Young chronic patients and changes in the state hospital population.
The number of young adult chronic patients, particularly males, has risen not only in community mental health programs but also among the inpatient populations of state hospitals. To assess the chronicity of these young adult patients, the authors divided the state hospital inpatient census into three groups based on length of stay. They found a considerable increase in the proportion of male admissions age 21 to 44 who remained hospitalized for three months or more. The three groups also differed in patient characteristics and prognosis for release. The authors conclude that the increasing number and proportion of younger patients, with their markedly different service needs, will almost inevitably alter the nature of the state hospital program for decades to come.


Current practices of preoperative bowel preparation among North American colorectal surgeons.
In North America, the rate of infections following colorectal surgery decreased after the introduction of oral antibiotic bowel preparation against colonic microflora. Eight hundred eight board-certified colorectal surgeons were surveyed for their current bowel preparation practices before elective procedures. The 471 responders (58%) all use mechanical preparation: oral polyethylene glycol solution (70.9% of the respondents), oral sodium phosphate solution with or without bisacodyl (28.4%), and "traditional" methods of dietary restriction, cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral neomycin and erythromycin or metronidazole are combined with a perioperative parenteral antibiotic. Most individuals start the preparation as outpatients the day before surgery, and the parenteral drugs are added to the regimen 1-2 hours before the procedure. The use of outpatient bowel preparation is increasing; however, patient selection is critical, and education is needed to reduce the rate of complications.


Factors Influencing Cecal Intubation Time during Retrograde Approach Single-Balloon Enteroscopy.
Background and Aim. The predisposing factors for prolonged cecal intubation time (CIT) during colonoscopy have been well identified. However, the factors influencing CIT during retrograde SBE have not been addressed. The aim of this study was to determine the factors influencing CIT during retrograde SBE. Methods. We investigated patients who underwent retrograde SBE at a medical center from January 2011 to March 2014. The medical charts and SBE reports were reviewed. The patients' characteristics and procedure-associated data were recorded. These data were analyzed with univariate analysis as well as multivariate logistic regression analysis to identify the possible predisposing factors. Results. We enrolled 66 patients into this study. The median CIT was 17.4 minutes. With univariate analysis, there was no statistical difference in age, sex, BMI, or history of abdominal surgery, except for bowel preparation (P = 0.021). Multivariate logistic regression analysis showed that inadequate bowel preparation (odds ratio 30.2, 95% confidence interval 4.63-196.54; P < 0.001) was the independent predisposing factors for prolonged CIT during retrograde SBE. Conclusions. For experienced endoscopist, inadequate bowel preparation was the independent predisposing factor for prolonged CIT during retrograde SBE.


Racial/ethnic disparities in the HIV and substance abuse epidemics: communities responding to the need.
In 1998, community leaders prompted members of the Black and Hispanic Congressional Caucuses to urge President Clinton to declare HIV/AIDS a crisis in the African American and Latino communities; their advocacy resulted in the formation of the Minority AIDS Initiative. As part of this initiative, the Center for Substance Abuse Prevention (CSAP) of the Substance Abuse and Mental Health Services Agency funded the Substance Abuse and HIV Prevention Youth and Women of Color Initiative (CSAP Initiative). The CSAP Initiative is the first major federal effort to develop community-based integrated HIV and substance abuse prevention approaches targeting racial/ethnic populations that have been disproportionately impacted by HIV/AIDS. This article describes the current state of HIV prevention research involving racial/ethnic minority populations and the current status of the CSAP Initiative. The data collected through the CSAP Initiative, implemented by 47 community organizations, will help to fill the existing knowledge gap about how to best prevent HIV in these communities. This data collection effort is an unparalleled opportunity to learn about risk and protective factors, including contextual factors, that are critical to the prevention of HIV/AIDS in African American, Latino, and other racial/ethnic minority communities but that are often not investigated.


Developmental Biology: Computational and Experimental Approaches.
Developmental biology studies ontogenesis, the individual development of an organism from the time of fertilization in sexual reproduction or its expelling from the maternal organism in asexual reproduction to the end of an organism's life, with all phenotypical characters typical of this biological species and supporting the normal course of all biochemical processes and morphogenesis [...].


Treatment of acute-onset hypertension in pregnancy: A network meta-analysis of randomized controlled trials comparing anti-hypertensives and route of administration.
Consensus on the relative efficacy of available antihypertensive agents used in pregnancy is lacking. To compare treatment success with antihypertensives and categorize by route of administration. MEDLINE, Embase, PubMed, Web of Science, Scopus, CINAHL, and clinicaltrials.gov were searched without date restriction. Peer-reviewed randomized controlled trials (RCTs) comparing pharmacologic agents used to treat hypertension in parturients were included. Evaluated treatment groups included IV-labetalol (BBIV), IV-hydralazine (DIV), oral-nifedipine (CCBPO), sublingual nifedipine (CCBSL), IV-calcium channel blocker (nonspecific)(CCBIV), IV-nitroglycerine (NTG), epoprostenol infusion (PRO), IV-ketanserin (5HT2B), IV-diazoxide (BZO), oral-nifedipine + methyldopa (CCBAG), oral-methyl-dopa (AAG), and oral prazosin (ABPO). Seventy-four studies (8324 patients) were eligible post PRISMA guidelines screening. Results were pooled using a Bayesian-approach for success of treatment (study defined target blood pressure), time to achieve target pressure, and neonatal intensive-care admissions. Treatment success (primary outcome, 55 trials with 5518 patients) was analyzed. Surface under the cumulative ranking curve (SUCRA) was categorized for 13 drugs, CCBPO (0.84) followed by CCBSL (0.78) were most likely to be effective in achieving target blood pressure. After sub-grouping by presence/absence of preeclampsia, CCB-PO ranked highest for both [(0.82) vs. (0.77), respectively]. Serotonin antagonists (0.99) and nitroglycerin (0.88) ranked highest for time to target pressure. NICU admissions were lowest for alpha-2 agonists (0.89), followed by BB PO (0.82) and hydralazine IV (0.49). Oral calcium-channel blockers ranked highest for treatment success. Ketanserin achieved target blood pressure fastest, warranting additional research. The results should be interpreted with caution as SUCRA values may not indicate whether the differences between interventions have clinically meaningful effect sizes.


FOXC1: an emerging marker and therapeutic target for cancer.
The Forkhead box C1 (FOXC1) transcription factor is involved in normal embryonic development and regulates the development and function of many organs. Most recently, a large body of literature has shown that FOXC1 plays a critical role in tumor development and metastasis. Clinical studies have demonstrated that elevated FOXC1 expression is associated with poor prognosis in many cancer subtypes, such as basal-like breast cancer (BLBC). FOXC1 is highly and specifically expressed in BLBC as opposed to other breast cancer subtypes. Its functions in breast cancer have been extensively explored. This review will summarize current knowledge on the function and regulation of FOXC1 in tumor development and progression with a focus on BLBC, as well as the implications of these new findings in cancer diagnosis and treatment.


Outpatients' satisfaction with healthcare services received at a district hospital in Botswana.
To investigate patient satisfaction regarding healthcare services at a district hospital. The research question was: what is the level of patient satisfaction regarding service delivery? An observational cross-sectional descriptive study conducted in September 2019. A district hospital in Botswana serving a population of 90 000. Outpatients from the Eye clinic, Casualty and Outpatient Department, Sexual Reproductive Health clinic and Infectious Diseases Control Centre were selected for the study. 240 stable outpatients over 17 years selected through consecutive sampling participated voluntarily after giving informed consent. The level of satisfaction was measured using 19 questions on five-point Likert scales ranging from strongly disagree 1, disagree 2, unsure 3, agree 4 to strongly agree 5. A binary outcome was created into satisfied and unsatisfied using the mean score as the cut-off point. Age, gender, employment, education and departments were independent variables. 65% (95% CI: 58-71%) were satisfied but unsatisfied with: doctor's politeness (66.9%; 95% CI: 60-73%), explaining (67.8%; 95% CI: 61-73%), privacy (65.6%; 95% CI: 59-72%), skills (67.4%; 95% CI: 61-73%), confidence (67.4% 95% CI: 61-73%), compassion (66.5%; 95% CI: 60-72%) and waiting time (49.2%; 95% CI: 42-57%). Department visited predicted satisfaction (p=0.002); those from the Eye clinic and Sexual Reproductive Health clinic were satisfied compared to others. Satisfaction was generally high but lower regarding specified services and departments visited. There is a need for targeted interventions. Studies are needed to explore reasons for lower satisfaction in Casualty, Outpatient Department and Infectious Diseases Control Centre. None declared.


Routine early postoperative computed tomography angiography after coronary artery bypass surgery: clinical value and management implications.
Computed tomography angiography (CTA) is broadly used for long-term follow-up of graft patency after coronary artery bypass graft surgery (CABG). However, its clinical value in the early postoperative setting has not been established yet. We evaluated the benefit of adding CTA to the routine clinical work-up after CABG on patient management. A total of 305 consecutive patients (269 males, median age 68 years) underwent CABG and postoperative CTA with a median of 6 days after surgery. Graft patency and additional imaging findings were assessed and their influence on diagnosis and clinical management was evaluated. Graft occlusion or high-grade stenosis was found in 15% of the patients. Additional findings were reported in 44% of the patients, including pericardial (2%) and pleural effusion (27%), large pneumothorax (11%), pulmonary infection (4%), cardiac or vascular thrombus (2%), pulmonary embolism (2%), sternal dehiscence (1%) and additional incidental findings requiring follow-up (6%). CT findings initiated new diagnostic and/or therapeutic measures in 15% of the patients, 47% of those with diseased grafts and 19% of patients with non-graft-related findings. No adverse events related to CTA were documented. Early routine postoperative assessment of CABG with CTA reveals both cardiac and non-cardiac findings with a high frequency, affecting clinical management in a substantial proportion of patients.


