Are current machine learning applications comparable to radiologist classification of degenerate and herniated discs and Modic change? A systematic review and meta-analysis.
Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists. A PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed. 1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets. This review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.


Driving better and safer HER2-specific CARs for cancer therapy.
Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity. Furthermore, we also discuss the main strategies for improving the safety of HER2 CAR-based cancer therapies.


Interpretation of anthropogenic impacts (agriculture and urbanization) on tropical deltaic river network through the spatio-temporal variation of stable (N, O) isotopes of NO(-)3.
For the first time, the dual isotope approach was applied to trace the sources of impacts and to identify the governing biogeochemical processes in a river network in the tropical deltaic region of the Red River (Vietnam). Our long term surveys concluded that water in this river network was severely impacted by anthropogenic activities. Analysis has shown strong spatio-temporal variation of nitrate isotopes; ranges of δ(15)N-[Formula: see text] and δ(18)O-[Formula: see text] were from -5 to 15 ‰ and from -10 to 10 ‰, respectively. Average values of δ(15)N-[Formula: see text] and δ(18)O-[Formula: see text] in the dry season, when fertilizer is applied, were 3.54 and 3.15 ‰, respectively. In the rainy season, the values changed to 6.41 and -2.23 ‰, respectively. Denitrification and biological assimilation were active throughout the year, but were especially enhanced during fertilization time. Mineralization of domestic organic matter and consequent nitrification of mineralized [Formula: see text] were the dominant processes, particularly during the rainy period.


An autopsy case of granulocyte colony-stimulating factor-producing pancreatic adenosquamous carcinoma.
A 60-year-old female was admitted to hospital with a continuous fever, a decreased appetite, and abdominal pain. Laboratory tests showed an elevated peripheral leukocyte count (13,800/μl) and increased C-reactive protein (19.1 mg/dl) and carbohydrate antigen 19-9 (4057 U/ml) levels. Abdominal contrast-enhanced computed tomography showed multiple bulky hypovascular nodules in the liver, swelling of the paraaortic lymph nodes, and a hypovascular mass (diameter 3.0 cm) in the pancreatic body. The serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were 172 pg/μl and 541 pg/µl, respectively. Liver biopsy specimens revealed an adenosquamous carcinoma, which was positively immunostained for G-CSF. We diagnosed the patient with G-CSF-producing pancreatic cancer with multiple metastases. Four courses of gemcitabine with dexamethasone and one course of nab-paclitaxel and gemcitabine were administered. Although the pancreatic tumor and paraaortic lymph node metastases decreased in size, the liver metastases continued to grow. The patient died 4 months after the diagnosis of pancreatic cancer. An autopsy resulted in the tumor being diagnosed as poorly differentiated adenosquamous pancreatic carcinoma, which was histopathologically G-CSF-positive. Although G-CSF-producing pancreatic adenosquamous carcinomas are extremely rare, they have been encountered more frequently in recent years. In such cases, chemotherapy combined with dexamethasone might be effective at temporarily improving the patient's condition.


Surgical exploration of 71 free flaps in crisis following head and neck reconstruction.
The medical records of patients who had undergone a free flap reconstruction after radical resection of oral cancer between January 2009 and December 2013 at the study hospital in China were reviewed retrospectively. Of the 1550 patients who underwent free flap reconstructions, 71 were explored for suspected flap compromise caused by postoperative thrombosis. Patient demographic data, clinicopathological data of the tumour, details of the free flaps, and operative findings were assessed, and the medical records were analyzed to identify the reasons for intervention and the outcomes. Of the 71 flaps in crisis, 47 (66.2%) were salvaged. Free flap failure was 6.2-times more likely to develop in patients undergoing surgical exploration after 72 h (95% confidence interval 2.090-18.197, P=0.001). Of the 19 flaps identified as subject to delayed exploration, 14 failed and three had partial necrosis. Free flap failure was 3.4-times more likely to develop in patients with perforator flaps (95% confidence interval 1.222-9.719, P=0.019). The early detection of free flap failure is critical to flap salvage. The salvage success rate decreases significantly at >72 h after the initial operation. It appears to be more difficult to salvage a perforator flap.


Expression of genes that regulate follicle development and maturation during ovarian stimulation in poor responders.
Sex hormone-binding globulin (SHBG), androgen receptor (AR), LH beta polypeptide (LHB), progesterone receptor membrane component 1 (PGRMC1) and progesterone receptor membrane component 2 (PGRMC2) regulate follicle development and maturation. Their mRNA expression was assessed in peripheral blood mononuclear cells (PBMC) of normal and poor responders, during ovarian stimulation. Fifty-two normal responders and 15 poor responders according to the Bologna criteria were enrolled for IVF and intracytoplasmic sperm injection and stimulated with 200 IU of follitrophin alpha and gonadotrophin-releasing hormone antagonist. HCG was administered for final oocyte maturation. On days 1, 6 and 10 of stimulation, blood samples were obtained, serum hormone levels were measured, RNA was extracted from PBMC and real-time polymerase chain reaction was carried out to identify the mRNA levels. Relative mRNA expression of each gene was calculated by the comparative 2-DDCt method. Differences between mRNA levels of each gene on the same time point between the two groups were not significant. PGRMC1 and PGRMC2 mRNA levels were downregulated, adjusted for ovarian response and age. Positive correlations between PGRMC1 and AR (standardized beta = 0.890, P < 0.001) from day 1 to 6 and PGRMC1 and LHB (standardized beta = 0.806, P < 0.001) from day 1 to 10 were found in poor responders. PGRMC1 and PGRMC2 were positively correlated on days 6 and 10 in normal responders. PGRMC1 and PGRMC2 mRNA are significantly decreased during ovarian stimulation, with some potential differences between normal and poor responders.


Steroid-induced 'granulomas' in hypertrophic scar.
Intralesional steroids injected into hypertrophic scars and keloids can result in histiocytic and foreign body granulomatous reaction which may be confused with focal mucinosis or necrobiotic process such as rheumatoid nodule. An awareness of this possibility might avoid unnecessary investigations in the patient.


Photolabile micropatterned surfaces for cell capture and release.
A method for capture and release of cells was developed using a photolabile linker and antibody-attached glass surface with a poly(ethylene glycol) (PEG)-pattern.


Changes of cardiac and skeletal muscle in pigs following transport stress. An electron microscopic study.
After lorry transport (60--120 min), fattening pigs (100--120 kg living weight) with clinical signs of exhaustion and acute circulation insufficiency showed acute ultrastructural damage to the myocard and the skeletal muscle. These represent the morphological equivalent of a stress induced cardiomyopathy and are to be counted among the stress myopathies of the pig. These changes may be caused particularly by the high lactate production of the predominantly glycolytically operating skeletal muscles and by the effects of cardial catecholamine release following transport stress. Attention is drawn to the model character of these changes for similar processes in humans.


The between-day reproducibility of fasting, satiety-related analytes, in 8 to 11year-old boys.
The aim of the present study was to establish the between-day reproducibility of fasting plasma GLP-17-36, glucagon, leptin, insulin and glucose, in lean and overweight/obese 8-11year-old boys. A within-group study design was utilised wherein the boys attended two study days, separated by 1week, where a fasting fingertip capillary blood sample was obtained. Deming regression, mean difference, Bland-Altman limits of agreement (LOA) and typical imprecision as a percentage coefficient of variation (CV %), were utilised to assess reproducibility between-days. On a group level, Deming regression detected no evidence of systematic or proportional bias between-days for all of the satiety-related analytes however, only glucose and plasma GLP-17-36 displayed low typical and random imprecision. When analysed according to body composition, good reproducibility was maintained for glucose in the overweight/obese boys and for plasma GLP-17-36, in those with lean body mass. The present findings demonstrate that the measurement of glucose and plasma GLP-17-36 by fingertip capillary sampling on a group level, is reproducible between-days, in 8-11year-old boys. Comparison of blood glucose obtained by fingertip capillary sampling can be made between lean and overweight/obese 8-11year-old boys. Presently, the comparison of fasting plasma GLP-17-36 according to body weight is inappropriate due to high imprecision observed in lean boys between-days. The use of fingertip capillary sampling in the measurement of satiety-related analytes has the potential to provide a better understanding of mechanisms that affect appetite and feeding behaviour in children.


X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development.
HUWE1 is a HECT-domain ubiquitin E3 ligase expressed in various tissues. Although HUWE1 is known to promote degradation of the tumor suppressor p53, given a growing list of its substrates, in vivo functions of HUWE1 remain elusive. Here, we investigated the role of HUWE1 in the female reproductive system. Homozygous deletion of Huwe1 in mouse oocytes of primary follicles caused oocyte death and female infertility, whereas acute depletion of HUWE1 protein by Trim-Away technology did not impact oocytes from antral follicles. Interestingly, oocytes from Huwe1 heterozygous females matured and fertilized normally, but the majority of embryos that lacked maternal Huwe1 were arrested at the morula stage after fertilization. Consequently, Huwe1 heterozygous females only produced wild-type pups. Concomitant knockout of p53 did not recover fertility of the Huwe1 knockout females. These findings make HUWE1 a unique and critical maternal factor indispensable for maintaining the quality of oocytes and embryos.


A peculiar new Helina Robineau-Desvoidy (Diptera: Muscidae) from Mexico and Panama.
Helina sinaloensis n. sp. (Diptera: Muscidae) is described and illustrated from Mexico and Panama. The new species shows a unique combination of characters and can be distinguished from the other species of the genus by the prosternum with lateral cilia, pre-alar seta absent, anepimeron bare, katepimeron setulose, postalar wall setulose and scutellum with setulae on lateroventral margin.


