Benefits of global mutant huntingtin lowering diminish over time in a Huntington's disease mouse model.
We have developed an inducible Huntington's disease (HD) mouse model that allows temporal control of whole-body allele-specific mutant huntingtin (mHtt) expression. We asked whether moderate global lowering of mHtt (~50%) was sufficient for long-term amelioration of HD-related deficits and, if so, whether early mHtt lowering (before measurable deficits) was required. Both early and late mHtt lowering delayed behavioral dysfunction and mHTT protein aggregation, as measured biochemically. However, long-term follow-up revealed that the benefits, in all mHtt-lowering groups, attenuated by 12 months of age. While early mHtt lowering attenuated cortical and striatal transcriptional dysregulation evaluated at 6 months of age, the benefits diminished by 12 months of age, and late mHtt lowering did not ameliorate striatal transcriptional dysregulation at 12 months of age. Only early mHtt lowering delayed the elevation in cerebrospinal fluid neurofilament light chain that we observed in our model starting at 9 months of age. As small-molecule HTT-lowering therapeutics progress to the clinic, our findings suggest that moderate mHtt lowering allows disease progression to continue, albeit at a slower rate, and could be relevant to the degree of mHTT lowering required to sustain long-term benefits in humans.


Perceived age is associated with bone status in women aged 25-93 years.
Higher perceived age (PA) is reported to be associated with age-related diseases. Because osteoporosis is considered an age-related disease, we hypothesized that age perceived from photographs is associated with bone mineral density (BMD)/trabecular bone score (TBS) when controlled for chronological age. This is a cross-sectional study of 460 women aged 25-93 years. BMD/TBS was measured. Twenty physicians assessed age from facial and whole-body photographs. Residual PA (R(PACA)) was calculated from the regression of PA on chronological age. Participants were divided into "looking old" (LO) or "looking young" (LY). Linear mixed models and general linear models fitted with BMD/TBS as outcome and either R(PACA) or LO/LY as an independent variable, considering chronological age. Estimates of R(PACA) were all negative; i.e., an increase in R(PAC) is associated with lower BMD, consistent with the hypothesis (e.g., β -0.29%; 95% confidence interval (CI) 0.55, 0.03). Statistical significance of the association of age-adjusted facial R(PACA) with BMD was found. Adjusted for body mass index (BMI), menopause, and hormone replacement therapy, higher R(PACA) from all photographic presentations were significantly associated with lower BMD based on statistical significance. BMD/TBS was in all analyses higher in the group LY compared with LO, when adjusted for age and BMI (e.g., β 4.37%; 95 CI 0.62, 8.26), but statistical significance was obtained only from the BMD analyses. A higher PA was significantly associated with a lower BMD/TBD, and the size of association in older women indicates that it might have value as part of the clinical assessment of osteoporotic risk.


Prototype Development of the Intelligent Hydrogel Wound Dressing and Its Efficacy in the Detection of Model Pathogenic Wound Biofilms.
The early detection of wound infection in situ can dramatically improve patient care pathways and clinical outcomes. There is increasing evidence that within an infected wound the main bacterial mode of living is a biofilm: a confluent community of adherent bacteria encased in an extracellular polymeric matrix. Here we have reported the development of a prototype wound dressing, which switches on a fluorescent color when in contact with pathogenic wound biofilms. The dressing is made of a hydrated agarose film in which the fluorescent dye containing vesicles were mixed with agarose and dispersed within the hydrogel matrix. The static and dynamic models of wound biofilms, from clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis, were established on nanoporous polycarbonate membrane for 24, 48, and 72 h, and the dressing response to the biofilms on the prototype dressing evaluated. The dressing indicated a clear fluorescent/color response within 4 h, only observed when in contact with biofilms produced by a pathogenic strain. The sensitivity of the dressing to biofilms was dependent on the species and strain types of the bacterial pathogens involved, but a relatively higher response was observed in strains considered good biofilm formers. There was a clear difference in the levels of dressing response, when dressings were tested on bacteria grown in biofilm or in planktonic cultures, suggesting that the level of expression of virulence factors is different depending of the growth mode. Colorimetric detection on wound biofilms of prevalent pathogens (S. aureus, P. aeruginosa, and E. faecalis) is also demonstrated using an ex vivo porcine skin model of burn wound infection.


The blossoming of bioethics at NIH.
The establishment of the Department of Clinical Bioethics at the Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH) has coincided with a burgeoning of interest and activity related to bioethical issues at NIH. The department has precipitated a reexamination and revitalization of existing bioethics activities in the Clinical Center and has launched new programs especially in the areas of education and research. In addition, the department contributes to the work of others throughout NIH who address bioethical issues.


BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac Cushions.
Formation of the cardiac valves is an essential component of cardiovascular development. Consistent with the role of the bone morphogenetic protein (BMP) signaling pathway in cardiac valve formation, embryos that are deficient for the BMP regulator BMPER (BMP-binding endothelial regulator) display the cardiac valve anomaly mitral valve prolapse. However, how BMPER deficiency leads to this defect is unknown. Based on its expression pattern in the developing cardiac cushions, we hypothesized that BMPER regulates BMP2-mediated signaling, leading to fine-tuned epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. In the BMPER-/- embryo, EMT is dysregulated in the atrioventricular and outflow tract cushions compared with their wild-type counterparts, as indicated by a significant increase of Sox9-positive cells during cushion formation. However, proliferation is not impaired in the developing BMPER-/- valves. In vitro data show that BMPER directly binds BMP2. In cultured endothelial cells, BMPER blocks BMP2-induced Smad activation in a dose-dependent manner. In addition, BMP2 increases the Sox9 protein level, and this increase is inhibited by co-treatment with BMPER. Consistently, in the BMPER-/- embryos, semi-quantitative analysis of Smad activation shows that the canonical BMP pathway is significantly more active in the atrioventricular cushions during EMT. These results indicate that BMPER negatively regulates BMP-induced Smad and Sox9 activity during valve development. Together, these results identify BMPER as a regulator of BMP2-induced cardiac valve development and will contribute to our understanding of valvular defects.


Decreased expression of SATB2: a novel independent prognostic marker of worse outcome in laryngeal carcinoma patients.
To investigate the expression and role of special AT-rich sequence-binding protein-2 (SATB2) in laryngeal squamous cell carcinoma (LSCC) tissue and cell line (HEp2), and to evaluate the clinical and prognostic significance of SATB2 protein in patients with LSCC. The expression of SATB2 was examined in LSCC tissue and HEp2 cells by Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth curve assay and colony formation assay were used to verify the effect of SATB2 on the proliferation and tumor progression ability of HEp2 cells. Tumor formation assay in nude mice was used to analyze the effect of SATB2 on the tumorigenicity of HEp2 cells. The status of SATB2 protein in carcinoma tissues is much lower than that in paracarcinoma tissues. The overall survival of the patients with high SATB2 expression was significantly higher than the low SATB2 expression group. Lower or negative SATB2 expression was significantly correlated with advanced clinical staging, histological grade and tumor recurrence. In vitro experiments demonstrated that over-expression of SATB2 in HEp2 cells inhibited cell proliferation and tumor progression ability, and down-regulation of SATB2 showed the opposite effects. Over-expression of SATB2 repressed the tumorigenicity of HEp2 cells by in vivo experiments. Moreover, multivariate analysis suggested that SATB2 expression might be an independent prognostic indicator for the survival of LSCC patients after curative surgery. SATB2 might involve in the development and progression of LSCC as a tumor suppressor, and thereby may be a valuable prognostic marker for LSCC patients.


Chemotherapy port "Twiddler's syndrome". A need for preinjection radiography.
Potentially serious extravasation of vincristine occurred when a chemotherapy port, inadvertently withdrawn from the subclavian vein by the patient, was injected. Plain radiography suggested withdrawal of port tubing which was later proven by contrast injection. The need for awareness of possible patient manipulation of their indwelling ports and routine preinjection radiography is suggested.


Gut lymphomas.
Gut lymphoma still remains the subject of much debate and controversy with respect to pathological classification, clinical staging and treatment. This is mainly due to the fact that most studies reported retrospective non-randomized evaluations of small series and lacked uniformity in histological classification, patients' characteristics and type of treatment. Moreover, most of the historical series were published before the recognition of MALT as the origin of most GI lymphomas. Hence, there is a compelling need for the use of modern histological criteria for primary GI lymphomas because of their unique histology, special features and origin in mucosal tissue. General adoption of the histological classification proposed in 1988 by Isaacson et al (Table 1) can be recommended which follows the general principles of the Kiel Classification and includes the MALT lymphomas as a particular disease entity. Combination chemotherapy is the treatment of choice for gut lymphomas with aggressive histology and multiple node involvement or disseminated disease. The effectiveness of combination chemotherapy in advanced disease has excited a reconsideration of the role of primary surgery in less advanced cases where surgery has, historically, been the initial procedure of choice. This is particularly true for gastric lymphomas where it is possible that, in future, surgery will be resorted to as a potential approach for salvage when complete remission is not achieved with conservative therapy. For primary intestinal lymphoma, however, there are as yet no studies which clearly demonstrate that surgery is not necessary. With respect to the group of localized low-grade MALT lymphomas of the stomach and the indolent nature of the disease make plausible a conservative approach, with antibiotic eradication of H. pylori as the sole initial treatment. This may avert or at least postpone the indication for surgical resection in the majority of patients.


