[The assay of transcriptional activation effect of TR3 and deletion mutation in the yeast two hybrid system].
To assay the transcriptional activation effect of TR3 and it's deletion mutation in yeast two hybrid system. The total length of TR3 and TR3/delta1-690 gene was amplified by PCR method and cloned into pGBKT7 vector. Bait vector of pGBKT7-TR3 and pGBKT7-TR3/delta1-690 was transformed into AH109 competence yeast. Then self activation of the recombination vector was tested by assay the activity of beta-galactosidae. The pGBKT7-TR3 and pGBKT7-TR3/AM 690 vector was successfully constructed. The filter paper containing beta-galactosidae didn't changed to blue showed that the reporter gene wasn't activationed. TR3 and TR3/delta1-690 hadn't the activity of transcriptional activation.


Immunization of Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH vaccine prevents synaptic deficits of Alzheimer's disease.
The amyloid cascade hypothesis is widely accepted by researchers as the mechanism of Alzheimer's disease. Active immunization to eliminate Aβ depositions has been used in preclinical and clinical studies. Aβ3-10-KLH is a vaccine of the Aβ3-10 peptide combined with keyhole limpet hemocyanin (KLH). We immunized 2.5-month-old Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH peptide and Aβ1-42 peptide to eliminate Aβ deposits in the brains of these transgenic mice. The results of immunohistochemical staining and transmission electron microscopy detection indicated that our new vaccine was more advantageous in protecting synaptic function and structure than the Aβ1-42 peptide. Aβ3-10-KLH peptide is an effective vaccine in the treatment of Alzheimer's disease.


Repeated Transcranial Direct Current Stimulation Induces Behavioral, Metabolic and Neurochemical Effects in Rats on High-Calorie Diet.
Due to its high prevalence, obesity is considered an epidemic, which stimulated research on non-invasive methods to reduce excess body fat. Transcranial direct current stimulation (tDCS) is a non-invasive technique used to modulate the activity of cerebral cortex, which has already found increasing interest in medicine as a promising methodology. The aim of this study was to analyze the impact of tDCS on feeding behavior, metabolic abnormalities and neurotransmitters in certain brain areas involved in appetite control of obese rats. The male Wistar rats were divided into five subgroups depending on consumed diet effect (lean, obese) and tDCS type (anodal, cathodal, sham, and no stimulation). Two 10-min daily sessions of tDCS for 8 consecutive days of the study were applied. Rats subjected to active tDCS (anodal right or cathodal left of the prefrontal cortex) had reduced appetite and showed lesser body weight gain than the animals subjected to sham procedure or those receiving no stimulation at all. Furthermore, tDCS contributed to reduction of epididymal fat pads and to a decrease in blood concentration of leptin. Neurochemical examination revealed that tDCS modulated serotonin pathways of the reward-related brain areas and contributed to a significant decrease in the density of D2 but not D1 dopamine receptors in the dorsal striatum, recorded 5 h after the last stimulation. No significant effect of tDCS on dopamine and it's metabolites in examined brain regions was observed. It seems that the hypothalamus was not affected by tDCS application as no changes in measured neurotransmitters were detected at any examined time point. However, these results do not exclude the possibility of the delayed response of the monoamines in the examined brain areas to tDCS application. Altogether, these findings imply that repeated tDCS of the prefrontal cortex may change feeding behavior of obese rats. Either right anodal or left cathodal tDCS were sufficient to decrease food intake, to reduce body adiposity and to normalize other metabolic anomalies. These beneficial effects can be at least partially explained by changes in serotoninergic and in lesser extent dopaminergic system activity within some brain areas belonging to reward system.


Hemorrhagic pericardial effusion in beta-thalassemia major: report of a case.
Although sterile pericardial effusion occurs in about half of the patients with massive iron overload, hemorrhagic pericardial effusion is rarely seen in beta-thalassemia major patients. A 10-year-old girl with beta-thalassemia major who was diagnosed in her early infancy developed a massive hemorrhagic pericardial effusion. She was receiving blood transfusions every 4-6 weeks without chelating therapy with an average hemoglobin (Hb) level of 6-9 g/dL. Progressive hepatospenomegaly was noted during the course. She had complained of orthopnea with palpitation and bilateral leg edema before admission. After evaluation, a massive pericardial effusion was found and pericardiocentesis was performed twice, which revealed a bloody and uncoagulable effusion. Finally a pericardial window was performed to eliminate the bloody effusion. Negative etiological evaluations of blood and pericardial effusion were reported. Pathological examination of the pericardial biopsy revealed hemosiderosis with a few lymphocytic infiltrates. We report this case for its rarity and its necessity for urgent treatment.


Modeling auditory-visual evoked eye-head gaze shifts in dynamic multisteps.
In dynamic visual or auditory gaze double-steps, a brief target flash or sound burst is presented in midflight of an ongoing eye-head gaze shift. Behavioral experiments in humans and monkeys have indicated that the subsequent eye and head movements to the target are goal-directed, regardless of stimulus timing, first gaze shift characteristics, and initial conditions. This remarkable behavior requires that the gaze-control system 1) has continuous access to accurate signals about eye-in-head position and ongoing eye-head movements, 2) that it accounts for different internal signal delays, and 3) that it is able to update the retinal ( TE) and head-centric ( TH) target coordinates into appropriate eye-centered and head-centered motor commands on millisecond time scales. As predictive, feedforward remapping of targets cannot account for this behavior, we propose that targets are transformed and stored into a stable reference frame as soon as their sensory information becomes available. We present a computational model, in which recruited cells in the midbrain superior colliculus drive eyes and head to the stored target location through a common dynamic oculocentric gaze-velocity command, which is continuously updated from the stable goal and transformed into appropriate oculocentric and craniocentric motor commands. We describe two equivalent, yet conceptually different, implementations that both account for the complex, but accurate, kinematic behaviors and trajectories of eye-head gaze shifts under a variety of challenging multisensory conditions, such as in dynamic visual-auditory multisteps.


[Intestinal motility following jejunal resection: electromyography study in the rat].
The influences of massive resections on motility of the small intestine remain poorly known. The aim of our study was to determine the effects of jejunal resection on the pattern of occurrence of the migrating myoelectric complex and its postprandial inhibition. The experiments were performed over a period of 1 month after surgery. Transections were done on the jejunum or on the ileum in sham-operated animals. Ten days after resection, the motility of the anastomosed jejunal and ileal segments was dissociated. After one month, a functional continuity appeared through the anastomosis: the whole intestine worked synchronously at the same rhythm as the ileum. Food intake induced an increase in the frequency of the migrating myoelectric complexes measured 10 days after surgery. An adaptative phenomenon appeared after 30 days, the postprandial motor activity returning to its control level.


Medical treatment of migraine: from mechanisms of action to contraindications.
Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).


Coronary artery bypass graft patients' perception about the risk factors of illness: Educational necessities of second prevention.
Patients' beliefs about the cause of cardiac disease (perceived risk factors) as part of the global psychological presentation are influenced by patients' health knowledge. Hence, the present study aimed to assess the relationship between actual and perceived risk factors, identification of underestimated risk factors, and indication of underestimation of every risk factor. In this cross-sectional study, data of 313 coronary artery bypass graft (CABG) patients admitted to one hospital in the west of Iran were collected through a demographic interview, actual risk factors' checklist, open single item of perceived risk factors, and a life stressful events scale. Data were analyzed by means of Spearman's correlation coefficients and one-sample Z-test for proportions. Although there are significant relations between actual and perceived risk factors related to hypertension, family history, diabetes, smoking, and substance abuse (P < 0.05), there is no relation between the actual and perceived risk factors, and patients underestimate the role of actual risk factors in disease (P < 0.001). The patients underestimated the role of aging (98.8%), substance abuse (95.2%), overweight and obesity (94.9%), hyperlipidemia (93.1%), family history (90.3%), and hypertension (90%) more than diabetes (86.1%), smoking (72.5%), and stress (54.7%). Cardiac patients seem to underestimate the role of aging, substance abuse, obesity and overweight, hyperlipidemia, family history, and hypertension more than other actual risk factors. Therefore, these factors should be highlighted to patients to help them to (i) increase the awareness of actual risk factors and (ii) promote an appropriate lifestyle after CABG surgery.


Historical perspective on microalgal and cyanobacterial acclimation to low- and extremely high-CO(2) conditions.
Reports in the 1970s from several laboratories revealed that the affinity of photosynthetic machinery for dissolved inorganic carbon (DIC) was greatly increased when unicellular green microalgae were transferred from high to low-CO(2) conditions. This increase was due to the induction of carbonic anhydrase (CA) and the active transport of CO(2) and/or HCO(3) (-) which increased the internal DIC concentration. The feature is referred to as the 'CO(2)-concentrating mechanism (CCM)'. It was revealed that CA facilitates the supply of DIC from outside to inside the algal cells. It was also found that the active species of DIC absorbed by the algal cells and chloroplasts were CO(2) and/or HCO(3) (-), depending on the species. In the 1990s, gene technology started to throw light on the molecular aspects of CCM and identified the genes involved. The identification of the active HCO(3) (-) transporter, of the molecules functioning for the energization of cyanobacteria and of CAs with different cellular localizations in eukaryotes are examples of such successes. The first X-ray structural analysis of CA in a photosynthetic organism was carried out with a red alga. The results showed that the red alga possessed a homodimeric beta-type of CA composed of two internally repeating structures. An increase in the CO(2) concentration to several percent results in the loss of CCM and any further increase is often disadvantageous to cellular growth. It has recently been found that some microalgae and cyanobacteria can grow rapidly even under CO(2) concentrations higher than 40%. Studies on the mechanism underlying the resistance to extremely high CO(2) concentrations have indicated that only algae that can adopt the state transition in favor of PS I could adapt to and survive under such conditions. It was concluded that extra ATP produced by enhanced PS I cyclic electron flow is used as an energy source of H(+)-transport in extremely high-CO(2) conditions. This same state transition has also been observed when high-CO(2) cells were transferred to low CO(2) conditions, indicating that ATP produced by cyclic electron transfer was necessary to accumulate DIC in low-CO(2) conditions.