Damage to pig bile duct caused by intraluminal brachytherapy using a (125)I ribbon.
Stent occlusion by tumor ingrowth or overgrowth is the main cause of jaundice recurrence after metal stent insertion in patients with malignant obstructive jaundice (MOJ). The application of intraluminal brachytherapy (ILBT) in patients with MOJ results in local control of malignant tumors, which prolong stent patency. To evaluate the safety of ILBT in pig bile ducts using ribbons of iodine-125 ((125)I) seeds. Sixteen healthy pigs were randomly assigned to four groups of four pigs each. A (125)I seed ribbon was implanted into the common bile duct of each animal through an incision in the duct wall, and was fixed by suturing. The four groups of animals were sacrificed at 15, 30, 60, and 120 days after ribbon implantation, respectively. Serum bilirubin concentrations, alanine aminotransferase concentrations, and white blood cell counts before and after implantation were compared within each group. Pathological changes to the bile duct wall were observed using a light microscope. Morphological changes in biliary epithelial cells and organelles were observed with electron microscopy. (125)I ribbons were successfully implanted in all animals without surgery-related death. We found no significant difference in pre- and post-implant serum bilirubin, alanine aminotransferase, or white blood cell counts. Light and electron microscopy showed that the most severe bile duct damage occurred in the 15-day group, which exhibited necrosis and detachment of numerous epithelial cells, and infiltration of inflammatory cells. Repair and proliferation of the bile duct epithelium began 30 days after implantation and was nearly complete at 60 days. This study demonstrated the safety of ILBT using a (125)I ribbon in the pig bile duct. (125)I seed ribbons may be used in the treatment of MOJ in humans.


Inhibition of secreted aspartyl proteinase activity in biofilms of Candida species by mycogenic silver nanoparticles.
Candida species are pleomorphic, commensal fungi associated with candidiasis. The extracellular hydrolytic-secreted aspartyl proteinases are recognized as chief agents for pathogenesis of Candida species, involved in the degradation of proteins and adhesion during biofilm formation. This study aimed at exploring inhibitory effect of mycogenic silver nanoparticles (Ag NPs) against C. albicans and non-albicans' biofilm growth and aspartyl proteinase enzyme activity in-vitro. Biofilm forming, drug-resistant clinical isolates of C. albicans (n = 25) and non-albicans (n= 20) were assessed for their ability to reduce the metabolic and aspartyl proteinase activities using XTT assay and spectrophotometric analysis at different concentrations of mycogenic Ag NPs. After 24 h of incubation, significant reduction (>50%) in metabolic activity was observed with 100 ppm mycogenic Ag NPs. Incubation time has greater inhibitory effect against Candida spp. biofilms secreted aspartyl proteinase after treatment with 100 ppm mycogenic Ag NPs. Inhibition of secreted aspartyl proteinase by mycogenic Ag NPs provides an insight towards the mechanism for the treatment of Candida-associated infections involving biofilms-related infections.


Structure elucidation of procyanidin oligomers by low-temperature 1H NMR spectroscopy.
Procyanidin dimers and trimers, needed as reference compounds for biological studies, have been synthesized from various natural sources using a semisynthetic approach and purified by high-speed countercurrent chromatography (HSCCC). In the past, it has been difficult to elucidate the structure of these compounds, especially the determination of the interflavanoid bond. Here, the structure of two B-type procyanidin dimers, with (+)-catechin ((+)-C) in the upper unit, and eight C-type procyanidin trimers, with (-)-epicatechin ((-)-EC) in the upper unit, have been elucidated using low-temperature (1)H NMR spectroscopy, as well as circular dichroism (CD) spectroscopy. This is the first time NOE interactions have been used to characterize the interflavanoid linkage in underivatized procyanidin trimers. Complete analyses of procyanidin C1 (-)-EC-4β→8-(-)-EC-4β→8-(-)-EC, (-)-EC-4β→8-(-)-EC-4β→8-(+)-C, (-)-EC-4β→6-(-)-EC-4β→8-(-)-EC, (-)-EC-4β→6-(-)-EC-4β→8-(+)-C, (-)-EC-4β→8-(-)-EC-4β→6-(-)-EC, (-)-EC-4β→8-(-)-EC-4β→6-(+)-C, (-)-EC-4β→8-(+)-C-4α→8-(-)-EC, procyanidin C4 (-)-EC-4β→8-(+)-C-4α→8-(+)-C, and procyanidin dimers B6 (+)-C-4α→6-(+)-C and B8 (+)-C-4α→6-(-)-EC are presented.


Struggles for medical legitimacy among women experiencing sexual pain: A qualitative study.
Given the prominent role of medical institutions in defining what is "healthy" and "normal," many women turn to medicine when experiencing pain during intercourse (dyspareunia). The medical encounter can become a contest between patients and providers when physicians do not grant legitimacy to patients' claims of illness. Drawing on interviews conducted from 2007 to 2008 and 2011 to 2012 with 32 women experiencing dyspareunia (ages 18-60 years) and living in New York City and its surrounding areas, this study examined women's and their physicians' claims regarding bodily expertise, particularly women's perceptions of physician invalidation, their understanding of this invalidation as gendered, and the consequences for women's pursuit of medicalization. Women overwhelmingly sought a medical diagnosis for their dyspareunia, in which they believed that providers would relieve uncertainty about its origin, give treatment alternatives, and permit them to avoid sexual activity. When providers did not give diagnoses, women reported feeling that their bodily self-knowledge was dismissed and their symptoms were attributed to psychosomatic causes. Furthermore, some women linked their perceptions of invalidation to both historical and contemporary forms of gender bias. Exploration of women's struggles for medical legitimacy may lead to a better understanding of the processes by which medicalization of female sexuality takes place.


Manipulation under Anesthesia Following TKA with Persona IQ: A Case Series.
Although surgical devices and techniques continue to improve, regular post-operative monitoring of patients is required to ensure the best outcomes. New technological advances have allowed physicians to monitor the daily recovery of total knee arthroplasty (TKA) patients. This report is the first to describe the utilization of an implantable gait monitoring device and its capacity to detect poor early post-operative outcomes. Two patients, a 78-year-old male and a 34-year-old female, were assessed post-TKA utilizing remote gait kinematics and clinical evaluations and determined to need manipulation under anesthesia due to severely limited range of motion. One patient, a 51-year-old female, with good clinical outcomes, was used for comparison. Remote monitoring may provide an earlier indication than clinical evaluations in identification of TKA patients at risk of poor outcomes and may who need intervention. The use of remote kinematic gait data in earlier identification of patients at risk has the potential to help improve outcomes for the broader population of TKA patients.


The Effect of Leaf Stacking on Leaf Reflectance and Vegetation Indices Measured by Contact Probe during the Season.
The aims of the study were: (i) to compare leaf reflectance in visible (VIS) (400-700 nm), near-infrared (NIR) (740-1140 nm) and short-wave infrared (SWIR) (2000-2400 nm) spectral ranges measured monthly by a contact probe on a single leaf and a stack of five leaves (measurement setup (MS)) of two broadleaved tree species during the vegetative season; and (ii) to test if and how selected vegetation indices differ under these two MS. In VIS, the pigment-related spectral region, the effect of MS on reflectance was negligible. The major influence of MS on reflectance was detected in NIR (up to 25%), the structure-related spectral range; and weaker effect in SWIR, the water-related spectral range. Vegetation indices involving VIS wavelengths were independent of MS while indices combining wavelengths from both VIS and NIR were MS-affected throughout the season. The effect of leaf stacking contributed to weakening the correlation between the leaf chlorophyll content and selected vegetation indices due to a higher leaf mass per area of the leaf sample. The majority of MS-affected indices were better correlated with chlorophyll content in both species in comparison with MS-unaffected indices. Therefore, in terms of monitoring leaf chlorophyll content using the contact probe reflectance measurement, these MS-affected indices should be used with caution, as discussed in the paper. If the vegetation indices are used for assessment of plant physiological status in various times of the vegetative season, then it is essential to take into consideration their possible changes induced by the particular contact probe measurement setup regarding the leaf stacking.


An adult with atopic dermatitis and repeated short-term fasting.
It has been reported that nutritional stress, such as short-term fasting and long-term energy restriction, has a suppressive effect on allergic dermatitis in experimental animals. Furthermore, clinical study has demonstrated a positive association between weight loss by low-energy diet and improvement in patients with atopic dermatitis. In this report, a 23-year-old female with atopic dermatitis received a treatment of repeated short-term fasting. 24-hour fasting was conducted once a week for a period of 20 weeks. On the fasting day, the amount of energy intake was 200 kcal. No medication was administered during the trial period. Clinical symptoms were evaluated using the Scoring Atopic Dermatitis index, and IgE, lactase dehydrogenase-5, and number of eosinophils were measured. At the end of the trial, body weight was reduced and clinical symptoms improved, whereas no improvements in laboratory findings were shown. For sufficient evidence of the effects of fasting, additional controlled study is needed.


