Determinants of workers' well-being during the COVID-19 outbreak: An exploratory study.
Inspired by the Conservation of Resource theory (Hobfoll, 1989), this study investigated the role of a broad set of personal vulnerabilities, social, and work-related stressors and resources as predictors of workers' well-being during the COVID-19 outbreak. Participants were 594 workers in Italy. Results showed that personality predispostions, such as positivity, neuroticism and conscientiousness as well as key aspects of the individuals' relationship with their work (such as job insecurity, type of employment contract or trust in the organization) emerged as factors promoting (or hampering) workers' adjustment during the COVID -19 outbreak. Interactions between stressors and resources were also found and discussed. The online version contains supplementary material available at 10.1007/s12144-021-02408-w.


Expansion of the ω-oxidation system AlkBGTL of Pseudomonas putida GPo1 with AlkJ and AlkH results in exclusive mono-esterified dicarboxylic acid production in E. coli.
The AlkBGTL proteins coded on the alk operon from Pseudomonas putida GPo1 can selectively ω-oxidize ethyl esters of C6 to C10 fatty acids in whole-cell conversions with Escherichia coli. The major product in these conversions is the ω-alcohol. However, AlkB also has the capacity to overoxidize the substrate to the ω-aldehyde and ω-acid. In this study, we show that alcohol dehydrogenase AlkJ and aldehyde dehydrogenase AlkH are able to oxidize ω-alcohols and ω-aldehydes of esterified fatty acids respectively. Resting E. coli expressing AlkBGTHJL enabled exclusive mono-ethyl azelate production from ethyl nonanoate, with an initial specific activity of 61 U gcdw-1 . Within 2 h, this strain produced 3.53 mM mono-ethyl azelate, with a yield of 0.68 mol mol-1 . This strain also produced mono-ethyl dicarboxylic acids from ethyl esters of C6 to C10 fatty acids and mono-methyl azelate from methyl nonanoate. Adding ethyl nonanoate dissolved in carrier solvent bis-(2-ethylhexyl) phthalate enabled an increase in product titres to 15.55 mM in two-liquid phase conversions. These findings indicate that E. coli expressing AlkBGTHJL is an effective producer of mono-esterified dicarboxylic acids from fatty acid esters.


Reliable gastric tonometry after coronary artery surgery: need for acid secretion suppression despite transient failure of acid secretion.
To study the need for suppression of gastric acid secretion for reliable intragastric partial pressure of carbon dioxide (PCO2) tonometry by evaluating the effect of an oral dose of sodium bicarbonate before and after administration of the H2-blocker ranitidine to mimic CO2 generation following the buffering of acid by bicarbonate in patients after cardiac surgery. Prospective, open, non-randomized clinical study. Cardiothoracic intensive care unit at a university hospital. 10 patients after elective coronary artery bypass surgery. An oral dose of 500 mg sodium bicarbonate before and after acid secretion suppression by 100 mg ranitidine as an intravenous bolus given at approximately 3 h after surgery (day 0) and on the first postoperative day (day 1). Intragastric PCO2 (iPCO2; tonometry), gastric juice pH (aspirate) and arterial blood gas values were measured. On day 0, the iPCO2 was 25 +/- 5 mmHg before and 31 +/- 5 mmHg after the bicarbonate dose, 29 +/- 5 mmHg after ranitidine infusion, and 31 +/- 5 mmHg after the bicarbonate dose following the ranitidine infusion (NS). On day 1, the basal iPCO2 was 32 +/- 4 mmHg and it increased to 56 +/- 25 mmHg following bicarbonate (p < 0.01). After ranitidine, the iPCO2 was 33 +/- 4 mmHg before and 40 +/- 14 mmHg after bicarbonate (NS). Basal gastric juice pH was > 4 in nine of ten patients on day 0 and > 4 in seven of ten patients on day 1. Pharmacological suppression of gastric acid secretion is mandatory for reliable iPCO2 tonometry after cardiopulmonary bypass surgery, even when gastric acid secretion is transiently inhibited. In fact, gastric acid secretion was inhibited immediately after surgery, but returned on the first postoperative day in most patients, as judged from the bicarbonate back titration of gastric acid, even when gastric juice pH was relatively high.


Identification of a unique splicing regulatory cluster in hepatitis B virus pregenomic RNA.
HBV particles with genome derived from spliced mRNAs accumulate in patients with virus-derived severe liver necrosis and fibrosis. We investigated the role of an intronic element (intronic splicing silencer-long, ISS(L)) on splicing of HBV minigene transcripts. Removal of the entire ISS(L) showed two-fold increase in splicing while shorter deletions within ISS(L) indicated isolated clusters of activator and repressor domains. Activator domains stimulated splicing in presence of PRE, a long HBV 3' exon and even when present in a heterologous context. Mutations in the repressor domain unexpectedly augmented repression. The role of this intronic splicing regulatory element could be important for HBV pathogenesis.


Effect of intrathecal amino acid receptor antagonists on basal blood pressure and pressor responses to brainstem stimulation in normotensive and hypertensive rats.
The importance of spinal cord amino acid receptors in the regulation of blood pressure was investigated in normotensive (Wistar Kyoto, WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive (SPR) rats. Also investigated was the possible role of these spinal cord receptors in mediating pressor changes evoked by electrical stimulation of two separate areas of the rostral ventrolateral medulla (RVLM) containing different neuronal populations, either the adrenaline-containing C1 area or the serotonin-containing B3 area. Intrathecal administration of the amino acid receptor antagonist kynurenate (KYN), or the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2APV), reduced basal blood pressure in anesthetized SHR and SPR in a dose-dependent manner, but were ineffective or elicited only small decreases in WKY. In all three strains, electrical stimulation in RVLM, in either the C1 or B3 area, evoked frequency-dependent pressor responses. Administration of 2APV or KYN was effective in attenuating these pressor responses in all three strains of rats. The effects of stimulation in the RVLM-B3 area were virtually abolished by administration of 2APV followed by the serotonin receptor antagonist methysergide. The results suggest that spinal cord excitatory amino acid receptors are important in blood pressure regulation in rats. Amino acid receptors, perhaps of the NMDA subtype, appeared to mediate pressor responses to stimulation of the RVLM-C1 and RVLM-B3 regions in both normotensive and hypertensive animals. On the other hand, excitatory amino acid receptor antagonists reduced basal blood pressure only in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)


A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation.
Tumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments.


Depletion and Maturation of Myeloid-Derived Suppressor Cells in Murine Cancer Models.
Myeloid-derived suppressor cells (MDSC) are known to inhibit functions of T and NK cells. MDSC have been shown to be generated and to accumulate under chronic inflammatory conditions that are typical for cancer. Therefore, it would be highly beneficial to find ways to diminish the number and immunosuppressive functions of these cells in tumor-bearing hosts. Here we describe current protocols to deplete MDSC or induce their maturation in preclinical tumor models that could lead to the attenuation of their immunosuppressive functions.


Searching for a definition for pharmacologically refractory constipation: A systematic review.
Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients. A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed. Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies. There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.


[Effect of cocarboxylase on hyperlactatemia and hyperpyruvicemia induced by phenformin in dogs].
In the normal anesthetized dog, a cocarboxylase perfusion considerably reduced the increase in blood lactate and pyruvate levels provoked by the intraduodenal injection of phenformin (30 mg/kg); furthermore it seems to counteract the increase of the lactates/pyruvates ratio and opposes the fall in blood pH.


Down-regulation of cell surface CXCR6 expression during T cell activation is predominantly mediated by calcineurin.
CXCR6, the receptor for the membrane-anchored chemokine, CXCL16, is expressed on a subset of CCR5-bearing memory T cells, and may play a role in recruiting these cells to sites of inflammation. Here, we set out to determine the effect of T cell activation on CXCR6 expression. Highly purified human peripheral blood T cells were cultured for 7-8 days in presence of IL-2 (400 U/ml) to enhance CXCR6 expression. Overnight stimulation with anti-CD3 mAb+anti-CD28 mAb, which resulted in CD69 induction and cytokine (IL-2 and IFN-gamma) production, reduced cell surface expression of CXCR6 by 85% and that of CCR5 by 76%. The Ca(2+) ionophore, ionomycin (125-500 ng/ml), also markedly diminished CXCR6 expression (85%), but without inducing CD69 expression or cytokine production, and reduced CCR5 expression by only 40%. In contrast, the phorbol esters, PdBu or PMA had little effect on CXCR6 expression (23% reduction) but induced CD69 expression and caused a profound down-regulation (92%) of CCR5 expression. Moreover, CCR7, whose expression was low on CXCR6(+) T cells, was little affected by any of these modes of activation. The down-regulation of CXCR6 expression induced by CD3/CD28 activation was blocked by the broad kinase inhibitor, staurosporine, and by the src kinase inhibitor, PP2, but not by the MEK1 inhibitor, U0106. Most interestingly, the calcineurin inhibitor, FK506, consistently inhibited CD3/CD28-induced CXCR6 down-regulation. FK506 also blocked the decrease of CXCR6 expression caused by ionomycin, whereas staurosporine or PP2 had no effect on this decrease. Altogether, these data indicate that CXCR6 expression is down-regulated, independent of CCR5 or CD69 expression and of cytokine induction, by T cell activation signals that involve predominantly the Ca(2+)-dependent calcineurin pathway.