Study of two tungstates Ca0.5 Cd0.5 WO4 and Ca0.2 Cd0.8 WO4 by transmission electron microscopy.
To better understand the role of crystal structures and local disorder in the photonic properties of the system (1 - x)CaWO4 - xCdWO4 with 0 < x < 1, two specific phases with compositions x = 0.5 (scheelite phase) and 0.8 (wolframite phase) have been studied by scanning and transmission electron microscopies. High-resolution electron microscopy images and image simulations, associated with X-ray diffraction data, allowed confirming the lattices and space groups I41 /a and P2/c of the two scheelite and wolframite phases, at the local scale. The electron microscopy data show the existence of a high degree of crystallization associated with statistical distribution of Ca or Cd atoms on a Ca1- x Cdx site in each lattice.


Orthopoxvirus strains defective in surface antigen induction.
Various strains of vaccinia, variola, whitepox, monkeypox and cowpox viruses were examined for their capacity to induce a specific early antigen detectable on the surface of infected cells. The Elstree strain of vaccinia, two strains of variola minor and white variants of cowpox and monkeypox viruses lacked the capacity to induce the antigen. Variation of the parent cowpox and monkeypox viruses to white variants was always accompanied by the loss of the antigen-inducing capacity.


Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up.
35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (PHV) the INR remained below 2.0 for 0-19d (median 7) with no thromboembolic events. 10 patients received heparin, although a therapeutic level was rarely achieved. 13 patients with PHV were restarted on OAC and followed for a median 23.5 months. One patient had recurrent intracranial bleeding. 3/13 patients had cerebral embolic events despite anticoagulation. We conclude that in PHV patients temporary cessation of OAC is safe and the risk of recurrent bleeding after restarting OAC is low.


Modulation of MRP1-like efflux activity in human erythrocytes caused by membrane perturbing agents.
The effect of membrane perturbing agents on the efflux (37 degrees C, 60 min) of the fluorescent probe 2', 7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was studied. Several anionic amphiphiles (detergents) markedly inhibited BCPCF efflux (IC50 < or = 40 microM). Most zwitter-ionic amphiphiles were inefficient inhibitors. Non-ionic and cationic amphiphiles had minor effects or increased efflux. Of the aliphatic inhibitors, C12-homologues were the most efficient. Hexanol, ethanol, methyl-beta-cyclodextrin (MbetaCD) and diamide (+ washing) did not influence BCPCF efflux. It is suggested that amphiphiles affect BCPCF efflux by modulating multi-drug resistance protein 1 (MRP1, ABCC1) activity. A negative charge of amphiphiles is essential for the inhibitory effect, while alkyl chain length modulates inhibition. MRP1-mediated BCPCF efflux appears to be relatively insensitive to non-specific plasma membrane modification.


Richer color vocabulary is associated with better color memory but not color perception.
The potential interaction between color naming and psychophysical color recognition has been historically debated. To study this interaction, here we utilized two approaches based on individual differences in color naming and variation of color name density along the color wheel. We tested a pool of Persian speaking subjects with a simple color matching task under two conditions: perceptual and memory-based matching. We also asked subjects to freely name 100 evenly sampled hues along the color wheel. We found that, individuals who possess more names to describe the color wheel have a strong edge in color memorization over those with fewer names. Nevertheless, having more or fewer color names was not related to the subjects' performance in perceptual color matching. We also calculated the density of color names along the color wheel and observed that parts of the color wheel with higher density of color names are held in memory more accurately. However, similar to the case of individual differences, the density of color names along the wheel did not show any correlation with perceptual color matching performance. Our results demonstrate a strong link between color naming and color memorization both across different individuals and different parts of the color wheel. These results also show that low-level perceptual color matching is not related to color naming, suggesting that the variation in color naming-among the individuals and across the color wheel-is neither the cause nor the effect of variation in low-level color perception.


Psychopathology in children of inpatients with depression: a controlled study.
One quarter of 29 parents hospitalized for depression had children with episodes of depression (eight out of a total of 75 children). None of the children in 41 families with well parents had episodes of depression (a total of 152 children). The differences were significant at the .01 level. It is suggested that symptoms "equivalent" to depression such as hyperactivity, deviant behavior, and learning difficulties are not required in establishing clinical depression in childhood. The methodological shortcomings in this study were discussed.


Discussing coronary risk with patients to improve blood pressure treatment: secondary results from the CHECK-UP study.
Hypertension is common among patients with dyslipidemia but is often poorly treated. The objective of this analysis was to evaluate how a decision aid, used by primary care physicians to improve lipid therapy, impacted on the treatment of hypertension. Data were analyzed from patients enrolled in a randomized trial focusing primarily on the treatment of dyslipidemia. Patients received usual care or a coronary risk profile every three months to monitor the risk reduction following lifestyle changes and/or pharmacotherapy to treat dyslipidemia. Hypertension management was assessed based on a post hoc analysis of individuals whose blood pressure exceeded current national hypertension guidelines. There were 2,631 subjects who completed the study. Among 1,352 patients without diagnosed hypertension, 30% were above target on at least three consecutive visits. Among 1,279 individuals with known hypertension, 69% were above target on at least two consecutive visits. Overall, patients receiving risk profiles were more likely to receive appropriate antihypertensive therapy (OR = 1.40, 95% CI 1.11-1.78) compared to those receiving usual care. After adjustment for inter-physician variability and potential confounders, the use of the risk profile was associated with an increased likelihood of starting therapy (OR = 1.78, 95% CI 1.06-3.00) or modifying therapy (OR = 1.40, 95% CI 1.03-1.91). In this clinical trial of dyslipidemia management, inadequately controlled hypertension was common, occurring in nearly 50% of individuals. Ongoing coronary risk assessment was associated with more appropriate blood pressure management. Cardiovascular risk assessment decision aids should be further evaluated in a randomized trial of hypertension therapy.


Arrhythmia detection and classification using ECG and PPG techniques: a review.
Electrocardiogram (ECG) and photoplethysmograph (PPG) are non-invasive techniques that provide electrical and hemodynamic information of the heart, respectively. This information is advantageous in the diagnosis of various cardiac abnormalities. Arrhythmia is the most common cardiovascular disease, manifested as single or multiple irregular heartbeats. However, due to the continuous manual observation, it becomes troublesome for experts sometimes to identify the paroxysmal nature of arrhythmia correctly. Moreover, due to advancements in technology, there is an inclination towards wearable sensors which monitor such patients continuously. Thus, there is a need for automatic detection techniques for the identification of arrhythmia. In the presented work, ECG and PPG-based state-of-the-art methods have been described, including preprocessing, feature extraction, and classification techniques for the detection of various arrhythmias. Additionally, this review exhibits various wearable sensors used in the literature and public databases available for the evaluation of results. The study also highlights the limitations of the current techniques and pragmatic solutions to improvise the ongoing effort.


"Lipid rescue" for tricyclic antidepressant cardiotoxicity.
Tricyclic antidepressant (TCA) toxicity results predominantly from myocardial sodium-channel blockade. Subsequent ventricular dysrhythmias, myocardial depression, and hypotension cause cardiovascular collapse. Animal studies have demonstrated the effectiveness of intravenous lipid-emulsion in treating TCA cardiotoxicity. We report a case of dothiepin (tricyclic antidepressant) overdose causing refractory cardiovascular collapse, which seemed to be successfully reversed with lipid-emulsion therapy (Intralipid(®); Fresenius, Cheshire, UK). Lipid emulsions are a potentially novel therapy for reversing cardiotoxicity seen in TCA overdose. Research is required into the role of lipid emulsion in the management of poisoning by oral lipophilic agents.


A new score for predicting neonatal very low birth weight mortality risk in the NEOCOSUR South American Network.
To develop and validate a model for very low birth weight (VLBW) neonatal mortality prediction, based on commonly available data at birth, in 16 neonatal intensive care units (NICUs) from five South American countries. Prospectively collected biodemographic data from the Neonatal del Cono Sur (NEOCOSUR) Network between October 2000 and May 2003 in infants with birth weight 500 to 1500 g were employed. A testing sample and crossvalidation techniques were used to validate a statistical model for risk of in-hospital mortality. The new risk score was compared with two existing scores by using area under the receiver operating characteristic curve (AUC). The new NEOCOSUR score was highly predictive for in-hospital mortality (AUC=0.85) and performed better than the Clinical Risk Index for Babies (CRIB) and the NICHD risk models when used in the NEOCOSUR Network. The new score is also well calibrated - it had good predictive capability for in-hospital mortality at all levels of risk (HL test=11.9, p=0.85). The new score also performed well when used to predict in hospital neurological and respiratory complications. A new and relatively simple VLBW mortality risk score had a good prediction performance in a South American network population. This is an important tool for comparison purposes among NICUs. This score may prove to be a better model for application in developing countries.


Dislocation of both interphalangeal joints of one finger.
A rare type of dislocation involving both interphalangeal joints of one finger is described. The mechanism of injury is discussed, and the importance of immobilizing the finger in the correct position is stressed.


Phenethyl isothiocyanate induces cell cycle arrest and reduction of alpha- and beta-tubulin isotypes in human prostate cancer cells.
This study was to investigate the effect of phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, on the expression of alpha- and beta-tubulins, which are the main components of microtubules in prostate cancer cells. Flow cytometry, light microscopy and western blot were used to study the cell cycle distribution, morphology changes and the expression of alpha- and beta-tubulins in prostate cancer cells treated with PEITC. The results showed that PEITC-induced G2-M cell phase arrest and inhibited the expression of alpha- and beta-tubulin proteins in a number of human prostatic carcinoma cell lines. Further, it is showed that this inhibitory effect could be reversed by antioxidant N-acetyl cysteine and proteasome inhibitor MG132. Finally, it is concluded that PEITC inhibited the expression of alpha- and beta-tubulins in prostate cancer cells, which is at least related to the oxygen reaction species and protein degradation.


