Impact of gestational hypertension and pre-eclampsia on preterm birth in China: a large prospective cohort study.
To investigate the impact of gestational hypertension and pre-eclampsia on preterm birth. The data were collected from the China-US Collaborative Project for Neural Tube Defect Prevention; this was a large population-based cohort study. We selected participants registered in two southern provinces, for whom we had exact information on gestational blood pressure and pregnancy outcomes, and who were not affected by chronic hypertension. In total, 200 103 participants were recruited from 1993 to 1995. Preterm birth was defined as a singleton pregnancy and birth before 37 gestational weeks. The incidences of gestational hypertension and pre-eclampsia were 5.47% and 5.44%, respectively, for women who gave birth at full term, and 5.63% and 7.33%, respectively, for those who gave birth preterm. After adjusting for potential confounders, the risk ratios (RRs) of preterm birth in women with gestational hypertension and pre-eclampsia were 1.04 (95% CI 0.98 to 1.11) and 1.39 (95% CI 1.25 to 1.55), respectively. The associations were stronger for early-onset (<28 weeks of gestation) gestational hypertension (adjusted RR=2.13, 95% CI 1.71 to 2.65) and pre-eclampsia (adjusted RR=8.47, 95% CI 5.59 to 12.80). Pre-eclampsia was associated with a higher risk of preterm birth. The early-onset gestational hypertension and pre-eclampsia were associated with more severe risks than late-onset conditions.


Rituximab for steroid-refractory chronic graft-versus-host disease.
B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome-encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti-B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P < .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome-encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti-B-cell therapy with rituximab may be beneficial for patients with steroidrefractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396.


[Embracement and anxiety symptoms in patients before cardiac surgery].
This is a randomized clinical trial, aimed to compare the frequency and intensity of symptoms of anxiety in patients of preoperative cardiac surgery who received empathic behavior from nurse or family or those who received no specific type of empathic behavior. The sample consisted of 66 patients in preoperative of cardiac surgery, which were divided in three groups: empathic behavior by nurses, without specific empathic behavior and by family. Anxiety was assessed at two points in time: before and after the intervention. The instrument used was developed and validated by Suriano, comprising 19 defining characteristics of the nursing diagnosis anxiety. It was observed that the reduction of anxiety symptoms was higher in the group receiving empathic behavior of relatives when compared to the other two groups. The results suggested that encouraging the participation of family members can contribute to the reduction of anxiety symptoms in patients in preoperative cardiac surgery.


ENDOR-assisted study of the stable EPR spectrum of X-irradiated alpha-L-sorbose single crystals: MLCFA and simulation decomposition analyses.
After X irradiation of single crystals of alpha-L-sorbose at 295 K, previous electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), and ENDOR-induced EPR (EI-EPR) results have indicated the formation of at least 10 different free radicals, and also that conceivably each carbon in the pyranose ring is a possible radical center. The radicals appear to be formed mostly by net H-abstraction reactions followed by standard elimination (e.g. beta-OH elimination) reactions or proton shifts, in turn leading to ring opening and fragmentation. In the present work, EPR spectra were recorded at room temperature with the external magnetic field along each of the three crystallographic axes subsequent to careful annealing at different temperatures using a high-temperature cavity. Each of the three sets of spectra was subjected to a maximum likelihood common factor analysis (MLCFA) that contributed to a better understanding of the spectral decays. Furthermore, the most stable spectra were simulated by optimization of previous ENDOR and EI-EPR results. The optimized EPR parameters resulted in excellent simulations of the experimental stable sorbose spectra and hence provided an improved insight of their spectral compositions.


The female athlete triad. A growing health concern.
The number of female athletes participating at the high school, collegiate, and elite levels has increased nearly 10-fold since the passage of Title IX. President Nixon signed title IX into law in 1972. It required that all schools receiving federal funding provide equal opportunities for men and women. With this large increase in high-level female athletes comes a special set of medical and orthopaedic issues. One of the most important is the female athlete triad. The triad consists of disordered eating, amenorrhea, and premature osteoporosis. Currently, this problem is largely unrecognized. The purpose of this article is to help to educate orthopaedic nurses about this important issue so that we can detect the triad early and help address this growing national health issue.


Reporting of Sample Size Parameters in Randomized Controlled Trials Published in Prosthodontic Journals.
An important consideration in the proper planning of randomized controlled trials (RCTs) is the determination of sample size. A study may fail to answer its research question if the sample size is inadequate, while a large enough sample size may be impractical to implement. The purpose of this study is to describe the reporting of sample size methodology and parameters used in RCTs published in prosthodontic journals. A MEDLINE search for publications categorized as RCTs was conducted for articles in The Journal of Prosthodontics and The Journal of Prosthetic Dentistry published from 2008 to 2017. The Abstract and Methodology sections of RCTs identified were reviewed, and the following data recorded: reporting of method used to calculate sample size and reporting of parameters used for sample size calculation - type I error (α), type II error (β) or power, minimal clinically relevant difference (MCRD), and variability. The search strategy retrieved 96 articles; 42 met inclusion criteria for RCTs and were reviewed. Fifty percent (21) of RCTs reported how sample size was determined, but only 17% (7) of RCTs reported all 4 parameters. Type I error (α) was reported in 90% (38) of RCTs, 38% (16) reported power, while only 26% (11) and 12% (5) reported MCRD and variability, respectively. Methodology and parameters used for sample size determination are inadequately reported in RCTs published in prosthodontic journals.


Accuracy of self-reported birth outcomes relative to birth certificate data in an Internet-based prospective cohort study.
The accuracy of birth outcome data provided by Internet-based cohort study participants has not been well studied. We compared self-reported data on birth characteristics in Pregnancy Study Online (PRESTO), an Internet-based prospective cohort study of North American pregnancy planners, with birth certificate data. At enrolment, participants were aged 21-45 years, attempting conception, and not using fertility treatment. Women completed online questionnaires during preconception, early and late pregnancy, and postpartum. We requested birth certificate data during 2014-2019 from seven health departments in states with the most participants. After restricting to singleton births, we assessed specificity, sensitivity, and agreement comparing self-reported data from postpartum questionnaires with birth certificate data for gestational age at delivery (GA) and birthweight (grams). Our primary measure of self-reported GA (weeks) was calculated as [280-(due date-birth date)]/7. We used log-binomial regression to assess predictors of agreement. We linked 85% (771/909) of women in selected states. Median age of women was 30 years (range: 21-42), 84% had ≥ 16 years of education, nearly 96% were married, 12% had household incomes <$50 000, 32% were parous, and 85% identified as non-Hispanic White. Median recall interval was 6 months. Among those with self-reported data, 89% reported the same GA as the birth certificate and 98% reported GA within 1 week of the birth certificate. Self-report of preterm birth (GA < 37 weeks) agreed with information from birth certificates for 100% of women; sensitivity was 100%, and specificity was 99%. Self-reported low birthweight (<2500 grams) agreed with birth certificates for 93% of women; sensitivity and specificity were 93% and ≥99%, respectively. Predictors of poorer agreement included higher parity and longer pregnancy attempt time for GA, and lower education and longer recall interval for birthweight. Self-reported data on GA and birthweight from an Internet-based cohort showed high accuracy compared with birth certificates.


Lipidomic Analysis Reveals Differences in the Extent of Remyelination in the Brain and Spinal Cord.
During demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form. Although myelin comprises over 70% lipids, relatively little is known about how the CNS lipidome changes during demyelination and remyelination. In this study, we obtained a longitudinal lipidomic profile of the brain, spinal cord, and serum using a genetic mouse model of demyelination, known as Plp1-iCKO-Myrf. The mass spectrometry data is available at the Metabolomics Workbench, where it has been assigned Study ID ST002958. This model has distinct phases of demyelination and remyelination over the course of 24 weeks, in which loss of motor function peaks during demyelination. Using principal component analysis (PCA) and volcano plots, we have demonstrated that the brain and spinal cord have different remyelination capabilities and that this is reflected in different lipidomic profiles over time. We observed that plasmalogens (ether-linked phosphatidylserine and ether-linked phosphatidylcholine) were elevated specifically during the early stages of active demyelination. In addition, we identified lipids in the brain that were altered when mice were treated with a remyelinating drug, which may be CNS biomarkers of remyelination. The results of this study provide new insights into how the lipidome changes in response to demyelination, which will enable future studies to elucidate mechanisms of lipid regulation during demyelination and remyelination.


Perspectives on Strengthening Cancer Research and Control in Latin America Through Partnerships and Diplomacy: Experience of the National Cancer Institute's Center for Global Health.
According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region.


AIDS dementia complex and HIV-1 infection: a view from the clinic.
The AIDS dementia complex (ADC) is a clinical syndrome which characteristically presents as a "subcortical dementia" with cognitive, motor and behavioral changes. While the pathogenesis remains puzzling in a number of critical aspects, ADC likely relates in a fundamental way to HIV-1, itself, rather than to a secondary, opportunistic condition. This review focuses on some of the clinical information which bears on the pathogenesis of this syndrome and its relation to HIV-1 infection. This information derives from studies of the clinical character of ADC, its epidemiology and natural history, cerebrospinal fluid analysis, neuroimaging results, clinical correlates of pathological findings and its response to antiviral therapy.