Performance of two Picea abies (L.) Karst. stands at different stages of decline : VI. Nutrient concentration.
A declining Picea abies (L.) Karst. stand produced as much foliage and branches as a healthy stand but less stemwood at a similar leaf area index and climate. Nutrient analyses revealed that most biomass components at the declining site had lower concentrations of calcium and magnesium, but similar nitrogen and potassium (except for lower potassium in younger needles) and higher phosphorus, manganese and aluminum than the respective components at the healthy site. Comparison of these data with the results from studies on the nutrition and growth of P. abies seedlings (Ingestad 1959) led to the conclusion that the healthy stand is in a balanced nutritional state, while trees at the declining stand have only 56% of the foliar magnesium concentration required to permit growth at a rate which could be achieved at their nitrogen status. It appears that acidic deposition, which involves an input of nitrogen and a leaching of cations from the soil, causes an imbalance in the availability of nitrogen and magnesium. Growth is eventually reduced as magnesium becomes limiting.


Novel insights on perils and promises of miRNA in understanding colon cancer metastasis and progression.
Colorectal cancer (CRC) is the third highest frequent malignancy and ultimate critical source of cancer-associated mortality around the world. Regardless of latest advances in molecular and surgical targeted medicines that have increased remedial effects in CRC patients, the 5-year mortality rate for CRC patients remains dismally low. Evidence suggests that microRNAs (miRNAs) execute an essential part in the development and spread of CRC. The miRNAs are a type of short non-coding RNA that exhibited to control the appearance of tumor suppressor genes and oncogenes. miRNA expression profiling is already being utilized in clinical practice as analytical and prognostic biomarkers to evaluate cancer patients' tumor genesis, advancement, and counteraction to drugs. By modulating their target genes, dysregulated miRNAs are linked to malignant characteristics (e.g., improved proliferative and invasive capabilities, cell cycle aberration, evasion of apoptosis, and promotion of angiogenesis). This review presents an updated summary of circulatory miRNAs, tumor-suppressive and oncogenic miRNAs, and the potential reasons for dysregulated miRNAs in CRC. Further we will explore the critical role of miRNAs in CRC drug resistance.


Flat-panel detector volumetric CT for visualization of subarachnoid hemorrhage and ventricles: preliminary results compared to conventional CT.
The aim of this study was to compare flat-panel volumetric CT (VCT) to conventional CT (cCT) in the visualization of the extent of subarachnoid hemorrhage (SAH) and the width of the ventricles in patients with acute SAH. Included in the study were 22 patients with an acutely ruptured cerebral aneurysm who received VCT during coil embolization. VCT image quality, the extent of SAH (using a modified Fisher score and total slice number with SAH visible) and the width of the ventricles (Evans index) were evaluated by two experienced neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten patients undergoing VCT for reasons other than SAH served as negative controls. Interobserver agreement in rating image quality was excellent for cCT (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and RAD2 on VCT images in all patients. The modified Fisher scores underestimated the extent of SAH on VCT images in comparison with cCT images. Pearson's correlation coefficient (r) regarding the number of image slices with SAH visible on cCT images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for RAD2. The r value for the degree of interobserver agreement for the number of slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n=19), respectively. The width of the ventricles measured in terms of the Evans Index showed excellent concordance between the modalities (r=0.81 vs. 0.82). Our preliminary results indicate that VCT is helpful in evaluating SAH in the angiography suite. Additionally, reliable evaluation of ventricle width is feasible. However, there are limitations with regard to the visibility of SAH on VCT images in comparison to cCT images.


αCaMKII autophosphorylation controls exploratory activity to threatening novel stimuli.
Autophosphorylation of αCaMKII is regarded as a 'molecular memory' for Ca(2+) transients and a crucial mechanism in aversely, but less so in appetitively, motivated learning and memory. While there is a growing body of research implicating αCaMKII in general in behavioral responses to threat or fearful stimuli, little is known about the contribution of the autophosphorylation. The present study asked how αCaMKII autophosphorylation controls anxiety-like behavioral responses toward novel, potentially threatening stimuli. We tested homozygous and heterozygous T286A αCaMKII autophosphorylation deficient mice and wild types in a systematic series of behavioral tests. Homozygous mutants were more active in the open field test and showed reduced anxiety-related behavior in the light/dark test, but these findings were confounded by a hyperlocomotor phenotype. The analysis of elevated plus maze showed significantly reduced anxiety-related behavior in the αCaMKII autophosphorylation-deficient mice which appeared to mediate a hyperlocomotor response. An analysis of home cage behavior, where neither novel nor threatening stimuli were present, showed no differences in locomotor activity between genotypes. Increased locomotion was not observed in the novel object exploration test in the αCaMKII autophosphorylation-deficient mice, implying that hyperactivity does not occur in response to discrete novel stimuli. The present data suggest that the behavior of αCaMKII autophosphorylation-deficient mice cannot simply be described as a low anxiety phenotype. Instead it is suggested that αCaMKII autophosphorylation influences locomotor reactivity to novel environments that are potentially, but not necessarily threatening.


Contextual factors favouring success in the accreditation process in Colombian hospitals: a nationwide observational study.
To identify context factors associated with and predicting success in the hospital accreditation process, and to contribute to the understanding of the relative relevance of context factors and their organizational level in the success of QI initiatives. Analytical study of cases and controls in a sample of hospitals of medium and high complexity in Colombia. Cases (n = 16) are accredited hospitals by the time of preparation of the study (2016) and controls (n = 38) are similar facilities, which have not succeeded to obtain accreditation. Eligibility criteria for both groups included complexity (medium and high), having emergency services, an official quality assurance license, and being in operation for at least 15 years. Besides eligibility criteria, geographical location, and type of ownership (public/private) are used to select controls to match cases. Context measures are assessed using a survey instrument based on the MUSIQ model ("Model for Understanding Success in Quality") adapted and tested in Colombia. Statistical analysis includes descriptive measures for twenty-three context factors, testing for significant statistical differences between accredited and non-accredited hospitals, and assessing the influence and strength of association of context factors on the probability of success in the accreditation process. A multivariate model assesses the predictive probability of achieving accreditation. Eighteen (78.3%) of the twenty-three context factors are significantly different when comparing cases and controls hospitals, particularly at the Microsystem level; all factors are statistically significant in favor of accredited hospitals. Five context factors are strongly associated to the achievement of accreditation but in the logistic multivariable model, only two of them remain with significant OR, one in the Macrosystem, "Availability of economic resources for QI" (OR: 22.1, p: 0,005), and the other in the Microsystem, "Involvement of physicians" (OR: 4.9, p: 0,04). This study has applied an instrument, based on the MUSIQ model, which allows assessing the relevance of different context factors and their organizational level in hospitals, to explain success in the accreditation process in Colombia. Internal macrosystem and microsystem seem to be more relevant than external environment factors.


Investigation of contrast mechanisms for MRI phase signal-based proton beam visualization in water phantoms.
The low sensitivity and limitation to water phantoms of convection-dependent MRI magnitude signal-based proton beam visualization hinder its in vivo applicability in MR-integrated proton beam therapy. The purpose of the present study was, therefore, to assess possible contrast mechanisms for MRI phase signal-based proton beam visualization that can potentially be exploited to enhance the sensitivity of the method and extend its applicability to tissue materials. To assess whether proton beam-induced magnetic field perturbations, changes in material susceptibility or convection result in detectable changes in the MRI phase signal, water phantom characteristics, experiment timing, and imaging parameters were varied in combined irradiation and imaging experiments using a time-of-flight angiography pulse sequence on a prototype in-beam MRI scanner. Velocity encoding was used to further probe and quantify beam-induced convection. MRI phase signal-based proton beam visualization proved feasible. The observed phase difference contrast was evoked by beam-induced buoyant convection with flow velocities in the mm/s range. Proton beam-induced magnetic field perturbations or changes in magnetic susceptibility did not influence the MRI phase signal. Velocity encoding was identified as a means to enhance the detection sensitivity. Because the MRI phase difference contrast observed during proton beam irradiation of water phantoms is caused by beam-induced convection, this method will unlikely be transferable to tightly compartmentalized tissue wherein flow effects are restricted. However, strong velocity encoded pulse sequences were identified as promising candidates for the future development of MRI-based methods for water phantom-based geometric quality assurance in MR-integrated proton beam therapy.


Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons.
A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis time-courses. CEP-1347 (500 nM), an mixed-lineage kinase 3 inhibitor, prevented MKK7 activation and cell death following exposure of CGN cultures to LK-induced apoptosis. Western blot analysis revealed that levels of phosphorylated c-Jun were elevated between 30 min and 10 h of CGN apoptosis, temporally consistent with MKK7 activation. These data suggest that MKK7 is responsible for activating the JNK pathway during LK-induced CGN apoptosis.


A metallo base-pair incorporating a terpyridyl-like motif: bipyridyl-pyrimidinone.Ag(I).4-pyridine.
The design and characterization of a geometrically unique, metallo base-pair motif is reported.


Strand-specific LINE-1 transcription in mouse F9 cells originates from the youngest phylogenetic subgroup of LINE-1 elements.
LINE-1 (L1) is a mammalian family of highly repeated DNA sequences that are members of a class of transposable elements whose movement involves an RNA intermediate. Both structural and evolutionary data indicate that the L1 family consists of a small number of active transposable elements interspersed with a large number of L1 pseudogenes. In the mouse, the longest, characterized L1 sequences span about 7000 base-pairs and contain two long open reading frames. Two subfamilies of mouse L1 elements, A and F, have been defined on the basis of the type of putative transcriptional regulatory sequence found at the 5' end. In order to identify a transcribed subset of L1 elements in mouse F9 teratocarcinoma cells, we have examined the strand-specificity of L1 transcription by Northern analysis and compared the open reading frame-1 sequences of ten A-type cDNAs with fifteen genomic A-type L1 elements. Transcripts containing A-type sequence are far more abundant than those containing F-type sequence. Although the majority of L1 RNA in F9 cells appears to be transcribed non-specifically from both strands, our results provide evidence for a subpopulation of variable length, strand-specific transcripts arising from A-type transcriptional regulatory sequences. F9 cell cDNA sequences, which share greater than 99.5% sequence identity with one another, represent a homogeneous subset of the genomic L1 population. Examination of genomic mouse L1 sequences reveals three types of length polymorphism in a defined segment of the first open reading frame. Phylogenetic analysis shows a correlation between the type of length polymorphism in the first open reading frame and the relative age of an individual A-type genomic L1 element. Comparison of the cDNA and genomic sequences indicates that the youngest subgroup of A-type L1 elements is preferentially transcribed in F9 cells. This subgroup may be currently dominating the L1 dispersal process in mice.


