Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy.
Low-dose ultrasound seems to be an effective method to enhance wound healing, particularly in chronic venous leg ulcers. The aim of our investigation was to examine the effect of 30 kHz low-dose ultrasound in local treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Twenty-four patients with chronic ulcerations of the leg due to chronic venous insufficiency were randomised in placebo-controlled parallel groups in a single-blind clinical study. Patients were randomised to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10 min of footbathing, with application of 30 kHz continuous ultrasound 100 mW/cm2 three times a week. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Colour photographs of the ulcers were taken under standard conditions at the same time. After each treatment local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5% in the ulcerated area. In contrast the mean ulcerated area decreased by 55.4% in the ultrasound group (p<0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm+/-0.04 mm and in the placebo patients 0.03 mm+/-0.03 mm. Patients recorded only minor side-effects such as a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area. The application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.


Metabolic effects of fatty acid-bearing albumin on a proximal tubule cell line.
In glomerular disease, fatty acids carried on albumin are taken up by the proximal tubule with filtered albumin. We postulate that the fatty acids carried on filtered albumin could contribute to the deleterious effects of proteinuria. The effects of fatty acid-albumin complexes on lipid metabolism have been studied in opossum kidney (OK) cells, a proximal tubule cell line. OK cells transported two-thirds of [14C]palmitate-albumin (5 mg/ml) intracellularly within 16 h. [14C]palmitate-albumin was distributed into phosphatidylcholines, phosphatidylinositols, and tri- and diglycerides. 14C-labeled unsaturated fatty acid albumins (oleate, linoleate, and arachidonate) showed preferential incorporation into triglycerides, with lesser incorporation into phospholipids. Studies of total lipid pools showed that fatty acid-albumin uptake produced a particularly marked increase in total triglyceride levels (approximately 10-fold). Oil red O staining of OK cells cultured with oleate-albumin showed a marked increase in intracellular lipid droplets, compared with cells cultured with delipidated albumin, consistent with triglyceride accumulation. Less than 1% of [14C]palmitate taken up was isolated as intracellular free fatty acid. Less than 5% of [14C]palmitate internalized was oxidized to 14CO2. Different fatty acids, when taken up by the OK cell, have distinct metabolic fates. Each fatty acid is incorporated in a characteristic fashion into certain complex lipids, possibly dependent on the presence or absence of double bonds. We propose that this may have functional consequences for the proximal tubule in the human nephrotic syndrome.


Neuro-toxic and Reproductive Effects of BPA.
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility. This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its analogues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction. BPA has potential human health hazard associated with gestational, peri- and neonatal exposure. Beginning with BPA's disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal differentiation, synaptic plasticity, neuroinflammation, neuro-degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releasing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy. BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting results have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This review offers new insights on these issues with the aim to find the "fil rouge", if any, that characterize BPA's mechanism of action with outcomes on neuronal function and reproduction.


The efficiency of protein compartmentalization into the secretory pathway.
Numerous proteins targeted for the secretory pathway are increasingly implicated in functional or pathological roles at alternative cellular destinations. The parameters that allow secretory or membrane proteins to reside in intracellular locales outside the secretory pathway remain largely unexplored. In this study, we have used an extremely sensitive and quantitative assay to measure the in vivo efficiency of signal sequence-mediated protein segregation into the secretory pathway. Our findings reveal that segregation efficiency varies tremendously among signals, ranging from >95 to <60%. The nonsegregated fraction is generated by a combination of mechanisms that includes inefficient signal-mediated translocation into the endoplasmic reticulum and leaky ribosomal scanning. The segregation efficiency of some, but not other signal sequences, could be influenced in cis by residues in the mature domain or in trans by yet unidentified cellular factors. These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins.


Prenatal administration of methadone in the rat increases offspring acoustic startle amplitude at age 3 weeks.
Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 21-23 days of age, acoustic startle amplitude was measured for each treated and control animal. Because prenatal methadone exposure resulted in reduced body weight at the time of testing, it was necessary to analyze startle amplitude using weight as a covariate. This analysis showed that the methadone treated offspring had a significantly enhanced mean startle amplitude compared with the controls. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged state of CNS hyperexcitability similar to clinical descriptions of human infants undergoing opiate abstinence.


The acetyltransferase p300 regulates NRF2 stability and localization.
The transcription factor NRF2 plays a key role in the protection against environmental stress and maintaining cellular homeostasis. The acetyltransferase p300 is a known component of the NRF2 transcriptional complex and promotes its transcriptional activity. In this study we describe a novel mechanism by which p300 facilitates NRF2 activity. p300 physically interacts with NRF2 and interferes with NRF2-KEAP1 complex formation. In particular, p300 increases NRF2 protein abundance and stability, thereby promoting NRF2 nuclear localization. Notably, the acetyltransferase activity of p300 was indispensable for the stabilizing effects towards NRF2. Furthermore, overexpression of p300 protected HEK293T cells from oxidative stress and increased viability. Together our study uncovers a link between p300 and control of NRF2-KEAP1 signaling via regulation of NRF2 stability and this may act as a novel checkpoint on the adaptation to oxidative stress.


The stress-Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches.
Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.


Contribution of multiple isolating barriers to reproductive isolation between a pair of phytophagous ladybird beetles.
Reproductive isolation between species may often be attained by multiple isolating barriers, but the components are rarely studied in animal taxa. To elucidate the nature of multiple isolating barriers, we quantified the strength of three premating barriers, including ecologically based ones (seasonal, habitat, and sexual), two postmating-prehatching barriers (reduced egg hatchability and conspecific sperm precedence [CSP]), and one posthatching barrier, including four components of F(1) hybrid reduced fitness, between two phytophagous ladybird beetles, Henosepilachna vigintioctomaculata and H. pustulosa. We detected five positive barriers (habitat isolation, sexual isolation, reduced egg hatchability, CSP, and reduced egg hatchability in backcrosses of F(1) hybrids). None of these barriers entirely prevents gene exchange when it acts alone, but jointly they generate nearly complete reproductive isolation even between sympatric populations. Host fidelity contributed most strongly to reproductive isolation by reducing interspecific hybridization through several important types of ecological isolation, including microspatial, habitat, and seasonal isolation. The existence of multiple isolating barriers likely helps keep reproductive isolation stable and robust, by complementing changes in the strength of leaky barriers. This complementarity of multiple isolating barriers yields the concept of robustness of reproductive isolation, which is important when considering the long-term maintenance of species boundaries in coexisting species pairs.


Extracorporeal shock wave treatment for non-inflammatory chronic pelvic pain syndrome: a prospective, randomized and sham-controlled study.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a clinical syndrome characterized by pain in the perineum, pelvis, suprapubic area, or external genitalia and variable degrees of voiding and ejaculatory disturbance. The analgesic effect of extracorporeal shock wave treatment (ESWT) was an interesting phenomenon with an unclear mechanism discovered by chance in the applications for urolithiasis, on which ESWT has become an increasingly popular therapeutic approach as an alternative option for the treatment of a number of soft tissue complaints. In this study, we aimed to evaluate the feasibility and efficacy of ESWT in non-inflammatory (IIIB) CP/CPPS. Men diagnosed with IIIB CP/CPPS were randomized to either ESWT (group 1, n = 40) or the control (group 2, n = 40). Group 1 received 20 000 shock wave impulses in 10 sessions over a two-week period, whereas group 2 received only a sham procedure. The total scores and sub-domain scores of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) for both groups were assessed at baseline, mid-treatment, end-point, and 4-week and 12-week follow-up visits. The mean total NIH-CPSI score of group 1 was significantly decreased from baseline at all post-treatment time points (P < 0.01 for all). Decreases in pain domain and quality of life (QOL) scores were also significant. In group 2, no significant decreases of total NIH-CPSI score and pain domain score were found at all post-treatment time points. At the end-point of treatment, 71.1% of group 1 exhibited perceptible improvement in total NIH-CPSI compared with 27.0% of group 2 (P < 0.001); additionally, 28.9% of group 1 exhibited clinically significant improvement compared with 10.8% of group 2 (P < 0.01). Moreover, a greater number of patients in group 1 at 4-week and 12-week follow-up were rated as responders (perceptible and clinically significant response) compared with group 2. ESWT exhibits a potentially therapeutic role in the treatment of CP/CPPS.


[Characteristics of neonates with and without a single umbilical artery. Analysis of two consecutive series of neonates with and without congenital defects].
The implications of the presence of a single umbilical artery (SUA) are unknown. Although most articles are based on selected samples, they suggest a relationship between SUA and malformations. Consequently, prenatal detection of SUA causes concern, since there are no definitive guidelines that can be followed after identification of this abnormality. The objective of this study was to comparatively analyze SUA in two series of consecutive births, with and without congenital defects. A total of 19,909 cases and 19,148 controls from the Registry of the Spanish Collaborative Study on Congenital Malformations were studied. The variables analyzed were sex, birth weight, length, occipito-frontal circumference, gestational age, prematurity, delivery by caesarean section, umbilical cord length, placental weight, survival at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations included relative frequency, odds ratios (OR) and 95 % confidence intervals, the chi-square test, Fisher's p-value, and Student's t-test. SUA was found in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures showed secular variation due to improvements in prenatal diagnosis and interruption of some pregnancies. When cases with and without SUA were compared, those with SUA had lower values of somatometry at birth, umbilical cord length and gestational age and had a higher risk for oligohydramnios, polyhydramnios, caesarean section, and death in the first 72 hours. Among controls, the only differences were a shorter umbilical cord and a higher frequency of oligohydramnios among infants with SUA. The results suggest that certain malformations associated with SUA could cause some of the differences among cases. Shortening of the umbilical cord and oligohydramnios could be related to SUA, as these abnormalities were found in both cases and controls. Comparison of cases and controls suggests that the etiopathogenesis of SUA could differ in the two groups.