G-Protein-Coupled Receptor (GPCR) Signaling in the Carotid Body: Roles in Hypoxia and Cardiovascular and Respiratory Disease.
The carotid body (CB) is an important organ located at the carotid bifurcation that constantly monitors the blood supplying the brain. During hypoxia, the CB immediately triggers an alarm in the form of nerve impulses sent to the brain. This activates protective reflexes including hyperventilation, tachycardia and vasoconstriction, to ensure blood and oxygen delivery to the brain and vital organs. However, in certain conditions, including obstructive sleep apnea, heart failure and essential/spontaneous hypertension, the CB becomes hyperactive, promoting neurogenic hypertension and arrhythmia. G-protein-coupled receptors (GPCRs) are very highly expressed in the CB and have key roles in mediating baseline CB activity and hypoxic sensitivity. Here, we provide a brief overview of the numerous GPCRs that are expressed in the CB, their mechanism of action and downstream effects. Furthermore, we will address how these GPCRs and signaling pathways may contribute to CB hyperactivity and cardiovascular and respiratory disease. GPCRs are a major target for drug discovery development. This information highlights specific GPCRs that could be targeted by novel or existing drugs to enable more personalized treatment of CB-mediated cardiovascular and respiratory disease.


Enhancing recruitment of healthy African American volunteers in a city with a small African American community: results from a dietary supplement crossover trial.
To describe strategies for enhancing recruitment of African Americans to a longterm intervention study requiring frequent blood draws and follow-up visits, in a city with relatively few African Americans. The intervention study was a 14-month, double-blind, crossover study evaluating the effects of three oral folic acid doses on blood homocysteine levels. The goal was to have 40 African Americans complete the study, in addition to 160 participants from other races and ethnicities. Of 707 healthy, adult men and women recruited, 57 were African Americans. Recruitment advice was sought from African American community leaders interested in health research and the advice can be attributable to the success of recruitment. As suggested by the community leaders, our female African American project manager made oral presentations to select community groups. Word-of-mouth support from community leaders and study participants helped recruitment. Although the adult Seattle population is 7.4% African American, the group completing the study comprised 15% African Americans. Retention in the dietary intervention was 74% (31 out of 42) among African Americans, 81% (158 out of 196) among non-African Americans--a statistically non-significant difference. Advice from African American community leaders about targeting appropriate civic/professional groups, churches, and community organizations can lead to effective recruitment of African Americans. Advice should be sought before beginning recruitment and endorsement for the study should be obtained. Effective retention of African American participants is possible for intervention studies requiring multiple blood draws and follow-up visits.


Elevated AA/EPA Ratio Represents an Inflammatory Biomarker in Tumor Tissue of Metastatic Colorectal Cancer Patients.
Chronic inflammation increases the risk of developing certain types of cancer, such as colorectal cancer (CRC). The oxidative metabolism of polyunsaturated fatty acids (PUFAs) has a strong effect on colonic tumorigenesis and the levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) can contribute to the development of an inflammatory microenvironment. Aim of this study was to evaluate the possible differences in the AA/EPA ratio tissue levels between CRC patients with and without synchronous metastases. Moreover, the expression of the most important inflammatory enzymes and mediators, linked with the AA/EPA ratio, have been also assessed. Sixty-eight patients with CRC were enrolled in the study, of which 33 patients with synchronous metastasis. Fatty acid profile analysis in tissue samples was done to examine the levels of AA and EPA. High levels of the AA/EPA ratio were detected in tumor tissue of patients with metastatic CRC. Moreover, an increase of expression of the main enzymes and mediators involved in inflammation was also detected in the same samples. The lipidomic approach of inflammation allows to evaluate lipid homeostasis changes that occur in cancer and in its metastatic process, in order to identify new biomarkers to be introduced into clinical practice.


Inhibition of liver regeneration by chronic alcohol administration.
Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% hepatectomy in 240 rats receiving a nutritionally adequate diet containing 36% of their calories as ethanol for three weeks and their pair-fed controls receiving a liquid diet where ethanol is isocalorically replace with carbohydrates. Criteria of liver regeneration were: incorporation of 3H-thymidine in hepatocyte DNA (cpm/10 microgram DNA) and number of hepatocyte labelled nuclei on autoradiography per 100 high power fields. Controls displayed the usual response with peak activity of liver regeneration at 24 hours. Consumption of ethanol was associated with a statistically significant reduction of liver regeneration by both criteria for up to 72 hours after a 70% hepatectomy and delayed the peak of regenerative activity by 24 hours. This inhibiting effect was not related to the presence of alcohol in blood nor to hepatic microsomal enzyme induction by ethanol nor to widespread necrosis of hepatocytes. This effect was reversible after one week of abstinence. This impairment of liver cell renewal by ethanol may be of major significance in the severity and outcome of alcohol-related liver injury.


Isobavachin, a main bioavailable compound in Psoralea corylifolia, alleviates lipopolysaccharide-induced inflammatory responses in macrophages and zebrafish by suppressing the MAPK and NF-κB signaling pathways.
Psoralea corylifolia L. (PC) is widely used in traditional medicines to treat inflammatory and infectious diseases. Isobavachin (IBC) is a bioavailable prenylated flavonoid derived from PC that has various biological properties. However, little information is available on its anti-inflammatory effects and mechanisms of action. In this study, we aimed to determine the anti-inflammatory effects of IBC in vitro and in vivo by conducting a mechanistic study using murine macrophages. We evaluated the modulatory effects of IBC on the production of pro-inflammatory cytokines and mediators in murine macrophages. In addition, we examined whether IBC inhibits lipopolysaccharide (LPS)-induced inflammatory responses in a zebrafish model. Alterations in inflammatory response-associated genes and proteins were determined using quantitative reverse transcriptional polymerase chain reaction (RT-qPCR) and Western blotting analysis. IBC markedly reduced the overproduction of inflammatory mediators, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear translocation of nuclear factor-kappa B (NF-κB) in macrophages induced by lipopolysaccharides (LPS). In addition, excessive NO, ROS, and neutrophil level induced by LPS, were suppressed by IBC treatment in a zebrafish inflammation model. Collectively, bioavailable IBC inhibited on the inflammatory responses by LPS via MAPK and NF-κB signaling pathways in vitro and in vivo, suggesting that it may be a potential modulatory agent against inflammatory disorders.


"Cannon balls or pus balls" in pap smears: a case report.
A 50-year old female presented with the chief complaint of a discharge per vaginum, which was there for the past 15 days. A routine PAP smear was received in the Department of Pathology, Government Medical College, Patiala, India. After its fixation and staining, it was examined under the microscope. It showed the Trichomonas vaginalis infection, with the neutrophils forming cannon balls at places. Neutrophils in the PAP smear are a nonspecific finding, particularly if they are low in numbers or if they are seen in the premenstrual and the menstrual phases. The neutrophils which are adherent to the squamous cells are called "cannon balls" or "pus balls", which are common in the Chlamydia infection. This case is being presented because of the presence of these rare morphological structures i.e. "cannon balls" or "pus balls".


Bistability of cell-matrix adhesions resulting from nonlinear receptor-ligand dynamics.
Bistability is a major mechanism for cellular decision making and usually results from positive feedback in biochemical control systems. Here we show theoretically that bistability between unbound and bound states of adhesion clusters results from positive feedback mediated by structural rather than biochemical processes, namely by receptor-ligand dissociation and association dynamics that depend nonlinearly on mechanical force and receptor-ligand separation. For small cell-matrix adhesions, we find rapid switching between unbound and bound states, which in the initial stages of adhesion allows the cell to explore its environment through many transient adhesions.


Occupational exposure to wood dust and risk of lung cancer: the ICARE study.
In a previous analysis of data from a French population-based case-control study (the Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE) study), 'having ever worked' in wood-related occupations was associated with excess lung cancer risk after adjusting for smoking but not for occupational factors. The present study aimed to investigate the relationship between lung cancer risk and wood dust exposure after adjusting for occupational exposures. Data were obtained from 2276 cases and 2780 controls on smoking habits and lifelong occupational history, using a standardised questionnaire with a job-specific questionnaire for wood dust exposure. Logistic regression models were used to calculate ORs and 95% CIs adjusted for age, area of residence, tobacco smoking, the number of job periods and exposure to silica, asbestos and diesel motor exhaust (DME). No significant association was found between lung cancer and wood dust exposure after adjustment for smoking, asbestos, silica and DME exposures. The risk of lung cancer was slightly increased among those who were exposed to wood dust more than 10 years, and had over 40 years since the first exposure. Our findings do not provide a strong support to the hypothesis that wood dust exposure is a risk factor for lung cancer. This study showed the importance of taking into account smoking and occupational coexposures in studies on lung cancer and wood dust exposure. Further studies evaluating the level and frequency of exposure during various tasks in woodwork are needed.