Mass Cytometry of Follicular Lymphoma Tumors Reveals Intrinsic Heterogeneity in Proteins Including HLA-DR and a Deficit in Nonmalignant Plasmablast and Germinal Center B-Cell Populations.
Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the nonmalignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, nonmalignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue. Diversity in cellular phenotype between tumors was greater for the malignant B cells than for nonmalignant B or T cells. The malignant B-cell population bore little phenotypic similarity to any healthy B-cell subset, and unexpectedly clustered closer to naïve B-cell populations than GC B-cell populations. Among the nonmalignant B cells within FL tumors, a significant lack of GC and plasmablast B cells was observed relative to tonsil controls. In contrast, nonmalignant T cells in FL tumors were present at levels similar to their cognate tonsillar T-cell subsets. Mass cytometry revealed that diverse HLA-DR expression on FL cells within individual tumors contributed greatly to tumor heterogeneity. Both malignant and nonmalignant B cells in the tumor bore little phenotypic resemblance to healthy GC B cells despite the presence of T follicular helper cells in the tumor. These findings suggest that ongoing signaling interactions between malignant B cells and intra-tumor T cells shape the tumor microenvironment. © 2016 International Clinical Cytometry Society.


Predictors of outcome for aortic valve replacement in patients with aortic regurgitation and left ventricular dysfunction: a change in the measuring stick.
Although left ventricular function is generally regarded as a key determinant of prognosis in aortic regurgitation, predictors of outcome of aortic valve replacement based on this factor have recently been questioned. This study was performed to examine the role of indexes of left ventricular function in predicting the outcome of surgery in patients with aortic regurgitation and left ventricular dysfunction. Fourteen patients with aortic regurgitation with a preoperative ejection fraction of less than 0.55 (average 0.45 +/- 0.02) who underwent aortic valve replacement were studied. The patients had 82 (58%) of a possible 140 predictors of negative outcome preoperatively, but 12 of the 14 patients had a decrease in symptoms and an increase in ejection fraction into the normal range after operation (average postoperative ejection fraction 0.59 +/- 0.04). Although improvement occurred despite the presence of many negative predictors of outcome, there was a significant correlation between postoperative ejection fraction and eight of the tested preoperative predictors. Preoperative end-systolic dimension correlated best (r = -0.91) with postoperative ejection fraction. An end-systolic dimension of 60 mm correlated with a postoperative ejection fraction of 0.55. The results indicate that preoperative ventricular function is still an important determinant of outcome of aortic valve replacement for aortic regurgitation. However, current medical and surgical techniques permit a better prognosis in the presence of reduced ventricular function than was previously considered possible.


Transluminal dilatation and stent placement in obstructed ureters in dogs through the use of percutaneous nephropyelostomy.
Through an artificially created ureteral obstruction in the dog, a ureteral stent was placed with the aid of a percutaneous nephrostomy tube. The stent was removed after two weeks. This resulted in permanent relief of the obstruction in the treated animals. In contrast to this, the control animals remained completely obstructed with resultant hydronephrosis and loss of kidney. It is proposed that this method can be used in humans where nephropyelostomy had been placed and where surgical correction of the obstructed ureter is not feasible.


Skill, corporality and alerting capacity in an account of sensory consciousness.
We suggest that within a skill-based, sensorimotor approach to sensory consciousness, two measurable properties of perceivers' interaction with the environment, "corporality" and "alerting capacity", explain why sensory stimulation is experienced as having a "sensory feel", unlike thoughts or memories. We propose that the notions of "corporality" and "alerting capacity" make possible the construction of a "phenomenality plot", which charts in a principled way the degree to which conscious phenomena are experienced as having a sensory quality.


Evaluation of polyurethane foam passive air sampler (PUF) as a tool for occupational PAH measurements.
Routine monitoring of workplace exposure to polycyclic aromatic hydrocarbons (PAHs) is performed mainly via active sampling. However, active samplers have several drawbacks and, in some cases, may even be unusable. Polyurethane foam (PUF) as personal passive air samplers constitute good alternatives for PAH monitoring in occupational air (8 h). However, PUFs must be further tested to reliably yield detectable levels of PAHs in short exposure times (1-3 h) and under extreme occupational conditions. Therefore, we compared the personal exposure monitoring performance of a passive PUF sampler with that of an active air sampler and determined the corresponding uptake rates (Rs). These rates were then used to estimate the occupational exposure of firefighters and police forensic specialists to 32 PAHs. The work environments studied were heavily contaminated by PAHs with (for example) benzo(a)pyrene ranging from 0.2 to 56 ng m-3, as measured via active sampling. We show that, even after short exposure times, PUF can reliably accumulate both gaseous and particle-bound PAHs. The Rs-values are almost independent of variables such as the concentration and the wind speed. Therefore, by using the Rs-values (2.0-20 m3 day-1), the air concentrations can be estimated within a factor of two for gaseous PAHs and a factor of 10 for particulate PAHs. With very short sampling times (1 h), our method can serve as a (i) simple and user-friendly semi-quantitative screening tool for estimating and tracking point sources of PAH in micro-environments and (ii) complement to the traditional active pumping methods.


Production and properties of monoclonal antibodies to guinea pig Ia antigens.
Although the use of monoclonal antibodies to characterize the Ia antigen system is still in its infancy, the usefulness of this approach is clearly apparent. Since xenogeneic immunization can be used to generate these antibodies, the chances are good that a greater variety of Ia types and determinants will be detected compared to those detected with conventional alloantisera. In addition, the advantages of unlimited quantity and constant specificity allow a much greater degree of standardization than was previously possible. Finally, monoclonal antibodies open up lines of investigation, such as the examination of correlations between the monoclonal antibody's inhibition of T-cell proliferation and the antibody's corresponding Ia epitope-binding characteristics, that it would be impossible to approach using conventional alloantisera.


[Comparative properties of sensitive to GABAA-ergic ligands, Cl(-), HCO3(-)-activated Mg2+-ATPase from brain plasma membranes of fish and rats].
Action of Cl(-) + HCO3(-) ions on Mg2+-ATPase from brain plasma membranes of fish and rats has been studied. Maximal effect of the anions on the <<basal>> Mg2+-ATPase activity is revealed in the presence of 10 mM Cl(-) and 3 mM HCO3(-) at physiological values of pH of incubation medium. The studied Cl(-), HCO3(-)-activated Mg2+-ATPases of both animal species, by their sensitivity to SH-reagents (5,5-dithiobis-nitrobenzoic acid, N-ethylmaleimide), oligomycin, and orthovanadate, are similar to transport ATPase of the P-type, but differ from them by molecular properties and by sensitivity to ligands of GABAA-receptors. It has been established that the sensitive to GABAA-ergic ligands, Cl(-), HCO3(-)-activated Mg2+-ATPase from brain of the both animal species is protein of molecular mass around 300 kDa and of Stocks' radius 5.4 nm. In fish the enzyme is composed of one major unit of molecular mass approximately 56 kDa, while in rats--of three subunits of molecular masses about 57, 53, and 45 kDa. A functional and structural coupling of the ATP-hydrolyzing areas of the studied enzyme to sites of binding of GABAA-receptor ligands is suggested.


Selective cytotoxicity of tumor cells induced by liposomes containing plant phosphatidylinositol.
Liposomes containing highly purified phosphatidylinositol (PI) from plant origin selectively killed tumor cells from 8 out of 9 cultured cell lines, but did not kill 4 types of normal cells. Other phospholipids, including PI or phosphatidylserine from animal origin, synthetic phosphatidic acid, phosphatidylglycerol, or phosphatidylcholine, were not cytotoxic. Cholesterol enrichment of cells, shown by other investigators to inhibit tumor development, was slightly cytotoxic in this system, but the toxic effect of cholesterol was minor compared to the massive cytotoxicity induced by plant PI.


Rare case of apatinib acquired resistance induced by point mutation of WRN p.V697F through activation of the PI3K/AKT apoptosis-inhibiting pathway.
Targeted therapy has become the main treatment for non-small cell lung cancer (NSCLC). Apatinib is a new antiangiogenic antitumor drug developed in China which targets vascular endothelial growth factor receptor-2 (VEGFR-2). We recently treated a 50-year-old female patient who underwent a bronchoscopic biopsy and was subsequently pathologically diagnosed with squamous cell carcinoma of NSCLC. EML4-ALK and MINPP1 & PAPSS2-PTEN fusions were found to be present in tumor tissue and blood. Sequential targeted therapy was commenced with gemcitabine + cisplatin, docetaxel, tegafur, gimeracil, oteracil potassium capsules + carboplatin, and other third-line chemotherapy involving antineoplastic therapy, but unfortunately the patient showed primary drug resistance to this treatment regimen. Crizotinib was administered but was found to be ineffective. After two months of treatment, the disease had progressed and next generation sequencing (NGS) was subsequently performed. Apatinib was administered thereafter and the patient's symptoms improved after one week. Following administration for one month, CT scan revealed that the primary lung tumor lesions were significantly necrotic and they were narrowed. The patient's symptoms of coughing, phlegm production, and wheezing had also reduced. Her lung disease was under stable control 2.5 months later, but abdominal CT unfortunately revealed a suspected new nidus in the liver. A third gene mutation detection test showed that ALK and PTEN genetic mutations were obviously decreased; however, the patient was found to have developed WRN p.V697F (c.G2089T) point mutation, which was a new gene mutation. We suspected that the WRN gene mutation had led to apatinib resistance. We determined the absolute position of this point mutation to be chr8:30969131 with a transcript number of NM_000553.4. We retrieved information on human somatic cells from the ExAC, 1000 Genomes Browser, ESP database and PubMed databases. All the results indicated that the mutation identified in this study has not been previously reported worldwide.


