SMCHD1 regulates a limited set of gene clusters on autosomal chromosomes.
Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situations result in the incomplete epigenetic repression of the D4Z4-encoded retrogene DUX4 in somatic cells, leading to the aberrant expression of DUX4 in the skeletal muscle. In mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance. To investigate the global effects of harboring heterozygous SMCHD1 mutations on DNA methylation in humans, we combined 450k methylation analysis on mononuclear monocytes from female heterozygous SMCHD1 mutation carriers and unaffected controls with reduced representation bisulfite sequencing (RRBS) on FSHD2 and control myoblast cell lines. Candidate loci were then evaluated for SMCHD1 binding using ChIP-qPCR and expression was evaluated using RT-qPCR. We identified a limited number of clustered autosomal loci with CpG hypomethylation in SMCHD1 mutation carriers: the protocadherin (PCDH) cluster on chromosome 5, the transfer RNA (tRNA) and 5S rRNA clusters on chromosome 1, the HOXB and HOXD clusters on chromosomes 17 and 2, respectively, and the D4Z4 repeats on chromosomes 4 and 10. Furthermore, minor increases in RNA expression were seen in FSHD2 myoblasts for some of the PCDHβ cluster isoforms, tRNA isoforms, and a HOXB isoform in comparison to controls, in addition to the previously reported effects on DUX4 expression. SMCHD1 was bound at DNAseI hypersensitivity sites known to regulate the PCDHβ cluster and at the chromosome 1 tRNA cluster, with decreased binding in SMCHD1 mutation carriers at the PCDHβ cluster sites. Our study is the first to investigate the global methylation effects in humans resulting from heterozygous mutations in SMCHD1. Our results suggest that SMCHD1 acts as a repressor on a limited set of autosomal gene clusters, as an observed reduction in methylation associates with a loss of SMCHD1 binding and increased expression for some of the loci.


Circulating high-sensitivity C-reactive protein and soluble CD40 ligand are inter-related in a cohort of women with polycystic ovary syndrome.
Insulin resistance (IR), the fundamental metabolic alteration in women with polycystic ovary syndrome (PCOS), has recently been reported to represent, in part, a chronic low-grade inflammatory state. This study aimed to assess the inter-relationship between the plasma levels of high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) - both inflammatory factors - and the pathogenesis of IR among women with PCOS. This study compared 44 women with PCOS with a group of control women without PCOS (n = 39). Participants were matched for age, blood pressure and degree of obesity. Enzyme-linked immunosorbent assay was used to measure the two inflammatory factors. Fasting glucose and insulin were assayed and used to calculate the IR indices. Significant elevations in the plasma levels of both inflammatory factors were observed in women with PCOS compared with the control women: 3.17 (2.23-3.89) vs 2.05 (0.93-2.82) mg/l for hs-CRP and 2.46 (1.08-4.16) vs 0.82 (0.43-1.26) ng/ml for sCD40L, respectively. Interestingly, among women with PCOS, the two inflammatory factors were significantly positively correlated with each other (r = 0.465, p = 0.002), as well as with the IR indices. This association remained significant even after adjustment for body mass index as a measure of obesity. Independent of obesity, women with PCOS suffer low-grade inflammation that is correlated with IR. The observed inter-relationships suggest that CRP in collaboration with the CD40-CD40L system may have a role in the pathogenesis of PCOS.


Electrodynamic coupling of electric dipole emitters to a fluctuating mode density within a nanocavity.
We investigate the impact of rotational diffusion on the electrodynamic coupling of fluorescent dye molecules (oscillating electric dipoles) to a tunable planar metallic nanocavity. Fast rotational diffusion of the molecules leads to a rapidly fluctuating mode density of the electromagnetic field along the molecules' dipole axis, which significantly changes their coupling to the field as compared to the opposite limit of fixed dipole orientation. We derive a theoretical treatment of the problem and present experimental results for rhodamine 6G molecules in cavities filled with low and high viscosity liquids. The derived theory and presented experimental method is a powerful tool for determining absolute quantum yield values of fluorescence.