Interspecific recombination between two ruminant alphaherpesviruses, bovine herpesviruses 1 and 5.
Homologous recombination between different species of alphaherpesviruses has been described between herpes simplex viruses 1 and 2 but has not yet been observed between other alphaherpesviruses. In the present study we chose to assess to what extent in vitro recombination can occur between members of a well-defined group of closely related viruses such as ruminant alphaherpesviruses. At 24 h after infection of epithelial bovine kidney cells with a double-deleted mutant of bovine herpesvirus 1 (BoHV-1) (containing green fluorescent protein and red fluorescent protein genes) and different ruminant alphaherpesviruses, four types of progeny viruses were detected and distinguished according to their phenotype. Frequent recombination events between identical or different strains of BoHV-1 were observed (up to 30%), whereas only two BoHV-1/BoHV-5 recombinants were identified, and no recombinants between BoHV-1 and less closely related caprine and cervine herpesviruses were detected. Restriction analysis of the genomes of the two BoHV-1/BoHV-5 recombinants showed different genetic backgrounds. One possessed a restriction pattern close to BoHV-1, whereas the other one was close to BoHV-5. This exhaustive analysis of each combination of coinfection in a unique situation of five closely related alphaherpesviruses revealed the importance of a high degree of genetic relatedness and similar parental virus growth kinetics for successful interspecific recombination.


Objective measures of physical activity, white matter integrity and cognitive status in adults over age 80.
The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age = 87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean ± SD/day: 1766 ± 1345 steps, 202 ± 311 kcal, 211 ± 39 min, 1.8 ± 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.


From prevention to treatment. Issues for school-aged children of alcoholics.
Empirical and anecdotal evidence concerning the variables that mediate and moderate the relationship between parental alcoholism and child vulnerability has been used as the basis for a growing number of prevention and treatment programs for school-aged children of alcoholics. Common intervention foci include information on alcohol and alcoholism, the dynamics of alcoholic families, common social and emotional reactions (e.g., embarrassment, loneliness, guilt, depression, anger), skill building (e.g., problem solving, communication, expression of feelings), coping strategies for living in an alcoholic home, and general social and emotional support. The primary modality is a small group, which is usually time-limited. Groups are conducted in schools, community agencies, and mental health or drug treatment centers. Research on the effectiveness of several of these programs has yielded positive results with respect to a variety of psychosocial measures, although most studies share some common methodological shortcomings (e.g., lack of appropriate control groups, lack of longitudinal assessments of effects). More rigorous evaluation, as well as continued and expanded program development and outreach, is recommended.


Circ-CARD6 inhibits oxidative stress-induced apoptosis and autophagy in ARPE-19 cells via the miR-29b-3p/PRDX6/PI3K/Akt axis.
Oxidative stress-induced damage and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD) and hereditary retinopathy diseases (HRDs). This study aimed to elucidate the roles and mechanisms of circ-CARD6 and miR-29b-3p in oxidative stress-induced RPE and provide new ideas for the diagnosis and treatment of retinopathy disease (RD). A model of oxidative stress-induced RPE (ARPE-19) was established, and the level of malondialdehyde (MDA) and concentration of reactive oxygen species (ROS) were detected by a DCFH-DA fluorescent probe and MDA kit. The cell viability was measured by a CCK-8 assay. The expression of PRDX6/PI3K/Akt axis genes and proteins related to apoptosis and autophagy were determined by RT‒qPCR and Western blot analyses. The dual-luciferase reporter system confirmed the targeting relationship between miR-29b-3p and circ-CARD6 and between miR-29b-3p and PRDX6. In H2O2-treated ARPE-19 cells, the expression of circ-CARD6 and PRDX6 was decreased, while the expression of miR-29b-3p was increased. The overexpression of circ-CARD6 inhibits oxidative stress-induced increases in ROS, apoptosis and autophagy in ARPE-19 cells. circ-CARD6 targets miR-29b-3p, miR-29b-3p targets PRDX6, and circ-CARD6 regulates PRDX6 via miR-29b-3p. Further studies showed that circ-CARD6 acts as a competitive endogenous RNA of miR-29b-3p to affect the expression of PRDX6, thereby inhibiting autophagy and apoptosis in ARPE-19 cells. circ-CARD6 can inhibit oxidative stress and apoptosis by regulating the miR-29b-3p/PRDX6/PI3K/Akt axis.


On-line cardiac mapping: an analog approach using video and multiplexing techniques.
A video and multiplexing system is described that provides a source of display in real-time, slow-motion, and stop-frame modes of ventricular activation. The displayed image, consisting of a matrix of 112 dots, is arranged to represent a polar projection of the ventricles. The dots brighten at the time of local cardiac activation, which is sensed by an electrode array monitoring the myocardium. Experiments in in situ canine hearts have provided detailed depictions at 8.3-ms intervals of the ventricular activation sequence during sinus and ventricularly paced rhythm. The origin of ventricular paced beats can be located with an accuracy of less than 5 mm. Coronary occlusion produces a defect in the displayed image that outlines the ischemic area and demonstrates regions of delayed conduction. This approach to ventricular mapping provides a detailed on-line display of activation with a recording capacity of 1 h. The system offers a practical, inexpensive alternative to computerized methods of investigating ventricular arrhythmias in both the experimental and intraoperative environment.


Social Medicine: Twitter in Healthcare.
Social media enables the public sharing of information. With the recent emphasis on transparency and the open sharing of information between doctors and patients, the intersection of social media and healthcare is of particular interest. Twitter is currently the most popular form of social media used for healthcare communication; here, we examine the use of Twitter in medicine and specifically explore in what capacity using Twitter to share information on treatments and research has the potential to improve care. The sharing of information on Twitter can create a communicative and collaborative atmosphere for patients, physicians, and researchers and even improve quality of care. However, risks involved with using Twitter for healthcare discourse include high rates of misinformation, difficulties in verifying the credibility of sources, overwhelmingly high volumes of information available on Twitter, concerns about professionalism, and the opportunity cost of using physician time. Ultimately, the use of Twitter in healthcare can allow patients, healthcare professionals, and researchers to be more informed, but specific guidelines for appropriate use are necessary.


Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma.
Human genes NY-ESO-1, MAGE-1 and MAGE-3 code for antigens which are expressed in malignancies of various histological types but not in normal tissues except testis. These antigens might therefore represent potential targets for specific immunotherapy. We studied the expression of genes NY-ESO-1, MAGE-1 and MAGE-3 in 98 neuroblastoma tumors by reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1 was expressed in 66%, NY-ESO-1 in 36% and MAGE-3 in 33% of the tumors. NY-ESO-1 gene expression was associated with age older than one year (p = 0.017), more differentiated tumor histology (p = 0.044), elevated urinary vanillylmandelic acid (VMA, p = 0.018) and normal serum ferritin levels (p = 0.023). MAGE-1 expression correlated significantly with normal serum ferritin levels (p = 0.009) and absence of MycN amplification (p = 0.007) while MAGE-3 expression was associated with absence of metastasis (p = 0.027). We conclude that approximately 70% of the neuroblastoma tumors express at least one of the genes coding for NY-ESO-1, MAGE-1 or -3, respectively.


Reversible osmotic blood-brain barrier disruption in humans: implications for the chemotherapy of malignant brain tumors.
The blood-brain barrier seems to be an important factor in drug access to malignant brain tumors. Successful experimental reversible disruption of the blood-brain barrier in animals provided the basis for a clinical evaluation of osmotic disruption in five patients with primary and metastatic malignant brain tumors. Good to excellent blood-brain barrier disruption was achieved in four patients with a single nontransient complication, a superficial wound infection at the burr hole site in the first patient. Reversible, transient osmotic barrier disruption was achieved 15 times in five patients without additional toxicity. Computed tomography and radionuclide brain imaging were shown to be useful noninvasive monitors of the adequacy and extent of barrier disruption. These studies also provide further evidence that the barrier is at least partially intact in human tumors because in one patient a metastsis was seen only after barrier disruption.


Patient care outcomes: a league of their own.
Managed care has ushered in a whole new way of providing patient care. This era of health care delivery is heavily focused on the attainment of defined outcomes. While many types of outcome indicators exist, the types gaining in importance are related to patient care. This article examines the concept of patient outcomes and relates them to an actual example of one condition and related medical and nursing diagnoses. The importance of measurements in the overall care delivery process and the documentation of discharge outcomes are also discussed. A methodology for outcomes measurement determination is featured.


Limited airway effects in mild asthmatics after exposure to air pollution in a road tunnel.
Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum. Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2 h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected. The median PM(2.5) and PM(10) levels during the exposure occasions in the road tunnel were 80 (range 41-93) μg/m(3) and 183 (72-213) μg/m(3) respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1 s (FEV(1)) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure. We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2 h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants.


Azimuthal anisotropy of π⁰ production in Au+Au collisions at sqrt((s)NN)=200 GeV: path-length dependence of jet quenching and the role of initial geometry.
We have measured the azimuthal anisotropy of π⁰ production for 1<p(T)<18 GeV/c for Au+Au collisions at sqrt((s)NN)=200 GeV. The observed anisotropy shows a gradual decrease for 3≲p(T)≲7-10 GeV/c, but remains positive beyond 10 GeV/c. The magnitude of this anisotropy is underpredicted, up to at least ∼10 GeV/c, by current perturbative QCD (PQCD) energy-loss model calculations. An estimate of the increase in anisotropy expected from initial-geometry modification due to gluon saturation effects and fluctuations is insufficient to account for this discrepancy. Calculations that implement a path-length dependence steeper than what is implied by current PQCD energy-loss models show reasonable agreement with the data.