31ièmes Journées Franco-Belges de Pharmacochimie: Meeting Report.
The "Journées Franco-Belges de Pharmacochimie" is a recognized two-day annual meeting on Medicinal Chemistry that is renowned for the advanced science presented, conviviality, and outstanding opportunities for senior and young scientists to exchange knowledge. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report.


Athletic overuse injuries in children. A 30-month prospective follow-up study at an outpatient sports clinic.
A 30-month prospective follow-up study of children's overuse injuries at an outpatient sports clinic was carried out to determine the number, profile, and specific features of these injuries compared with those of young adults. During this period 74 athletically active boys (less than or equal to 15 years), 83 girls, 255 men (21-30 years), and 77 women visited the station because of an overuse sports injury of the musculoskeletal system. About one-third of the patients of each group did not seek medical help until more than 6 months after the onset of the symptoms. The injuries most commonly affected the lower extremities, with the knee joint involved in about one third of patients. In girls and women, the lower back (13%) was significantly more frequently affected than in boys and men (6%) (p less than 0.01). Thirty two percent of all boys' overuse problems were classified as exercise-induced growth disorders and osteochondritic pains (apophysitides, etc.), but in girls only 13% had a similar basis. The most common diagnosis among boys was Osgood-Schlatter's disease (13 patients, 18%); in girls it was nonspecific synovitis of the knee (9, 16%).


Bioactive albumin-based carriers for tumour chemotherapy.
Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.


Factors influencing apnea and bradycardia of prematurity - implications for neurodevelopment.
Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. To characterize the influence of neonatal factors on ABP and to determine the relationship of ABP to neurodevelopmental outcome. ABP was described in very low birth weight infants (n = 83) using the frequency and severity of ABP episodes with a clinical score considering heart rate, oxygenation, duration and interventions performed during each episode. Neonatal factors were analyzed for their relationship to ABP using regression analysis. Neurodevelopment was investigated using the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II at a corrected age of 13 months. Power of ABP parameters to predict outcome was assessed by logistic regression analysis. ABP typically started within the first week after birth. Spontaneous resolution occurred at a postmenstrual age (PMA) of 36.0 +/- 2.2 (31.1-44.1) weeks. A delayed resolution (>36 weeks PMA) and a higher average daily ABP score during a defined developmental period (31-37 weeks PMA) were associated with a higher incidence of unfavorable outcome (MDI or PDI <69 or death). ABP is an age-specific phenomenon. However, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.


Interpersonal Psychotherapy for Adolescents With Mood and Behavior Dysregulation: Evidence-Based Case Study.
Interpersonal psychotherapy for depressed adolescents, an evidence-based psychotherapy, has been adapted for youth with chronic irritability and excessive reactivity (i.e., temper outbursts), to create Interpersonal Psychotherapy for Mood and Behavior Dysregulation (IPT-MBD). Youth with chronic irritability and excessive reactivity were originally conceptualized as severe mood dysregulation (SMD) and in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) as disruptive mood dysregulation disorder. Because outbursts are the most prominent symptom, behavioral management strategies are typically a common focus of treatment. These outbursts, along with other mood symptoms, result in significant impairment in multiple domains, with a particularly adverse impact on interpersonal functioning. For this reason improving relationships is an important target for treatment. We present an evidence-based case study of an adolescent who met research criteria for SMD and who received the IPT-MBD intervention as part of a research study. Monthly ratings assessing severity and improvement of SMD symptoms were conducted by an independent evaluator. This adolescent had an overall improvement in SMD symptoms, attended all scheduled therapy sessions, and parent and teen reported satisfaction with the treatment. We discuss factors that may influence the effectiveness of this treatment.


Bone density correlates with clinical outcomes after ankle fracture fixation.
Osteoporosis and decreased bone density are known to increase fracture incidence and severity. Although much is known regarding the effects of bone density on fracture risk and the treatment options for prevention of fragility fractures, whether bone quality alters clinical outcomes after fracture fixation is unknown. The purpose of this study was to determine whether bone quality correlates with clinical outcomes after fracture fixation. A prospective database of all operatively treated ankle fractures by a single surgeon from 2003 to 2013 was used to identify patients. All patients included in the study had preoperative computed tomography (CT) imaging of the injured ankle and postoperative CT imaging of the contralateral ankle. Hounsfield unit (HU) measurement values were determined by placing an elliptical region of interest confined to the cancellous metaphyseal region of the distal tibia and fibula. The primary and secondary clinical outcomes included Foot and Ankle Outcome Scores (FAOS) and ankle range of motion (ROM). Included patients had at least 12 months of clinical outcome data. Sixty-four patients met the inclusion criteria. Comparison of HU values from the injured and contralateral side demonstrated almost perfect agreement (ICC(2,1) = 0.938), suggesting that HU values can be accurately measured in the setting of a fracture. Increased HU values of the injured distal tibia and fibula significantly correlated with improved outcomes in four of five FAOS domains, including pain, activities of daily living, sports, and quality of life (beta = 0.285-0.344; P ≤ 0.05 for all). Range of motion outcomes did not significantly correlate with HU values. Our results suggest that decreased bone quality, as measured using preoperative CT, significantly correlates with inferior short-term clinical outcomes. These results have significant implications for integrating bone quality into treatment algorithms for fracture patients.


[Human radiation action of radon and its daughter disintegration products].
Radon-222 and its daughter disintegration products are present within all the buildings without except, which is an inevitable source of radiation both in the dwellings and in working places. There may be higher concentrations of radon in some regions. Seasonal radon level changes depending on ambient air temperature and atmospheric pressure have been found in the atmospheric ground layers. The results of the performed sanitary-and-epidemiological studies may state that there is a cause-and-effect relationship between the level of radon in the air of accommodations and the higher incidence of lung cancer. Radon-resistant structures of dwellings, removal of the soil sources of radon, as well as air filtration and efficient ventilation of premises are basic methods for decreasing the concentration of radon.


Graptopetalum paraguayense ameliorates chemical-induced rat hepatic fibrosis in vivo and inactivates stellate cells and Kupffer cells in vitro.
Graptopetalum paraguayense (GP) is a folk herbal medicine with hepatoprotective effects that is used in Taiwan. The aim of this study was to evaluate the hepatoprotective and antifibrotic effects of GP on experimental hepatic fibrosis in both dimethylnitrosamine (DMN)- and carbon tetrachloride (CCl(4))-induced liver injury rats. Hepatic fibrosis-induced rats were fed with the methanolic extract of GP (MGP) by oral administration every day. Immunohistochemistry, biochemical assays, and Western blot analysis were performed. The effects of MGP on the expression of fibrotic markers and cytokines in the primary cultured hepatic stellate cells (HSCs) and Kupffer cells, respectively, were evaluated. Oral administration of MGP significantly alleviated DMN- or CCl(4)-induced liver inflammation and fibrosis. High levels of alanine transaminase, aspartate transaminase, bilirubin, prothrombin activity and mortality rates also decreased in rats treated with MGP. There were significantly decreased hydroxyproline levels in therapeutic rats compared with those of the liver-damaged rats. Collagen I and alpha smooth muscle actin (α-SMA) expression were all reduced by incubation with MGP in primary cultured rat HSCs. Furthermore, MGP induced apoptotic cell death in activated HSCs. MGP also suppressed lipopolysaccharide-stimulated rat Kupffer cell activation by decreasing nitric oxide, tumor necrosis factor-α and interleukin-6 production, and increasing interleukin-10 expression. The results show that the administration of MGP attenuated toxin-induced hepatic damage and fibrosis in vivo and inhibited HSC and Kupffer cell activation in vitro, suggesting that MGP might be a promising complementary or alternative therapeutic agent for liver inflammation and fibrosis.


Drinking water and pregnancy outcome in central North Carolina: source, amount, and trihalomethane levels.
In spite of the recognition of potentially toxic chemicals in chlorinated drinking water, few studies have evaluated reproductive health consequences of such exposure. Using data from a case-control study of miscarriage, preterm delivery, and low birth weight in central North Carolina, we evaluated risk associated with water source, amount, and trihalomethane (THM) concentration. Water source was not related to any of those pregnancy outcomes, but an increasing amount of ingested water was associated with decreased risks of all three outcomes (odds ratios around 1.5 for 0 glasses per day relative to 1-3 glasses per day, falling to 0.8 for 4+ glasses per day). THM concentration and dose (concentration x amount) were not related to pregnancy outcome, with the possible exception of an increased risk of miscarriage in the highest sextile of THM concentration (adjusted odds ratio = 2.8, 95% confidence interval = 1.1-2.7), which was not part of an overall dose-response gradient. These data do not indicate a strong association between chlorination by-products and adverse pregnancy outcome, but given the limited quality of our exposure assessment and the increased miscarriage risk in the highest exposure group, more refined evaluation is warranted.