Synchronous bilateral seminoma: report of a case and literature review.
Bilateral occurrence of a primary testicular tumor is unusual. The reported incidence of bilateral germ cell tumors of the testes has been between 0.5 and 7% and the majority of these cancers (90%) are metachronous. We report the case of a 27-year-old man with synchronous bilateral seminoma and discuss the value of the histopathological diagnosis in therapy and prognosis. The related literature is concisely reviewed.


Collaboration between schools of nursing and local education agencies to provide health care services to pre-kindergarten through twelfth grade students: elements of cooperative agreements.
Establishing cooperative relationships between schools of nursing and local education agencies for the delivery of health care services to children from pre-school through the twelfth grade is a process all too often characterized by numerous legal, insurance, and administrative roadblocks. While nursing faculty and their students may wish to cooperate with professional educators and their students to enhance the health care of the children, there are obstacles. Both institutions are represented by attorneys, insurance companies and others who must attend to aspects of the process other than direct health care delivery. A model for joint planning and a list of elements of effective agreements are offered as a way of engaging all parties in a constructive and useful process of collaboration.


Optimizing the Benefit of CNS Radiation Therapy in the Pediatric Population-PART 1: Understanding and Managing Acute and Late Toxicities.
Radiation therapy continues to be a key component in the management of pediatric malignancies. Increasing the likelihood of cure while minimizing late treatment toxicity in these young patients remains the primary goal. Within the realm of central nervous system neoplasms, efforts to further improve the efficacy of radiation therapy continue, while balancing risks of damage to uninvolved tissue. Radiation therapy can result in second malignancies, as well as cerebrovascular, neurotoxic, neurocognitive, endocrine, psychosocial, and quality-of-life effects. In this article we describe these acute and late effects and their implications, and we highlight strategies that have emerged to reduce both the volume of tissue that is irradiated and the radiation dose delivered. The feasibility, efficacy, and risks of these newer approaches to radiation therapy continue to be evaluated and monitored; robust outcome data are needed.


Improving intelligence: a literature review.
Intelligence is associated with performance on a wide range of cognitive tasks and is a reliable predictor for educational and professional success. Therefore, the development of effective training regimens that aim to improve intelligence is of high interest. In recent years, there has been accumulating evidence that certain interventions have a positive impact on intelligence. The aim of the present paper is to provide a literature review on such studies. Despite promising results, we conclude that there are still many unknown variables and that the mechanisms that underlie improvements in intelligence are not well understood. More work is needed in order to disentangle these involved processes and to further refine existing training regimens.


Denosumab Therapy for Giant Cell Tumor of Bone Pulmonary Metastasis.
A 68-year-old female was diagnosed with giant cell tumor of bone (GCTB) metastatic to her lungs. The patient was treated with IV denosumab for the course of 4.5 years for these metastases. The metastatic tumor burden decreased significantly after only 3 months of therapy. The size of the metastases has been stable for over 4 years. Denosumab therapy has promise in the treatment of GCTB, including pulmonary metastasis. However, the long-term role of denosumab for pulmonary metastases is yet to be determined.


Influence of growth factors on an insulin-producing cell line (RINm5F).
The influence of IGF-I, insulin and epidermal growth factor (EGF) as well as glucose as control was studied on both growth and function of RINm5F cells, an insulin-producing cell line derived from rat insulinoma tissue. [3H]thymidine incorporation and DNA content (fluorometrically) were measured for estimating cell growth, insulin release and biosynthesis [( 3H]leucine incorporation) as parameters for cell function. There was a significant increase in both [3H] thymidine incorporation and DNA content into RIMm5F cells by glucose already at very low concentrations. IGF-I and high concentrations of insulin too were able to stimulate cell growth (insulin also in additional experiments with isolated rat islets). EGF, however, was without growth effect on this cell line (in contrast to previous own results in isolated islets). Insulin secretion and biosynthesis were also increased by very low glucose concentrations. IGF-I and EGF were ineffective regarding these functional parameters in RINm5F cells. Besides for glucose, our results demonstrate a role for IGF-I and insulin, but not for EGF, in regulating growth of these cells.


Collagenase expression by normal human eosinophils.
Collagenolytic activity was detected in extracts from human blood eosinophilic granulocytes. To characterize this collagenase, we compared extracts from isolated populations of eosinophils and neutrophils. Significant collagenase activity against type I and II collagens was present in extracts from both cell populations. Although collagenase activity was present in eosinophils, the cells did not stain with antibodies specific for fibroblast, neutrophil collagenase, or collagenase-3. In contrast, neutrophils immunostained positively with antibody to neutrophil collagenase. Western blot analysis confirmed the presence of immunoreactive protein in neutrophil extracts but not in the eosinophil extracts. Reverse transcription-polymerase chain reaction using primers specific for all three known collagenases of an eosinophil cell suspension from peripheral blood that had 3% contamination with immature neutrophils showed a polymerase chain reaction product only with neutrophil collagenase oligonucleotide primers, but not with fibroblast collagenase or collagenase-3 primers. Eosinophil collagenase would appear to have a unique antigenic structure and may represent a new enzyme.


Seamless adaptive servo-ventilation therapy after triple-valve surgery.
A 70-year-old man with severe multivalvular disease, atrial fibrillation, and kyphoscoliosis, had Cheyne-Stokes respiration with central sleep apnea. After triple-valve surgery with the maze procedure, adjunctive adaptive servo-ventilation therapy was initiated on the first postoperative day and continued seamlessly in the postoperative period. Seamless adaptive servo-ventilation therapy as an adjunct to triple-valve surgery is more likely to prevent heart failure remodeling without worsening of pulmonary hypertension and recurrence of atrial fibrillation.


Association of adjuvant aromatase inhibitor with cataract risk in postmenopausal women with breast cancer.
Aromatase inhibitor (AI) is a cornerstone drug for endocrine therapy of postmenopausal hormone receptor-positive breast cancer. The relationship between AI medication and subsequent cataract risk is yet inconclusive. A total of 1,697 postmenopausal, early-staged, and hormone receptor-positive breast cancer patients from the prospectively-maintained database of the Breast Surgery Department at Fudan University Shanghai Cancer Center were included, with 542 patients received no endocrine therapy and 1,155 treated with AI only. We explored the influence the use of AI or not and the duration of AI on the subsequent incidence of cataract. A total of 146 (8.6%) cataracts were observed in the whole study population. The incidence of cataract is highly related to age, with incidence of cataract in patients <50 years old, 50-60 years, ≥60 years was 2.9%, 6.9%, and 13.3%, respectively (P<0.001). There was no significant relationship between adjuvant AI use and cataract (7.4% in no endocrine group vs. 9.2% in the AI group) with an adjusted hazard ratio of 1.20 (95% confidence interval: 0.8-1.7, P=0.30). The incidence of cataract in patients with long-term AI (more than 5 years) could be high up to 14.7%, but without statistical significance compared to those the shorter duration (P=0.52). There is no significant association between use of AI and cataract in postmenopausal breast cancer patients. Of note, age is an important risk factor for cataract and it is necessary to surveil the eye health in postmenopausal elderly women.


Bone marrow stromal cells protect acute myeloid leukemia cells from anti-CD44 therapy partly through regulating PI3K/Akt-p27(Kip1) axis.
The anti-CD44 monoclonal antibody (mAb) A3D8 induces differentiation or apoptosis in vitro in various subtypes of acute myeloid leukemia (AML) via p27(Kip1) upregulation. Bone marrow (BM) stromal cells play a vital role in the development of chemoresistance in AML cells attached to the stroma. To investigate the effect of BM stroma adhesion induced AML resistance to A3D8, we developed a co-culture system composed of an AML-derived cell line (NB4) cultured with either a human BM stroma cell line (HS-5) or mesenchymal stem cells (MSCs). We found that NB4 cells adhered to HS-5 cells or MSCs developed resistance against the anti-proliferative effects of A3D8, and this action is caused by the activation of PI3K/Akt signaling following p27(Kip1) down-regulation and cytoplasmic re-localization. The stromal co-culture-induced resistance can be partially abolished by inhibiting the PI3K/Akt signaling pathway. Such findings were confirmed in two additional AML-derived cell lines as well as in primary AML cells. Our results suggest that BM stroma can induce A3D8 resistance in part via the PI3K/Akt-p27(Kip1) axis, and blocking PI3K/Akt pathway maybe necessary for anti-CD44 treatment on AML in BM microenvironment.


Cardiovascular risk scores in asymptomatic carotid stenosis: A validation study with ultrasonographic parameters.
We evaluated the feasibility of the Framingham stroke risk score (FSRS) and atherosclerotic cardiovascular disease (ASCVD) risk scores for asymptomatic carotid stenosis (ACS). In addition, we developed novel risk prediction models for ischemic stroke and composite outcomes by combining ultrasonographic parameters and conventional cardiovascular risk scores. We retrospectively enrolled 612 patients with ACS greater than 50% over 7 years and evaluated them using transcranial Doppler and carotid duplex ultrasonography. In total, 150 patients were included in the analysis. During the mean 5-year follow-up, 6 ischemic strokes and 25 composite events were detected. Among all ultrasonographic parameters, only a higher peak-systolic velocity/end-diastolic velocity ratio was detected and significantly associated with an increased risk of relevant ischemic stroke (hazard ratio: 1.502, 95% confidence interval: 1.036-1.968). The C-statistics of the FSRS and ASCVD risk scores were 0.646 and 0.649, respectively, for relevant ischemic stroke, and 0.612 and 0.649, respectively, for composite outcomes. C-statistics of the FSRS and ASCVD risk scores combined with ultrasonographic parameters increased to 0.937 and 0.941, respectively, for ischemic stroke, and 0.856 and 0.886, respectively, for composite outcomes. The study suggests that inclusion of ultrasonographic parameters in conventional cardiovascular scores helps identify the risk of further vascular events in ACS patients.