Longitudinal Analysis of Disease Burden in Refractory and Nonrefractory Generalized Myasthenia Gravis in the United States.
To compare temporal trends in clinical and health care resource utilization (HRU) outcomes in people with refractory and nonrefractory generalized myasthenia gravis (gMG). A retrospective analysis of data from adults with gMG in the Myasthenia Gravis Foundation of America Patient Registry. gMG status (ever-refractory or always nonrefractory) and clinical (Myasthenia Gravis-Activities of Daily Living [MG-ADL] scores, exacerbations) and HRU outcomes were determined from questionnaires self-completed 6-monthly for up to 4 years. The probability of each outcome was compared for the 2 groups over time. The mean MG-ADL score and the probability of experiencing each outcome were significantly greater in the ever-refractory versus nonrefractory groups during each year of follow-up. Between-group differences in time trends were statistically significant for intensive care and feeding-tube use. People who have ever had refractory gMG may have worse functional status, more exacerbations, and higher HRU than people with consistently nonrefractory disease.


Trends in access block 2011 to 2013: the Redcliffe National Emergency Access Target experience.
To evaluate the impact of the introduction of National Emergency Access Target (NEAT) on access block and long-stay patients in Redcliffe Hospital ED, and to evaluate the possibility of forward compliance with the 2014 and 2015 NEAT thresholds. Redcliffe hospital is a major urban district hospital in Brisbane with more than 55,000 adult and paediatric patients per annum. We evaluated aggregate Emergency Department Information System data for the years 2011, 2012 and 2013 to correlate presentations, NEAT compliance, access block and the number of long-stay patients in our department. There has been a significant reduction in both access block and our number of long-stay patients corresponding with improvements in NEAT compliance. Our forward analysis suggests that without substantial improvements in the NEAT for admitted patients, compliance with 2014 and 2015 thresholds is unlikely to be achievable. NEAT has been a driver of significant improvements in access block at our institution. We see significant issues with raising the NEAT threshold to the proposed 90% in 2015, and support recent calls for re-evaluation and modification of the target.


I.2. Mechanics of materials.
Mechanics of materials is the science of forces applied on a body and response of the body in terms of deformation. Different type of loadings on bodies with different geometries or made of different material give rise to different deformations. Last but not the least, this science allows to predict the failure of a body under certain loading condition hence makes it possible to optimize the design for that particular condition.


Interference in bacteriophage growth by a resident plasmid lambda dv. II. Role of the promoter-operator.
The susceptibilities to interference by lambdadv of a set of lambda phages differing in the genetic structure of their right promoter-operator (pRoR) were compared. For this purpose mutant phages were added to lambdadv-carrier cells at various multiplicities, and abilities to escape from interference, as represented by percentages of infected complexes to produce progeny phages, were compared. It was observed that phages that carry strongly constitutive pRoR were able to escape from interference at a low multiplicity of infection, whereas phages with weakly constitutive pRoR were able to escape only when a large number of these genomes entered into a cell. Several mutations in the pRoR were arranged in order of their constitutivity, or ability to escape from interference. Next, the abilities of a set of lambdadv plasmids differing in their pRoR to cause interference were compared. The results showed that interference increased with increase in constitutivity of the pRoR in the plasmid genome. These observations are thought to reflect a regulatory system of the plasmid replicon, and a possible mechanism for the system is discussed.


First Principles Calculation of Protein-Protein Dimer Affinities of ALS-Associated SOD1 Mutants.
Cu,Zn superoxide dismutase (SOD1) is a 32 kDa homodimer that converts toxic oxygen radicals in neurons to less harmful species. The dimerization of SOD1 is essential to the stability of the protein. Monomerization increases the likelihood of SOD1 misfolding into conformations associated with aggregation, cellular toxicity, and neuronal death in familial amyotrophic lateral sclerosis (fALS). The ubiquity of disease-associated mutations throughout the primary sequence of SOD1 suggests an important role of physicochemical processes, including monomerization of SOD1, in the pathology of the disease. Herein, we use a first-principles statistical mechanics method to systematically calculate the free energy of dimer binding for SOD1 using molecular dynamics, which involves sequentially computing conformational, orientational, and separation distance contributions to the binding free energy. We consider the effects of two ALS-associated mutations in SOD1 protein on dimer stability, A4V and D101N, as well as the role of metal binding and disulfide bond formation. We find that the penalty for dimer formation arising from the conformational entropy of disordered loops in SOD1 is significantly larger than that for other protein-protein interactions previously considered. In the case of the disulfide-reduced protein, this leads to a bound complex whose formation is energetically disfavored. Somewhat surprisingly, the loop free energy penalty upon dimerization is still significant for the holoprotein, despite the increased structural order induced by the bound metal cations. This resulted in a surprisingly modest increase in dimer binding free energy of only about 1.5 kcal/mol upon metalation of the protein, suggesting that the most significant stabilizing effects of metalation are on folding stability rather than dimer binding stability. The mutant A4V has an unstable dimer due to weakened monomer-monomer interactions, which are manifested in the calculation by a separation free energy surface with a lower barrier. The mutant D101N has a stable dimer partially due to an unusually rigid β-barrel in the free monomer. D101N also exhibits anticooperativity in loop folding upon dimerization. These computational calculations are, to our knowledge, the most quantitatively accurate calculations of dimer binding stability in SOD1 to date.


Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss.
Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca(2+) oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12(fl/fl) cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss.


Use of Psychotropic Drugs during the COVID-19 pandemic in Minas Gerais, Brazil.
To describe the profile of dispensation of mental health drugs by analyzing trends in use before and during the COVID-19 pandemic within the Unified Health System (Sistema Único de Saúde [SUS]). Pharmacoepidemiological study based on the retrospective analysis of records regarding the dispensation of psychotropic medicines in the SUS database in the state of Minas Gerais between 2018 and 2021, considering the periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). A database with the records of dispensation of municipalities was created, and the consistency of releases was verified using the Analysis of Variance (ANOVA) test. Medicine consumption was measured in a defined daily dose (DDD) per 1,000 inhabitants/day for SUS, and the difference between periods was evaluated using Student's t-test. During the COVID-19 pandemic, there was an increase in the consumption of psychotropic drugs in SUS-MG. The most consumed medicines were fluoxetine hydrochloride, diazepam and phenobarbital sodium (DDD=5.89; 3.42; 2.49) in the Basic Pharmaceutical Services Component(CBAF), and olanzapine, risperidone and quetiapine hemifumarate (DDD=0.80; 0.47; 0.38) in the Specialized Pharmaceutical Services Component (CEAF). The highest percentage increase in consumption was attributed to clonazepam (75.37%) and lithium carbonate (35.35%), in CBAF, and levetiracetam (3,000.00%) and memantine hydrochloride (340.0%) in CEAF. The change in the psychotropic drug dispensation profile during the COVID-19 pandemic highlights the need to produce more studies to complete, confirm or rule out this profile and monitor the use of psychotropic drugs by the population in the post-pandemic context.


Cancer Survivors' Social Context in the Return to Work Process: Narrative Accounts of Social Support and Social Comparison Information.
Purpose Returning to work is a process that is intertwined with the social aspects of one's life, which can influence the way in which that person manages their return to work and also determines the support available to them. This study aimed to explore cancer patients' perceptions of the role of their social context in relation to returning to work following treatment. Methods Twenty-three patients who had received a diagnosis of either urological, breast, gynaecological, or bowel cancer participated in semi-structured interviews examining general perceptions of cancer, work values and perceptions of the potential impact of their cancer diagnosis and treatment on work. Interviews were analysed using the iterative process of Framework Analysis. Results Two superordinate themes emerged as influential in the return to work process: Social support as a facilitator of return to work (e.g. co-workers' support and support outside of the workplace) and Social comparison as an appraisal of readiness to return to work (e.g. comparisons with other cancer patients, colleagues, and employees in other organisations or professions). Conclusions Two functions of the social context of returning to work after cancer were apparent in the participants' narrative: the importance of social support as a facilitator of returning to work and the utilisation of social comparison information in order to appraise one's readiness to return to work. The role of social context in returning to work has largely been absent from the research literature to date. The findings of this study suggest that social support and social comparison mechanisms may have a significant impact on an individual's successful return to the workplace.


Roseburia spp.: a marker of health?
The genus Roseburia consists of obligate Gram-positive anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, especially butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is associated with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.


Changing response rates from Māori and non-Māori in national sleep health surveys.
To understand declining response rates in New Zealand sleep health surveys by examining contextual changes and specific aspects of the questionnaires and research design that may have contributed. From 1999-2008, four population surveys were undertaken, seeking to recruit equal numbers of Māori and non-Māori, consistent with the Kaupapa Māori principle of equal explanatory power; using the electoral roll as a sampling frame and including extensive follow-up. In successive surveys, there were fewer respondents in all age groups. Response rates from Māori were lower in all surveys and the percentage decline was greater than for non-Māori. Between 1999 and 2008, the response rates from the initial mail-out decreased by 50% and the proportion of the sample that were uncontactable increased by 50%. Identified societal trends included decreased currency of electoral roll address information, declining use of listed landline telephone numbers, and possibly declining willingness to participate from increasing respondent burden. Contributing study design features may have included changes in Māori leadership, increasing complexity of questions and saliency of the research topic to potential participants. The declining response rate in sleep population surveys is likely to be due to a number of factors. The pros and cons of using the electoral roll as a sampling frame in mail surveys should be carefully considered.