Determination of mercury in blood, urine and saliva for the biological monitoring of an exposure from amalgam fillings in a group with self-reported adverse health effects.
It has been argued that the release of mercury from amalgam fillings is of toxicological relevance. The aim of the study was to determine the internal mercury exposure of two groups differing in their attitude towards possible health hazards by mercury from amalgam fillings. It was to be examined if the two groups differ with regard to the mercury concentration in different biological matrices and to compare the results with current reference values. Blood, urine and saliva samples were analyzed from 40 female subjects who claimed to suffer from serious health damage due to amalgam fillings ("amalgam sensitive subjects"). 43 female control subjects did not claim any association ("amalgam non-sensitive controls"). Mercury was determined by means of cold vapour atomic absorption spectrometry. Number and surfaces of amalgam fillings were determined by dentists for each subject. Median (range) mercury levels in blood were 2.35 (0.25-13.40) micrograms/l for "amalgam sensitive subjects" and 2.40 (0.25-10.50) micrograms/l for "amalgam non-sensitive controls". In urine, the median mercury concentrations were 1.55 (0.06-14.70) micrograms/l and 1.88 (0.20-8.43) micrograms/g creatinine respectively. No significant differences could be found between the two groups. Mercury levels in blood and urine of the examined subjects were within the range of background levels in the general population including persons with amalgam fillings. Stimulated saliva contained 76.4 (6.7-406.0) micrograms mercury/l in "amalgam sensitive subjects" and 57.0 (2.8-559.0) micrograms mercury/l in controls (not significant). Mercury levels in saliva did not correlate with the concentrations in blood and urine, but merely with the number of amalgam fillings or of the filling surfaces. Mercury in saliva is therefore not recommended for a biological monitoring.


Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease.
Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65+/-8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and non-elevated uric acid levels (233+/-10 microM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10(-7) to 10(-5) microM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein; p<0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh (n=13), oxypurinol markedly attenuated ACh-induced vasoconstriction (-23+/- 4 vs -15+/- 4% at ACh 10(-5) microM, p<0.05) and significantly increased CBF (16+/-17 vs 62+/-18% at ACh 10(-5) microM, p<0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8+/- 4.2 vs 5.2+/- 0.7%, p>0.05) or CBF (135+/-75 vs 154+/-61%, p>0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.


The effect of borderline diabetes on the risk of dementia and Alzheimer's disease.
To verify the hypothesis that borderline diabetes may increase the risk of dementia and Alzheimer's disease, a community-based cohort of 1,173 dementia- and diabetes-free individuals aged >or=75 years was longitudinally examined three times to detect patients with dementia and Alzheimer's disease (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria). Borderline diabetes was defined as a random plasma glucose level of 7.8-11.0 mmol/l. Data were analyzed using Cox proportional hazards models. During the 9-year follow-up, 397 subjects developed dementia, including 307 Alzheimer's cases. At baseline, 47 subjects were identified with borderline diabetes. Borderline diabetes was associated with adjusted hazard ratios (95% CIs) of 1.67 (1.04-2.67) for dementia and 1.77 (1.06-2.97) for Alzheimer's disease; the significant associations were present after additional adjustment for future development of diabetes. Stratified analysis suggested a significant association between borderline diabetes and Alzheimer's disease only among noncarriers of APOE epsilon4 allele. There was an interaction between borderline diabetes and severe systolic hypertension on the risk of Alzheimer's disease (P = 0.04). We conclude that borderline diabetes is associated with increased risks of dementia and Alzheimer's disease; the risk effect is independent of the future development of diabetes. Borderline diabetes may interact with severe systolic hypertension to multiply the risk of Alzheimer's disease.


Inflammatory mediators: a causal link to hypertension during preeclampsia.
Preeclampsia (PE) is a hypertensive disorder that occurs after 20 weeks of gestation, implicating the placenta as a key offender. PE is associated with an imbalance among B lymphocytes, CD4+ T lymphocytes, NK cells and increased inflammatory cytokines. During early onset PE, trophoblast invasion and placentation are impaired, leading to reduced blood flow to the fetus. In all spectrums of this disorder, a shift towards a pro-inflammatory state where regulatory cells and cytokines are decreased occurs. Specifically, inflammatory CD4+ T-cells and inflammatory cytokines are increased while CD4+ T regulatory cells (Tregs) and immunosuppressive cytokines such as IL-4 and IL-10 are decreased resulting in B cell activation, production of autoantibodies, endothelial dysfunction and hypertension associated with PE. However, the stimulus for these imbalances is unknown and need to be fully understood so that effective treatments that target the pathogenesis of the disease can be designed. Therefore, this review will focus on the pathways involving CD4+ , TH1, TH2, Tregs, TH17s, B cells, and NK cells in the pathophysiology of PE. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.


Itraconazole comedication increases systemic levels of inhaled fluticasone in lung transplant recipients.
After lung transplantation (LTx), inhaled corticosteroids may be prescribed and at the same time prophylaxis against fungal infections with itraconazole is common. In our center, the addition of inhaled fluticasone propionate to systemic immunosuppression resulted in clinical Cushing's syndrome in 4 lung transplant recipients on itraconazole comedication. The current study was undertaken to compare systemic levels of inhaled fluticasone in patients with and without concomitant itraconazole therapy. The single-center, prospective controlled study was performed in the LTx program in Zurich, Switzerland. Twenty stable recipients, 1-7 years after LTx, on a prednisone maintenance dose (5-7.5 mg/day) gave informed consent and were assigned to 2 groups: (A) without itraconazole comedication and (B) currently on itraconazole, being continued during the study period. The patients of both groups started inhalation of 1 mg fluticasone propionate twice daily for 14 days with a powder disc inhaler. Plasma fluticasone levels were measured before the start of the study and on day 14. Fluticasone levels before starting the treatment were below the detection limit in all 17 patients (7 in group A and 10 in group B) adhering to the study protocol. Baseline characteristics (underlying disease, age at LTx, time since LTx, FEV(1)) were comparable between the 2 groups. On study day 14, plasma fluticasone levels had increased to detectable levels in all patients (A: 273 +/- 124 pg/ml, B: 701 +/- 131 pg/ml), i.e. to significantly higher (p = 0.038) concentrations in patients on itraconazole. Itraconazole comedication substantially increases systemic levels of inhaled fluticasone, most likely by inhibiting the cytochrome P450 3A4 enzyme system and thus the clearance of fluticasone. Accumulation of fluticasone can result in increased systemic effects and therefore comedication has to be taken into consideration when inhaled fluticasone is prescribed.


Resonant-type rotating piezoelectric motor with inchworm-inertia composite impact.
A resonant-type rotating piezoelectric motor with inchworm-inertia composite impact was designed and manufactured. It mainly comprises a stator, rotor, support shaft, and frame. The motor stator includes a clamp, driver, central connecting block, preload structure, and other auxiliary mechanisms. The clamp and driver of the motor work in a resonant state. The motor structure was optimized by using the finite element software COMSOL 5.2. Through the finite element simulation analysis, the first-order bending vibration of the clamp and the driver was selected as the working mode, and the consistency of the resonance frequency coupling was optimized and adjusted. By coordinating the bending vibration of the clamp and driver in the vertical staggered direction, the clamping foot drives the rotor to realize the unidirectional continuous rotation. The motor prototype was designed and processed, while the experimental device platform was established to verify the working principle of the motor, and the comprehensive performance of the motor was analyzed and tested. When the input driving voltage was 240 VP-P, the driving frequency was 161 Hz, and the preload torque of the motor was 6.9 N mm, the maximum no-load speed of the motor reached 3.23 rad/s and the maximum load torque reached 10.35 N mm. Under the same conditions, the maximum resolution of the motor rotation angle was 0.69°.


Troxerutin exerts neuroprotection in 6-hydroxydopamine lesion rat model of Parkinson's disease: Possible involvement of PI3K/ERβ signaling.
Parkinson's disease (PD) is a neurodegenerative disease with progressive loss of mesencephalic dopaminergic neurons of the substantia nigra and with multiple incapacitating motor and non-motor symptoms. Troxerutin is a natural bioflavonoid with nephro- and hepato-protective, antioxidant, and anti-inflammatory properties. In this study, we evaluated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with troxerutin at a dose of 150mg/kg/day for 1 week. Results showed that troxerutin mitigates apomorphine-induced motor asymmetry and lowered the latency to initiate and the total time in the narrow beam task and this beneficial effect was lost following central application of estrogen receptor β (ERβ) antagonist or phosphatidylinositol 3-kinase (PI3K) inhibitor. In addition, troxerutin reduced striatal malondialdehyde (MDA) as an index of lipid peroxidation, reactive oxygen species, glial fibrillary acid protein (GFAP) as a marker of astrogliosis, and DNA fragmentation as an apoptotic marker with no significant alteration of catalase activity and nitrite level. Meanwhile, troxerutin was capable to prevent loss of nigral tyrosine hydroxylase (TH)-positive neurons. These findings indicate neuroprotective potential of troxerutin in 6-OHDA rat model of PD through mitigation of apoptosis, astrogliosis, and oxidative stress and part of its effect is dependent on PI3K/ERβ signaling.