Experimental allergic encephalomyelitis: a neurourological study.
To assess the neurourological disturbances produced by the perivascular inflammatory process in the acute phase of experimental allergic encephalomyelitis, we carried out a controlled study. Forty-six New Zealand male rabbits were inoculated with an encephalitogenic preparation. Twenty-seven of them developed neurological deficits in an average of 9.3 days postinoculation. A sample of 19 subjects was used as a control. The subjects were studied within 2 days after the manifestation of the first sign of encephalomyelitis. An average of eight successive cystosphincterograms were recorded. Their entire central nervous system was removed intact and suspended in 10% neutral buffered Formalin solution for 2 weeks, then cut into segments, embedded in paraffin, and finally stained with hematoxylin-eosin and Luxol Fast Blue. The results demonstrated a significant reduction of mean vesical capacity, maximum urethral pressure, and mean urethral pressure in the group with encephalomyelitis. Furthermore, we found a significant negative correlation between the average number of cellular perivascular infiltrates in the spinal sacral segment and urethral pressures. The results showed a significant negative correlation between supreamesencephalic inflammation and mean vesical capacity.


Suppressors of RNA silencing encoded by plant viruses and their role in viral infections.
RNA silencing as a robust host defense mechanism against plant viruses is generally countered by virus-encoded silencing suppressors. This strategy is now increasingly recognized to be used by animal viruses as well. We present here an overview of the common features shared by some of the better studied plant viral silencing suppressors. We then briefly describe the characteristics of the few reported animal viral suppressors, notably their extraordinary ability of cross-kingdom suppression. We next discuss the basis for biased protection of viral RNA and subviral parasites by silencing suppressors, the link between movement and silencing suppression, the influence of temperature on the outcome of viral infection and the effect of viral silencing suppressors on the microRNA pathway.


On the thermodynamical and biological interpretation of the Gompertzian mortality rate distribution.
"Thermodynamical" foundations of a Gompertzian representation of mortality rate distribution vs. age are reviewed. The two fundamental assumptions of the original model (as developed by Strehler and Mildvan) are: (1) challenges that threaten the lives of organisms of a given species have an exponential distribution in harmfulness; and (2) vitality ("energetic" reserve to be used to counteract the challenges and restore proper function of the organism) declines linearly with age. It is proposed that the external environment should not only be characterized by a "temperature", but also by a "pressure" (related to the average time between successive hits). While recent progress of health sciences have essentially lowered the "temperature" factor, future progress might also lower the "pressure" factor. The effect of this would be to provide only a slight extension of observed longevity in humans. Internal cause(s) of ageing that lead to death are not specified in the model (except that they should be compatible with the linear decline in vitality). It is shown that death cannot be attributed to a slowing down of the recovery machinery that restores the organism's state following a challenge or a disease. A mechanism of this kind would instead lead to a gamma- (rather than a Gompertzian) distribution of ages at death, at great ages. Whatever the modalities of the challenges (they are, of course, not necessarily of a literally energetic nature), the model is shown to assume that death is linked to single, large amplitude challenges, rather than to the conjunction of independent, small amplitude damages. The concept of programmed longevity is proposed and integrated into the model. In this new model, Gompertzian distributions are characterized by the two parameters alpha (slope) and L (longevity) rather than by the two traditional parameters alpha and R0 (mortality rate at birth). This new presentation is more parsimonious than the original one, in that only alpha (not L) is temperature dependent. Models with fixed longevity automatically display a negative correlation between ln R0 and alpha, as was noted by Strehler and Mildvan. There exists a definite lag of time (of 23-29 years) between longevity and the most probable age at death. Assuming that the human species has a maximum programmed longevity of 120 years, this implies that the progress of health sciences will allow the present survival curve to evolve, not towards a rectangular shape as previously believed, but rather to a given limiting curve such as is depicted.


Low-cost commercial graphite-rich pencils subjected to electron irradiation for passive radiation dosimetry.
Various thicknesses of 2B grade polymer pencil lead graphite (PPLG) were used in the present study, which focussed on the alteration in crystalline lattice and the structural defect caused by the electron irradiation dosage ranging from 0.5 to 20 Gy delivered by an Elekta HD Linac. The fundamental trap parameters i.e. kinetics order (b), activation energy (E), and frequency factor (s) of the PPLG samples have been estimated using the initial rise and peak shape approaches by fitting the thermoluminescence (TL) glow peaks of the PPLG samples exposed to 20 Gy. The lifetime of the TL glow peak is also presented, which provides information on the stability of the TL signal at maximum temperatures. Raman, Photoluminescence (PL), and X-ray diffraction (XRD) spectra are being used to observe the structural changes that have occurred as a result of the radiation doses. These spectroscopies offer an understanding of the physical parameters that are related to the defects and taking part in the luminescence process. When all of the data are taken into account, it is anticipated that 0.3 mm PPLG is an effective material for dosimetry. The results of these lines of research are intended to educate the innovation of versatile graphite radiation dosimeters as a low-cost efficient system for radiation detection. The studied PPLG offers tissue equivalence as well as high spatial resolution, both are desirable criteria for a material to be used in the monitoring of ionising radiation or a variety of medical applications.


MAPseq: highly efficient k-mer search with confidence estimates, for rRNA sequence analysis.
Ribosomal RNA profiling has become crucial to studying microbial communities, but meaningful taxonomic analysis and inter-comparison of such data are still hampered by technical limitations, between-study design variability and inconsistencies between taxonomies used. Here we present MAPseq, a framework for reference-based rRNA sequence analysis that is up to 30% more accurate (F½ score) and up to one hundred times faster than existing solutions, providing in a single run multiple taxonomy classifications and hierarchical operational taxonomic unit mappings, for rRNA sequences in both amplicon and shotgun sequencing strategies, and for datasets of virtually any size. Source code and binaries are freely available at https://github.com/jfmrod/mapseq. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Electron transfer from excited tryptophan to cytochrome c: mechanism of phosphorescence quenching?
Parvalbumin, aldolase and liver alcohol dehydrogenase (ADH), proteins exhibiting long-lived phosphorescence lifetimes at room temperature, were examined for their reactivity with ferricytochrome c (cytochrome c Fe3+) as an external electron acceptor. Illumination of a reaction mixture containing protein and cytochrome c in the absence of oxygen brought about reduction of cytochrome c in relation to the duration of light. The largest portion of reduced cytochrome c was found with a sample containing ADH, where a 50% reduction of cytochrome c was reached after 5 min of illumination with a xenon lamp. Parvalbumin and aldolase were about half as effective under the same conditions. Several lines of evidence support the idea that the reaction of cytochrome c occurred by a long-range electron transfer from the excited triplet state of tryptophan. First, cytochrome c quenches the tryptophan phosphorescence and with parvalbumin, its bimolecular quenching rate constant, kq, was 2.9 x 10(6) M-1 s-1. Second, when the illuminated reaction mixture was supplied with 0.2 mM to 1 mM nitrite, a concentration range of nitrite which quenches the tryptophan phosphorescence but not the fluorescence, the amount of reduced cytochrome c on illumination markedly decreased. Finally, for all illuminated protein samples, the extent of cytochrome c reduction occurred parallel to a decrease in tryptophan content as judged from a decrease in fluorescence intensity and/or a decrease in tryptophan absorption at 280 nm.


Association of full blood count findings with risk of mortality in children with Klebsiella pneumoniae bloodstream infection at a south african children's hospital.
Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), is a leading cause of hospital-associated childhood mortality. There are limited data on how poor outcomes of KPBSI can be predicted in poorly resourced areas. This study aimed to assess if the profile of differential counts from full blood counts (FBC) taken at two time points in children with KPBSI could be used to predict the risk of death. We conducted a retrospective study of a cohort of children admitted to hospital between 2006 and 2011 with KPBSI. FBC collected within 48 h (T1) of blood culture and 5-14 days later (T2), were reviewed. Differential counts were classified as abnormal if they were higher or lower than laboratory ranges for normal results. The risk of death was assessed for each category of differential counts. Risk ratios adjusted (aRR) for potential confounders were used to estimate the effect of cell counts on risk of death using multivariable analysis. Data were stratified by HIV status. Of 296 children, median age 5 (IQR:2-13) months, 82 were HIV -infected. Ninety-five (32%) children with KPBSI died. Mortality in HIV-infected and uninfected children was 39/82 (48%) and 56/214 (26%), respectively (p < 0.001). Independent associations with mortality were observed with leucopenia, neutropenia and thrombocytopenia. Risk of mortality in HIV-uninfected children with thrombocytopenia at T1 and T2 was aRR 2.5 (95% CI: 1.34-4.64) and 3.18 (95% CI: 1.31-7.73) respectively, whereas the mortality risk in the HIV-infected group with thrombocytopaenia at T1 and T2 was aRR 1.99 (95% CI: 0.94-4.19) and 2.01 (95% CI: 0.65-5.99) respectively. Neutropenia in the HIV-uninfected group at T1 and T2, showed aRR 2.17 (95% CI: 1.22-3.88) and aRR 3.70 (95% CI 1.30-10.51) respectively, while in the HIV-infected group, they were aRR 1.18 (95% CI 0.69-2.03) and aRR 2.05 (95% CI 0.87-4.85) at similar time points. Leucopenia at T2 was associated with mortality in HIV-uninfected and HIV-infected patients, aRR 3.22 (95%CI 1.22-8.51) and aRR 2.34 (95% CI 1.09-5.04) respectively. Persistent high band cell percentage at T2 in HIV-infected children indicated a risk of mortality of aRR 2.91 (95% CI 1.20-7.06). Abnormal neutrophil counts and thrombocytopenia are independently associated with mortality in children with KPBSI. In resource-limited countries haematological markers have the potential to predict KPBSI mortality.


