[Analysis of the structure of cardiac rhythm in auricular fibrillation with the aid of a specialized computer].
In 37 patients with atrial fibrillation of varying etiology the electron-computer technique was used in recording the cardiointervalogram and interval histogram and also in determining a number of indices characterizing distinctive features of the R-R intervals distribution. When analyzing the available data not was taken of a tendency towards appearance of definite types of the interval histograms, variations in the mean level of the cardiointervalogram, resembling the so-called slow waves observable in the sinus rhythm. During repeated investigations made in the same patients features of a single type in the distribution of the R-R intervals were apparent. In the course of conservative therapy of atrial fibrillation a certain stereotypy in the R-R intervals distribution was noted, it being indicative of an increased arrhythmicity in the work of the heart occurring simultaneously with the slowing down of the cardiac contractions.


Reproducibility of urinary phthalate metabolites in first morning urine samples.
Phthalates are ubiquitous in our modern environment because of their use in plastics and cosmetic products. Phthalate monoesters--primarily monoethylhexyl phthalate and monobutyl phthalate--are reproductive and developmental toxicants in animals. Accurate measures of phthalate exposure are needed to assess their human health effects. Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans. To explore these aspects, we measured seven phthalate monoesters and creatinine concentration in two consecutive first-morning urine specimens from 46 African-American women, ages 35-49 years, residing in the Washington, DC, area in 1996-1997. We measured phthalate monoesters using high-pressure liquid chromatography followed by tandem mass spectrometry on a triple quadrupole instrument using atmospheric pressure chemical ionization. We detected four phthalate monoesters in all subjects, with median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for monoethylhexyl phthalate (mEHP). These were similar to concentrations reported for other populations using spot urine specimens. Phthalate levels did not differ between the two sampling days. The Pearson correlation coefficient between the concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5 for mBzP. These results suggest that even with the short half-lives of phthalates, women's patterns of exposure may be sufficiently stable to assign an exposure level based on a single first morning void urine measurement.


The Efficiency of Direct Maturation: the Comparison of Two hiPSC Differentiation Approaches into Motor Neurons.
Motor neurons (MNs) derived from human-induced pluripotent stem cells (hiPSC) hold great potential for the treatment of various motor neurodegenerative diseases as transplantations with a low-risk of rejection are made possible. There are many hiPSC differentiation protocols that pursue to imitate the multistep process of motor neurogenesis in vivo. However, these often apply viral vectors, feeder cells, or antibiotics to generate hiPSC and MNs, limiting their translational potential. In this study, a virus-, feeder-, and antibiotic-free method was used for reprogramming hiPSC, which were maintained in culture medium produced under clinical good manufacturing practice. Differentiation into MNs was performed with standardized, chemically defined, and antibiotic-free culture media. The identity of hiPSC, neuronal progenitors, and mature MNs was continuously verified by the detection of specific markers at the genetic and protein level via qRT-PCR, flow cytometry, Western Blot, and immunofluorescence. MNX1- and ChAT-positive motoneuronal progenitor cells were formed after neural induction via dual-SMAD inhibition and expansion. For maturation, an approach aiming to directly mature these progenitors was compared to an approach that included an additional differentiation step for further specification. Although both approaches generated mature MNs expressing characteristic postmitotic markers, the direct maturation approach appeared to be more efficient. These results provide new insights into the suitability of two standardized differentiation approaches for generating mature MNs, which might pave the way for future clinical applications.


Assessing functional impairment in a working military population: the Walter Reed functional impairment scale.
Measurement of functional impairment is a priority for the military and other professional work groups routinely exposed to stressful traumatic events as part of their occupation. Standard measures of impairment used in general or chronically ill populations contain many items not suitable for these populations, and include mental health symptoms items that are not true measures of functioning. We created a new, 14-item scale-the Walter Reed Functional Impairment Scale-to assess functioning in 4 domains (physical, occupational, social, and personal). We asked 3,380 soldiers how much difficulty they currently have in each of the 4 domains on a 5-point scale. Behaviorally based psychosocial and occupational performance measures and general health questions were used to validate the scale. The utility of the scale was assessed against clinical measures of psychopathology and physical health (depression, posttraumatic stress disorder [PTSD], general health, generalized physical symptoms). We utilized Cronbach's alpha, item response theory, and the score test for trend to establish consistency of items and the validity of the scale. The scale exhibited excellent reliability (Cronbach's α= 0.92) and validity. The individual items and quartiles of sum scores were strongly correlated with negative occupational and social performance, and the utility of the scale was demonstrated by strong correlations with depression, PTSD, and high levels of generalized physical symptoms. This scale exhibits excellent psychometric properties in this sample of U.S. soldiers and, pending future research, is likely to have utility for other healthy occupational groups.


A new Cretaceous terrestrial ecosystem from Gondwana with the description of a new sauropod dinosaur.
A unique site at the northern area of Patagonia (Neuquén, Argentina) reveals a terrestrial ecosystem preserved in a detail never reported before in a Late Cretaceous deposit. An extraordinary diversity and abundance of fossils was found concentrated in a 0.5 m horizon in the same quarry, including a new titanosaur sauropod, Futalognkosaurus dukei n.gen., n.sp, which is the most complete giant dinosaur known so far. Several plant leaves, showing a predominance of angiosperms over gymnosperms that likely constituted the diet of F. dukei were found too. Other dinosaurs (sauropods, theropods, ornithopods), crocodylomorphs, pterosaurs, and fishes were also discovered, allowing a partial reconstruction of this Gondwanan continental ecosystem.


Oxidative Stress and Endoplasmic Reticular Stress Interplay in the Vasculopathy of Hypertension.
Under physiologic conditions, reactive oxygen species (ROS) function as signalling molecules that control cell function. However, in pathologic conditions, increased generation of ROS triggers oxidative stress, which plays a role in vascular changes associated with hypertension, including endothelial dysfunction, vascular reactivity, and arterial remodelling (termed the vasculopathy of hypertension). The major source of ROS in the vascular system is NADPH oxidase (NOX). Increased NOX activity drives vascular oxidative stress in hypertension. Molecular mechanisms underlying vascular damage in hypertension include activation of redox-sensitive signalling pathways, post-translational modification of proteins, and oxidative damage of DNA and cytoplasmic proteins. In addition, oxidative stress leads to accumulation of proteins in the endoplasmic reticulum (ER) (termed ER stress), with consequent activation of the unfolded protein response (UPR). ER stress is emerging as a potential player in hypertension as abnormal protein folding in the ER leads to oxidative stress and dysregulated activation of the UPR promotes inflammation and injury in vascular and cardiac cells. In addition, the ER engages in crosstalk with exogenous sources of ROS, such as mitochondria and NOX, which can amplify redox processes. Here we provide an update of the role of ROS and NOX in hypertension and discuss novel concepts on the interplay between oxidative stress and ER stress.


[Enkephalins and gastrin fragments: possible existence of different analgesic mechanisms].
The mechanism of analgetic action of pentagastrin, its tripeptide fragment (MAF), synthetic met- and leu-enkephalins was studied in rats. The analgetic effect of the peptides was evaluated from the tail extracting test. Also, the content of biogenic amines in the rat brain and interaction of the peptides with opiate receptors of the guinea-pig ileum were examined. It was demonstrated that analgesia induced by pentagastrin or MAF differs from that obtained after intraventricular injection of the enkephalins. The effect of the latter ones is not consequent on their interaction with classic opiate receptors. It was also discovered that pentagastrin, MAF and enkephalins produce a different action on metabolism of biogenic amines. The possibility of analgesia unmediated by specific peptide binding to opiate receptors is discussed.


Ly49A transgenic mice provide evidence for a major histocompatibility complex-dependent education process in natural killer cell development.
The Ly49 natural killer (NK) cell receptors are class I MHC-specific inhibitory receptors that are distributed to overlapping NK cell subsets. The formation of the Ly49 receptor repertoire was examined with transgenic mice that express Ly49A in all NK cells. In MHC class I-deficient mice, the Ly49A transgene did not prevent expression of endogenous Ly49 genes. However, in H-2(d) mice that express a Ly49A ligand, the transgene caused clear alterations in the endogenous Ly49 repertoire. The frequency of NK cells expressing another H-2(d)-specific receptor, Ly49G2(+), was substantially reduced. Reduced numbers of cells expressing endogenous Ly49A was suggested by reduced endogenous Ly49A mRNA levels. These results support the existence of an MHC-dependent education process that limits the number of NK cells that coexpress multiple self-specific Ly49 receptors. Ligand-dependent downregulation of Ly49 cell surface levels was also examined. Cell-surface downregulation occurred even when the transgene was expressed at low levels. The results demonstrate that downregulation of Ly49A cell surface levels is a posttranscriptional event, and argue against a model in which Ly49 receptors are calibrated to specific cell surface levels depending on the available class I ligands.