Association Between Digital Device Utilization and Asthenopia Among Medical Students at King Khalid University.
Background Digital eye strain has become a serious concern due to the exponential increase in the usage of digital devices in recent years. This study aimed to assess the prevalence of digital eye strain among medical students. Methods A cross-sectional study was conducted over a period of one month, from 15th June to 15th July 2023, among undergraduate medical students at King Khalid University, Aseer Region, Saudi Arabia. An online survey was carried out using a structured questionnaire that was circulated through social media platforms (Facebook, Messenger, Instagram, Telegram, and WhatsApp). Results A total of 300 students were enrolled in this study. The prevalence of ocular problems, in descending order, was as follows: asthenopia had the highest prevalence at 30.5% (94), followed by conjunctivitis at 9.4% (29); squint, glaucoma, and cataract had lower prevalence rates of 3.9% (12), 1.6% (5), and 1.6% (5), respectively. The majority of participants used digital devices for fun (92.9% (286)) and study (95.5% (294)). Significant positive correlations were found between asthenopia and the hours spent on digital devices for studying (r = 0.161, p = 0.005), communication (r = 0.146, p = 0.011), and entertainment (r = 0.206, p < 0.001). Conclusions A substantial number of medical students are experiencing asthenopia. Prolonged usage of these devices is linked to a higher prevalence of asthenopia.


[Pelvic actinomycosis simulating adnexal malignant tumor].
The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists.


Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies.
Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed.


The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.
Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.


CA125, Galectin-3 and FGF-23 are interrelated in heart failure with reduced ejection fraction.
Carbohydrate Antigen 125 (CA125) is the most widely used biomarker in ovarian cancer screening. In patients with heart failure (HF), increased levels of CA125 have been observed and related to disease severity. Our objective was to determine the association of CA125 levels with two biomarkers of adverse remodeling in HF patients with reduced ejection fraction (HFrEF). CA125 circulating levels were determined with an electrochemiluminscent immunoassay. Concentrations of B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and Fibroblast Growth Factor 23 (FGF23) were also measured by immunoassays. CA125 levels were increased in HFrEF, were associated to disease severity according NYHA classes. Median CA125 concentration was also significantly related to cardiovascular mortality. CA125 concentrations were positively and significantly associated to Galectin-3 and FGF23. Concentrations of CA125 are increased in patients with HFrEF, associated to disease severity and adverse cardiovascular outcomes. CA125 levels are also correlated to Galectin-3 and FGF-23, two biomarkers related to fibrosis and cardiovascular remodeling.


Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy.
The high incidence of age-related diseases in the increasing population of elderly people has stimulated interest in the search for protective agents that have the capability of preventing premature aging and delaying the onset of degenerative disorders. To preserve health in old age becomes a primary goal for biomedicine, because the increasing longevity in our societies is associated with a rise in morbidity. The difficulties in finding new approaches and safe strategies for prevention, intervention, and treatment are related to the lack of theoretical background as well as to insufficient models to test the efficacy of anti-aging agents. Melatonin is a prime candidate for slowing the aging process and targeting its underlying pathology. Melatonin has profound gerontoprotective and antioxidant activities. Because enhanced oxidative stress plays a crucial role in the aging process and chronic diseases associated with senescence, the adminstration of a potent amphiphilic antioxidant agent with high bioavailability such as melatonin may become a promising, safe, and effective intervention strategy to slow aging and the initiation and progression of age-related disorders. Investigations on melatonin and its anti-aging activity may be of great benefit in increasing life quality of the elderly.


[Cellular immunologic parameters in thyroid diseases].
Between October 1984 and June 1987 in 45 patients (9 males, 36 females) pre- and postoperatively the immunocompetent cells in the peripheral blood were measured using OKT- and LEU-11-antigens. 20 patients suffered from malignant and 25 patients from benign diseases. For statistical analysis, H-test according to Kruskal and Wallis was used. Preoperatively, the total account of T-lymphocytes was decreased in patients with thyroid carcinomas, but showed no differences compound to patients with benign diseases postoperatively. No differences were observed in lymphocytic subpopulations in all groups. Parallely, in 50 patients (14 males, 36 females) immunocompetent cells were counted in the resected specimens. There were investigated 29 carcinomas and 21 benign thyroid lesions using the LEU-antigens. Between the group with malignant diseases and that with benigne lesions of the thyroid, no statistically significant differences were observed.


3D Light-Sheet Fluorescence Microscopy of Cranial Neurons and Vasculature during Zebrafish Embryogenesis.
Precise 3D spatial mapping of cells and their connections within living tissues is required to fully understand developmental processes and neural activities. Zebrafish embryos are relatively small and optically transparent, making them the vertebrate model of choice for live in vivo imaging. However, embryonic brains cannot be imaged in their entirety by confocal or two-photon microscopy due to limitations in optical range and scanning speed. Here, we use light-sheet fluorescence microscopy to overcome these limitations and image the entire head of live transgenic zebrafish embryos. We simultaneously imaged cranial neurons and blood vessels during embryogenesis, generating comprehensive 3D maps that provide insight into the coordinated morphogenesis of the nervous system and vasculature during early development. In addition, blood cells circulating through the entire head, vagal and cardiac vasculature were also visualized at high resolution in a 3D movie. These data provide the foundation for the construction of a complete 4D atlas of zebrafish embryogenesis and neural activity.


Calcium dynamics in dendritic spines and spine motility.
A dendritic spine is an intracellular compartment in synapses of central neurons. The role of the fast twitching of spines, brought about by a transient rise of internal calcium concentration above that of the parent dendrite, has been hitherto unclear. We propose an explanation of the cause and effect of the twitching and its role in the functioning of the spine as a fast calcium compartment. Our molecular model postulates that rapid spine motility is due to the concerted contraction of calcium-binding proteins. The contraction induces a stream of cytoplasmic fluid in the direction of the dendritic shaft, thus speeding up the time course of spine calcium dynamics, relative to pure diffusion. Simulations indicate that chemical reaction rate theory at the molecular level can explain spine motility. They reveal two time periods in calcium dynamics, as measured recently by other researchers. It appears that rapid motility in dendritic spines increases the efficiency of calcium conduction to the dendrite and speeds up the emptying of the spine. This could play a major role in the induction of synaptic plasticity. A prediction of the model is that alteration of spine motility will modify the time course of calcium in the dendritic spine and could be tested experimentally.


An Innovative Nurse Practitioner Curricular Design Using an Adaptive Learning Platform, Adaptive Case Studies, and Telehealth Simulations: A Feasibility Study.
This project explored the feasibility of implementing an innovative cross-curricular framework using an adaptive learning (AL) platform and telehealth simulations. To determine the feasibility of implementing an innovative cross-curricular framework using an AL platform and telehealth simulations. A mixed-method pilot study was conducted using novel AL modules, adaptive case studies, and telehealth simulation. Quantitative data analysis demonstrated significant correlations within and across demographics using the Technology Acceptance Model (TAM) and Simulation Effectiveness Tool-Modified (SET-M). Specifically, significant correlations are evident between TAM ease of use items 1-6, 8, and 10 and TAM usefulness 1, 3, and 9, with SET-M items 3 and 5-15. Thematic analysis revealed that participants felt that the overall project was worthwhile and increased confidence in telehealth. Participants found the technology used in this study was easy and useful, and they indicated a positive experience with telehealth simulation. Overall, this study demonstrated that implementation of AL using our paradigm is feasible and supports further investigation into implementing a cross-curricular framework using an AL platform and telehealth simulations.


Pharmacological stimulation of nuclear factor (erythroid-derived 2)-like 2 translation activates antioxidant responses.
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcriptional, translational, and post-translational levels. It is well-known that Nrf2 is regulated at the protein level by proteasomal degradation via Kelch-like ECH-associated protein 1 (Keap1), but how Nrf2 is regulated at the translational level is less clear. Here, we show that pharmacological stimulation increases Nrf2 levels by overcoming basal translational repression. We developed a novel reporter assay that enabled identification of natural compounds that induce Nrf2 translation by a mechanism independent of Keap1-mediated degradation. Apigenin, resveratrol, and piceatannol all induced Nrf2 translation. More importantly, the pharmacologically induced Nrf2 overcomes Keap1 regulation, translocates to the nucleus, and activates the antioxidant response. We conclude that translational regulation controls physiological levels of Nrf2, and this can be modulated by apigenin, resveratrol, and piceatannol. Also, targeting this mechanism with novel compounds could provide new insights into prevention and treatment of multiple diseases in which oxidative stress plays a significant role.


A phosphoglucomutase-like gene essential for the optimal expression of methicillin resistance in Staphylococcus aureus: molecular cloning and DNA sequencing.
We describe here the cloning and sequencing of a new auxiliary gene identified by Tn551 insertional mutagenesis of the highly and homogeneously methicillin-resistant Staphylococcus aureus strain COL. The insertionally inactivated mutant RUSA315 had intact mecA and normal amounts of PBP2A, but drastically reduced antibiotic resistance (drop in methicillin MIC from 1600 to 1.5 micrograms ml-1), a unique heterogeneous phenotype, and a compositional change in the cell wall characterized by the complete disappearance of the unsubstituted disaccharide pentapeptide from the peptidoglycan. Cloning in E. coli followed by sequencing located the Tn551 insert omega 720 in an open reading frame of 451 codons, provisionally called femR315, defining a polypeptide with a deduced amino acid sequence that showed over 26% sequence identity and 57% overall sequence similarity with the phosphoglucomutase (PGM) gene of E. coli. The Tn551 insertion site of a previously described mutant 12F (femD) also lies in the same gene as femR315. The wild-type form of femR315 subcloned in a shuttle vector fully restored expression of high level (parental) methicillin resistance in mutant RUSA315. The exact biochemical function of femR315 is not known. However, enzymes similar to PGM catalyze the isomerization of hexose and hexosamine phosphates leading to the formation of glucosamine-1-P, which is an obligate precursor in the biosynthesis of UDP-N-acetylglucosamine (UDP-NAGA). We propose that the suppression of methicillin resistance in RUSA315 is related to some functional or quantitative abnormality of UDP-NAGA metabolism.