A sensitive and improved throughput UPLC-MS/MS quantitation method of total cytochrome P450 mediated arachidonic acid metabolites that can separate regio-isomers and cis/trans-EETs from human plasma.
A method for the detection and quantification of hydroxyl and epoxy arachidonic acid (AA) metabolites in human plasma was developed using liquid-liquid extraction, phospholipid saponification followed by derivatization of the acid moiety and liquid chromatographic tandem mass spectrometric detection. Derivatization with a pyridinium analog allowed for detection in the positive ion mode, greatly improving sensitivity and the stability of the more labile AA metabolites. The entire method utilizes a 96-well plate format, increasing sample throughput, and was optimized to measure 5-, 8-, 9-, 11-, 12-, 15-, 19-, and 20- hydroxyeicosatetraenoic acid (HETE), 5,6-, 8,9-, 11,12-, and 14,15- dihydroxyeicosatrienoic acid (DHET), and the regio- and cis-/ trans- isomers of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). The method was validated for its applicability over the FA concentration range found in human plasma. Using 100 μL aliquots of pooled human plasma, EET levels, particularly 5,6-EET, were observed to be higher than previously reported, with measured concentrations of 23.6 ng/ml for 5,6-EET, 5.6 ng/mL for 5,6-trans-EET, 8.0 ng/mL for 8,9-EET, 1.9 ng/mL for 8,9-trans-EET, 8.8 ng/mL for 11,12-EET, 3.4 ng/mL for 11,12-trans-EET, 10.7 ng/mL for 14,15-EET, and 1.7 ng/mL 14,15-trans- EET. This method is suitable for large population studies to elucidate the complex interactions between the eicosanoids and various disease states and may be used for quantitation of a wide variety of fattyacids beyond eicosanoids from small volumes of human plasma.


Neonatal paratesticular abscess mimicking perinatal torsion.
Management of perinatal torsion varies between centers from urgent surgical exploration and contralateral fixation to conservative nonoperative management. We present a case of paratesticular abscess in a neonate mimicking a perinatal torsion which may influence management of this condition in some cases.


An Observational Study Investigating Potential Risk Factors and Economic Impact for Bovine Ischaemic Teat Necrosis on Dairy Farms in Great Britain.
Bovine ischaemic teat necrosis (ITN) is an emerging disease of unknown aetiology that affects the teats of dairy cattle. It causes economic and animal welfare issues with many animals being culled. No effective treatments or epidemiological data to inform control strategies are currently available. The aim of this observational study was to investigate farmer-reported experiences and identify potential farm-level risk factors. In January 2018, a questionnaire was sent to a random sample of 1,855 Great Britain (GB) dairy farmers. A usable response rate of 12.3% was obtained. Fifty-one per cent [95% confidence interval (CI): 44.4-57.8%] of farmers reported having experienced ITN on their farm between 1985 and 2018. Rising numbers of farms indicated that ITN is an emerging disease with 46.3% of farmers reporting the first case in the 3 years up to 2018. At the animal level, 47.3% (95% CI: 38.7-55.9%) of the cases occurred during the first lactation and 78.9% (95% CI: 75.2-82.6%) within the first 90 days in milk. Only 20.8% (95% CI: 15.9-26.4%) of the cases were reported to recover, whereas 22.8% (95% CI: 17.8-28.5%) of the cases required culling. The remaining cases experienced complications such as loss of a teat and/or mastitis. From these data, the cost of ITN, through production losses and expenditure, was estimated to be £1,121 per farm per year. The costs were estimated at £720, £860 and £2,133 for recovered, complicated and culled cases, respectively. Univariable and multivariable logistic regression models were used to explore the associations between the presence of ITN on farm and various risk factors. The presence of udder cleft dermatitis (UCD) (odds ratio 2.80; 95% CI: 1.54-5.07; p < 0.01) and chapped teats (odds ratio 6.07; 95% CI: 1.96-18.76; p < 0.01) in the milking herd was associated with the presence of ITN at the farm level. This is the first national questionnaire of ITN within GB and highlights the association of UCD and chapped teats with ITN at the farm level. While there are many limitations and potential bias around farmer questionnaires, these findings highlight several key areas for further disease investigation and possible intervention.


The flow of an Eyring Powell Nanofluid in a porous peristaltic channel through a porous medium.
In a porous medium, we have examined sinusoidal two-dimensional transport enclosed porous peristaltic boundaries having an Eyring Powell fluid with a water containing [Formula: see text]. The determining momentum and temperature equations are solved semi-analytically by using regular perturbation method and Mathematica. In present research only free pumping case and small amplitude ratio is studied. Mathematical and pictorial consequences are investigated for distinct physical parameters of interest like porosity, viscosity, volume fraction and permeability to check the effects of flow velocity and temperature.


Inhibition of epidermal growth factor-induced cell transformation by tannins.
The mouse epidermal JB6 cell system is a well developed model for studying tumor promotion, and the JB6 Cl 41 promotion sensitive (P+) cell line, in which transformed colonies are induced by epidermal growth factor (EGF), was used to test the anti-tumor promoting effect of seven tannins and two triterpenoids. We found that six tannins, ellagitannins (compounds 1, 2, 3 and 4) and chromone gallates (compounds 6 and 7), significantly blocked EGF-induced cell transformation in a concentration-dependent manner. The inhibition of cell transformation by the tannins was not due to growth inhibition. The ellagitannins, but not the chromone gallates, significantly attenuated EGF-induced activator protein 1 (AP-1) activation, a transcription factor. Compounds 1 and 3, among the ellagitannins analysed, inhibited the EGF-induced phosphorylation of extracellular-signal regulated protein kinases and p38 kinases, which regulate AP-1 activation. On the other hand, compounds 3 and 4 suppressed EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. In addition, all tannins that blocked cell transformation markedly inhibited EGF-induced activation of Akt, a downstream effector of PI3K. Because signal-transduction pathways, including AP-1 and PI3K pathways, have been focused as prime targets for chemopreventive phytochemicals, our results suggest that inhibition by tannins of EGF-induced neoplastic transformation in JB6 cells is related to blocking of Akt activation, and also attenuation of AP-1 activation for ellagitannins.


Antimicrobial protection of two controlled release silver nanoparticles on simulated silk cultural relic.
Silver nanoparticles coated with organic-inorganic hybrid silica or inorganic silica have antimicrobial ability, and the coating can also effectively improve the dispersion and stability of the particles. The slow release of silver ions (Ag+) can improve the antimicrobial activity of silver nanoparticles. The synthesized nanoparticles are light yellow, which does not affect the look and feel of the silk cultural relics and meets the requirements of the principle of minimum interference. Two kinds of silver-based nanoparticles were synthesized: silver core-shell nanoparticle (Ag@mSiO2) and silver yolk-shell nanoparticle (Ag@YSiO2). The morphology, surface properties and Ag+ release efficiency of two nanoparticles were characterized. The antimicrobial effects of two nanoparticles on Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were compared. Both of Ag@mSiO2 and Ag@YSiO2 had uniform size and good stability. Two nanoparticles had pore structure and silver nanocore, which provided the basis for the dissolution and exchange of Ag+. Because more silver ions were released, Ag@mSiO2 had higher antimicrobial activity than Ag@YSiO2 for A. niger and P. citrinum. For various silk samples, Ag@mSiO2 exhibited excellent antimicrobial properties. Meanwhile, there was little change in the color and tearing strength of Ag@mSiO2 coated silk.


1,5-Anhydroglucitol × glycated hemoglobin A1c/100 as a potential biomarker for islet β-cell function among patients with type 2 diabetes.
This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A1c/100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels. Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes. The mean AHI level was 1.0 (0.7-1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9-1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-β, insulin generation index, insulin sensitivity index, and DI increased (all Pfor trend < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), showing a decreasing trend (Pfor trend < 0.05). The AHI could reflect the variation in glycemic disorder and the function of islet β cells. The lower the AHI, the worse the glycemic disorder, as well as the islet β-cell function.


A putative α-glucoside transporter gene BbAGT1 contributes to carbohydrate utilization, growth, conidiation and virulence of filamentous entomopathogenic fungus Beauveria bassiana.
Carbohydrate transporters are critical players mediating nutrient uptake during saprophytic and pathogenic growth for most filamentous fungi. For entomopathogenic fungi, such as Beauveria bassiana, assimilation of α-glucosides, in particular, trehalose, the major carbohydrate constituent of the insect haemolymph, has been hypothesized to represent an important ability for infectious growth within the insect hemocoel. In this study, a B. bassiana α-glucoside transporter homolog was identified and genetically characterized via generation of a targeted gene disruption mutant. Trehalose utilization was compromised in the mutant strain. In addition, inactivation of the α-glucoside transporter resulted in decreased conidial germination, growth, and yield on various carbohydrates (α-glucosides, monosaccharides and polyols) as compared to the wild-type strain. Insect bioassays revealed decreased mean lethal mortality time using both topical and intrahemocoel injection assays, although final mortality levels were comparable in both the mutant and wild type. Gene expression profiles showed altered expression of other putative transporters in the knockout mutant as compared to the wild type. These results highlighted complex sugar utilization and responsiveness in B. bassiana and the potential role for trehalose assimilation during fungal pathogenesis of insects.


Standpoints of Roma women regarding reproductive health.
Little is known about the reproductive health of Roma women in Slovenia. The aim of this study is to present the standpoints of Roma women regarding reproductive health, the degree to which primary healthcare services are available to Roma women and the reproductive health circumstances which lead most Roma women to decide to visit a gynaecologist. A qualitative research study was carried out. Forty-four adult Roma women from the Hudeje/Vejar settlement in the Dolenjska region, Slovenia, took part in the research. The collected material was processed by means of inductive (qualitative) content analysis. The coding procedure was supported by the QDA software Atlas.ti. Eighteen categories and six themes were identified that enable with the relevant codes an understanding of the standpoints of Roma women regarding reproductive health. The research results showed that the cultural needs of Roma women should be taken into account in their comprehensive healthcare treatment. Roma women wish for equal treatment when health is in question, drawing attention to better communication and the problem of ethnic discrimination in medical facilities. Roma women also feel a need to be educated and to receive professional advice, such as appropriate lectures and/or workshops dealing with reproductive health that would ensure them a higher quality of life over time. The research results call attention to the necessity of recognising both the need to educate Roma women as well as the need for different approaches to the provision of healthcare services in the field of reproductive health with such a sensitive group of female inhabitants. It will be necessary to familiarise them with preventive programmes and to implement such programmes, to inform them of possible diseases and to encourage them in a friendly and easy-to-understand manner to regularly visit their gynaecologist.