Effective degradation of tetracycline by magnetic palygorskite synthesized with different dosages of NaOH.
In the process of preparing magnetic palygorskite from waste pickling liquor of the steel industry, the dosage of NaOH will affect the properties of the magnetic palygorskite. The experimental results showed that magnetic palygorskite can be effectively prepared when NaOH dosage is between 255 and 330 g/L. Vibration sample magnetometry proved that different NaOH dosages can affect the saturation magnetization of magnetic palygorskite. The catalytic performance of five catalysts synthesized with different NaOH dosages hardly changed after five cycles of Fenton-like catalytic degradation of tetracycline (TC). The magnetic palygorskite prepared by this method had good catalytic performance even when the catalyst preparation conditions were magnified ten times, which can provide a reference for large-scale preparation of magnetic palygorskite.


Enhancing Wheat Disease Diagnosis in a Greenhouse Using Image Deep Features and Parallel Feature Fusion.
Since the assessment of wheat diseases (e.g., leaf rust and tan spot) via visual observation is subjective and inefficient, this study focused on developing an automatic, objective, and efficient diagnosis approach. For each plant, color, and color-infrared (CIR) images were collected in a paired mode. An automatic approach based on the image processing technique was developed to crop the paired images to have the same region, after which a developed semiautomatic webtool was used to expedite the dataset creation. The webtool generated the dataset from either image and automatically built the corresponding dataset from the other image. Each image was manually categorized into one of the three groups: control (disease-free), disease light, and disease severity. After the image segmentation, handcrafted features (HFs) were extracted from each format of images, and disease diagnosis results demonstrated that the parallel feature fusion had higher accuracy over features from either type of image. Performance of deep features (DFs) extracted through different deep learning (DL) models (e.g., AlexNet, VGG16, ResNet101, GoogLeNet, and Xception) on wheat disease detection was compared, and those extracted by ResNet101 resulted in the highest accuracy, perhaps because deep layers extracted finer features. In addition, parallel deep feature fusion generated a higher accuracy over DFs from a single-source image. DFs outperformed HFs in wheat disease detection, and the DFs coupled with parallel feature fusion resulted in diagnosis accuracies of 75, 84, and 71% for leaf rust, tan spot, and leaf rust + tan spot, respectively. The methodology developed directly for greenhouse applications, to be used by plant pathologists, breeders, and other users, can be extended to field applications with future tests on field data and model fine-tuning.


Features of ENT Cases in the Emergency Department of a Tertiary Hospital in Greece: A Prospectively Driven Data Collection Study.
Primary healthcare is the pillar of a well-functioning healthcare system. General practitioners (GPs) should have a broad skillset to cope with the various conditions they encounter in everyday practice. Ear, nose, and throat (ENT) cases are some of the most common reasons for seeking care. The study aimed to define the frequency and type of ENT disorders seen in the emergency department of a tertiary hospital in Greece. All patients examined by an ENT specialist in the emergency department setting, within a year, were recorded, as well as all referrals from private practice or primary care facilities. From September to December 2021, data were collected from patients who agreed to complete a two-minute survey, namely, the Generalized Anxiety Disorder Scale (GAD-2) questionnaire. During the study year, 4542 cases were documented, from which the most common conditions listed were external otitis (6.9%/314), epistaxis (6.7%/305), and impacted earwax (5.7%/261). The diagnoses that led to hospitalization were 336 and the most common were peritonsillar abscess (16.4%/55), epistaxis (8.0%/27), and facial nerve paralysis (7.4%/25). Referrals from GPs working in the public sector represented more than the half of the total. There was a significant correlation between an increased number of hospital visits and an increased GAD-2 score, in the semester before the current visit (p < 0.001). Referrals to ENT specialists represent around 5% of all cases examined, and about 8% of all visits required hospitalization. Interdisciplinary clinical and research investment into GP training is compulsory to regulate ENT referrals by GPs.