Minimally invasive osteosynthesis of adult tibia fractures by means of rigid fixation with anatomic locked plates.
Main principle of biological fixation by minimally invasive locked plate osteosynthesis (MILPO) in lower extremity long bone fractures is relative stability which is provided by using long plate with limited number of screws. Some biomechanical studies have been reported about this issue. However, clinical studies are still missing. The aims of this retrospective extended case series were to evaluate the clinical and radiological results of adult tibia fractures treated by MILPO and the effect of plate length and screw density on complication rates. Twenty tibia fractures in 19 patients (mean age 42.3 years) operated by MILPO were reviewed. According to the AO classification, diaphyseal and metaphyseal fractures without intraarticular extensions were simple and wedge-type fractures, whereas all intraarticular fractures were comminuted. Number of screws, cortices and empty screw holes proximal and distal to the fracture, plate-span ratio (plate length divided by overall fracture length), plate-screw density (number of inserted screws divided by number of plate holes), fixation failures, delayed or nonunion, malalignment and leg length discrepancy were documented. Mean follow-up was 16 (range 12-26) months. On average, 4 screws with 6 cortices were used both proximally and distally in all fractures. Only in diaphyseal fractures, one screw hole close to the fracture was omitted. Average plate-screw density and plate-span ratio were 0.68 and 4, respectively. Mean union time was 3 months. There were no cases of delayed or nonunion on the final follow-up. Plate bending was observed in one patient who had fair result. The remaining 18 (94.8 %) patients showed good and excellent results. Satisfactory results can be achieved despite low plate-span ratio and high plate-screw density in simple and wedge-type diaphyseal fractures of the tibia. Additionally, plate-screw density can be higher at metaphysis in intraarticular fractures, in which essential point is a perfectly stable fixation that provides early motion.


Candidate pathogenicity factor/effector proteins of 'Candidatus Phytoplasma solani' modulate plant carbohydrate metabolism, accelerate the ascorbate-glutathione cycle, and induce autophagosomes.
The pathogenicity of intracellular plant pathogenic bacteria is associated with the action of pathogenicity factors/effectors, but their physiological roles for most phytoplasma species, including 'Candidiatus Phytoplasma solani' are unknown. Six putative pathogenicity factors/effectors from six different strains of 'Ca. P. solani' were selected by bioinformatic analysis. The way in which they manipulate the host cellular machinery was elucidated by analyzing Nicotiana benthamiana leaves after Agrobacterium-mediated transient transformation with the pathogenicity factor/effector constructs using confocal microscopy, pull-down, and co-immunoprecipitation, and enzyme assays. Candidate pathogenicity factors/effectors were shown to modulate plant carbohydrate metabolism and the ascorbate-glutathione cycle and to induce autophagosomes. PoStoSP06, PoStoSP13, and PoStoSP28 were localized in the nucleus and cytosol. The most active effector in the processes studied was PoStoSP06. PoStoSP18 was associated with an increase in phosphoglucomutase activity, whereas PoStoSP28, previously annotated as an antigenic membrane protein StAMP, specifically interacted with phosphoglucomutase. PoStoSP04 induced only the ascorbate-glutathione cycle along with other pathogenicity factors/effectors. Candidate pathogenicity factors/effectors were involved in reprogramming host carbohydrate metabolism in favor of phytoplasma own growth and infection. They were specifically associated with three distinct metabolic pathways leading to fructose-6-phosphate as an input substrate for glycolysis. The possible significance of autophagosome induction by PoStoSP28 is discussed.


Role of the steroid receptor coactivator SRC-3 in cell growth.
Steroid receptor coactivator 3 (SRC-3/p/CIP/AIB1/ACTR/RAC3/TRAM-1) is a member of the p160 family of nuclear receptor coactivators, which includes SRC-1 (NCoA-1) and SRC-2 (TIF2/GRIP1/NCoA2). Previous studies indicate that SRC-3 is required for normal animal growth and is often amplified or overexpressed in many cancers, including breast and prostate cancers. However, the mechanisms of SRC-3-mediated growth regulation remain unclear. In this study, we show that overexpression of SRC-3 stimulates cell growth to increase cell size in prostate cancer cell lines. Furthermore, our results indicate that overexpression of SRC-3 can modulate the AKT signaling pathway in a steroid-independent manner, which results in the activation of AKT/mTOR signaling concomitant with an increase in cell size. In contrast, down-regulation of SRC-3 expression in cells by small interfering RNA decreases cell growth, leading to a smaller cell size. Similarly, in SRC-3 null mutant mice, AKT signaling is down-regulated in normally SRC-3-expressing tissues. Taken together, these results suggest that SRC-3 is an important modulator for mammalian cell growth.


Low Dose Dexmedetomidine Attenuates Hemodynamic Response to Skull Pin Holder Application.
The application of skull pin holder elicits an adverse hemodynamic response that can be deleterious; there are many drugs that have been used to attenuate this response. We have conducted this study to evaluate the efficacy of intravenous (i.v.) dexmedetomidine on attenuation of hemodynamic responses to skull pin head holder application and to compare the effectiveness of two doses of i.v. dexmedetomidine (1 μg/kg and 0.5 μg/kg bolus). Ninety American Society of Anesthesiologists physical Status I-III patients undergoing craniotomy were randomized into three groups of thirty each. After intubation, patients in Group A received 1 μg/kg of i.v. dexmedetomidine, Group B received 0.5 μg/kg of i.v. dexmedetomidine, whereas Group C received an equivalent quantity of normal saline. Hemodynamic parameters were monitored regularly after skull pin insertion. There was no significant difference in the monitored hemodynamic parameters among the three groups from baseline until intubation. Heart rate (HR) and mean arterial pressure (MAP) increased significantly at skull pin insertion and subsequent points in Group C, whereas the values decreased in Groups A and B (P < 0.05). Patients in Group A showed a higher and sustained attenuation of MAP. Patients in Group C had a higher incidence of tachycardia and hypertension requiring additional measures to attenuate the response. Dexmedetomidine in either dosage (1 μg/kg or 0.5 μg/kg) was effective in attenuating hemodynamic response to skull pin insertion. Dexmedetomidine in doses of 0.5 μg/kg was as effective in attenuating the HR and MAP response to skull pin insertion as compared to a dose of 1 μg/kg.


Cell growth suppression of astrocytoma C6 cells by glial fibrillary acidic protein cDNA transfection.
The cellular functions of the intermediate filament family including glial fibrillary acidic protein (GFAP) are not well known yet beyond their roles as structural elements of cells. Expression of GFAP, which is specific in astrocytes and regulated developmentally, suggests its involvement in cell growth and differentiation of astrocytes. We transfected murine GFAP cDNA into a rat astrocytoma C6 cell line to assess the specific effect of GFAP on cells. Two stable GFAP-transfected cell lines, GFC6-5 and GFC6-6, exhibited a series of morphological and growth characteristics that distinguish them from their counterparts, i.e., NeoC6 cells transfected only with the neomycin-resistant gene, and native C6 cells. Both GFC6-5 and GFC6-6 cells showed elongated cell shapes with extended processes rich in GFAP, markedly suppressed cell growth, and decreased bromodeoxyuridine uptake. Western blot analysis revealed a remarkable increase of GFAP expression in GFC6-5 and GFC6-6 compared with that in NeoC6 and C6, in contrast to similar vimentin expression in all cell lines. The results indicate that the expression of GFAP has dramatic effects on cell morphology and cell growth suppression in C6 cells, suggesting that GFAP may function as a tumor suppressor in astrocytoma.


Percutaneous radiofrequency ablation near large vessels in beagle livers: the impact of time and distance on the ablation zone.
To investigate the effects of ablation time and distance between the radiofrequency ablation (RFA) electrode tip and a large vessel on the ablation zone in beagle livers. Sixty-one percutaneous RFA coagulation zones were created near large vessels in 10 beagle livers in vivo. The ablated lesions were divided into four groups based on ablation time and distance between the electrode tip and a large vessel (group A, 3 min 0.5 cm; group B, 3 min 0 cm; group C, 5 min 0.5 cm; group D, 5 min 0 cm). The ablated area, long-axis diameters, short-axis diameters, and vessel wall injury were examined. With a fixed ablation time, the ablation zone created with the electrode tip at 0.5 cm from the large vessel was significantly larger than at 0 cm (p < .05). At a fixed distance between the electrode tip and vessel, the ablation zone created for 5 min was significantly larger than for 3 min (p < .05). The frequency of vessel wall injury in the 0 cm groups was significantly higher than that in the 0.5 cm groups (37.5% vs. 6.9%; p = .003, odds ratio, 7.43). The ratio of width to depth (Dw/Dz) was larger in the 0.5 cm groups than in the 0 cm groups (p < .001). The ablation zone increased with longer ablation times and greater distances between the RFA tip and large vessels for perivascular lesions. The distance between the needle tip and blood vessels is an important factor that affects the overall ablation outcome.