Influence of osmotic pressure on adhesion of lipid vesicles to solid supports.
The adhesion of lipid vesicles to solid supports represents an important step in the molecular self-assembly of model membrane platforms. A wide range of experimental parameters are involved in controlling this process, including substrate material and topology, lipid composition, vesicle size, solution pH, ionic strength, and osmotic pressure. At present, it is not well understood how the magnitude and direction of the osmotic pressure exerted on a vesicle influence the corresponding adsorption kinetics. In this work, using quartz crystal microbalance with dissipation (QCM-D) monitoring, we have experimentally studied the role of osmotic pressure in the adsorption of zwitterionic vesicles onto silicon oxide. The osmotic pressure was induced by changing the ionic strength of the solvent across an appreciably wider range (from 25 to 1000 mM NaCl outside of the vesicle, and 125 mM NaCl inside of the vesicle, unless otherwise noted) compared to that used in earlier works. Our key finding is demonstration that, by changing osmotic pressure, all three generic types of the kinetics of vesicle adsorption and rupture can be observed in one system, including (i) adsorption of intact vesicles, (ii) adsorption and rupture after reaching a critical vesicle coverage, and (iii) rupture just after adsorption. Furthermore, theoretical analysis of pressure-induced deformation of adsorbed vesicles and a DLVO-type analysis of the vesicle-substrate interaction qualitatively support our observations. Taken together, the findings in this work demonstrate that osmotic pressure can either promote or impede the rupture of adsorbed vesicles on silicon oxide, and offer experimental evidence to support adhesion energy-based models that describe the adsorption and spontaneous rupture of vesicles on solid supports.


Immunoregulatory mechanisms of the eye.
Immune-privileged sites, such as the the internal compartments of the eye, and perhaps the brain, are physiological adaptations that act to modify systemic immune responses such that effector mechanisms that invoke locally destructive inflammation are suppressed. In the case of the eye, the parenchymal cells of the iris and ciliary body create an intraocular microenvironment that alters both the induction and expression of immunity to antigens placed within the eye. The immunosuppressive properties of the intraocular microenvironment are mediated by cytokines, especially transforming growth factor-beta (TGF beta). This cytokine has been demonstrated to endow intraocular antigen-presenting cells with the capacity to induce an atypical or deviant form of immunity to intraocular antigens which is selectively deficient in T cells that mediate delayed hypersensitivity. Moreover, TGF beta, along with other intraocular factors, can impair the intraocular expression of pre-existing cell-mediated immunity by inhibiting antigen-driven activation of primed T cells. The strategies employed by the eye to engender specialized immune responses appropriate to its physiological functions are discussed in terms of other privileged sites such as the brain.


Characterization of ovarian tissue based on quantitative analysis of photoacoustic microscopy images.
In this paper, human ovarian tissue with malignant and benign features was imaged ex vivo using an optical-resolution photoacoustic microscopy (OR-PAM) system. The feasibility of PAM to differentiate malignant from normal ovarian tissues was explored by comparing the PAM images morphologically. Based on the observed differences between PAM images of normal and malignant ovarian tissues in microvasculature features and distributions, seven features were quantitatively extracted from the PAM images, and a logistic model was used to classify ovaries as normal or malignant. 106 PAM images from 18 ovaries were studied. 57 images were used to train the seven-parameter logistic model, and a specificity of 92.1% and a sensitivity of 89.5% were achieved; 49 images were then tested, and a specificity of 81.3% and a sensitivity of 88.2% were achieved. These preliminary results demonstrate the feasibility of our PAM system in mapping microvasculature networks as well as characterizing the ovarian tissue, and could be extremely valuable in assisting surgeons for in vivo evaluation of ovarian tissue during minimally invasive surgery.


Western blot detection of PrP Sc in archived paraffin-embedded brainstem from scrapie-affected sheep.
Scrapie is a naturally occurring fatal neurodegenerative disease of adult sheep and goats, one of a group of mammalian diseases known as transmissible spongiform encephalopathies (TSE) or prion diseases. Immunoassays that identify disease-associated prion protein (PrP Sc) are integral to the diagnosis of scrapie and other prion diseases. Results obtained by either immunohistochemistry (IHC) or Western blot (WB) assay are generally adequate for the definitive diagnosis. Approved or accepted methods for WB diagnosis of TSEs requires the use of fresh or frozen nonfixed tissue samples, whereas formalin-fixed, paraffin-embedded tissue is required for the localization of PrP Sc by IHC. Because disparate processing methods are used for these accepted diagnostic techniques, separate tissue samples are collected from the same animal. Occasions arise in which there is either insufficient quantity of tissue available to complete analysis by both techniques or initial tissue processing is incompatible with one of the assays. Also, results between the assays may differ because of the vagaries of sampling, especially in case material that contains moderate-to-low levels of PrP Sc. The present article describes a method to conduct a WB assay from the same paraffin-embedded brainstem sample used for the IHC diagnosis of experimentally induced sheep scrapie.


Development and utilization of 8-azidopurine nucleotide photoaffinity probes.
The 8-azidopurine analogs of adenosine and guanine nucleotides have proved to be very useful probes for nucleotide-binding sites. In most systems they have proved to be effective mimics of the natural compounds with 1) both 8-azidoadenosine-3',5'-monophosphate and 8-azidoguanosine-3',5'-monophosphate activating their respective kinases, 2) 8-azidoguanosine-5'-triphosphate effecting tubulin polymerization and activation of adenylate cyclase, and 3) 8-azidoadenosine-5'-triphosphate appearing to be a substrate for a large number of ATPases and several kinases. As photoprobes they have been used to 1) isolate and study active site peptides; 2) determine the membrane sidedness and cellular location of binding sites; 3) detect the availability of various nucleotide-binding sites as cells progress through development, maturation, infectious stages, etc.; 4) study membrane-soluble partitioning of binding sites relative to nucleotide regulation of a biochemical process; 5) detect nucleotide-binding sites exposed by small molecules such as Ca2+ and calmodulin; and 6) detect potential catalytic and regulatory subunits of protein kinases found in preparations that actively phosphorylate endogenous substrates. The difference between the gamma-32P-labeled 8-azidopurine nucleotide triphosphate and the alpha-32P-labeled species has been used to study the in situ hydrolysis of the nucleotides on specific protein receptors and determine the fate of the produced nucleotide diphosphate. Such factors are important in studying the molecular dynamics of such systems as tubulin polymerization, G-actin to F-actin conversions, and GTP activation of adenylate cyclase. A review of techniques used and data obtained with these probes is presented.


Analysis on controlling factors for the synthesis of carbon nanotubes and nano-onions in counterflow diffusion flames.
It is important to identify the dominant factors for governing the growth of carbon nanotubes (CNTs) and nano-onions (CNOs). A diffusion flame of a gas mixture of methane-ethylene was used as the carbon and heat sources and Ni as the catalyst for the synthesis of CNTs and CNOs. The effects of CH4/C2H4 ratio in the fuel side and oxygen concentration in the oxidizer side for counterflow diffusion flames were investigated. It was found that oxygen concentration can greatly affect the morphologies of synthesized products with a threshold of 30% distinguishing the formation of CNO or CNT. CNOs were fabricated at higher oxygen concentrations (30%, 40%, 50%), and CNTs were synthesized only at lower oxygen concentrations (21%, 30%). The fuel composition has minor effects on the morphologies except for the threshold value of oxygen concentration (30%). More carbon sources are required for the synthesis of CNOs than for CNTs, but the temperature requirements are similar (1140-1160 K for CNTs, 1070-1160 K for CNOs). The nanostructures were synthesized as long as the fuel concentration is sufficiently high regardless of the oxygen concentration. Higher fabrication tendency was found for ethylene as fuel to form nanostructures than for methane.


Prevalence of Polypharmacy and Risks of Potentially Inappropriate Medication Use in the Older Population in a Developing Country: A Systematic Review and Meta-Analysis.
Polypharmacy and potentially inappropriate medication (PIM) use in older populations (65+ years) have not yet been investigated by meta-analyses in developing countries. This systematic literature review and meta-analysis aimed to investigate the prevalence of polypharmacy and PIM use and major risk factors associated with PIM prescribing in older adults in Ethiopia. We searched PubMed/MEDLINE, Scopus, Embase, and Google Scholar databases to identify relevant studies published between January 1990 and October 2020. Observational studies reporting the prevalence and association of risk factors with polypharmacy and PIM use in the older population were meta-analyzed. A multilevel meta-analysis was conducted to pool the prevalence estimates, and the risk of PIM use was reported as a relative risk (RR) with a 95% confidence interval (CI). We identified by systematic literature review 404 articles. Of those, 8 studies fulfilled inclusion criteria, comprising a total sample of 2,608 participants. The overall prevalence of polypharmacy and PIM use pooled by meta-analysis in the Ethiopian older population was 33 and 37%, respectively. The risk factors of PIM use were analyzed in the meta-analysis (particularly polymorbidity, polypharmacy, gender, and older age), and only older age of 65+ (RR: 1.71, 95% CI: 1.16-2.51) was significantly associated with PIM use. This first meta-analysis from a developing country revealed a high prevalence of polypharmacy and PIM use in the Ethiopian older population. There was no awareness about the risk of PIMs in patients with polypharmacy and polymorbidity, and older age significantly predicted PIM use. Interventions ensuring rational geriatric pharmacotherapy are essential in developing countries in order to reduce the expected burden of PIM-related geriatric morbidity, higher costs, and mortality.