Extensive facial adenoma sebaceum: successful treatment with mechanical dermabrasion: case report.
This report documents the successful elimination of disfiguring sebaceous adenomas from the face of a 21-year-old male patient with mechanical dermabrasion.


The impact of childhood maltreatment on women's reproductive health, with a focus on symptoms of polycystic ovary syndrome.
Childhood maltreatment leads to lifelong health risks, particularly in women. Although reproductive health has been linked to such maltreatment, limited literature exists on its association with polycystic ovary syndrome (PCOS). In a sample of psychiatrically healthy women, we evaluated the impact of child maltreatment (subtypes of abuse and neglect) on women's reproductive health outcomes, specifically PCOS. The 237 psychiatrically healthy women, aged between 18 and 79 years, were control participants in a case-control study (SHARED ROOTS), conducted in Cape Town, South Africa, between May 2014 and June 2017. Probable PCOS was based on a history of symptoms of ovulatory dysfunction and hyperandrogenism or a diagnosis of PCOS. We conducted hierarchical logistic regression models to assess which child maltreatment subtypes (emotional, physical and sexual abuse and emotional and physical neglect) were significantly associated with PCOS, controlling for sociodemographic and clinical factors. Probable PCOS was present in 29 (12.2 %) women. Emotional abuse (31.6 %) was the most frequent type of child maltreatment and was significantly associated with PCOS (OR = 5.11, CI 1.87; 13.98), including when other maltreatment types were accounted for (OR = 3.90, CI 1.27; 12.02). Physical abuse was associated with PCOS (OR = 4.21, CI 1.43; 12.38), but was not significant when other maltreatment types were factored in. Child maltreatment is independently associated with PCOS in women without psychiatric disorders. In the context of all maltreatment subtypes, emotional abuse remained associated with PCOS, suggesting its unique effect on this endocrinopathy.


Kinetics of factor Xa inhibition by tissue factor pathway inhibitor.
Tissue factor pathway inhibitor is a multivalent, Kunitz-type proteinase inhibitor. It directly inhibits factor Xa and, in a factor Xa-dependent fashion, produces feedback inhibition of the factor VIIa/tissue factor catalytic complex which is responsible for the initiation of coagulation. Human recombinant TFPI (rTFPI) produced in Escherichia coli was used to define the kinetic constants describing the human factor Xa:TFPI interaction. The inactivation of factor Xa by E. coli-rTFPI is indistinguishable from that of rTFPI produced in mammalian SK-hepatoma cells, suggesting that post-translational modifications such as glycosylation and phosphorylation do not play a major role in the inhibitory process. The slow, tight-binding inhibition of factor Xa follows the scheme: [formula: see text] Where the enzyme (E) and inhibitor (I) form an initial, immediate collision complex (EI) that then isomerizes slowly to a tightened final EI* complex. In the absence of other additions, the initial Ki (=k2/k1) and final Ki* for the inhibition of factor Xa by E. coli-rTFPI are 1.24 nM and 26.4 pM, respectively. In the presence of calcium ions (5 mM) the interaction between factor Xa and rTFPI is substantially weaker, with a Ki of 42.7 nM and Ki* of 85.2 pM. The addition of other components of the prothrombinase complex produces enhanced factor Xa inhibition predominantly through an effect on the initial Ki. In the presence of calcium ions and saturating concentrations of phospholipids and factor Va, the Ki and Ki* for factor Xa inactivation are 2.04 nM and 52.3 pM. The enhancing effect of heparin on the inhibitory process is concentration dependent and exhibits an optimum, reminiscent of the "template" model for heparin's acceleration of thrombin and factor IXa inhibition by antithrombin III. At optimal concentrations, the major mechanism of heparin action is also a reduction in the Ki of the initial encounter complex between factor Xa and rTFPI.


Three-dimensional finite element analysis of anterior fixed partial denture supported by implants with different materials.
Implant restoration in the anterior region was a great challenge for dentists. The aim of the study was to use three-dimensional finite element analysis to analyze the feasibility of the fixed partial denture supported by two diverse material implants in the maxillary anterior region, to provide a theoretical basis for clinical therapy. Based on CBCT data, a three-unit fixed partial denture supported by two endosseous implants with a diameter of 3.5 mm and a length of 10 mm inserted in the upper left central incisor and canine was created. The materials of the implant were verified in seven models. Titanium (Ti), zirconia (Zr) and titanium-zirconia (TiZr) were used for the implant materials. A total load of 150 N was applied on the prosthesis units at 45˚ to the long axis of the abutment. The maximal displacement of the implant was 6.1 µm in the titanium implant at the canine region in the TiZr-Ti model. The stresses in the cortical bone and strains in the spongious bone were below the physiological upper limits. The highest value of the maximal stress in cortical bone was 78 MPa, observed in the left central incisor region of Zr-TiZr model. And the highest value of the maximal strain in the spongious bone was 1738 μstrain around the titanium implant of the Ti-TiZr model. From the biomechanical point of view, fixed partial denture supported by two diverse material implants in the maxillary anterior region is an acceptable treatment option.


Efficacy of rechallenge transcatheter arterial chemoembolization after lenvatinib treatment for advanced hepatocellular carcinoma.
We evaluated the efficacy of rechallenge transcatheter arterial chemoembolization (TACE) after lenvatinib (LEN) treatment in patients with previous TACE failure/refractoriness. We enrolled 63 consecutive patients with a history of TACE failure/refractoriness prior to LEN treatment as a first-line systemic therapy. We reviewed the clinical backgrounds and courses of the patients. In total, 25 patients underwent rechallenge TACE after LEN due to LEN-refractoriness (17 cases) or intolerance (8 cases). A complete or partial response was obtained for 13 (65.0%) of the 20 patients whose therapeutic effects were determined. The survival rate of patients who underwent rechallenge TACE was significantly higher than that of patients who did not undergo rechallenge TACE (median survival time, not reached vs 403 days, P = 0.015). Rechallenge TACE significantly reduced the risk of death in univariate (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.08-0.69, P = 0.008) and multivariate analyses (HR 0.26, 95% CI 0.08-0.80, P = 0.019). If complete or partial response was obtained by rechallenge TACE, the median survival time of these patients was significantly longer than those of the progressive disease (PD) group (P = 0.05), and the median survival time of the PD group after rechallenge TACE was not different from that of the group who did not undergo rechallenge TACE (P = 0.36). We did not observe a decrease in the ALBI score after TACE. Rechallenge TACE after LEN is an effective treatment that may result in a favorable prognosis.


Treatment of lateralisation and subluxation of the hip in cerebral palsy with Botulinum toxin A: preliminary results based on the analysis of migration percentage data.
It has been reported that cerebral palsy patients with adductor spasm and lateralisation/subluxation of the hip can be treated with Botulinum toxin A, but statistical evaluation is lacking. We present the radiological results in 5 patients. The follow-up ranged from 18 (5 patients) to 24 months (4 patients). Reimers' migration percentage was chosen as parameter for lateralisation/subluxation. Statistical analysis was performed by the Wilcoxon test. The migration percentage improved from 51% to 44% at 9 months, 37% at 18 months, and 34% at 24 months. The improvement was significant from the 9th to the 18th month (p=0.04).


Use of holmium laser for umbilical cord transection in a monoamniotic pregnancy threatened by an acardiac co-twin: a case report.
Twin reversed arterial perfusion sequence is a rare complication of monochorionic multifetal pregnancies. In this syndrome, the acardiac twin has a nonfunctional heart, while the other twin, the pump twin, has normal development. The pump twin perfuses the acardiac twin and is therefore at risk for cardiac decompensation. In monoamniotic cases, the normal co-twin is also at risk of sudden death due to cord entanglement. Treatment consists of coagulation and transection of the acardiac's umbilical cord. We report the first intrauterine use in pregnancy of a Ho:yttrium aluminum garnet laser to safely and successfully transect the umbilical cord after Nd:yttrium aluminum garnet coagulation. A 30-year-old Caucasian woman was referred to our fetal-maternal medicine unit at 9 weeks gestation with a monochorionic-monoamniotic twin pregnancy complicated by an acardiac twin. After counseling, she opted for an elective intervention to minimize the risks to the pump twin. At 16 weeks, fetoscopy was performed using a single 2-mm entry port. Through this port, a 1.0-mm fetoscope and a 0.365-mm laser fiber were introduced. Under fetoscopic sight and ultrasound (Doppler) guidance, the umbilical cord of the acardiac twin was first coagulated by laser energy using a Nd:yttrium aluminum garnet laser and then, using the same fiber, transected using a Ho:yttrium aluminum garnet laser. The patient underwent cesarean section at 38 weeks and delivered a healthy baby. We present the first report on intrauterine use of an Ho:yttrium aluminum garnet laser in human pregnancy. Ho:yttrium aluminum garnet laser energy can be successfully and safely used for umbilical cord transection and carries fewer risks than other methods of transection.