Effect of treatment of rats with dexamethasone in vivo on gluconeogenesis and metabolite compartmentation in subsequently isolated hepatocytes.
Hepatocytes prepared from rats treated with dexamethasone for 2 or 3h and maintained in the presence of 10 microM-dexamethasone in the preparation and incubation buffers showed significantly elevated rates of gluconeogenesis compared with those prepared from control animals. Dexamethasone treatment also increased the sensitivity of the cells to glucagon and the catecholamines. Analysis of the concentrations of metabolites in the gluconeogenic pathway indicated that dexamethasone decreased the intracellular concentration of pyruvate and increased those of phosphoenolpyruvate, acetyl-CoA and citrate, suggesting a stimulation of the reaction(s) converting pyruvate into phosphoenolpyruvate. This was substantiated by analysis of the pattern of metabolites found in the mitochondrial compartment after digitonin fractionation of the cells. Inclusion of 3-mercaptopicolinate in the incubation enhanced the effect of the hormone on the distribution of metabolites. Thus, in the absence of an effect of the steroid at the level of phosphoenolpyruvate carboxykinase or pyruvate kinase, dexamethasone treatment still increased the formation of malate, aspartate and citrate from pyruvate, indicating a stimulation in the intact cell of pyruvate carboxylase. It is suggested that the stimulation of pyruvate carboxylase is a result of a general activation of mitochondrial function, with an increase in the intramitochondrial concentrations of acetyl-CoA and ATP, a decrease in glutamate and an enhanced intramitochondrial [ATP]/[ADP] ratio.


Dietitians' Perspectives on Teaching Nutrition to Medical Students.
The provision of nutrition care by health professionals can facilitate improved patient nutrition behaviors. Some education institutions include nutrition in their medical curriculum; however, doctors and medical students continue to lack competence in providing nutrition care. Dietitians are increasingly teaching nutrition to medical students, yet evidence on the topic remains anecdotal. It is important to understand the experiences of these dietitians to support improvements in undergraduate medical nutrition education. The aim of this study was to explore dietitians' perspectives of teaching nutrition to medical students. A qualitative study was conducted in collaboration with the Need for Nutrition Education/Innovation Programme (NNEdPro). Twenty-four dietitians who had provided nutrition education to medical students participated in individual semistructured interviews. Participants were from Australia (n = 5), New Zealand (n = 1), the United States (n = 6), Canada (n = 5), the United Kingdom (n = 5), Germany (n = 1), and Finland (n = 1). Data analysis was conducted using a constant comparative approach to thematic analysis. The dietitians expressed confidence in their ability to teach medical students and believed that they were the most appropriate professionals to administer the education. However, they were not confident that medical students graduate with sufficient nutrition competence and attributed this to poor curriculum planning for nutrition. Dietitians had access to useful resources and tools to support education, with opportunity to contribute further to integration of nutrition throughout medical curricula. This study suggests that dietitians are likely appropriate nutrition teachers in medical education. However, optimizing dietitians' role requires their further involvement in curriculum planning and development. Including dietitians as members of medical faculty would facilitate their input on nutrition throughout the curriculum, which could enhance the nutrition education of medical students.


Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source.
In fragment-based drug discovery, hundreds or often thousands of compounds smaller than ~300 Da are tested against the protein of interest to identify chemical entities that can be developed into potent drug candidates. Since the compounds are small, interactions are weak, and the screening method must therefore be highly sensitive; moreover, structural information tends to be crucial for elaborating these hits into lead-like compounds. Therefore, protein crystallography has always been a gold-standard technique, yet historically too challenging to find widespread use as a primary screen. Initial XChem experiments were demonstrated in 2014 and then trialed with academic and industrial collaborators to validate the process. Since then, a large research effort and significant beamtime have streamlined sample preparation, developed a fragment library with rapid follow-up possibilities, automated and improved the capability of I04-1 beamline for unattended data collection, and implemented new tools for data management, analysis and hit identification. XChem is now a facility for large-scale crystallographic fragment screening, supporting the entire crystals-to-deposition process, and accessible to academic and industrial users worldwide. The peer-reviewed academic user program has been actively developed since 2016, to accommodate projects from as broad a scientific scope as possible, including well-validated as well as exploratory projects. Academic access is allocated through biannual calls for peer-reviewed proposals, and proprietary work is arranged by Diamond's Industrial Liaison group. This workflow has already been routinely applied to over a hundred targets from diverse therapeutic areas, and effectively identifies weak binders (1%-30% hit rate), which both serve as high-quality starting points for compound design and provide extensive structural information on binding sites. The resilience of the process was demonstrated by continued screening of SARS-CoV-2 targets during the COVID-19 pandemic, including a 3-week turn-around for the main protease.


Results of in situ fusion for isthmic spondylolisthesis.
Between 1976 and 1990, we treated 56 isthmic spondylolisthesis patients with an average age of 15 + 4 (range, 4 + 9 to 27 +/- 2) with in situ bilateral transverse process fusions utilizing autogenous iliac bone graft. None of the patients had a decompression or instrumentation placed. Radiographic fusion was determined from standing spot lateral radiographs and either Ferguson AP or standing AP views of the lumbosacral junction. The radiographic fusion patterns were categorized into the following four grades: (A) definitely solid (n = 28, 50%)--solid big trabeculated bilateral fusion masses; (B) possibly solid (n = 10, 18%)--unilateral large fusion mass with contralateral small fusion mass; (C) probably not solid (n = 6, 11%)--small, thin fusion masses bilaterally; (D) definitely not solid (n = 12, 21%)--graft resorption bilaterally or fusion mass with obvious bilateral pseudarthrosis. This fusion pattern is best determined by the Ferguson ("true AP") radiograph of the lumbosacral junction. Despite this surprisingly low fusion rate, overall clinical improvement was noted in > 80% of patients with preoperative symptoms of back pain, leg pain, or hamstring tightness. We recommend this critical assessment of fusion grades to determine fusion success in this patient population.


Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits.
One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates.


Inconsistencies and open questions regarding low-dose health effects of ionizing radiation.
The effects on human health of exposures to ionizing radiation at low doses have long been the subject of dispute. In this paper we focus on open questions regarding the health effects of low-dose exposures that require further investigations. Seemingly contradictory findings of radiation health effects have been reported for the same exposed populations, or inconsistent estimates of radiation risks were found when different populations and exposure conditions were compared. Such discrepancies may be indicative of differences in sensitivities among the applied methods of epidemiological analysis or indicative of significant discrepancies in health consequences after comparable total exposures of different populations under varying conditions. We focus first on inconsistencies and contradictions in presentations of the state of knowledge by different authoritative experts. We then review studies that found positive associations between exposure and risks in dose ranges where traditional notions (generalized primarily from high-dose studies of A-bomb survivors or exposed animals) would have predicted negligible effects. One persistent notion in many reviews of low-dose effects is the hypothesis of reduced biological effectiveness of fractionated low-dose exposures, compared to that of the same acute dose. This assumption is not supported by data on human populations. From studies of populations that live in contaminated areas, more and more evidence is accumulating on unusual rates of various diseases other than radiation-induced malignancies, health effects that are suspected to be associated with relatively low levels of internal exposures originating from radioactive fallout. Such effects include congenital defects, neonatal mortality, stillbirths, and possibly genetically transmitted disease. A range of open questions challenges scientists to test imaginative hypotheses about induction of disease by radiation with novel research strategies.


Increased sensitization in urban vs. rural environment--rural protection or an urban living effect?
In a population-based longitudinal cohort study, we tested the hypothesis that children growing up in a high-traffic polluted urban area (UA) in the Athens' basin have higher prevalence of allergies and sensitization when compared with those growing up in a Greek provincial rural area (RA). We recruited 478 and 342 children aged 8-10 living in the UA and the RA, respectively. Respiratory health was assessed by a parent-completed questionnaire in three phases: 1995-96 (phase 1), 1999-2000 (phase 2), 2003-04 (phase 3) and skin-prick testing to common indoor and outdoor aeroallergens was performed at phases 1 and 2. Reported asthma and eczema did not differ between the two areas, whereas reported hay fever was persistently more prevalent in the UA than in the RA (16.5%, 17.0%, 18.2% vs. 7.0%, 8.3%, 9.6%, respectively). Sensitization was more prevalent in the UA at both phases (19.0% vs. 12.1% in phase 1, 20.0% vs. 14.1% in phase 2). Residential area contributed independently to sensitization to >or=1 aeroallergens (OR: 0.29; 95% CI: 0.13-0.66; p = 0.003) and to polysensitization (OR: 0.28; 95% CI: 0.10-0.82; p = 0.020) in phase 1. These associations were independent of farming practices. No significant contributions were found in phase 2. Our results suggest that long-term exposure to urban environment is associated with a higher prevalence of hay fever but not of asthma or eczema. The negative association between rural living and the risk of atopy during childhood, which is independent of farming practices, implies that it is mainly driven by an urban living effect.