Anaphylaxis on reperfusion during liver transplantation with coagulopathy.
We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish. The trigger for anaphylaxis was postulated to be passive transfer of immunoglobulin to the recipient. Anesthesiologists should be notified of donor factors to anticipate anaphylaxis. In this report, we discuss coagulopathy of anaphylaxis and contrast it with disseminated intravascular coagulation.


Community-Based Participatory Research and its Potential Role in Supporting Diversity in Genomic Science.
This paper seeks to understand why targeted efforts to recruit subjects from underrepresented communities have failed to meaningfully increase diversity of genomic reference data. We review a variety of mechanisms that have attempted to establish trust with communities underrepresented in genomic research, including sophisticated informed consent, broad consent, community consultation, and initiatives designed to diversify the scientific workforce. We also analyze the ability of deep community engagement of the type advanced by community-based participatory research (CBPR) to address deficiencies in previous strategies to build trust. Previous strategies to build trust do not fully address key concerns related to the foundational aims and projects of scientific inquiry. The techniques of CBPR are well suited to address these concerns and thus build trust. Community engagement strategies show tremendous promise in supporting participation of underrepresented communities in genomic research.


Multicomponent Cyclopropane Synthesis Enabled by Cu-Catalyzed Cyclopropene Carbometalation with Organoboron Reagent: Enantioselective Modular Access to Polysubstituted 2-Arylcyclopropylamines.
The use of functional-group-tolerant organoboron in lieu of basic organometallic reagents in base-metal-catalyzed cyclopropene carbometalation opens three-component cyclopropane synthesis, as exemplified by the modular assembly of the highly medicinally relevant 2-arylcyclopropylamine (ACPA) framework via stereoselective carboamination. The highly enantioselective version has been realized to afford enantioenriched ACPAs with up to all three cyclopropyl carbons as stererogenic centers in one operation, representing the first example of enantioselective multicomponent cyclopropane synthesis. The reaction significantly improves the efficiency of ACPA synthesis and may inspire the development of other multicomponent cyclopropane syntheses beyond amination.


Management of Osmoprotectant Uptake Hierarchy in Bacillus subtilis via a SigB-Dependent Antisense RNA.
Under hyperosmotic conditions, bacteria accumulate compatible solutes through synthesis or import. Bacillus subtilis imports a large set of osmostress protectants via five osmotically controlled transport systems (OpuA to OpuE). Biosynthesis of the particularly effective osmoprotectant glycine betaine requires the exogenous supply of choline. While OpuB is rather specific for choline, OpuC imports a broad spectrum of compatible solutes, including choline and glycine betaine. One previously mapped antisense RNA of B. subtilis, S1290, exhibits strong and transient expression in response to a suddenly imposed salt stress. It covers the coding region of the opuB operon and is expressed from a strictly SigB-dependent promoter. By inactivation of this promoter and analysis of opuB and opuC transcript levels, we discovered a time-delayed osmotic induction of opuB that crucially depends on the S1290 antisense RNA and on the degree of the imposed osmotic stress. Time-delayed osmotic induction of opuB is apparently caused by transcriptional interference of RNA-polymerase complexes driving synthesis of the converging opuB and S1290 mRNAs. When our data are viewed in an ecophysiological framework, it appears that during the early adjustment phase of B. subtilis to acute osmotic stress, the cell prefers to initially rely on the transport activity of the promiscuous OpuC system and only subsequently fully induces opuB. Our data also reveal an integration of osmostress-specific adjustment systems with the SigB-controlled general stress response at a deeper level than previously appreciated.


Use of site-directed mutagenesis to probe the role of Cys149 in the formation of charge-transfer transition in glyceraldehyde-3-phosphate dehydrogenase.
Oligonucleotide-directed mutagenesis was employed to produce mutants of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Escherichia coli and Bacillus stearothermophilus. Three different mutants proteins--His176----Asn, Cys149----Ser, Cys149----Gly--were isolated from one or both of the enzymes. The study of the properties of these mutants has shown that Cys149 is clearly responsible for the information of a charge-transfer transition, named the Racker band, observed during the NAD+ binding to apoGAPDH. This result excludes a similarity between the Racker band and the charge-transfer transition observed following the alkylation of GAPDH by 3-chloroacetyl pyridine-adenine dinucleotide.


Influence of Chemotherapy Within 30 Days Before ICU Admission on Mortality in Critically Ill Medical Patients With Cancer.
The main objective was to determine whether the administration of chemotherapy (CT) during the month before intensive care unit (ICU) admission of medical patients with cancer influences the survival rate. The design was a single-institution observational cohort study in an ICU of a tertiary university hospital. Our cohort included 248 oncology patients admitted to the ICU from 2005 to 2014 due to nonsurgical problems. Seventy-six (30.6%) patients had received CT in the month before admission (CT group) and 172 did not receive CT (control group). The main outcome measures were ICU, hospital, 30-day, 90-day, and 1-year mortalities. We performed survival analysis using the Kaplan-Meier estimator, comparing both groups using the log-rank test, and multivariate analysis using Cox regression adjusted for gender, age, maximum Sequential Organ Failure Assessment (SOFA), and delta maximum SOFA to calculate the hazard ratios (HRs) and their respective 95% confidence intervals. This association was also evaluated by a graphic representation of survival. The CT group presented an ICU mortality rate of 27.6% versus 25.5% in the control group. The multivariate analysis adjusted for age, sex, and delta maximum SOFA showed significant differences between the groups (HR: 2.12; P = .009). The hospital mortality rate was 55.3% in the CT group compared to 45.4% in the control group (adjusted HR: 1.81; P = .003). At 30 days, the mortality rate was 56.6% in the CT group compared to 46.5% in the control group (adjusted HR: 1.69; P = .008). Mortality at 90 days was 65.8% in the CT group versus 59.9% in the control group (adjusted HR: 1.47; P = .03). One-year mortality was also higher in the CT group (79% vs 72.7%, adjusted HR: 1.44; P = .02). The administration of CT in the month before ICU admission in patients with cancer was associated with higher mortality in the ICU, in the hospital, and 30 and 90 days after admission when adjusted for the increase in organ failure measured by delta maximum SOFA. We provide useful new information for decision-making about ICU management of patients with cancer.


New therapies in systemic lupus erythematosus.
A new understanding of the pathogenesis of autoimmunity, the mechanisms of action of older drugs, the advent of target-specific biological therapies and pharmacogenomics has created multiple treatment options for the patient with systemic lupus erythematosus. These include topical therapies, more selective non-steroidal anti-inflammatory agents, hormonal interventions and a new generation of immune suppressives. Currently available strategies also include the use of intravenous gamma globulin, apheresis, stem-cell transplantation and antileprosy preparations alone or in combination with immune suppressives. A handful of biologicals have been studied in clinical trials. After two decades without new options for lupus patients practitioners now have a full menu of improved therapeutic options.


Thai tsunami victim identification overview to date.
The boxing day tsunami of 26 December 2004 caused devastation and loss of life around the Indian ocean. International disaster victim identification efforts were centred in Thailand, with many odontologists from over 20 countries contributing to the examination of deceased, collection of antemortem information, comparison and reconciliation of data. The contribution of forensic odontology to the identification process conducted in Thailand in response to the tsunami devastation is presented in a composite of short reports focused on the five phases associated with disaster victim identification. To date 1,474 deceased have been identified. Dental comparison has been the primary identifier in 79% of cases and a contributor in another 8%, a total of 87%.


Postoperative pain in older people: a review of the literature.
The literature review was conducted to explore those factors which complicate pain management in older people to inform future research, education and nursing practice in this area. Acute pain management in hospitalized older people is complex because of the physiological changes of ageing, pharmacological factors and under-representation of this patient group in reported research about assessing acute pain. A review of the literature was undertaken using electronic databases and specified search terms, some hand searching was also used and included the grey literature, textbooks and conference proceedings. A computerized literature search was carried out using CINAHL, Bandolier, Cochrane, Medline, the British Nursing Index and the International Association for the Study of Pain website for the period 1992-2004. The search terms were acute pain, older people, elder care, pain assessment and acute pain services. Thirty-seven research-based reviews and published studies and 17 policy documents were included. Managing acute pain well in older adults involves understanding the influence of a series of integrated factors: attitudes and beliefs, physiological ageing processes, pharmacological factors and the social construction of the older person in healthcare contexts. This review offers new insight into those factors which, taken together, add complexity to managing acute pain in older people well. Moreover, nurses are the professional group mainly responsible for assessing pain, administering and now prescribing analgesia and evaluating the quality of pain relief in older people. On this basis, they are also the group most likely to effect improved patient outcomes.


mRNA nuclear export and human disease.
Export of mRNA from the nucleus is a central process in eukaryotic gene expression that has been implicated in several human diseases. Much of our understanding of how an mRNA is transported to the cytoplasm is derived from studies using yeast and fly models. We present here different mechanisms by which aberrant nuclear retention of mRNA can cause human disease. Emerging evidence that implicates the mRNA export factor GLE1 in two lethal motor neuron disorders is discussed and we highlight surprising links to regulatory mechanisms that were first observed many years ago in yeast. These examples illustrate how model organisms have aided in our elucidation of complex human disorders through analysis of basic cellular processes.


Exomer: A coat complex for transport of select membrane proteins from the trans-Golgi network to the plasma membrane in yeast.
A yeast plasma membrane protein, Chs3p, transits to the mother-bud neck from a reservoir comprising the trans-Golgi network (TGN) and endosomal system. Two TGN/endosomal peripheral proteins, Chs5p and Chs6p, and three Chs6p paralogues form a complex that is required for the TGN to cell surface transport of Chs3p. The role of these peripheral proteins has not been clear, and we now provide evidence that they create a coat complex required for the capture of membrane proteins en route to the cell surface. Sec7p, a Golgi protein required for general membrane traffic and functioning as a nucleotide exchange factor for the guanosine triphosphate (GTP)-binding protein Arf1p, is required to recruit Chs5p to the TGN surface in vivo. Recombinant forms of Chs5p, Chs6p, and the Chs6p paralogues expressed in baculovirus form a complex of approximately 1 MD that binds synthetic liposomes in a reaction requiring acidic phospholipids, Arf1p, and the nonhydrolyzable GTPgammaS. The complex remains bound to liposomes centrifuged on a sucrose density gradient. Thin section electron microscopy reveals a spiky coat structure on liposomes incubated with the full complex, Arf1p, and GTPgammaS. We termed the novel coat exomer for its role in exocytosis from the TGN to the cell surface. Unlike other coats (e.g., coat protein complex I, II, and clathrin/adaptor protein complex), the exomer does not form buds or vesicles on liposomes.