Molecular cloning of hormone-responsive genes from the yeast Saccharomyces cerevisiae.
A method for identifying yeast genes whose transcription is differentially regulated was developed. The technique is based on incorporation of the analog 4-thiouridine into nascent RNAs, which allows their purification. The purified RNAs are used to prepare cDNA copies for screening of genomic DNA libraries by hybridization. Using this procedure, several cloned yeast DNA segments were found whose transcription in MATa haploids in vivo is apparently modulated in dramatic fashion within 10-15 min after exposure to the mating pheromone, alpha factor. Subsequent analysis indicated that these sequences fall into three major classes: (i) genes expressed in vegetatively growing cells that are no longer transcribed after alpha-factor administration ("turn-off" genes); (ii) genes whose expression is increased 10- to 20-fold after exposure of the MATa cells to alpha factor ("turn-up" genes); and (iii) genes that are expressed only after alpha-factor treatment ("turn-on" genes). The first class may encode products required for cell cycle progression; the third class may code for products uniquely involved in the mating process.


Activity of roxithromycin against respiratory pathogens.
The usefulness of macrolides in treating respiratory infections has been established for over thirty years. Currently, a great deal of interest is being focused on roxithromycin, a new semisynthetic derivative of erythromycin which is more stable than erythromycin under acidic conditions and exhibits improved pharmacokinetic properties. In this study, special attention is paid to the results of recent multicenter studies in Italy aimed at evaluating the in vitro activity of roxithromycin versus erythromycin against a wide range of respiratory pathogens. Considering that a high degree of overlap was observed between the roxithromycin-susceptible and the erythromycin-susceptible strains, whereas a significant proportion of erythromycin-resistant strains shifted to the intermediate category with roxithromycin, there appeared to be cross-susceptibility rather than cross-resistance between the two macrolides.


Hydrothermal Synthesis of Ultrasmall Pt Nanoparticles as Highly Active Electrocatalysts for Methanol Oxidation.
Ultrasmall nanoparticles, with sizes in the 1-3 nm range, exhibit unique properties distinct from those of free molecules and larger-sized nanoparticles. Demonstrating that the hydrothermal method can serve as a facile method for the synthesis of platinum nanoparticles, we successfully synthesized ultrasmall Pt nanoparticles with an average size of 2.45 nm, with the aid of poly(vinyl pyrrolidone) (PVP) as reducing agents and capping agents. Because of the size effect, these ultrasmall Pt nanoparticles exhibit a high activity toward the methanol oxidation reaction.


A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish.
Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization.


MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1.
Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. However, the role of miRNAs in the regulation of stem cell growth and differentiation is not well understood. We show herein that microRNA (miR)-134 levels are maximally elevated at day 4 after retinoic acid-induced differentiation or day 2 after N2B27-induced differentiation of mouse embryonic stem cells (mESCs), but this change is not observed during embryoid body differentiation. The elevation of miR-134 levels alone in mESCs enhances differentiation toward ectodermal lineages, an effect that is blocked by a miR-134 antagonist. The promotion of mESC differentiation by miR-134 is due, in part, to its direct translational attenuation of Nanog and LRH1, both of which are known positive regulators of Oct4/POU5F1 and mESC growth. Together, the data demonstrate that miR-134 alone can enhance the differentiation of mESCs to ectodermal lineages and establish a functional role for miR-134 in modulating mESC differentiation through its potential to target and regulate multiple mRNAs.