[Sudden cardiac death: the seven questions all cardiologists must answer to].
The implantable cardioverter cardiodefibrillator (ICD), has changed the view related to prevention and treatment of sudden cardiac arrest (SCA). However, some issues are still matter of discussion. Answers for the main questions are briefly exposed. 1. According to worldwide statistics, the manual incidence of SCA varies between 750 and 100 people per million inhabitants. 2. Nearly 25% of SCA are related to individuals with severe heart disease and low ejection fraction, but the remaining 75% there are scare or no antecedents at all, plus normal left ventricular function. 3. In subjects with history of severe heart disease, the risk of SCA prevention and cannot replace the ICD indication. 5. Except in particular cases, EP testing is not the right tool for risk stratification of SCA. 6. In the population with minor or without antecedents of heart disease, family history of SCA below 40 years old, or some features in the ECG (delta wave, long QT interval, etc), would be the unique sign of risk for developing SCA. 7. Although inappropriate shocks and eventually myocardial injury due to shock therapy may occur, the ICD still is the best therapy for prevention and treatment of SCA.


Analysis of flow-induced transcriptional response and cell alignment of different sources of endothelial cells used in vascular tissue engineering.
Endothelialization of tissue-engineered vascular grafts has proven crucial for implant functionality and thus clinical outcome, however, the choice of endothelial cells (ECs) is often driven by availability rather than by the type of vessel to be replaced. In this work we studied the response to flow of different human ECs with the aim of examining whether their response in vitro is dictated by their original in vivo conditions. Arterial, venous, and microvascular ECs were cultured under shear stress (SS) of 0, 0.3, 3, 1, 10, and 30 dyne/cm2 for 24 h. Regulation of flow-induced marker KLF2 was similar across the different ECs. Upregulation of anti-thrombotic markers, TM and TPA, was mainly seen at higher SS. Cell elongation and alignment was observed for the different ECs at 10 and 30 dyne/cm2 while at lower SS cells maintained a random orientation. Downregulation of pro-inflammatory factors SELE, IL8, and VCAM1 and up-regulation of anti-oxidant markers NQO1 and HO1 was present even at SS for which cell alignment was not observed. Our results evidenced similarities in the response to flow among the different ECs, suggesting that the maintenance of the resting state in vitro is not dictated by the SS typical of the tissue of origin and that absence of flow-induced cell orientation does not necessarily correlate with a pro-inflammatory state of the ECs. These results support the use of ECs from easily accessible sources for in vitro vascular tissue engineering independently from the target vessel.


Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity.
In recent years, there has been an increasing demand for the development of faster and more efficient technologies for the generation of monoclonal antibodies against challenging targets that are weakly immunogenic or available only in limited amounts. Typical classes of such targets are cell surface antigens such as G-protein related receptors (GPCRs) or ion channels. We have developed transgenic (Tg) mice and rabbits that overexpress the neonatal Fc receptor (FcRn), resulting in an augmented humoral immune response even if challenging antigens are used for immunization. The impressively enhanced FcRn-mediated immune reactions are characterized by improved IgG protection and enhanced antigen presentation leading to greater number of antigen-specific T-helper and B-cell activation in lymphoid organs. Notably, these animals do not show any sign of autoimmunity and can be efficiently bred. FcRn overexpression thus leads to a number of practical benefits for improved generation of monoclonal and polyclonal antibodies against multiple antigens, including weakly immunogenic epitopes or tiny amounts of proteins. This review summarizes our current understanding about the mechanisms by which FcRn overexpression leads to such a significantly enhanced humoral immune response.


Ultrafast dynamics of the ns (n = 3,4) and 3d Rydberg states of O2.
The ultrafast dynamics of the lowest optically accessible Rydberg states of molecular oxygen (O2) has been studied by time resolved transient ionization. The process was triggered by the absorption of two pump photons in the 304 nm-220 nm range which corresponds to an energy range of 8.2 eV-11.3 eV, and probed by ionization with photons at 800 nm. From the analysis of the experimental data different time constants ranging from a few femtoseconds to hundreds of picoseconds were found. The identification of the states responsible for the measured lifetimes revealed important facts about the dynamics of the Rydberg states in this energy range, underlying the importance of the coupling between Rydberg and valence states in the relaxation mechanisms of the molecule.


Gastrointestinal Histoplasmosis: A Case Series.
Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.


Role of compression modalities in a prophylactic program for deep vein thrombosis.
During the past decade, we have learned a great deal about the etiology, pathogenesis, diagnosis, and treatment of thromboembolic disease. Subcutaneous heparin has emerged as a major deterrent worldwide for thrombosis prevention but is associated with the potential risk of bleeding and cannot be used in certain patient situations. External compression modalities have emerged as major alternate forms of prophylaxis. We have learned that these devices stimulate the fibrinolytic system, prevent stasis and the endothelial injury that can accompany extreme venous distention. Since they are not associated with bleeding or other serious complications, they are attractive methods for most surgeons, including those performing delicate or complex surgical procedures. Independent studies worldwide have demonstrated their effectiveness in reducing deep vein thrombosis, as recognized by the NIH Consensus Development Panel, and the evidence is compelling that DVT efficacy is a valid marker for PE efficacy. Since these devices reduce the incidence of deep vein thrombosis, they almost certainly must prevent pulmonary emboli; however, a properly designed protocol should be conducted to validate these assumptions. Evidence suggests that full-leg sequential compression is superior to calf compression, but further study is necessary. We believe that a hospital-wide plan, including risk-factor assessment and application of clinical management guidelines, including all available modalities, is important to provide the maximum protection of patients with the lowest risk of side effects. Such a program has been very successful in our community.


Priorities and Progress in Gram-negative Bacterial Infection Research by the Antibacterial Resistance Leadership Group.
Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients. The ARLG has conducted pharmacokinetic studies to inform the optimal dosing of antibiotics that are important in the treatment of drug-resistant gram-negative bacteria, including oral fosfomycin, intravenous minocycline, and a combination of intravenous ceftazidime-avibactam and aztreonam. In addition, randomized clinical trials have assessed the safety and efficacy of step-down oral fosfomycin for complicated urinary tract infections and single-dose intravenous phage therapy for adult patients with cystic fibrosis who are chronically colonized with P. aeruginosa in their respiratory tract. Thus, the focus of investigation in the ARLG has evolved from improving understanding of drug-resistant gram-negative bacterial infections to positively affecting clinical care for affected patients through a combination of interventional pharmacokinetic and clinical studies, a focus that will be maintained moving forward.


The floating Meckel.
A 10-year-old girl was hospitalized because of abdominal pain and significant gastrointestinal bleeding for 3 days with hematocrit of 28% and hemoglobin of 6.1 mmol/L. Gastroscopy and abdominal ultrasound did not reveal any gastrointestinal abnormalities and parameters of coagulation were normal. Because a Meckel diverticulum is one of the most common causes of lower gastrointestinal bleeding in children, a Tc-99m pertechnetate scan (Meckel's scan) was performed to identify ectopic gastric mucosa. Normally, a Meckel diverticulum is found in the right lower quadrant.


A review of methodologies evaluating in-vivo superficial vein properties: focus on compliance and reactivity.
The saphenous vein (SV) is a hindlimb superficial vein which has aroused a considerable interest because of its implication in chronic venous disease and its use in coronary artery or lower limb bypass grafts. The morphology and patency of the SV are commonly assessed for diagnosis and management, but the dynamic properties of the vein (compliance, elasticity and reactivity, less widely studied) are also fundamental issues. The subject of this review is neither to review the pathologies, nor the treatments or surgical procedures. The goal is to gather together all existing types of investigation on the superficial vein and to focus on the dynamic venous properties in vivo. The data collected indicate that plethysmography (PG) and ultrasound (US) are extensively used to evaluate SV patency, reflux and morphology. Their use to evaluate superficial vein compliance is less widespread but highly necessary. The protocols used via venous occlusion are described and the various parameters used to accurately measure compliance and distensibility versus elasticity are presented and discussed. The advantage of US diameter measurement is shown, including additional pulsatile compliance evaluation. The overview of venous reactivity greatly differs, being poorly studied in vivo, mainly by optical methods in humans or US echotracking in animals. Existing methodologies are potent but could be certainly developed and improved further for better characterization of the SV in human and for investigations of new devices, surgical techniques and pharmacological treatment in preclinical animal studies.


