HFX studies. A fraction size of 2.25 Gy provided good disease control regardless of SIB administration.


Waist circumference and the risk of hypertension and prediabetes among Filipino women.
To examine waist circumference as a risk factor for having hypertension only, impaired fasting glucose only, or both hypertension and impaired fasting glucose, and assess whether the associations vary according to overweight status. Furthermore, optimal cut-offs for waist circumference in overweight women and non-overweight women were explored. Data from 1,871 women aged 35-68 years in the 2005 Cebu Longitudinal Health and Nutrition Survey were used. Multinomial logistic regressions were used to model how waist circumference influenced the likelihood of having the three illness categories compared to having neither condition. Waist circumference cut-offs were explored using receiver operating characteristic analysis. Adjusted for age and other confounders, each cm increase in waist circumference increased the odds of hypertension by 5 % for non-overweight women and 3 % for overweight women; impaired fasting glucose by 9 and 3 % for non-overweight and overweight women, respectively; and hypertension and impaired fasting glucose by 17 % among non-overweight versus 9 % for overweight women. Waist circumference cut-offs for non-overweight women were lower than overweight women. Waist circumference was significantly associated with impaired fasting glucose and both hypertension and impaired fasting glucose, and the associations vary by overweight status.


Workshop report treating hepatitis C in HIV-infected patients: where are we now?
The 1st International Workshop on HIV and Hepatitis Coinfection was held in Noordwijk, the Netherlands, 2-4 December 2004. This report outlines issues raised at the workshop concerning the treatment of hepatitis C in HIV-coinfected patients. Clinical trials using pegylated interferon in combination with ribavirin have provided positive outcomes, although clinicians still face a number of challenges in learning how best to use these drugs.


nAChR-induced octopamine release mediates the effect of nicotine on a startle response in Drosophila melanogaster.
Biogenic amines (BAs) play a central role in the generation of complex behaviors in vertebrates and invertebrates, including the fly Drosophila melanogaster. The comparative advantages of Drosophila as a genetic model to study the contribution of BAs to behaviors stumble upon the difficulty to access the fly brain to ask relevant physiological questions. For instance, it is not known whether the activation of nicotinic acetylcholine receptors (nAChRs) induces the release of BAs in fly brain, a phenomenon associated to several behaviors in vertebrates. Here, we describe a new preparation to study the efflux of BAs in the adult fly brain by in vitro chronoamperometry. Using this preparation we show that nAChR agonists including nicotine induce a fast, transient, dose-dependent efflux of endogenous BAs, an effect mediated by α-bungarotoxin-sensitive nAChRs. By using different genetic tools we demonstrate that the BA whose efflux is induced by nAChR activation is octopamine (Oct). Furthermore, we show that the impairment of a mechanically induced startle response after nicotine exposure is not observed in flies deficient in Oct transmission. Thus, our data show that the efflux of BAs in Drosophila brain is increased by nAChR activation as in vertebrates, and that then AChR-induced Oct release could have implications in a nicotine-induced behavioral response.


New modification of model-free approach to analysis of nuclear magnetic relaxation data in proteins.
A formal approach to the analysis of 13C magnetic relaxation data in proteins has been developed. It is based on the concepts of one of the authors on the internal motions in solid polymers (Fedotov, V.D., Pulse NMR in bulk polymers, Doctoral dissertation, Kazan, USSR, 1981). According to this approach the intermolecular motions in proteins are considered as anisotropic ones and described in terms of a spectrum of correlation times. To characterize the motions a set of formal microdynamic parameters has been introduced. They are: the anisotropy parameter (a measure of spatial restriction of motion), the most probable correlation time, the parameter of the correlation time distribution width. The analysis of protonated carbon relaxation in globular proteins (bovine pancreatic trypsin inhibitor and ribonuclease S) and polymers has been carried out by the model-free approach. Microdynamic parameters of CH3-, CH2-, aromatic CH-groups have been considered within the framework of the diffusional rotation-oscillation models. To explain the backbone CH-group relaxation the model of the defect diffusion has been applied. The distinctive feature of the results obtained is the broad correlation time distribution for all groups of any type. The causes of nonexponential correlation function of local motion have been discussed. To elucidate the nature of the correlation time the carbon magnetization decays in the wide range of microdynamic parameter values imitating various experimental conditions have been calculated.