Effects of a pulmonary rehabilitation program with balance training on patients with COPD.
Patients with chronic obstructive pulmonary disease (COPD) have balance impairments. However, pulmonary rehabilitation (PR) is associated with only minor improvements in functional balance. Therefore, there is a need to explore the role of balance training within PR. This study aimed at assessing the effects of a PR program, with a specific component of balance training, on functional balance of patients with COPD. Outpatients with COPD (N = 22, age = 68.0 ± 11.8 years; forced expiratory volume in 1 second = 72.2 ± 22.3% predicted) participated in a 12-week PR program including exercise training and psychosocial support and education. Exercise training sessions comprised endurance, strength, and a specific component of balance training. The Timed Up and Go (TUG) test was used to assess functional balance before and after the PR. Health-related quality of life (St George's Respiratory Questionnaire), quadriceps muscle strength (10 repetition maximum), and exercise tolerance (6-minute walk test) were also assessed. Patients demonstrated significant improvements in TUG scores after PR (mean change -1.7 ± 1.4 seconds; P = .001; effect size = 1.249). Before PR, 9 (41%) participants and after PR only 1 (4.5%) participant had a TUG performance worse than the average performance of age-matched healthy peers (P = .008). The St George's Respiratory Questionnaire symptoms score (P = .012), quadriceps muscle strength (P = .001), and exercise tolerance (P = .001) were also improved. Pulmonary rehabilitation with a specific component of balance training had a large effect on functional balance in patients with COPD. Findings highlight the value of including balance training in PR programs. Further research is needed to determine the optimal intervention to improve balance and its specific components among patients with COPD.


Characterization of proliferative cells in malignant melanomas and their inflammatory infiltrates.
Distinct changes in the antigenic phenotypes of mononuclear cells infiltrating primary and metastatic malignant melanomas (MM) have been shown to characterize distinct steps of melanoma progression. The purpose of our study is to establish whether the growth fraction of malignant melanoma cells is related to the mononuclear cell subtypes. Using monoclonal antibody Ki67, the presence of a nuclear antigen in proliferating cells of both tumor and inflammatory infiltrate cells was established in 20 primary recurrent and metastatic cutaneous melanomas. Monoclonal antibodies against lymphocyte and macrophage subsets were also applied in situ. Numerous CD8 and CD4 positive cells and natural killer (NK) cells were detected in all the infiltrates. A low CD4+/CD8+ ratio was observed in most tumors with a high proliferative activity. The presence of positive CD1+ cells seemed also to be correlated with a high activity. Our data suggest a correlation between inflammatory cell subsets and proliferative activity of MM.


Critical point of electrolyte mixtures.
The critical behavior of electrolyte mixtures was studied using grand canonical Monte Carlo simulations. Mixtures consist of large multivalent macroions and small monovalent co- and counterions. The system can be viewed as a binary mixture of macroions (with their counterions) and salt (co- and counterion pair). The primitive model description was used, in which the ions are point charges with a hard core and the solvent is treated as a uniform dielectric continuum. The grand canonical simulations are based on insertions and removals of neutral molecules: macroion with its counterions or coions and a counterion. We propose a distance biasing method that enables direct grand canonical simulations up to charge asymmetry of 10:1. We calculated the critical loci that connect the salt-free state, which consists of only macroions and counterions, with the pure salt state using mixed-field finite-size scaling with no pressure mixing. The critical parameters are determined for macroion to counterion charge asymmetries of 2:1, 3:1, and 10:1. Our results suggest that binary electrolyte mixtures are type-I mixtures, where the two components mix continuously.


Methods for Quantification of Soil-Transmitted Helminths in Environmental Media: Current Techniques and Recent Advances.
Limiting the environmental transmission of soil-transmitted helminths (STHs), which infect 1.5 billion people worldwide, will require sensitive, reliable, and cost-effective methods to detect and quantify STHs in the environment. We review the state-of-the-art of STH quantification in soil, biosolids, water, produce, and vegetation with regard to four major methodological issues: environmental sampling; recovery of STHs from environmental matrices; quantification of recovered STHs; and viability assessment of STH ova. We conclude that methods for sampling and recovering STHs require substantial advances to provide reliable measurements for STH control. Recent innovations in the use of automated image identification and developments in molecular genetic assays offer considerable promise for improving quantification and viability assessment.


Genkwadaphnin induces IFN-γ via PKD1/NF-κB/STAT1 dependent pathway in NK-92 cells.
The flower buds of Daphne genkwa Sieb. et Zucc. have been used as a traditional Chinese medicine although their functional mechanisms have not been discovered yet. We have studied the potential effects of the plant extracts on natural killer (NK) cell activation, and isolated an active fraction. Genkwadaphnin (GD-1) displayed a potent efficacy to induce IFN-γ transcription in NK cells with concentration- and time-dependent manners. GD-1 treatment triggered the phosphorylation of PKD1, a member of PKC family, MEK and ERK, resulting in IKK activation to induce IκB degradation, and the nuclear localization of p65, an NF-κB subunit, which regulates IFN-γ transcription. GD-1 effect on IFN-γ production was blocked by the addition of Rottlerin, a PKC inhibitor, CID 755673, a PKD inhibitor, or Bay11-7082, an IKKα inhibitor. The nuclear localization of p65 was also inhibited by the kinase inhibitors. Secreted IFN-γ activates STAT1 phosphorylation as autocrine-loops to sustain its secretion. GD-1 induced the phosphorylation of STAT1 probably through the increase of IFN-γ. STAT1 inhibitor also abrogated the sustained IFN-γ secretion. These results suggest that GD-1 is involved in the activation of PKD1 and/or ERK pathway, which activate NK-κB triggering IFN-γ production. As positive feedback loops, secreted IFN-γ activates STAT1 and elongates its production in NK-92 cells.


The Bacteroides glycocalyx as visualized by differential interference contrast microscopy.
The glycocalyx of eight strains representing six species of Bacteroides was examined by differential interference contrast microscopy. Wet mounts in India ink were prepared from bacteria cultured in broth and on an agar medium; the wet mounts were observed by phase-contrast microscopy and differential interference contrast microscopy. With differential interference contrast microscopy, all bacteria demonstrated a glycocalyx, which included capsules surrounding single cells and microcolonies, strands of glycocalyx connecting cells and microcolonies, detached slime, and solid masses of glycocalyx in which innumerable bacteria were enmeshed. Bacteria showed comparable amounts of glycocalyx by visual observation with differential interference contrast microscopy whether grown on plates or in broth. Serial transfers of cultures did not diminish the amount of glycocalyx. Differential interference contrast microscopy proved to be a superior method to phase contrast for examining wet preparations of Bacteroides.


Combining cytology and microcrystal detection in nonpurulent joint fluid benefits the diagnosis of septic arthritis.
To evaluate the performance of combined cytology and microcrystal detection in joint fluid for diagnosing septic arthritis. Retrospective single-center study of joint fluid samples from patients with manifestations suggesting acute or chronic arthritis. The absolute leukocyte count (/mm3) was recorded; as well as the differential counts, particularly of neutrophils (%). Microcrystals were sought and bacteriological cultures performed. Septic arthritis was defined as positive cultures of joint fluid or blood samples. Diagnostic performance was assessed based on sensitivity, specificity, the receiver-operating characteristics (ROC) curve with the area under the curve (AUC), and the positive and negative likelihood ratios (LR+ and LR-). Two hundred and eight joint fluid samples were included. The diagnoses were septic arthritis (n=28), chondrocalcinosis (n=41), gout (n=28), rheumatoid arthritis (n=33), spondyloarthritis (n=31), osteoarthritis (n=18), and undifferentiated arthritis (n=29). Among cytological parameters, those having the best diagnostic performance were the neutrophil count (cutoff, >50,000/mm3), the leukocyte count (cutoff, >50,000/mm3), and the percentage of neutrophils (cutoff, >95%); corresponding LR+ values were 8.93, 5.76, and 4.55, respectively. Neutrophil percentages lower than 80% had an LR- value of 0.07. Combining these cytological variables with the absence of crystals improved the diagnostic performance, yielding LR+ values of 11.36, 10.94, and 10.82 for neutrophils >95%, neutrophils >50,000/mm3, and leukocytes >50,000/mm3, respectively. Combining cytological characteristics of joint fluid with the absence of crystals benefits the diagnosis of septic arthritis.


Potatoes, glycemic index, and weight loss in free-living individuals: practical implications.
The role of glycemic index (GI) and foods with negative attributes related to GI as part of a weight loss regimen has not been thoroughly assessed in free-living individuals. This study examined the effects of a dietary prescription for energy intake modification, GI, and potato consumption on weight loss, dietary prescription adherence, body composition, and glucose control in a free-living, self-selecting overweight population. Ninety overweight (body mass index [BMI] 29.6 ± 3.9) men and women were randomly assigned to one of 3 groups for 12 weeks. Two groups were counseled to reduce their energy intake by 500 kcal/day and consume diets that were predominantly composed of either low- or high-GI foods (low glycemic index energy reduced [LGI-ER] or high glycemic index energy reduced [HGI-ER] diet, respectively). The third group received no energy restriction, GI provision, or nutritional counseling. All groups were instructed to consume 5-7 servings of potatoes per week. Changes in weight, body composition, glucose tolerance, and triglycerides were determined at baseline and 12 weeks. There were no significant differences in weight loss or changes in body composition between the groups; however, modest weight loss and body composition changes were seen from week 0 to week 12 for all groups (p < 0.05). Difficulty achieving the prescribed GI diets was evident in this free-living setting. There were no significant changes within or among treatments for fasting concentrations of triglycerides, glucose tolerance, insulin, or insulin sensitivity. The results indicate that in a free-living population of men and women, weight loss is associated with energy intake reduction. Potato intake did not cause weight gain and following either a high- or low-GI dietary prescription was difficult for free-living subjects, emphasizing the complex nature of changing dietary patterns.