Early Impella Support in Postcardiac Arrest Cardiogenic Shock Complicating Acute Myocardial Infarction Improves Short- and Long-Term Survival.
Early mechanical circulatory support with Impella may improve survival outcomes in the setting of postcardiac arrest cardiogenic shock after out-of-hospital cardiac arrest complicating acute myocardial infarction. However, the optimal timing to initiate mechanical circulatory support in this particular setting remains unclear. Therefore, we aimed to compare survival outcomes of patients supported with Impella 2.5 before percutaneous coronary intervention (pre-PCI) with those supported after percutaneous coronary intervention (post-PCI). Retrospective single-center study between September 2014 and December 2019 admitted to the Cardiac Arrest Center in Marburg, Germany. Out of 2,105 patients resuscitated from out-of-hospital cardiac arrest due to acute myocardial infarction with postcardiac arrest cardiogenic shock between September 2014 and December 2019 and admitted to our regional cardiac arrest center, 81 consecutive patients receiving Impella 2.5 during admission coronary angiogram were identified. Survival outcomes were compared between those with Impella support pre-PCI to those with support post-PCI. A total of 81 consecutive patients with infarct-related postcardiac arrest shock supported with Impella 2.5 during admission coronary angiogram were included. All patients were in profound cardiogenic shock requiring catecholamines at admission. Overall survival to discharge and at 6 months was 40.7% and 38.3%, respectively. Patients in the pre-PCI group had a higher survival to discharge and at 6 months as compared to patients of the post-PCI group (54.3% vs 30.4%; p = 0.04 and 51.4% vs 28.2%; p = 0.04, respectively). Furthermore, the patients in the early support group demonstrated a greater functional recovery of the left ventricle and a better restoration of the end-organ function when Impella support was initiated prior to percutaneous coronary intervention. Our results suggest that the early initiation of mechanical circulatory support with Impella 2.5 prior to percutaneous coronary intervention is associated with improved hospital and 6-month survival in patients with postcardiac arrest cardiogenic shock complicating acute myocardial infarction.


Cardiac Protection of Valsartan on Juvenile Rats with Heart Failure by Inhibiting Activity of CaMKII via Attenuating Phosphorylation.
Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan (Sham + Val) or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups. Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration. Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281.


Signaling in H2O2-induced increase in cell proliferation in Barrett's esophageal adenocarcinoma cells.
Mechanisms whereby acid reflux may accelerate the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have previously shown that NADPH oxidase NOX5-S generates reactive oxygen species (ROS) when Barrett's metaplastic cells are exposed to acid. Besides metaplastic cells, other H(2)O(2)-producing cells (e.g., inflammatory cells) present in BE mucosa may produce additional ROS, which may also affect metaplastic cells contributing to esophageal tumorigenesis. In this study, we investigate whether exogenous H(2)O(2) stimulates cell proliferation by increasing NOX5-S expression. Low dose (10(-13) M) of H(2)O(2) significantly increased thymidine incorporation, NOX5-S mRNA, and protein expression in a Barrett's EA cell line FLO. H(2)O(2)-induced increase in NOX5-S expression was significantly inhibited by knockdown of nuclear factor (NF)-κB1 p50 with p50 small interfering RNA (siRNA) in EA cell lines FLO and OE33. H(2)O(2) significantly increased p65 phosphorylation and the luciferase activity in FLO cells transfected with a NF-κB activation reporter plasmid pNF-κB-Luc. H(2)O(2)-induced increase in luciferase activity in FLO cells was significantly decreased by knockdown of extracellular signal-regulated kinase 2 (ERK2) mitogen-activated protein kinase (MAPK). Overexpression of p50 and p65 remarkably increased the luciferase activity in FLO cells transfected with a NOX5-S reporter plasmid NOX5-LP. In addition, H(2)O(2)-induced thymidine incorporation in FLO cells was significantly decreased by the MAPK kinase 1/2 inhibitor 2'-amino-3'methoxyflavone (PD98059) and ERK2 siRNA but not by ERK1 siRNA. Likewise, H(2)O(2)-induced increase in NOX5-S expression was significantly decreased by ERK2 siRNA in FLO and OE33 cells. We conclude that a low dose of H(2)O(2) increases cell proliferation. H(2)O(2)-induced increase in cell proliferation may depend on sequential activation of ERK2 MAPK, NF-κB1 p50, and NOX5-S.


Hypertension therapy in the elderly.
Hypertension in the elderly (persons 60 years of age or older) is a major clinical and public health problem. Blood pressure-related morbidity from cardiovascular disease increases steeply after 50 years of age and, with advancing age, becomes increasingly concentrated among persons with clinical hypertension. The data supporting treatment of all forms of hypertension in the elderly are robust. This review focuses on the rationale for treatment, specific treatment strategies, and age-related hemodynamic and pathophysiologic aberrations in the aged individual with hypertension.


Use of lithium in the medically ill.
For more than one hundred years (about 1845-1950), lithium salts were used to treat disorders belonging to 'the uric acid diathesis' ('gouty diseases'). It was introduced into modern psychiatry as an antimanic agent, but its current use is mostly as a prophylactic in bipolar and unipolar manic-depressive illness. In the present context, however, this psychiatric use may, in some instances, create special nonpsychiatric problems such as lithium poisoning, renal diabetes insipidus, and weight gain. Moreover, most lithium patients are outpatients, so that medical complaints caused by the treatment are in most cases presented to the general practitioner, the neurologist, the nephrologist, the cardiologist, etc. rather than to the psychiatrist. Lithium treatment is frequently accompanied by both short-term and long-term side effects and some of these, e.g. the thyroid-depressing effect and leukocytosis, may be medically exploited. Like manic-depressive illness, some medical disorders such as certain types of headache have a periodic course and appear to respond favorably to long-term lithium treatment. Cooperation between researchers in biological psychiatry and nephrologists has resulted in the suggestion that lithium may be used as an indicator of proximal sodium and water reabsorption, which has later led to the suggestion that the renal lithium clearance is an indicator of proximal renal tubular function.


Passive ranging of a moving target in the direct-arrival zone in deep sea using a single vector hydrophone.
The vector hydrophone covers more comprehensive sound field information over the sound pressure hydrophone. The passive target ranging method based on the shallow-located unmanned platform equipped with vector hydrophones is explored based on the measured surface ship data acquired in the deep-sea area in December 2021. First, a bearings-only target motion analysis (TMA) algorithm is proposed, determining the motion state of a moving target (e.g., azimuth angle, abeam time, heading angle, and the ratio of velocity to initial distance) in accordance with its horizontal bearing time recording (BTR) data. Subsequently, the loss function is built following the situation information and the average complex acoustic intensity to determine the real-time grazing angle of the target. Last, the real-time range of the target is determined in accordance with the situation information and the grazing angle. As revealed by the comparison of the calculated value of the sea trial data with the GPS trajectory, the average distance error of the target reaches 11.6%, the root mean square error (RMSE) of the grazing angle is 1.99°, the RMSE of the velocity is 1.9 kn, and the RMSE of the abeam time reaches 51.4 s.


Conserved network motifs allow protein-protein interaction prediction.
High-throughput protein interaction detection methods are strongly affected by false positive and false negative results. Focused experiments are needed to complement the large-scale methods by validating previously detected interactions but it is often difficult to decide which proteins to probe as interaction partners. Developing reliable computational methods assisting this decision process is a pressing need in bioinformatics. We show that we can use the conserved properties of the protein network to identify and validate interaction candidates. We apply a number of machine learning algorithms to the protein connectivity information and achieve a surprisingly good overall performance in predicting interacting proteins. Using a 'leave-one-out' approach we find average success rates between 20 and 40% for predicting the correct interaction partner of a protein. We demonstrate that the success of these methods is based on the presence of conserved interaction motifs within the network. A reference implementation and a table with candidate interacting partners for each yeast protein are available at http://www.protsuggest.org.


Anaesthetic management of the patient with acute ischaemic stroke.
Anaesthetic management of the acute stroke patient demands consideration of the penumbra as the central focus. Recent studies have shown that patients who receive general anaesthesia for endovascular therapy for acute ischaemic stroke have worse outcomes than those who receive local anaesthesia. Although baseline condition of the patients in these studies differed, we should heed the warnings evident in the results. 'Time is brain': therapy should be quickly provided. Arterial pressure should be monitored carefully upon induction, avoiding a drastic reduction, and allowing for a reduction in arterial pressure upon recanalization. Keeping these factors in mind, anaesthetic technique (general, monitored anaesthesia care, or local) must be selected considering the individual patient's risks and benefits. Unfortunately, there are no proven neuroprotective strategies to date for use in acute ischaemic stroke.


Aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.
Aptamers are single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) oligonucleotides, which are able to bind their target with high selectivity and affinity. Owing to their multiple talents, aptamers combined with nanoparticles are nanosystems well qualified for the development of new biomedical devices for analytical, imaging, drug delivery and many other medical applications. Because of their target affinity, aptamers can direct the transport of aptamer-nanoparticle conjugates. The binding of the aptamers to the target "anchors" the nanoparticle-aptamer conjugates at their site of action. In this way, nanoparticle-based bioimaging and smart drug delivery are enabled, especially by use of systematically developed aptamers for cancer-associated biomarkers. This review article gives a brief overview of recent relevant research into aptamers and trends in their use in cancer diagnostics and therapy. A concise description of aptamers, their development and functionalities relating to nanoparticle modification is given. The main part of the article is dedicated to current developments of aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.