Magnesia-zirconia based mimetic biomembrane chromatography for predicting human drug absorption.
In this paper, a novel mimetic biomembrane chromatography stationary phase of magnesia-zirconia composite matrix were prepared with the Lewis acid-base interaction between phosphatidylcholine's residue phosphonate group and Lewis acid sites of magnesia-zirconia composite; the retention factors of a chemically diverse set of drugs on the new stationary phase were determined; the drugs logK(mbm) values were correlationed with the absorbed fraction of drugs orally administered in humans (%F(a)) and a hyperbolic relationship was obtained. Meanwhile, the relationship between the logK(mbm) values and hydrophobic parameters (logP(oct) and logD(oct)) were discussed. The usefulness of the new column for predicting oral drug absorption in humans is demonstrated by comparing this model with IAM, ILC and BMC models. Results show that the logK(mbm) values have good relationship with logK(W)(IAM), logK(BMC) and have moderate to fair relationship with logK(s) determined on four different ILC column (EPL, PC, PC-PE, PC-PS). Therefore, the logK(mbm) values can provide key information about the transport properties of drugs and this chromatographic model may be applicable for prediction of drug uptake through epithelial cell membranes during the drug discovery process.


Expression of the ExeAB complex of Aeromonas hydrophila is required for the localization and assembly of the ExeD secretion port multimer.
Aeromonas hydrophila secretes protein toxins via the type II pathway, involving the products of at least two operons, exeAB (gspAB) and exeC-N (gspC-N). In the studies reported here, aerolysin secretion was restored to C5.84, an exeA::Tn5-751 mutant, by overexpression of exeD alone in trans. Expression studies indicated that these results did not reflect a role of ExeAB in the regulation of the exeC-N operon. Instead, immunoblot analysis showed that ExeD did not multimerize in C5.84, and fractionation of the membranes showed that the monomeric ExeD remained in the inner membrane. Expression of ExeAB, but not either protein alone, from a plasmid in C5.84 resulted in increases in the amount of multimeric ExeD, which correlated with increases in aerolysin secretion. Pulse-chase analysis also suggested that the induction of ExeAB allowed multimerization of previously accumulated monomer ExeD. In C5.84 cells overproducing ExeD, it multimerized even in the absence of ExeAB and, although most remained in the inner membrane, an amount similar to that in wild-type outer membranes fractionated with the outer membrane of the overproducing cells. These results indicate that the secretion defect of exeAB mutants is a result of an inability to assemble the ExeD secretin in the outer membrane. The localization and multimerization of overproduced ExeD in these mutants further suggests that the ExeAB complex plays either a direct or indirect role in the transport of ExeD into the outer membrane.


Percutaneous ventricular assist device in hypertrophic obstructive cardiomyopathy with cardiogenic shock: bridge to myectomy.
We present the case of a 69-year-old woman with end-stage hypertrophic obstructive cardiomyopathy who developed cardiogenic shock. She underwent emergent placement of a percutaneous left ventricular assist device (TandemHeart) in the catheterization lab as a bridge support device until a septal myectomy could be performed as definitive treatment. This case suggests a novel and promising use of the TandemHeart as a bridge to myectomy.


Altered expression of major immune regulatory molecules in peripheral blood immune cells associated with breast cancer.
The purpose of this study was to clarify the alterations of major immune regulators in peripheral blood mononuclear cells (PBMCs) of cancer patients and to analyze the association with the disease progression in breast cancer patients. The study included 6 healthy volunteers (HVs), 12 primary breast cancer (PBC) patients, and 30 metastatic breast cancer (MBC) patients. The expression of immune regulators such as, CCR6, CD4, CD8, CD14, CD40, CD56, CD80, CTLA4, CXCR4, FOXP3, IDO-1, IDO-2, NKG2D, NRP-1, PD-1, and PD-L1 mRNA in PBMCs was measured by quantitative RT-PCR. Analysis of variance with contrasts was performed to find expression patterns of the three groups (HVs, PBC, MBC). We clarified the alterations of mRNA of major immune regulators PD-L1, FOXP3, CD80, CD40, and CD14 in PBMCs of cancer patients and the association of these alternations with disease progression. Furthermore, PD-L1 expression was correlated with serum interferon-γ production. Our data suggested that mRNA expressions of PD-L1, FOXP3, CD80, CD40 and CD14 in PBMCs are affected by disease progression. Understanding the roles of these various interactions will be of importance to future studies aiming to uncover biomarkers for predicting response to immune therapy.


Fatalities associated with NPS stimulants in the Greater Cologne area.
This study centres on the prevalence of new psychoactive substances (NPS) stimulant use, and its relevance as a cause of death amongst individuals between the ages of 12 and 35 in the greater Cologne area. An automated solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed for the determination of 97 stimulants in urine (including conventional stimulants, e.g. amphetamine and MDMA), of which 68 analytes were fully validated for quantification. Samples of urine or kidney tissue (in cases where urine was unavailable) of 268 deceased were collected, during autopsy, between January 2011 and May 2017 and analyzed. Blood (if available) was also investigated in cases where urine/kidney samples were tested positive for NPS. An intake of stimulants (including NPS stimulants) was proven in 50 cases. In 33 cases, only conventional stimulants were detected. A total of 17 cases were tested positive for NPS. Of the 17 NPS-positive cases, 13 were also tested positive for other conventional drugs of abuse (mostly amphetamine and MDMA). In six NPS-positive cases, at least three different NPS were proven to be ingested. Due to the determined blood concentrations, NPS was assigned as the leading cause of death, or of toxicological relevance, in the cause of death in only 5 cases. In two of the cases, NPS was judged to be a component of a multidrug poisoning, but of minor relevance.


[The effect of progesterone uterine therapeutic system on dysmenorrhoea: prostaglandin F2alpha levels in menstrual blood (author's transl)].
The menstrual flow of five dysmenorrhoeic women was collected, four cycles with and two cycles without local intrauterine administration of progesterone (Progestasert). The menstrual flow of three eumenorrhoeic women served as control. Menstrual blood was collected by tampons stored in butyl-alcohol saturated with water. Prostaglandin F2alpha (PGF2alpha) was measured after purification and extraction by radioimmunoassay. The PGF2alpha production rate and concentration per ml of menstrual blood from dysmenorrhoeic women differed significantly from those of eumenorrhoeic women. In the treated cycles the PGF2alpha levels were significantly decreased (2 alpha less than or equal to 0,01), corresponding to eumenorrhoeic levels. These values were in accordance with the clinical results and indicate that uterine PG-synthesis is under progesterone control.


Outcome of patients undergoing liver transplantation for primary sclerosing cholangitis.
The purpose of this study was to determine the outcome of patients with inflammatory bowel disease who underwent liver transplantation for primary sclerosing cholangitis. All patients who underwent liver transplantation for primary sclerosing cholangitis at our institution were identified. A review of patients' hospital and office charts was performed; all patients were then contacted, and a detailed survey was administered by telephone. Sixty-nine patients were identified. There were 53 males (76.8 percent) and 16 females, with a mean age of 45.3 (+/- 13.3) years. Fifty-two (75.4 percent) of the 69 patients had documented inflammatory bowel disease; of these, 40 had ulcerative colitis (76.9 percent), 11 had Crohn's disease, and 1 had indeterminate colitis. Thirty-one patients (60 percent) were diagnosed with inflammatory bowel disease before primary sclerosing cholangitis, with a mean interval to diagnosis of primary sclerosing cholangitis of 10.8 (+/- 10.3) years. Seven patients had both diagnoses made at roughly the same time, and 14 patients initially were diagnosed with primary sclerosing cholangitis and subsequently were found to have inflammatory bowel disease, with a mean interval of 5.2 (+/- 4.4) years; 5 (35.7 percent) of those 14 patients were only diagnosed with inflammatory bowel disease after their liver transplant. The mean time from diagnosis of primary sclerosing cholangitis to liver transplantation was 6.1 (+/- 4.9) years. Since their transplant, 30.8 percent of patients rated their colitis as worse, 38.5 percent felt it was unchanged, and 30.8 percent felt that their colitis was better controlled. Eight (15.4 percent) of the 52 patients with inflammatory bowel disease denied having any knowledge of an increased risk of colorectal neoplasia. Four patients have required colectomy for colorectal neoplasia after liver transplantation, at a mean of 4.7 years after transplantation. Of the patients with inflammatory bowel disease, 42 (80.1 percent) had at least 1 posttransplant surveillance colonoscopy. Eight of the remaining ten patients had a colectomy, leaving only two patients (3.8 percent) who had not been surveyed. However, only 32 (61.5 percent) of the patients with inflammatory bowel disease have been on a surveillance regimen that would approximately conform to current screening recommendations. The activity of inflammatory bowel disease after transplantation is highly variable. Patients appeared to lack knowledge of their increased risk for colorectal neoplasia. Colorectal cancer is an uncommon but important complication in patients after liver transplantation for primary sclerosing cholangitis, and ongoing surveillance is required. Patients may require education to increase their awareness of the cancer risk and compliance with surveillance.


