Hypernatremia: correction rate and hemodialysis.
Severe hypernatremia is defined as serum sodium levels above 152 mEq/L, with a mortality rate ≥60%. 85-year-old gentleman was brought to the emergency room with altered level of consciousness after refusing to eat for a week at a skilled nursing facility. On admission patient was nonverbal with stable vital signs and was responsive only to painful stimuli. Laboratory evaluation was significant for serum sodium of 188 mmol/L and water deficit of 12.0 L. Patient was admitted to medicine intensive care unit and after inadequate response to suboptimal fluid repletion, hemodialysis was used to correct hypernatremia. Within the first fourteen hours, sodium concentration only changed 1 mEq/L with a fluid repletion; however, the concentration dropped greater than 20 mEq/L within two hours during hemodialysis. Despite such a drastic drop in sodium concentration, patient did not develop any neurological sequela and was at baseline mental status at the time of discharge.


A simple and sensitive LC-MS/MS method for quantitation of peimine and its pharmacokinetic in beagle dogs.
A simple LC-MS/MS method was developed for determination and pharmacokinetic study of peimine in beagle dogs. The chromatographic separation was carried out on a Agilent Zobax SB C18 column with a mobile phase consisting of acetonitrile-10 mmol/L ammonium formate (35:65, v/v) at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by MRM via electro spray ionization source with positive mode. The standard curve for peimine was linear (r>0.999) over the concentration range of 1-200 ng/mL with a lower limit of quantification of 1 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 15% and the accuracy (relative error) was <5% at 3 quality control levels. This simple, fast and highly sensitive method was fully validated and successfully applied to a preclinical pharmacokinetic study of peimine in dogs after oral and intravenous administration.


Species Identification of Caviar Based on Multiple DNA Barcoding.
This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.


Quenching of oscillations via attenuated coupling for dissimilar electrochemical systems.
The coupled dynamics of two similar and disparate electrochemical cells oscillators are analyzed. For the similar case, the cells are intentionally operated at different system parameters such that they exhibit distinct oscillatory dynamics ranging from periodic to chaotic. It is observed that when such systems are subjected to an attenuated coupling, implemented bidirectionally, they undergo a mutual quenching of oscillations. The same holds true for the configuration wherein two entirely different electrochemical cells are coupled via bidirectional attenuated coupling. Therefore, the attenuated coupling protocol seems to be universally efficient in achieving oscillation suppression in coupled oscillators (similar or heterogeneous oscillators). The experimental observations were verified by numerical simulations using appropriate electrodissolution model systems. Our results indicate that quenching of oscillations via attenuated coupling is robust and therefore could be ubiquitous in coupled systems with a large spatial separation prone to transmission losses.


Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure.
Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status. The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association. In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status. There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001). Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.


A systematic review of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal syndrome in pediatric intensive care.
This systematic review aimed to evaluate the quality of clinical practice guidelines (CPGs) and recommendations for managing pain, sedation, delirium, and iatrogenic withdrawal syndrome in pediatric intensive care (PICU). The objectives included evaluating the quality of recommendations, synthesizing recommendations, harmonizing the strength of the recommendation (SoR) and the certainty of evidence (CoE), and assessing the relevance of supporting evidence. A comprehensive search in four electronic databases (Medline, Embase.com, CINAHL and JBI EBP Database), 9 guideline repositories, and 13 professional societies was conducted to identify CPGs published from January 2010 to the end of May 2023 in any language. The quality of CPGs and recommendations was assessed using the AGREE II and AGREE-REX instruments. Thematic analysis was used to synthesize recommendations, and the GRADE SoR and CoE harmonization method was used to interpret the credibility of summary recommendations. A total of 18 CPGs and 170 recommendations were identified. Most CPGs were of medium-quality, and three were classified as high. A total of 30 summary recommendations were synthesized across each condition, focused on common management approaches. There was inconsistency in the SoRs and CoE for summary recommendations, those for assessment showed the highest consistency, the remaining were conditional, inconsistent, inconclusive, and lacked support from evidence. This systematic review provides an overview of the quality of CPGs for these four conditions in the PICU. While three CPGs achieved high-quality ratings, the overall findings reveal gaps in the evidence base of recommendations, patient and family involvement, and resources for implementation. The findings highlight the need for more rigorous and evidence-based approaches in the development and reporting of CPGs to enhance their trustworthiness. Further research is necessary to enhance the quality of recommendations for this setting. The results of this review can provide a valuable foundation for future CPG development. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=274364, PROSPERO (CRD42021274364).


Promoting Advance Care Planning for Persons with Dementia: Study Protocol for the LEAD (Life-Planning in Early Alzheimer's and Other Dementias) Clinical Trial.
Due to the insidious progression of Alzheimer's disease and related dementias (ADRD), surrogate decision-makers typically make medical and long-term-care decisions for a care recipient, most often a family care partner. Unfortunately, many care recipient/care partner dyads have failed to engage in advance care planning or have lost the opportunity to do so due to the cognitive decline of the care recipient. To address this need, our team created a validated dementia-focused advance care planning tool known as the LEAD Guide (Life-Planning in Early Alzheimer's and Other Dementias). With funding from the National Alzheimer's Association and in consultation with our community advisory board, we developed a preliminary web-based intervention. This intervention integrates the LEAD Guide with self-paced educational modules that lead dyads through conversations and dementia-focused advance care planning processes. In this concept paper, we describe the aims of our funded R01 clinical trial (National Institute on Aging), where we aim to refine our preliminary web-based platform for use in a 5-month mixed-method NIH Stage-1 behavioral intervention. Using a sample of diverse community-based ADRD dyads (n = 60), we aim to: 1) describe the acceptability, usability, and feasibility of the intervention, 2) assess the initial efficacy of the intervention on the primary outcome (decision-making self-efficacy), and secondary outcomes (relationship quality, subjective well-being, anxiety) as perceived by both the care recipient and the care partner, and 3) examine advance care planning congruence as a mechanism of action. The LEAD clinical trial addresses public health challenges by guiding and supporting families through challenging advance care planning conversations, facilitating the transfer of knowledge regarding care preferences and values from the care recipient to the care partner, with the ultimate goal of improving the quality of life for both individuals with ADRD and their care partners.


From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales.
Computer simulations of electrical behaviour in the whole ventricles have become commonplace during the last few years. The goals of this article are (i) to review the techniques that are currently employed to model cardiac electrical activity in the heart, discussing the strengths and weaknesses of the various approaches, and (ii) to implement a novel modelling approach, based on physiological reasoning, that lifts some of the restrictions imposed by current state-of-the-art ionic models. To illustrate the latter approach, the present study uses a recently developed ionic model of the ventricular myocyte that incorporates an excitation-contraction coupling and mitochondrial energetics model. A paradigm to bridge the vastly disparate spatial and temporal scales, from subcellular processes to the entire organ, and from sub-microseconds to minutes, is presented. Achieving sufficient computational efficiency is the key to success in the quest to develop multiscale realistic models that are expected to lead to better understanding of the mechanisms of arrhythmia induction following failure at the organelle level, and ultimately to the development of novel therapeutic applications.


Heterogeneous Pyrolysis: A Route for Epitaxial Growth of hBN Atomic Layers on Copper Using Separate Boron and Nitrogen Precursors.
Growth of hBN on metal substrates is often performed via chemical vapor deposition from a single precursor (e.g., borazine) and results in hBN monolayers limited by the substrates catalyzing effect. Departing from this paradigm, we demonstrate close control over the growth of mono-, bi-, and trilayers of hBN on copper using triethylborane and ammonia as independent sources of boron and nitrogen. Using density functional theory (DFT) calculations and reactive force field molecular dynamics, we show that the key factor enabling the growth beyond the first layer is the activation of ammonia through heterogeneous pyrolysis with boron-based radicals at the surface. The hBN layers grown are in registry with each other and assume a perfect or near perfect epitaxial relation with the substrate. From atomic force microscopy (AFM) characterization, we observe a moiré superstructure in the first hBN layer with an apparent height modulation and lateral periodicity of ∼10 nm. While this is unexpected given that the moiré pattern of hBN/Cu(111) does not have a significant morphological corrugation, our DFT calculations reveal a spatially modulated interface dipole layer which determines the unusual AFM response. These findings have improved our understanding of the mechanisms involved in growth of hBN and may help generate new growth methods for applications in which control over the number of layers and their alignment is crucial (such as tunneling barriers, ultrathin capacitors, and graphene-based devices).