A comparison of planar, laser-induced fluorescence, and high-sensitivity interferometry techniques for gas-puff nozzle density measurements.
The distribution of argon gas injected by a 12-cm-diameter triple-shell nozzle was characterized using both planar, laser-induced fluorescence (PLIF) and high-sensitivity interferometry. PLIF is used to measure the density distribution at a given time by detecting fluorescence from an acetone tracer added to the gas. Interferometry involves making time-dependent, line-integrated gas density measurements at a series of chordal locations that are then Abel inverted to obtain the gas density distribution. Measurements were made on nominally identical nozzles later used for gas-puff Z-pinch experiments on the Saturn pulsed-power generator. Significant differences in the mass distributions obtained by the two techniques are presented and discussed, along with the strengths and weaknesses of each method.


Electronic structure of compound I in human isoforms of cytochrome P450 from QM/MM modeling.
Human cytochromes P450 play a vital role in drug metabolism. The key step in substrate oxidation involves hydrogen atom abstraction or C=C bond addition by the oxygen atom of the Compound I intermediate. The latter has three unpaired electrons, two on the Fe-O center and one shared between the porphyrin ring and the proximal cysteinyl sulfur atom. Changes in its electronic structure have been suggested to affect reactivity. The electronic and geometric structure of Compound I in three important human subfamilies of cytochrome P450 (P450, 2C, 2B, and 3A) that are major contributors to drug metabolism is characterized here using combined quantum mechanical/molecular mechanical (QM/MM) calculations at the B3LYP:CHARMM27 level. Compound I is remarkably similar in all isoforms, with the third unpaired electron located mainly on the porphyrin ring, and this prediction is not very sensitive to details of the QM/MM methodology, such as the DFT functional, the basis set, or the size of the QM region. The presence of substrate also has no effect. The main source of variability in spin density on the cysteinyl sulfur (from 26 to 50%) is the details of the system setup, such as the starting protein geometry used for QM/MM minimization. This conformational effect is larger than the differences between human isoforms, which are therefore not distinguishable on electronic grounds, so it is unlikely that observed large differences in substrate selectivity can be explained to a large extent in these terms.


Hydrogen sulfide evokes neurite outgrowth and expression of high-voltage-activated Ca2+ currents in NG108-15 cells: involvement of T-type Ca2+ channels.
We investigated if stimulation of T-type Ca(2+) channels with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H(2)S), could cause neuronal differentiation of NG108-15 cells. Like dibutyryl cyclic AMP (db-cAMP), treatment with NaHS at 1.5-13.5 mM for 16 h enhanced neurite outgrowth in a concentration-dependent manner. Synergistic neuritogenic effect was obtained in the cells stimulated with NaHS in combination with db-cAMP at subeffective concentrations. Exposure to NaHS or db-cAMP for 2 days resulted in enhancement of expression of high-voltage-activated currents consisting of N-, P/Q-, L- and also other types, but not of T-type currents. Mibefradil, a pan-T-type channel blocker, abolished the neuritogenesis induced by NaHS, but not by db-cAMP. The NaHS-evoked neuritogenesis was also completely blocked by pretreatment with BAPTA/AM, a chelator of intracellular Ca(2+), and by zinc chloride at a concentration known to selectively inhibit Ca(v)3.2 isoform of T-type Ca(2+) channels, but not Ca(v)3.1 or Ca(v)3.3. Further, L-ascorbate, recently proven to selectively inhibit Ca(v)3.2, abolished the neuritogenic effect of NaHS, but not db-cAMP. Our data thus demonstrate that NaHS/H(2)S is a novel inducer of neuronal differentiation in NG108-15 cells, as characterized by neuritogenesis and expression of high-voltage-activated currents, and suggest the involvement of T-type Ca(2+) channels, especially Ca(v)3.2.


Importance of fibrosis 4 index score and mode of anti-fungal treatment to the outcome of Cryptococcal meningitis in hepatitis B virus-infected patients.
Hepatitis B virus (HBV) and the associated cirrhosis are risk factors for cryptococcal meningitis (CM). However, the clinical features of co-infection with HBV and CM are unclear. Seventy-nine HBV-infected CM patients and 79 HBV-uninfected CM patients were enrolled in a case-control matching study from 476 CM patients. Fibrosis 4 index (FIB4) was used for assessment of HBV-related fibrosis/cirrhosis. Demographic characteristics, symptoms, routine blood tests, liver function and cerebrospinal fluid (CSF) profiles were compared between the two groups. Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality. Male gender was associated with HBV-infected CM patients (p = .006). CM patients with HBV experienced similar frequencies of symptoms but had lower white blood cell (WBC) (p < .001), platelet (p < .001) and albumin (p = .012), and increased aspartate amino transaminase (AST) (p = .009) and total bilirubin (TBIL) levels (p < .001). Patients with and without HBV infection had similar 10-week cumulative survival rates (85.9 ± 4.2% vs. 78.6 ± 5.4%, p = .569). The hazard ratio was 3.7 times higher for those with FIB4 ≥ 3.25 (p = .020) and 4.5 times higher for those with HBV infection not treated with Amphotericin B + flucytosine ± fluconazole (p = .023). HBV-infected CM population experience lower WBC, platelet and albumin, and higher AST and TBIL. Ten-week survival rate was similar between HBV-infected and HBV-uninfected CM patients. CM patients with high FIB4 or not treated with Amphotericin B + flucytosine ± fluconazole are at a higher risk of death.


The diversity of tick-borne bacteria and parasites in ticks collected from the Strandja Nature Park in south-eastern Bulgaria.
Ticks are important carriers of many different zoonotic pathogens. To date, there are many studies about ticks and tick-borne pathogens (TBP), but only a few were carried out in Bulgaria. The present study intends to detect the prevalence of tick-borne bacteria and parasites occurring at the Black Sea in Bulgaria to evaluate the zoonotic potential of the tick-borne pathogens transmitted by ticks in this area. In total, cDNA from 1541 ticks (Dermacentor spp., Haemaphysalis spp., Hyalomma spp., Ixodes spp. and Rhipicephalus spp.) collected in Bulgaria by flagging method or from hosts was tested in pools of ten individuals each for Anaplasma phagocytophilum, Babesia spp., Borrelia burgdorferi (s.l.), Rickettsia spp. and "Candidatus Neoehrlichia mikurensis" via conventional and quantitative real-time PCR. Subsequently, samples from positive pools were tested individually and a randomized selection of positive PCR samples was purified, sequenced, and analyzed. Altogether, 23.2% of ticks were infected with at least one of the tested pathogens. The highest infection levels were noted in nymphs (32.3%) and females (27.5%). Very high prevalence was detected for Rickettsia spp. (48.3%), followed by A. phagocytophilum (6.2%), Borrelia burgdorferi (s.l.) (1.7%), Babesia spp. (0.4%) and "Ca. Neoehrlichia mikurensis" (0.1%). Co-infections were found in 2.5% of the tested ticks (mainly Ixodes spp.). Sequencing revealed the presence of Rickettsia monacensis, R. helvetica, and R. aeschlimannii, Babesia microti and B. caballi, and Theileria buffeli and Borrelia afzelli. This study shows very high prevalence of zoonotic Rickettsia spp. in ticks from Bulgaria and moderate to low prevalence for all other pathogens tested. One should take into account that tick bites from this area could lead to Rickettsia infection in humans and mammals.


Dependent care, caregiver burden, and self-care agency of spouse caregivers.
A convenience sample of 113 spouse caregivers was used to examine the relationships between dependent care, caregiver burden, and self-care agency. Subjects were the spouses of radiation oncology or chemotherapy patients in a large metropolitan hospital. The Denyes Self-Care Agency Instrument was used to measure self-care agency. The Task Scale was used to operationalize dependent care, and the Burden Scales were used to measure caregiver burden. Demographic data were collected on the number of weeks in the caregiver role, presence of health problems in the caregiver, gender, age, income, and education. In the total sample, subjective burden was negatively and significantly related to self-care agency and objective burden, in addition, dependent care and objective burden were also negatively related. When the data were divided into subsamples based on gender, several of the relationships were in opposite directions. The most notable of these were the relationships between dependent care and self-care agency. It is evident that interventions should take these gender differences into account.


Transactions between child social wariness and observed structured parenting: evidence from a prospective adoption study.
This investigation examined the mutual influences between structured parenting and child social wariness during toddlerhood using a longitudinal adoption design. The sample consisted of 361 adoption-linked families, each including an adopted child, adoptive parents, and a birth mother. Heightened social wariness in children at age 18 months predicted reduced levels of observed structured parenting (i.e., less directive parenting with fewer commands and requests) in adoptive mothers at age 27 months. Adoptive fathers' lower structured parenting at age 18 months predicted subsequent elevation in child social wariness. Birth mothers' history of fear-related anxiety disorders was not associated with child social wariness. Findings highlight the role of dynamic family transactions in the development of social wariness during toddlerhood.


TIPIT: a randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: magnetic resonance imaging and magnetic resonance angiography protocol.
Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis. The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease. Trial registration Current Controlled Trials ISRCTN89493983.