A comprehensive review of motor innervation of the hand: variations and clinical significance.
The objective of the present review is to assemble the recognized anatomical variations, classifications, and clinical evidence with regard to innervation of the hand and discuss the clinical significance of these variations. The material for this review was obtained by exploring PubMed and Google Scholar (search terms: hand innervation, variations of ulnar nerve, variations of median nerve, variations of radial nerve) as well as from standard anatomy texts. This initial search returned approximately 300 articles, which was reduced by abstract or title review. Reviewing the reference lists of significant papers uncovered further studies missed in the initial search. A few standard anatomy texts were also consulted for normal anatomy. The median and ulnar nerves frequently display a number of significant deviations from the traditionally taught branching patterns. The traditionally taught innervation of the hand is also found to be highly variable. This is especially evident with regard to the motor innervation of thenar muscles. These variations may be explained by the often under-recognized anastomoses that exist in the hand, such as the motor Riche-Cannieu Anastomosis. Some of these variations are associated significant clinical consequences. The median and ulnar nerves display many anatomical variations, often with significant clinical implications. Awareness about these variations is clinically important when interpreting clinical examination findings, electrophysiological and radiological investigation as well as during management of patients in terms of surgical and anesthetic procedures.


Selenium-Functionalized Graphene Oxide That Can Modulate the Balance of Reactive Oxygen Species.
Graphene oxide (GO) is an important two-dimensional material since it is water-soluble and can be functionalized to adapt to different applications. However, the current covalent functionalization methods usually require hash conditions, long duration, and sometimes even multiple steps, while noncovalent functionalization is inevitably unstable, especially under a physiological environment where competing species exist. Diselenide bond is a dynamic covalent bond and can respond to both redox conditions and visible light irradiation in a sensitive manner. Thus, in this work by combining the stimuli response of diselenide bond and the oxidative/radical attackable nature of GO, we achieved the in situ covalent functionalization of GO simply by stirring GO with diselenide-containing molecules in aqueous solution. The covalent functionalization was proved by Fourier transform infrared, time-of-flight secondary ion mass spectrometry, atomic force microscopy, thermogravimetric analysis, and so forth, and the functionalization mechanism was deduced to involve both redox reaction and radical addition reaction according to the X-ray photoelectron spectrscopy, atomic emission spectroscopy, and Raman spectroscopy. Moreover, we modified GO with a biocompatible diselenide-containing polymer (mPEGSe)2 and found selenium-functionalized GO could modulate the balance of reactive oxygen species (ROS). GOSe could decrease ROS level by accelerating the reduction of peroxides when the ROS concentration is high while boosting the ROS level by in situ generating ROS when its concentration is relatively low.


Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction.
The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient's 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.


Knowledge, attitude and practices associated with condom use among antenatal women.
The basic principles of HIV prevention lay emphasis on three important behaviours: abstinence, monogamous relationship and condom use. Among the three, condoms use alone can reduce the likelihood of infection by 90 percent. A quantitative study using interview schedule was conducted in which 100 women were interviewed. Simple random sampling technique was used to draw the required number of subjects from the sampling frame. The study revealed that the condom use as means of protection against HIV in India is low though it has been successful as a means of family planning device, since 70 percent of women agreed that there is no need to use condom if oral contraceptives were used. Socioeconomic characteristics such as education and economic status of women are found to be significantly associated with HIV awareness and condom use (p = 0.05). The sexual division of power plays an important role in sexual behaviour among women. The study highlights the need to implement policies that support women's education for behavioural change.


Overdose Risk and Acquiring Opioids for Nonmedical Use Exclusively from Physicians in Vancouver, Canada.
A primary response to the alarming rise in overdose and mortality due to nonmedical prescription opioid (PO) use has been to restrict opioid prescribing; however, little is known about the relationship between obtaining opioids from a physician and overdose risk among people who use POs nonmedically and illicit street drugs. Objectives: Investigate the relationship between non-fatal overdose and acquiring POs exclusively from physicians for the purposes of engaging in nonmedical PO use. Methods: Data were collected between 2013 and 2016 among participants in two harmonized prospective cohort studies of people who use drugs in Vancouver: the At-Risk Youth Study (ARYS) and the Vancouver Injection Drug Users Study (VIDUS). Analyses were restricted to participants who engaged in nonmedical PO use and used generalized estimating equations. Results: Among 599 participants who used POs nonmedically, 82 (14%) individuals reported acquiring POs exclusively from a physician and 197 (33%) experienced a non-fatal overdose at some point over the study period. Acquiring POs exclusively from physicians was significantly and negatively associated with non-fatal overdose in the bivariate analysis (Odds Ratio = 0.60, 95% Confidence Interval (CI): 0.39-0.94) but not the final multivariate analysis (Adjusted Odds Ratio =0.87, 95% CI: 0.53-1.44). Conclusions: Compared to individuals who acquired POs from friends or the streets, participants who acquired POs exclusively from a physician were not at an increased risk of non-fatal overdose. Although responsible opioid prescribing is an important priority, additional strategies to address nonmedical PO use are urgently needed to reduce overdose and related morbidity and mortality.