Intraocular pressure-dependent retinal vascular change in adult chronic open-angle glaucoma patients.
Intraocular pressure (IOP)-dependent retinal vascular changes were investigated in 33 eyes of 33 adult chronic open-angle glaucoma (COAG) patients by measuring major retinal vascular calibers at the optic disc border before and after mean (+/- standard deviation) IOP reduction from 35.3 (+/- 7.2) to 16.5 (+/- 4.7) mmHg for 11.2 (+/- 13.5) weeks. Both mean arterial and venous calibers were significantly reduced (P less than 0.0001 for each), from 87.8 (+/- 14.2) and 128.3 (+/- 20.8) microns at high IOP to 82.0 (+/- 13.8) and 121.4 (+/- 18.5) microns at low IOP. Arterial and venous caliber decreases correlated positively with magnitude of IOP reduction (r = 0.503, P less than 0.01 and r = 0.555, P less than 0.001, respectively). While the IOP-dependent retinal arterial caliber change was highly significant in patients 55 years of age or younger (r = 0.636, P less than 0.01) and in the overall study group, it was not significant in patients older than 55 years (r = 0.205, P greater than 0.1). Age seems to be more influential than magnitude of IOP reduction in patients older than 55. Thus, diminished IOP-dependent retinal arterial caliber change in the elderly may be one factor contributing to the higher incidence and prevalence of glaucoma in this population.


Dynamics of a mobile RNA of potato involved in a long-distance signaling pathway.
BEL1-like transcription factors interact with Knotted1 types to regulate numerous developmental processes. In potato (Solanum tuberosum), the BEL1 transcription factor St BEL5 and its protein partner POTH1 regulate tuber formation by mediating hormone levels in the stolon tip. The accumulation of St BEL5 RNA increases in response to short-day photoperiods, inductive for tuber formation. RNA detection methods and heterografting experiments demonstrate that BEL5 transcripts are present in phloem cells and move across a graft union to localize in stolon tips, the site of tuber induction. This movement of RNA to stolon tips is correlated with enhanced tuber production. Overexpression of BEL5 transcripts that include the untranslated sequences of the BEL5 transcript endows transgenic lines with the capacity to overcome the inhibitory effects of long days on tuber formation. Addition of the untranslated regions leads to preferential accumulation of the BEL5 RNA in stolon tips under short-day conditions. Using a leaf-specific promoter, the movement of BEL5 RNA to stolon tips was facilitated by a short-day photoperiod, and this movement was correlated with enhanced tuber production. These results implicate the transcripts of St BEL5 in a long-distance signaling pathway that are delivered to the target organ via the phloem stream.


[Complement (C3)-activating material in synovial fluid from patients with rheumatoid arthritis].
Synovial fluid from patients with the following diagnoses was investigated: - rheumatoid arthritis (RA) - rheumatoid arthritis with benign development (BRA) - osteoarthrosis (A) The sediment was isolated by ultracentrifugation, its C3 cleaving activity measured by 2-dimensional electrophoresis and its concentration if IgG, IgM, IgA, C3, C4 and C3-proactivator by immunoprecipitation. There is evidence that there is more C3 cleaving activity in RA than in osteoarthrosis. Activity levels of BRA were between those of osteoarthrosis and RA. Although there was no significant difference in the IgG-, IgM- or IgA-level of the 3 mentioned diagnoses after 21 minutes of centrifugation (133 000 g), it was possible to demonstrate more C3 breakdown products in RA than in osteoarthrosis and BRA. Very big molecules seem to be responsible for the generation of C3 cleaving products. These observations are not only of theoretical interest but seem also to be useful diagnostically.


FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemotherapy.
The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities.


Practice-Level Documentation of Alcohol-Related Problems in Primary Care.
Rates of alcohol-associated deaths increased over the past 20 years, markedly between 2019 and 2020. The highest rates are among individuals aged 55 to 64 years, primarily attributable to alcoholic liver disease and psychiatric disorders due to use of alcohol. This study investigates potential geographic disparities in documentation of alcohol-related problems in primary care electronic health records, which could lead to undertreatment of alcohol use disorder. To identify disparities in documentation of alcohol-related problems by practice-level social deprivation. A cross-sectional study using secondary data from the Integrating Behavioral Health and Primary Care clinical trial (September 21, 2017, to January 8, 2021) was performed. A national sample of 44 primary care practices with co-located behavioral health services was included in the analysis. Patients with 2 primary care visits within 2 years and at least 1 chronic medical condition and 1 behavioral health condition or at least 3 chronic medical conditions were included. The primary exposure was practice-level Social Deprivation Index (SDI), a composite measure based on county income, educational level, employment, housing, single-parent households, and access to transportation (scores range from 0 to 100; 0 indicates affluent counties and 100 indicates disadvantaged counties). Documentation of an alcohol-related problem in the electronic health record was determined by International Classification of Diseases, 9th Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes or use of medications for alcohol use disorder in past 2 years. Multivariable models adjusted for alcohol consumption, screening for a substance use disorder, urban residence, age, sex, race and ethnicity, income, educational level, and number of chronic health conditions. A total of 3105 participants (mean [SD] age, 63.7 [13.0] years; 64.1% female; 11.5% Black, 7.0% Hispanic, 76.7% White, and 11.9% other race or chose not to disclose; 47.8% household income <$30 000; and 80.7% urban residence). Participants had a mean (SD) of 4.0 (1.7) chronic conditions, 9.1% reported higher-risk alcohol consumption, 4% screened positive for substance use disorder, and 6% had a documented alcohol-related problem in the electronic health record. Mean (SD) practice-level SDI score was 45.1 (20.9). In analyses adjusted for individual-level alcohol use, demographic characteristics, and health status, practice-level SDI was inversely associated with the odds of documentation (odds ratio for each 10-unit increase in SDI, 0.89; 95% CI, 0.80 to 0.99; P = .03). In this study, higher practice-level SDI was associated with lower odds of documentation of alcohol-related problems, after adjusting for individual-level covariates. These findings reinforce the need to address primary care practice-level barriers to diagnosis and documentation of alcohol-related problems. Practices located in high need areas may require more specialized training, resources, and practical evidence-based tools that are useful in settings where time is especially limited and patients are complex.


In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.
Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.


Coupling ex vivo electroporation of mouse retinas and luciferase reporter assays to assess rod-specific promoter activity.
Ex vivo electroporation of mouse retinas is an established tool to modulate gene expression and to study cell type-specific gene expression. Here we coupled ex vivo electroporation to luciferase reporter assays to facilitate the study of rod-photoreceptor-specific gene promoters. The activity of the rod-specific proximal bovine rhodopsin promoter was significantly increased in C57BL/6J wild-type retinas at postnatal days 1 and 7 by 3.4-fold and 8.7-fold respectively. In C57BL/6J Nr2e3(rd7/rd7) retinas, where the rod photoreceptor-specific nuclear receptor Nr2e3 is not expressed, a significant increase by 2.5-fold was only observed at postnatal day 7. Cone-specific S-opsin promoter activity was not modulated in C57BL/6J wild-type and Nr2e3(rd7/rd7) retinas. Taken together, we describe an easily implementable protocol to assess rod-specific promoter activity in a physiological context resembling that of the developing postnatal mouse retina.


Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance.
Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.


Resolving DNA at efficiencies of more than a million plates per meter using bare narrow open capillaries without sieving matrices.
We report a novel approach for effectively separating DNA molecules in free solution. The method uses a bare narrow open capillary without any sieving matrices to resolve a wide size-range of DNA fragments at efficiencies of more than a million plates per meter routinely.


Adapting the Smart-seq2 Protocol for Robust Single Worm RNA-seq.
Most nematodes are small worms that lack enough RNA for regular RNA-seq protocols without pooling hundred to thousand of individuals. We have adapted the Smart-seq2 protocol in order to sequence the transcriptome of an individual worm. While developed for individual Steinernema carpocapsae and Caenorhabditis elegans larvae as well as embryos, the protocol should be adaptable for other nematode species and small invertebrates. In addition, we describe how to analyze the RNA-seq results using the Galaxy online environment. We expect that this method will be useful for the studying gene expression variances of individual nematodes in wild type and mutant backgrounds.


Pressure and temperature spin crossover sensors with optical detection.
Iron(II) spin crossover molecular materials are made of coordination centres switchable between two states by temperature, pressure or a visible light irradiation. The relevant macroscopic parameter which monitors the magnetic state of a given solid is the high-spin (HS) fraction denoted n(HS), i.e., the relative population of HS molecules. Each spin crossover material is distinguished by a transition temperature T(1/2) where 50% of active molecules have switched to the low-spin (LS) state. In strongly interacting systems, the thermal spin switching occurs abruptly at T(1/2). Applying pressure induces a shift from HS to LS states, which is the direct consequence of the lower volume for the LS molecule. Each material has thus a well defined pressure value P(1/2). In both cases the spin state change is easily detectable by optical means thanks to a thermo/piezochromic effect that is often encountered in these materials. In this contribution, we discuss potential use of spin crossover molecular materials as temperature and pressure sensors with optical detection. The ones presenting smooth transitions behaviour, which have not been seriously considered for any application, are spotlighted as potential sensors which should stimulate a large interest on this well investigated class of materials.