Giant Left Atrial Myxoma Causing Mitral Valve Obstruction and Concomitant Coronary Artery Disease.
We describe a 56-year old male patient who presented with congestive heart failure and had undergone echocardiography that showed a mobile, giant left atrial mass which caused obstruction in the left ventricular outflow tract. The patient underwent a coronary angiography before operation that showed severe stenosis in the left anterior descending and circumflex artery. The patient underwent resection of the mass and coronary artery bypass grafting. The pathology of the mass was myxoma and patient had a satisfactory outcome.


Cytotoxicity of intracellular aβ42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate.
Oligomeric forms of β-amyloid (Aβ(42)) peptides associated with Alzheimer's disease (AD) disrupt cellular Ca(2+) regulation by liberating Ca(2+) into the cytosol from both extracellular and intracellular sources. We elucidated the actions of intracellular Aβ by imaging Ca(2+) responses to injections of Aβ oligomers into Xenopus oocytes. Two types of signal were observed: (1) local, "channel-like" transients dependent on extracellular Ca(2+) influx, which resembled signals from amlyoid pores formed by extracellular application of oligomers; and (2) local transients and global Ca(2+) waves, resembling Ca(2+) puffs and waves mediated by inositol trisphosphate (IP(3)). The latter responses were suppressed by antagonists of the IP(3) receptor (caffeine and heparin), pretreatment with the G(i)(o)-protein inhibitor pertussis toxin, and pretreatment with lithium to deplete membrane inositol lipids. We show that G-protein-mediated stimulation of IP(3) production and consequent liberation of Ca(2+) from the endoplasmic reticulum by intracellular Aβ oligomers is cytotoxic, potentially representing a novel pathological mechanism in AD which may be further exacerbated by AD-linked mutations in presenilins to promote opening of IP(3) receptor/channels.


Factors associated with suicide in people who use drugs: a scoping review.
Suicide is a significant contributor to global mortality. People who use drugs (PWUD) are at increased risk of death by suicide relative to the general population, but there is a lack of information on associated candidate factors for suicide in this group. The aim of this study was to provide a comprehensive overview of existing evidence on potential factors for death by suicide in PWUD. A scoping review was conducted according to the Arksey and O'Malley framework. Articles were identified using Medline, CINAHL, PsycINFO, SOCIndex, the Cochrane Database of Systematic Reviews and the Campbell Collaboration Database of Systematic Reviews; supplemented by grey literature, technical reports, and consultation with experts. No limitations were placed on study design. Publications in English from January 2000 to December 2021 were included. Two reviewers independently screened full-text publications for inclusion. Extracted data were collated using tables and accompanying narrative descriptive summaries. The review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The initial search identified 12,389 individual publications, of which 53 met the inclusion criteria. The majority (87%) of included publications were primary research, with an uncontrolled, retrospective study design. The most common data sources were drug treatment databases or national death indexes. Eleven potential factors associated with death by suicide among PWUD were identified: sex; mental health conditions; periods of heightened vulnerability; age profile; use of stimulants, cannabis, or new psychoactive substances; specific medical conditions; lack of dual diagnosis service provision; homelessness; incarceration; intravenous drug use; and race or ethnicity. Opioids, followed by cannabis and stimulant drugs were the most prevalent drugs of use in PWUD who died by suicide. A large proportion of evidence was related to opioid use; therefore, more primary research on suicide and explicit risk factors is required. The majority of studies exploring factors associated with death by suicide among PWUD involved descriptive epidemiological data, with limited in-depth analyses of explicit risk factors. To prevent suicide in PWUD, it is important to consider potential risk factors and type of drug use, and to tailor policies and practices accordingly.


LATE EVALUATION OF PATIENTS UNDERGOING MANIPULATION OF THE KNEE AFTER TOTAL ARTHROPLASTY.
We compared gains in range of motion in patients who underwent manipulation within 12 weeks of total knee arthroplasty (TKA) and after this period. We also evaluated maintenance of the arc obtained from knee manipulation in late follow-up, along with factors associated with poorer outcomes. The study was divided into two groups according to the time after TKA; the surgeries took place between January 2008 and December 2014. When comparing the range of motion between early and late manipulations, the group that underwent manipulation within 12 weeks of the TKA exhibited better outcomes, but these were not statistically significant. We observed that 14.3% of cases retained the same range attained at the time of manipulation. In late evaluation after manipulation, 47.7% of the sample had a range of less than 90 degrees. The significant risk factors for recurrence of knee stiffness in the long term are poor range of motion before TKA and before manipulation, female sex, and secondary arthritis. Women previously diagnosed with secondary osteoarthritis and poor range of motion before TKA or manipulation are at higher risk for late stiffness. Level of Evidence III, Retrospective Comparative Study.


The need for mechanical ventilation in a child exposed to a laundry detergent pod.
Laundry detergent pods (LDPs) are a new, concentrated form of detergent covered by a membrane of polyvinyl alcohol or other water-soluble material. In contrast to traditional laundry detergents, the spectrum of responses to exposure to LDPs ranges from mild to life-threatening events. This is a case report of a 3-year-old male who ingested part of an LDP, leading to a depressed level of consciousness, upper airway obstruction, and severe respiratory distress. The patient required intubation and mechanical ventilation for 2 days before being discharged. This rare, severe clinical pattern demonstrates the potential toxicity of these laundry detergents. In the literature, few cases that required intubation and ventilation have been reported. To our knowledge, this is also the first case of LDP exposure reported from Turkey.


Primary cytotoxicity against the envelope glycoprotein of human immunodeficiency virus-1: evidence for antibody-dependent cellular cytotoxicity in vivo.
Fresh peripheral blood mononuclear cells from human immunodeficiency virus-1 (HIV-1) seropositive donors can lyse target cells expressing the envelope glycoprotein in vitro. In most cases, this antigen-specific lysis is not mediated by T lymphocytes. Lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing different forms of the envelope protein of HIV-1 were used as target cells in chromium-release assays of primary cytotoxic effector cells and of antibody-dependent cellular cytotoxicity (ADCC). By depleting effector cells of CD16+ lymphocytes, or by blocking target cell lysis with an anti-human IgG serum, primary env-specific lysis was found to be due to ADCC, the effector cells being armed in vivo with specific, cytophilic antibodies. This phenomenon is dependent on cell surface expression of the envelope protein and is directed against both gp120 and gp41. Human HIV-1 antibody-positive sera are able to mediate ADCC against HIV-infected CD4+ T lymphocytes, suggesting a possible role of ADCC in the natural infection.


DNA microarray-based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity.
In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain-derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR-enhanced hippocampal functions; a high-throughput whole-genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11-fold compared to WR, resulting in muscular adaptation for the fast-twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up-regulated (>1.5-fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down-regulated (<0.75-fold change) genes. Functional categorization using both pathway- or specific-disease-state-focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down-regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary-RWR-related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions.


Integrating the prevention of mother-to-child transmission of HIV into primary healthcare services after AIDS denialism in South Africa: perspectives of experts and health care workers - a qualitative study.
Integrating Prevention of Mother-to-Child Transmission (PMTCT) programmes into routine health services under complex socio-political and health system conditions is a priority and a challenge. The successful rollout of PMTCT in sub-Saharan Africa has decreased Human Immunodeficiency Virus (HIV), reduced child mortality and improved maternal health. In South Africa, PMTCT is now integrated into existing primary health care (PHC) services and this experience could serve as a relevant example for integrating other programmes into comprehensive primary care. This study explored the perspectives of both experts or key informants and frontline health workers (FHCWs) in South Africa on PMTCT integration into PHC in the context of post-AIDS denialism using a Complex Adaptive Systems framework. A total of 20 in-depth semi-structured interviews were conducted; 10 with experts including national and international health systems and HIV/PMTCT policy makers and researchers, and 10 FHCWs including clinic managers, nurses and midwives. All interviews were conducted in person, audio-recorded and transcribed. Three investigators collaborated in coding transcripts and used an iterative approach for thematic analysis. Experts and FHCWs agreed on the importance of integrated PMTCT services. Experts reported a slow and partial integration of PMTCT programmes into PHC following its initial rollout as a stand-alone programme in the aftermath of the AIDS denialism period. Experts and FHCWs diverged on the challenges associated with integration of PMTCT. Experts highlighted bureaucracy, HIV stigma and discrimination and a shortage of training for staff as major barriers to PMTCT integration. In comparison, FHCWs emphasized high workloads, staff turnover and infrastructural issues (e.g., lack of rooms, small spaces) as their main challenges to integration. Both experts and FHCWs suggested that working with community health workers, particularly in the post-partum period, helped to address cases of loss to follow-up of women and their babies and to improve linkages to polymerase-chain reaction (PCR) testing and immunisation. Despite organised efforts in South Africa, experts and FHCWs reported multiple barriers for the full integration of PMTCT in PHC, especially postpartum. The results suggest opportunities to address operational challenges towards more integrated PMTCT and other health services in order to improve maternal and child health.