Neuroepithelial bodies and solitary neuroendocrine cells in the lungs of amphibia.
In the lungs of 12 species of Amphibia investigated so far, solitary neuroendocrine (NE) cells, as well as groups of these cells called "neuroepithelial bodies" (NEB), are observed. They occur in the position strategic to monitoring gas composition, mainly in the ciliated epithelium of the apical part of the septa. A great diversity in the structure of NEB is observed. The NE cells and NEB in Amphibia are predominantly of the "closed type," separated from the air space by a thin cytoplasmic layer of ciliated cells, goblet cells or pneumocytes. In two species, Bufo marinus and Ambystoma tigrinum, the "open type" of NEB occur, where NEB communicate with the air space, by apical cells in Bufo and type II NE cells in Ambystoma. Both types of cells possess single atypical cilia with an 8+1 microtubule arrangement and microvilli on the free surface. Single and grouped NE cells are characterized by small dense core vesicles (DCV) dispersed in the cytoplasm. In Salamandra and Ambystoma the second type of NE cells with large DCV are observed. The DCV represent sites of storage of serotonin and several neuropeptides. The basal parts of NEB and of some solitary cells are invested by the intraepithelial sensory nerve terminals, both afferent and efferent morphologically. In the lungs of Amphibia, similarly to other vertebrates, NE cells, which act as endocrine/paracrine receptors, form epithelial endocrine systems.


Examining the Impact of Maternal Individual Features on Children's Behavioral Problems in Adoptive Families: The Role of Maternal Temperament and Neurobiological Markers.
The first year after adoption constitutes a sensitive period for both strengthening the new emotional bond in the family and checking its appropriate development by adoption services. A key variable for children's catch-up are adoptive parents' socioemotional and individual features. The aim of this study is to investigate links between adoptive mothers' individual features and behavioral problems in their children in the first year after adoption placement, by testing the moderating role of both age at adoption and maternal genetic polymorphisms. Seventy-eight adoptive mothers completed temperament and genetic measures. Mothers showed a specific pattern of interaction between basic temperament traits and genetic markers in their assessment of children's behavioral problems; dopamine D4 receptor gene and children's age at adoption are two moderators in the association in which mothers' temperament was affecting the evaluation of their children's behavioral problems. Findings highlight a still undervalued area of parenting resources in the process of post-institutionalized children's catch-up after adoption placement, by showing how individual features count in the commonly measured variable of children's behavioral and emotional problems. This could help in orienting identification and choice of key variables for family assessment after adoption placement, thus contributing in fostering children's healthy development.


Non-Hebbian properties of long-term potentiation enable high-capacity encoding of temporal sequences.
A hypothesis commonly found in biological and computational studies of synaptic plasticity embodies a version of the 1949 postulate of Hebb that coactivity of pre- and postsynaptic elements results in increased efficacy of their synaptic contacts. This general proposal presaged the identification of the first and still only known long-lasting synaptic plasticity mechanism, long-term potentiation (LTP). Yet the detailed physiology of LTP induction and expression differs in many specifics from Hebb's rule. Incorporation of these physiological LTP constraints into a simple non-Hebbian network model enabled development of "sequence detectors" that respond preferentially to the sequences on which they were trained. The network was found to have unexpected capacity (e.g., 50 x 10(6) random sequences in a network of 10(5) cells), which scales linearly with network size, thereby addressing the question of memory capacity in brain circuitry of realistic size.


Serum cholesterol determined by liquid chromatography with 6-chlorostigmasterol as internal standard.
We describe an accurate and precise method for determining serum cholesterol by high-performance liquid chromatography (HPLC). After addition of 6-chlorostigmasterol as internal standard, serum is treated with alcoholic potassium hydroxide. Subsequently the cholesterol and internal standard are extracted from the mixture into n-hexane and then derivatized to phenylurethanes for measurement by HPLC with ultraviolet detection. The effective chromatographic separation and the use of an appropriate internal standard make this procedure free from interferences by other serum sterols and precise. The mean cholesterol concentration in Standard Reference Material (SRM) 909 (human serum) assayed by this procedure (4.346 mmol.g-1 x L-1) agreed well with the value assigned by the National Institute of Standards and Technology (4.359 mmol.g-1 x L-1). Within-run and total CVs were 0.56% and 0.78%, respectively. Therefore the performance of this procedure is sufficiently good to allow its use as a candidate reference method for serum cholesterol determination.


Inflammatory and hyperalgesic effects of oxidized multi-walled carbon nanotubes in rats.
We evaluated local inflammatory activity of oxidized multiwalled carbon nanotubes in rat experimental models of acute inflammation (paw edema and hyperalgesia) by analyzing their toxicity in non-mesoendothelial tissues. Subcutaneous injection of the nanotubes induced paw edema, that was maximal in the first 2 h after administration at 0.1 mg/kg (43.25 +/- 3.8 AUC) and 1 mg/kg (30.1 +/- 1.8 AUC) compared to saline (18.32 +/- 02.05 AUC). The histopathological analysis showed acute inflammation characterized by vasodilatation, edema formation, neutrophil infiltrate and tissue damage. The nanotubes also elicited hyperalgesic response, seen by the increase of animal paw withdrawal that was maximal in the first 3 hours. The data obtained at the 3rd h was: 75 +/- 9.3% (0.01 mg/kg), 58 +/- 8.3% (0.1 mg/kg) and 53 +/- 6.69% (1 mg/kg) in relation with saline (28 +/- 3.5%). In conclusion, the oxidized multiwalled carbon nanotubes elicit inflammatory and hyperalgesic effects associated to severe tissue damage in rats.


A Qualitative Exploration of Nurse Faculty Experiences Related to the Sudden Unanticipated Death of a Nursing Student.
Nurse faculty serve as teachers, role models, and mentors to nursing students. This unique relationship results in a myriad of feelings when a student dies. Limited research exists in examining faculty grief related to the sudden unanticipated death of a nursing student. To explore the experiences of nurse faculty following the sudden unanticipated death of a nursing student. Researchers conducted a phenomenological qualitative study. The source of qualitative data included a demographic questionnaire and in-depth interviews with 13 participants throughout the geographical regions of the United States. Six following themes emerged: (1) leadership response, (2) grief experience, (3) role uncertainty, (4) grief triggers, (5) cannot help but think what if, and (6) acknowledging a life unfulfilled. This study yields a rich understanding of the unique grief experiences of nurse faculty, warranting the need for further dialogue, faculty education, policy development, and supportive interventions for faculty and administrative leaders.


Association of interleukin-10-1082 G/G genotype with lower mortality of acute respiratory distress syndrome in a Chinese population.
We investigate whether interleukin-10 (IL-10)-1082 G/G genotype is associated with the mortality rate of acute respiratory distress syndrome (ARDS) in a hospital-based case-control study in China conducted on 314 patients with ARDS and 210 controls admitted to an intensive care unit for sepsis, trauma, aspiration, or massive transfusions. IL-10-1082 promoter polymorphisms were analyzed with polymerase chain reaction amplification followed by restriction fragment length polymorphism. Mortality was recorded if it occurred within 30 days from admission. The -1082G/G genotype was associated with lower frequency of ARDS (odds ratios=0.51; 95% confidence intervals: 0.34-0.76; p=0.001), and in patients with ARDS, it was associated with lower mortality within 30 days (odds ratios=0.44; 95% confidence intervals: 0.25-0.76; p=0.003) than in controls. We conclude that IL-10-1082 G/G genotype is associated with a decreased rate development of ARDS and mortality in this Chinese population.


Ternary I-III-VI quantum dots luminescent in the red to near-infrared.
We report the synthesis of a size series of copper indium selenide quantum dots (QDs) of various stoichiometries exhibiting photoluminescence (PL) from the red to near-infrared (NIR). The synthetic method is modular, and we have extended it to the synthesis of luminescent silver indium diselenide QDs. Previous reports on QDs luminescent in the NIR region have been primarily restricted to binary semiconductor systems, such as InAs, PbS, and CdTe. This work seeks to expand the availability of luminescent QD materials to ternary I-III-VI semiconductor systems.


Expectations for ambulatory services in traditional and office-practice pharmacies.
Expectation for and satisfaction with pharmaceutical services reported by patrons of an office-practice pharmacy were compared with those of patrons of a traditional pharmacy. In a rural town served by a traditional pharmacy and an office-practice pharmacy, questionnaires were sent in May 1980 to 25% of the households listed in the telephone directory. The questionnaire elicited respondent characteristics, pharmacy-use patterns, and expectation and satisfaction levels for 16 pharmaceutical services described in the APhA- AACP standards of practice. Overall mean expectation and satisfaction scores were computed. Sixty-two percent of the 529 questionnaires were returned. Of the respondents, 39% patronized the office practice exclusively, 44% the traditional pharmacy. Patrons of the office practice expressed significantly higher expectation and satisfaction scores than patrons of the traditional pharmacy. Patrons of the office-practice pharmacy also reported more frequent consultation with a pharmacist regarding drug-therapy and health issues. Controlling for the frequency of contact, office-practice patrons still reported higher expectation and satisfaction scores. Only 18% of office-practice patrons reported purchasing nonprescription drugs in a pharmacy compared with 42% of the patrons of the traditional pharmacy. By providing pharmacist contact in an appropriate ambulatory setting, increased patient satisfaction with and expectations for pharmaceutical services may ensue.


Adding fast-acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18-week, open-label, phase 3 trial (onset 3).
To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen vs basal-only insulin. In this open-label, randomized, 18-week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimization of prior once-daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment-emergent adverse events; hypoglycaemic episodes. HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal-only group); estimated treatment difference [95% confidence interval] -0.94% [-1.17; -0.72]; -10.3 mmol/mol [-12.8; -7.8]; P < .0001. Reductions from baseline in overall mean 2-hour PPG and overall PPG increment for all meals (self-measured plasma glucose profiles) were statistically significant in favour of BB treatment ( P < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient-years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal-only treatment. In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal-only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.