AIDS: relationship to alcohol and other drugs.
Most people who are exposed to AIDS do not get the syndrome. It seems clear that there must be cofactors. Most people with AIDS have a history of alcohol or other drug use, and many of the drugs used have been shown to suppress the immune system. The correlation between drug use and development of AIDS in several populations is striking, and it is suggested that definitive research into this possible cofactor be urgently initiated. The elimination of cofactors may present an immediate way to control this epidemic. Suggestions are made as to how and why alcohol and drug treatment professionals should become a part of this effort.


Evaluation of volatile ion-pair reagents for the liquid chromatography-mass spectrometry analysis of polar compounds and its application to the determination of methadone in human plasma.
A liquid chromatography method using volatile ion-pairing reagents and tandem mass spectrometry was developed to obviate observed matrix effect for ionizable polar compounds. The present study investigated the addition of volatile ion-pair reagents to the reconstitution solution instead of the mobile phase to enhance the efficiency of chromatographic separation and minimize the sensitivity loss due to the formation of ion-pairs. The volatile ion-pair reagents used were perfluorinated carboxylic acids with n-alkyl chains: heptafluorobutanoic acid (HFBA), nonafluoropentanoic acid (NFPA), tridecafluoroheptanoic acid (TDFHA) and pentadecafluorooctanoic acid (PDFOA). The model analytes evaluated were N-methylnicotinamide (MNA) chloride, N-methyl 2-pyridone 5-carboxamide (2PY) and phenylephrine. The effects of alkyl chain length and the concentrations of the ion-pair reagents on the retention of analytes were studied, as well as the effect of pH on the retention of phenylephrine. The volatile ion-pair reagents in the reconstitution solution showed significant effect on the retention of the ionizable polar compounds, and the sensitivity of detection was improved for plasma samples through decreasing the matrix effect. This methodology was successfully applied to establish a quantitative assay for the polar drug substance methadone in human plasma with a concentration range from 0.1 to 50 ng/mL. Ion-pair reagents not only shifted the retention time but also reduced the carry-over peak for methadone.


Genome-Scale Transcript Analyses of Human Neutrophils.
Transcriptome analyses of unicellular and multicellular organisms have changed fundamental understanding of biological and pathological processes across multiple scientific disciplines. Over the past 15 years, studies of polymorphonuclear leukocyte (PMN or neutrophil) gene expression on a global scale have provided new insight into the molecular processes that promote resolution of infections in humans. Herein we present methods to analyze gene expression in human neutrophils using Affymetrix oligonucleotide microarrays and next-generation sequencing. Notably, the procedures utilize commercially available reagents and materials and thus represent a standardized approach for evaluating PMN transcript levels.


A Foundational Science Department's Transition to an Online Community.
Like many medical school department's around the world, we needed to pivot, almost instantly to an online community. As a large and diverse foundational science department, grounded in a culture of collegiality and collaboration, we faced a host of challenges beyond immediate remote teaching. Of paramount concern to departmental leadership was-how do we maintain our culture while working remotely?


Black disc morphology during routine lumbar discectomy with subsequent diagnosis of enterococcal discitis.
Enterococcus faecalis is reported infrequently as an infectious cause of discitis. In the literature, the diagnosis is commonly made based on the clinical picture coupled with blood cultures, imaging, and tissue cultures. A 62-year-old male with chronic lower back pain underwent lumbar decompression for a lumbar disc. At surgery, the patient had significant black discoloration of the disc material. Later, the cultures demonstrated E. faecalis infectious discitis. Here is an example of enterococcal lumbar discitis found during a routine lumbar discectomy. As operative cultures revealed E. faecalis, the patient required not one but two operations (i.e., second for seroma/ hematoma due to infection) following which antibiotic therapy eradicated the infection.


Comparative analysis and forecasting of COVID-19 cases in various European countries with ARIMA, NARNN and LSTM approaches.
In this study, confirmed COVID-19 cases of Denmark, Belgium, Germany, France, United Kingdom, Finland, Switzerland and Turkey were modeled with Auto-Regressive Integrated Moving Average (ARIMA), Nonlinear Autoregression Neural Network (NARNN) and Long-Short Term Memory (LSTM) approaches. Six model performance metric were used to select the most accurate model (MSE, PSNR, RMSE, NRMSE, MAPE and SMAPE). According to the results of the first step of the study, LSTM was found the most accurate model. In the second stage of the study, LSTM model was provided to make predictions in a 14-day perspective that is yet to be known. Results of the second step of the study shows that the total cumulative case increase rate is expected to decrease slightly in many countries.


Fatty acid chain-shortening activity in the pulmonary type II cell.
Type II cells obtained from fetal rabbit lung tissue in culture were incubated with [14C]palmitic and [14C]stearic acids labeled at either the carboxyl or the terminal methyl groups. Significant chain shortening of [18-14C]stearic acid to radiolabeled palmitic acid was observed, with little chain shortening of palmitic acid to myristic acid. Incorporation of 14C into palmitic acid by beta-oxidation followed by de novo fatty acid biosynthesis was not detectable under the same experimental conditions. The palmitic acid supplied by chain shortening was preferentially incorporated into phosphatidylcholine instead of other lipids. Fatty acid chain-shortening activity in the type II cell appears to be capable of increasing the amount and relative proportion of palmitic acid available for phosphatidylcholine biosynthesis.


Adverse effects of a high-glucose diet on body weight and plasma calcium and 1,25-dihydroxyvitamin D3 levels in calcium-deficient growing rats.
We tested the hypothesis that dietary calcium would lead to greater impairment of body weight gain and calcium homeostasis if rats are fed a diet with a high glucose content compared with our standard diet in which the carbohydrate is supplied by whole wheat flour. Groups of female rats at 21 days of age were given either of two equivalent calcium-deficient diets with carbohydrate supplied either by glucose (LCaG) or by wheat flour (LCaW). Control rats were fed the wheat-flour diet containing 0.4% calcium. Since previous studies indicated divergent effects of glucose-based and flour-based diets on body weight in vitamin D-deficient rats, we designed a parallel study with vitamin D-deprived rats. Compared with rats fed the LCaW diet, the rats fed the LCaG diet had inferior body weight gain and more severe hypocalcemia (1-2 mg/ml lower) over a 40-day period, and no significant elevation of the plasma 1,25(OH)2D3 level at 61 days of age. Rats fed the LCaW diet maintained a 3-fold elevation of plasma 1,25(OH)2D3 relative to the level of control rats fed the 0.4% calcium diet. The dry weight and percent ash of tibias were similarly reduced in the two calcium-restricted groups compared to the control group. Among the vitamin D-deprived rats, those fed the glucose diet had poorer weight gain than those fed the wheat flour diet. However, both groups had similarly depressed serum calcium level, tibia ash content and 1,25(OH)2D3 level. Thus, a glucose diet combined with calcium restriction or vitamin D deprivation appears to accentuate the impairment of body weight gain and, when combined with calcium restriction, it also accentuates the impairment of calcium homeostasis and interferes with the adaptive increase in plasma 1,25(OH)2D3.


Characteristics of an Italian diabetic population and long-term changes in glycaemic control at varying body weight categories.
To describe the characteristics of a diabetic population in a primary care setting, and to evaluate changes in glycaemic control at varying body weight categories. We collected 4,610 valid baseline and three years follow-up paired data sheets sent from 77% of the general practitioners adhering to our shared-care program (257 GPs out of 521) for people with type 2 diabetes. Three conventional body weight categories were defined: "normal" (BMI, < or = 25 kg/m2), "overweight" (BMI 25.0-29.9), "obesity" (BMI > or = 30). According to weight status we calculated descriptive statistics and follow-up paired changes. A fifth of the diabetic patients had a "normal" BMI, about 45% was "overweight" and 34% was "obese". At follow-up, the glycaemic control significantly improved both in "normal" and "overweight" people, while it significantly worsened in "obese" ones. Our data confirm the crucial role played by body weight and its changes in diabetic patients.


A rapid method for the determination of deoxycytidylate deaminase activity in pregnancy serum.
A method is described for determining the activity of deoxycytidylate deaminase in serum. The ammonia liberated from deoxycytidine monophosphate has been specifically determined by enzymatic amination of alpha-ketoglutarate using glutamate dehydrogenase. The concurrent oxidation of NADH2 at 340 nm was proportional to the ammonia liberated from deoxycytidine monophosphate. Using the technique described, a result would be available to the clinician in under 4.5 h. The "normal activity" for deoxycytidine deaminase in normal male, female and pregnancy sera has been determined.


Is conventional radiography still relevant for evaluating the acromioclavicular joint?
Conventional radiography using an anteroposterior view of the acromioclavicular (AC) joint is the gold standard for evaluating arthritic degeneration. Based on a standardised AP view of the AC joint, the objective of this study was to determine whether this radiographic view is reliable and reproducible for evaluating the AC joint space. A cadaver scapula-clavicle unit, free of osteoarthritis, was used for this study. The scapula was positioned in a stand; and then with fluoroscopy guidance, a strict AP view of the AC joint was taken. Starting from this "0" position, a radiograph was taken by varying the angle by 5°, 10°, and 15° in every plane in space. All radiographs were taken during a single session to ensure the distance between the X-ray tube and scapula did not change. The images were then exported to OsiriX for processing; the superior and inferior AC distance and the joint area were measured. There was no reproducibility in the AC joint measurements as a function of the incidence angle relative to a strict AP view. Conventional radiography using an AP view of the AC joint cannot be used to do a fine analysis of arthritic degeneration of this joint. It is likely that only CT scan or MRI is sufficient to analyse osteoarthritis in this joint. IV, basic science study.