Deadly addiction: India and Pakistan on the nuclear brink.
The effects of nuclear weapons on Hiroshima and Nagasaki and the political and moral context surrounding their use are discussed. The rationale for development of the Indian and Pakistani nuclear weapons programmes are summarised and critically examined in comparison to the costs of the programmes and the social needs, which could have been addressed. Alternative routes to provide peace and security are proposed, both for India, Pakistan, and other nuclear-weapon states, with particular emphasis on the role of physicians and other health workers.


Association Between miR-146a rs2910164 Polymorphism and Breast Cancer Susceptibility: An Updated Meta-Analysis of 9545 Cases and 10030 Controls.
Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC. Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC. Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility. In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.


Organizing the oocyte: RNA localization meets phase separation.
RNA localization is a key biological strategy for organizing the cytoplasm and generating both cellular and developmental polarity. During RNA localization, RNAs are targeted asymmetrically to specific subcellular destinations, resulting in spatially and temporally restricted gene expression through local protein synthesis. First discovered in oocytes and embryos, RNA localization is now recognized as a significant regulatory strategy for diverse RNAs, both coding and non-coding, in a wide range of cell types. Yet, the highly polarized cytoplasm of the oocyte remains a leading model to understand not only the principles and mechanisms underlying RNA localization, but also links to the formation of biomolecular condensates through phase separation. Here, we discuss both RNA localization and biomolecular condensates in oocytes with a particular focus on the oocyte of the frog, Xenopus laevis.


Indirect aqueous carbonation of CaSO4·2H2O with aspartic acid as a recyclable additive.
Calcium leaching using additives is the most critical step in the indirect aqueous carbonation process of CaSO4·2H2O. However, recovery of the soluble additives from the sulfate-rich carbonation filtrate limits the large-scale industrial implementation of current carbonation technologies. To address this issue, we employed aspartic acid (Asp) as a leaching additive. The dissolution capability of CaSO4·2H2O in aqueous ammonia was found to improve significantly owing to the complexation effect between Asp and the Ca2+ ions. The maximum amount of dissolved CaSO4·2H2O was determined according to the competitive relationship between the complexing effect and the inhibitory effect of free ammonia molecules on the dissociation of CaSO4·2H2O, and the solution pH influences such competition. The precipitation of CaCO3 was examined by monitoring the variations in the pH and conductivity of the carbonation reaction system. As a result, the shift in the Asp dissociation equilibrium extended the induction period, and the growth period was divided into three stages according to the relative difference between the consumption and formation rates of CO3 2-. Moreover, it was determined that the carbonation products consisted of stable spherical vaterite particles. The recovery of Asp was also demonstrated at its isoelectric point, with a recovery efficiency of >80% being achieved, and recycling experiments confirmed the stability of the recycled Asp. Finally, the amount of dissolved CaSO4·2H2O and the total carbonation efficiency during cycling were determined as 16.3 ± 0.4 g L-1 and 46.5 ± 1.9%, respectively.


Robotic-Assisted Radical Prostatectomy with the Use of Barbed Sutures.
The aim of this study is to analyze the principal advantages of posterior muscolo-fascial reconstruction using knotless barbed sutures (BS) during robot-assisted radical prostatectomy (RARP). We analyzed the available evidence regarding the efficacy and safety of principal BS (Quill™ SRS Angiotech Pharmaceuticals Inc., Vancouver, Canada; V-Loc™ Medtronic, Dublin, Ireland; STRATAFIX™ Ethicon Inc., Somerville, New Jersey; Filbloc® Assut Europe S.p.A., Rome, Italy). We analysed the principal outcomes (operative time and suturing time of urethra-vesical anastomosis, length of catheterization, hospital stay, and postoperative complications rate) reported in literature. In light of our experience, we believe that the utilization of BS during RARP is safe as the development of a new surgical technique of urethrovesical anastomosis offers advantages in terms of continence rate, length of catheterization, and other surgical outcomes. Other studies (prospective trials) are necessary to investigate the real benefits of BS in comparison to conventional sutures (CS).


Quantum-well-induced giant spin-orbit splitting.
We report on the observation of a giant spin-orbit splitting of quantum-well states in the unoccupied electronic structure of a Bi monolayer on Cu(111). Up to now, Rashba-type splittings of this size have been reported exclusively for surface states in a partial band gap. With these quantum-well states we have experimentally identified a second class of states that show a huge spin-orbit splitting. First-principles electronic structure calculations show that the origin of the spin-orbit splitting is due to the perpendicular potential at the surface and interface of the ultrathin Bi film. This finding allows for the direct possibility to tailor spin-orbit splitting by means of thin-film nanofabrication.


Direct Gallbladder Indocyanine Green Injection Fluorescence Cholangiography During Laparoscopic Cholecystectomy.
Intravenous injection of indocyanine green (ICG) is used to illuminate extrahepatic biliary anatomy. Fluorescence of biliary structures may lower surgical complications that can arise due to inadvertent injury to the common bile duct. We describe a method of injecting ICG directly into the gallbladder to define the cystic duct and common bile duct anatomy. A standard laparoscopic cholecystectomy was performed using a laparoscope with near-infrared imaging capability. Before dissection, the gallbladder was punctured with a cholangiogram catheter or a pigtail catheter to aspirate the bile within the gallbladder. The aspirated bile is mixed with ICG solution, which is reinjected into the gallbladder to fluoresce the gallbladder, cystic duct, and common bile duct structures. Eleven patients underwent direct gallbladder ICG injection for fluorescence cholangiography during cholecystectomy. Direct gallbladder ICG injection clearly defined the extrahepatic biliary anatomy, including the cystic duct-common bile duct junction, by fluorescence. In addition, the dissection plane between the gallbladder and the liver is highlighted with the gallbladder ICG fluorescence. Direct gallbladder ICG injection provides immediate visualization of extrahepatic biliary structures and clarifies the dissection plane between the gallbladder and the liver bed.


Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes.
Recent investigation has focused on identifying signaling pathways that inhibit cardiac hypertrophy, a major risk factor for cardiovascular morbidity and mortality. In this context, nitric oxide (NO), signaling via cGMP and cGMP-dependent protein kinase type I (PKG I), has been recognized as a negative regulator of cardiac myocyte (CM) hypertrophy. However, the underlying mechanisms are poorly understood. Here, we show that PKG I inhibits CM hypertrophy by targeting the calcineurin-NFAT signaling pathway. Calcineurin, a Ca2+-dependent phosphatase, promotes hypertrophy in part by activating NFAT transcription factors which induce expression of hypertrophic genes, including brain natriuretic peptide (BNP). Activation of PKG I by NO/cGMP in CM suppressed NFAT transcriptional activity, BNP induction, and cell enlargement in response to alpha(1)-adrenoreceptor stimulation but not in response to adenoviral expression of a Ca2+-independent, constitutively active calcineurin mutant, thus demonstrating NO-cGMP-PKG I inhibition of calcineurin-NFAT signaling upstream of calcineurin. PKG I suppressed single L-type Ca2+-channel open probability, [Ca2+]i transient amplitude, and, most importantly, L-type Ca2+-channel current-induced NFAT activation, indicating that PKG I targets Ca2+-dependent steps upstream of calcineurin. Adenoviral expression of PKG I enhanced NO/cGMP inhibitory effects upstream of calcineurin, confirming that PKG I mediates NO/cGMP inhibition of calcineurin-NFAT signaling. In CM overexpressing PKG I, NO/cGMP also suppressed BNP induction and cell enlargement but not NFAT activation elicited by constitutively active calcineurin, which is consistent with additional, NFAT-independent inhibitory effect(s) of PKG I downstream of calcineurin. Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy.


Diagnosing epilepsy in older adults: what does it mean for the primary care physician?
Acute and chronic seizures (epilepsy) occur frequently in older adults. However, despite their high prevalence, the condition is often overlooked or misdiagnosed because seizures mimic other common spells in the aged. The causes of seizures in older adults are often the sequelae of highly prevalent conditions that occur in this age group, eg, stroke, dementia, and head trauma. Recognizing and correctly diagnosing seizures can lead to a number of effective treatments. This article reviews the causes and presentation of seizures in older adults and offers an approach for diagnosis.


Genetic Penetrance of Macular Telangiectasia Type 2.
The apparent genetic penetrance of macular telangiectasia type 2 (MacTel) is important for gene discovery studies and for clinical risk assessment of affected individuals' family members. To determine the genetic penetrance of MacTel. Descriptive cross-sectional study of patients with MacTel at a tertiary referral eye center. From 2008 to 2016, consecutive patients with MacTel were independently identified, and all of their available siblings and parents were recruited. Seventeen probands with MacTel were included in the study who satisfied the requirement of having at least 1 parent or sibling willing and able to participate. Data from these 17 families were included for the analysis of apparent genetic penetrance. Determination of MacTel genetic penetrance in probands' parents and siblings. Of 80 study participants, 50 (62.5%) were women. The mean (SD) age of study participants with MacTel was 61.2 (14.0) years (range, 23-81 years) and without MacTel was 60.7 (16.4) years (range, 24-92 years). There were 17 MacTel probands, and there was a high rate of enrollment of living siblings and parents: 52 of 71 living siblings (73%) and 11 of 12 parents (92%). Of 52 enrolled siblings, 9 (17%) were affected. Of 11 enrolled parents, 3 (27%) had MacTel. Apparent genetic penetrance was calculated to be 0.35 (95% CI, 0.14-0.6) by sibling analysis and 0.55 (95% CI, 0.02-1.00) by parent analysis. Combining the sibling and parent analyses, the apparent penetrance was calculated to be 0.38 (95% CI, 0.19-0.57). The genetic penetrance of MacTel in rigorously phenotyped multiple large families is described. Families such as these could be critical for successful identification of MacTel genes.