Novel isoprenylated proteins identified by an expression library screen.
Isoprenylated proteins are involved in eukaryotic cell growth and signal transduction. The protein determinant for prenylation is a short carboxyl-terminal motif containing a cysteine, to which the isoprenoid is covalently attached via thioether linkage. To date, isoprenylated proteins have almost all been identified by demonstrating the attachment of an isoprenoid to previously known proteins. Thus, many isoprenylated proteins probably remain undiscovered. To identify novel isoprenylated proteins for subsequent biochemical study, colony blots of a Glycine max cDNA expression library were [3H]farnesyl-labeled in vitro. Proteins identified by this screen contained several different carboxyl termini that conform to consensus farnesylation motifs. These proteins included known farnesylated proteins (DnaJ homologs) and several novel proteins, two of which contained six or more tandem repeats of a hexapeptide having the consensus sequence (E/G)(G/P)EK(P/K)K. Thus, plants contain a diverse array of genes encoding farnesylated proteins, and our results indicate that fundamental differences in the identities of farnesylated proteins may exist between plants and other eukaryotes. Expression library screening by direct labeling can be adapted to identify isoprenylated proteins from other organisms, as well as proteins with other post-translational modifications.


Synthesis and renin inhibitory properties of a new soluble pepstatin derivative.
A new pepstatin derivative, pepstatinyl arginine methyl ester hydrochloride (pepstatinyl-Arg-O-Me), was synthesized with the aim of increasing water solubility without altering capacity to inhibit the renin-angiotensinogen reaction. Pepstatinyl-Arg-O-Me was shown to inhibit in vitro the reaction between either rat or purified hog renin and the natural rat renin substrate. In a fluorimetric assay, this derivative competitively inhibited the reaction between purified hog renin and a synthetic N-acetyl-tetradecapeptide renin substrate with a Ki of the same order of magnitude as that of pepstatin. In urethaneanesthetized ganglion-blocked rats, binephrectomized 24 hr before the experiments, both the plasma reinin concentration and the rise in blood pressure following intravenous injection of hog renin were inhibited by pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-O-Me inhibited the 1.4 mumoles/kg. The in vivo inhibitory effect of 1.4 mumoles/kg of pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-Op-Me inhibited the reaction of endogenous and exogenous renin with plasma substrate both in vitro and in vivo.


Geometric constraints on neuronal connectivity facilitate a concise synaptic adhesive code.
The nervous system contains trillions of neurons, each forming thousands of synaptic connections. It has been suggested that this complex connectivity is determined by a synaptic "adhesive code," where connections are dictated by a variable set of cell surface proteins, combinations of which form neuronal addresses. The estimated number of neuronal addresses is orders of magnitude smaller than the number of neurons. Here, we show that the limited number of addresses dictates constraints on the possible neuronal network topologies. We show that to encode arbitrary networks, in which each neuron can potentially connect to any other neuron, the number of neuronal addresses needed scales linearly with network size. In contrast, the number of addresses needed to encode the wiring of geometric networks grows only as the square root of network size. The more efficient encoding in geometric networks is achieved through the reutilization of the same addresses in physically independent portions of the network. We also find that ordered geometric networks, in which the same connectivity patterns are iterated throughout the network, further reduce the required number of addresses. We demonstrate our findings using simulated networks and the C. elegans neuronal network. Geometric neuronal connectivity with recurring connectivity patterns have been suggested to confer an evolutionary advantage by saving biochemical resources on the one hand and reutilizing functionally efficient neuronal circuits. Our study suggests an additional advantage of these prominent topological features--the facilitation of the ability to genetically encode neuronal networks given constraints on the number of addresses.


Cyclic GMP synthesis by human retinal pigment epithelial cells is mainly mediated via the particulate guanylyl cyclase pathway.
Cyclic 3',5'-guanosine monophosphate (cGMP), a central molecule in the phototransduction cascade, is also involved in a number of other physiological processes in the retina, like stimulating the absorption of subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump. The aim of this study was to quantify cGMP synthesis by RPE cells and to investigate the role of two separate enzymatic pathways (soluble versus particulate guanylyl cyclase) in its production. cGMP expression was evaluated by immunochemistry and radioimmunoassay following culture of the D407 RPE cell line in the presence of a nonselective phosphodiesterase inhibitor (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). Stimulation of the particulate guanylyl cyclase in RPE cells with ANP resulted in high intra- and extracellular cGMP levels. Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation of cGMP levels compared to controls. These results show that cultured human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the particulate guanylyl cyclase pathway.


Combining ctnnb1 genetic variability with epidemiologic factors to predict lung cancer susceptibility.
Early detection and diagnosis of lung cancer remain challenging but would improve patient prognosis. The goal of this study is to develop a model to estimate the risk of lung cancer for a given individual. We conducted a case-control study to develop a predictive model to identify individuals at high risk for lung cancer. Clinical data from 500 lung cancer patients and 500 population-based age- and gender-matched controls were used to develop and evaluate the model. Associations between environmental variants together with single nucleotide polymorphisms (SNPs) of beta-catenin (ctnnb1) and lung cancer risk were analyzed using a logistic regression model. The predictive accuracy of the model was determined by calculating the area under the receiver operating characteristic (ROC) curve. Prior diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis, family history of cancer, and smoking are lung cancer risk factors. The area under the curve (AUC) was 0.740, and the sensitivity, specificity, and Youden index were 0.718, 0.660, and 0.378, respectively. Our risk prediction model for lung cancer is useful for distinguishing high-risk individuals.


Filling cavities or restoring teeth?
Teeth seldom fracture under normal functional loading. This indicates that the natural tooth design is optimized for the distribution of regular masticatory forces by means of its properties and structure. When a tooth is restored with an intracoronal restoration, however, the incidence of tooth fracture increases. Since remaining tissues do not change, the restorative actions apparently alter the original stress distributions. In this study, the effect of different restoration types (unbonded amalgam and bonded composite restorations) were compared with the original stress conditions of the intact tooth, using finite element analysis. It was shown that an unbonded amalgam restoration did not restore the original stress conditions but led to much higher stresses in the buccal and lingual enamel and to higher tensile stresses in the cavity floor. The unbonded amalgam thus filled the cavity but did not restore the tooth. In contrast, a bonded composite restoration restored the original stress pattern in the tooth if there was no polymerization shrinkage. Polymerization shrinkage causes residual tensile stresses in the dentin around the cavity and in the buccal and lingual enamel. Residual tensile stresses in the buccal and lingual enamel are momentary compensated by compressive stress components during occlusal loading. It was concluded that bonding and elimination of residual stresses are prerequisites for restoring the original tooth integrity.


Burden of Anemia among Human Immunodeficiency Virus-Positive Adults on Highly Active Antiretroviral Therapy at Hawassa University Compressive Specialized Hospital, Hawassa, Ethiopia.
Anemia is the most common hematologic abnormality associated with human immunodeficiency virus (HIV)-infected patients and affects 60% to 80% of patients in late-stage disease. It has a considerable impact on the progression of HIV to advanced stages. This study aimed at assessing the burden of anemia in adult HIV-infected patients who are on highly active antiretroviral therapy (HAART) and have follow-up at Hawassa University Comprehensive Specialized Hospital (HUCSH) Antiretroviral therapy (ART) clinic. A hospital-based retrospective study was conducted among HIV-positive adults on HAART at Hawassa University Compressive Specialized Hospital. The systematic sampling method was used to choose a total of 244 study participants. Data on demographic characteristics, related factors of anemia, latest hemoglobin, CD4, and ART regimens were collected using a structured data abstraction format. The data were cleaned and analyzed using SPSS version 21.0 after being manually checked for completeness. Multivariable logistic regression was carried out to detect elements associated with anemia. A P value of <0.05 was used as a cutoff point to announce statistical significance. The records of 244 patients were examined in total. Anemia was present in 29.9% (95% CI 23.8-35.2) among adult HIV patients. Female sex (AOR: 2.576, 95% (CI: 1.295-5.127)), having tuberculosis (TB) (AOR: 4.873, 95% (CI: 1.534-15.484)), taking a zidovudine (ZDV)-containing ART regimen (AOR: 5.216, 95% (CI: 1.239-21.962)), having clinical WHO stage IV and III diseases (AOR: 3.077, 95% CI (1.244-7.612)), having body mass index (BMI) <18.5 kg/m2 (AOR: 2.391, 95% (CI: 1.138-5.023)), and taking cotrimoxazole prophylaxis (AOR: 3.860 95% (CI: 1.097-13.576)) were substantially linked to the development of anemia among adult HIV patients. Conclusion and Recommendation. This study showed that anemia is still a problem among HIV patients on HAART. The burden of anemia was found to be high among patients with advanced WHO clinical stages, having a BMI less than 18.5 kg/m2, TB/HIV coinfection, being on AZT-based ART regimens, and taking cotrimoxazole preventive therapy (CPT). Consequently, it is suggested that early preventative interventions, such as serial hemoglobin follow-up, iron supplementation, and education about dietary consumption, be undertaken targeting the aforementioned groups. In addition, the preferred first-line ART regimen as per the latest national and WHO guidelines is recommended, especially for the above groups.


LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases.
Lipid metabolism is an essential biological process involved in nutrient adjustment, hormone regulation, and lipid homeostasis. An irregular lifestyle and long-term nutrient overload can cause lipid-related diseases, including atherosclerosis, myocardial infarction (MI), obesity, and fatty liver diseases. Thus, novel tools for efficient diagnosis and treatment of dysfunctional lipid metabolism are urgently required. Furthermore, it is known that lncRNAs based regulation like sponging microRNAs (miRNAs) or serving as a reservoir for microRNAs play an essential role in the progression of lipid-related diseases. Accordingly, a better understanding of the regulatory roles of lncRNAs in lipid-related diseases would provide the basis for identifying potential biomarkers and therapeutic targets for lipid-related diseases. This review highlighted the latest advances on the potential biomarkers of lncRNAs in lipid-related diseases and summarised current knowledge on dysregulated lncRNAs and their potential molecular mechanisms. We have also provided novel insights into the underlying mechanisms of lncRNAs which might serve as potential biomarkers and therapeutic targets for lipid-related diseases. The information presented here may be useful for designing future studies and advancing investigations of lncRNAs as biomarkers for diagnosis, prognosis, and therapy of lipid-related diseases.