A Case Report of Acquired Factor X Deficiency in a Patient With Multiple Myeloma.
Multiple myeloma is a plasma cell neoplasm characterized by clonal proliferation of immunoglobulin producing terminally differentiated B cells. Classically patients are described to present with bone pain, hypercalcemia, anemia, and/or renal impairment. A less described clinical manifestation related to the myeloma is acquired coagulation abnormalities including paraprotein interfering with the coagulation cascade or exhibiting specific antibody activity. Factor X deficiency is reported in patients with secondary amyloidosis. We describe a patient who presented with bleeding tendency and an abnormal prothrombin and activated partial thromboplastin times (PT/PTT) due to factor X deficiency. A thorough workup revealed the diagnosis of multiple myeloma with the presence of monoclonal lambda light chain restricted plasma cells with qualifying end-organ damage without evidence of amyloidosis. Prior to the ultimate diagnosis, the patient succumbed to septic shock and acute respiratory distress syndrome due to Streptococcus Pneumonia infection.


Clinical hurdles for the transplantation of cardiomyocytes derived from human embryonic stem cells: role of molecular imaging.
Over the past few years, human embryonic stem cells (hESCs) have gained popularity as a potentially ideal cell candidate for tissue regeneration. In particular, hESCs are capable of cardiac lineage-specific differentiation and confer improvement of cardiac function following transplantation into animal models. Although such data are encouraging, there remain significant hurdles before safe and successful translation of hESC-based treatment into clinical therapy, including the ability to assess cells following transplant. To this end, molecular imaging has proven a reliable methodology for tracking the long-term fate of transplanted cells. Imaging reporter genes that are introduced into the cells before transplantation enable non-invasive and longitudinal studies of cell viability, location and behaviour in vivo. Therefore, molecular imaging is expected to play an increasing role in characterizing the biology and physiology of hESC-derived cardiac cells in living subjects.


Indications for the tracheoesophageal diversion procedure and the laryngotracheal separation procedure.
Impaired protective function of the larynx can lead to intractable aspiration, a severe and potentially fatal disorder. If medical therapy fails to prevent intractable aspiration, surgical separation of the upper respiratory tract from the digestive tract is necessary to prevent recurrent contamination of the respiratory system in these patients. Two such surgical procedures are the tracheoesophageal diversion procedure and the laryngotracheal separation procedure. Our approach to patients with intractable aspiration and the indications for the use of these surgical procedures for the prevention of aspiration are discussed.


On models and vases: body dissatisfaction and proneness to social comparison effects.
When and why do media-portrayed physically attractive women affect perceivers' self-evaluations? In 6 studies, the authors showed that whether such images affect self-evaluations depends jointly on target features and perceiver features. In Study 1, exposure to a physically attractive target, compared with exposure to an equally attractive model, lowered women's self-evaluations. Study 2 showed that body-dissatisfied women, to a greater extent than body-satisfied women, report that they compare their bodies with other women's bodies. In Study 3, body-dissatisfied women, but not body-satisfied women, were affected by both attractive models and nonmodels. Furthermore, in Study 4, it was body-dissatisfied women, rather than body-satisfied women, who evaluated themselves negatively after exposure to a thin (versus a fat) vase. The authors replicated this result in Study 5 by manipulating, instead of measuring, body dissatisfaction. Finally, Study 6 results suggested that body dissatisfaction increases proneness to social comparison effects because body dissatisfaction increases self-activation.