Grip Force and 3D Push-Pull Force Estimation Based on sEMG and GRNN.
The estimation of the grip force and the 3D push-pull force (push and pull force in the three dimension space) from the electromyogram (EMG) signal is of great importance in the dexterous control of the EMG prosthetic hand. In this paper, an action force estimation method which is based on the eight channels of the surface EMG (sEMG) and the Generalized Regression Neural Network (GRNN) is proposed to meet the requirements of the force control of the intelligent EMG prosthetic hand. Firstly, the experimental platform, the acquisition of the sEMG, the feature extraction of the sEMG and the construction of GRNN are described. Then, the multi-channels of the sEMG when the hand is moving are captured by the EMG sensors attached on eight different positions of the arm skin surface. Meanwhile, a grip force sensor and a three dimension force sensor are adopted to measure the output force of the human's hand. The characteristic matrix of the sEMG and the force signals are used to construct the GRNN. The mean absolute value and the root mean square of the estimation errors, the correlation coefficients between the actual force and the estimated force are employed to assess the accuracy of the estimation. Analysis of variance (ANOVA) is also employed to test the difference of the force estimation. The experiments are implemented to verify the effectiveness of the proposed estimation method and the results show that the output force of the human's hand can be correctly estimated by using sEMG and GRNN method.


Overexpression of MicroRNA-148b-3p stimulates osteogenesis of human bone marrow-derived mesenchymal stem cells: the role of MicroRNA-148b-3p in osteogenesis.
Mesenchymal stem cells (MSCs) are attractive choices in regenerative medicine and can be genetically modified to obtain better results in therapeutics. Bone development and metabolism are controlled by various factors including microRNAs (miRs) interference, which are small non-coding endogenous RNAs. In the current study, the effects of forced miR-148b expression was evaluated on osteogenic activity. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transduced with bicistronic lentiviral vector encoding hsa-miR-148b-3p or -5p and the enhanced green fluorescent protein. Fourteen days post-transduction, immunostaining as well as Western blotting were used to analyze osteogenesis. Overexpression of miR-148b-3p increased the osteogenic differentiation of human BM-MSCs as demonstrated by anenhancement of mineralized nodular formation and an increase in the levels of osteoblastic differentiation biomarkers, alkaline phosphatase and collagen type I. Since lentivirally overexpressed miR-148b-3p increased osteogenic differentiation capability of BM-MSCs, this miR could be applied as a therapeutic modulator to optimize bone function.


Risk factors for late right ventricular systolic dysfunction in pediatric patients with repaired tetralogy of Fallot.
To evaluate independent risk factors for late right ventricular systolic dysfunction after correction of Tetralogy of Fallot (TOF) in a single-centre, retrospective and observational clinical trial.Patients less than 3 years of age who underwent correction of TOF and subsequently routine clinical follow-up of more than 36 months were included in this study and were divided either into an experimental group (right ventricular systolic dysfunction) or a control group (normal right ventricular systolic function) according to the tricuspid annular peak systolic velocity (TAPSV) value measured by pulsed wave-tissue Doppler imaging (pulsed wave-TDI). The relevant data of all selected patients were investigated and analyzed. From January 2012 to December 2012, a total of 113 consecutive eligible patients were enrolled in this study and were divided either into an experimental group (n = 41) or control group (n = 72). Through univariate analysis and subsequent logistic regression, low preoperative arterial oxygen saturation (OR = 1.66, 95%CI 1.22-4.58, P = 0.0163), age less than 6 months at the time of surgery (OR = 3.45, 95%CI 1.87-9.17, P = 0.0021), and transannular patch (OR = 2.15, 95%CI 1.31-5.38, P = 0.0015) were 3 independent risk factors for late right ventricular systolic dysfunction after correction of TOF.This clinical trial suggested low preoperative arterial oxygen saturation was associated with late right ventricular systolic dysfunction after correction of TOF, and appropriate age at the time of surgery and selection of a proper surgical method to reconstruct the right ventricular outflow tract contributed to improving late right ventricular systolic function in pediatric patients with repaired TOF.


ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a "Toggle Switch" of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells.
There is great interest in understanding how the cancer stem cell population may be maintained in solid tumors. Here, we show that tumor cells exhibiting stem-like properties and expression of pluripotency markers NANOG and OCT4 can arise from original differentiated tumor cells freshly isolated from human glioblastomas (GBM) and that have never known any serum culture conditions. Induction of EGR1 by EGFR/ERK signaling promoted cell conversion from a less aggressive, more differentiated cellular state to a self-renewing and strongly tumorigenic state, expressing NANOG and OCT4. Expression of these pluripotency markers occurred before the cells re-entered the cell cycle, demonstrating their capacity to change and dedifferentiate without any cell divisions. In differentiated GBM cells, ERK-mediated repression of miR-199a-3p induced EGR1 protein expression and triggered dedifferentiation. Overall, this signaling pathway constitutes an ERK-mediated "toggle switch" that promotes pluripotency marker expression and stem-like features in GBM cells. SIGNIFICANCE: This study defines an ERK-mediated molecular mechanism of dedifferentiation of GBM cells into a stem-like state, expressing markers of pluripotency.See related commentary by Koncar and Agnihotri, p. 3195.


Altered immunoregulation in otitis media with effusion in children: presence of serum immuno-inhibitory factors.
In the present study serum immuno-inhibitory factors in children with otitis media with effusion (OME) were evaluated. The study included 23 children with OME and 23 healthy age-and-sex-matched controls. Serum inhibitory activity (SIA) was expressed as the inhibition index of proliferative response to T-cells lectins. In almost all the children with OME the indices reflecting T-cell proliferation were below the range of those in the control group. The results suggest that the activity of the factor(s) which affect T-cell proliferation may be included in mechanisms contributing to the persistence of OME in children. Further studies are needed in order to establish the cellular and molecular aspects of serum inhibitory activity, as well as its significance in the pathogenesis of OME.


[Clinical microbiology in the 21 century].
The number of compromised patients has remarkably increased, with the recent advancement of medical treatment. This fact may account for the increase in the rate of hospital infection. Occupational infection of health care workers from blood-borne virus is another problem. During the recent increase in hospital infections, clinical microbiology laboratories in many countries performed expanded routine work and research. These situations were studied through questionnaires sent to countries with membership in the Hospital Infection Society. An inquiry into the tasks of clinical microbiology in the 21 century was made in order to establish more effective and useful system of the laboratories.


Proteins associated with heat-induced leaf senescence in creeping bentgrass as affected by foliar application of nitrogen, cytokinins, and an ethylene inhibitor.
Heat stress causes premature leaf senescence in cool-season grass species. The objective of this study was to identify proteins regulated by nitrogen, cytokinins, and ethylene inhibitor in relation to heat-induced leaf senescence in creeping bentgrass (Agrostis stolonifera). Plants (cv. Penncross) were foliar sprayed with 18 mM carbonyldiamide (N source), 25 μM aminoethoxyvinylglycine (AVG, ethylene inhibitor), 25 μM zeatin riboside (ZR, cytokinin), or a water control, and then exposed to 20/15°C (day/night) or 35/30°C (heat stress) in growth chambers. All treatments suppressed heat-induced leaf senescence, as shown by higher turf quality and chlorophyll content, and lower electrolyte leakage in treated plants compared to the untreated control. A total of 49 proteins were responsive to N, AVG, or ZR under heat stress. The abundance of proteins in photosynthesis increased, with ribulose-1,5-bisphosphate carboxylase/oxygenase affected by all three treatments, chlorophyll a/b-binding protein by AVG and N or Rubisco activase by AVG. Proteins for amino acid metabolism were upregulated, including alanine aminotransferase by three treatments and ferredoxin-dependent glutamate synthase by AVG and N. Upregulated proteins also included catalase by AVG and N and heat shock protein by ZR. Exogenous applications of AVG, ZR, or N downregulated proteins in respiration (enolase, glyceraldehyde 3-phosphate dehydrogenase, and succinate dehygrogenase) under heat stress. Alleviation of heat-induced senescence by N, AVG, or ZR was associated with enhanced protein abundance in photosynthesis and amino acid metabolism and stress defense systems (heat shock protection and antioxidants), as well as suppression of those imparting respiration metabolism.


Influence of the Draining Lymph Nodes and Organized Lymphoid Tissue Microarchitecture on Susceptibility to Intradermal Trypanosoma brucei Infection.
Infection of the mammalian host with African trypanosomes begins when the tsetse fly vector injects the parasites into the skin dermis during blood feeding. After injection into the skin, trypanosomes first accumulate in the draining lymph node before disseminating systemically. Whether this early accumulation within the draining lymph node is important for the trypanosomes to establish infection was not known. Lymphotoxin-β-deficient mice (LTβ-/- mice) lack most secondary lymphoid tissues, but retain the spleen and mesenteric lymph nodes. These mice were used to test the hypothesis that the establishment of infection after intradermal (ID) T. brucei infection would be impeded in the absence of the skin draining lymph nodes. However, LTβ-/- mice revealed greater susceptibility to ID T. brucei infection than wild-type mice, indicating that the early accumulation of the trypanosomes in the draining lymph nodes was not essential to establish systemic infection. Although LTβ-/- mice were able to control the first parasitemia wave as effectively as wild-type mice, they were unable to control subsequent parasitemia waves. LTβ-/- mice also lack organized B cell follicles and germinal centers within their remaining secondary lymphoid tissues. As a consequence, LTβ-/- mice have impaired immunoglobulin (Ig) isotype class-switching responses. When the disturbed microarchitecture of the B cell follicles in the spleens of LTβ-/- mice was restored by reconstitution with wild-type bone marrow, their susceptibility to ID T. brucei infection was similar to that of wild-type control mice. This effect coincided with the ability to produce significant serum levels of Ig isotype class-switched parasite-specific antibodies. Thus, our data suggest that organized splenic microarchitecture and the production of parasite-specific Ig isotype class-switched antibodies are essential for the control of ID African trypanosome infections.


Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial.
Short-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy for improved prognosis, it is important to determine the optimal mix of chemotherapy, immunotherapy and SCRT. Fifty treatment-naïve patients with operable LARC (T3-4 and/or N+) will be recruited. Patients will be synchronously treated with capecitabine plus oxaliplatin (CAPOX) chemotherapy, tislelizumab and preoperative split-course hypofraction radiotherapy (SCHR) (5×7 Gy) before surgery. Chemotherapy for CAPOX starts on day 1 of every 21-day cycle: on day 1, oxaliplatin 130 mg/m2 will be injected intravenously. On days 1-14, capecitabine 1000 mg/m2 was ingested two times a day. Simultaneously, tocilizumab 200 mg will be given intravenously on the first day of every 21-day cycle. A single 7 Gy SCHR treatment (day 7 of each 21-day cycle) will be delivered five times during the seventh day of treatment. The primary endpoint will be pathological complete response. The secondary outcomes will be the 3-year disease-free survival, local recurrence rate, overall survival, sphincter-sparing surgery rate, R0 resection rate, predictive biomarkers and quality of life. The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (XAHFMU) (No. 2021YF025-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. NCT05176964.


[Old and new risks: In pursuit of other forms of protection].
Based on the concept of health as openness to risk, as outlined by Canguilhem in 1946, the authors seek to distinguish between risks that require social protection networks and those that should be tolerated as part of the human condition. To understand this issue, the article analyzes the historical emergence of the risk concept as viewed in early industrial society and its link to the idea of dangerousness and risk as analyzed by Robert Castel in his work From Dangerousness to Risk and L'Insegurité Sociale: Qu'est-ce Qu'etre Protegé? The authors discuss the continuities and discontinuities in these classical risks, with their social protection structures, and the emerging awareness of multiple hazards in late modernity.


Impact of excluding cases with known chromosomal abnormalities on the prevalence of structural birth defects, Hawaii, 1986-1999.
Chromosomal abnormalities are more common in the presence of structural birth defects. However, much of the literature have only provided chromosomal abnormality rates for one or a few structural birth defects at a time. This study calculated the chromosomal abnormality rates for a number of structural birth defects using data from the Hawaii Birth Defects Program (HBDP) for deliveries during 1986-1999 and evaluated the impact of exclusion of cases with chromosomal abnormalities when calculating birth prevalence. The chromosomal abnormality rates were highest for endocardial cushion defect (40%) and omphalocele (27%), while no chromosomal abnormalities were reported for pyloric stenosis, persistent cloaca, and deficiency of lower limbs. The majority of chromosomal abnormality rates fell within a certain range, with 32 (63%) of the birth defect categories having chromosomal abnormality rates of 5-15%. The chromosomal abnormality rates also tended to be higher for multiple than for isolated cases. For three of the structural birth defects (ventricular septal defect, atrial septal defect, endocardial cushion defect), the birth prevalence of the defect, when cases with a chromosomal abnormality were excluded, was significantly lower than the birth prevalence that included those cases. Chromosomal abnormality rates varied by type of structural birth defect and presence of other major structural birth defects. For at least several structural birth defects, exclusion of cases with chromosomal abnormalities significantly underestimated the birth prevalence. This underestimation may be important, depending on the purpose of the analysis.


PTSD Among Shidu Parents in China: The Roles of Personality Types and Social Support.
Background: The psychological problems of Shidu Parents (SDP) under the China's One-Child Policy have been documented. The purpose of this study was to investigate the relationships among personality types, social support, and post-traumatic stress disorder (PTSD) in SDP. Methods: The PTSD Checklist-Civilian Version (PCL-C), The Big Five Personality Traits (NEO), and Social Support Revalued Scale (SSRS) were administered to the sample of 149 SDP who were over 50 years old and had lost their only child more than one year ago. Results: Among SDP, mothers were more likely to develop PTSD than fathers (χ2 = 11.16, p < 0.01). Parents who were extraverted had a lower risk of developing PTSD-related symptoms (χ2 = 8.58, p < 0.01), and the effect of neuroticism was significant (χ2 = 23.73, p < 0.01). The more social support parents utilized, the lower the incidence of PTSD (t = 4.56, p < 0.01). The result of multilevel linear regression showed that sex, neuroticism, and objective social support remained significantly different after combining all personality types and social support systems in the same model. Social support partially mediated the relationship between neuroticism and PTSD. Meanwhile, it was a complete mediator between extraversion and PTSD. Conclusions: Female sex/gender, neuroticism, and introversion were risk factors of developing PTSD, while receiving social support protected SDP from developing PTSD symptoms. Losing an only child is undoubtedly an enormous disaster for the family, which has become a huge, unavoidable social problem that must be addressed in China.


Fetal umbilical velocimetry for the surveillance of pregnancies complicated by placenta previa.
Continuous-wave Doppler studies of the umbilical arteries were performed on 100 women with placenta previa prior to delivery in the third trimester and 100 control subjects matched for gestational age and with normally implanted placentas. The ratio of the maximum (systole [S]) and minimum (diastole [D]) velocities appeared to reflect downstream vascular resistance. An S:D ratio of greater than or equal to 3.0 indicated elevation. There was a statistically higher S:D ratio in the placenta previa group as compared to the control group, and that difference persisted even when growth-retarded fetuses were excluded from both groups. Placenta previa patients with S:D ratios greater than or equal to 3.0 were associated with a statistically higher incidence of adverse pregnancy outcomes. The sensitivity, specificity, and positive and negative predictive value of an elevated S:D ratio in predicting adverse pregnancy outcomes were 90.0%, 93.8%, 62.0% and 98.5%, respectively. Our data suggest that (1) placenta previa patients are at increased risk of intrauterine growth retardation and adverse pregnancy outcomes, (2) placenta previa patients with normal S:D ratios are at no greater risk of adverse outcomes than are controls, (3) when the S:D ratio is elevated in placenta previa patients, it is more likely to be associated with adverse pregnancy outcomes, and (4) placenta previa patients without growth failure have a higher S:D ratio than do those with normally implanted placentas. Umbilical artery velocimetry appears to be a useful adjunct to ultrasound in the surveillance of pregnancies complicated by placenta previa.


Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients.
Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.


Family Caregivers' Psychosocial Well-being in the Context of the Great Recession.
The economic instability of the Great Recession contributed to a rise in multigenerational households as more individuals took on unanticipated care responsibilities for older family members while navigating financial uncertainties. Guided by the life course perspective, this study compared the psychological and social well-being of family caregivers and examined the moderating influences of financial challenges experienced during the Great Recession. Filial and sandwiched caregivers (N = 138; Mage = 52.80; SDage = 11.25) from the Refresher Cohort of the Midlife in the United States (MIDUS) survey provided information on demographics, caregiving, financial challenges, and well-being. Findings from regression analyses showed that sandwiched caregivers exhibited lower environmental mastery and positive relations with others than filial caregivers (p = .07). Moderation analyses showed that sandwiched caregivers with fewer than average financial challenges exhibited lower social actualization than the other family caregivers (p = .01). Study findings underscore the need to support family caregivers' psychosocial well-being as they navigate caregiving responsibilities and financial disruptions.


Type B Aortic Dissections: Current Guidelines for Treatment.
Stanford type B aortic dissections (TBADs) involve the descending aorta and can present with complications, including malperfusion syndrome or aortic rupture, which are associated with significant morbidity and mortality if left untreated. Clinical diagnosis is straightforward, typically confirmed using CT angiography. Treatment begins with immediate anti-impulse medical therapy. Acute TBAD with complications should be repaired with emergent thoracic endovascular aortic repair (TEVAR). Uncomplicated TBAD with high-risk features should undergo TEVAR in the subacute phase. Open surgical repair is seldom required and reserved only for select cases. It is critical to follow these patients clinically and radiographically in the outpatient setting.


[Textual research on Дх.09319, a fragment of Dunhuang literature preserved in Russia].
Дх.09319, a fragment collected in the page 150 of Volume 14 of Dunhuang Literature Preserved in Russia, is damaged around the page, and only 6 lines of the text are remained. It is one of versions of San bu jiu hou lun (Treatise on Three Positions and Nine Indicators) in Su wen (Plain Questions), and different from another version of Dunhuang, Дх.00613+ P.3287. The two versions cannot be spliced together, but the former can supplement the texts of the latter. In addition, Дх.09319 is also significant to the collation of the missing popular version of San bu jiu hou lun of later generation.