Ventricular Arrhythmias in Patients with Spontaneous Coronary Artery Dissection: Findings from the Gulf Spontaneous Coronary Artery Dissection (Gulf SCAD) Registry.
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome in young women, with a wide clinical spectrum of severity. Ventricular arrhythmia (VA) can occur and worsen prognosis. The current study compared in-hospital and follow-up adverse cardiovascular events in patients with and without VA at presentation. Eighty-three cases of SCAD were collected retrospectively from 4 Gulf countries (KSA, UAE, Kuwait, and Bahrain) during the period from January 2011 to December 2017. We divided the patients into 2 groups: those with and without VA at presentation. VA was defined as ventricular tachycardia and/or ventricular fibrillation. In-hospital (recurrent VA, cardiogenic shock, death, implantable cardioverter-defibrillator placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) events were compared among the 2 groups. The median age of patients in the study was 44 (37-55) years. Forty-two (51%) were women. VA occurred in 10 (12%) patients in the first 24-hour of hospitalization, and 5 (50%) of those patients had recurrent in-hospital VA. Among those with recurrent VA, 1 died during hospitalization and 1 died within the first year following hospital discharge. In-hospital adverse cardiovascular events were significantly more frequent for patients with SCAD who presented with VA. However, follow-up events were not statistically significant between those with and without VA at presentation.


Microcidal effects of a new pelleting process.
The microcidal efficiency of a new pelleting process was evaluated in four trials. Also, different methods of measuring temperature and moisture were compared and attempts were made to determine the influence on efficiency of pH changes occurring during processing. In the new process, the traditional boiler-conditioner was replaced by an Anaerobic Pasteurizing Conditioning (APC) System. Microcidal efficiency of the APC System, by itself or in conjunction with a pellet mill, appeared to be 100% against Escherichia coli and nonlactose-fermenters, 99% against aerobic mesophiles, and 90% against fungi. These levels of efficiency were attained when the temperature and moisture of feed conditioned in the APC System for 4.6 +/- .5 min were 82.9 +/- 2.4 C and 14.9 +/- .3%, respectively. On-line temperature probes were reliable and provided quick, accurate estimates of feed temperature. The near infrared scanner and microwave oven methods of measuring moisture were much quicker but less accurate than the in vacuo method. There were no differences among the pH of samples of raw, conditioned, and pelleted feed.


Changes in leg cycling muscle synergies after training augmented by functional electrical stimulation in subacute stroke survivors: a pilot study.
Muscle synergies analysis can provide a deep understanding of motor impairment after stroke and of changes after rehabilitation. In this study, the neuro-mechanical analysis of leg cycling was used to longitudinally investigate the motor recovery process coupled with cycling training augmented by Functional Electrical Stimulation (FES) in subacute stroke survivors. Subjects with ischemic subacute stroke participated in a 3-week training of FES-cycling with visual biofeedback plus usual care. Participants were evaluated before and after the intervention through clinical scales, gait spatio-temporal parameters derived from an instrumented mat, and a voluntary pedaling test. Biomechanical metrics (work produced by the two legs, mechanical effectiveness and symmetry indexes) and bilateral electromyography from 9 leg muscles were acquired during the voluntary pedaling test. To extract muscles synergies, the Weighted Nonnegative Matrix Factorization algorithm was applied to the normalized EMG envelopes. Synergy complexity was measured by the number of synergies required to explain more than 90% of the total variance of the normalized EMG envelopes and variance accounted for by one synergy. Regardless the inter-subject differences in the number of extracted synergies, 4 synergies were extracted from each patient and the cosine-similarity between patients and healthy weight vectors was computed. Nine patients (median age of 75 years and median time post-stroke of 2 weeks) were recruited. Significant improvements in terms of clinical scales, gait parameters and work produced by the affected leg were obtained after training. Synergy complexity well correlated to the level of motor impairment at baseline, but it did not change after training. We found a significant improvement in the similarity of the synergy responsible of the knee flexion during the pulling phase of the pedaling cycle, which was the mostly compromised at baseline. This improvement may indicate the re-learning of a more physiological motor strategy. Our findings support the use of the neuro-mechanical analysis of cycling as a method to assess motor recovery after stroke, mainly in an early phase, when gait evaluation is not yet possible. The improvement in the modular coordination of pedaling correlated with the improvement in motor functions and walking ability achieved at the end of the intervention support the role of FES-cycling in enhancing motor re-learning after stroke but need to be confirmed in a controlled study with a larger sample size. ClinicalTrial.gov, NCT02439515. Registered on May 8, 2015, .


Cognitive-behavioral therapy, light therapy, and their combination in treating seasonal affective disorder.
The need to develop supplementary or alternative treatments for seasonal affective disorder (SAD) is underscored by the significant minority (47%) of SAD patients that is refractory to light therapy, the persistence of residual symptoms despite light treatment, and poor long-term compliance with light use. Because preliminary studies suggest that cognitive and behavioral factors are involved in SAD, cognitive-behavioral therapy (CBT) warrants investigation as a possible treatment option. We piloted a 6-week randomized clinical trial to compare a standard light therapy protocol; a novel, SAD-tailored, group CBT intervention; and their combination in ameliorating and remitting a current SAD episode and as prophylaxis against episode recurrence. Depressive symptom severity and remission rates were assessed at post-treatment and at a 1-year follow-up visit to examine long-term treatment durability. CBT, light therapy, and their combination all demonstrated significant reductions in depressive symptoms on two different outcome measures. Remission rates varied by measure, but did not reach statistical significance. During the subsequent winter, CBT, particularly in combination with light therapy, appeared to improve long-term outcome regarding symptom severity, remission rates, and relapse rates. No CBT-treated participant, with or without light, experienced a full SAD relapse compared to over 60% of those treated with light alone. These results should be viewed as preliminary and are limited by the small sample size (n=23) and lack of a control group. The nearly half of SAD patients who do not remit with light alone may benefit from CBT as an adjunct or alternative treatment, especially as a prophylaxis against episode recurrence.


TERT polymorphisms rs2853669 and rs7726159 influence on prostate cancer risk in Russian population.
Telomere length and telomerase activity have been hypothesized to play a role in cancer development. The aim of our study was to investigate the association of allelic variants of three functional polymorphisms rs2853669, rs2736100, and rs7726159 in the telomerase reverse transcriptase (TERT) gene with the risk of the breast cancer and prostate cancer in Russian population. Six hundred sixty women with breast cancer, 372 men with prostate cancer, and corresponding control groups of 523 women and 363 men were included in the present case-control study. We observed an association of allele rs2853669 C with increased risk of prostate cancer (co-dominant model TC vs. TT OR = 1.65, P = 0.002; additive model OR = 1.42, P = 0.005; dominant model: OR = 1.64, P = 0.001) and allele rs7726159 A with reduced risk of this malignancy (сo-dominant model: AA vs. CC OR = 0.42, P = 0.002; additive model: OR = 0.69, P = 0.002; dominant model: OR = 0.67, P = 0.01; recessive model: OR = 0.48, P = 0.005). None of the studied polymorphisms showed an association with the risk of breast cancer. Our results provide evidence that the TERT gene variability modulate prostate cancer predisposition in ethnical Russians.


Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence.
The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


Citric-acid cycle, 50 years on. Modifications and an alternative pathway in anaerobic bacteria.
Many anaerobic bacteria can completely oxidize organic matter to CO2 with either sulfur, sulfate, or protons as electron acceptor. The sulfur-reducing bacteria and one genus of sulfate reducers use a modified citric-acid cycle with a novel anaplerotic sequence as pathway of terminal respiration. All other anaerobes use an alternative pathway, in which carbon monoxide dehydrogenase is a key enzyme and in which acetyl-CoA is cleaved into two C1 units at the oxidation level of CH3OH and CO. Thus almost 50 years after the discovery of the citric acid cycle by Hans Krebs in 1937, a second pathway for acetyl-CoA oxidation was found.


A five year diagnostic follow-up of 1,840 patients after a first episode non-schizophrenia and non-affective psychosis.
It is not clear which patients with a first psychotic episode will develop schizophrenia. We performed a diagnostic follow-up of patients treated for a first time non-affective, non-schizophrenia psychosis and explored potential predictors of a subsequent schizophrenia or schizoaffective diagnosis. This register-based cohort study comprises individuals born between 1973 and 1978 in Sweden, with a first hospital-treated psychosis excluding schizophrenia, schizoaffective disorder, bipolar disorder and depressive disorder with psychotic symptoms (n=1840). The patients were followed for five years regarding subsequent diagnoses. Psychiatric, social, family history of psychiatric illness, premorbid intellectual level, head injuries and obstetrical complications were investigated by logistic regression as predictors of schizophrenia or schizoaffective diagnosis. During the follow-up, 18% were diagnosed with schizophrenia or schizoaffective disorder, 5% were diagnosed with bipolar disorder, whereas 29% were not re-admitted to a psychiatric clinic. Patients with a first-degree relative hospitalized for schizophrenia and/or bipolar disorder had an increased risk of subsequent diagnosis for schizophrenia or schizoaffective disorder (odds ratio 1.9 and 95% confidence interval 1.1 to 3.0)), whereas previous severe criminality was associated with a decreased risk (odds ratio 0.5, 95% confidence interval 0.3-0.8). Diagnostic outcome was diverse after a first non-schizophrenia and non-affective psychosis. Family history of severe mental illness and no previous conviction for severe criminality were the strongest risk factors for a future schizophrenia or schizoaffective diagnosis.