Akt2-Dependent Beneficial Effect of Galanin on Insulin-Induced Glucose Uptake in Adipocytes of Diabetic Rats.
Glucose uptake occurs via the activation of an insulin-signaling cascade, resulting in the translocation of glucose transporter 4 (GLUT4) to the plasma membrane of adipocytes and myocytes. Recent research found that galanin could boost insulin-induced glucose uptake. This study aimed to explore whether activation of Akt2 mediates the beneficial effects of galanin on insulin-induced glucose uptake in the adipocytes of diabetic rats. In this experiment, insulin, galanin and MK-2206, an Akt inhibitor, were injected individually or in combination into diabetic rats once a day for ten days. Then, glucose uptake and pAkt2 and its downstream proteins were examined in adipocytes. Administration of galanin significantly enhanced insulin-induced 2-Deoxy-D-[3H]glucose uptake; GLUT4 and vesicle-associated membrane protein 2 contents in plasma membranes; and pAkt2Thr308/Ser473 and Akt2 mRNA expression levels in adipocytes. In addition, Akt2 downstream proteins including phosphorylated AS160 were increased, but the levels of phosphorylated forkhead box O1 and glycogen synthase kinase-3β were reduced. Treatment with MK-2206 may block the beneficial effects of galanin on these insulin-induced events. The results of this study suggest that phosphorylation of Akt2 mediates the beneficial effects of galanin on insulin-induced glucose uptake in the adipocytes of diabetic rats.


Complete atrioventricular block, shock, and hyperkalemia induced by toxic adenoma of the thyroid gland.
The case of a 74-year-old woman with toxic thyroid adenoma, presenting as complete heart block, is described. Upon admission the patient was in a state of circulatory collapse with metabolic acidosis and hyperkalemia. After initiation of right ventricular pacing the circulatory and metabolic disorders rapidly normalized without any other specific therapy. Since treatment and attainment of the euthyroid state the patient has had no conduction delays or arrhythmias. Complete heart block in thyrotoxicosis is uncommon and previous reports relate to its occurrence in Graves' disease, usually complicated by infectious disorders. This is the only case known to us of complete heart block in toxic thyroid adenoma.


Spinal anesthesia for transurethral resection operations: bupivacaine versus levobupivacaine.
This study tested the hypothesis that 0.5% levobupivacaine might be a good alternative to 0.5% plain bupivacaine for local spinal anesthesia during transurethral resection (TUR) operations. A prospective, randomized, double-blinded study was conducted on 50 male ASA I-III patients aged >60 years who were scheduled for elective transurethral resection operations. After routine monitoring, spinal anesthesia was performed with patients in the left lateral position using a 25G Quincke needle in the L3-4 interspace with a midline approach. Group B (N.=25) received 2.5 mL of 0.5% plain bupivacaine and Group L (N.=25) received 2.5 mL of 0.5% levobupivacaine via intratechal injection. The characteristics of sensory and motor block, hemodynamic data, side effects, and patient and surgeon satisfaction were recorded. Patients were observed until the level of sensory block was S1 and the Bromage score was 0. There were no significant differences between the two groups for patient demographic data, American Society of Anesthesiologists (ASA) classification, type and duration of operation, side effects, and patient and surgeon satisfaction. Hemodynamic parameters were similar in both groups before and during the operation. The highest level of sensory block was T(7)(T(3)-T(10)) in Group B and T9(T4-T12) in Group L (P=0.001). Administration of 0.5% levobupivacaine may be a good alternative to 0.5% plain bupivacaine for local spinal anesthesia during TUR operations.


Clozapine following ECT: a two-step treatment.
Some candidates for clozapine treatment may be unable to be given the drug. They may be so severely ill that they cannot or will not ingest a pill; their psychosis may have so compromised their physical status that use of clozapine, which produces a broad range of side effects, would be unsafe; and/or they may require a very rapid control of their behavior. Two case reports are described of patients who, although candidates for clozapine, were unable to take or be given the drug. Initial treatment with electroconvulsive therapy (ECT) was tried in both patients prior to use of clozapine. In the two cases described, treatment with ECT prior to clozapine stabilized the patients enough that clozapine could be administered. In both cases, the clozapine appeared to perpetuate the initial clinical response produced by the ECT. These case reports suggest that a two-step strategy of ECT followed by clozapine treatment may both facilitate the use of clozapine in some patients and perpetuate the clinical stability produced by ECT alone.


Trans 18-carbon monoenoic fatty acid has distinct effects from its isomeric cis fatty acid on lipotoxicity and gene expression in Saccharomyces cerevisiae.
Epidemiological studies have suggested that an excess intake of trans-unsaturated fatty acids increases the risk of coronary heart disease. However, the mechanisms of action of trans-unsaturated fatty acids in eukaryotic cells remain unclear. Since the budding yeast Saccharomyces cerevisiae can grow using fatty acids as the sole carbon source, it is a simple and suitable model organism for understanding the effects of trans-unsaturated fatty acids at the molecular and cellular levels. In this study, we compared the physiological effects of Δ9 cis and trans 18-carbon monoenoic fatty acids (oleic acid and elaidic acid) in yeast cells. The results obtained revealed that the two types have distinct effects on the expression of OLE1, which encodes Δ9 desaturase, and lipotoxicity in are1Δare2Δdga1Δlro1Δ and gat1Δ cells. Our results suggest that cis and trans 18-carbon monoenoic fatty acids exert different physiological effects in the regulation of gene expression and processing of excess fatty acids in yeast.


High-resolution imaging spectrometer for recording absolutely calibrated far ultraviolet spectra from laser-produced plasmas.
An imaging spectrometer was designed and fabricated for recording far ultraviolet spectra from laser-produced plasmas with wavelengths as short as 155 nm. The spectrometer implements a Cassegrain telescope and two gratings in a tandem Wadsworth optical configuration that provides diffraction limited resolution. Spectral images were recorded from plasmas produced by the irradiation of various target materials by intense KrF laser radiation with 248 nm wavelength. Two pairs of high-resolution gratings can be selected for the coverage of two wavebands, one grating pair with 1800 grooves/mm and covering approximately 155-175 nm and another grating pair with 1200 grooves/mm covering 230-260 nm. The latter waveband includes the 248 nm KrF laser wavelength, and the former waveband includes the wavelength of the two-plasmon decay instability at 23 the KrF laser wavelength (165 nm). The detection media consist of a complementary metal oxide semiconductor imager, photostimulable phosphor image plates, and a linear array of 1 mm(2) square silicon photodiodes with 0.4 ns rise time. The telescope mirrors, spectrometer gratings, and 1 mm(2) photodiode were calibrated using synchrotron radiation, and this enables the measurement of the absolute emission from the laser-produced plasmas with temporal, spatial, and spectral resolutions. The spectrometer is capable of measuring absolute spectral emissions at 165 nm wavelength as small as 5x10(-7) J/nm from a plasma source area of 0.37 mm(2) and with 0.4 ns time resolution.


"The Real Thing I Struggle with is Other People's Perceptions": The Experiences of Autistic Performing Arts Professionals and Attitudes of Performing Arts Employers in the UK.
This research examined in-depth the employment experiences of autistic performing arts professionals and the attitudes and adjustments of performing arts employers. We interviewed 18 autistic performing arts professionals and 19 performing arts employers. Autistic performing arts professionals described facing challenges in the workplace. Some autistic professionals had access to support, but the majority felt that there was not enough available and highlighted many ways in which they could be better supported. Performing arts employers varied in their experiences of working with autistic people, many had limited knowledge about autism-specific support or relied on other professionals to provide it. These findings shed light on current unmet support needs of autistic performing arts professionals, and provide key recommendations for research and practice.


Parosteal (juxtacortical) osteogenic sarcoma. A roentgenological study of 30 patients.
Detailed analysis of the roentgen findings in 30 well-documented cases of parosteal osteogenic sarcoma (POS) was made. The supposedly characteristic periosteal lucency (cleavage plane) was found in only 30% of the patients. While most tumors were densely ossified, the radiodensity was uniform in only 27%. The surface of the tumor was usually irregular and a truly smooth surface was seen in only 24%. Four patients underwent arteriography; there was vessel displacement by the tumors but all were avascular. No correlation between the histologic grade of tumor and roentgen signs was found.


Non-NMDA receptors in frog retina: an immunocytochemical study.
Glutamate is one of the main neurotransmitters in the retina. Its effects are mediated by a large number of ionotropic and metabotropic membrane receptors. The distribution of ionotropic AMPA receptor subunits GluR1-4, kainate receptor subunits GluR5-7 and KA2, delta receptors 1-2, as well as the metabotropic receptor mGluR6 were studied in the frog retina. Indirect immunofluorescence was used to localize the different receptor subunits. Results showed that all subunits, with the exception of GluR1 and GluR5, are widely distributed in the retina. They are mainly located in both plexiform layers: the outer (OPL) and the inner one (IPL), where punctate labelling, a sign of synaptic localization, is observed. The metabotropic receptor mGluR6 is localised only in the OPL. The AMPA receptor subunit GluR4 is localised on the glial Müller cells of the retina. The vast majority of the subunits possess specific patterns of labelling that indicate that they are involved with different retinal functions. The significance of the AMPA receptors and involvement of glia in modulation of synaptic transmission are discussed.