Thermal trauma-induced changes in the synthesis of rat serum proteins.
Infliction of non-lethal scalding was found to cause an increase in the rate of incorporation of 35S-methionine into albumin and globulin fractions of rat serum proteins, the the increase being remarkably higher for alpha- and beta-globulins than for albumin and gamma-globulins The most pronounced enhancement was associated with the 60- and 70-kd constituents of beta-globulins, the 34-, 55- and 136-kd polypeptides of alpha-2-globulins and the 50-, 60-, 125- and 145-kd polypeptides of alpha-1-globulins. The response of serum proteins to the heat shock was similar, though the changes were significantly less pronounced.


Correction to: scBFA: modeling detection patterns to mitigate technical noise in large-scale single-cell genomics data.
Following publication of the original article [1], the following two errors were found in formulae.


Delirium and cerebrospinal fluid S100B in hip fracture patients: a preliminary study.
Delirium is associated with an increased risk of long-term cognitive decline, suggesting the possibility of concurrent central nervous system (CNS) injury. S100B is a putative biomarker of CNS injury and elevated serum levels in delirium have been reported. Here we hypothesize that delirium is associated with raised concentrations of cerebrospinal fluid (CSF) S100B. Forty-five patients with hip fracture aged over 60 and awaiting surgery under spinal anesthesia were assessed for delirium pre- and post-operatively. CSF S100B levels were measured in samples collected at the onset of surgery. Participants with pre-operative delirium (N = 8) had elevated Log10 CSF S100B (mean: -0.156; SD: 0.238) compared with those without delirium (mean: -0.306; SD: 0.162), Student's t-test t = 2.18, df = 43, p = 0.035. This study provides preliminary evidence of elevated CSF S100B in current delirium, consistent with findings in serum and with other studies showing elevated S100B in the presence of diverse forms of CNS injury.


Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart.
In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.


Expression of adrenomedullin mRNA in adrenocortical tumors and secretion of adrenomedullin by cultured adrenocortical carcinoma cells.
Immunoreactive-adrenomedullin concentrations and the expression of adrenomedullin mRNA were studied in the tumor tissues of adrenocortical tumors. Northern blot analysis showed the expression of adrenomedullin mRNA in tumor tissues of adrenocortical tumors, including aldosterone-producing adenomas, cortisol-producing adenomas, a non-functioning adenoma and adrenocortical carcinomas, as well as normal parts of adrenal glands and pheochromocytomas. On the other hand, immunoreactive-adrenomedullin was not detected in about 90% cases of adrenocortical tumors (<0.12 pmol/g wet weight (ww)). Immunoreactive-adrenomedullin concentrations ranged from 0.44 to 198.2 pmol/g ww in tumor tissues of pheochromocytomas and were 9.2 +/- 1.2 pmol/g ww (mean +/- SD, n = 4) in normal parts of adrenal glands. Adrenomedullin mRNA was expressed in an adrenocortical adenocarcinoma cell line, SW-13 and immunoreactive-adrenomedullin was detected in the culture medium of SW-13 (48.9 +/- 1.8 fmol/10(5) cells/24h, mean +/- SEM, n = 4). On the other hand, immunoreactive-adrenomedullin was not detectable in the extract of SW-13 cells (<0.09 fmol/10(5) cells), suggesting that adrenomedullin was actively secreted from SW-13 cells without long-term storage. These findings indicate that adrenomedullin is produced and secreted, not only by pheochromocytomas, but also by adrenocortical tumors. Undetectable or low levels of immunoreactive-adrenomedullin in the tumor tissues of adrenocortical tumors may be due to very rapid secretion of this peptide soon after the translation from these tumors.


Colon-specific mutual amide prodrugs of 4-aminosalicylic acid for their mitigating effect on experimental colitis in rats.
Mutual amide prodrugs of 4-aminosalicylic acid with D-phenylalanine and L-tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10 h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86-91% over a period of 20 h, with half-lives ranging between 343 and 412 min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.


Bone marrow and splenic histology in hairy cell leukaemia.
Hairy cell leukaemia is a rare chronic neoplastic B-cell lymphoproliferation that characteristically involves blood, bone marrow and spleen with liver, lymph node and skin less commonly involved. Histologically, the cells have a characteristic appearance with pale/clear cytoplasm and round or reniform nuclei. In the spleen, the infiltrate involves the red pulp and is frequently associated with areas of haemorrhage (blood lakes). The cells stain for B-cell related antigens as well as with antibodies against tartrate-resistant acid phosphatase, DBA44 (CD72), CD11c, CD25, CD103, CD123, cyclin D1 and annexin A1. Mutation of BRAF -V600E is present and antibody to the mutant protein can be used as a specific marker. Bone marrow biopsy is essential in the initial assessment of disease as the bone marrow may be inaspirable or unrepresentative of degree of marrow infiltration as a result of the tumour associated fibrosis preventing aspiration of the tumour cell component. Bone marrow biopsy is important in the assessment of therapy response but in this context staining for CD11c and Annexin A1 is not helpful as they are also markers of myeloid lineage and identification of low level infiltration may be obscured. In this context staining for CD20 may be used in conjunction with morphological assessment and staining of serial sections for cyclin D1 and DBA44 to identify subtle residual infiltration. Staining for CD79a and CD19 is not recommended as these antibodies will identify plasma cells and can lead to over-estimation of disease. Staining for CD20 should not be used in patients following with anti-CD20 based treatments. Down regulation of cyclin D1 and CD25 has been reported in patients following BRAF inhibitor therapy and assessment of these antigens should not be used in this context. Histologically, hairy cell leukaemia needs to be distinguished from other B-cell lymphoproliferations associated with splenomegaly including splenic marginal zone lymphoma, splenic diffuse red pulp small B-cell lymphoma and hairy cell leukaemia variant. This can be done by assessment of the spleen but as this is now rarely performed in this disorder distinction is almost always possible by a combination of morphological and immunophenotypic studies on bone marrow trephine biopsy, which can be supplemented by assessment of BRAF-V600E mutation assessment in borderline cases.


[Implantable cardioverter defibrillator].
This article aims to give an overview over important articles in the field of implantable cardioverter defibrillator (ICD) therapy in 2012. Important publications concern analyses on therapy efficacy and safety of the subcutaneous ICD, gender-specific differences in the complication rate and prognosis after ICD implantation, the necessity of intraoperative testing of the defibrillation threshold and the impact of preventive measures to reduce ICD therapies on prognosis after device implantation. The relevance of the study findings for daily clinical practice is briefly discussed.


A Decision Support System for the Prediction of Drug Predisposition Through Personality Traits.
The topic of recreational drug consumption is still largely controversial around the globe. Factors that predispose people and lead to initial drug use include, among others, personality traits. The study of personality is a well-established domain of psychology, with multiple models having been developed, which are capable of predicting predisposition to a certain degree. Furthermore, addiction and other mental health issues carry stigma, which inhibits affected people from reaching out for support. Online web-based tools and automated systems have shown to be fairly effective in tackling stigma by eliminating the human factor. As such, a web-based decision support system (DSS) is developed and made publicly available, in order to inform users about their drug predisposition through an online personality survey. To accomplish the latter, the DSS utilizes multiple machine learning algorithms to extract patterns of personality, as modeled by the Big Five personality traits. The utilized algorithms turn out to be effective at predicting drug use for most of the 17 drugs that are considered, even in cases of high-class imbalance.


Field fate of Amaranthus patulus seeds subjected to leaf-canopy inhibition of germination.
The germination of seeds of Amaranthus patulus Bertol., is known to be sensitive to leaf-transmitted light. Seeds were enclosed in transparent polyester-mesh envelopes and placed horizontally in 10-cm deep soil or on the soil surface, beneath a closed vegetation cover in the field. Changes in the numbers of firm intact seeds and of germinable seeds were traced for up to 3 years by periodical retrievals and germination tests. Rapid loss of germinable seeds, mainly due to germination, was observed in the buried seed population, in which only 20% of seeds maintained their germinability after 1 year, and a negligible number after 3 years. In contrast, the seeds placed on the soil surface maintained germinability relatively well: over 80% of seeds remained germinable after 1 year and a low percentage still preserved their germinability after 3 years. Assuming exponential decay in germinability, the decay rates on and in the soil were calculated from the data of the 1-year experiment to be 0.21 and 0.84 year-1 respectively. The fate of seeds that were exposed to canopy light on the soil for a month and then buried was shown to be almost the same as that of the seeds which had been continuously in 10-cm deep soil. Correspondingly, the possibility of the induction of secondary (induced) dormancy by exposure to canopy light was excluded in a laboratory experiment, in which it was found that the imbibed seeds suffering leaf-canopy inhibition of germination exuded some diffusible germination inhibitor responsible for apparent dormancy. Estimation of numbers of A. patulus in the seed bank of an early successional field showed that 3,500 seeds/m2 remained in the soil to the depth of 10 cm after 3 years' exclusion of the species following the production of 700,000 seeds/m2, by a population explosively established after experimental induction of secondary succession.


Optical and structural investigation on sodium borosilicate glasses doped with Cr2O3.
In this work, Sodium borosilicate glasses with chemical composition of 60% SiO2-20% B2O3-20%Na2O doped with different contents of Cr2O3 were prepared by melting-quenching method. Physical, structural and optical properties of glasses were investigated by studying density and molar volume, Fourier Transform Infrared (FT-IR) Spectra and UV-visible absorption spectroscopy. The results showed an increase in density of glasses with the increase of Cr2O3 that can be due to addition of oxide with high molar mass. The optical absorption spectra of un-doped glass reveals UV absorption due to trace iron impurities with no visible band however Cr2O3 doped glasses shows absorption in visible range that are characteristic. Increasing of Cr3+ ions in the glassy microstructure of samples provides a semiconducting character to Sodium borosilicate glass by reducing the direct and indirect optical band gaps of glass samples from 3.79 to 2.59 (ev) and 3.36 to 2.09 (ev), respectively. These changes could be attributed to the role of Cr3+ ions as the network former which asserts improvement of semiconducting behavior in presence of Cr2O3.