Technetium-99m-ECD brain SPECT in cerebral palsy: comparison with MRI.
Hypoxic brain injury is one of the major causes of cerebral palsy. Therefore, this study was performed to evaluate cerebral perfusion impairments in these patients using 99mTc-ECD brain SPECT. Fifty-one patients (31 boys, 20 girls; age range 6 mo to 6 yr, 11 mo) with clinical manifestations of cerebral palsy underwent brain SPECT after intravenous injection of 99mTc-ECD. The clinical subtypes of cerebral palsy were spastic diplegia (n = 35), spastic quadriplegia (n = 11), spastic hemiparesis (n = 2), choreoathetoid (n = 2) and mixed (n = 1). Transaxial, coronal and sagittal images obtained with a brain-dedicated annular crystal gamma camera were qualitatively analyzed and compared with the findings of magnetic resonance imaging (MRI). In SPECT, thalamic hypoperfusion was seen in all patients except one (98%), followed by hypoperfusion in the temporal lobe (52.9%, n = 27), basal ganglia (41.2%, n = 21), cerebellum (39.2%, n = 20) and extratemporal cortices (21.6%, n = 11). However, MR imaging demonstrated thalamic abnormality in seven (13.7%), basal ganglia in two (3.9%), extratemporal cortical defect in five (9.8%) and cerebellar atrophy in one (1.9%). Instead, white matter changes such as periventricular leukomalacia or ischemia (56.9%, n = 25) and thinning of corpus callosum (49%, n = 25) were the major findings. Brain SPECT is useful in the diagnosis of cerebral palsy and is more sensitive in the detection of cortical, subcortical nuclei and cerebellar abnormalities. MRI is superior in the detection of white matter changes.


Fluorescence studies on the interaction between yeast seryl-tRNA synthetase and its substrates.
Substrate-induced variations in the native fluorescence of seryl-tRNA synthetase from yeast have been used to evaluate the binding equilibria with its ligands. Binding of L-serine to the enzyme can be detected by equilibrium dialysis but not by fluorescence quenching. Hence, in contrast to ATP and tRNA(Ser), L-serine does not induce any fluorescence-sensitive conformational change of the synthetase. A comparison of the binding constants for ATP (2 X10(4) M-1) and seryl adenylate (1 x10(6) M-1) indicates that the activation reaction is mainly driven by the higher affinity of seryl adenylate to the enzyme. tRNA(Ser) and seryl-tRNA(Ser) though causing rather different maximal fluorescence quenching are bound to the enzyme with similar stoichiometry and association constant. The implications of this result are discussed with respect to the mechanism of the aminoacylation reaction. It is also shown that the enzyme clearly is capable of discriminating L-serine from other amino acids, ATP from other nucleotidetriphosphates and AMP, and tRNA(SER) from other tRNA species in the binding processes. The spectral properties, the effects of outside quenchers and the fluorescence decay times of the free enzyme and the enzyme-substrate complexes are discussed with respect to the intercalation hypothesis of Hélène.


The acute effects of alcohol on auditory thresholds.
There is very little knowledge about alcohol-induced hearing loss. Alcohol consumption and tolerance to loud noise is a well observed phenomenon as seen in the Western world where parties get noisier by the hour as the evening matures. This leads to increase in the referrals to the "hearing aid clinic" and the diagnosis of "cocktail party deafness" which may not necessarily be only due to presbyacusis or noise-induced hearing loss. 30 healthy volunteers were recruited for this trial which took place in a controlled acoustic environment. Each of the individuals was required to consume a pre-set amount of alcohol and the hearing was tested (using full pure tone audiogram) pre- and post- alcohol consumption over a broad range of 6 frequencies. Volunteers who achieve a minimum breath alcohol threshold level of 30 u/l had to have second audiogram testing. All the volunteers underwent timed psychometric and visuo-spatial skills tests to detect the effect of alcohol on the decision-making and psychomotor co-ordination. Our results showed that there was a positive association between increasing breath alcohol concentration and the magnitude of the increase in hearing threshold for most hearing frequencies. This was calculated by using the Pearson Regression Coefficient Ratio which was up to 0.6 for hearing at 1000 Hz. Over 90% of subjects had raised auditory thresholds in three or more frequencies; this was more marked in the lower frequencies. Alcohol specifically blunts lower frequencies affecting the mostly 1000 Hz, which is the most crucial frequency for speech discrimination. In conclusion alcohol does appear to affect auditory thresholds with some frequencies being more affected than others.


Role of microbial and chemical composition in toxicological properties of indoor and outdoor air particulate matter.
Ambient air particulate matter (PM) is increasingly considered to be a causal factor evoking severe adverse health effects. People spend the majority of their time indoors, which should be taken into account especially in future risk assessments, when the role of outdoor air particles transported into indoor air is considered. Therefore, there is an urgent need for characterization of possible sources seasonally for harmful health outcomes both indoors and outdoors. In this study, we collected size-segregated (PM(10-2.5), PM(2.5-0.2)) particulate samples with a high volume cascade impactor (HVCI) simultaneously both indoors and outdoors of a new single family detached house at four different seasons. The chemical composition of the samples was analyzed as was the presence of microbes. Mouse macrophages were exposed to PM samples for 24 hours. Thereafter, the levels of the proinflammatory cytokines, NO-production, cytotoxicity and changes in the cell cycle were investigated. The putative sources of the most toxic groups of constituents were resolved by using the principal component analysis (PCA) and pairwise dependencies of the variables were detected with Spearman correlation. Source-related toxicological responses clearly varied according to season. The role of outdoor sources in indoor air quality was significant only in the warm seasons and the significance of outdoor microbes was also larger in the indoor air. During wintertime, the role of indoor sources of the particles was more significant, as was also the case for microbes. With respect to the outdoor sources, soil-derived particles during a road dust episode and local wood combustion in wintertime were the most important factors inducing toxicological responses. Even though there were clear seasonal differences in the abilities of indoor and outdoor air to induce inflammatory and cytotoxic responses, there were relatively small differences in the chemical composition of the particles responsible of those effects. Outdoor sources have only a limited effect on indoor air quality in a newly built house with a modern ventilation system at least in a low air pollution environment. The most important sources for adverse health related toxicological effects were related to soil-derived constituents, local combustion emissions and microbes.


Retraction of muscle afferents from the rat ventral horn during development.
The postnatal reorganization of rat proprioreceptive muscle afferent spinal terminal fields was explored by labelling transganglionically afferents from extensor digitorum communis with cholera toxin B sub-unit at different ages. Immunocytochemistry revealed labelled afferents in all segments examined (C4-T2) as well as retrogradely labelled motoneurones (C5-T1). Dorsal horn innervation appeared similar at all ages, but there were striking changes in the ventral horn. Many afferent boutons were seen closely apposed to labelled motoneurone proximal dendrites at postnatal day 7 (P7) and P14, but in the adult such contacts were almost entirely confined to distal dendrites. Between P7 and adult, a significant decrease in bouton density was found in the area dorsomedial to the labelled motoneurones that contained labelled dendrites and antagonist motoneurones. This anatomical reorganization may explain both the increasing stretch reflex threshold and its concomitant decrease in magnitude with age, and the reduction in excitatory connections to antagonist motoneurones, previously described in developmental neurophysiological studies.


Liquid serial dilution is inferior to solid media for isolation of cultures representative of the phylum-level diversity of soil bacteria.
Representatives of only four well-characterized bacterial phyla were isolated from a pasture soil by using liquid serial dilution culture. In contrast, members of Acidobacteria, Verrucomicrobia, and Gemmatimonadetes and of other poorly represented bacterial lineages were isolated in earlier experiments with solidified versions of the same media. We conclude that, contrary to expectation, liquid serial dilution culture is inferior to culturing on solid media for isolating representatives of many bacterial phyla from soil.


In-Plane Anisotropic Rectification and Photovoltaic Effects on ZnO Nonpolar (101̅0) Crystal Plane and the Physical Mechanism.
The concept of spontaneous electric field (Es) in polar structures is crucial for understanding the physical and chemical properties of compound semiconductors and improving their performanes. However, this concept has not been widely accepted so far. Here, we show the first observation of rectification and photovoltaic effects in the polar [0001] direction on the nonpolar ZnO (1010) crystal plane. However, no rectification and photovoltaic effects are observed in the nonpolar [1210] direction perpendicular to the [0001]. When a stress was applied in the [0001] direction of the ZnO single crystal, the rectification and photovoltaic effects are abated and disappeared. The disappearance of the two effects results from the pressure-induced disappearance of the polar structure. The results fully demonstrated that the rectification and photovoltaic effects arise from the existence of Es in the polar [0001] direction. The Es motivates the directional transfer of the electrons and photocreated charges along the [0001] direction, and the rectification and photovoltaic effects are thus observed. These results provide direct evidence for the polar structure theory and suggest that the polar structures can be employed to develop new types of photovoltaic and other electronic and photoelectronic devices.