Mechanisms that limit regression of myocardial fibrosis following removal of left ventricular pressure overload.
Left ventricular pressure overload (LVPO) can develop from antecedent diseases such as aortic valve stenosis and systemic hypertension and is characterized by accumulation of myocardial extracellular matrix (ECM). Evidence from patient and animal models supports limited reductions in ECM following alleviation of PO, however, mechanisms that control the extent and timing of ECM regression are undefined. LVPO, induced by 4 wk of transverse aortic constriction (TAC) in mice, was alleviated by removal of the band (unTAC). Cardiomyocyte cross-sectional area, collagen volume fraction (CVF), myocardial stiffness, and collagen degradation were assessed for: control, 2-wk TAC, 4-wk TAC, 4-wk TAC + 2-wk unTAC, 4-wk TAC + 4-wk unTAC, and 4-wk TAC + 6-wk unTAC. When compared with 4-wk TAC, 2-wk unTAC resulted in increased reactivity of collagen hybridizing peptide (CHP) (representing initiation of collagen degradation), increased levels of collagenases and gelatinases, decreased levels of collagen cross-linking enzymes, but no change in CVF. When compared with 2-wk unTAC, 4-wk unTAC demonstrated decreased CVF, which did not decline to control values. At 4-wk and 6-wk unTAC, CHP reactivity and mediators of ECM degradation were reduced versus 2-wk unTAC, whereas levels of tissue inhibitor of metalloproteinase (TIMP)-1 increased. ECM homeostasis changed in a time-dependent manner after removal of LVPO and is characterized by early increases in collagen degradation, followed by a later dampening of this process. Tempered ECM degradation with time is predicted to contribute to the finding that normalization of hemodynamic overload alone does not completely regress myocardial fibrosis.NEW & NOTEWORTHY In this study, a murine model demonstrated persistent interstitial fibrosis and myocardial stiffness following alleviation of pressure overload.


Determination of in vitro synergy when three antimicrobial agents are combined against Mycobacterium tuberculosis.
We determined the in vitro antimycobacterial activity of rifampicin, isoniazid and a third agent in combination using a three-dimensional chequerboard in Middlebrook 7H9 broth microdilutions. Of 28 agents screened, ethambutol, streptomycin, clarithromycin, minocycline, ciprofloxacin, levofloxacin, sparfloxacin, gatifloxacin and sitafloxacin were potentially synergistic. A further three-dimensional chequerboard assay quantitatively looked for synergy against ten clinical isolates of Mycobacterium tuberculosis, including seven multidrug-resistant isolates. Sitafloxacin, gatifloxacin and clarithromycin showed significant synergy, with fractional inhibitory concentration indices ranging from 0.41 to 0.79, 0.39 to 0.90 and 0.48 to 0.95, respectively. It is concluded that three-dimensional chequerboard assay can quantitatively determine antimycobacterial synergy, and that fluoroquinolones and antibacterial agents such as clarithromycin are effective against multidrug-resistant isolates of M. tuberculosis when combined with rifampicin and isoniazid.


Oxysterols: From redox bench to industry.
More and more attention is nowadays given to the possible translational application of a great number of biochemical and biological findings with the involved molecules. This is also the case of cholesterol oxidation products, redox molecules over the last years deeply investigated for their implication in human pathophysiology. Oxysterols of non-enzymatic origin, the excessive increase of which in biological fluids and tissues is of toxicological relevance for their marked pro-oxidant and pro-inflammatory properties, are increasingly applied in clinical biochemistry as molecular markers in the diagnosis and monitoring of several human and veterinary diseases. Conversely, oxysterols of enzymatic origin, the production of which is commonly under physiological regulation, could be considered and tested as promising pharmaceutical agents because of their antiviral, pro-osteogenic and antiadipogenic properties of some of them. Very recently, the quantification of oxysterols of non-enzymatic origin has been adopted in a systematic way to evaluate, monitor and improve the quality of cholesterol-based food ingredients, that are prone to auto-oxidation, as well as their industrial processing and the packaging and the shelf life of the finished food products. The growing translational value of oxysterols is here reviewed in its present and upcoming applications in various industrial fields.


Accuracy controls: assessing trueness (bias).
Testing quality control samples is routine in the clinical laboratory but typically these are precision controls that monitor only the reproducibility (random error) of an assay and not trueness/bias (systematic error). To assess bias, accuracy controls that address both systematic error (trueness) and random error (precision) are needed. A properly prepared trueness control can be used to assess both bias and precision, as accuracy is defined by both random and systematic error. Providers of reference materials, such as metrology institutes and manufacturers are best suited to provide accuracy controls.


Impacts of sun protection and skin care habits in the biophysical and morphological properties of young men skin.
Previous studies have demonstrated that UVB radiation may cause changes in the epidermal permeability barrier and in the stratum corneum hydration. It is also well known that sun exposure causes erythema, skin cancer, and other physiologic alterations. Furthermore, because of the cultural barrier, men usually apply less sunscreen. The objective of this study was to evaluate the cosmetic use and sun protection habits of young men, correlating their lifestyle with the biophysical and morphological skin characteristics, as well as to study how skin unprotected sun exposure can affect these features even in young people. 60 participants between 18 and 28 years old were divided into two groups: with photoprotection habits (PP habits) and without photoprotection habits (No PP habits). They were questioned about their sunscreen and cosmetic products use. The skin parameters were evaluated using biophysical and skin imaging techniques. 60% of the participants did not apply sunscreen often, and 80% did not consume other skin care products. No PP habits group presented an increase in the transepidermal water loss-TEWL and sebum level, as well as a reduction in the stratum corneum water content and dermis echogenicity. The skin characteristics evaluated in this study were correlated with the sun protection habits and skin care behavior showing that men face some sociocultural barrier to start the use of cosmetic products. Thus, it is important to consider this information for the dermatological clinical and development of cosmetic products for men's skin.


Gender and ethnic differences in cancer patients' needs for help: an Internet survey.
Although a number of studies have reported different domains of cancer patients' needs for help, very little is known about gender and ethnic differences in those needs. Gender differences have been implicitly assumed in most studies, and specific ethnic groups have been focused on rather than comparing several ethnic groups. The purpose of this pilot study was to explore cancer patients' needs for help among four major ethnic groups in the US, to determine gender and ethnic differences in needs, and to provide direction for future studies. This was a descriptive and comparative pilot study using a feminist perspective. A total of 110 self-identified cancer patients were recruited through both Internet and community settings using a convenience sampling method. The instruments included sociodemographic questions, the Cancer Needs Questionnaire-Short Form, and the Supportive Care Needs Survey. The data were analyzed using descriptive statistics and inferential statistics including the Mann-Whitney U tests and Kruskal-Wallis tests. The findings indicated that there was no significant gender difference in all domains of needs for help. There were significant ethnic differences in all domains of needs except communication and sexual needs. Asians reported the lowest scores in most domains of needs for help while Hispanics reported the highest scores in most domains of needs for help. The findings indicated certain ethnic differences in cancer patients' needs for help and suggest further in-depth qualitative investigations on cultural beliefs and attitudes that may influence needs, with a careful examination of gender sensitivity and cultural competence of the instruments measuring cancer patients' needs for help.


Fetal adrenocortex-medulla interactions and changes of pituitary in mouse embryos with an ectopic corticotrophic tumor.
Using a model of an ectopic corticotrophic tumor transplanted in mouse embryos, we now report several new findings. One relates to fetal adrenocortex-medulla interactions and others to feedback regulation of the pituitary by adrenal products or other factors in mouse embryos.


When does fetal head rotation occur in spontaneous labor at term: results of an ultrasound-based longitudinal study in nulliparous women.
Improved information about the evolution of fetal head rotation during labor is required. Ultrasound methods have the potential to provide reliable new knowledge about fetal head position. The aim of the study was to describe fetal head rotation in women in spontaneous labor at term using ultrasound longitudinally throughout the active phase. This was a single center, prospective cohort study at Landspitali - The National University Hospital of Iceland, Reykjavík, Iceland, from January 2016 to April 2018. Nulliparous women with a single fetus in cephalic presentation and spontaneous labor onset at ≥37 weeks' gestation were eligible. Inclusion occurred when the active phase could be clinically established by labor ward staff. Cervical dilatation was clinically examined. Fetal head position and subsequent rotation were determined using both transabdominal and transperineal ultrasound. Occiput positions were marked on a clockface graph with 24 half-hour divisions and categorized into occiput anterior (≥10- and ≤2-o'clock positions), left occiput transverse (>2- and <4-o'clock positions), occiput posterior (≥4- and ≤8 o'clock positions), and right occiput transverse positions (>8- and <10-o'clock positions). Head descent was measured with ultrasound as head-perineum distance and angle of progression. Clinical vaginal and ultrasound examinations were performed by separate examiners not revealing the results to each other. We followed the fetal head rotation relative to the initial position in the pelvis in 99 women, of whom 75 delivered spontaneously, 16 with instrumental assistance, and 8 needed cesarean delivery. At inclusion, the cervix was dilated 4 cm in 26 women, 5 cm in 30 women, and ≥6 cm in 43 women. Furthermore, 4 women were examined once, 93 women twice, 60 women 3 times, 47 women 4 times, 20 women 5 times, 15 women 6 times, and 3 women 8 times. Occiput posterior was the most frequent position at the first examination (52 of 99), but of those classified as posterior, most were at 4- or 8-o'clock position. Occiput posterior positions persisted in >50% of cases throughout the first stage of labor but were anterior in 53 of 80 women (66%) examined by and after full dilatation. The occiput position was anterior in 75% of cases at a head-perineum distance of ≤30 mm and in 73% of cases at an angle of progression of ≥125° (corresponding to a clinical station of +1). All initial occiput anterior (19), 77% of occiput posterior (40 of 52), and 93% of occiput transverse positions (26 of 28) were thereafter delivered in an occiput anterior position. In 6 cases, the fetal head had rotated over the 6-o'clock position from an occiput posterior or transverse position, resulting in a rotation of >180°. In addition, 6 of the 8 women ending with cesarean delivery had the fetus in occiput posterior position throughout the active phase of labor. We investigated the rotation of the fetal head in the active phase of labor in nulliparous women in spontaneous labor at term, using ultrasound to provide accurate and objective results. The occiput posterior position was the most common fetal position throughout the active phase of the first stage of labor. Occiput anterior only became the most frequent position at full dilatation and after the head had descended below the midpelvic plane.