Pseudotumor cerebri syndrome in children: Clinical characteristic and re-classification.
To describe the clinical characteristics of children with pseudotumor cerebri syndrome (PTCS) who were diagnosed according to the modified Dandy criteria and to reclassify them according to the newly proposed diagnostic criteria by Freidman. This retrospective study included the period from January 2016-to July 2021. 50 patients were included; 34 males and 16 females with a male to female ratio of 2.1:1. The average age at onset of symptoms was 8 years. Obesity was noticed in 6 (12%) patients; 34 (68%) had symptoms upon presentation. The most common presenting symptom was headache (28 patients; 56%), papilledema was present in 33 (66%) patients. Most patients (37; 74%) had an initial cerebrospinal fluid (CSF) pressure ≥280 mmH2O. At last follow-up, papilledema resolved in 11/32 (34.3%) patients, and headache resolved in 17/23 (74%) patients. 22/50 (44%) patients fulfilled the definite criteria proposed by Freidman, 11/50 (22%) fulfilled the probable, 10/50 (20%) were categorized as possible, and 7 (14%) patients were categorized as unmet. PTCS is a chronic condition. Managing patients who do not have papilledema or who do not meet the newly proposed higher CSF pressure is challenging. Although, applying the newly proposed criteria captured most of our patients, however, around one quarter were managed based on clinical experience. This study indicates a strong need for future guidelines tailored specifically for children, taking into consideration that the cut-off point of CSF pressure might not be similar for all populations.


A new variant of chromosome 16.
A new variant of chromosome 16 with an additional C-band negative segment in the proximal region of the short arm is described. This variant chromosome was found in four cases, two of which were detected prenatally. In three probands the variant chromosome 16 was inherited from a phenotypically normal father.


Structural and functional characterization of major platelet membrane components derived by limited proteolysis of glycoprotein IIIa.
The authors isolated a product of proteolytic degradation of glycoprotein IIIa (GPIIIa) which is formed on the surface of human platelets during incubation with chymotrypsin and which was previously described as the 66 kDa platelet membrane component. This component migrated with an apparent Mr 62,400 in a non-reduced system of sodium dodecyl sulfate polyacrylamide gel electrophoresis. In a reduced system it yielded two major subunits migrating with apparent Mr 14,000-17,000 and 65,000. The low-molecular weight component began with the NH2-terminal sequence of GPIIIa (GPNICTTR...) and the larger component with residue 348 of GPIIIa (GKIRSKKA...) as deduced from a cDNA clone of this glycoprotein. The two subunits appeared to be linked by one or more S-S bridges supporting the contention that GPIIIa is a highly folded molecule on the platelet membrane. In contrast to GPIIIa, the '66 kDa component' did not bind to GRGDSPK-agarose, to fibrinogen-agarose nor to insolubilized monoclonal antibody recognizing the GPIIb/IIIa complex. The exposure of fibrinogen receptors during the course of incubation of platelets with chymotrypsin preceded the formation of the '66 kDa component' characterized in this study. An intermediate product of GPIIIa proteolysis migrating with an apparent Mr 120,000 in a non-reduced system and Mr 80,000 in a reduced system was identified as a precursor of the '66 kDa component'. The '120 kDa component' was not retained on GRGDSPK-agarose or on fibrinogen-agarose but it was retained on insolubilized antibody recognizing the GPIIb/IIIa complex. Incubation of platelets with porcine pancreatic elastase or human granulocytic elastase resulted in the formation of similar proteolytic degradation fragments.


Helospectin-like peptides: immunochemical localization and effects on isolated cerebral arteries and on local cerebral blood flow in the cat.
Helospectin I and II and helodermin are nonamidated, vasoactive intestinal peptide (VIP)-like peptides, isolated from the salivary gland venom of the lizards Heloderma suspectum and Heloderma horridum. Helospectin I has 38 amino acid residues and differs from helospectin II in that it has an additional serine residue at the C-terminus. Numerous nerve fibers containing helospectin-like immunoreactivity (LI) and a few fibers containing helodermin-LI were present in the adventitia and at the adventitia-media border of cat cerebral arteries. In the sphenopalatine ganglion, numerous nerve cell bodies containing helospectin-LI were seen. Double immunostaining revealed that helospectin-LI nerve cell bodies coexisted with VIP-containing cell bodies. Radioimmunoassay showed high levels of helospectin-LI in extracts of cerebral vessels from the circle of Willis (27.4 pg/mg [wt/wt]). Helospectin I and II and helodermin (10(-10) to 10(-6) mol/L) produced concentration-dependent relaxations of feline middle cerebral arteries amounting to 50% to 80% of precontraction induced by U46619. The maximum effects and the potency were similar to that of VIP. Neither of these peptides elicited endothelium-dependent relaxations. Intracerebral microinjection of helospectin and helodermin produced a moderate concentration-dependent increase of the cerebral blood flow of alpha-chloralose anesthetized cats. The maximum increase (21 +/- 5%) was observed after the injection of 5 microg helodermin, whereas 16 +/- 7% was seen with helospectin I and 19 + 5% with helospectin II. The results suggest that helospectin/helodermin-like peptides co-localize with VIP in perivascular nerve fibers originating in the sphenopalatine ganglion. They seem to have strong and potent vasodilator effects.


Alkali and alkaline earth elements in maternal serum and occurrence of orofacial clefts in offspring.
Alkali elements (AEs) and alkaline earth elements (AEEs) play critical roles in numerous physiological and pathological processes. However, the effects of maternal exposure to AEs and AEEs on the risk for fetal orofacial clefts (OFCs) remain unclear. We explored the associations between levels of eight AEs and AEEs in maternal serum during pregnancy and occurrence of fetal OFCs. Concentrations of four AEs and four AEEs in maternal serum of 130 OFC cases and 260 non-malformed controls were assessed. Multilevel mixed-effects logistic regression and bayesian kernel machine regression (BKMR) were performed to evaluate the single and combined effects, respectively, of exposure to AEs and AEEs on OFC risk. When individual elements were analyzed separately as categorical variables, the odds of OFCs increased by 2.08-fold (1.10-3.93) and 2.35-fold (1.24-4.45) for sodium and by 1.98-fold (1.04-3.77) and 1.92-fold (1.21-3.61) for strontium but decreased by 0.54-fold (0.29-0.98) and 0.42-fold (0.22-0.78) for potassium in the second and third tertiles, respectively, with the lowest tertile concentration being used as the referent. When all eight elements were considered as a mixture, potassium and calcium showed protective effects, whereas sodium and strontium increased odds of OFCs in the BKMR model. No joint effect on OFC risk was observed when the eight elements were considered as a mixture. Taken together, higher levels of sodium and strontium in maternal serum were associated with an increased odds of fetal OFCs, whereas higher levels of potassium in maternal serum were associated with a decreased odds of OFCs.


Prevalence of Lens Opacities in Adult Chinese Americans: The Chinese American Eye Study (CHES).
We determined the age- and sex-specific prevalence of posterior subcapsular (PSC), nuclear, cortical, and mixed lens opacities in a population-based sample of Chinese-American adults. A population-based sample of Chinese-Americans 50 years and older, from 10 census tracts in Monterey Park, CA, USA, underwent a detailed interview and a comprehensive clinical examination that included assessment of different types of lens opacities by the slit-lamp-based Lens Opacities Classification System II (LOCS II). All lens changes (including pseudophakia/aphakia), PSC, nuclear, and/or cortical opacities, were evaluated and graded. Of the 5782 eligible subjects, 4582 (79.2%) Chinese Americans aged 50 years and older completed a comprehensive eye examination. Of the participants with LOCS II grading (n = 4234/4582, 92%), 3.0% had PSC opacities, 38.1% had nuclear opacities, and 23.4% had cortical opacities. The prevalence of all lens changes was 48.0% for all age groups and was higher by 10-year increasing age groups (P < 0.0001). The prevalence of visual impairment in the better-seeing eye with cortical only, nuclear only, PSC only, and mixed opacities was 3.9%, 5.0%, 14.3%, and 9.4%, respectively. A total of 454 (9.9%) individuals had undergone cataract extraction in at least one eye. Chinese Americans have a high prevalence of visual impairment associated with lens opacities, and a high prevalence of nuclear opacities. Public health policies and programs designed to improve cataract detection and treatment could help reduce the burden of visual impairment in Chinese Americans.


First Confirmed Case of Canine Mortality Due to Dihydroanatoxin-a in Central Texas, USA.
The frequency of dogs becoming ill or dying from accidental exposure to cyanotoxins, produced by cyanobacteria, is increasing throughout the United States. In January and February of 2021, two dogs died and five dogs became ill after swimming in Lake Travis, central Texas, USA; one deceased dog (C1) was subjected to pathological testing. Algal materials, sediment samples, zebra mussel viscera, periphyton from shells, as well as fluids and tissues from the digestive tract of C1 were investigated for the following cyanotoxins: anatoxin-a, homoanatoxin-a, dihydroanatoxin-a (dhATX), cylindrospermopsin, saxitoxin, and microcystins. Necropsy results of C1 indicated neurotoxicosis with significant levels of dhATX in the duodenum tissues (10.51 ng/g dry weight (DW)), jejunum tissue (6.076 ng/g DW), and stomach contents (974.88 ng/g DW). Algae collected near the site of C1's death contained levels of dhATX, ranging from 13 to 33 µg/g. By comparison, dhATX was detected at much lower concentrations in sediment samples (310.23 ng/g DW) and the periphyton on zebra mussel shells (38.45 ng/g DW). While dhATX was suspected in the deaths of canines from an event in Texas in 2019, this is the first report linking dhATX neurotoxicosis through pathological findings in Texas and potentially in the United States.