Defective neutrophil migration in granuloma annulare, necrobiosis lipoidica, and sarcoidosis.
The neutrophil mobility in patients with granuloma annulare, necrobiosis lipoidica, and sarcoidosis was tested using both in vivo and in vitro techniques. Use of a skin window chamber for measurement of chemotaxis in vivo demonstrated defective neutrophil migration in each group. This contrasted with the finding that, in vitro, chemotaxis toward casein and endotoxin-activated sera was normal. The importance of this dissociation is discussed. Abnormal neutrophil accumulation at sites of inflammation may be of importance in the pathogenesis of these granulomatous disorders.


Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through Nrf2/ROS pathway.
Seven cardenolides isolated from the ethanol extract of the stems of Calotropis gigantea were evaluated in vitro against human cancer cells and the structure-activity relationships were discussed. The results demonstrated that a compound, named CGN (coroglaucigenin), had better anti-proliferative activity with the IC50 value less than 6 μM among these compounds. Further, we found that CGN displayed much lower cytotoxicity to normal lung epithelial cells (BEAS-2B) than cancer cells (A549). Especially, our results demonstrated that treatment with CGN (1 μM) combined with X-ray irradiation induced higher radiosensitivity in human lung cancer cells (A549, NCI-H460, NCI-H446) but not in BEAS-2B. The expression levels of nuclear transcription factor Nrf2 and Nrf2-driven antioxidant molecule NQO-1 reduced in A549 cells after combined treatment compared to the radiation only. However, CGN had no toxicity and the levels of antioxidant molecules expression were higher in BEAS-2B cells when given the similar treatment as A549 cells. These results suggest that CGN is a very promising potential sensitizer for cancer radiotherapy, which not only inhibits the proliferation of cancer cells but also enhances the radiosensitivity of cancer cells through suppressing the expression of antioxidant molecules while there is no influence for normal cells.


Caffeic Acid Modulates miR-636 Expression in Diabetic Nephropathy Rats.
We investigated the action of caffeic acid in regulating miR-636 expression level in kidney of streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were orally treated with caffeic acid at 40 mg/kg/day for 8 weeks. At the end of the treatment, body and kidney weight and blood glucose levels were determined, blood, urine, and kidneys were collected for biochemical and histological examination. Expression levels of miR-636 were determined in liver by qRT-PCR. Induction of diabetic nephropathy by streptozotocin was evidenced by displayed elevated levels of serum creatinine, blood urea nitrogen, microalbuminuria and urinary albumin/creatinine ratio in addition to renal hypotrophy. Caffeic acid (CA) can ameliorate renal damage and significantly decreased the fasting blood glucose, cholesterol and triglyceride in diabetic rats. CA treatment improved histological architecture in the diabetic kidney. CA significantly down regulate miR-636 expression level in the kidney of diabetic rats in comparison to healthy group. Overall, caffeic acid down regulates miR-636 expression level which is involved in development of diabetic nephropathy and might therefore be potential attractive therapeutic agent to pursue in DN.


Physical therapy for patients with knee and hip osteoarthritis: supervised, active treatment is current best practice.
Most patients with knee and hip osteoarthritis (OA) should be treated in primary care by non-surgical treatments. Building on substantial evidence from randomised trials, exercise therapy and education, typically delivered by physical therapists, are core first line treatments universally recommended in treatment guidelines for OA alongside weight loss, if needed. Exercise therapy provides at least as effective pain relief as pharmacological pain medications, without serious adverse effects; furthermore, the treatment effect from exercise therapy is similar, irrespective of baseline pain intensity and radiographic OA severity. Exercise therapy should be individualised to the preferences and needs of the individual patient, but at least 12 supervised sessions, 2 sessions per week, are required initially to obtain sufficient clinical benefit. Structured patient education concerning OA and its treatment options, including self-management, is important to retain motivation and adherence to an exercise programme and thereby maintain the effects over the long-term. If treatment effects from exercise therapy and patient education are insufficient, the physical therapist can deliver supplementary interventions that include knee orthoses and manual treatment.


Functional performance as a predictor of injurious falls in older adults.
To determine whether a performance battery and its components aid in predicting injurious falls. Longitudinal analysis; prospective cohort study. Clinical site. Boston-area community-dwelling adults (N = 755; mean age ± SD 78.1 ± 5.4, 64.1% female, 77.6% white). Baseline functional performance was determined according to the Short Physical Performance Battery (SPPB), measuring balance, gait speed, and five repeated chair stands. Fall history (past year) and efficacy in performing 10 daily activities without falling were assessed. Falls were assessed using a daily calendar over 4 years. Injurious falls were defined as resulting in fractures, sprains, dislocations, pulled or torn muscles, ligaments, or tendons or seeking medical attention. Poorest chair stand performance (≥16.7 seconds) was associated with greater hazard of injurious falls than in all other chair stand performance groups (hazard ratio (HR) = 1.96, 95% confidence interval (CI) = 1.18-3.26 for ≥ 16.7 vs. 13.7-16.6 seconds; HR = 1.65, 95% CI = 1.07-2.55 for ≥ 16.7 vs. 11.2-13.6 seconds, HR = 1.60, 95% CI = 1.03-2.48 for ≥ 16.7 vs. <11.2 seconds). SPPB did not predict injurious falls. Fall history predicted injurious falls (HR = 1.82, 95% CI = 1.39-2.39); falls efficacy did not. Fall history and a slow chair stand (<16.7 seconds) had a 2-year cumulative incidence rate of an injurious fall of 46% (95% CI = 0.34-0.58), nearly the combined rate of a positive fall history (0.29, 95% CI = 0.25-0.34) and a slow chair stand alone (0.21, 95% CI = 0.13-0.30). An easily administered chair stand test may be sufficient for evaluating performance as part of a risk stratification strategy for injurious falls.


Fabrication of a novel ZnIn2S4/g-C3N4/graphene ternary nanocomposite with enhanced charge separation for efficient photocatalytic H2 evolution under solar light illumination.
Design and synthesis of efficient photocatalyst systems for a large volume of hydrogen (H2) evolution under solar light is still a great challenge. To obtain high photocatalytic activity, graphene-based semiconductor photocatalysts are gaining heightened attention in the field of green and sustainable fuel production due to their good electronic properties, high surface area and chemical stability. Herein, we demonstrate an efficient, novel and smart architecture of a graphene-based ZnIn2S4/g-C3N4 nanojunction by a simple hydrothermal process for H2 generation. In the present study, graphene (G) is chosen as the electron mediator and ZnIn2S4 (ZIS) and g-C3N4 (CN) are chosen as two different semiconductor photocatalysts to construct a smart architecture for the ternary photocatalytic system. Different characterization techniques such as XRD, TGA, FT-IR, SEM, TEM, HR-TEM, XPS, BET, and UV-vis DRS were employed to ensure the successful integration of graphene, ZnIn2S4, and g-C3N4 in the nanocomposite. As a result, high and efficient H2 evolution (477 μmol h-1 g-1) is attained for the graphene-based ZnIn2S4/g-C3N4 nanocomposite. Transient photocurrent experiments, ESR, PL, and time-resolved PL studies suggested that the intimate ternary nanojunction effectively promotes fast charge transfer and thereby enhances photocatalytic H2 evolution.


Cyclic AMP induces morphological changes of vascular smooth muscle cells by inhibiting a Rac-dependent signaling pathway.
Cyclic AMP (cAMP) is a pleiotropic second messenger that regulates numerous cellular processes. In vascular smooth muscle cells (VSMCs), these include cell proliferation, migration, and contractility. Here we show that cAMP-elevating agents induce dramatic morphological changes in VSMCs, characterized by cell rounding and formation of long branching processes. The stellate morphology is associated with disassembly of actin stress fibers and lamellipodia, loss of focal adhesions, and the formation of small F-actin rings. Because of the importance of Rho family GTPases in regulating actin dynamics, we analyzed their individual roles in the cAMP phenotype. We found that pharmacological or genetic inhibition of Rac mimics cAMP effect in inducing a stellate morphology of VSMCs. Expression of activated Rac1 prevents forskolin-induced cAMP stellation, suggesting that cAMP affects cell morphology by inhibiting Rac function. Consistent with this, treatment with forskolin inhibits agonist-stimulated Rac activation in VSMCs. We further show that activated Rac1 containing the F37A effector loop substitution fails to rescue the cAMP phenotype. Our results suggest that cAMP modulates the morphology of VSMCs by inhibiting a Rac-dependent signaling pathway.


Effects of visual cortical lesions on receptive-field properties of single units in superior colliculus of the rabbit.
1. One hundred seventy-nine single units were studied in the superior colliculus of seven Dutch-belted rabbits following ablation of the ipsilateral visual cortex. The response characteristics of these units were compared with those of 284 single units recorded from the superior colliculus of 20 intact animals. 2. In both the upper and lower parts of the stratum griseum superficiale and in the stratum griseum intermediate, there were smaller proportions of direction-selective visual units in the decorticated animals than in normal ones. 3. In the upper stratum griseum superficiale, a larger proportion of units responded to stroboscopic illumination in the decorticated animals than in normal ones. Also, in the decorticated animals, there was a larger proportion of units whose responses to a small moving stimulus were inhibited by the simultaneous presentation of stroboscopic illumination. 4. In both the upper and lower parts of the stratum griseum superficiale, a larger proportion of visual units responded well to stationary stimuli and a smaller proportion of visual units showed habituation in decorticated animals compared to normal ones. 5. In the lower stratum griseum superficiale, the receptive fields of units were larger and were more elongated in the anterior-posterior dimension in the decorticated animals than in normal ones. 6. In the two preparations, units did not differ in responsiveness or spontaneous activity; and visual units did not differ in the sustained or transient nature of their responses, the selectivity for light or dark stimuli, the selectivity for onset or offset of the stimuli, or the selectivity for stimulus velocity. 7. This study provides evidence for the importance of the visual corticotectal projection in the elaboration of the visual receptive-field properties of units in the superior colliculus of the rabbit. In addition, this study shows that the subdivisions of the superior colliculus are differentially affected by the loss of the visual corticotectal projection.