Dual inhibition of ErbB1 and ErbB2 in cancer by recombinant human prolidase mutant hPEPD-G278D.
ErbB1 and ErbB2 are oncogenic cell surface receptor tyrosine kinases, linked to many forms of human cancer, and are major cancer therapeutic targets. Many lines of evidence indicate that targeting ErbB1 and ErbB2 is an important cancer therapeutic approach. We recently found that a recombinant enzymatically-inactive mutant of human prolidase, i.e., hPEPD-G278D, is an inhibitory ligand of ErbB2 and strongly inhibits ErbB2-overexpressing cells in vitro and in vivo. hPEPD-G278D also binds to ErbB1. Here, we show that hPEPD-G278D binds to ErbB1 with high affinity, initially activating ErbB1 but later silencing it, and that deletion of subdomain 2 in ErbB1 extracellular domain abolishes the binding. The proliferation of ErbB1-overexpressing cells is strongly inhibited by hPEPD-G278D, regardless of ErbB2 expression or cell type, whereas cells lacking ErbB1 and ErbB2 are insensitive to it. In contrast, EGF, another ErbB1 ligand, either stimulates or mildly inhibits cell proliferation. Moreover, hPEPD-G278D treatment of mice bearing ErbB1-overexpressing tumors leads to tumor regression, which is accompanied by down regulation and decreased phosphorylation of ErbB1 and ErbB2 as well as decreased phosphorylation of downstream signaling molecules and activation of apoptosis in the tumor tissues. We conclude that hPEPD-G278D is a dual inhibitor of ErbB1 and ErbB2 and selectively targets cancer cells overexpressing ErbB1 and/or ErbB2. Moreover, our finding that both receptors are silenced in cancer cells by hPEPD-G278D highlights an unusual consequence of ligand-receptor interaction.


Treatment considerations for clinicians in applying evidence-based practice to complex presentations in child trauma.
Professionals in the child trauma field, eager to bring best practices to children and their families who have suffered from traumatic life events, have developed a number of evidence-based treatments (EBTs) and promising practices available for adoption and implementation into community practice. Clinicians and researchers alike have raised questions about "if, when, and how" these EBTs can be applied to some of the more complex trauma presentations seen in real world practice. The authors take an evidence-based practice approach, including critical appraisal of clients' unique needs and preferences, utilizing applicable trauma treatment core components and current EBTs, and emphasizing monitoring strategies of client progress, particularly when needing to adapt EBTs for select clients.


Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are significantly raised in blood lipids by the intake of four walnuts a day in humans.
Ingestion of alpha linolenic acid (ALA), with the richest source among dry fruits such as walnuts, is associated with cardiovascular prevention. The aim of this study was to selectively evaluate the effects of moderate walnut consumption on the levels of ALA and its metabolic derivatives in human blood. After a 2-week run-in period, 10 volunteers consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks. Fatty acid profiles, with special attention to levels of ALA and long chain polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected from fingertips. The data indicate that the administration of a few walnuts a day for 3 weeks significantly increases blood levels, not only of ALA (from 0.23+/-0.07 SD to 0.47+/-0.13 SD), but also of its longer chain derivative eicosapentaenoic acids (EPA) (from 0.23+/-0.37 to 0.82+/-0.41) with levels remaining elevated over basal values after washout. The findings of this pilot study indicate that plant ALA in appropriate food items favourably affects the n-3 LC-PUFA status.


[Spontaneous cerebral calcium embolism].
Calcium embolism is an uncommon cause of stroke which may not be diagnosed in cases which do not involve cardiac surgery or catheterization. The emboli may come from cardiac valves or calcified atheroma of the aortic or carotid arteries. Two patients with cerebral infarcts secondary to spontaneous calcium embolism confirmed by neuro imaging. In both cases on CT scans there were dense points corresponding to calcified material within the middle cerebral artery or one of its branches. In the first case migration of the calcified point following the course of the artery was observed. Cranial CAT scans are essential for diagnosis of calcium embolism. Migration of the calcified point confirms the diagnosis. It is still not clear whether valve replacement is necessary in these patients and treatment with antiaggregants and/or anticoagulants is controversial.


Eight cases of lower respiratory tract infection caused by Stomatococcus mucilaginosus.
Stomatococcus mucilaginosus was isolated from 8 patients suffering from lower respiratory tract infections over a 4-y period (1999-2003). The infections ranged from mild cases of pneumonia to a life-threatening case of recurrent lung abscesses in a neutropenic patient. The various strains were cultured from specimens obtained by bronchoscopy, blood, and sputum specimens. All strains were fully susceptible to rifampicin, vancomycin and gentamicin. They showed variable susceptibility to penicillin and ciprofloxacin. S. mucilaginosus is likely to be under-reported as a pathogen due to difficulties in obtaining samples for culture as well as misidentification due to its biochemical characteristics.


A functional viewpoint on paradoxical sleep-related brain regions.
Slow wave sleep is a condition for paradoxical sleep (PS) expression. The lower brain stem is able to produce the known PS phenomena but, in order to do so in all its functional magnitude, it depends on the rest of the brain. There are physiological conditions that appear as necessary to develop the PS. A group of basic functions, i.e., respiration, cardiovascular, brain oxygen availability, temperature, etc., have to go on in a non-homeostatic fashion during this state. Other conditions to be met are: the cut-off of the motor output and a different central control of the sensory input. During PS, phasic pO2 changes were observed in some nuclear structures characterized by a dramatic increase in the amplitude of oscillations. These changes were found in a number of subcortical, cerebellar and brain stem regions and were never observed neither in the neocortex, the specific thalamic nuclei nor in the white matter. It is postulated that these variations are due to a local increase in neuronal activity in PS during a decrease of the local homeostatic oxygen control. All the physiological changes above mentioned have a common anatomical denominator: the pons and medulla. Upon this region, proposed as the PS FINAL COMMON REGION, conveges rostral and caudal information making it the executor of all PS phenomena. The pons, on the other hand, has a bioelectrical activity of its own during PS, i.e., the ponto-geniculo-occipital spikes (PGO). This activity spreads through the brain and cerebellum. The cerebellum also participates in sleep physiology: the pO2 oscillations pattern and PGO are present in all of its parts, cortex and nuclei, being, the spike activity, dependent of a cholinergic pontine region. The pons shows a particular duality during PS. It is part of the FINAL COMMON REGION for PS phenomena and, at the same time, it is the origin of the PGO activity.


Unified Protocol for Cobalt-Catalyzed Oxidative Assembly of Two Aryl Metal Reagents Using Oxygen as an Oxidant.
The first cobalt-catalyzed oxidative cross-coupling reaction of two aryl metal reagents is described. An equivalent amount of two aryl Grignard or lithium reagents, after mediation by an equivalent amount of simple ClTi(OEt)3, was facilely assembled under the catalysis of 1 mol % of CoCl2/10 mol % of DMPU using oxygen. The cross-couplings between various aryl metal reagents, especially between two structurally similar aryl Grignard reagents, proceeded smoothly and selectively and, thus, provided a highly general and efficient method for the construction of biaryl compounds.


Phase-sensitive method for background-compensated photoacoustic detection of NO2 using high-power LEDs.
A photoacoustic (PA) sensor has been developed for the detection of nitrogen dioxide (NO(2)). Ten amplitude-modulated high-power light emitting diodes (LEDs), emitting a total optical power of 9 W at 453 nm, are used to excite the photoacoustic signal in NO(2). The LEDs are attached to the circumference of a cylindrical PA cell. The induced longitudinal acoustics waves are detected using two electromechanical film stacks, located at the ends of the cell. Background signal cancelation is achieved by using phase-sensitive detection of the difference signal of the two pressure transducers. The phase-sensitive approach allows for improved dynamic range and sensitivity. A detection limit of 10 parts per billion by volume was achieved for flowing NO(2) gas sample in an acquisition time of 2.1 s, corresponding to a minimum detectable absorption coefficient of 1.6 × 10(-7) cm(-1) Hz(-1/2). The developed sensor has potential for compact, light-weight, and low-cost measurement of NO(2).


The natural history of bacterial colonization of the newborn in a maternity hospital (Part II).
The object of this study was to determine the sources from which the newborn infant derives his bacterial flora during the first 5 days after birth. Detailed bacteriological data was obtained from 193 mothers antenatally and during labour, and from their infants on the day of birth and on Day 5. Organisms were typed by appropriate methods and the 193 mother-baby pairs declared to be a 'match' or a 'non-match' according as to whether or not identical bacteria were isolated from both members of the pair. Weekly swabs from hands and noses of staff were taken throughout the 12 months of the study. Swabs were also taken from the environment and air samples from different areas in the hospital. In approximately one third of infants the colonizing bacteria are derived from their mothers, in over 70 per cent of instances from the mother's rectum. The mother's birth canal is not a common source of bacteria and there is no direct relationship with the noses or hands of staff. Artificial feeds are not a source of the colonizing bacteria. The overall distribution of the bacterial species in the infants differed from that found in the hospital environment but this does, none the less, constitute a reservoir of bacteria which is being continually replenished from human sources. Pathogens such as Staph, aureus and Strep. pyogenes are no longer commonly found in newborn infants in the modern maternity hospital, but the need for continual vigilance and an efficient bacteriological service in all maternity units has been in no way diminished.