Paracentral corneal dellen: a rare sign of Graves ophthalmopathy.
To report a rare sign, paracentral corneal dellen that developed in a middle-aged female patient with Graves ophthalmopathy. A paracentral corneal dellen developed in the left eye in a 42-year-old woman who was diagnosed as Graves ophthalmopathy. The patient had remarkable upper eyelid retraction, upper eyelid lag and upward motility restriction. The Graves ophthalmopathy was classified as Grade IV according to NOSPECS classification. Local artificial tear film and 0.3% Tobramycin eye drops were administered to both eyes. Twenty-four hours later, the left corneal dellen disappeared. Graves ophthalmopathy can lead to paracentral corneal dellen because of severe upper eyelid retraction and upward motility restriction of the eye in spite of the lack of lagophthalmos. Artificial tear drop and antibiotic eye drop therapy helped even though the patient did not have corneal exposure.


Rapid and Sensitive Detection of Bacteria Response to Antibiotics Using Nanoporous Membrane and Graphene Quantum Dot (GQDs)-Based Electrochemical Biosensors.
The wide abuse of antibiotics has accelerated bacterial multiresistance, which means there is a need to develop tools for rapid detection and characterization of bacterial response to antibiotics in the management of infections. In the study, an electrochemical biosensor based on nanoporous alumina membrane and graphene quantum dots (GQDs) was developed for bacterial response to antibiotics detection. Anti-Salmonella antibody was conjugated with amino-modified GQDs by glutaraldehyde and immobilized on silanized nanoporous alumina membranes for Salmonella bacteria capture. The impedance signals across nanoporous membranes could monitor the capture of bacteria on nanoporous membranes as well as bacterial response to antibiotics. This nanoporous membrane and GQD-based electrochemical biosensor achieved rapid detection of bacterial response to antibiotics within 30 min, and the detection limit could reach the pM level. It was capable of investigating the response of bacteria exposed to antibiotics much more rapidly and conveniently than traditional tools. The capability of studying the dynamic effects of antibiotics on bacteria has potential applications in the field of monitoring disease therapy, detecting comprehensive food safety hazards and even life in hostile environment.


Predictors of ineffectual radial arterial pressure monitoring in valvular heart surgery.
Unexpected sustained underestimation of the central aortic pressure by the radial arterial pressure commonly develops following cardiopulmonary bypass (CPB) in valvular heart surgery (VHS), leading to an inappropriate use of vasopressors. The study aim was to identify clinical predictors leading to a sustained inappropriate difference between the radial and femoral arterial pressure (IDRF) in VHS. A total of 200 patients undergoing VHS was studied prospectively. Those patients who developed sustained IDRF (systolic IDRF > or =10 mmHg and/or mean IDRF > or =5 mmHg) from immediately after discontinuation of CPB until the end of the surgery were compared with patients who did not develop any IDRF. Data from seven patients who required second aortic cross-clamping and re-CPB were excluded from the analysis; thus, data from 193 patients were analyzed. In total, 53 patients (27.5%) developed sustained IDRF, whereas 80 patients (41.4%) did not develop any IDRF. In multivariate analysis, female gender, the presence of atrial fibrillation and diuretic use were identified as independent preoperative predictors; longer-duration aortic cross-clamping and use of larger amounts of vasopressin during CPB were identified as independent operative risk factors of the sustained IDRF. When an erroneously low radial arterial pressure is suspected following CPB in this subset of patients undergoing VHS, monitoring of the femoral or axillary arterial pressure should be considered to guide hemodynamic management, as there is an increased risk of persistence of this phenomenon.


Inflammation and gut-brain axis link obesity to cognitive dysfunction: plausible pharmacological interventions.
Obesity prevalence is increasing steadily throughout the world's population in most countries and in parallel the prevalence of metabolic disorders including cardiovascular diseases and type 2 diabetes is also rising, but less is reported about excessive adiposity relationship with poorer cognitive performance, cognitive decline and dementia. Some human clinical studies have evidenced that obesity is related to the risk of the development of mild cognitive impairment, in the form of short-term memory and executive function deficits, as well as dementia and Alzheimer's disease. The precise mechanisms that underlie the connections between obesity and the risk of cognitive impairment are still largely unknown but potential avenues of further research include insulin resistance, the gut-brain axis, and systemic mediators and central inflammation processes. A common feature of metabolic diseases is a chronic and low-grade activation of the inflammatory system. This inflammation may eventually spread from peripheral tissue to the brain, and recent reports suggest that neuroinflammation is an important causal mechanism in cognitive decline. This inflammatory status could be triggered by changes in the gut microbiota composition. Consumption of diets high in fat and sugar influences the microbiota composition, which may lead to an imbalanced microbial population in the gut. Thus, it has recently been hypothesized that the gut microbiota could be part of a mechanistic link between the consumption of high fat and other unbalanced diets and impaired cognition, termed 'gut-brain axis'. The present review will aim at providing an integrative analysis of the effects of obesity and unbalanced diets on cognitive performance and discusses some of the potential mechanisms involved, namely inflammation and changes in gut-brain axis. Moreover, the review aims to analyze anti-inflammatory drugs that have been tested for the treatment of cognition and obesity, recently approved anti-obesity drugs that could also have an impact on central nervous system, and bioactive food compounds that modulate gut microbiota and could have an impact through the gut-brain axis. In this era of precision nutrition medicine, it is imperative to identify the various metabolic-neurocognitive phenotypes in order to understand the processes that drive these diseases so that targeted therapeutic strategies to prevent and successfully manage these complex, multifactorial diseases could be designed and developed.


Comparison of sensory conduction techniques in the diagnosis of mild idiopathic carpal tunnel syndrome: which finger, which test?
To compare the sensitivity of different electrodiagnostic tests on the same hand affected by mild carpal tunnel syndrome (CTS), 189 hands with the clinical diagnosis of CTS and 61 hands of healthy persons were evaluated prospectively. On all hands, median sensory studies from digits 1, 2, 3, 4, and the palm-to-wrist segment from digit 3 and medial motor latency were recorded. Sixty-two hands with delayed motor latency (>4.2 ms) were excluded to ensure that only mild cases were enrolled. Sensory median-radial latency differences from the thumb, median-ulnar latency difference between second and fifth digits, and median-ulnar latency difference from the fourth digit were calculated in each limb. Sensory studies of only one median innervated digit failed to diagnose 15-20% of hands. Conduction velocity at the palm-to-wrist segment was the most sensitive, diagnosing 99% of cases. In comparative tests, median radial sensory latency difference from the first digit was the most sensitive (94%), and median ulnar latency difference from the fourth digit was the least (85%) sensitive. Segmental measurement has the highest diagnostic yield and may be used first in the evaluation of CTS.


The role of the thymus in the pathogenesis of myasthenia gravis.
Myasthenia gravis is an organ-specific autoimmune disease characterized by the production of anti-acetylcholine receptor antibodies. In this review, I describe the pathophysiological importance of the altered chemokine receptor-mediated signaling in the thymus and peripheral blood of myasthenia gravis patients. The epidemiological and clinical features of myasthenia gravis are also discussed.


Is it time to pull the plug on 12-hour shifts? Part 3. harm reduction strategies if keeping 12-hour shifts.
This article is part 3 of the series "Pulling the Plug on 12-Hour Shifts." In part 1 (March 2010), the authors provided an update on recent evidence that challenges the current scheduling paradigm and supports the lack of safety of long work hours. Part 2 (April 2010) described the barriers to change and challenges for the nurse executive in moving away from the practice of 12-hour shifts. This article presents strategies for mitigating the effects of 12-hour shifts for nurses who continue to work 12-hour shifts despite the potential risks to their health and to patient safety.


Scaling analyses for hyperpolarization transfer across a spin-diffusion barrier and into bulk solid media.
By analogy to heat and mass transfer film theory, a general approach is introduced for determining hyperpolarization transfer rates between dilute electron spins and a surrounding nuclear ensemble. These analyses provide new quantitative relationships for understanding, predicting, and optimizing the effectiveness of hyperpolarization protocols, such as Dynamic Nuclear Polarization (DNP) under magic-angle spinning conditions. An empirical DNP polarization-transfer coefficient is measured as a function of the bulk matrix 1H spin density and indicates the presence of two distinct kinetic regimes associated with different rate-limiting polarization transfer phenomena. Dimensional property relationships are derived and used to evaluate the competitive rates of spin polarization generation, propagation, and dissipation that govern hyperpolarization transfer between large coupled spin ensembles. The quantitative analyses agree closely with experimental measurements for the accumulation, propagation, and dissipation of hyperpolarization in solids and provide evidence for kinetically-limited transfer associated with a spin-diffusion barrier. The results and classical approach yield general design criteria for analyzing and optimizing polarization transfer processes involving complex interfaces and composite media for applications in materials science, physical chemistry and nuclear spintronics.


Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms.
Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839.