Using height-for-age differences (HAD) instead of height-for-age z-scores (HAZ) for the meaningful measurement of population-level catch-up in linear growth in children less than 5 years of age.
Evidence from studies conducted in nutritionally deprived children in low- and middle-income countries (LIMC) in past decades showed little or no population-level catch-up in linear growth (mostly defined as reductions in the absolute height deficit) after 2 years of age. Recent studies, however, have reported population-level catch-up growth in children, defined as positive changes in mean height-for-age z-scores (HAZ). The aim of this paper was to assess whether population-level catch-up in linear growth is found when height-for-age difference (HAD: child's height compared to standard, expressed in centimeters) is used instead of HAZ. Our premise is that HAZ is inappropriate to measure changes in linear growth over time because they are constructed using standard deviations from cross-sectional data. We compare changes in growth in populations of children between 2 and 5 years using HAD vs. HAZ using cross-sectional data from 6 Demographic and Health Surveys (DHS) and longitudinal data from the Young Lives and the Consortium on Health-Orientated Research in Transitional Societies (COHORTS) studies. Using HAD, we find not only an absence of population-level catch-up in linear growth, but a continued deterioration reflected in a decrease in mean HAD between 2 and 5 years; by contrast, HAZ shows either no change (DHS surveys) or an improvement in mean HAZ (some of the longitudinal data). Population-level growth velocity was also lower than expected (based on standards) in all four Young Lives data sets, confirming the absence of catch-up growth in height. We show no evidence of population-level catch-up in linear growth in children between 2 to 5 years of age when using HAD (a measure more appropriate than HAZ to document changes as populations of children age), but a continued deterioration reflected in a decrease in mean HAD. The continued widening of the absolute height deficit after 2 years of age does not challenge the critical importance of investing in improving nutrition during the first 1000 days (i.e., from conception to 2 years of age), but raises a number of research questions including how to prevent continued deterioration and what is the potential of children to benefit from nutrition interventions after 2 years of age. Preventing, rather than reversing linear growth retardation remains the priority for reducing the global burden of malnutritionworldwide.


Influence of the stabilisation of organic materials on their biopesticide effect in soils.
Some organic materials have shown a suppressive effect on several diseases induced by soilborne plant pathogens. We have carried out a laboratory experiment (microcosm) to ascertain the influence of the stabilisation process of sewage sludge on it biopesticide effect when Pythium ultimum or Phytophthora sp. were introduced to soil as pathogens for pea or pepper. When P. ultimum was introduced there was a 63.8% reduction in the weight of the stems grown in the control, 47.6% in the presence of sewage sludge, but only 24.7% with compost. The same biopesticide effect was evident from the weight of the roots. The biopesticide effect was also strong when compost was used as organic amendment in the presence of Phytophthora, as could be seen from stem and shoot weight and length. The data showed that the degree of stabilisation of the organic material (compost) had a positive influence on it biopesticide effect. The changes undergone by a soil after the addition of organic materials helped to explain the biopesticide effect of the amendment. The organic treatments reduced P. ultimum and Phytophthora sp. populations.