Simple quality assurance based on filtered back projection for geometrical/irradiation accuracy in single-isocenter multiple-target stereotactic radiotherapy.
In single-isocenter multiple-target stereotactic radiotherapy (SIMT-SRT), it is difficult to evaluate both the geometrical accuracy and absorbed dose measurement when irradiating off-isocenter targets. This study aimed to develop a simple quality assurance (QA) method to evaluate off-isocenter irradiation position accuracy in SIMT-SRT and compare its feasibility with that of a commercial device. First, we created two types of inserts and metallic balls with a diameter of 5 mm to be inserted into a commercially available phantom (SIMT phantom). Second, we developed a dedicated analysis software using Python for the Winston-Lutz test (WLT). Third, an image processing software, including the filtered back-projection algorithm, was developed to analyze the images obtained using an electronic portal imaging device (EPID). Fourth, the feasibility of our method was evaluated by comparing it with the results of WLT using two commercially available phantoms: WL-QA and MultiMet-WL cubes. Notably, 92% of the results in one-dimensional deviations were within 0.26 mm (EPID pixel width). The correlation coefficients were 0.52, 0.92, and 0.96 in the left-right, superior-inferior, and anterior-posterior directions, respectively. In the WLT, a maximum two-dimensional deviation of 0.70 mm was detected in our method, while the deviation in the other method was within 0.5 mm. The advantage of our method is that it can evaluate the geometrical accuracy at any gantry angle during dynamic rotation irradiation using a filtered back-projection algorithm, even if the target is located off the isocenter. Our method can perform WLT at arbitrary positions and is suitable for the QA of dynamic rotation irradiation using an EPID.


Cephalic Tetanus: A Case Report In 68-Year-Old Man.
Cephalic tetanus is an emergency condition, which is commonly observed in child age group here we report a case of 68-year-old man with the complain of right sided weakness for one day, associated with difficulty in breathing and speech, history of fall also present, case was diagnosed as cephalic tetanus. Here we report a case of cephalic tetanus in an elderly patient.


Red and green aequorins for simultaneous monitoring of Ca2+ signals from two different organelles.
Simultaneous control of different functions by calcium signals is possible because of subcellular compartmentalization. Targeted chemiluminescent Ca2+ probes, such as aequorins (AEQs) are optimal for detecting signals originating in different subcellular domains, but imaging is difficult because of low photon yield causing poor spatiotemporal resolution. To overcome this problem, we have co-expressed two spectrally distinct AEQs in different subcellular locations within the same cells. Seven chimeric proteins containing either green- or red-emitting AEQs, with different targeting sequences and Ca2+ affinities, have been designed and tested. We show here evidence for physical and functional independence of the different probes. Cytosolic Ca2+ signals were mirrored in the nucleus, but amplified inside mitochondria and endoplasmic reticulum, and had different time courses in the various locations. Our results demonstrate that these novel tools permit simultaneous and independent monitoring of [Ca2+] in different subcellular domains of the same cell.


Cannabinoid self-administration increases dopamine release in the nucleus accumbens.
In the present study, dopamine release was monitored during cannabinoid self-administration in rats to achieve a detailed understanding of the way in which dopamine mediates the reinforcing effects of cannabinoids. Extracellular dopamine levels were measured in the shell of the nucleus accumbens of either Lister Hooded or Long Evans rats trained to self-administer the cannabinoid CB1 receptor agonist WIN 55,212-2. A significant relationship between extracellular dopamine levels and bar-pressing rates was observed in both strains, as the dopamine content appreciably increased in respect to basal values during cannabinoid intake. Importantly, dopamine was not modified when trained rats were shifted to vehicle self-administration suggesting that an enhanced activity of the mesolimbic dopamine pathway underlies cannabinoid-taking behaviour.


Cytology of embryonal rhabdomyosarcoma: a cytologic, light microscopic, electron microscopic, and immunohistochemical study of seven cases.
A correlated cytologic and histologic study of seven cases of embryonal rhabdomyosarcoma is presented. The diagnosis of rhabdomyosarcoma was established by light and electron microscopy and immunohistochemistry of the operative specimens. The cytologic appearance of the smears corresponded well with the histopathologic findings. Cytologically, two main cell types were distinguished: a predominant primitive, small round cell with scant cytoplasm and a large cell with an abundant cytoplasm, sometimes tadpole- or ribbon-shaped. The tumor cells were often enclosed in a background of mucosubstances. The lack of cytologic features proving rhabdomyoblastic differentiation, such as cross-striation, necessitates the use of additional methods in the cytologic diagnosis of embryonal rhabdomyosarcoma. The value of the embedding technique for ultrastructural analysis and immunohistochemistry in the demonstration of desmin in aspirates is emphasized in the diagnosis of embryonal rhabdomyosarcoma.


High frequency shoot regeneration from nodal and shoot tip explants in Holarrhena antidysenterica L.
Shoot tip and nodal segment explants of Holarrhena antidysenterica when cultured on MS medium containing BAP (1.0-3.0 mg/l) with NAA (0.2-1.0 mg/l) and BAP (1.0-3.0 mg/l) with Kn. (0.2-1.0 mg/l) produced multiple shoots. Maximum multiple shoots was found in MS medium supplemented with BAP (2.0 mg/l) and NAA (0.5 mg/l). Subculture on the same medium resulted in rapid shoot multiplication at an average rate of 16 new shoots per subculture. Addition of urea (100 mg/l) in the medium increased the number of shoots up to 22 per culture. For best rooting, the shoots were excised from the culture flask and implanted individually on half strength MS medium with 0.5 mg/l each of IBA, IAA and NAA. After 20 days of transfer on root induction medium 95% rooting was achieved. Regenerated plantlets were successfully acclimatized and established in soil. About 90% of plantlets survived under open field conditions.


Association of Single Nucleotide Polymorphism rs2228570 with Lumbar Disc Degeneration: A Case-Control Study and Meta-Analysis.
To examine the association between single nucleotide polymorphisms (SNPs) rs2228570, rs731236, rs7975232, and rs1544410 and lumbar disc degeneration (LDD) predisposition. A search strategy was carried out, and the data were extracted after being chosen by the inclusion and exclusion criteria. Pooled odds ratios and 95% confidence intervals were calculated to assess the association between the aforementioned SNPs and LDD under allelic, dominant, recessive, heterozygous, and homozygous genetic models. In addition, a case-control study involving 46 LDD cases and 45 controls was also performed in the analysis to verify the result. A total of 17 studies were included in this meta-analysis. The pooled results did not show any association between vitamin D receptor (VDR) gene polymorphisms and LDD. But, interestingly, in subgroup analysis, the rs2228570 polymorphism was associated with LDD under the allelic (OR = 0.70, 95% CI = 0.56-0.87, p = 0.002), recessive (OR = 0.60, 95% CI = 0.43-0.84, p = 0.003), and homozygous (OR = 0.47, 95% CI= 0.28-0.79, p = 0.004) genetic models in the Asian population. SNPs rs731236 and rs7975232 still did not show any obvious association. We obtained a similar result from the case-control study: rs2228570 had an obvious relationship with LDD under allelic and homozygous genetic models. At the same time, we found that rs2228570 was also associated with the degree of low back pain (visual analogue scale, VAS score) in LDD population. SNP rs2228570 was significantly associated with LDD predisposition and the degree of low back pain in the Asian population.


Vibronic Coupling in Vitamin B12: A Combined Spectroscopic and Computational Study.
Understanding the diverse reactivities of vitamin B12 and its derivatives, collectively called cobalamins, requires detailed knowledge of their geometric and electronic structures. Electronic absorption (Abs) and resonance Raman (rR) spectroscopies have proven invaluable in this area, particularly when used in concert with computational techniques such as density functional theory (DFT). There remain, however, lingering uncertainties in the computational description of electronic excited states of cobalamins, particularly surrounding the vibronic coupling that impacts the Abs bandshapes and gives rise to rR enhancement of vibrational modes. Past computational analyses of the vibrational spectra of cobalamins have either neglected rR enhancement or calculated rR enhancement for only a small number of modes. In the present study, we used the recently developed ORCA_ASA computational tool in conjunction with the popular B3LYP and BP86 functionals to predict Abs bandshapes and rR spectra for vitamin B12. The ORCA_ASA/B3LYP-computed Abs envelope in the visible spectral region and rR spectra of vitamin B12 agree remarkably well with our experimental data, while BP86 fails to reproduce both. This finding represents a significant advance in our understanding of how these two commonly used density functionals differently model the electronic properties of cobalamins. Guided by the computed frequencies for the Co-C stretching and Co-C-N bending modes, we identified, for the first time, isotope-sensitive features in our rR spectra of 12CNCbl and 13CNCbl that can be assigned to these modes. A normal coordinate analysis of the experimentally determined Co-C stretching and Co-C-N bending frequencies indicates that the Co-C force constant for vitamin B12 is 2.67 mdyn/Å, considerably larger than the Co-C force constants reported for alkylcobalamins.


X-ray effects on single nerve fibers.
Electrophysiological responses of median and lateral giant nerve fibers of the earthworm were recorded during exposure, in vitro, to x-rays. In response to external stimulation, during x-irradiation, these nerve fibers showed initially an increase in conduction velocity, a rise in spike amplitude, a decrease in relative refractory period, and an increase in sensitivity. These responses represent an enhancement of activity, attributable to bombardment with x-rays, rarely found in other biological systems. They were followed by deterioration of activity and eventual block, representative of the lethal action of x-rays, commonly observed in other biological systems. Several properties of the enhancement of activity were noted: The time at which maximum activity of one factor occurred did not coincide with the time at which the maxima of other activities occurred; spike amplitude, for example, was observed to increase while conduction velocity had already reached its maximum and was rapidly declining. The energy supplied by bombardment with x-rays did not act synergistically during the time of the enhanced response; that is, concomitant irradiation was not necessary in order to produce the enhanced response, once the nerve had been altered by x-irradiation. Once the nerve was responding in an enhanced manner, cessation of irradiation for short periods of time had no effect on the response. The phenomenon was therefore due to an irreversible alteration of the nerve fiber itself.


Creating Best Practices for the Submission of Actionable Food and Feed Testing Data Generated in State and Local Laboratories.
Laboratory accreditation provides a level of standardization in laboratories and confidence in generated food and feed testing results. For some laboratories, ISO/IEC 17025:2005 accreditation may not be fiscally viable, or a requested test method may be out of the scope of the laboratory's accreditation. To assist laboratories for whom accreditation is not feasible, the Association of Public Health Laboratories Data Acceptance Work Group developed a white paper entitled "Best Practices for Submission of Actionable Food and Feed Testing Data Generated in State and Local Laboratories." The basic elements of a quality management system, along with other best practices that state and local food and feed testing laboratories should follow, are included in the white paper. It also covers program-specific requirements that may need to be addressed. Communication with programs and end data users is regarded as essential for establishing the reliability and accuracy of laboratory data. Following these suggested best practices can facilitate the acceptance of laboratory data, which can result in swift regulatory action and the quick removal of contaminated product from the food supply, improving public health nationally.