Development and early testing of a simple subcutaneous counterpulsation device.
The intra-aortic balloon pump has been widely and successfully used as a treatment for cardiac dysfunction, but it only has short-term applications. To overcome this limitation, a superficial counterpulsation device (CPD) is being developed to provide extended counterpulsation support to promote myocardial recovery. The CPD is a valveless, monoport, pneumatically driven, 40-ml sac that is intended to be implanted in a pacemaker-type pocket in the subclavian fossa. The sac is designed to fill in systole and empty during diastole through an outflow graft anastomosed to the subclavian artery. A feasibility study was conducted to investigate acute hemodynamic responses to the CPD in eight calves with diminished cardiac function. The CPD augmented aortic diastolic pressure, reduced left ventricular peak systolic and aortic ejection pressures by up to 18%, and increased diastolic coronary flow by up to 21% and stroke volume by up to 12%. A cadaver fit study demonstrated that the human subclavian artery is a reasonable anastomosis site to consider and that the 40-ml CPD needs to be reduced in size to provide a better anatomical fit. The clinical attractiveness of this approach is that it may provide extended support through a subcutaneous surgical procedure.


The relationship between testosterone levels and Peyronie's disease.
Aetiologic and predisposing factors are still controversial about Peyronie's disease (PD). However, it is thought to be the result of connective tissue disorder or healing defect. Androgens are known to affect collagen metabolism and wound healing in the body. The aim of this study was to investigate the relationship between PD and low testosterone levels. One hundred and forty-seven Peyronie patients and 137 healthy volunteers were included in the study. In both groups, demographic data, medical history, physical examination and erectile capacity were recorded. Blood samples were collected from all subjects in the early morning hours after an overnight fast. The mean level of serum total testosterone was lower in men with PD compared with the controls (3.9 ± 1.1 vs. 4.2 ± 1.7 ng/ml respectively) (p = .062). However, statistically significant relationship was not found between PD and low serum testosterone levels. There was no significant correlation between penile plaque dimension or penile curvature degree and testosterone levels. Large randomised-controlled prospective studies are needed to reveal this possible association.


Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression.
Gene mutations in APC, K-ras, and p53 are thought to be essential events for colorectal cancer development. Recent data seem to indicate that K-ras and p53 mutations rarely co-exist in the same tumor, indicating that these alterations do not represent a synergistic evolutionary pathway. Moreover, an inverse relation between K-ras gene activation and BRAF mutations has been demonstrated, suggesting alternative pathways for colorectal cancer transformation. To reconstruct the chronological modulation of these gene mutations during cell transformation and colorectal cancer progression, mutations of p53, K-ras, and BRAF genes were analyzed by Single Strand Conformation Polymorphism (SSCP) or sequencing analysis in 100 colorectal cancer samples, evenly distributed among different Dukes' stages. We found mutations in p53, K-ras, and BRAF genes in 35%, 30%, and 4% of tumors, respectively, and observed a minimal or no co-presence of these gene alterations. Moreover, the frequency of molecular p53 mutations increased as tumor stage increased, suggesting an important role for this gene in the progression of colorectal cancer. Conversely, K-ras or BRAF genes were not related to tumor stage or location. These data seem to indicate the absence of a co-presence of the genes, highlighting the possibility of multiple pathways for colorectal tumor progression. Moreover, mutations in p53, K-ras, and BRAF are not present in about one-third of colorectal cancers and therefore other gene mutations need to be investigated to better understand molecular mechanisms at the basis of cell transformation and the progression of colorectal cancer.


A Photoelectrochemical Sensor Based on DNA Bio-Dots-Induced Aggregation of AuNPs for Methionine Detection.
Based on DNA bio-dots-induced aggregation of gold nanoparticles (AuNPs), a methionine (Met) photoelectrochemical (PEC) sensor with CS-GSH-CuNCs/TiO2 NPs as the photoelectric conversion element and AuNPs as the specific recognition element was constructed. First, a TiO2 NPs/ITO electrode and CS-GSH-CuNCs were prepared, and then the CS-GSH-CuNCs/TiO2 NPs/ITO photosensitive electrode was obtained by self-assembly. Next, DNA bio-dots were modified to the upper surface of the electrode using a coupling reaction to assemble the DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Amino-rich DNA bio-dots were used to induce the aggregation of AuNPs on the electrode surface via Au-N interactions and prepare the AuNPs/DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Due to the fluorescence resonance energy transfer (FRET) between CS-GSH-CuNCs and AuNPs, the complexation chance of electron-hole (e--h+) pair in CS-GSH-CuNCs increased, which, in turn, led to a decrease in photocurrent intensity. When Met was present, AuNPs aggregated on the electrode surface were shed and bound to Met since the Au-S interaction is stronger than the Au-N interaction, resulting in the recovery of the photocurrent signal. Under optimal conditions, the photocurrent intensity of the PEC sensor showed good linearity with the logarithm of Met concentration in the range of 25.0 nmol/L-10.0 μmol/L with the limit of detection (LOD) of 5.1 nmol/L (S/N = 3, n = 10).


Effect of pH on red blood cell deformability.
The effect of pH on the red blood cell (RBC) deformability, which is a consequence of a change of cell membrane elastic properties is studied experimentally. With the intention to reduce the effects on deformability of cell geometry and cytoplasmic viscosity, we measured the deformability of the cells with the same volume at various pH of cell suspension from 6.2 to 8.0. Constant cell volume was achieved by varying osmolarity. Deformability was quantified by measuring the elongation of RBCs subjected to velocity gradient in a transparent cone-plate rheoscope. Observed significant decrease of deformability at lower pH leads to the conclusion that membrane elastic properties could be affected by pH changes in the range from 6.2 to 8.0.


Efficacy and safety of biological agents in adult-onset Still's disease.
To describe the efficacy and safety of different biological agents in a large cohort of 20 patients with adult-onset Still's disease (AOSD). We retrospectively evaluated 20 patients with severe or refractory AOSD treated with at least one biological agent (anakinra, etanercept, tocilizumab, and adalimumab), followed up for at least 12 months at our Institution. We collected and analysed data on the disease course, treatment outcome, and adverse effects, and compared our data with other published series. The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. In eight patients the biological agent that was first administered proved ineffective, and a switch to a different biologic was necessary. In three patients a third biologic was necessary to achieve disease control. The biologics eventually determined a clinical response in all patients. Patients with systemic disease showed better responses than patients with chronic articular disease (p < 0.05). Biological agents allowed either the withdrawal or the tapering of corticosteroid therapy (p < 0.0001) and of disease-modifying anti-rheumatic agents (DMARDs; p < 0.05). Three patients experienced herpes zoster reactivation. This is the longest follow-up of a cohort of AOSD patients treated with biological agents. Our data show that biologics are safe and generally effective in the long-term management of AOSD, particularly in cases with systemic disease, and suggest that a clinical response can be obtained in almost all AOSD patients, although a switch to drugs with a different mechanism of action may be necessary.


[Laser scotometry in macular diseases].
Retinal sensitivity is examined by projecting the aiming beam of an argon krypton laser photocoagulator onto the fundus through a contact lens. Even at normal intensity the brightness of the projected aiming on the retina is much greater than the maximum-intensity light target in ordinary scotometry. The discrepancy between scotomata when comparing the results of ordinary and laser scotometry suggests a potential for recovery of visual function, especially in macular diseases. This examination is practicable even if there is slight opacity of the media. By setting the laser beam at sufficiently low intensity, relative scotomata can be detected.


Histologic evaluation of intraoral skin grafts and pedicle flaps in humans.
Histologic evaluation of biopsy specimens from six split-thickness skin grafts and seven pedicle flaps was made two months to 15 years after intraoral cancer reconstruction. In the transplanted skin, there was persistence of all epidermal layers with production of orthokeratin and melanin, and persistence of papillary and reticular dermis with viable hair follicles and sweat glands. The junction of epidermis and mucosa was distinguished by a strongly positive PAS staining of the mucosal epithelium. There were no differences in the observations on split-thickness grafts and pedicle flaps. After 15 years of exposure to an intraoral environment, "mucosalization" of the skin was not evident.


Increased aqueous flare is associated with thickening of inner retinal layers in eyes with retinitis pigmentosa.
Retinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes, and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina,nerve fiber layer(NFL),ganglion cell layer(GCL),inner plexiform layer(IPL),inner nuclear layer(INL),outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration.


[Pigment formation and other biological properties of staphylococci].
A comparison was made of the pigment-forming capacity and the enzymatic activity, growth rate, virulence and sensitivity to antibiotics and egg lysozyme in 397 pigment, 203 pigment-free strains of staphylococci and 24 pigment-free Staph aureus mutants. Pigment formation did not always correlate with the general biological activity of the cultures, the rate of their growth and the sensitivity to antibiotics and lysozyme. Pigment-free staphylococcus mutants retained the principal properties of the initial strains (including the virulence and sensitivity to antibiotics and egg lysozyme) more frequently. It is supposed that the marker determining the pigment formation in staphylococci was not connected with the markers determining the most significant pathogenicity properties and also antibiotic resistance.


Appearance of chemically treated root canal walls in the scanning electron microscope.
The dissolving effects of seven endodontic solutions on unprepared root canal walls of young intact human premolars were evaluated with the scanning electron microscopy. After incubation at 37 degrees C in distilled water or isotonic saline for 10 min the predentinal surfaces showed no changes as compared with untreated controls. The demineralizers Decal and Largal Ultra had little effect on the organic tissues but caused some decalification where mineralized dentin was exposed. Nelex caused concentration-dependent coagulation of the residual pulp tissue, making typical ring structures on the surfaces. Sodium hypochlorite at 2.5% and 5.0% dissolved most of the predentin, exposing the globular appearance of the mineralizing front. Salvizol produced small globules on otherwise intact surfaces. Dissolution of both the organic and inorganic tissue of the root canal wall would require the combined use of two of the solutions studied.