Toxicological characteristics of the main lipid oxidation products.
This article gives a brief overview of the available scientific data on the toxicity of lipid oxidation products. The description is logically divided into two parts: the toxicity of primary oxidation products (lipid peroxides) and toxicity of secondary oxidation products (carbonyl compounds). Mechanisms of their toxic effect, indicating the most sensitive target organ, as well as the metabolic pathways and main products of their metabolism and half-lethal doses of the main products of oxidation are characterized. It is noted that the most toxic products among them are secondary products of lipid oxidation, in particular, the acrolein with a half-lethal dose of 7-46 mg per kg body weight. It is concluded that the accent in the control of lipid and lipid containing food safety must be shifted to identify specific, the most toxic, secondary lipid oxidation products.


Intrathyroidal parathyroid carcinoma: a case report with clinical and histological findings.
The chance of an intrathyroidal occurrence of a parathyroid gland is about 1-3%. Among the causes of hyperparathyroidism, parathyroid cases occur in less than 1% of patients. Here we present the case of a 63 year old Saudi female suffering from an intrathyroidal parathyroid carcinoma. The suspicion coming from the clinical investigations that the removed tumor tissue may be a parathyroid carcinoma could be confirmed by histology. Additionally non-radioactive in situ hybridization to localize mRNA transcripts for Cyclin D1 and immunohistochemical localization of Cyclin D1 was performed. Although parathyroid adenoma and carcinoma have disparate natural history, it can be difficult to differentiate between the two entities. Clinical presentation, operative findings may raise suspicion, but may not be conclusive especially if there is no evidence of invasion or metastasis, especially if the gland was intrathyroidal.


Neuroprotective effects of madecassoside in early stage of Parkinson's disease induced by MPTP in rats.
In this study, we investigated the neuroprotective effects of madecassoside, isolated from the Chinese medicinal herb Centella asiatica, in the rat model of early phase of parkinsonism. During intragastric administrations of madecassoside for 7 days, the rats were injected with MPTP on the 7th day. And for the following 14 days, madecassoside were also administered. On the 14th day, the behavioral tests were assessed after 1h of administration. And then, the rats were sacrificed, substantia nigra and striatum were dissected. The content of DA, MDA, GSH, and Bcl-2/Bax gene expression levels and BDNF protein level was determined. Treatment with madecassoside was found to improve locomotor dysfunction and to protect dopaminergic neuron by antagonizing MPTP induced neurotoxicity. Madecassoside significantly attenuated the MPTP-induced reduction of dopamine in the striatum. The MDA contents were significantly decreased while the GSH levels, Bcl-2/Bax ratio and protein expression of BDNF were significantly increased in madecassoside treated groups. These results indicated that madecassoside was effective in recovering MPTP-induced early signs of parkinsonism via its neuroprotective effects including reversing the depletion of DA, antioxidant activity, increasing ratio of Bcl-2/Bax, increasing protein expression of BDNF.


c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.
The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.
The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out some gastrointestinal events. Plasma xylose appearance was delayed in association with a strong decrease in gastrointestinal transit, while anandamide did not alter transporter-mediated glucose absorption. Interestingly, transit was nearly normalized by coinjection of SR141716 and AM630 (CB1R and CB2R antagonist, respectively), and AM630 also reduced the delay of plasma glucose appearance induced by anandamide. When gastric emptying was bypassed by direct glucose administration in the duodenum, anandamide still reduced plasma glucose appearance in wild-type but not in CB1R(-/-) mice. In conclusion, our findings demonstrated that acute activation of intestinal ECS reduced postprandial glycemia independently on intestinal glucose transport but rather inhibiting gastric emptying and small intestine motility and strongly suggest the involvement of both CB1R and CB2R.


A qualitative analysis of stress and coping in Korean immigrant women in middle-age and older-adulthood.
This qualitative grounded theory study explored stress-coping mechanisms in 14 Korean immigrant women (age ≥40) in the USA, by analyzing existing focus group data about relevant concepts that had been collected in a parent study. Using content analysis, stressors related primarily to socioenvironmental changes following immigration: language barriers, lack of trusting human relationships, and role changes were identified. Both healthy (activities, church, staying busy) and unhealthy (being alone and keeping negative feelings inside) coping strategies were reported by participants. The findings reveal unique aspects of stress-coping among Korean women who had immigrated after being culturally engrained with Confucian influences.


Comparison of ultrasound guided pulsed radiofrequency of genicular nerve with local anesthetic and steroid block for management of osteoarthritis knee pain.
To compare ultrasound-guided pulsed radiofrequency (PRF) of the genicular nerve with the genicular nerve block using local anesthetic and steroid for management of osteoarthritis (OA) knee pain. Thirty patients with OA knee were randomly allocated to receive either ultrasound-guided PRF of the genicular nerve (PRF group) or nerve block with bupivacaine and methylprednisolone acetate (local anesthetic steroid [LAS] group). Verbal numeric rating scale (VNRS) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores were measured at pre-procedure and 1-, 4-, and 12-weeks post-procedure. VNRS scores decreased significantly (P < 0.001) in both the groups at 12 weeks and other follow up times compared to baseline. Seventy-three percent of patients in the PRF group and 66% in the LAS group achieved effective pain relief (≥ 50% pain reduction) at 12 weeks (P > 0.999). There was also a statistically significant (P < 0.001) improvement in WOMAC scores in both groups at all follow up times. However, there was no intergroup difference in VNRS (P = 0.893) and WOMAC scores (P = 0.983). No complications were reported. Both ultrasound-guided PRF of the genicular nerve and blocks of genicular nerve with local anesthetic and a steroid provided comparable pain relief without any complications. However, PRF of the genicular nerve is a procedure that takes much more time and equipment than the genicular nerve block.


Psychodynamic treatment of depressed adolescents.
Depression may be conceptualized as the response to the loss of meaning or satisfaction sufficient to affect the individual's optimal view of the self. At each stage of the life cycle, the failure to achieve developmental tasks threatens the concept of the self, producing a phase-specific vulnerability to depression. Adolescence presents particular stresses by forcing the youngster to relinquish the relative familiarity and security of a childhood psychosocial role and create a sense of self independent of family, without childhood denial mechanisms, and of value to a new peer culture. Most individuals experience a sense of loss, confusion, apprehension, and dysphoria during this difficult period of transition. Many who seek psychotherapy require only a secure holding environment that will support their self-esteem as they create new avenues of worth and satisfaction. A few, however, are so hampered by psychosocial limitations that they cannot master this developmental passage without more extensive therapeutic assistance.


[A case of intravascular large B-cell lymphoma with rapidly progressive cognitive impairment after cerebral infarction].
A 67-year-old man started to show symptoms of dementia and developed convulsions accompanied by presyncope. Since an old cerebral infarction was found, he was given a diagnosis of symptomatic epilepsy, treated with antiepileptics. Dementia progressed rapidly, resulting in admission to a dementia ward. There were no physical abnormalities, and only slight elevations of LDH and CRP were noted. He suddenly developed a fever between 38°C and 39°C. Only the serum concentration of soluble IL-2 receptor was elevated at 6,430 U/L. Although a malignant tumor of the lymphatic system was suspected, there was no swelling noted in the superficial lymph nodes. The patient suddenly developed hypoxemia, thrombocytopenia, and an increase in fibrin degradation products. Pulmonary thromboembolism was suspected, but contrast-enhanced chest CT did not reveal any abnormalities. Bone marrow aspiration did not detect any infiltrations of lymphoid cells but was suggestive of hemophagocytic syndrome. After that, a new cerebral infarction occurred. Based on the course, intravascular lymphoma, which causes microvascular occlusions in various organs, was considered probable. Prednisolone was administered at a dose of 60 mg daily and skin biopsy was scheduled. However, the patient experienced a sudden deterioration and died. In autopsy, immunostain with CD20 showed that the arteriolae, capillaries, and venulae of thoracic and abdominal organs were filled with cells of large B-cell lymphoma. The presence of similar cerebrovascular lesions was not confirmed, but can reasonably be speculated. Thus, the present case suggests that it is necessary to consider intravascular lymphoma when dementia rapidly progresses for unknown reasons.


Risk factors, characteristics, and outcomes of candidemia in an adult intensive care unit in Turkey.
Thirty-six patients with candidemia and 37 control patients were included consecutively to determine the characteristics of candidemia episodes. The patients with candidemia had higher mortality with higher Sequential Organ Failure Assessment scores and frequency of use of a central venous catheter, total parenteral nutrition, and broad-spectrum antibiotics; chronic renal failure with replacement therapy; and longer stay in an intensive care unit. Candida albicans was the predominant species followed by Candida glabrata, Candida tropicalis, and Candida parapsilosis. All isolates of C glabrata were itraconazole-resistant.


Role of SPECT/CT in sentinel lymph node detection in patients with breast cancer.
The purpose of this study was to conduct a systematic review of the published literature to assess the role (indications, advantages, and limitations) of SPECT/CT for the detection of sentinel lymph node (SLN) in breast cancer. The authors searched PubMed for published literature in English addressing this topic. Eleven studies, published since 2006, focused on the role and value of SPECT/CT for SLN detection (SLND). They showed that SPECT/CT improved sentinel node detection and anatomical localization. One study suggested that SPECT/CT may provide a more accurate staging. Limitations for SLND with SPECT/CT include extra time and inconvenience for the patient and additional radiation dose. SPECT/CT is a valuable tool for SLND, especially in difficult cases, when planar lymphoscintigraphy shows no SLN or unexpected lymphatic drainage.