Effects of the Implementation of an Emergency Surgical Pattern in Patients with Rhegmatogenous Retinal Detachment: A Retrospective Observational Study.
To analyze the effects of the implementation of emergency surgical patterns in patients with rhegmatogenous retinal detachment (RRD) and provide evidence for promoting emergency surgical patterns for RRD. We reviewed the electronic medical records of 346 patients (348 eyes) who underwent surgical repair of RRD at the Zhongshan Ophthalmic Center in Southern China. A total of 140 patients (140 eyes) in the routine inpatient surgery group were collected at the fundus disease department between January 2019 and December 2019, and 206 patients (208 eyes) in the emergency surgery group were collected at the ophthalmic emergency department between January 2021 and December 2021. Demographics, best-corrected visual acuity (BCVA) expressed as the logarithm of the minimum angle of resolution (logMAR), the status of the macula before surgery, time to presentation, treatment interval, and postoperative BCVA measured at least three months follow-up were compared. The preoperative BCVA (logMAR) of the emergency surgery group and the inpatient surgery group were 1.0 (0.4-1.7) and 1.4 (0.7-1.7), respectively, with significant differences between groups (P < 0.001). However, patients had a shorter time to presentation (7 days vs. 21 days, P < 0.001), shorter treatment interval (2 days vs. 12 days, P < 0.01), and significantly better postoperative BCVA (logMAR 0.5 vs. logMAR 1.0, P < 0.001) in the emergency surgery group than in the inpatient surgery group. There was no significant difference in primary anatomical success between the two groups (P=0.802). The median follow-up for the emergency surgery group and the inpatient surgery group were 6.08 months and 6.2 months, respectively, with no significant differences (P > 0.05). Patients who underwent emergency surgical patterns of RRD had better visual outcomes after surgery than patients with routine inpatient surgery, which might be attributed to a shorter duration, shorter treatment interval, and the preoperative status of the macula in the emergency surgery pattern. Emergency surgical patterns for RRD should be considered to achieve better surgical outcomes in suitable patients.


Low-κ, narrow linewidth III-V-on-SOI distributed feedback lasers with backside sampled Bragg gratings.
We demonstrate a heterogeneously integrated III-V-on-SOI distributed feedback laser with a low grating strength (κ < 40 cm-1) and a narrow linewidth of Δν = 118 kHz. The laser operates single mode with a side-mode suppression ratio over 45 dB, provides a single-sided waveguide-coupled output power of 22 mW (13.4 dBm) and has a wall-plug efficiency of 17%. The dynamic characteristics were also evaluated, obtaining an intrinsic 3 dB modulation bandwidth of 14 GHz and a photon lifetime of 8 ps. Large-signal intensity modulation using a 231-1 PRBS pattern length revealed open eye diagrams up to 25 Gb/s and a penalty on the dynamic extinction ratio lower than 1 dB after transmission over a 2 km standard single mode optical fiber.


Commonwealth Care Alliance. A new approach to coordinated care for the chronically ill and frail elderly that organizationally integrates consumer involvement.
While medical care is becoming more effective, our health care system is becoming increasingly fragmented from both a care and a financing perspective. This article summarizes our experience with integrating the delivery of care for catastrophically ill and frail elderly. We argue that true integration can only be done within a framework of a financing mechanism that gives all providers the financial incentive to deliver integrated care. Under such a financial arrangement, nurse practitioners and social workers provide much of the care within the home environment. This results in a higher quality care delivery system within a limited budget.


Periodic trends in lanthanide and actinide phosphonates: discontinuity between plutonium and americium.
The hydrothermal reactions of trivalent lanthanide and actinide chlorides with 1,2-methylenediphosphonic acid (C1P2) in the presence of NaOH or NaNO(3) result in the crystallization of three structure types: RE[CH(2)(PO(3)H(0.5))(2)] (RE = La, Ce, Pr, Nd, Sm; Pu) (A type), NaRE(H(2)O)[CH(2)(PO(3))(2)] (RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy; Am) (B type), or NaLn[CH(2)(PO(3)H(0.5))(2)]·(H(2)O) (Ln = Yb and Lu) (C type). These crystals were analyzed using single crystal X-ray diffraction, and the structures were used directly for detailed bonding calculations. These phases form three-dimensional frameworks. In both A and B, the metal centers are found in REO(8) polyhedra as parts of edge-sharing chains or edge-sharing dimers, respectively. Polyhedron shape calculations reveal that A favors a D(2d) dodecahedron while B adopts a C(2v) geometry. In C, Yb and Lu only form isolated MO(6) octahedra. Such differences in terms of structure topology and coordination geometry are discussed in detail to reveal periodic deviations between the lanthanide and actinide series. Absorption spectra for the Pu(III) and Am(III) compounds are also reported. Electronic structure calculations with multireference methods, CASSCF, and density functional theory, DFT, reveal localization of the An 5f orbitals, but natural bond orbital and natural population analyses at the DFT level illustrate unique occupancy of the An 6d orbitals, as well as larger occupancy of the Pu 5f orbitals compared to the Am 5f orbitals.