Randomized controlled trial on the comparison of chest tube drainage and needle aspiration in the treatment of primary spontaneous pneumothorax.
To evaluate the efficacy of the chest tube drainage (CTD) and the needle aspiration (NA) in the treatment of primary Spontaneous pneumothorax (SP). In a randomized controlled trial, seventy patients suffering SP were divided equally into two subgroups, as follows: (A) CTD and (B) NA. The immediate and one-week rate of the treatments was the primary endpoints. Postoperative complications, length of hospital stay and incidence of pneumothorax recurrence during one-year follow up were also recorded. The immediate success of treatment was 68.5% and 54.2% of patients in CTD and NA groups, respectively that showed no significant difference between study groups (P: 0.16). The complete lung expansion after one week observed in 32 (91.4%) of NA group and 33 (94.2%) patients in CTD group (P: 0.5). Pneumothorax recurrence was detected in 13 patients (4 in NA and 9 in CTD group) (P: 0.11). Mean pain intensity was significantly lower in the NA group at the first hour after the procedure, the first postoperative day and the first week after the intervention (P< 0.001). Needle aspiration (NA) can be applied as a first step treatment in patients with primary SP, considering its advantages.


White-nose syndrome restructures bat skin microbiomes.
The skin microbiome is an essential line of host defense against pathogens, yet our understanding of microbial communities and how they change when hosts become infected is limited. We investigated skin microbial composition in three North American bat species (Myotis lucifugus, Eptesicus fuscus, and Perimyotis subflavus) that have been impacted by the infectious disease, white-nose syndrome, caused by an invasive fungal pathogen, Pseudogymnoascus destructans. We compared bacterial and fungal composition from 154 skin swab samples and 70 environmental samples using a targeted 16S rRNA and internal transcribed spacer amplicon approach. We found that for M. lucifugus, a species that experiences high mortality from white-nose syndrome, bacterial microbiome diversity was dramatically lower when P. destructans was present. Key bacterial families-including those potentially involved in pathogen defense-significantly differed in abundance in bats infected with P. destructans compared to uninfected bats. However, skin bacterial diversity was not lower in E. fuscus or P. subflavus when P. destructans was present despite populations of the latter species declining sharply from white-nose syndrome. The fungal species present on bats substantially overlapped with the fungal taxa present in the environment at the site where the bat was sampled, but fungal community composition was unaffected by the presence of P. destructans for any of the three bat species. This species-specific alteration in bat skin bacterial microbiomes after pathogen invasion may suggest a mechanism for the severity of white-nose syndrome in M. lucifugus but not for other bat species impacted by the disease.IMPORTANCEInherent complexities in the composition of microbiomes can often preclude investigations of microbe-associated diseases. Instead of single organisms being associated with disease, community characteristics may be more relevant. Longitudinal microbiome studies of the same individual bats as pathogens arrive and infect a population are the ideal experiment but remain logistically challenging; therefore, investigations like our approach that are able to correlate invasive pathogens to alterations within a microbiome may be the next best alternative. The results of this study potentially suggest that microbiome-host interactions may determine the likelihood of infection. However, the contrasting relationship between Pd and the bacterial microbiomes of Myotis lucifugus and Perimyotis subflavus indicate that we are just beginning to understand how the bat microbiome interacts with a fungal invader such as Pd.


Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytoma.
Before the advent of the operating microscope and the carbon dioxide laser, reoperations were performed in less than 5% of patients with malignant astrocytoma. Between 1978 and 1981, a consecutive series of 74 adult patients were prospectively treated therapy, all patients eligible for further treatment were offered reoperation with the microscope and/or laser before treatment with Phase I agents (microwave hyperthermia, dimethyl sulfoxide (DMSO)-Adriamycin, DMSO-Cytoxan, or azaridinylbenzoquinone (AZQ)). Forty-six per cent of the patients were referred from outside institutions for intensive treatment. In 36 months, 40 patients received second operations directed at their tumor and had a median calculated survival from the time of reoperation of 37 weeks. The length of survival after the second operation was independent of patient age, performance status, tumor grade, and interoperative interval. Sixty-five per cent of patients under 40 and 48% of patients over 40 underwent reoperation with minimal morbidity and no deaths. The single most important prognostic factor for survival in both reoperated and single-operated patients was age. Tumor grade had no influence on survival in the series as a whole, in patients under 40 years of age, or in reoperated patients. The calculated median survival for the entire series was 15 months, with a predicted 2-year survival rate of 0.25. These figures include all patients treated without exclusion for incomplete radiotherapy or chemotherapy. It is concluded that reoperation for malignant astrocytoma is safe, feasible, and of potential benefit in combination with other therapies. The routine use of reoperation to "set up" other treatment modalities deserves further study.


Critical casimir forces and colloidal phase transitions in a near-critical solvent: a simple model reveals a rich phase diagram.
From experimental studies, it is well known that colloidal particles suspended in a near-critical binary solvent exhibit interesting aggregation phenomena, often associated with colloidal phase transitions and assumed to be driven by long-ranged solvent-mediated (SM) interactions (critical Casimir forces), set by the (diverging) correlation length of the solvent. We present the first simulation and theoretical study of an explicit model of a ternary mixture that mimics this situation. Both the effective SM pair interactions and the full ternary phase diagram are determined for Brownian disks suspended in an explicit two-dimensional supercritical binary liquid mixture. Gas-liquid and fluid-solid transitions are observed in a region that extends well away from criticality of the solvent reservoir. We discuss to what extent an effective pair-potential description can account for the phase behavior we observe. Our study provides a fresh perspective on how proximity to the critical point of the solvent reservoir might influence colloidal self-assembly.


Evidence-based treatments for couples with unexplained infertility: a guideline.
To provide evidence-based recommendations to practicing physicians and others regarding the effectiveness and safety of therapies for unexplained infertility. ASRM conducted a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1968 through 2019. The ASRM Practice Committee and a task force of experts used available evidence and informal consensus to develop evidence-based guideline recommendations. Outcomes of interest included: live-birth rate, clinical pregnancy rate, implantation rate, fertilization rate, multiple pregnancy rate, dose of treatment, rate of ovarian hyperstimulation, abortion rate, and ectopic pregnancy rate. The literature search identified 88 relevant studies to inform the evidence base for this guideline. Evidence-based recommendations were developed for the following treatments for couples with unexplained infertility: natural cycle with intrauterine insemination (IUI); clomiphene citrate with intercourse; aromatase inhibitors with intercourse; gonadotropins with intercourse; clomiphene citrate with IUI; aromatase inhibitors with IUI; combination of clomiphene citrate or letrozole and gonadotropins (low dose and conventional dose) with IUI; low-dose gonadotropins with IUI; conventional-dose gonadotropins with IUI; timing of IUI; and in vitro fertilization and treatment paradigms. The treatment of unexplained infertility is by necessity empiric. For most couples, the best initial therapy is a course (typically 3 or 4 cycles) of ovarian stimulation with oral medications and intrauterine insemination (OS-IUI) followed by in vitro fertilization for those unsuccessful with OS-IUI treatments.


Identification of a novel paternally expressed transcript adjacent to snRPN in the Prader-Willi syndrome critical region.
Small nuclear ribonucleoprotein-associated polypeptide N (snRPN) and an anonymous transcript, PAR-5, are two of the paternally expressed transcripts mapped to the Prader-Willi syndrome critical region. Using long-range PCR, we have isolated the genomic interval between snRPN and PAR-5, identified a novel transcript in this region, and termed it PAR-SN. Northern analysis demonstrates that PAR-SN is expressed in brain, skeletal muscle, and heart. Like snRPN and PAR-5, PAR-SN is expressed exclusively from the paternal homolog in cultured lymphoblasts. Sequence analysis of the transcript revealed no significant open reading frame but did include a polymorphic dinucleotide repeat (CA)17.


Hybrid capture of 964 nuclear genes resolves evolutionary relationships in the mimosoid legumes and reveals the polytomous origins of a large pantropical radiation.
Targeted enrichment methods facilitate sequencing of hundreds of nuclear loci to enhance phylogenetic resolution and elucidate why some parts of the "tree of life" are difficult (if not impossible) to resolve. The mimosoid legumes are a prominent pantropical clade of ~3300 species of woody angiosperms for which previous phylogenies have shown extensive lack of resolution, especially among the species-rich and taxonomically challenging ingoids. We generated transcriptomes to select low-copy nuclear genes, enrich these via hybrid capture for representative species of most mimosoid genera, and analyze the resulting data using de novo assembly and various phylogenomic tools for species tree inference. We also evaluate gene tree support and conflict for key internodes and use phylogenetic network analysis to investigate phylogenetic signal across the ingoids. Our selection of 964 nuclear genes greatly improves phylogenetic resolution across the mimosoid phylogeny and shows that the ingoid clade can be resolved into several well-supported clades. However, nearly all loci show lack of phylogenetic signal for some of the deeper internodes within the ingoids. Lack of resolution in the ingoid clade is most likely the result of hyperfast diversification, potentially causing a hard polytomy of six or seven lineages. The gene set for targeted sequencing presented here offers great potential to further enhance the phylogeny of mimosoids and the wider Caesalpinioideae with denser taxon sampling, to provide a framework for taxonomic reclassification, and to study the ingoid radiation.