Otoprotective effects of ethosuximide in NOD/LtJ mice with age-related hearing loss.
Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+. We hypothesized that the apoptotic pathway may be blocked through the inhibition of T-type Ca2+ channels in cochlear cells in NOD/LtJ mice. NOD/LtJ mice were divided into 2 groups as follows: the ethosuximide-treated and untreated (control) groups. Ethosuximide was administered by intraperitoneal injection every other day from post-natal day seven (P7) until the mice were 8 weeks of age. Following treatment, auditory-evoked brainstem response (ABR) thresholds and distortion product oto-acoustic emission (DPOAE) of the mice in the 2 groups were measured at different time points. Morphometric analysis and the expression of genes involved in the T-type Ca2+-mediated apoptotic pathway were monitored. The ABR and DPOAE results revealed that the NOD/LtJ mice exhibited early-onset and rapidly progressive AHL. A histological examination revealed that hair cell degeneration coincided with the progression of hearing loss. Hair cell and SGN was were significantly lower and auditory function was significantly improved in the ethosuximide-treated group compared to the untreated group. Our data thus indicate that ethosuximide prevents the degeneration of cochlear cells by regulating the expression of genes in apoptotic pathways. Our findings suggest that activating the T-type Ca2+ channel and downstream genes may be key pathological mechanisms responsible for AHL in NOD/LtJ mice.


[Effects of Endovascular Treatment on Cranial Nerve Palsy due to Unruptured Intracranial Aneurysms].
This study aimed to assess the effects of endovascular treatment on cranial nerve palsy due to unruptured intracranial aneurysms. Endovascular coiling was performed in 203 patients with intracranial aneurysms between April 2002 and March 2012 in our hospital. Of these patients, 8(3.9%)presented with cranial nerve palsy due to unruptured intracranial aneurysms. Cranial nerve palsy involved the oculomotor nerve in 8 patients and the optic nerve in 2 patients. Two patients had both optic nerve and oculomotor nerve dysfunction. Patients with incomplete oculomotor nerve palsy at admission were more likely to have full recovery after coiling. Optic nerve dysfunction did not improve after coiling. Incomplete oculomotor nerve palsy, early treatment(≤15 days), and small aneurysms(≤10 mm)were likely to be associated with complete recovery after coiling. This study indicates that endovascular coiling may resolve cranial nerve palsy due to unruptured intracranial aneurysms in patients who have incomplete oculomotor nerve palsy due to small aneurysms and are treated as early as possible after symptom onset.


The rabbit brachial plexus as a model for nerve repair surgery--histomorphometric analysis.
One of the most devastating injuries to the upper limb is trauma caused by the avulsion. The anatomical structure of the rabbit's brachial plexus is similar to the human brachial plexus. The aim of our study was to analyze the microanatomy and provide a detailed investigation of the rabbit's brachial plexus. The purpose of our research project was to evaluate the possibility of utilizing rabbit's plexus as a research model in studying brachial plexus injury. Studies included histomorphometric analysis of sampled ventral branches of spinal nerves C5, C6, C7, C8, and Th1, the cranial trunk, the medial part of the caudal trunk, the lateral part of the caudal trunk and peripheral nerve. Horizontal and vertical analysis was done considering following features: the axon diameter, fiber diameter and myelin sheath. The number of axons, nerve area, myelin fiber density and minimal diameter of myelin fiber, minimal axon diameter and myelin area was marked for each element. The changes between ventral branches of spinal nerves C5-Th1, trunks and peripheral nerve in which the myelin sheath, axon diameter and fiber diameter was assessed were statistically significant. It was found that the g-ratio has close value in the brachial plexus as in the peripheral nerve. The peak of these parameters was found in nerve trunks, and then decreased coherently with the nerves travelling peripherally.


Prenatal Exposure to Folic Acid and Antidepressants and Language Development: A Population-Based Cohort Study.
The aim of the study was to determine the effect of simultaneous use of folic acid supplements and selective serotonin reuptake inhibitors (SSRIs) by pregnant women on language development in their offspring at the age of 3 years. We conducted a cohort study of 45,266 women with 51,747 singleton pregnancies in the population-based Norwegian Mother and Child Cohort study (1999-2008). The association between the use of SSRIs with and without concomitant folic acid and language competence in the offspring was investigated using multinomial logistic regression. Self-reported use of folic acid supplements and SSRIs was prospectively collected in 4-week intervals during pregnancy and validated with prescription data and plasma concentrations, respectively. The children's language competence was measured by a validated language grammar rating scale and classified into 3 categories. Women reported the use of folic acid in 44,417 (85.8%) and SSRI in 372 (0.7%) of the pregnancies, 260 used the 2 simultaneously. Compared with women who used folic acid and no SSRIs, the adjusted relative risk ratio of lower language competence rose with the increased duration of simultaneous use of folic acid and SSRIs. After simultaneous use at 4 to 8 four-week intervals, the relative risk ratio reached 4.5 (95% confidence interval, 2.5-8.0) and 5.7 (2.5-13.0) for the intermediate and most delayed category, respectively, using the best language competence category as the reference. The use of SSRIs without folic acid was not significantly associated with an increased risk. We detected a significant association between long-term use of SSRIs during pregnancy and delayed language competence in the offspring only when folic acid supplementation was used concomitantly. This surprising result warrants further studies.


Endothelial signaling and the dynamic regulation of arterial tone: A surreptitious relationship.
The endothelium is an integrated layer of cells whose dynamic regulation governs arterial tone development and the matching of blood flow delivery to tissue energetic demand. Investigating the structural and electrical properties of native endothelial cells has been a challenging prospect, with efforts often restricted to traditional myographic techniques. Concerted experimental attention, along with recent technical advances, has broadened the investigative tool kit, deepening mechanistic insights. This overview in part of a STI centered on the endothelium and how key structural/electrical properties guide arterial tone development and integrated network behavior. Articles are written in a provocative, opinionated manner to provoke deeper thought and to highlight areas of investigative deficiency.


Acute yellow phosphorus poisoning. "Smoking stool syndrome".
Three cases of acute phosphorus poisoning are reported. The source of this poison was a rodenticide, which may be in more common use presently because of the increasing resistance of rodents to warfarin derivatives. The safest method of managing poisoning from this highly toxic substance is prevention. Two of the patients had a history of previous medicine overdose.


Evolution of scaling emergence in large-scale spatial epidemic spreading.
Zipf's law and Heaps' law are two representatives of the scaling concepts, which play a significant role in the study of complexity science. The coexistence of the Zipf's law and the Heaps' law motivates different understandings on the dependence between these two scalings, which has still hardly been clarified. In this article, we observe an evolution process of the scalings: the Zipf's law and the Heaps' law are naturally shaped to coexist at the initial time, while the crossover comes with the emergence of their inconsistency at the larger time before reaching a stable state, where the Heaps' law still exists with the disappearance of strict Zipf's law. Such findings are illustrated with a scenario of large-scale spatial epidemic spreading, and the empirical results of pandemic disease support a universal analysis of the relation between the two laws regardless of the biological details of disease. Employing the United States domestic air transportation and demographic data to construct a metapopulation model for simulating the pandemic spread at the U.S. country level, we uncover that the broad heterogeneity of the infrastructure plays a key role in the evolution of scaling emergence. The analyses of large-scale spatial epidemic spreading help understand the temporal evolution of scalings, indicating the coexistence of the Zipf's law and the Heaps' law depends on the collective dynamics of epidemic processes, and the heterogeneity of epidemic spread indicates the significance of performing targeted containment strategies at the early time of a pandemic disease.


Prophylactic and therapeutic interventions for bleeding in dengue: a systematic review.
The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (<1%), during epidemics, due to the large number of people affected, overall mortality rates can be significant. The risk of clinically significant bleeding in dengue is unpredictable and often contributes to an adverse outcome. This systematic review focuses on the evidence for prophylactic and therapeutic interventions for bleeding in dengue infection. PubMed, CINAHL, Cochrane Library, Embase and Google Scholar were searched for randomized, quasi-randomized and non-randomized, prospective or retrospective studies that had a control group alongside an intervention aimed at stopping or preventing bleeding in dengue infection. Eleven studies that included 1904 patients in 12 study arms were eligible. These assessed the role of platelet transfusion [two randomized controlled trials (RCTs) and three non-randomized studies], plasma transfusion (one RCT), recombinant activated factor VII (one RCT), anti-D globulin (two RCTs), immunoglobulin (one RCT) and interleukin 11 (one RCT) as prevention or treatment for bleeding. Due to significant heterogeneity in study design and outcome reporting, a meta-analysis was not performed. Currently there is no evidence that any of the above interventions would have a beneficial effect in preventing or treating clinically significant bleeding in dengue.