The assessment of cognitive function in advanced HIV-1 infection and AIDS dementia complex using a new computerised cognitive test battery.
The validity of a new computerised battery called CogState was determined in 60 individuals with advanced human immunodeficiency virus-1 (HIV-1) infection from which eleven were assessed as AIDS dementia complex (ADC) stage 1 or 2. Twenty-one seronegative individuals were recruited as controls. Participants were evaluated with a brief computerised examination, lasting 10-15 min, assessing reaction time, accuracy in working memory and learning. They were also assessed with a standard neuropsychological examination lasting 1h 30 min on average. The computerised assessment demonstrated a good sensitivity of 81.1% and specificity of 69.9% as well as good positive predictive value (81%) and acceptable construct validity (.45-.62). Slowed reaction time and learning deficits in the computerised battery were characteristic of ADC. This study supports the utility of a brief computerised battery in the detection of HIV-associated neurocognitive impairment that could be used for wide-scale screening.


Assessment of magnesium-based biomaterials: from bench to clinic.
Despite the high potential of biodegradable magnesium (Mg) alloys as a new generation of biomaterials for orthopaedic and cardiovascular implantation, their high corrosion rate in body fluid limits their suitability for clinical applications. Extensive research has been performed to improve the corrosion resistance of Mg-based biomaterials. Researchers have also been working to develop new testing and assessment techniques to evaluate the corrosion performance and other in vitro and in vivo properties of their modified Mg alloys. The objective of this review is to present the principles and operation procedures of commonly used standard methods for assessment of Mg-based biomaterials from bench to clinic. The pros and cons of each of these methods are discussed, together with factors for consideration to choose the right methodology. This review also presents the current state and challenges in understanding the testing of Mg-based biomaterials.


A preliminary time-of-flight neutron diffraction study of Streptomyces rubiginosus D-xylose isomerase.
The metalloenzyme D-xylose isomerase forms well ordered crystals that diffract X-rays to ultrahigh resolution (<1 A). However, structural analysis using X-ray diffraction data has as yet been unable to differentiate between several postulated mechanisms that describe the catalytic activity of this enzyme. Neutrons, with their greater scattering sensitivity to H atoms, could help to resolve this by determining the protonation states within the active site of the enzyme. As the first step in the process of investigating the mechanism of action of D-xylose isomerase from Streptomyces rubiginosus using neutron diffraction, data to better than 2.0 A were measured from the unliganded protein at the Los Alamos Neutron Science Center Protein Crystallography Station. Measurement of these neutron diffraction data represents several milestones: this is one of the largest biological molecules (a tetramer, MW approximately 160 000 Da, with unit-cell lengths around 100 A) ever studied at high resolution using neutron diffraction. It is also one of the first proteins to be studied using time-of-flight techniques. The success of the initial diffraction experiments with D-xylose isomerase demonstrate the power of spallation neutrons for protein crystallography and should provide further impetus for neutron diffraction studies of biologically active and significant proteins. Further data will be measured from the enzyme with bound substrates and inhibitors in order to provide the specific information needed to clarify the catalytic mechanism of this enzyme.


Rational design of central selective acetylcholinesterase inhibitors by means of a "bio-oxidisable prodrug" strategy.
This work deals with the design of a bio-oxidisable prodrug strategy for the development of new central selective acetylcholinesterase inhibitors. This prodrug approach is expected to reduce peripheral anticholinesterase activity responsible for various side effects observed with presently marketed AChE inhibitors. The design of these new AChE inhibitors in quinoline series is roughly based on cyclic analogues of rivastigmine. The key activation step of the prodrug involves an oxidation of an N-alkyl-1,4-dihydroquinoline 1 to the corresponding quinolinium salt 2 unmasking the positive charge required for binding to the catalytic anionic site of the enzyme. The synthesis of a set of 1,4-dihydroquinolines 1 and their corresponding quinolinium salts 2 is presented. An in vitro biological evaluation revealed that while all reduced forms 1 were unable to exhibit any anticholinesterase activity (IC50 > 10(6) nM), most of the quinolinium salts 2 displayed high AChE inhibitory activity (IC50 ranging from 6 microM to 7 nM). These preliminary in vitro assays validate the use of these cyclic analogues of rivastigmine in quinoline series as appealing chemical tools for further in vivo development of this bio-oxidisable prodrug approach.


Pregnant moments: the process of conception in infertile couples.
This report is an explication of the process of conception in infertile couples as illuminated by 24 infertile couples and a comparison group of 6 couples with no fertility impairments. Employing techniques generic to grounded theory research, the investigators found that infertile couples lived conception as a series of biological and phenomenological moments. The process of biomedically-assisted conception consisted of three components including: (a) forcing conception; (b) resolving conceptional ambiguity; and (c) reconciling conception as an idea and as an event. The findings suggest the need for a re-examination of current orientations to pregnancy time and space and appraisal of couples' interpretations of conception. In addition, the convergence of the conception experiences of infertile and fertile couples raises questions about the meaning of normal conception in the current technological context of reproduction.


Barriers to Optimal End-of-Life Care for Adolescents and Young Adults With Cancer: Bereaved Caregiver Perspectives.
Adolescents and young adults (AYAs; aged 15-39 years) with cancer frequently receive intensive measures at the end of life (EoL), but the perspectives of AYAs and their family members on barriers to optimal EoL care are not well understood. We conducted qualitative interviews with 28 bereaved caregivers of AYAs with cancer who died in 2013 through 2016 after receiving treatment at 1 of 3 sites (University of Alabama at Birmingham, University of Iowa, or University of California San Diego). Interviews focused on ways that EoL care could have better met the needs of the AYAs. Content analysis was performed to identify relevant themes. Most participating caregivers were White and female, and nearly half had graduated from college. A total of 46% of AYAs were insured by Medicaid or other public insurance; 61% used hospice, 46% used palliative care, and 43% died at home. Caregivers noted 3 main barriers to optimal EoL care: (1) delayed or absent communication about prognosis, which in turn delayed care focused on comfort and quality of life; (2) inadequate emotional support of AYAs and caregivers, many of whom experienced distress and difficulty accepting the poor prognosis; and (3) a lack of home care models that would allow concurrent life-prolonging and palliative therapies, and consequently suboptimal supported goals of AYAs to live as long and as well as possible. Delayed or absent prognosis communication created lingering regret among some family caregivers, who lost the opportunity to support, comfort, and hold meaningful conversations with their loved ones. Bereaved family caregivers of AYAs with cancer noted a need for timely prognostic communication, emotional support to enhance acceptance of a poor prognosis, and care delivery models that would support both life-prolonging and palliative goals of care. Work to address these challenges offers the potential to improve the quality of EoL care for young people with cancer.


Early changes in peritumorous oedema and contralateral white matter after dexamethasone: a study using proton magnetic resonance spectroscopy.
To study the mechanism of action of steroids in patients with peritumorous oedema. To investigate early cerebral metabolic changes proton magnetic resonance spectroscopy (1H-MRS) was used before and 11 to 14 hours after treatment with dexamethasone (12 mg oral loading and 4 mg four times daily maintenance). Nine patients (two men, seven women, mean age 54) with pronounced oedema associated with various intracranial tumours (two astrocytomas, three meningiomas, two glioblastoma, and two metastases) were examined using MRI and MRS. SE1500/135 volume selected MRS (mean volume 21 ml) were performed on an oedematous region and a contralateral region. All spectra were acquired with and without water suppression. Metabolite peak area ratios were determined. Regions of oedema had significantly (P < 0.01) higher unsuppressed water than the contralateral regions, as expected. There was no change at this early time point after dexamethasone. The ratio of the area of choline containing compounds to that creatine and phosphocreatine compounds was determined after which the serial ratios of these before and after were calculated (a serial ratio of 1.0 would indicate no change in the choline to creatine ratios after steroid administration). The mean serial ratios for the area of oedema were 1.02 (SEM 0.08) and 1.10 (0.08) for the contralateral volume of interest, indicating no significant changes. However, significant changes (P < 0.02) were found in the N-acetyl-aspartate (NAA)/choline serial ratios (0.86 (0.06) in the area of oedema, 1.20 (0.10) in contralateral brain) and the NAA/creatine serial ratios (0.86 (0.08) for the oedema, 1.25 (0.11) in contralateral brain). Such rapid changes may be explained either by relatively large alterations in the relaxation characteristics of NAA or, more controversially, by actual changes in the amounts of NAA. It is proposed that steroids act primarily by causing early metabolic changes that are later expressed in improvements in intracranial volume relations.