[Spontaneous hemorrhage in liver neoplasms. Experience at an institution].
Retrospective review of a single Institution experience with the management of hepatic neoplasms complicated with spontaneous bleeding. In a 11 years period from 1980 to 1990 we reviewed the medical charts of patients treated at our Institution with the diagnosis of hepatic neoplasms complicated with sudden bleeding. We recorded demographic information, clinical manifestations, treatment and outcome. A review of the world literature was done. We found six patients with the diagnosis of liver tumors complicated with sudden bleeding. Five patients were female with a age range from 30 to 67 years old. Four of them had an adenoma (three of them single and one multiple) and the fifth had a non-parasitic cyst. Seventy-five per cent of the patients with the diagnosis of adenoma had used in the past oral contraceptives for at least three years. The sixth patient was a male with a ruptured hepatocellular carcinoma. Three patients were admitted in shock. Successful transcatheter hepatic arterial embolization was performed in two patients; the third required operative hemostasis. Major hepatic resections were performed in three patients including a total hepatectomy and liver transplant. All patients recovered satisfactorily. The spontaneous rupture of benign and malignant tumors of the liver is not a common phenomenon, but is a serious complication. The experience of our Institution and the reports of literature favor CT scan and arteriogram as the most effective diagnostic methods in this group of patients, but arteriogram has the advantage of its therapeutic potential. The long term prognosis of this patients depends of their pathological diagnosis.


Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779].
Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy. Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter. Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed. Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.


Effects of Job Burnout and Emotional Labor on Objective Structured Clinical Examination Performance Among Interns and Residents in Taiwan.
Medical education faces challenges concerning job burnout and emotional labor among junior physicians, which poses a potential threat to the quality of medical care. Although studies have investigated job burnout and emotional labor among physicians, empirical research on the association between job burnout, emotional labor, and clinical performance is lacking. This study investigated the effects of job burnout and emotional labor on clinical performance by using the objective structured clinical examination (OSCE) scores of interns and residents. Specifically, this cross-sectional study utilized the Maslach Burnout Inventory and the Emotional Labor Questionnaire as measurement instruments. A total of 225 interns and residents in central Taiwan answered structured questionnaires before beginning their OSCE. The major statistical analysis method employed was logistic regression. After adjustment for covariates, first-year residents were less likely than other residents to obtain high OSCE scores. The odds of high OSCE performance among interns and residents with high interaction component scores in emotional labor were significantly higher than those with low interaction scores. A high score in the interaction dimension of emotional labor was associated with strong clinical performance. The findings suggest that interventions which motivate positive attitudes and increase interpersonal interaction skills among physicians should receive higher priority.


Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.
Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.


Treatment of hemophagocytic lymphohistiocytosis with chemotherapy and bone marrow transplantation: a single-center study of 22 cases.
Twenty-two children with hemophagocytic lymphohistiocytosis were treated with a chemotherapy regimen consisting of VP16-213, corticosteroids, and intrathecal methotrexate. A sustained clinical and biologic complete remission was obtained in 15 children and a partial remission in one child; six children died early of opportunistic infection (n = 4) or of disease progression (n = 2). Of the 16 children who were placed in first remission, 10 received maintenance chemotherapy alone, while six underwent bone marrow transplantation (HLA matched in five, HLA mismatched in one). Of the children who received chemotherapy alone, only two are in long-term remission after cessation of treatment. The remaining eight patients relapsed after a mean period of 5.4 months (range 2 to 8 months). Further treatment using the same regimen induced second remissions of short duration; death occurred after a median period of 2.3 months (range 0.5 to 6 months). A total of nine patients received allogeneic bone marrow transplantation (BMT). Among the six children transplanted in remission, four are in long-term unmaintained remission, 1 to 6 years after HLA-matched BMT. However, the relapse that occurred in one patient 1 year post BMT is difficult to interpret because the donor, the patient's 5-year-old sister, also developed the disease 1 year later. An HLA-nonidentical BMT resulted in unmaintained remission for 1 year, with autologous hematologic reconstitution followed by disease relapse. HLA-nonidentical BMT failed in three other patients with active disease at time of transplant. The poor long-term results of chemotherapy alone justify the use of related HLA-matched BMT in complete remission.


Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy.
Membranoproliferative glomerulonephritis (MPGN) is an immune complex-mediated glomerulonephritis characterized by subendothelial and mesangial deposition of immune complexes. Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal gammopathy is a less widely recognized cause of MPGN. We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal gammopathy with MPGN. Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies. Of 126 patients with MPGN, 20 did not have workup for hepatitis B or C. Of the remaining 106 patients, 25 (23.5%) were positive for hepatitis B or C. Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies. Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal gammopathy. Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal gammopathy. Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying gammopathy. On the basis of the bone marrow biopsy, monoclonal gammopathy of undetermined significance was the most common entity associated with MPGN. Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia. Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy.


Novel brainstem syndrome associated with prostate carcinoma.
Two patients successfully treated for prostatic cancer developed a progressive neurologic syndrome beginning with loss of voluntary horizontal eye movements followed by severe, persistent muscle spasms of the face, jaw, and pharynx. Both had mild gait unsteadiness, and one exhibited facial and abdominal myoclonus. Extensive diagnostic studies, including MRIs of the brainstem (with and without contrast), were normal. CSF examination showed mild pleocytosis and elevated IgG. Quantitative eye movement recordings documented selective involvement of voluntary horizontal saccades with sparing of horizontal slow eye movements. Neither patient had antineuronal antibodies in the blood. Postmortem examination revealed perivascular chronic inflammatory cells and microglial infiltration of the pons and medulla. One patient also had perivascular infiltrates in both mesial temporal lobes. Neuronal loss was localized to the pontine tegmentum, the medullary sensory nuclei, and the cerebellum. Brainstem motor nuclei were preserved. The clinical and pathologic findings suggest an autoimmune process (probably paraneoplastic) with selective damage to a subpopulation of brainstem neurons critical for horizontal eye movements and recurrent inhibition of bulbar nuclei.


Evaluation of a case management service to reduce sickness absence.
It is unclear whether and to what extent intensive case management is more effective than standard occupational health services in reducing sickness absence in the health care sector. To evaluate a new return to work service at an English hospital trust. The new service entailed intensive case management for staff who had been absent sick for longer than 4 weeks, aiming to restore function through a goal-directed and enabling approach based on a bio-psycho-social model. Assessment of the intervention was by controlled before and after comparison with a neighbouring hospital trust at which there were no major changes in the management of sickness absence. Data on outcome measures were abstracted from electronic databases held by the two trusts. At the intervention trust, the proportion of 4-week absences that continued beyond 8 weeks fell from 51.7% in 2008 to 49.1% in 2009 and 45.9% in 2010. The reduction from 2008 to 2010 contrasted with an increase at the control trust from 51.2% to 56.1%-a difference in change of 10.7% (95% CI 1.5-20.0%). There was also a differential improvement in mean days of absence beyond 4 weeks, but this was not statistically significant (1.6 days per absence; 95% CI -7.2 to 10.3 days). Our findings suggest that the intervention was effective, and calculations based on an annual running cost of £57 000 suggest that it was also cost-effective. A similar intervention should now be evaluated at a larger number of hospital trusts.


Is the incidence of differentiated thyroid cancer increased in patients with thyrotropin-secreting adenomas? Report of three cases from a large consecutive series.
Patients with a thyrotropin-secreting pituitary adenoma (TSHoma) are exposed to unregulated and inappropriately high levels of thyrotropin (TSH). Given the rarity of this condition, it is not known whether this chronic TSH stimulation of the thyroid gland might represent a risk factor for the development of differentiated thyroid cancer (DTC). We analyzed the incidence of DTC in a large cohort of patients with TSHomas. The study population consisted of all consecutive patients who underwent neurosurgery for a TSHoma between 1990 and 2013. Criteria for the diagnosis of TSHoma in patients without previous thyroid ablative procedures included elevated free thyroid hormones and normal/high serum TSH concentrations, presence of a lesion at magnetic resonance imaging (MRI), and abnormal response of TSH to at least one dynamic test. Patients who had received thyroid ablative procedures were required to have a pituitary lesion on MRI and TSH levels not suppressed while on levothyroxine therapy at doses causing elevation of free thyroid hormone levels. Sixty-two patients (32 females, 30 males) underwent surgery for a TSHoma at our center. Among them, 3 patients had a coexistent diagnosis of DTC with an estimated incidence of 4.8%. In 2 patients, DTC was diagnosed during the evaluation for suspected TSH-dependent hyperthyroidism, whereas in the third patient, diagnosis of DTC preceded the detection of the pituitary tumor. The elevated incidence of DTC in patients with TSHoma suggests a possible role of TSH hypersecretion in the development of thyroid tumors. A formal high-resolution ultrasound of the thyroid is recommended in patients diagnosed with a TSHoma, especially if a long history of the pituitary tumor is suspected. Moreover, suspicion about the presence of TSHoma should be raised by the lack of suppression of TSH levels despite adequate doses of levothyroxine after thyroidectomy for DTC.


Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle.
Extended periods of skeletal muscle disuse results in muscle atrophy and weakness. Currently, no therapeutic treatment is available for the prevention of this problem. Nonetheless, growing evidence suggests that prevention of disuse-induced oxidative stress in inactive muscle fibers can delay inactivity-induced muscle wasting. Therefore, this study tested the hypothesis that dietary supplementation with the antioxidant astaxanthin would protect against disuse muscle atrophy, in part, by prevention of myonuclear apoptosis. Wistar rats (8 weeks old) were divided into control (CT, n = 9), hindlimb unloading (HU, n = 9), and hindlimb unloading with astaxanthin (HU + AX, n = 9) groups. Following 2 weeks of dietary supplementation, rats in the HU and HU + AX groups were exposed to unloading for 7 days. Seven-day unloading resulted in reduced soleus muscle weight and myofiber cross-sectional area (CSA) by ~30 and ~47 %, respectively. Nonetheless, relative muscle weights and CSA of the soleus muscle in the HU + AX group were significantly greater than those of the HU group. Moreover, astaxanthin prevented disuse-induced increase in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei. We conclude that astaxanthin supplementation prior to and during hindlimb unloading attenuates soleus muscle atrophy, in part, by suppressing myonuclear apoptosis.


Galanin stimulates neurite outgrowth from sensory neurons by inhibition of Cdc42 and Rho GTPases and activation of cofilin.
We and others have previously shown that the neuropeptide galanin modulates neurite outgrowth from adult sensory neurons via activation of the second galanin receptor; however, the intracellular signalling pathways that mediate this neuritogenic effect have yet to be elucidated. Here, we demonstrate that galanin decreases the activation state in adult sensory neurons and PC12 cells of Rho and Cdc42 GTPases, both known regulators of filopodial and growth cone motility. Consistent with this, activated levels of Rho and Cdc42 levels are increased in the dorsal root ganglion of adult galanin knockout animals compared with wildtype controls. Furthermore, galanin markedly increases the activation state of cofilin, a downstream effector of many of the small GTPases, in the cell bodies and growth cones of sensory neurons and in PC12 cells. We also demonstrate a reduction in the activation of cofilin, and alteration in growth cone motility, in cultured galanin knockout neurons compared with wildtype controls. These data provide the first evidence that galanin regulates the Rho family of GTPases and cofilin to stimulate growth cone dynamics and neurite outgrowth in sensory neurons. These findings have important therapeutic implications for the treatment of peripheral sensory neuropathies.


Enhancing antitumor by immunization with fusion of dendritic cells and engineered tumor cells.
A novel approach for a dentritic cells (DCs)-based tumor vaccine was developed for the formation of hybrid-engineered J558 after fusion with DCs. To make the hybrid-tumor vaccine generate more efficient specific CTL cytotoxicity against wild-type tumor cells, we genetically engineered tumor cells with mIL-12 gene prior to the cell fusion. mIL-12 was detected at 870 +/- 60 pg/(10(5) cells/ml) in the culture supernatants and the fusion ratio was about 30% by the co-focal microscopic analysis. Vaccination of mice with DCs fused with engineered J558 induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. These results suggest that this approach of using DCs fused with engineered tumor cells could be applied in clinical settings of DCs-based cancer vaccines.


Governing nursing through reflection: a discourse analysis of reflective practices.
This paper is a report of a study to analyse reflection as discourse and a technology of confession which produces a certain desirable subjectivity within nursing practice. Reflection and reflective practice are common themes in nursing practices and in the literature on nursing. These practices are often construed as positive and empowering, and more critical analyses of them are needed. A Foucauldian-inspired discourse analysis based on the concepts of governmentality and technologies of the self was conducted. Transcripts of interviews conducted in 2006-07 with 42 managers, supervisors, teachers and participants in an in-service programme to prepare healthcare assistants to become Licensed Practice Nurses in the elder care sector were analysed. Reflection as confession operates as a governing technology within the nursing practice analysed. Programme participants are encouraged to reflect and scrutinize themselves about their work as a way to improve their competencies and practice. Through appraisals, they are invited to reflect about themselves as way to achieve their desires. In this way, active, responsible, problem-solving, self-governing practitioners are constructed. Through a Foucauldian reading of reflective practices it is possible to illustrate that reflection is not a neutral or apolitical practice. Instead, it is a governing practice that does something, in discursive terms, to nursing subjectivity - something that can create a space for reflection about what reflection discursively does to subjectivity.


[The effect of thyroliberin on the structural characteristics of rat erythrocytes].
The effect of regulatory peptide thyrotropin-releasing hormone (TRH) on the structure of the plasma membrane and morphology of rat erythrocytes was studied using a spin probe and scanning electron microscopy. EPR spectra of the spin probe introduced in the intramembrane space demonstrate that TRH at 10(-7) and 10(-3) M induces structural changes in the erythrocyte membrane. Scanning electron microscopy showed that introduction of TRH at 10(-11), 10(-7), and 10(-3) M in the erythrocyte suspension increased the proportion of discocytes as compared to the control. This effect is due to TRH-induced cell transformation in discocytes. The obtained data suggest that TRH affects the membrane structure and the morphology of erythrocytes, changes the functional activity of these cells and, thus, indirectly influences the rate of the oxygen supply to tissue.


Dietary patterns in the population living in the Sámi core areas of Norway--the SAMINOR study.
To identify dietary patterns and to investigate their association with selected life-style and demographic factors, ethnicity and self-perceived health. Study design. Population-based cross-sectional design, using food frequency questionnaires. A total of 12,811 subjects aged 36-79 years participated from the municipalities in Norway where more than 5-10% of the population reported to be Simi in the 1970 Census, in addition to some selected districts. The data were collected during 2003-2004. A principal component analysis was used to assess the associations among food variables. Seven principal components were then used as input in a cluster analysis. Five dietary patterns were identified and labelled "reindeer", "fish", "average", "fruits and vegetables" and "Westernised, traditional marine". The reindeer pattern was highly represented by subjects with three generations of Sámi language (Sámi I), obese subjects and those with low levels of physical activity. The fish pattern was dominated by women and had the largest proportion of individuals who reported their health as being "not so good" (35%). However, this pattern had the largest proportion of subjects in the oldest age categories. The fruits and vegetables pattern was characterised by a health-conscious life-style, included more women than men, and had the largest proportion of subjects reporting "very good" health. Ethnicity did not play a major role in predicting dietary patterns except for the reindeer pattern, especially in the inland areas. In the dietary cluster analysis we identified five distinct dietary patterns that were also characterised by additional life-style factors.


The clinical usefulness of procalcitonin measurement for assessing the severity of bacterial infection in critically ill patients requiring corticosteroid therapy.
Markers of inflammation, such as C-reactive protein (CRP) and white blood cell count, have, because of their low specificity, proven far from ideal in identifying patients with sepsis. Procalcitonin (PCT) has been shown to be a useful marker for differentiating patients with bacterial infection from other acute inflammatory conditions. Corticosteroid therapy has been demonstrated to be effective for treating patients with septic shock, late-phase acute respiratory distress syndrome (ARDS), or functional adrenal insufficiency, and the use of corticosteroid in critical illness has recently increased. It is also well established that corticosteroid modulate inflammatory variables in acute inflammatory conditions. The purpose of this study was to evaluate the clinical usefulness of PCT measurement for assessing the severity of bacterial infection in patients requiring corticosteroid therapy. Six patients with confirmed bacterial infectious diseases or suspected infectious diseases and requiring corticosteroid therapy were enrolled in the study. Levels of PCT and CRP were measured. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score were calculated to evaluate the severity of sepsis. 1) There was no significant correlation between the serum concentration of PCT and the plasma level of CRP in patients requiring corticosteroid therapy. 2) The PCT concentration was significantly correlated with the SOFA score (R(2)=0.467, p<0.0001) and the APACHE II score (R(2)=0.308, p=0.0003). However, no significant correlations was found between the CRP concentration and the SOFA score (R(2)=0.054, p=0.15) or the APACHE II score (R(2)=0.043, p=0.20). 3) Data sets were divided into two groups: septic shock and non-septic shock. No significant differences were present in CRP levels between the groups. However, significant differences were apparent in PCT concentrations (p<0.001). PCT can be a more sensitive and useful marker than CRP for evaluating the severity and progression of sepsis in patients requiring corticosteroid therapy. Further studies are needed to confirm these results in larger groups of patients.