The influence of adrenergic agonists and their antagonists on isolated salivary glands of ixodid ticks.
Various drugs elicit fluid secretion by isolated salivary glands of two species of ixodid ticks (Dermacentor andersoni Stiles and Amblyomma hebraeum Koch). Among catecholamines, the following order of potency was observed: dopamine, epinine, noradrenaline = adrenaline and isoprenaline. The following drugs, in order of potency, were also agonists on this preparation: ergonovine, ergotamine, 6-hydroxydopamine, apomorphine, phenylephrine, norphenylephrine, beta-phenylethylamine, tyramine, D, L-dopa and octopamine. Nialamide increased the response to near-threshold concentrations of dopamine but had no intrinsic activity. Dopamine-induced secretion was depressed by phenoxybenzamine, alpha-flupenthixol, phentolamine, propranolol and dichloroisoprenaline, but only at conce,trations 10- to 1000-fold that of the agonist. Pimozide and spiperone (10(-6) M) augmented the maximum response of dopamine. The tick salivary gland, thus appears to contain one or several receptors differing pharmacologically from mammalian alpha-adrenergic, beta-adrenergic and dopamine receptors.


Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial.
Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49). Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.


Improved food intake and weight gain in adult patients following electroconvulsive therapy for depression.
Six elderly patients were referred for nutrition assessment and treatment because of poor dietary intake and weight loss associated with a major depressive illness. The patients underwent electroconvulsive therapy (ECT) administered by their psychiatrists approximately 3 times per week. During ECT, all patients increased their caloric intake (280 +/- 180 to 1,510 +/- 60 kcal/day, mean +/- SEM) to exceed their basal energy expenditure; major improvements in their depressive symptoms and weight gain were seen in five of the six patients. Increased caloric intake seen with ECT may be an early, clinical criterion for identifying the effectiveness of antidepressant therapy when depression is associated with anorexia and reduced energy intake.


Ictal clinical patterns and ictal EEG in a case of partial seizures of frontotemporal origin associated with complex symptomatology.
The patient was a 35-year-old, unmarried male whose epileptic psychomotor fits persisted since the age of 13. The author has observed the case for about 12 years, so that incomplete information concerning epileptic symptoms was considered to be compensated considerably by longitudinal observation, including ictal seizure and ictal EEG's. In this patient seizure with impaired consciousness which correspond rhythmic slow waves of EEG tracing might be a nuclear sign; several kinds of automatism then might be considered as postictal phenomenon. The most important of all was tonic seizure of psychomotor epilepsy particularly in the face which was not seen in the petit mal epilepsy. With observation of ictal period as well as ictal EEG, differential identification of centrencephalic epilepsy and psychomotor epilepsy may not be totally impossible. The case also showed a typical productive psychotic episodes of Landolt, which could be treated favorably by 10 mg of intravenous Haloperidol. This method, named as "pathologization" of Helmchen, was found by the present author as a useful treatmental means of choice.


Homologs of vertebrate growth factors in Drosophila melanogaster and other invertebrates.
The molecular characterization of a number of loci that control developmental processes in invertebrates has revealed that a subset of these genes encode products that are homologous to vertebrate growth factors. Genetic analyses of the autonomy of action and molecular analysis of the patterns of expression of these genes have demonstrated that products of some of these loci (e.g., the EGF homologs, Notch, Delta, lin-12, and glp-1) appear to act in a cell-autonomous manner, while the products of other such loci (e.g., the TGF-beta homolog decapentaplegic and the murine int-1 homolog wingless) act in a nonautonomous manner. Studies of a number of invertebrate EGF homologs, including Notch, Delta, lin-12, and glp-1, for which we are beginning to achieve some reasonable understanding, reveal three common themes. First, each of these loci had been implicated in the determination of cell fates. The products of these loci appear to act at the level of single cells (i.e., they are required for the local choice between alternative determined states). The action of each of these loci within the context of determinative processes is clearly pleiotropic; mutations in each of these genes are correlated with multiple developmental defects. Second, the preponderance of evidence indicates that products of each of these loci function in a cell-autonomous manner during development. This shared character implies that these loci do not encode precursors of EGF-like molecules that act, in turn, as diffusible effectors in determinative decisions. It appears, rather, that these molecules function in association with the membranes of the cells in which they are produced and may constitute components of a class of receptors required for sensing diverse cues that specify particular cell fates during development. Third, we propose that EGF-like sequences found within each of these products function as protein-protein contact motifs that are essential for intermolecular interactions that involve membrane-bound molecules and are central to determinative decisions during development. Assignment of such a function to these sequences is consistent with recent findings indicating that EGF-homologous sequences found in urokinase (Apella et al., 1987) and blood coagulation factor IX (Rees et al., 1988) constitute sites that are required for binding to appropriate interacting proteins and are distinct from the respective "active" sites of each molecule. Within the context of this proposal, products of the EGF-homologous invertebrate genes noted above would participate in the transfer of information required for the specification of cell fate from the extracellular compartment to the cell interior.(ABSTRACT TRUNCATED AT 400 WORDS)


Electroacupuncture reduces rectal distension-induced blood pressure changes in conscious dogs.
It has been shown that acupuncture relieves symptoms of abdominal pain and bloating in patients with irritable bowel syndrome (IBS). However, the mechanism of beneficial effects of acupuncture still remains unproven. The aim of the present study was to investigate the mechanisms of the antinociceptive effects of acupuncture in conscious dogs. We evaluated the increase in mean arterial blood pressure (MAP) caused by rectal distension as an index of visceral pain. Electroacupuncture (EA; 10 Hz) at ST-36 (lower leg), but not at BL-21 (back), significantly reduced the increase in MAP in response to rectal distension (30 and 40 cm3). The antinociceptive effect of EA at ST-36 was abolished by pretreatment with naloxone (a central and peripheral opioid receptor antagonist) but not by naloxone methiodide (a peripheral opioid receptor antagonist). These results suggest that EA at ST-36 may reduce visceral pain via central opioid pathway. Acupuncture may be useful to treat visceral hypersensitivity in IBS patients.


[What may be expected of palliative chemotherapy of recurrent tumors of the upper airways and the digestive tract?].
In 16 patients with recurrences of squamous cell cancer of the upper aerodigestive system a combination-chemotherapy was performed in three cycles. On the 1st day of each cycle 20 mg/m2 methotrexate and 15 mg bleomycin, on the 2nd day 60 mg/m2 cis-diamminedichloroplatinum and from day 3 until day 8 15 mg bleomycin was given daily. Only half the patients received all 3 planned cycles. The overall response rate for complete or partial remission (more than 50% tumor-shrinkage) was 37% (1 complete, 5 partial remissions). Median duration of remissions was 2.6 months (1-6 months). Life quality (modified Karnowsky Index) was improved in 5 patients, tumor pain could be reduced in 7 patients. The median survival time was 4.3 months. The results are compared to those of other authors.


Utilizing artificial neural network to simulate and predict the hydraulic performance of free water surface constructed wetlands.
Optimizing the hydraulic performance of free water surface constructed wetlands (FWS CWs) is of great economic and ecological value. However, there is a complex nonlinear relationship between the hydraulic performance and design parameters of FWS CWs. In this study, an artificial neural network (ANN) was applied to simulate and predict the hydraulic performance corresponding to different combinations of design parameters, and orthogonal design L9 (34) was used to determine the optimal combination of the important hyperparameters of the ANN. Based on the convenient scenario prediction ability of ANN, sensitivity analysis of different design parameters was carried out by the control variate method and full factor experiment. The results showed that the combination of 3 hidden layers, 15 neural nodes in each hidden layer, 0.001 learning rate, and 8 batch sizes was optimal for the established ANN model, achieving a coefficient of determination of 0.828 in the validation set and a satisfactory prediction effect in the test set. The narrow feature distribution interval in the training set restricted the generalization ability of the ANN model to some extent. Of the four continuous design parameters, the water depth and aspect ratio had an important influence on the effective volume ratio. The layout of inlet and outlet was the most influential design parameter, as confirmed by the full factor experiment of five factors and four levels. The established ANN allowed real-time implementation in an extended scenario at a low cost. This study suggests that the ANN can simultaneously project complex and uncertain effects of several design parameters on wetland performance. In future research, acquiring further comprehensive, impartial, and unbiased experimental datasets is necessary to establish a more robust and generalizing ANN model that can guide the optimal design of FWS CWs.


The formation of helical tubular vesicles by binary monolayers containing a nickel-chelating lipid and phosphoinositides in the presence of basic polypeptides.
Binary lipid monolayers consisting of equimolar proportions of a phosphoinositide and a nickel-chelating lipid formed helical tubular vesicular structures, which appeared to be induced and/or stabilized by myelin basic protein (MBP). Another basic polypeptide, poly-L-lysine, had a similar effect but not to as great a degree as MBP; the proteins thus appeared to act as polycations. Although, the nickel-chelating lipid is a synthetic product, other endogenous divalent cations such as Zn(2+), as well as phosphoinositides, are integral and dynamic components of the myelin sheath in vivo. There, comparable helical tubular structures might represent a means for sequestration of these lipids into domains of high local concentration, perhaps in regions where the membrane is greatly curved.