Selection of treatment modalities for hepatocellular carcinoma at stages T1 and T2: A preliminary analysis based on the Surveillance, Epidemiology, and End Results registry database.
To explore the selection of treatment modalities for hepatocellular carcinoma (HCC) at stages T1 and/or T2 and to compare the survival of patients treated with surgery alone vs radiation therapy (RT) alone. Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. The tumor-nodemetastasis (TNM) stage was established according to the American Joint Committee on Cancer (AJCC) Staging. After age, sex, TNM stage, and tumor extension were matched, the survival was further compared between patients undergoing surgery alone vs RT alone. Of 11967 patients at stages T1 (n=7829) and T2 (n=4138), 10449 (87.31%) underwent surgery alone, 1241 (10.37%) RT alone, and 277 (2.32%) surgery combined with RT. Compared with those treated with RT alone and in combination with surgery, patients treated with surgery alone were younger, with smaller tumor size, higher proportion of females, single lesion, and AJCC stage I/II, and lower proportion of regional and distant lymph nodes, bone, brain, and lung invasion. Among them, 758 pairs (surgery alone and RT alone) at stage T1 and 430 pairs (surgery alone and RT alone) at stage T2 were matched. Regardless of stage T1 or T2, patients undergoing surgery alone had a significantly better cumulative survival than those undergoing RT alone (p<0.001). The treatment selection of HCC was dependent on the age, sex, tumor size, number of lesions, and extrahepatic invasion. Surgery alone should be the preferred treatment modality of HCC at stages T1 and T2.


The Impaired Physician Program of the Medical Society of the District of Columbia.
Since its establishment in 1980, 128 physicians have been referred to the Impaired Physician Program of th Medical Society of the District of Columbia, of whom sixty-four have either successfully completed the program or are in stable recovery.


Intelligence in youth and health behaviours in middle age.
We investigated the association between intelligence in youth and a range of health-related behaviours in middle age. Participants were the 5347 men and women who responded to the National Longitudinal Survey of Youth 1979 (NLSY-79) 2012 survey. IQ was recorded with the Armed Forces Qualification Test (AFQT) when participants were aged 15 to 23 years of age. Self-reports on exercise (moderate activity, vigorous activity, and strength training), dietary, smoking, drinking, and oral health behaviours were recorded when participants were in middle age (mean age = 51.7 years). A series of regression analyses tested for an association between IQ in youth and the different health related behaviours in middle age, while adjusting for childhood socio-economic status (SES) and adult SES. Higher IQ in youth was significantly associated with the following behaviours that are beneficial to health: being more likely to be able to do moderate cardiovascular activity (Odds Ratio, 95% CI) (1.72, 1.35 to 2.20, p < .001) and strength training (1.61, 1.37 to 1.90, p < .001); being less likely to have had a sugary drink in the previous week (0.75, 0.71 to 0.80, p < .001); a lower likelihood of drinking alcohol heavily (0.67, 0.61 to 0.74, p < .001); being less likely to smoke (0.60, 0.56 to 0.65, p < .001); being more likely to floss (1.47, 1.35 to 1.59, p < .001); and being more likely to say they "often" read the nutritional information (1.20, 1.09 to 1.31, p < .001) and ingredients (1.24, 1.12 to 1.36, p < .001) on food packaging compared to always reading them. Higher IQ was also linked with dietary behaviours that may or may not be linked with poorer health outcomes (i.e. being more likely to have skipped a meal (1.10, 1.03 to 1.17, p = .005) and snacked between meals (1.37, 1.26 to 1.50, p < .001) in the previous week). An inverted u-shaped association was also found between IQ and the number of meals skipped per week. Higher IQ was also linked with behaviours that are known to be linked with poorer health (i.e. a higher likelihood of drinking alcohol compared to being abstinent from drinking alcohol (1.58, 1.47 to 1.69, p < .001)). A u-shaped association was found between IQ and the amount of alcohol consumed per week and an inverted u-shaped association was found between IQ and the number of cigarettes smoked a day. Across all outcomes, adjusting for childhood SES tended to attenuate the estimated effect size only slightly. Adjusting for adult SES led to more marked attenuation but statistical significance was maintained in most cases. In the present study, a higher IQ in adolescence was associated with a number of healthier behaviours in middle age. In contrast to these results, a few associations were also identified between higher intelligence and behaviours that may or may not be linked with poor health (i.e. skipping meals and snacking between meals) and with behaviours that are known to be linked with poor health (i.e. drinking alcohol and the number of cigarettes smoked). To explore mechanisms of association, future studies could test for a range of health behaviours as potential mediators between IQ and morbidity or mortality in later life.


Inferring circRNA-drug sensitivity associations via dual hierarchical attention networks and multiple kernel fusion.
Increasing evidence has shown that the expression of circular RNAs (circRNAs) can affect the drug sensitivity of cells and significantly influence drug efficacy. Therefore, research into the relationships between circRNAs and drugs can be of great significance in increasing the comprehension of circRNAs function, as well as contributing to the discovery of new drugs and the repurposing of existing drugs. However, it is time-consuming and costly to validate the function of circRNA with traditional medical research methods. Therefore, the development of efficient and accurate computational models that can assist in discovering the potential interactions between circRNAs and drugs is urgently needed. In this study, a novel method is proposed, called DHANMKF , that aims to predict potential circRNA-drug sensitivity interactions for further biomedical screening and validation. Firstly, multimodal networks were constructed by DHANMKF using multiple sources of information on circRNAs and drugs. Secondly, comprehensive intra-type and inter-type node representations were learned using bi-typed multi-relational heterogeneous graphs, which are attention-based encoders utilizing a hierarchical process. Thirdly, the multi-kernel fusion method was used to fuse intra-type embedding and inter-type embedding. Finally, the Dual Laplacian Regularized Least Squares method (DLapRLS) was used to predict the potential circRNA-drug sensitivity associations using the combined kernel in circRNA and drug spaces. Compared with the other methods, DHANMKF obtained the highest AUC value on two datasets. Code is available at https://github.com/cuntjx/DHANMKF .


Retrograde ejaculation following anterior lumbar surgery: a systematic review and pooled analysis.
The present systematic review and pooled analysis aims to assess the incidence and risk factors for the development of retrograde ejaculation (RE) following first-time open anterior lumbar surgery. A systematic MEDLINE review via PubMed was performed, identifying 130 clinical papers relating to the topic. Eighteen publications were selected according to predetermined inclusion and exclusion criteria and were used to determine the incidence of RE. Only the publications that provided data on surgical risk factors present specifically in the men in the study were included in the analysis of risk factors. Of the 2503 men included, there were 57 reported events of RE (2.3%). Of the cases for which long-term data were provided, 45.8% had resolved by final follow-up. There was a statistically significant increased risk associated with a transperitoneal as opposed to a retroperitoneal approach (8.6% vs 3.2%), as well as with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) as opposed to ALIF with bone graft or arthroplasty in controls (5.0% vs 1.8%). However, when excluding from analysis the patients operated on prior to the FDA's 2008 warning that commented on the drug's neuroinflammatory properties, there was no significant difference in rates of RE in patients receiving rhBMP-2 versus the control group (2.4% vs 2.5%). There was no significant difference in risk based on single- versus multilevel procedure or on ALIF versus arthroplasty. In a pooled analysis of currently published data on men undergoing first-time open anterior lumbar surgery, this study found an overall incidence of RE of 2.3%. Nearly half of these patients recovered, reporting resolution of symptoms anywhere between 3 months and 48 months. Analysis of risk factors was limited by a paucity of published literature segregating data by sex. However, there was an increased risk associated with rhBMP-2 only when including data collected prior to the FDA warning on its detrimental properties. The authors therefore posit that the risk of RE is probably overestimated in the literature, given that the vast majority of the data available were collected prior to this warning and given the subsequent implementation of precautions when handling rhBMP-2.


Pyrimidine and purine salvage deoxyribonucleoside metabolism in hepatic and renal homogenates from rats pretreated with propylthiouracil or L-thyroxine.
OBJECTIVES: In vitro activities of thymidine kinase (TK, EC 18.104.22.168), adenosine kinase (AK, EC 22.214.171.124) and deoxycytidine kinase (dCK, EC 18.104.22.168) enzymes involved in the salvage pathway of DNA precursor synthesis, in homogenates of the rat liver and kidney, were examined. Type I iodothyronine-5'-deiodinase (5'D-I) is the main enzyme responsible for peripheral metabolism of thyroid hormones. This occurs especially in the liver, kidney and muscle. The activity of 5'D-I is inhibited bypropylthiouracil (PTU), an antithyroid drug. METHODS: The liver and kidney were collected from rats pretreated in vivo with either a 0.1% solution of PTU in drinking water for 2 weeks or injected with levothyroxine (L-T(4), 50 &mgr;g/kg BW, daily) for 2 weeks. The enzyme activities were measured by ascending chromatography and expressed asthe amounts of radioactive reaction products of the phosphorylation of dThd (for TK), ofdAdo (for AK and dCK) and of dGuo (for dCK). RESULTS: In liver homogenates, PTU-pretreatment decreased the activities of the three enzymes when compared to control values and those of L-T(4)-treated animals; also L-T(4) injections decreased the AK and dCK activities in the liver homogenates. PTU-pretreatment increased TK activity and the rate of dGuo phosphorylation in kidney homogenates, when compared to controls and to the L-T(4)-pretreated animals. Conversely, both PTU- and L-T(4)-pretreatment reduced the rate of dAdo phosphorylation in kidney homogenates. CONCLUSION: Changes in the activities of examined enzymes which participate inpyrimidine orpurine metabolism of the salvage pathway of DNA synthesis in the liver afterPTU-pretreatment (as shown herein) are similar to the changes of the 5'D-I activity after PTU-treatment (as reported by others). Thus, the observations suggest a role of the salvage pathway of DNA synthesis in the peripheral metabolism of thyroid hormones.