Is a More Comprehensive Surgery Necessary in Patients With Uterine Serous Carcinoma?
Uterine serous carcinoma (USC) is an aggressive histologic subtype of endometrial cancer that shares similarities to serous ovarian cancer, with a propensity for spread to the upper abdomen, a high recurrence rate, and a poor prognosis. The aim of this study was to determine whether the traditional surgical staging procedure for endometrial cancer was adequate for USC or whether a more extensive surgery, similar to the staging procedure for ovarian cancer, needs to be performed. Specifically, the roles of omentectomy and sentinel lymph node (SLN) mapping were evaluated. We retrospectively identified cases of presumed clinical stage I USC at our institution from April 2005 to March 2014. Medical records were reviewed for the following information: age at diagnosis, preoperative imaging, operative findings, surgical procedure, and final histology with definitive International Federation of Gynecology and Obstetrics stage. A total of 39 patients with presumed clinical stage I USC were identified. According to the final pathology report, the surgical stage was as follows: 17 stage IA (44%), 8 stage IB (20%), 3 stage II (8%), 2 stage IIIA (5%), 6 stage IIIC1 (15%), 1 IIIC2 (3%), and 2 stage IVB (5%). Therefore, 14 patients (36%) were surgically upstaged, but none of the patients had their clinical disease upstaged by virtue of finding microscopic metastatic disease in an otherwise normal-looking omentum. Sentinel lymph node mapping was performed in 19 patients (42%). Sensitivity and negative predictive value of SLN mapping were 100% when at least 1 SLN was identified. The detection of microscopic disease in radiologically and clinically normal-appearing omentum seems to be rare in USC. Sentinel lymph node mapping seems to be valuable in the serous subtype of endometrial cancer. A less extensive surgery may be possible in patients with USC as it seems to provide the same information as a more extensive surgery.


Expression of v-rel induces mature B-cell lines that reflect the diversity of avian immunoglobulin heavy- and light-chain rearrangements.
The infection of newly hatched chickens with reticuloendotheliosis virus strain T (REV-T) and a nonimmunosuppressive helper virus, chicken syncytial virus, induces rapidly metastatic B-cell lymphomas. In vivo analysis of these tumors with monoclonal antibodies detected the expression of the B-cell surface markers immunoglobulin M (IgM), CIa, Bu2, and CLA-1, but not IgG, Bu1, or a T-cell surface marker, CT-1. Cell lines derived from tumors exhibited the same pattern of staining, suggesting that expression of cell surface markers does not change during in vitro cell line development. All cell lines examined synthesized IgM in varying amounts. Northern (RNA blot) analysis confirmed abundant expression of v-rel mRNA, and Southern analysis revealed rearrangement of both heavy- and light-chain immunoglobulin loci. Analysis of the light-chain locus demonstrated that 20 of 22 lines contained a single rearranged allele. With respect to specific restriction enzyme sites within the V lambda 1 gene, the active allele in any given clone was either diversified or nondiversified. In contrast, examination of the heavy-chain loci within these lines demonstrated that 16 of the 22 had both alleles rearranged. Further diversification of the V lambda 1 locus did not occur after prolonged in vitro passage of the cell lines. We propose that v-rel expression arrests diversification of the light-chain locus in these lymphoid cells, allowing the production of stable, clonal B-cell populations. The development of these and similar cell lines will make it possible to identify specific stages of avian lymphoid ontogeny and to study the mechanism of rearrangement and diversification in the avian B lymphocyte.


An autoregressive model-based particle filtering algorithms for extraction of respiratory rates as high as 90 breaths per minute from pulse oximeter.
We present particle filtering (PF) algorithms for an accurate respiratory rate extraction from pulse oximeter recordings over a broad range: 12-90 breaths/min. These methods are based on an autoregressive (AR) model, where the aim is to find the pole angle with the highest magnitude as it corresponds to the respiratory rate. However, when SNR is low, the pole angle with the highest magnitude may not always lead to accurate estimation of the respiratory rate. To circumvent this limitation, we propose a probabilistic approach, using a sequential Monte Carlo method, named PF, which is combined with the optimal parameter search (OPS) criterion for an accurate AR model-based respiratory rate extraction. The PF technique has been widely adopted in many tracking applications, especially for nonlinear and/or non-Gaussian problems. We examine the performances of five different likelihood functions of the PF algorithm: the strongest neighbor, nearest neighbor (NN), weighted nearest neighbor (WNN), probability data association (PDA), and weighted probability data association (WPDA). The performance of these five combined OPS-PF algorithms was measured against a solely OPS-based AR algorithm for respiratory rate extraction from pulse oximeter recordings. The pulse oximeter data were collected from 33 healthy subjects with breathing rates ranging from 12 to 90 breaths/ min. It was found that significant improvement in accuracy can be achieved by employing particle filters, and that the combined OPS-PF employing either the NN or WNN likelihood function achieved the best results for all respiratory rates considered in this paper. The main advantage of the combined OPS-PF with either the NN or WNN likelihood function is that for the first time, respiratory rates as high as 90 breaths/min can be accurately extracted from pulse oximeter recordings.


Changes in awareness and knowledge concerning mother-to-child infections among Japanese pregnant women between 2012 and 2018.
This study aimed to investigate the long-term changes in awareness of and knowledge about mother-to-child infections across 6 years in Japan. A questionnaire survey was conducted at our facility from October 2012 to January 2018, and the study periods were divided into 4 phases comprising 16 months each. A multiple-choice questionnaire assessed participants' awareness of the following 13 pathogens of mother-to-child infections: cytomegalovirus (CMV), Toxoplasma gondii (T. gondii), hepatitis B virus, rubella virus, herpes simplex virus, parvovirus B19, hepatitis C virus, human immunodeficiency virus, human T cell leukemia virus type-1, measles virus, varicella-zoster virus, Chlamydia trachomatis, and Treponema pallidum. For the selected four pathogens (i.e., CMV, rubella virus, T. gondii, and parvovirus B19), the questionnaire also evaluated participants' knowledge of transmission routes, the most susceptible time of infection that could yield severe fetal disease during pregnancy, the maximum frequency of fetal infection in cases of maternal infection, and methods to prevent maternal infection. In total, 1433 pregnant Japanese women were included in this study. There was no secular change in awareness of the pathogens concerning mother-to-child infections over time, and we also clarified that the detailed knowledge of the four pathogens of typical mother-to-child infections did not improve. Since knowledge about methods to prevent maternal infection is still insufficient for all pathogens, further advocacy is required to prevent mother-to-child infections.


Improved process for production of recombinant yeast-derived monomeric human G-CSF.
The human granulocyte colony-stimulating factor (hG-CSF) was efficiently secreted at high levels in fed-batch cultures of recombinant Saccharomyces cerevisiae. However, the secreted recombinant hG-CSF (rhG-CSF) was shown to exist as large multimers in the culture broth due to strong hydrophobic interaction. It was hardly monomerized even by urea at high concentration. This multimer has been reported to diminish specific receptor-binding activity of hG-CSF and causes undesirable problems in the downstream process. When the rhG-CSF was secreted to extracellular broth in the presence of a non-ionic surfactant (Tween 80) in the culture media, the multimerization of the secreted rhG-CSF was efficiently prevented in the fed-batch cultures. Also, the monomer fraction and secreted efficiency of rhG-CSF were significantly increased at the higher culture pH (6.5). Without using any denaturing agents, the secreted rhG-CSF monomer was easily purified with high recovery yield and purity via a simple purification process under acidic conditions, consisting of diafiltration, cation exchange, and gel filtration chromatography. A lyophilization process devoid of intermonomer aggregation was also designed using effective stabilizing agents.


Multi-aptamer-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of S. pneumoniae and S. aureus.
A novel nucleic acid aptamer nanoprobes-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of Streptococcus pneumoniae and Staphylococcus aureus is presented. In this fluorescence assay system, utilizing the hairpin allosteric effect caused by the aptamer binding to the target bacteria, the detection of S. pneumoniae is first achieved through changes in fluorescence due to FRET. Subsequently, a Cas12a protein mixture is added to detect S. aureus. The amplified output signal is triggered by two methods to ensure the sensitivity of the method: the synergistic FRET effect is achieved by the assembly of multi-aptamer through the conjugation of streptavidin-biotin, and the trans-cleavage function of CRISPR/Cas 12a. Under the optimized conditions, the proposed hairpin allosteric aptasensor could achieve high sensitivity (a detection limit of 135 cfu/mL) and broad-concentration quantification (dynamic range of 103-107 cfu/mL) of S. pneumoniae. The aptamer-assisted CRISPR system for S. aureus detection showed good linearity (R2 = 0.996) in the concentration range 102-108 cfu/mL, with a detection limit of 39 cfu/mL. No cross-reactivity with other foodborne pathogenic bacteria was observed in both systems. Taking only 55 min, this method of multiple pathogen detection proved to be promising.


Molecular cloning and phylogenetic analysis of small GTPase protein Tscdc42 from Trichinella spiralis.
A full-length of complementary deoxyribonucleic acid (Tscdc42) encoding a putative Rho-family small GTPase gene cdc42 was isolated from Trichinella spiralis, an economically important parasitic nematode of zoonosis. The uninterrupted open reading frame of TsCDC42 encodes a predicted protein of 147 amino acids and containing a highly conserved domain of CDC42. Comparison with selected sequences from the free-living nematode Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, Danio rerio, Mus musculus, and human showed that Tscdc42 is highly conserved. The highest identity of TsCDC42 with CDC42 from Drosophila is 67%, the similarity is up to 73%, the identity of TsCDC42 with the CDC42 homologue of C. elegans is 62%, and the similarity is up to 71%. Phylogenetic analysis of the amino acid sequence data, using the neighbor-joining and maximum parsimony methods, revealed that TsCDC42 is closely related to the molecule inferred from the cdc-42 gene of C. elegans. The transcript of TsCDC42 was analyzed during different stages of the worm.