Jackson-Pratt drainage in pediatric craniofacial reconstructive surgery: is it helping or hurting?
OBJECTIVE Jackson-Pratt drains (JPDs) are commonly employed in pediatric craniofacial reconstructive surgery (CRFS) to reduce postoperative wound complications, but their risk profile remains unknown. Perioperative blood loss and volume shifts are major risks of CFRS. The goal of this study was to evaluate the risks of JPD usage in CFRS, particularly with regard to perioperative blood loss, hyponatremia, intensive care unit (ICU) length of stay, and postoperative wound complications. METHODS The authors performed a retrospective review of data obtained in pediatric patients who underwent CFRS at a single institution, as performed by multiple surgeons between January 2010 and December 2014. Data were gathered from patients who did and did not receive JPDs at the time of surgery. Outcome measures were compared between the JPD and no-JPD groups. RESULTS The overall population 179 pediatric patients: 128 who received JPDs and 51 who did not. In their analysis, the authors found no significant differences in baseline patient characteristics between the two groups. The average JPD output over the first 48 hours was 222 ± 142 ml. When examining the immediate preoperative to immediate postoperative time period, no significant differences were noted between the groups with regard to the need for blood transfusion or changes in hemoglobin, hematocrit, or serum sodium levels. These differences were also not significant when examining the 48-hour postoperative period. Finally, no significant differences in hospital length of stay, ICU length of stay, or emergency department visits at 60 days were noted between the two groups. CONCLUSIONS In this retrospective study, the use of JPDs in pediatric CFRS was not associated with an increased risk of serious perioperative complications, although the benefits of this practice remain unclear.


Ciliated and microvillous structures of rat olfactory and nasal respiratory epithelia. A study using ultra-rapid cryo-fixation followed by freeze-substitution or freeze-etching.
The olfactory epithelium of the Sprague-Dawley rat showed structures which indicate that freeze-substitution after ultra-rapid cryo-fixation is a better method for its preservation than conventional fixation techniques. A new feature is that matrices of the distal parts of olfactory cilia range in their staining intensity from very dense to electron-lucent. Outlines of structures are smooth and membrane features can be clearly seen. The textures of mucus from olfactory and respiratory epithelia are distinctly different after freeze-fracturing and deep-etching following cryo-fixation. Olfactory cilia show no microtubule-attached axonemal structures. Cross-sectional diameters are smaller after freeze-substitution than after freeze-fracturing. Intramembranous particle densities are lower in nine regions of three cell types in cryo-fixed olfactory and respiratory epithelia than in those chemically fixed and cryoprotected. The fracture faces of membranes from etched, cryo-fixed cells have holes, a result which probably accounts for differences in particle density between cryo-fixed and chemically-fixed, cryo-protected cells. Particle diameters are usually the same using both methods. Densities of intramembranous particles and particles plus holes are highest in supporting cell processes, followed by endings and cilia of olfactory receptor cells, and are lowest in respiratory cilia. Particle densities at outer and inner surfaces are higher than those in either fracture face. Outer surfaces show a good correlation from region to region with densities summated over both fracture faces.


Synthesis and characterization of fast-swelling porous superabsorbent hydrogel based on starch as a hemostatic agent.
The body can't control massive bleeding without treatment. Different hemostatic agents have been prepared recently, but most of them are ineffective in severe bleeding and expensive or cause safety concerns. In this study, in order to achieve fast control of bleeding, we synthesized and characterized fast-swelling porous superabsorbent hydrogel (FSPSH) and investigated its use as a hemostatic agent. The FSPSH was prepared by grafting acrylic acid and acrylamide onto starch through free-radical polymerization in aqueous solution. The FSPSH was characterized by Fourier transform infrared, X-ray diffraction, field emission scanning electron microscope, and thermogravimetric analysis. Then, temporal swelling behavior and coagulation time experiments were used to predict the in vivo behavior of the FSPSH. The hemocompatibility of synthesized FSPSH was evaluated by hemolysis test and blood cells function. In vivo study using femoral artery injury in rat demonstrated the FSPSH's ability to aid in rapid hemostasis. Furthermore, monitoring the rat on first and seventh day after femoral artery injury also showed no harmful effect. This study indicates that FSPSH adsorbs fluid and swells, thus forms a physical barrier to blood loss. FSPSH, moreover, as hemostat is simple to use, lightweight, stable, and harmless.


Backwards Medicine: Female Atavism, Whiteness, and the Medical Profession in "The Pineal Eye".
This article examines atavism as a theory of racial science in the nineteenth-century United States that illuminates how the developing medical profession reinforced racial, class, and gender hierarchies to gain cultural authority. I use John S. Partridge's "The Pineal Eye," a little-known short story published in San Francisco's The Wave in 1894, as a case study that reveals how atavism was conceived as pathology within the purview of medical study. Partridge intertwines established atavistic discourse that asserted the Anglo-Saxon female body as paradoxically modern in terms of racial identity and primitive in terms of sex with scientific experimentation and male medical authority, resulting in evolutionary regression. Partridge portrays atavism as a lens with which to challenge medicine that relied on experimentation and scientific discovery rather than recuperative treatment. I argue that these connections between atavistic and medical discourse blur the boundaries between science and fiction during the period.


Continuous positive airway pressure treatment in sleep apnea prevents new vascular events after ischemic stroke.
A study was made of the role of continuous positive airway pressure (CPAP) treatment in the prevention of new vascular events following ischemic stroke or transient ischemic attack. Prospective study. Demographic data, vascular risk factors, clinical manifestations associated to sleep apnea-hypopnea syndrome, and neurologic parameters were recorded in a group of patients presenting with acute ischemic stroke at least 2 months previously. A polygraphic study was carried out 2 months after the acute episode in all patients, with the prescription of CPAP in the event of an apnea-hypopnea index (AHI) > or = 20. Two groups were defined: patients who could tolerate CPAP (group 1), and patients who could not tolerate CPAP after 1 month of initial adaptation (group 2). Patients with an AHI < 20 were excluded. The incidence of new vascular events was evaluated throughout follow-up (18 months) in all patients, with an analysis of the role of CPAP in protecting the patients against such events. Ninety-five patients were studied. Fifty-one patients (53.7%; mean age, 72.7 +/- 9.4 years [+/- SD]) presented with an AHI > or = 20, and 15 patients (29.4%) tolerated CPAP. The incidence of new vascular events was greater in group 2 (6.7%) vs group 1 (36.1%; long-rank, p = 0.03). Intolerance of CPAP increased the probability of a new vascular event fivefold (odds ratio, 5.09) adjusted for other vascular risk factors and neurologic indexes. We concluded that CPAP treatment during 18 months in patients with an AHI > or = 20 afforded significant protection against new vascular events after ischemic stroke.


Dietary Intervention in Infancy and Cognitive Function in Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project.
Consumption of saturated fatty acids (SAFAs), polyunsaturated fatty acids (PUFAs), cholesterol, and fiber have been linked with cognitive function in adults. We evaluated these associations from childhood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project (STRIP). STRIP recruited children aged 5 months and randomly assigned them into intervention/control groups. The intervention introduced a heart-healthy diet, characterized mainly by low consumption of SAFAs and cholesterol, through counseling at least biannually between age 7 months and 20 years. Diet was assessed repeatedly using food diaries. Six years after the end of the intervention phase, at age 26 years, the participants were invited to the first postintervention follow-up, which included cognitive testing that covered learning and memory, verbal memory, short-term working memory, reaction time, information processing, and cognitive flexibility and inhibitory control. We studied the associations of the STRIP intervention and the consumptions of SAFAs, PUFAs, cholesterol, and fiber within these cognitive domains. Participants in the STRIP intervention group had better cognitive flexibility and inhibitory control and were better able to manage conflicting information and ignore task-irrelevant information (0.18 SD higher in the intervention group, adjusted for sex and socioeconomic status). No associations were observed with the dietary components studied. The infancy-onset STRIP intervention, which promoted a heart-healthy diet, was favorably associated with cognitive flexibility and inhibitory control at age 26 years. No associations were found for the intervention targets studied, indicating that these specific dietary components did not underlie the observed effect of the intervention.