Causes of poor postoperative improvement after reverse total shoulder arthroplasty.
Although reverse total shoulder arthroplasty (RTSA) has been successful in improving pain and function in most patients, some patients fail to improve clinically. The present study used a large registry of RTSA patients to evaluate associations between patient-related factors and poor postoperative improvement after RTSA. A prospectively collected shoulder arthroplasty registry was queried for consecutive patients who underwent RTSA from 2007 to 2013. Patients with baseline and minimum 2-year postoperative American Shoulder and Elbow Surgeons (ASES) scores were included. Poor postoperative improvement was defined as a change in the ASES of less than 12 points. Multivariate logistic regression analysis was used to identify independent risk factors. A total of 150 patients met inclusion and exclusion criteria. Logistic regression revealed that male sex (adjusted odds ratio [OR], 7.9; P = .004), presence of an intact rotator cuff at the time of surgery (adjusted OR, 4.8; P = .025), depression (adjusted OR, 11.2; P = .005), a higher baseline ASES score (P < .001), and higher total number of medical comorbidities (P = .035) were associated with poor postoperative improvement after RTSA. Surrogates for better preoperative function after RTSA, such as a higher baseline ASES score and intact rotator cuff at the time of surgery, correlated with poor postoperative improvement. In addition, male sex, depression, and total number of medical comorbidities also correlated with poor postoperative improvement. Interestingly, factors such as patient age and indication for surgery were not found to correlate with poor improvement after RTSA.


Optimized application of surface-enhanced laser desorption/ionization time-of-flight MS to differentiate Francisella tularensis at the level of subspecies and individual strains.
Francisella tularensis, the causative agent of tularaemia, is a potential agent of bioterrorism. The phenotypic discrimination of the closely related F. tularensis subspecies and individual strains with traditional methods is difficult and time consuming, often producing ambiguous results. Surface-enhanced laser desorption/ionization time-of-flight MS (SELDI-TOF MS) was used in this study to discriminate the different species and subspecies of the genus Francisella. We tested 18 Francisella strains including at least one representative of each species/subspecies on four different types of chromatographic chip surfaces. Multivariate analysis (hierarchical clustering and principal component analysis) allowed grouping of the strains according to their designated subspecies. Furthermore, single strains within F. tularensis subspecies could be discriminated.


Cancer and Tumor-Associated Childhood Stroke: Results From the International Pediatric Stroke Study.
The prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer- and tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry. Children aged 29 days to less than 19 years with arterial ischemic stroke or cerebral sinovenous thrombosis enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests. Cancer or tumor was present in 99 of 2968 children (3.3%) with arterial ischemic stroke and 64 of 596 children (10.7%) with cerebral sinovenous thrombosis. Among children in whom cancer type was identified, 42 of 88 arterial ischemic stroke cases (48%) had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 cerebral sinovenous thrombosis cases (78%) had hematologic malignancies and eight (14%) had brain tumors. Of 54 cancer-associated arterial ischemic stroke cases with a known cause, 34 (63%) were due to arteriopathy and nine (17%) were due to cardioembolism. Of 46 cancer-associated cerebral sinovenous thrombosis cases with a known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer were less likely than children without cancer to receive antithrombotic therapy for arterial ischemic stroke (58% vs 80%, P = 0.007) and anticoagulation for cerebral sinovenous thrombosis (71% vs 87%, P = 0.046). Recurrent arterial ischemic stroke (5% vs 2%, P = 0.04) and cerebral sinovenous thrombosis (5% vs 1%, P = 0.006) were more common among children with cancer. Cancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for children with cancer are needed.


Temporal trends (1977-2007) and ethnic inequity in child mortality in rural villages of southern Guinea Bissau.
Guinea Bissau is one of the poorest countries in the world, with one of the highest under-5 mortality rate. Despite its importance for policy planning, data on child mortality are often not available or of poor quality in low-income countries like Guinea Bissau. Our aim in this study was to use the baseline survey to estimate child mortality in rural villages in southern Guinea Bissau for a 30 years period prior to a planned cluster randomised intervention. We aimed to investigate temporal trends with emphasis on historical events and the effect of ethnicity, polygyny and distance to the health centre on child mortality. A baseline survey was conducted prior to a planned cluster randomised intervention to estimate child mortality in 241 rural villages in southern Guinea Bissau between 1977 and 2007. Crude child mortality rates were estimated by Kaplan-Meier method from birth history of 7854 women. Cox regression models were used to investigate the effects of birth periods with emphasis on historical events, ethnicity, polygyny and distance to the health centre on child mortality. High levels of child mortality were found at all ages under five with a significant reduction in child mortality over the time periods of birth except for 1997-2001. That period comprises the 1998/99 civil war interval, when child mortality was 1.5% higher than in the previous period. Children of Balanta ethnic group had higher hazard of dying under five years of age than children from other groups until 2001. Between 2002 and 2007, Fula children showed the highest mortality. Increasing walking distance to the nearest health centre increased the hazard, though not substantially, and polygyny had a negligible and statistically not significant effect on the hazard. Child mortality is strongly associated with ethnicity and it should be considered in health policy planning. Child mortality, though considerably decreased during the past 30 years, remains high in rural Guinea Bissau. Temporal trends also suggest that civil wars have detrimental effects on child mortality. Current Controlled Trials ISRCTN52433336.


Optimization of intradermal vaccination by DNA tattooing in human skin.
The intradermal administration of DNA vaccines by tattooing is a promising delivery technique for genetic immunization, with proven high immunogenicity in mice and in nonhuman primates. However, the parameters that result in optimal expression of DNA vaccines that are applied by this strategy to human skin are currently unknown. To address this issue we set up an ex vivo human skin model in which DNA vaccine-induced expression of reporter proteins could be monitored longitudinally. Using this model we demonstrate the following: First, the vast majority of cells that express DNA vaccine-encoded antigen in human skin are formed by epidermal keratinocytes, with only a small fraction (about 1%) of antigen-positive epidermal Langerhans cells. Second, using full randomization of DNA tattoo variables we show that an increase in DNA concentration,needle depth, and tattoo time all significantly increase antigen expression ( p < 0.001), with DNA concentration forming the most critical variable influencing the level of antigen expression. Finally, in spite of the marked immunogenicity of this vaccination method in animal models, transfection efficiency of the technique is shown to be extremely low, estimated at approximately 2 to 2000 out of 1 x 10(10) copies of plasmid applied. This finding, coupled with the observed dependency of antigen expression on DNA concentration, suggests that the development of strategies that can enhance in vivo transfection efficacy would be highly valuable. Collectively, this study shows that an ex vivo human skin model can be used to determine the factors that control vaccine-induced antigen expression and define the optimal parameters for the evaluation of DNA tattoo or other dermal delivery techniques in phase 1 clinical trials.


Neuro-effector characteristics of sweat glands in the human hand activated by irregular stimuli.
Intraneural electrical stimulation of cutaneous fascicles in the median nerve was performed in 24 normal subjects and the effects on sweating within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (wvpp). The aims were: (1) to investigate the response variability between repeated stimulation sequences in the same skin site and between different sites and (2) to compare quantitative effects of regular and irregular stimulation on skin resistance and wvpp. Regional axillary anaesthesia of the brachial plexus eliminated spontaneous and reflex sympathetic activity. With repeated irregular stimulation sequences skin resistance responses from the same skin site varied only slightly between trials. Differences between response curves from two skin sites in the same subject or from different subjects were also small but significantly greater (P < 0.01) than differences between responses to repeated stimulation in the same site. Irregular stimulation with average frequencies of 0.49 Hz and 3.51 Hz gave greater resistance responses than if the same number of stimuli were delivered regularly (P < 0.01). The difference was most pronounced at 0.49 Hz. At an average frequency of 0.49 Hz the stimulation usually evoked no changes of wvpp whereas an average frequency of 3.51 Hz caused an increase of wvpp which was greater with irregular than with regular stimulation in all subjects. We conclude that: (1) sweat responses to sudomotor nerve traffic vary slightly due to local factors in the skin or the terminal nerve endings and (2) irregular sudomotor nerve traffic evokes more sweat than if the same impulses occur regularly.