General and Specific Effects of Stereo Learning.
Technological advancements in virtual reality challenge the human vision, especially stereopsis, a function, which characterizes how two eyes coordinate to form a unified three-dimensional (3D) representation of the external world and is found to be deficient in 30% of the normal population. Although a few previous studies have consistently found that the perceptual learning of stereopsis significantly improved stereoacuity, an underlying mechanism of stereo learning remains heavily debated. Here, we trained subjects with normal stereo vision (assessed with the FLY Stereo Acuity Test) to judge stereopsis containing three types of binocular disparity orders (i.e., zero-, first-, and second-order), aiming to systematically examine the characteristics and plasticity of stereo learning. Thirty subjects were randomly assigned to the three training groups (each for the zero-, first-, or second-order disparity separately). The disparity thresholds were measured before and after training. The disparity threshold was measured in 10 additional control subjects only at the pre- and post-training phase. Stereoscopic images were displayed through a shutter goggle, which is synchronized to a monitor. We found that the training significantly improved the zero-, first-, and second-order disparity threshold by 52.42, 36.28, and 14.9% in the zero-order training condition; 30.44, 63.74, and 21.07% in the first-order training condition; and 30.77, 25.19, and 75.12% in the second-order training condition, respectively. There was no significant improvement in the control group. Interestingly, the greatest improvements in the first- and second-order disparity threshold were found in the corresponding disparity training group; on the contrary, the improvements in the zero-order disparity threshold were comparable across all the three disparity training groups. Our findings demonstrated both general (related to the zero-order disparity) and specific improvements (related to the first- and second-order disparity) in stereo learning, suggesting that stereo training occurs at different visual processing stages and its effects might depend on the specific training sites.


Asymptotic Tracking Control for Uncertain Nonlinear Strict-Feedback Systems With Unknown Time-Varying Delays.
It is nontrivial to achieve asymptotic tracking control for uncertain nonlinear strict-feedback systems with unknown time-varying delays. This problem becomes even more challenging if the control direction is unknown. To address such problem, the Lyapunov-Krasovskii functional (LKF) is used to deal with the time delays, and the neural network (NN) is applied to compensate for the time-delay-free yet unknown terms arising from the derivative of LKF, and then an NN-based adaptive control scheme is constructed on the basis of backstepping technique, which enables the output tracking error to converge to zero asymptotically. Besides, with a milder condition on time delay functions, the notorious singularity issue commonly encountered in coping with time delay problems is subtly settled, which makes the proposed scheme simple in structure and inexpensive in computation. Moreover, all the signals in the closed-loop system are ensured to be semiglobally uniformly ultimately bounded, and the transient performance can be improved with proper choice of design parameters. Both the theoretical analysis and numerical simulation are carried out to validate the relevance of the proposed method.


A 10-year retrospective review of airline transport pilots aged 60 to 63 in Japan.
On May 14, 1991, the Japanese Ministry of Transport issued an official notice allowing medically certified airline transport pilots aged 60 to 63 yr old (aged pilot) to work on non-scheduled flights. Since September 24, 1996, the official notice was revised to allow them to work on scheduled flights. The regulation requires pilots to pass both routine and additional aviation medical examinations. Ten years have passed since the first regulation, so the medical records and the present status of aged pilots were reviewed and summarized. By the end of October 2000, 159 pilots had undergone their first additional examination. Two pilots failed due to coronary ischemia, two due to brain infarction, and one due to complete right bundle branch block (CRBBB) on ECG. One pilot failed the examination at the age of 62 due to coronary ischemia and another at the age of 62.5 due to atrial fibrillation. Thirteen pilots retired prior to the age of 63 for unknown reasons. At the time of review, 44 pilots had reached the age of 63 and retired. Subsequent flight time as aged pilot was 83,872 h in total (617 +/- 483 h; mean +/- SD) with monthly flight time of 41 +/- 27 h. Japan Aircraft Accident Investigation Commision reported 323 accidents, including 27 airtransport accidents in the past 10 yr. There were no accidents involving any of the aged pilots. The review suggests that the aged pilots who are deemed medically qualified by the official notice criteria are flying safely without mishap incidence.


Lack of disulfiram-like reaction with metronidazole and ethanol.
Metronidazole, an effective antianaerobic agent, has been reported to have aversive properties when ingested with ethanol. This is thought to be due to the blocking of hepatic aldehyde dehydrogenase (ALDH) enzyme followed by the accumulation of acetaldehyde in the blood. However, based on animal studies and on only 10 human case reports, the existence of metronidazole-related disulfiram-like reaction has recently been questioned. To investigate the possible disulfiram-like properties of metronidazole and ethanol in human volunteers. Of 12 healthy male volunteers in this double-blind study, one-half received metronidazole for 5 days and the other half received placebo. All volunteers received ethanol 0.4 g/kg at the beginning of the study. Repeated blood samples were taken every 20 minutes for 4 hours, and blood acetaldehyde and ethanol concentrations were determined. Blood pressure, heart rate, and skin temperature were also measured every 20 minutes for objective signs of a possible disulfiram-like reaction. Volunteers also completed a questionnaire focusing on the subjective signs of disulfiram-like reaction. Metronidazole did not raise blood acetaldehyde or have any objective or subjective adverse effects when used together with ethanol. This study shows that metronidazole does not have an effect on blood acetaldehyde concentrations when ingested with ethanol and does not have any objective or subjective disulfiram-like properties. However, it is possible that disulfiram-like reaction can occur in some subgroups and by other mechanisms than the inhibition of hepatic ALDH.


Intracranial metastasis of a spinal cord astrocytoma--case report.
The authors report a case of cerebral metastasis from a spinal cord astrocytoma. The first metastatic tumor was controlled by radiation therapy. A second metastatic brain tumor was detected 2 years later, but attempts to control it through subtotal removal and chemotherapy failed. Metastasis from a spinal cord tumor to the brain is a rare event.


New Faces in Rural Places: Patterns and Sources of Nonmetropolitan Ethnoracial Diversity Since 1990.
Much of the research on ethnoracial diversity in nonmetropolitan America consists of case studies describing how the arrival of Hispanics has transformed a particular community. To complement this work, we examine the dimensions and sources of diversity for a sample of 10,000 nonmetro places. Two dimensions of diversity-magnitude and structure-are identified, and hypotheses about their changes and correlates are drawn from the spatial assimilation and locational persistence perspectives and relevant scholarship. Our analysis of 1990-2010 decennial census and American Community Survey data documents a pervasive upward trend in diversity magnitude. However, places tend to follow parallel rather than identical diversity trajectories and to retain the same type of racial-ethnic structure in 2010 that they exhibited 20 years earlier. Fixed effects regression models show that ethnoracial diversity gains are most likely in nonmetro communities with plentiful economic opportunities, fewer old residents, and growing total, foreign-born, and correctional populations. These correlates hold for micropolitan and rural places and across census regions. Though our results largely conform to locational persistence logic, we find that spatial assimilation still has some merit, underscoring the importance of incorporating multiple theoretical models in a segmented change perspective on nonmetropolitan diversity.


Application of a navigation system for contouring anatomical plasty of the distal end of the humerus.
The effectiveness of navigation systems in performing accurate orthopaedic surgery has been reported previously, but there have been no reports on the application of navigation in surgeries involving bone resection around the elbow joint. In this study, anatomical plasty or bone resection was performed to restore anatomical morphology in 10 cases of osteoarthritis of the elbow and deformity of the distal end of the humerus. Bone resection was performed on the distal end of the humerus using navigation and on the proximal end of the ulna via freehand surgery. Postoperatively, the elbow function was evaluated and pre- and postoperative CT images were used to measure the bone resection. There were no complications arising from the use of navigation, and elbow function was improved in all cases. By evaluating the CT images, it was found that navigated resection of the fossae of the distal humerus was more effective than freehand resection of the processes of the proximal ulna, thus confirming the usefulness of navigation. In future, to fully confirm this finding, it will be necessary to conduct prospective controlled studies of cases in which navigation is used to perform arthroplasty, including those that involve the proximal end of the ulna.


[Evaluation of social functioning ability of disabled children].
Since 1999, we have been trying to establish a reliable method for evaluating social functioning ability (SFA) of physically handicapped children, in cooperation with the Project of Comprehensive Study of Disability, Social Health, and Welfare supported by the Ministry of Health, Labor and Welfare, Japan. In this study, we investigated the reliability and accuracy of the 4th edition of "The Evaluation of SFA". This evaluation consists of 40 items in 15 areas. We examined 45 disabled patients (26 males and 19 females) aged 12-27 years (mean age, 16 years). The reliability was checked by agreement of evaluations of the same patient carried out by two examiners. The results showed good reliability (kappa value of 0.42). According to the results of questionnaires, 97% of the examiners regarded this evaluation to be useful. Although the score of SFA correlated with intelligent quotient/development quotient, the score did not correlate with motor disability level. We hope that this evaluation will be widely used to upgrade SFA of disabled children.