Do Acute Benefits of Interpersonal Psychotherapy for Posttraumatic Stress Disorder Endure?
The Psychotherapies for Chronic PTSD randomised trial found that three 14-week psychotherapies acutely benefitted patients with chronic posttraumatic stress disorder (PTSD). Previous research has reported sustained follow-up benefits for prolonged exposure (PE) and relaxation therapy (RT), but few comparable data exist for interpersonal psychotherapy (IPT). We describe 3-month follow-up for acute responders to all 3 treatments. Acute responders, defined a priori as ≥30% improved from baseline, were reevaluated after 3-month no-treatment follow-up by independent evaluators using the Clinician-Administered PTSD Scale (CAPS). Fifty of 110 initial study entrants met acute responder status at week 14. Forty-three (86%) responders entered follow-up: 23 remitters (CAPS ≤20) and 20 responders. At week 26, 27 had achieved remission status, 10 remained responders, and 6 had relapsed. Of week 14 remitters, 8 of 9 PE, all 8 IPT, and 4 of 6 RT patients remained remitted. Relapse rates were 7% (1/9) for PE, 10% (2/20) for IPT, and 33% (3/9) for RT. At week 26, PE showed greater improvement on CAPS than RT ( P = 0.048) and a trend for superiority over IPT ( P = 0.098), with no significant difference between IPT and RT. Depressive symptoms remained low during follow-up. These are the first systematic data on follow-up responder status and persistence of acute treatment benefits in patients receiving individual IPT for chronic PTSD. Patients generally maintained gains across treatments, fluctuating most in RT. Study limitations include small sample size and brief follow-up interval. PTSD research should employ response and remission criteria.


The Role of Social Engagement in Older Adults' Health.
The purpose of the current study was to explore the association between social engagement and the health status, cognition, and perceived well-being of older adults using data from the National Health and Aging Trends Study. Descriptive statistics, clustering, and regression modeling were performed to analyze the data. We used the regression model to identify statistically significant relationships between the representative variables and the extent to which participants participated in social activities. The most representative variable for each of the three clusters was selected and fitted to the regression model, which consists of (1) acute health problems and events, (2) cognitive and communication barriers, and (3) chronic conditions contributing to long-term health status. A regression model found that two factors-cognitive and communication barriers and chronic conditions contributing to long-term health status-were statistically significant in determining social engagement in older adults. Health care providers should consider various factors in planning and implementing social programs that can positively engage older adults. [Research in Gerontological Nursing, 15(3), 152-160.].


Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity.
In the present study, new Schiff's base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents.


Voluntary autonomous simulator based training in minimally invasive surgery, residents' compliance and reflection.
Knot tying and suturing skills in minimally invasive surgery (MIS) differ markedly from those in open surgery. Appropriate MIS training is mandatory before implementation into practice. The Advanced Suturing Course (ASC) is a structured simulator based training course that includes a 6-week autonomous training period at home on a traditional laparoscopic box trainer. Previous research did not demonstrate a significant progress in laparoscopic skills after this training period. This study aims to identify factors determining autonomous training on a laparoscopic box trainer at home. Residents (n = 97) attending 1 of 7 ASC courses between January 2009 and June 2011 were consecutively included. After 6 weeks of autonomous, training a questionnaire was completed. A random subgroup of 30 residents was requested to keep a time log. All residents received an online survey after attending the ASC. We performed outcome comparison to examine the accuracy of individual responses. Out of 97 residents, the main motives for noncompliant autonomous training included a lack of (training) time after working hours (n = 80, 83.3%), preferred practice time during working hours (n = 76, 31.6%), or another surgical interest than MIS (n = 79, 15.2%). Previously set training goals would encourage autonomous training according to 27.8% (n = 18) of residents. Thirty participants submitted a time log and reported an average 76.5-minute weekly training time. All residents confirmed that autonomous home practice on a laparoscopic box trainer is valuable. Autonomous practice should be structured and inclusive of adequate and sufficient feedback points. A minimally required practice time should be set. An obligatory assessment, including corresponding consequence should be conducted. Compliance herewith may result in increased voluntary (autonomous) simulator based (laparoscopic) training by residents.


Cytosine Iminyl Radical (cytN•) Formation via Electron-Induced Debromination of 5-Bromocytosine: A DFT and Gaussian 4 Study.
Halogen-substituted pyrimidines, such as 5-bromouracil and 5-iodouracil, have been used as radio therapeutic (RT) agents in cancer treatment. The radiosensitizing activity of 5-bromouracil is attributed to its reaction with electron which produce the highly reactive uracil-5-yl radical by dissociating the C5-Br bond. Using density functional methods and highly accurate Gaussian 4 (G4) theory, herein, we show that 5-bromocytosine (5-Brcyt) after reaction with electron, also, leads to the formation of cytosine-5-yl radical. However, our results show that this species can subsequently undergo a base-catalyzed tautomerization reaction to form the π-aminyl radical followed by a second tautomerization to the thermodynamically most stable σ-iminyl radical (cytN•). From the present theoretical calculations, we infer that the mechanism of the formation of cytN• by one-electron reduction of 5-Brcyt is straightforward and may take place in 5-Brcyt-labeled DNA in competition with the usual reactions expected for the cytosine-5-yl radical such as abstraction and water addition.


Chemical Fouling Reduction of a Submersible Steel Spectrophotometer in Estuarine Environments Using a Sacrificial Zinc Anode.
The availability of in situ spectrophotometers, such as the S::CAN spectro::lyser, has expanded the possibilities for high-frequency water quality data collection. However, biological and chemical fouling can degrade the performance of in situ spectrophotometers, especially in saline environments with rapid flow rates. A complex freshwater washing system has been previously designed to reduce chemical fouling for the S::CAN spectro::lyser spectrophotometer. In the current study, we present a simpler, cheaper alternative: the attachment of a sacrificial zinc anode. Results are presented detailing the S::CAN spectro::lyser performance with and without the addition of the sacrificial anode. Attachment of the zinc anode provided efficient corrosion protection during 2-wk deployments in a highly dynamic (average tidal range, 2.5 m) saline tidal saltmarsh creek at Groves Creek, Skidaway Institute of Oceanography, Savannah, GA.


Cloning, sequencing, and enzymatic activity of an inducible aldo-keto reductase from Chinese hamster ovary cells.
Treatment of Chinese hamster ovary (CHO) cells by the aldehyde containing calpain inhibitor I resulted in the induction of a 35-kDa protein that was partially sequenced and shown to be a member of the aldo-keto reductase superfamily (Inoue, S., Sharma, R. C., Schimke, R. T., and Simoni, R. D. (1993) J. Biol. Chem. 268, 5894-5898). Using rapid amplification of cDNA ends polymerase chain reaction, we have sequenced the cDNA for this protein (CHO reductase). This enzyme is a new member of the aldo-keto reductase superfamily and shows greatest amino acid sequence identity to mouse fibroblast growth factor-regulated protein and mouse vas deferens protein (92 and 80% sequence identity, respectively). The enzyme exhibits about 70% sequence identity with the aldose reductases (ALR2; EC 188.8.131.52) and about 47% with the aldehyde reductases (ALR1; EC 220.127.116.11). Northern analysis showed that it is induced in preference to either ALR1 or ALR2 and RNase protection assays showed gene expression in bladder, testis, jejunum, and ovary in descending order of expression. The cDNA for this inducible reductase was cloned into the pET16b vector and expressed in BL21(DE3) cells. Expressed CHO reductase showed kinetic properties distinct from either ALR1 or ALR2 including the ability to metabolize ketones. This protein joins a growing number of inducible aldo-keto reductases that may play a role in cellular regulation and protection.


[The effect of corticotherapy on respiratory muscles].
Skeletal muscle myopathy is one of the main side-effects of systemically administered corticosteroids, and involves respiratory as well as peripheral muscles. After prolonged treatment with moderate doses of either fluorinated or non-fluorinated corticosteroids, chronic myopathy may occur. In patients, such myopathy is characterized by the gradual onset of proximal limb muscle weakness and a sudden increase in creatine excretion in 24h urine. This myopathy is associated with a generalized fiber atrophy of the quadriceps in which myopathic changes are present. Since these changes were also observed in animal models, it was concluded that steroid treatment was responsible for them. After cessation of treatment, recovery of muscle force occurs but may be protracted. The severity of corticosteroid-induced myopathy appears to depend upon the type of steroid used, the treatment duration, the dose and the treatment regimen where repetitive burst treatment effects are worse than those obtained with continuous treatment with the same dose. During short-term treatment with massive doses of corticosteroids as frequently used to treat status asthmaticus, acute myopathy may develop and is characterized by generalized fiber necrosis and rhabdomyolysis. Because such necrosis was not observed in animal studies, it was suggested that the necrosis may result from the combined effect of corticosteroids with other agents such as aminoglycoside antibiotics and/or muscle relaxants.


Thrombocytosis in Whipple's disease.
Three men with Whipple's disease had platelet counts of 729,000-1,142,000 per mm3, which fell to normal as their illness responded to antibiotic therapy. Reports on Whipple's disease and hospital charts from the largest published series reveal thrombocytosis in 11 of the 24 patients whose counts were recorded. The prevalence of anemia, marrow infiltration, and classic manifestations of Whipple's disease did not differ between patients with and without thrombocytosis. The thrombocytosis of Whipple's disease is similar to that of celiac sprue, Crohn's disease, and ulcerative colitis.