A phosphorylcholine-based zwitterionic copolymer coated ZIF-8 nanodrug with a long circulation time and charged conversion for enhanced chemotherapy.
In recent years, zeolitic imidazolate framework-8 (ZIF-8) has become an attractive metal organic framework (MOF) material in drug delivery for cancer chemotherapy. However, as a drug delivery system, ZIF-8 still shows some disadvantages, such as short blood circulation time and poor tumor targeting, leading to reduced drug delivery efficiency and unsatisfactory treatment. Herein, we developed a phosphorylcholine-based zwitterionic copolymer coated ZIF-8 nanodrug (DOX@ZIF-8@P(MPC-co-C7A)), and the obtained nanodrug was prepared via a charge-conversional zwitterionic copolymer coating on DOX@ZIF-8 composites. In this system, DOX was encapsulated in the framework of ZIF-8, which could reduce the drug leakage in the bloodstream. The phosphorylcholine-based zwitterionic copolymer effectively extended the blood circulation time, resulting in enhanced tumor accumulation of the nanodrug. Once the nanodrug reached the tumor site, the surface charge of the system could rapidly convert to positive, resulting in an enhanced tumor cellular uptake. Finally, in the acidic environment inside intracellular organelles, DOX will be released rapidly for chemotherapy owing to the fast disintegration of ZIF-8 frameworks. Therefore, the obtained nanodrug could effectively inhibit the growth of A549-bearing tumors (93.2% tumor inhibition rate) with negligible side effects. Overall, this work significantly improved the drug delivery efficiency of ZIF-8, which may pave the way for the biomedical applications of ZIF-8 crystals in anti-tumor drug delivery.


Comparison of patient-centered outcomes measures between low-speed drilling without irrigation and high-speed drilling with irrigation: A randomized clinical trial.
To compare patient satisfaction during surgery, postoperative pain and inflammation and quality of life between high-speed drilling with irrigation and low-speed drilling without irrigation for implant bed preparation. Sixty-six posterior single edentulous patients were included in a randomized controlled clinical trial. Implant beds were created using high-speed drilling with irrigation (control group) or low-speed drilling without irrigation (test group). Patient satisfaction during surgery (in relation to drilling-time perception, vibration, pressure, noise, comfort, and drowning sensation) and postoperative pain and inflammation were evaluated using a 100-mm visual analogue scale (VAS)-based questionnaire. Quality of life was analyzed with a Likert scale (in relation to mouth opening, chewing, speaking, sleeping, daily routine, and job). The follow-up period was 7 days. Patient satisfaction in relation to drilling-time perception, vibration, pressure, and noise did not show statistically significant differences (p > .05). The highest scores of drowning sensation (p < .05) were correlated (moderate correlation (r = .57)) with lowest scores of comfort (p < .005). Both postoperative pain and inflammation means were significantly higher in the control group than in the test group. No significant differences in quality of life were observed during the postoperative period (p > .05). Low-speed drilling without irrigation for single implant site preparation was more comfortable for patients than high-speed drilling with irrigation, due to the correlation between important drowning sensation and low perceived comfort. Postoperative pain and inflammation were lower for low-speed drilling without irrigation. Further studies are needed to validate or refute these results.


Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys.
Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.


Filling the gap: Grassroots mask making in California during the Coronavirus pandemic.
In early months of 2020, California experienced a mask-making revolution during the Coronavirus pandemic. Media reports and personal pleas from the medical community regarding personal protective equipment shortages and rationing activated a female-led, voluntary response to protect frontline medical and essential workers, loved ones, and vulnerable populations. Mask makers impressed themselves into action, operating independent of the formal channels for emergency response to fill the gap in communities across the state using social media and crowdsourcing to match offers of assistance with needs. Makers provided protection to thousands of Californians using locally organized Facebook groups to share patterns, collaborate, problem solve, coordinate mask requests and distribution, and build community when the supply chain fell short. While many legitimate obstacles prevent the formal response community from coordinating with emergent volunteers, recognizing how efficient and effective they were during COVID-19 benefits the whole commu-nity approach to emergency management.


PASBio: predicate-argument structures for event extraction in molecular biology.
The exploitation of information extraction (IE), a technology aiming to provide instances of structured representations from free-form text, has been rapidly growing within the molecular biology (MB) research community to keep track of the latest results reported in literature. IE systems have traditionally used shallow syntactic patterns for matching facts in sentences but such approaches appear inadequate to achieve high accuracy in MB event extraction due to complex sentence structure. A consensus in the IE community is emerging on the necessity for exploiting deeper knowledge structures such as through the relations between a verb and its arguments shown by predicate-argument structure (PAS). PAS is of interest as structures typically correspond to events of interest and their participating entities. For this to be realized within IE a key knowledge component is the definition of PAS frames. PAS frames for non-technical domains such as newswire are already being constructed in several projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should enable more accurate applications in several areas where sentence understanding is required like machine translation and text summarization. In this article, we explore the need to adapt PAS for the MB domain and specify PAS frames to support IE, as well as outlining the major issues that require consideration in their construction. We introduce PASBio by extending a model based on PropBank to the MB domain. The hypothesis we explore is that PAS holds the key for understanding relationships describing the roles of genes and gene products in mediating their biological functions. We chose predicates describing gene expression, molecular interactions and signal transduction events with the aim of covering a number of research areas in MB. Analysis was performed on sentences containing a set of verbal predicates from MEDLINE and full text journals. Results confirm the necessity to analyze PAS specifically for MB domain. At present PASBio contains the analyzed PAS of over 30 verbs, publicly available on the Internet for use in advanced applications. In the future we aim to expand the knowledge base to cover more verbs and the nominal form of each predicate.


Wellness education for individuals with chronic mental illness living in the community.
The article reports a wellness education program developed to enhance and promote healthy life-style behaviors for individuals with chronic mental illness living in the community. Theoretical concepts from health promotion, wellness, and social learning were used in the development of this program. The program comprised three components: wellness education sessions, exercise/activity sessions, and a smoking reduction course.


Position statement. The right to accept or reject an assignment. American Nurses Association.
The American Nurses Association (ANA) believes that nurses should reject assignment that puts patients or themselves in serious, immediate jeopardy. ANA supports the nurses obligation to reject an assignment in these situations even where there is not a specific legal protection for rejecting such an assignment. The professional obligations to the nurse to safeguard clients are grounded in the ethical norms of the profession, the Standards of Clinical Nursing Practice and state nurse practice acts.


The Gladiator's Tears: Epiphora From Ancient Rome.
This article examines the clinical presentation of epiphora in Ancient Rome through the historico-medical analysis of the literary evidence provided by the verses by the poet Juvenal in his Satire VI. A gladiator's ophthalmological problem is interpreted as epiphora caused by traumatic injuries to the craniofacial region, compatible with those described in the palaeopathological literature. This analysis also focuses on the history of epiphora in antiquity and its treatment.


Barriers and facilitators to care for individuals with sickle cell disease in central North Carolina: The emergency department providers' perspective.
Sickle cell disease (SCD) is an inherited blood disorder associated with acute pain crisis and other complications that lead to frequent emergency department (ED) visits. To improve outcomes, the National Heart, Lung and Blood Institute (NHLBI) published recommendations for management of acute pain crisis. NHLBI also funded eight centers across the United States to participate in the Sickle Cell Disease Implementation Consortium. This six-year effort consists of two phases. Phase one involved conducting needs assessments of barriers and facilitators to SCD care. The aim of this study was to describe challenges and facilitators to caring for SCD from the perspective of ED providers in central North Carolina (NC). We conducted a needs assessment survey with ED providers throughout NC. We also conducted focus groups and an interview with ED providers from three healthcare facilities in central NC. One hundred and eleven surveys (60.6% physicians, 26% registered nurses, 13.5% physician assistants) were completed and 13 providers participated in 3 focus groups and 1 interview. Slightly more than half (50. 4%) utilized individualized dosing protocols to treat sickle cell pain. Only 32.4% of the providers were aware of the NHLBI SCD recommendations. Barriers to care from the survey included: patient behavior (67.57%), the opioid epidemic (67.57%), overcrowding (64.86%), and concern about addiction (49.55%). Perceived barriers to care identified in the focus groups and interview included: high patient volumes, lack of SCD care protocols, poor communication among providers and stigma. Facilitators to care included: individualized pain plans, comfort prescribing opioids and electronic medical records. SCD care is influenced by many factors. Our results illuminate the need for increased use of the NHLBI SCD recommendations, individualized pain protocols, and use of electronic medical records and other care-interventions, specifically geared towards improving provider knowledge and mitigating provider bias.


Role of contrast-enhanced ultrasonography in percutaneous radiofrequency ablation of liver metastases and efficacy evaluation.
To retrospectively investigate the role of contrast-enhanced ultrasonography (CEUS) in percutaneous radiofrequency ablation (RFA) in patients with liver metastases and evaluate the therapeutic efficacy of RFA assisted by CEUS. From May 2004 to September 2010, 136 patients with 219 liver metastatic lesions received CEUS examination 1 h before RFA (CEUS group), and other 126 patients with 216 lesions without CEUS examination in the earlier period were served as a historical control group. The mean tumor size was 3.2 cm and the mean tumor number was 1.6 in the CEUS group, while 3.4 cm and 1.7 in the control group, respectively (P>0.05). The clinical characteristics, recurrence results and survival outcomes were compared between two groups. In the CEUS group, two isoechoic tumors were not demonstrated on unenhanced ultrasonography (US), and 63 (47%) of 134 tumors examined with CEUS were 0.3 cm larger than with unenhanced US. Furthermore, in 18.4% of 136 patients, additional 1-3 tumors were detected on CEUS. The CEUS group showed higher early tumor necrosis and lower intrahepatic recurrence than the control group. The 3-year overall survival (OS) rate and the 3-year local recurrence-free survival (LRFS) rate in the CEUS group were 50.1% and 38.3%, in contrast to 25.3% and 19.3% in the control group, respectively (P=0.002 and P<0.001). CEUS provides important information for RFA treatment in patients with liver metastases and better therapeutic effect could be attained.