Influence of high tissue-absorbed dose on anti-thyroid antibodies in radioiodine therapy of Graves' disease patients.
The results of radioactive iodine (RAI) treatment for Graves' disease (GD) are related to the choice of diagnostic and dosimetry protocols, the steroid protection used, and the subsequent 131I dose. The effect of a high tissue-absorbed dose on the level of anti-thyroid antibodies (ATA) has been rarely considered. To estimate the effect of the first RAI therapy with a dose of 250 Gy on anti-thyreoperoxidase (anti-TPO) and anti-thyroid-stimulating hormone (TSH) receptor thyrotropin receptor antibody - TRAb levels in GD patients. The analysis encompassed 46 consecutive patients with clinical presentation of GD. We examined the serum levels of TSH, free thyroxine (FT4), anti-TPO, TRAb, thyroid volume (ThV), 131I effective half-life (EHL), introduction of steroid protection, levothyroxine dose used in thyroid replacement therapy - TRT, and effectiveness of treatment. As a result of RAI treatment, hypothyroidism was found in 35 patients (76.1%), euthyroidism in 7 patients (15.2%) and hyperthyroidism in 4 patients (8.7%). After RAI, we observed ThV reduction and increased anti-TPO (p = 0.001 and p = 0.001, respectively). It was found that a shorter EHL correlated with a higher baseline TRAb concentration and lower final anti-TPO serum concentration (p = 0.03 and p = 0.01, respectively). Lower final TRAb was found in patients with steroid protection (p = 0.049). Intergroup comparison of patients without steroid protection showed significantly higher final anti-TPO concentation (p = 0.02). Intergroup comparison of patients with TRT revealed significantly higher final anti-TPO concentration (p = 0.04). The application of a high absorbed dose of 250 Gy in GD resulted in high efficacy of RAI therapy at 1-year follow-up. An increased ATA level and its relationships with EHL and ThV reduction were observed at 1-year follow-up. There is a possible relationship between steroid protection and anti-TPO concentration.


Global Multimorbidity Patterns: A Cross-Sectional, Population-Based, Multi-Country Study.
Population ageing challenges health care systems due to the high prevalence and impact of multimorbidity in older adults. However, little is known about how chronic conditions present in certain multimorbidity patterns, which could have great impact on public health at several levels. The aim of our study was to identify and describe multimorbidity patterns in low-, middle-, and high-income countries. We analyzed data from the Collaborative Research on Ageing in Europe project (Finland, Poland, and Spain) and the World Health Organization's Study on Global Ageing and Adult Health (China, Ghana, India, Mexico, Russia, and South Africa). These cross-sectional studies obtained data from 41,909 noninstitutionalized adults older than 50 years. Exploratory factor analysis was performed to detect multimorbidity patterns. Additional adjusted binary logistic regressions were performed to identify associations between sociodemographic factors and multimorbidity. Overall multimorbidity prevalence was high across countries. Hypertension, cataract, and arthritis were the most prevalent comorbid conditions. Two or three multimorbidity patterns were found per country. Several patterns were identified across several countries: "cardio-respiratory" (angina, asthma, and chronic obstructive pulmonary disease), "metabolic" (diabetes, obesity, and hypertension), and "mental-articular" (arthritis and depression). A high prevalence of multimorbidity occurs in older adults across countries, with low- and middle-income countries gradually approaching the figures of richer countries. Certain multimorbidity patterns are present in several countries, which suggest that common underlying etiopathogenic factors may play a role. Deeper understanding of these patterns may lead to the development of preventive actions to diminish their prevalence and also give rise to new, comprehensive approaches for the management of these co-occurring conditions.


Presence of histamine and mast cells in chicken oviduct.
The purpose of the present study was: (1) to demonstrate immunocytochemically the localization of histamine in the wall of four chicken oviductal parts, i.e. infundibulum, magnum, isthmus, and shell gland, (2) to identify the presence of mast cells in chicken oviduct, and (3) to determine histamine concentration in oviductal tissue by the spectrofluorometric method. Experiments were carried out on Isa Brown laying hens decapitated just after oviposition. The specific immuno-reactivity for histamine and the presence of mast cells were found in the wall of all the examined oviductal parts. The immuno-reactive histamine was localized in epithelium, tubular glands, connective tissue layer, circular and longitudinal muscles, and endothelium and muscles of blood vessels. The intensity of immuno-positive reaction was as follows: infundibulum > shell gland > magnum = isthmus and correlated with quantitatively determined histamine level and tissue density of mast cells. It is suggested that mast cells are the main source of histamine in the chicken oviduct.


High-intensity focused ultrasound: past, present, and future in neurosurgery.
Since Lynn and colleagues first described the use of focused ultrasound (FUS) waves for intracranial ablation in 1942, many strides have been made toward the treatment of several brain pathologies using this novel technology. In the modern era of minimal invasiveness, high-intensity focused ultrasound (HIFU) promises therapeutic utility for multiple neurosurgical applications, including treatment of tumors, stroke, epilepsy, and functional disorders. Although the use of HIFU as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists, neurologists, or even neurosurgeons are familiar with it. In this extensive review, the authors intend to shed light on the current use of HIFU in different neurosurgical avenues and its mechanism of action, as well as provide an update on the outcome of various trials and advances expected from various preclinical studies in the near future. Although the initial technical challenges have been overcome and the technology has been improved, only very few clinical trials have thus far been carried out. The number of clinical trials related to neurological disorders is expected to increase in the coming years, as this novel therapeutic device appears to have a substantial expansive potential. There is great opportunity to expand the use of HIFU across various medical and surgical disciplines for the treatment of different pathologies. As this technology gains recognition, it will open the door for further research opportunities and innovation.


A new photolysis laser-induced fluorescence instrument for the detection of H2O and HDO in the lower stratosphere.
We present a new instrument, Hoxotope, for the in situ measurement of H(2)O and its heavy deuterium isotopologue (HDO) in the upper troposphere and lower stratosphere aboard the NASA WB-57. Sensitive measurements of deltaD are accomplished through the vacuum UV photolysis of water followed by laser-induced fluorescence detection of the resultant OH and OD photofragments. The photolysis laser-induced fluorescence technique can obtain S/N>20 for 1 ppbv HDO and S/N>30 for 5 ppmv H(2)O for 10 s data, providing the sensitivity required for deltaD measurements in the tropopause region. The technique responds rapidly to changing water concentrations due to its inherently small sampling volume, augmented by steps taken to minimize water uptake on instrument plumbing. Data from the summer 2005 Aura Validation Experiment Water Isotope Intercomparison Flights (AVE-WIIF) out of Houston, TX show agreement for H(2)O between Hoxotope and the Harvard water vapor instrument and for HDO between Hoxotope and the Harvard ICOS water isotope instrument, to within stated instrument uncertainties. The successful intercomparison validates Hoxotope as a credible source of deltaD data in the upper troposphere and lower stratosphere.


MLML2R: an R package for maximum likelihood estimation of DNA methylation and hydroxymethylation proportions.
Accurately measuring epigenetic marks such as 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) at the single-nucleotide level, requires combining data from DNA processing methods including traditional (BS), oxidative (oxBS) or Tet-Assisted (TAB) bisulfite conversion. We introduce the R package MLML2R, which provides maximum likelihood estimates (MLE) of 5-mC and 5-hmC proportions. While all other available R packages provide 5-mC and 5-hmC MLEs only for the oxBS+BS combination, MLML2R also provides MLE for TAB combinations. For combinations of any two of the methods, we derived the pool-adjacent-violators algorithm (PAVA) exact constrained MLE in analytical form. For the three methods combination, we implemented both the iterative method by Qu et al. [Qu, J., M. Zhou, Q. Song, E. E. Hong and A. D. Smith (2013): "Mlml: consistent simultaneous estimates of dna methylation and hydroxymethylation," Bioinformatics, 29, 2645-2646.], and also a novel non iterative approximation using Lagrange multipliers. The newly proposed non iterative solutions greatly decrease computational time, common bottlenecks when processing high-throughput data. The MLML2R package is flexible as it takes as input both, preprocessed intensities from Infinium Methylation arrays and counts from Next Generation Sequencing technologies. The MLML2R package is freely available at https://CRAN.R-project.org/package=MLML2R.


Optogenetic methods in drug screening: technologies and applications.
The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.


[Thoracic epidural anesthesia by the caudal route in pediatric anesthesia: age is a limiting factor].
To evaluate the success and degree of difficulty of inserting an epidural catheter into the caudal space in order to place its distal end at T10 in young patients. Forty-seven children up to 97 months old were studied. With the patients under general anesthesia with an orotracheal tube, a predetermined length of 18-G epidural catheter (Minipack: SYSTEM 2-Portex) was inserted to T10. X-rays were taken after surgery with 0.3 ml of iodine contrast. The catheter was considered well-placed if the distal end was between T10-T12; the approach was classified as easy, difficult or impossible. The catheter was placed at T12-T10 on 16 occasions: 6 in L1, 3 in L2, 4 in L3, 17 in L4-L5, and 1 in S1. T10-T12 was reached in 52% of patients under 1 year of age, but in only 17% of children older than 1 year. The L4-L5 epidural space was reached with 46 of 47 catheters. Advance was easy in 41 cases, with only 16 reaching the objective. Advance was difficult in 6 cases, with only 1 reaching L1 and none reaching T10-T12. All catheters were easily removed. It is not possible to guarantee the arrival of an 18-G epidural catheter to the thoracic epidural space by entering through the caudal route. In children over 1 year of age, the level of success decreases significantly. Easy advance of the catheter cannot be taken to be a sign of success.