Mechanisms compensating Na and water retention induced by long-term reduction of renal perfusion pressure.
Endogenous downregulation of plasma aldosterone (Aldo) concentration, despite increased plasma renin activity (PRA), has been suggested to compensate Na and water retention, which is induced by long-term reduction of renal perfusion pressure (rRPP). To determine whether fixed plasma Aldo concentration would prevent equilibration of 24-h Na and water balances during rRPP, chronically instrumented, freely moving beagle dogs were kept under standardized conditions (daily intake 5.5 mmol Na/kg body wt) and studied for 4 consecutive days under the following conditions: control without rRPP (protocol 1) and rRPP + infusion of Aldo (rRPP + Aldo, protocol 2). Because Aldo administration reduces PRA and, thereby, angiotensin II (ANG II) levels ANG II was additionally infused in protocol 3 (rRPP + ANG II + Aldo). During rRPP + Aldo, 24-h Na balances were never equilibrated. Daily Na retention was approximately 3.5 mmol/kg body wt on day 1 and decreased to approximately 1.6 mmol/kg body wt on day 4; 24-h water balances changed in a similar manner. PRA decreased stepwise. On all rRPP + ANG II + Aldo days, Na and water retentions were more extensive than during rRPP + Aldo. Daily Na retention decreased from approximately 4.4 mmol/kg body wt on day 1 to approximately 3.0 mmol/kg body wt on day 4. Plasma atrial natriuretic peptide increased during both protocols. It is concluded that 1) endogenous downregulation of components of the renin-angiotensin-aldosterone system is a pivotal compensatory mechanism to reduce Na and water retention and 2) natriuretic and diuretic factors seem to be of minor potency, because not even the sum of all could counterbalances the Na- and water-retaining effects of Aldo and ANG II.


Intensified primary cancer care: a randomized study of home care nurse contacts.
Newly diagnosed cancer patients (n=527) were randomised to intensified primary care or a control group. Intensified primary care comprised routines to improve general practitioners' and home care nurses' possibilities to support and monitor patients, i.e. increased information from specialist care, education and supervision in cancer care. The aims of this paper are to evaluate the effects of intensified primary care on cancer patients' home care nurse contacts, and to study if patients' use of home care services 6 months after diagnosis can be predicted. The intervention resulted in a marked increase of follow-up contacts. About 90% of intensified primary care patients reported such contacts, compared to 26% of control patients. The results indicate that standard care does not routinely include follow-up contacts, not even for the oldest (80+ years) or those with advanced disease. Only 27% and 36% of these groups of control patients reported follow-ups. Logistic regression analysis identified intensified primary care as the strongest predictor for reporting a continuing contact 6 months after diagnosis. Intensified primary care patients were 14 times more likely than controls to report a such contact. The strongest predictor of a continuing contact in the intensified primary care group was high age. Patients with advanced disease were more likely than patients with non-advanced disease to report a continuing contact, and living in a rural district was positively associated with reporting a contact. A majority of the patients (70%) assessed the time for the first contact as the 'right time' and estimated that the nurse gave expected support to a very large or large extent (67%). The results suggest that routines like those implemented through intensified primary care may be an effective strategy to increase the accessibility and continuity of care, especially for elderly people and for patients with a need for long-term contacts.


[The rithral macrobenthos community biogeography of southeastern Europe].
The rithral and hypocrenal (of small rapid streams) macrobenthos faunas of northern Greece, eastern Carpathians, montane Crimea, and northwestern Caucasus are comparatively analyzed based on original material. Peculiarities of the rheophile communities and faunas of each region and of the whole studied area are described. The area is provisionally divided into biogeographic unites based on rithral fauna; this classification is essentially different from those of other authors. The main faunistic border runs meridionally between Greece-Carpathians on one side and Caucasus-Crimea on the other. The present authors believe that the biogeographic variability of macrobenthos rithral faunas results from the position of regions containing rithron communities and from spatial ties between them. Three fundamental biogeographic zones, suggested to be ranked as subregions, are recognized in the West Palearctic: the Balkan-Alpine (West European), the Scandinavian-Ural (North European), and the Caucasian. All the data available fit the suggested scheme, which shows that this approach is of universal value to biogeographic analysis and to divisions of the rithral into biogeographic zones. The local-scale variability of rheophile macrobenthos fauna in the northwestern Caucasus is discussed. Significant faunistic similarity of territories comprising the studied area is shown, internal division into biogeographic zones is conducted, and the lowest scale border of the faunistic diversity of rheophile macrobenthos is established at about 100-150 km.


Effect of cholera toxin on cAMP levels and Na+ influx in isolated intestinal epithelial cells.
Freshly isolated chicken intestinal cells contain approximately 20 pmol adenosine 3',5'-cyclic monophosphate (cAMP)/mg cellular protein. Incubation with 3 micrograms/ml cholera toxin (CT) at 37 degrees C induces an elevation of cellular cAMP beginning 10-15 min after initial exposure. The response is linear with time for 40-50 min and causes a six- to eightfold increase over control levels at steady state. Dibutyryl cAMP and agents that increase cAMP production inhibit Na+ influx into the isolated enterocytes. Chlorpromazine completely abolishes the toxin-induced elevation of cAMP in the isolated cells and also reverses the effect on Na+ entry. The data provide evidence for a cAMP-mediated control of intestinal cell Na+ uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na+ during induction of intestinal secretory activity. Studies on the time-dependent effects of chlorpromazine on both intracellular cAMP concentration and Na+ influx suggest that the reactivation of the Na+ transport system after cAMP-induced inhibition is slow relative to the disappearance of cAMP.


Fabricating Graphene and Nanodiamonds from Lignin by Femtosecond Laser Irradiation.
This study demonstrates a new transformation path from lignin to graphene and nanodiamonds (NDs) by femtosecond laser writing in air at ambient temperature and pressure. Graphene nanoribbon rolls were generated at lower laser power. When the laser power was high, NDs could be obtained apart from graphene and onion-like carbon intermediates. These structures were confirmed by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. The effects of laser power and laser writing speed on the structure of laser-induced patterns were investigated. The results show that the laser power was more important than the writing speed for the synthesis of carbon nanoparticles, and high laser power contributed to enhanced electrically conductive performance. Therefore, the direct laser irradiation technique leads a simple, low-cost, and sustainable way to synthesize graphene and NDs and is promising for the fabrication of sensors and electric devices.


Cognition-Modulated Frontal Activity in Prediction and Augmentation of Antidepressant Efficacy: A Randomized Controlled Pilot Study.
Higher rostral anterior cingulate cortex (rACC) activity correlated with frontal theta power (frontalθ) is associated with better antidepressant responses. The antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) varied widely; however, the effects of TMS might be modulated by manipulating the pretreatment neural states. Therefore, we conducted a pilot study to investigate whether manipulated frontalθ before rTMS treatment could predict and augment antidepressant responses. A computerized rACC-engaging cognitive task (RECT) was exploited continuously for 10 min to patients with major depressive disorder. In total, 36 patients were randomized to 3 groups (Group-A: RECT[active] + rTMS[active]; Group-B: RECT[sham] + rTMS[active]; Group-C: RECT[active] + rTMS[sham]). Frontalθ and whole-brain glucose uptakes were assessed. We found that the RECT-modulated increases in frontalθ correlated well with rACC glucose uptakes. The treatment responders demonstrated a significant increase in frontalθ after RECT. Post-RECT frontalθ had good sensitivity/specificity in predicting antidepressant responses to rTMS. Group-A had more reduction in total depression scores, had more responders, and was more likely to achieve remission than other groups (Group-A [41.6%] > Group-B [16.6%] > Group-C [0%], P < 0.05). A significant enhancement in the post-1st-rTMS frontalθ was observed in Group-A responders but not in Group-B responders, supporting the argument that RECT-modulated rTMS augmented rTMS efficacy. In conclusion, this study suggests that manipulating pre-rTMS neural activity could predict and augment antidepressant effects to rTMS treatment.