Chemical and toxicological characterization of particulate emissions from diesel vehicles.
This paper presents a detailed chemical and toxicological characterization of the diesel particulate matter (PM) emitted from diesel vehicles running on a chassis dynamometer under different driving conditions. Chemical analyses were performed to characterize the contents of organic carbon (OC), elemental carbon (EC), and 31 polycyclic aromatic hydrocarbons (PAHs) in the collected PM samples. The OC-EC analysis results revealed that PM emissions from diesel vehicles in this study were dominated by OC and that the emission of vehicles equipped with diesel particulate filters had high OC/EC ratios. The PAH analysis results revealed that 4- and 5-ring PAHs were the dominant PAHs in the OC fraction of the PM samples. Particle toxicity was evaluated through three toxicological markers in human A549 cells, namely (1) acellular 2,7-dichlorofluorescein (DCFH) for oxidative potential, (2) interleukin-6 (IL-6) for inflammation, and (3) glutathione (GSH) for antioxidation after exposure. Statistical analyses revealed that vehicle sizes have statistically significant effects on the concentrations of the markers. Correlation analysis between PAHs and toxicological markers revealed that significant correlations existed between specific compounds and markers. Our results can be used as a reference by policy makers to formulate emission control strategies and as a dataset for other modeling studies.


B cell depletion reduces the development of atherosclerosis in mice.
B cell depletion significantly reduces the burden of several immune-mediated diseases. However, B cell activation has been until now associated with a protection against atherosclerosis, suggesting that B cell-depleting therapies would enhance cardiovascular risk. We unexpectedly show that mature B cell depletion using a CD20-specific monoclonal antibody induces a significant reduction of atherosclerosis in various mouse models of the disease. This treatment preserves the production of natural and potentially protective anti-oxidized low-density lipoprotein (oxLDL) IgM autoantibodies over IgG type anti-oxLDL antibodies, and markedly reduces pathogenic T cell activation. B cell depletion diminished T cell-derived IFN-gamma secretion and enhanced production of IL-17; neutralization of the latter abrogated CD20 antibody-mediated atheroprotection. These results challenge the current paradigm that B cell activation plays an overall protective role in atherogenesis and identify new antiatherogenic strategies based on B cell modulation.


[Effect of hydrocortisone on composition of polyphosphoinositides in liver cell nuclear membrane and rat brain].
The action of hydrocortisone in vivo was shown to cause changes both in the total amount of phospholipids and polyphosphoinositides of rat liver and brain nuclear membranes. The hormone increased the content of five from seven phospholipid fractions including the fraction of monophosphoinositide when acting in concentration and exposition leading to activation of biosynthetic processes. The increasing of monophosphoinositides amount was accompanied by the decreasing of triphosphoinositides content which indicated the redistribution among the phosphoinositides fractions under the steroid hormone action in both cell types.


Atorvastatin prevents left ventricular remodeling in spontaneously hypertensive rats.
Statins improve left ventricular (LV) remodeling in spontaneously hypertensive rats (SHRs). This study was designed to investigate the effects of atorvastatin administered in the early stage on LV remodeling in SHRs, and to explore the underlying mechanisms.Sixteen male 8-week-old SHRs were randomized to receive distilled water (SHR-DW) or atorvastatin (SHR-ATV) for 12 weeks. Age-matched male Wistar-Kyoto (WKY) rats gavaged with distilled water served as controls. LV remodeling was evaluated, myocardial CTGF expression levels were detected using Western blotting, and cardiomyocyte apoptosis was detected with the TUNEL method.Compared with WKY and SHR-DW, atorvastatin treatment significantly decreased systolic blood pressure in SHRs; atorvastatin significantly inhibited LV remodeling, as indicated by the reduced LV weight/body weight ratio (SHR-ATV: 4.0 ± 0.4 versus SHR-DW: 4.7 ± 0.4 mg/g, P < 0.05), cardiomyocyte diameter (SHR-ATV: 16.2 ± 2.8 versus SHR-DW: 19.0 ± 1.0 µm, P < 0.05), and interstitial fibrosis (SHR-ATV: 3.3 ± 2.1 versus SHR-DW: 4.5 ± 1.8%, P < 0.05). Compared with WKY, myocardial CTGF expression was significantly increased and cardiomyocyte apoptosis decreased in SHRs. Compared with the SHR-DW group, atorvastatin treatment significantly inhibited myocardial CTGF expression (SHR-ATV: 0.69 ± 0.21 versus SHR-DW: 1.12 ± 0.27, P < 0.05) and induced cardiomyocyte apoptosis in SHRs (SHR-ATV: 5.2 ± 0.6 versus SHR-DW: 1.9 ± 0.3%, P < 0.05).The results indicate that early-stage administration of atorvastatin effectively prevented LV remodeling in SHRs, and that inhibition of myocardial CTGF expression and induction of cardiomyocyte apoptosis may be the underlying mechanisms.


[The Institute of Anatomy in the centenary of the Medical Faculty of Lisbon University].
The authors join the celebrations of the Centenary of the establishment of the Faculdade de Medicina da Universidade de Lisboa, on the 22(nd) April 2011, through the historical account of one of its main pilasters, the Institute of Anatomy. It is discussed the scope of its creation at the time, the important work done, the presence and participation in major international evolutionary landmarks in Anatomy, current thinking and action, and the measures implemented to prepare the incoming medical generations. Finally it will be presented the challenges for the 21st century and the strategies to overcome them, which includes the development of the Institute of Anatomy at the Medical Faculty of Lisbon University, in order to create a major pedagogic-scientific study space, for teaching and research of human normal morphology, above all in vivo aspects more applied, the clinic and imaging pre- and post-graduate. There is a world of morphological investigations, basic and clinical, to be held, involving teachers, students, and even doctors and surgeons, with the privileged scientific and research support from the Institute of Anatomy of the Faculdade de Medicina da Universidade de Lisboa!


The Role of Actin Cytoskeleton in Memory Formation in Amygdala.
The central, lateral and basolateral amygdala (BLA) nuclei are essential for the formation of long-term memories including emotional and drug-related memories. Studying cellular and molecular mechanisms of memory in amygdala may lead to better understanding of how memory is formed and of fear and addiction-related disorders. A challenge is to identify molecules activated by learning that subserve cellular changes needed for memory formation and maintenance in amygdala. Recent studies show that activation of synaptic receptors during fear and drug-related learning leads to alteration in actin cytoskeleton dynamics and structure in amygdala. Such changes in actin cytoskeleton in amygdala are essential for fear and drug-related memories formation. Moreover, the actin cytoskeleton subserves, after learning, changes in neuronal morphogenesis and glutamate receptors trafficking in amygdala. These cellular events are involved in fear and drug-related memories formation. Actin polymerization is also needed for the maintenance of drug-associated memories in amygdala. Thus, the actin cytoskeleton is a key mediator between receptor activation during learning and cellular changes subserving long-term memory (LTM) in amygdala. The actin cytoskeleton may serve as a target for pharmacological treatment of fear memory associated with fear and anxiety disorders and drug addiction to prevent the debilitating consequences of these diseases.


The engagement of older people living with chronic lung disease in a peer support community-based exercise programme: A qualitative study.
Chronic lung disease is a common and complex condition. Pulmonary rehabilitation programmes-either hospital-based or in the community are recommended in evidence-based clinical practice guidelines. To explore the experience of older people with chronic lung disease involved in a peer support community-based exercise maintenance programme. Participants were a part of the Lungs in Action programme run in a local community leisure centre through Lung Foundation Australia. All the programme participants (n = 25) were invited by an independent person through email and/or letter to participate in the study and provided with a participant information and consent form. Participants who returned consent forms were scheduled for group interviews. Participants were recruited over a 2-week period between 30 August and 13 September 2022. We conducted qualitative group interviews using a semi-structured interview guide to explore the experiences of older people living with chronic lung disease. Data were analysed using reflexive thematic analysis. A total of 14 participants (eight female and six male) aged between 64 and 86 years were interviewed. Three themes emerged from the data: motivation, authentic social engagement, and sustainable achievement. Motivation stemmed from the participants' perceived health benefits, and from the trainers' motivation and encouragement. Participants discussed how sharing experiences created an environment of trust and understanding, fun and friendship. Social engagement and creating authentic relationships were key aspects raised by participants. Feeling more confident in themselves and being able to accomplish physical tasks, making activities of daily living more manageable featured highly in participants' responses. Community-based peer support exercise groups enable environments for people with chronic lung disease to maintain physical fitness, and to connect with others to form friendships and have fun.