Relationship between p53 and c-erbB-2 overexpression in tissue sections and cyst fluid cells of patients with ovarian cancer.
The expression of p53 protein and overexpression of c-erbB-2 oncoprotein was examined immunohistochemically and compared on frozen tissue sections and cyst fluid cells in patients with epithelial malignant and benign ovarian neoplasms. p53 was detected in 52.6% of carcinomas and c-erbB-2 expression was identified in 47.3% of cases. The relationship between p53 and c-erbB-2 overexpression in tissue sections and detached cyst fluid cells was evident. Moreover, a significant association between the presence of p53 and overexpression of c-erbB-2 proteins in tumor tissue sections and loose cyst fluid cells in individual patients was demonstrated. In tissue sections and loose cyst fluid cells of benign ovarian tumors no overexpression of p53 and c-erbB-2 proteins was found.


Analysis of Ecological Environment Problems and Countermeasures in Ideological and Political Education in Colleges and Universities.
At present, there are many problems in the mode and method of ideological and emotional education of college students. The state attaches great importance to this aspect and continues to increase investment, but the effect is not satisfactory. As an important field for cultivating high-level socialist talents, colleges and universities have played a huge role in promoting the ideological development and emotional education of college students. The emergence of this contradiction shows that traditional educational methods have their own shortcomings and need to expand their thinking and explore new research areas. Since the new era, the ideological education venues and teaching activities of colleges and universities have been greatly improved, but they are also facing many problems and challenges, which seriously affect the moral quality of college students and destroy the ideological education ecosystem of colleges and universities. From the perspective of the ecological crisis of education, this paper awakens and pays attention to the ecological problems of education, making it an inevitable trend of current education development and paving the way for future research. On this basis, the current situation of the ecology of political education of college students is analyzed, and the necessity of research is proposed. Analyzing the ideological and emotional education of college students from the perspective of ecology is essentially to regard the ideological education of college students as an ecosystem and deeply analyze the distribution of various components and elements of college students' ideological and political education. The ecology of college students' ideological education is the process, law, and overall ecological balance of various factors in the ideological education system of college students, as well as the methodological thinking and value orientation of the interaction between various factors and the environment. The changes of the ecological environment have a significant impact on people's state of mind. As college students growing up in the new environment, their thoughts, emotions, and values are all affected by the development of the ecological environment. Therefore, changes in the ecological environment, air quality, and water environment have increasingly obvious impacts on the living environment.


Effective Removal of Heavy Metals from Wastewater Using Modified Clay.
We report an economical and eco-friendly way to remove the heavy metal pollutant using modified clay. The modification of clay was done by calcining the natural clay from Kyushu region in Japan. Further, the removal efficiency for various pH and contact time was evaluated. The morphology of the clays was studied using the scanning electron microscopy (SEM). The structural and chemical analyses of modified clay were done by using X-ray diffraction (XRD), Raman spectroscopy, and Energy dispersion analysis (EDAX) to understand the properties related to the removal of heavy metal pollutant. Further, we studied the absorption efficiency of clay for various pH and contacting time using Ni polluted water. The modified clays show better removal efficiency for all pH with different saturation time. The adsorption follows pseudo-second order kinetics and the adsorption capacity of modified clay is 1.5 times larger than that of natural clay. The increase in the adsorption efficiency of modified clay was correlated to the increase in hematite phase along with increase in surface area due to surface morphological changes.


The impact of an aging population on curriculum development in Canadian undergraduate nursing education.
The rise in numbers of persons 65 years of age and older due to increased life expectancy is necessitating a revision in undergraduate nursing education. Since additional qualified nurses will be required to care for this expanding population, nursing programs must include sufficient relevant gerontological content delivered by competent faculty to prepare these practitioners. The authors review pertinent literature, present several surveys outlining the current status of gerontology content in nursing and other allied health programs, and argue for gerontological nursing to be a core component of undergraduate programs.


[The medical support of the Karelia front and its rear during the Great Patriotic War in 1941-1945].
The defense of the Zapolyarie continued from July 1941 to November 1944. The Karelia front with its medical service and rear institutions was organized in August 1941 for defense implementing. The medical support of the Karelia front and its rear was complicated by characteristics of transport system of the region, severe climate conditions, unfavorable epidemiological situation and insufficient number of medical institutions. In short terms, military and civil medical workers succeeded to organize system of evacuation of the wounded and ill persons, to develop hospital base of front of more than 17 thousand beds and to stabilize epidemiological situation. As a result, at relatively low surgical activity (20.9%) and hospital lethality (0.1%) medical workers of the Karelia front and its rear succeeded to return into service 84.2% of wounded and ill persons that is one of the highest indices in comparison with medical institutions of the oblasts of the central region of Russia. It is worth to emphasize that one of the characteristics of the front affected benevolently its medical support, was effective functioning of the Arkhangelskii state medical institute than being in rear, reoriented its pedagogic, research and curative activities to needs of war times.


Renal concentrating capacity test by desmopressin in children: intranasal or intravenous route?
Intranasal administration of desmopressin (dDAVP) is frequently used to test renal concentrating capacity in children. However, the bioavailability of intranasal dDAVP is about 10% and may be modified by nasal congestion. The study aimed to compare the efficacy of intranasal dDAVP with an equivalent dose of intravenous dDAVP for a renal concentrating capacity test in children. We studied 18 children aged 12.6 +/- 3.8 years weighing more than 20 kg in whom a dDAVP test was indicated as part of global renal function evaluation. Spray applicator (Minirin Spray) was used for intranasal administration (20-40 micrograms according to BW); the dose of intravenous dDAVP (Minirin IV) was reduced to 10% (2-4 micrograms according to BW). A randomized sequence was used for the first intranasal or intravenous dDAVP test; the second alternate test was repeated in the same children in a time interval ranging from 1 to 3 weeks. Osmolality of the urine (Uosm, mosm/kg) was determined before (T0), then 2 (T2) and 4 (T4) h after dDAVP administration. There was no significant difference in Uosm at T0 (intranasal = 480 +/- 212, intravenous = 443 +/- 168 mosm/kg), T2 (604 +/- 226 and 542 +/- 173 mosm/kg, respectively), and T4 (657 +/- 206 and 629 +/- 190 mosm/kg, respectively). There was an obvious correlation between intranasal and intravenous Uosm at T4 (r2 = 0.826; p = 0.001). Even if intravenous dDAVP is of theoretical interest, intranasal administration of dDAVP using a spray applicator can be considered as first-choice method for a renal concentrating capacity test in children weighing more than 20 kg.


Vitamin D-deficient diet rescues hearing loss in Klotho mice.
Klotho-deficient mice exhibit a premature aging syndrome, a feature of which is mild hearing loss. In the present study, the hearing phenotype of Klotho mice was characterized to better determine how well this phenotype resembles presbycusis in humans. It was demonstrated that Klotho animals have auditory-evoked brainstem response (ABR) threshold shifts of 14-18 dB in response to pure tone stimuli of 4, 8, 16 and 32 kHz, and similarly, in response to clicks; however, cochlear histology and spiral ganglion neuron density appeared normal in these mice. It was further demonstrated that a vitamin D-deficient diet normalizes serum calcitriol (1,25(OH)(2)D(3)) levels and prevents hearing loss in Klotho mice. It is concluded that hearing loss in Klotho mice is caused by elevated renal 1α-hydroxylase expression and consequent excessive production of calcitriol. These findings implicate the vitamin D metabolic pathway in hearing loss and pose questions as to the mechanism by which elevated calcitriol levels mediate such hearing loss.


Orthodontic considerations in adult surgical orthodontic cases.
The orthodontic considerations in orthognathic cases are based on a detailed understanding of the malocclusion, particularly a differential diagnosis of its facial, skeletal, and dental components, along with a recognition of the limitations of current orthodontic therapy. The goal is to develop a treatment plan that produces the optimal in esthetics, function, and stability while addressing the patient's chief complaint. Attention must be paid to the need to integrate the orthodontic component of treatment with the general dental and surgical phases of the patient's care.


Graduate Students' Perceived Preparedness and Confidence to Work With Individuals Who Use Augmentative and Alternative Communication.
Previous research shows that practicing speech-language pathologists do not feel confident working with augmentative and alternative communication (AAC) users. Studies examining the content of speech-language pathology graduate programs show that there has been an increase in AAC coursework and experiences offered during graduate training. What has not yet been determined is whether these requirements have influenced students' feelings of preparedness to work with AAC users. The purpose of this study was to examine speech-language pathology master's students' perceived preparedness and confidence to work with AAC users in relation to their educational experiences. A total of 726 graduate students completed a 25-item survey that solicited descriptions of their AAC training, coursework, and clinical experience, as well as their preparedness and confidence to work with AAC users after graduation. Analyses revealed statistically significant relationships between types and number of types of training experiences with feelings of preparedness and confidence. Results indicated that many participants did not feel prepared or confident to work with AAC users after graduation and that those with a greater variety of training experiences felt more prepared and confident to work with AAC users after graduation. The results enhance our understanding of the types and number of types of clinical experiences that might increase students' preparedness and confidence to work with AAC users.