Associations between age-related differences in occipital alpha power and the broadband parameters of the EEG power spectrum: A cross-sectional cohort study.
In adulthood, neurological structure and function are often affected by aging, with negative implications for daily life as well as laboratory-based tasks. Some of these changes include decreased efficiency modulating cortical activity and lower signal-to-noise ratios in neural processing (as inferred from surface electroencephalography). To better understand mechanisms influencing age-related changes in cortical activity, we explored the effects of aging on narrow-band alpha power (7.5-12.5 Hz) and broadband/aperiodic components that span a wider range (1.5-30.5 Hz) over the occipital region during eyes-open and eyes-closed wakeful rest in 19 healthy young adults (18-35 years) and 21 community-dwelling older adults (59+ years). Older adults exhibited a smaller change in alpha power across conditions compared to younger adults. Older adults also showed flatter aperiodic slopes in both conditions. These changes in narrow-band alpha are consistent with previous work and suggest that older adults may have a reduced ability to modulate state-specific activity. Differences in the aperiodic slope suggest age-related changes in the signal-noise-ratio in cortical oscillations. However, the relationship between narrow-band alpha modulation and the aperiodic slope was unclear, warranting further investigation into how these variables relate to each other in the aging process. In summary, aging is associated with a broadband flattening of the EEG power spectrum and reduced state-specific modulation of narrow-band alpha power, but these changes appear to be (at least partially) independent of each other. The present findings suggest that separate mechanisms may underlie age-related differences in aperiodic power and narrow-band oscillations.


[Exercise-dependent anaphylaxis].
The clinical features of exercise-induced anaphylaxis in 5 patients are described, with an accurate history, skin tests, IgE determinations and exercise tests. In these 5 patients we were able to distinguish three different forms of exercise-induced disease: exercise-induced anaphylaxis based upon an IgE-mediated allergy to foods, exercise-induced anaphylaxis without food allergy and cholinergic urticaria.


Percutaneous liver biopsy: retrospective study of primary and secondary hepatic lymphoma in twenty-one patients.
Hepatic lymphoma (HL) is categorized as primary and secondary hepatic lymphoma (PHL and SHL). This disorder can present as hepatic mass or mass-like lesion. Chemotherapy often is the first line treatment for patients with HL. Thus, an accurate pre-management histological diagnosis is essential to potentially improve clinical outcomes. The present study was to explore the prevalence of HL in ultrasound guided liver biopsies for hepatic mass or mass-like lesions, to investigate HL associated clinicopathological features, to raise the awareness of early recognition and proper diagnosis of this entity, and to assess specimen adequacy in needle core biopsy. Twenty-one cases of HL were enrolled. Clinical and pathological characteristics were evaluated, quality of biopsies was assessed and pertinent literature was reviewed. HL was diagnosed in 0.94% of 2242 liver biopsy cases with ambiguous clinical presentation, laboratory tests and image studies. There were two cases of PHL (0.09%), and nineteen cases of SHL (0.85%). Histopathologically, diffuse large B-cell lymphoma was the most common type, followed by B-cell lymphoma not otherwise specified, T-cell lymphoma, Hodgkin's lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Additionally, three lymphocytic infiltration patterns were documented microscopically. The nodular infiltration was the most common type. HL is a rare entity and histopathology along with ancillary tests remains the only way to make the diagnosis. Clinicians' awareness of this entity and early liver biopsy are essential in patient management.


An astroblastoma mimicking a cavernous malformation: case report.
Astroblastomas are rare glial neoplasms that usually occur in young adults and have a predilection for the cerebral hemispheres. Patients typically present with signs of increased intracranial pressure and seizures. Imaging studies reveal circumscribed, contrast-enhancing tumors that contain both cystic and solid components with variable peritumoral edema. Hemorrhage, which suggested the presence of a vascular lesion in this patient, has not been previously described as a feature of this neoplasm. The authors report the case of a 33-year-old woman who presented with spontaneous intraparenchymal hemorrhage. The collective radiographic data suggested the presence of a cavernous malformation. A right frontotemporal craniotomy was performed under frameless stereotactic image guidance. An astroblastoma was diagnosed after resection and neuropathological examination. A rare radiological to pathological correlation of astroblastoma is presented in which the evolving hematoma, as observed on magnetic resonance imaging scans, complicated the radiographic diagnosis of this lesion. The clinical, radiographic, and pathological features of astroblastomas, as well as the natural history of these rare glial neoplasms, are reviewed. This case illustrates the capacity of astroblastomas to hemorrhage, disguising the classic radiographic findings typical of this glial neoplasm.


Effects of low-intensity endurance and resistance training on mobility in chronic stroke survivors: a pilot randomized controlled study.
Chronic stroke survivors are exposed to long-term disability and physical deconditioning, effects that may impact their independence and quality of life. Community-based programs optimizing the dose of exercise therapy that are simultaneously low risk and able to achieve high adherence should be identified. We tested the hypothesis that an 8-week, community-based, progressive mixed endurance-resistance exercise program at lower cardiovascular and muscular load yielded more mobility benefits than a higher-intensity program in chronic stroke survivors. A two-arm, parallel-group, pilot randomized, controlled clinical trial. Hospital (recruitment); community-based adapted physical activity center (training). Thirty-five chronic stroke patients (mean age: 68.4±10.4 years; 27 males). Participants were randomized to a low-intensity experimental (LI-E; N.=18) or a high-intensity active control group (HI-C; N.=17). Patients in the LI-E group performed over-ground intermittent walking (weeks 1-8) and muscle power training with portable tools (weeks 5-8); patients in the HI-C group executed treadmill walking (weeks 1-8) and strength training with gym machines (weeks 5-8). Changes in mobility, assessed using the 6-Minute Walking Distance test, were the primary outcome. Secondary outcomes included quality of life (Short-Form-36 Questionnaire), gait speed (10-Meter Walking Test), balance (Berg Balance Scale) and muscle performance of the lower limbs (strength and power of the quadriceps and femoral biceps). After 8 weeks, the 6MWD revealed more improvement for the LI-E group than the HI-C group (P=0.009). The SF36 physical activity domain (P=0.012) and peak power of the femoral quadriceps and biceps were also significantly improved for the LI-E group (P=0.008 and P<0.001, respectively) compared with the HI-C. Gait speed, balance and lower-limb strength increased in both groups; no significant differences were noted. The muscle power of the affected limb was the muscle parameter most correlated with mobility in the entire population. A low-intensity exercise program exhibited better results in terms of mobility, quality of life and muscle power compared with a higher-intensity program. Data need to be confirmed in a larger trial. The effectiveness, low-intensity and possible implementation in poorly equipped community-based settings make the LI-E program potentially suitable for stroke survivors and frail individuals.


Paediatric epilepsy surgery in the posterior cortex: a study of 62 cases.
Past surgical series have emphasized the diagnostic complexity of posterior cortex epilepsy. Available data are sparse, especially in children, and most published series report a high number of surgical failures and post-operative neurological deficits. In this article, we present a paediatric cohort of 62 children who underwent surgery for drug resistant posterior cortex epilepsy before the age of 16 years with a mean post-operative follow-up of 6.94 years (range: 2-16). Mean age at epilepsy onset was 3.2 years and 28 children (45%) had onset before 1 year of age. The mean age at surgery was 7.9 years (range: 1-16). Daily seizures were present in 63% of children. MRI was positive in 58 cases (93.5%) and invasive stereo-EEG was judged mandatory in 24/62 (39%) of patients. Surgery was confined to the parietal lobe in 11 children, the occipital lobe in 8, the occipito-parietal region in four, the occipito-temporal region in 18, and involved both the temporal and parietal lobes in the remaining 21. Following surgery, 53 subjects (85.5%) remained seizure-free and among those who underwent a SEEG procedure, 75% achieved seizure freedom. Focal cortical dysplasia was the most frequent histopathological diagnosis (50%), followed by tumoural (24%) and gliotic lesions (14.5%). An older age at epilepsy onset, the presence of a rather restricted epileptogenic area, and a complete resection of the epileptogenic zone were predictive of a favourable surgical outcome. These results demonstrate that a good surgical outcome is possible in children with drug resistant posterior cortex epilepsy. Accurate analysis of the chronology of ictal semiology and electrophysiological features, viewed in the context of the complete electroclinical pattern, provides a topographical orientation for posterior cortex epilepsy and, together with the presence of a lesion detectable on imaging, may improve the rate of surgical success of posterior cortex epilepsy at paediatric age.


Bimatoprost 0.03% gel for cosmetic eyelash growth and enhancement.
To evaluate a bimatoprost gel for enhancing eyelash growth, adverse effects, and change in intraocular pressure (IOP). Prospective, double-masked, randomized controlled study. Fifty-two patients without ocular disease were assigned a control or bimatoprost 0.03% gel to apply to the eyelid margin once a day. The adjusted mean change in eyelash length from baseline to 6 months was 0.77 mm in the bimatoprost group and -0.12 mm in the control group (P = 0.004). Adverse effects were experienced by 2 of 16 patients (12.5%) in the control group and 9 of 36 patients (25%) in the bimatoprost gel group. Mean change in IOP from baseline to 6 months was 0.685 mmHg in the control group and -2.04 mmHg in the bimatoprost group (P = 0.009). Bimatoprost gel was effective in enhancing eyelash growth. The most common adverse effect for the bimatoprost gel was conjunctival and eyelid hyperemia, while the most severe was recurrent anterior uveitis. Mean IOP was reduced in subjects using the bimatoprost gel.


Stability of steepest descent with momentum for quadratic functions.
This paper analyzes the effect of momentum on steepest descent training for quadratic performance functions. We demonstrate that there always exists a momentum coefficient that will stabilize the steepest descent algorithm, regardless of the value of the learning rate. We also demonstrate how the value of the momentum coefficient changes the convergence properties of the algorithm.


Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort.
Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors' lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.