Designing a 20-residue protein.
Truncation and mutation of a poorly folded 39-residue peptide has produced 20-residue constructs that are >95% folded in water at physiological pH. These constructs optimize a novel fold, designated as the 'Trp-cage' motif, and are significantly more stable than any other miniprotein reported to date. Folding is cooperative and hydrophobically driven by the encapsulation of a Trp side chain in a sheath of Pro rings. As the smallest protein-like construct, Trp-cage miniproteins should provide a testing ground for both experimental studies and computational simulations of protein folding and unfolding pathways. Pro Trp interactions may be a particularly effective strategy for the a priori design of self-folding peptides.


Experimental evaluation of nonlinearities of small-sized insertable gradient coils.
A phase imaging technique is proposed to map out and quantify gradient nonlinearities of small-sized insertable gradient coils, assuming the whole-body system gradients are highly linear in the domain of interest. The theory is developed and simple equations are derived to allow quantification. It is applied to a 4-loop 18-cm diameter cylindrical gradient coil of optimal design. Experimental gradient nonlinearity maps are obtained for different fields of view. Gradient non-linearities are quantified locally and in regions of interest, showing close agreement with model data.


Mulberroside A repairs high fructose diet-induced damage of intestinal epithelial and blood-brain barriers in mice: A potential for preventing hippocampal neuroinflammatory injury.
Our previous studies showed that high fructose diet (HFrD)-driven gut dysbiosis caused fecal short-chain fatty acids (SCFAs) reduction and intestinal epithelial barrier (IEB) damage in mice, which might play an important role in hippocampal neuroinflammatory injury. Mulberroside A is reported to have neuroprotective effects in animal experiments, while the underlying mechanisms are not yet fully elucidated. Here, we investigated whether and how mulberroside A prevented HFrD-induced neuroinflammatory injury. HFrD-fed mice were treated orally with mulberroside A (20 and 40 mg/kg) for 8 weeks. Mulberroside A was found to inhibit hippocampal neuroinflammation and neurogenesis reduction in HFrD-fed mice. It reshaped gut dysbiosis, increased fecal and serum SCFAs contents, reactivated signaling of the colonic NLR family, pyrin domain containing 6 (NLRP6) inflammasome, and up-regulated Muc2 expression to prevent IEB damage, as well as subsequently, reduced serum endotoxin levels in this animal model. Additionally, mulberroside A inhibited oxidative stress in colon of HFrD-fed mice and hydrogen peroxide (H2 O2 )-stimulated Caco-2 cells. Blood-brain barrier (BBB) structure defects were also observed in HFrD-driven hippocampal neuroinflammatory injury of mice. Interestingly, mulberroside A maintained astrocyte morphology and up-regulated tight junction proteins to repair BBB structure defects in hippocampus dentate gyrus (DG). Our results demonstrated that mulberroside A was capable of preventing HFrD-induced damage of IEB and BBB in mice, which might contribute to the suppression of hippocampal neuroinflammatory injury.


The effects of exogenous glutathione on reduced glutathione level, glutathione peroxidase and glutathione reductase activities of rats with different ages and gender after whole-body Γ-irradiation.
Age-and gender-related changes on reduced glutathione (GSH) level, glutathione peroxidase (GPx) and glutathione reductase (GR) activities in the liver of rat exposed to different dose of whole-body g-ray irradiation were determined. In addition, the effect of administration of exogenous GSH on endogenous GSH levels, GPx and GR activities was investigated. For this aim, male and female rats aged 1 and 5 moths were divided into two groups as g-ray and g-ray+GSH. Both groups were again divided into four groups as irradiated with 2, 4, 6 and 8 Gy doses. GSH level and GPx activity did not change with age while GR activity was decreased with age. Gender-dependent changes in GPx and GR activities were observed, but GSH values were not affect by sex. GSH levels, GPx and GR activities were not observed dose-associated changes of g-irradiation. GSH level and GPx activity in the 8Gy group were increased by GSH. GR activities of old male rats were found to be increased by glutathione in the 6 and 8Gy groups. These results indicate that radiation and administration of exogenous GSH affect gender-and age-dependent GSH level, GPx and GR activities in the rats.


Longitudinal trends in the treatment of abdominal pain in an academic emergency department.
Abdominal pain is a top chief complaint of patients presenting to Emergency Departments (ED). Historically, uncertainty surrounded correct management. Evidence has shown adequate analgesia does not obscure the diagnosis, making it the standard of care. We sought to evaluate trends in treatment of abdominal pain in an academic ED during a 10-year period. We prospectively evaluated a convenience sample of patients in an urban academic tertiary care hospital ED from September 2000 through April 2010. Adult patients presenting with a chief complaint of abdominal pain were included in this study. Analgesic administration rates and times, pain scores, and patient satisfaction at discharge were analyzed to evaluate trends by year. There were 2,646 patients presenting with abdominal pain who were enrolled during the study period. Rates of analgesic administration generally increased each year from 39.9% in 2000 to 65.5% in 2010 (p value for trend <0.001). Similarly, time to analgesic administration generally decreased by year, from 116 min in 2000 to 81 min in 2009 (p < 0.001). There was no improvement in mean pain scores at discharge by year (p = 0.27) and 48% of patients during the 10-year period still reported moderate to severe pain at discharge. Patient satisfaction with pain treatment increased from a score of 7.1 to 9.0 during the study period (p < 0.005), following the trend of increase in analgesic administration. In patients presenting to the ED with abdominal pain, analgesia administration increased and time to medication decreased during the 10-year period. Despite overall improvements in satisfaction, significant numbers of patients presenting with abdominal pain still reported moderate to severe pain at discharge.


Structural inspection and protein motions modelling of a fungal glycoside hydrolase family 18 chitinase by crystallography depicts a dynamic enzymatic mechanism.
Chitinases degrade chitin into low molecular weight chitooligomers, which have a broad range of industrial, agricultural, and medical functions. Understanding the relationship between the diverse characteristics of chitinases and their functions is necessary for the improvement of functional enzymes that meet specific requirements. We report here a full crystallographic analysis of three complexes obtained from the chitinase Chit42 from Trichoderma harzianum, which represent different states along the enzymatic mechanism. The inactive double mutant D169A/E171A was submitted to soaking/crystallization experiments with hexa-N-acetyl-glucosamine (NAG6) or tetra-N-acetyl-glucosamine (NAG4), trapping the enzyme-substrate complex (Chit42-NAG6), the enzyme-products complex (Chit42-NAG4-NAG2) and a someway intermediate state. Structural comparison among the different complexes depicts the determinants defining the different subsites and revealed a previously unobserved dynamic on-off ligand binding process associated with a motion of its insertion domain, which might be accompanying the role or aromatics in processivity. An ensemble refinement performed to extract dynamic details from the diffraction data elucidates the implication of some highly flexible residues in the productive sliding of the substrate and the product release event. These positions were submitted to mutagenesis and the activity of the variants was investigated in the hydrolysis of NAG6, colloidal chitin and two chitosans with different polymerization and acetylation degree. All the changes affected the Chit42 hydrolytic activity therefore confirming the involvement of these positions in catalysis. Furthermore, we found the variants R295S and E316S improving the apparent catalytic efficiency of chitin and NAG6 and, together with E316A, enhancing the specific activity on chitosan. Therefore, our results provide novel insight into the molecular mechanisms underlying the hydrolysis of chitinous material by fungal chitinases, and suggest new targets to address engineering of these biotechnologically important enzymes.


A novel approach to the clinical evaluation of differential kinematics of the lumbar spine.
Clinical measurement of lumbar motion has traditionally been limited to range of motion (ROM). Despite this, deficits in angular velocities and accelerations are more pronounced compared to ROM in low back pain (LBP) sufferers. There is increasing interest in movement quality among manual therapists and therefore the ability to measure angular velocities and accelerations within the clinical environment is becoming increasingly important. The aims of this study were to (1) investigate the reliability of a clinic based inertial sensor system to measure ROM along with angular velocities and accelerations in low back pain sufferers; (2) introduce the feasibility and reliability of using the relationship between ROM and velocity to investigate movement trajectory and irregularity. Forty LBP sufferers completed three trials of spinal movements and lifting. The ROM curve was differentiated and double differentiated to yield angular velocities and accelerations. Repeated measures reliabilities were determined by comparisons of kinematic curves as well as peak values. ROM and angular velocity relationships were investigated for their use in describing the movement trajectory and irregularity. Results show excellent similarities of ROM and angular velocity curves and moderate-to-good similarities for angular acceleration curves. Peak value similarities were excellent with small error measurements for all variables. The quantification of ROM-angular velocity plots was reliable with small mean absolute differences in motion irregularity scores. Such a method was able to demonstrate differences in movement irregularity. This method provides clinicians with the ability to yield important additional movement related information including angular velocity, acceleration and movement irregularity.


Can a linear combination of gait principal component vectors identify hip OA stages?
Hip osteoarthritis (OA) has been shown to affect gait patterns of lower extremities. However, until now, no specific identifying gait characteristics for the various disease stages of hip OA have emerged. The present study addresses the following questions: (1) does a vector-based principal component analysis (PCA) discriminate between various disease stages? And, is this analysis more robust than using discrete gait variables? (2) Does the elimination of differences in walking speed affect the discriminatory robustness of a vector-based PCA? De-identified data sets of forty-five unilateral hip OA patients with varying disease stages and twenty-three age-matched, healthy control subjects were obtained from an available repository. PCA was performed on trial matrices consisting of all external joint moments and sagittal joint angles of one full gait cycle. Group differences in sagittal angles, external moments and the linear combination of PC vectors were investigated using spatial parameter mapping (SPM), a statistical vector field test. Several individual gait variables (i.e. joint moments or angles) demonstrated differences between healthy and moderately and/or severely affected subjects. Only the hip adduction moment could discriminate between the healthy and the early-stage OA group. There was no variable that could distinguish between all OA disease stages. In contrast, the linear combination of PC vectors demonstrated significant group differences between all stages of osteoarthritis; furthermore, these group differences stayed significant when matched speeds were input to the model.