A national program for lowering high blood cholesterol.
The National Institutes of Health have begun a new National Cholesterol Education Program. This program is modeled on the 15-year-old National High Blood Pressure Education Program, which has played a major role in improving the detection and treatment of hypertension in this country. Similar success can be predicted for the National Cholesterol Education Program, given the similarity between these two risk factors--hypertension and cholesterol--in (1) the accumulated scientific evidence for the benefit of intervention, (2) the availability of classification and treatment guidelines, and (3) the approach to professional and public health education programs. The new National Cholesterol Education Program guidelines recommend that all adults undergo a blood cholesterol measurement at least once every 5 years. Patients with a level greater than 200 mg/dl (confirmed by a second measurement) should be advised to adopt a step 1 fat-controlled diet. Patients with a cholesterol level greater than 240 mg/dl are candidates for intensive treatment with step 2 diet and sometimes drugs, as are those in the 200 to 240 mg/dl range who are at especially high risk because they already have coronary heart disease or two other risk factors. However, drugs for lowering blood cholesterol levels should be used only when the indication has been confirmed by measurements of low-density lipoprotein cholesterol and as a supplement to continuing the dietary treatment.


Comparison of Non-Gated vs. ECG-gated CT Angiography of Fontan Circulation in Patients with Implanted Stents in Pulmonary Branches.
Motion artifacts may degrade CT examination of Fontan pathway and hinder accurate diagnosis of in-stent restenosis. We retrospectively compared ECG-gated multi-detector computed tomography (CT) with non-ECG-gated CT in order to demonstrate whether or not one of the methods should be preferred. The study included 13 patients with surgically reconstructed Fontan pathway. A total of 16 CT examinations were performed between February 2010 and November 2015.The incidence of motion artifacts in Fontan pathway and pulmonary branches were analysed subjectively by two readers. The effective dose for each examination was calculated. Just in one non-gated CT examination was evidence of motion artifact in distal part of left pulmonary artery. The mean normalized effective radiation dose was 2.33 mSv (±0.62) for the non-ECG-gated scans and 4.55 mSv (±0.85) for the ECG-gated scans (p ≤ 0.05). Non-gated CT angiography with single phase reconstruction significantly reduces radiation dose without loss of image quality compared with ECG-gated CT angiography.


Editorial Commentary: Platelet-Rich Plasma Injections Produced a Significant Improvement in Most Patients With Rotator Cuff Tendinopathy.
Platelet-rich plasma (PRP) is an autologous blood product containing a high concentration of platelets, growth factors, and cytokines, which basic science studies have shown may improve tendinopathy. However, there is controversy over its clinical efficacy with randomized controlled trials and subsequent meta-analysis finding mixed results when treating shoulder rotator cuff tendinopathy. The effect of leukocyte concentration on PRP has been shown to be paramount, with different concentrations being favored for different pathologies. In those with tendinopathy, it is unclear whether leukocyte-rich or leukocyte-poor PRP is superior. Recent research shows that PRP injections produced a significant improvement in most patients with rotator cuff tendinopathy. However, improvement in symptoms and functional outcomes is worse in patients who have a partial-thickness rotator cuff tear compared with isolated tendinopathy without a partial tear. PRP may be more advantageous than corticosteroids. Both function as anti-inflammatories, but PRP may be potentially anabolic, whereas as corticosteroids have a catabolic effect on tendons, which may reduce repairability if patients proceed with surgery. Additionally, there are higher infection rates if patients ultimately go on to surgery within 3 months after corticosteroid injections. Ultimately, we must refine the indications for best use for PRP shoulder injections and determine the 5 R's: right patient, right drug, right dose, right route, and right time. Finally, we must remember that patients can first try conservative management, including physical therapy.


Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds.
A series of hydroxylic compounds (1-10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068-4003, 0.012-9.9 and 0.025-115 μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the KI values were calculated.


Trimipramine in physical illness with depression.
To assess whether tricyclic antidepressants are useful in patients with a serious physical disorder who develop symptoms of major depression, 42 medically ill outpatients who met RDC criteria for endogenous major depression and had a Raskin depression score of at least 7 were studied. The patients were randomly assigned to a 6-week trial of trimipramine or placebo under double-blind conditions. In the placebo group, depressive symptoms improved when the physical disorder improved; in the trimipramine group, improvement was seen in the depressive symptoms even when there was no concomitant improvement in physical condition.


Measurement of lipid profiles in the early postpartum period after hypertensive disorders of pregnancy.
The hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GHTN), are independent risk factors for future maternal cardiovascular disease. Epidemiologic evidence has demonstrated that women with HDP have abnormal cardiovascular risk factors in the early postpartum period, but this has not been fully characterized. This study aimed to assess the lipid profiles among women with PE, GHTN, and normal blood pressure in the first 4 years postpartum. Discharge Abstract Database was used to identify women hospitalized for a delivery in Calgary, Alberta, Canada, between January 2010 and December 2012 (N = 27,300). This was linked with Calgary Laboratory Services (for lipid levels) and the Pharmaceutical Information Network database (for lipid medication prescriptions) over the first 4 years postpartum (2010-2016). Logistic regression analysis was used to compare the frequency of lipid tests among HDP subtypes, adjusted for maternal age, gestational age at delivery, and parity. Only about half of the women with HDP had a lipid test in the first 4 years postpartum: 50.8% (PE) and 48.8% (GHTN) vs 41.5% in normotensive women (P < .001). Low-density lipoprotein cholesterol levels were significantly higher in women with HDP: 106.3 ± 35.2 mg/dL (2.75 ± 0.91 mmol/L) in PE, 102.5 ± 30.5 mg/dL (2.65 ± 0.79 mmol/L) in GHTN, and 96.7 ± 29.0 mg/dL (2.50 ± 0.75 mmol/L) in normotensive women (P < .001). Postpartum lipid screening helps identify women at risk of cardiovascular disease; however, only 50% of women with HDP were tested in the first years postpartum. As such, an early opportunity for primary CVD prevention strategies in young women may be lost.


Novel adaptive law for super-twisting controller: USV tracking control under disturbances.
A novel adaptive super-twisting control algorithm, for Unmanned Surface Vehicles (USV) tracking control is presented. The proposed adaptive law is obtained using a Lyapunov approach, to analyze the system closed-loop stability. Furthermore, several conditions are given to guarantee robustness in presence of unknown bounded disturbances/uncertainties, chattering mitigation and the finite-time convergence. This adaptive control strategy has the advantage that the controller gains, which are in terms of a single control parameter, requires adjusting a small number of parameters compared with other adaptive strategies, moreover and its dynamics is smooth, improving the controller performance. To assess the proposed control methodology effectiveness, a trajectory tracking control is designed and implemented on an unmanned surface vehicle under the action of bounded unknown uncertainties and external perturbations. Numerical simulations and experimental results conducted with a vessel prototype demonstrate the performance and advantages under payload variations and external environmental conditions. Finally, a comparative study between the proposed approach with other adaptive super-twisting works has been conducted.


Estimation of magnesium level in type 2 diabetes mellitus and its correlation with HbA1c level.
Type 2 diabetes mellitus (T2DM) is a common disease; the total number of diabetes patients is expected to reach 366 million by 2030. Magnesium has received considerable attention for its potential role in improving insulin sensitivity and preventing diabetes and its cardiovascular complications. Hypomagnesaemia is linked to poor control of type 2 diabetes mellitus, and depletion of serum magnesium occurs exponentially with duration of disease. The aim of this study was to measure serum magnesium level and the correlation of magnesium level with HbA1c in type 2 diabetes mellitus. In this cross-sectional study, we included 100 diabetic patients; blood is taken for measurement of both magnesium and HbA1c levels. Patients with risk factors of magnesium deficiency were not included. Of the total 100 patients recruited in our study, majority had diabetes for 8.0 years duration. The mean age of the patients was 53.97 ± 10.65 years, most of them were on oral hypoglycaemic agents (84.9%) followed by combination of oral hypoglycaemic agents and insulin (10.5%), and a small percentage were on insulin alone (4.7%). The mean of serum magnesium and HbA1c levels was 1.88 ± 0.25 mg/dL and 8.38% ± 1.53%, respectively. The majority of the patients had a normal level of magnesium (95.0%); however, most of them had uncontrolled blood glucose (82.0%). The study showed that the serum magnesium level and HbA1c are not significantly correlated (P = 0.462). Normal magnesium levels were observed in majority of patients, there is no significant correlation between serum magnesium and HbA1c levels in patients with T2DM, but larger-scale clinical trials are needed in future.


Benign solitary schwannoma of the foot. A case report and review of the literature.
Benign solitary schwannomas of the foot are a rare occurrence; only four cases have been previously reported. A schwannoma associated with the medial plantar nerve present for more than 40 years before the onset of symptoms was diagnosed in a 73-year-old man. Excision of the mass, with preservation of the involved nerve, was possible and successfully relieved symptoms.


Whether or not to accept a deceased donor kidney offer for a pediatric patient.
The expansion of the number of children on the deceased donor renal transplant waitlist has far outstripped the supply of organs in most countries, leading to numerous adjustments to increase supply and to maximize the utility of donor organs. The system for organ allocation varies by country based on local laws, priorities, and resources. Adjustments are made to optimize allocation, enhance post-transplant survival benefit, decrease unequal transplant access, and optimize utilization of donated kidneys. Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the human leukocyte antigen (HLA) match between the donor and the recipient, numerous recipient factors, the geographical location of the recipient, and the organ all affect the decision to accept the organ or not for a particular recipient. This decision must be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. In this manuscript, we highlight a representative case that helps to focus on important issues for the pediatric nephrologist to consider while making the decision to accept a deceased donor kidney offer for a particular pediatric patient.