Annotation of a hybrid partial genome of the coffee rust (Hemileia vastatrix) contributes to the gene repertoire catalog of the Pucciniales.
Coffee leaf rust caused by the fungus Hemileia vastatrix is the most damaging disease to coffee worldwide. The pathogen has recently appeared in multiple outbreaks in coffee producing countries resulting in significant yield losses and increases in costs related to its control. New races/isolates are constantly emerging as evidenced by the presence of the fungus in plants that were previously resistant. Genomic studies are opening new avenues for the study of the evolution of pathogens, the detailed description of plant-pathogen interactions and the development of molecular techniques for the identification of individual isolates. For this purpose we sequenced 8 different H. vastatrix isolates using NGS technologies and gathered partial genome assemblies due to the large repetitive content in the coffee rust hybrid genome; 74.4% of the assembled contigs harbor repetitive sequences. A hybrid assembly of 333 Mb was built based on the 8 isolates; this assembly was used for subsequent analyses. Analysis of the conserved gene space showed that the hybrid H. vastatrix genome, though highly fragmented, had a satisfactory level of completion with 91.94% of core protein-coding orthologous genes present. RNA-Seq from urediniospores was used to guide the de novo annotation of the H. vastatrix gene complement. In total, 14,445 genes organized in 3921 families were uncovered; a considerable proportion of the predicted proteins (73.8%) were homologous to other Pucciniales species genomes. Several gene families related to the fungal lifestyle were identified, particularly 483 predicted secreted proteins that represent candidate effector genes and will provide interesting hints to decipher virulence in the coffee rust fungus. The genome sequence of Hva will serve as a template to understand the molecular mechanisms used by this fungus to attack the coffee plant, to study the diversity of this species and for the development of molecular markers to distinguish races/isolates.


[The influence of several anions on sonoluminescence].
1.1 MHz ultrasound was used to induce sonoluminescence in air-saturated solutions dissolved five kinds of anions in different ranges: NO3-: 0.2-20 mg x L(-1), F- : 4-20 mg x L(-1), Cl- : 5-25 mg x L(-1), HCO3- : 8-30 mgx L(-1), SO4(2-) : 0.4-40 mg x L(-1). It was found that four kinds of the anions, Cl- , NO-, HCO3- and SO4(2-) at the above mentioned concentrations have no influence on sonoluminescence. However, only F- in the range of 4-20 mg x L(-1) can quench the sonoluminescence. The quenching mechanism was analyzed.


Should activated sludge models consider influent seeding of nitrifiers? Field characterization of nitrifying bacteria.
This study revealed the presence of nitrifying bacteria in influent municipal wastewaters reaching full-scale biological wastewater treatment plants. Respirometric assays showed that the influent nitrifiers were active following a 5- to 8-hour period of metabolic induction. Diversity analyses by pyrosequencing of functional gene PCR (polymerase chain reaction) amplicon suggested that the nitrifiers in the influent stream likely seeded activated sludge bioreactors since the most abundant operational taxonomic units in the influent and mixed liquor were the same. Based on the estimated seeding intensity of 0.3 g of nitrifiers per day per gram of nitrifiers already present, the absolute minimum solids retention time (SRT) was reduced by approximately 56% at 5 °C as compared to non-seeding conditions. This can have important repercussions on the design and sizing of bioreactors operating in cold climates and calls for a need to fine-tune process modelling by considering the contribution of autotrophic nitrifying biomass from municipal influent streams.


[Genes and epilepsy I: epilepsy and genetic alterations].
Epilepsy is a neurological disorder characterized by spontaneous and recurrent seizures with an estimated prevalence of 2-3 % in the world population. Epileptic seizures are the result of paroxystic and hypersynchronous electrical activity, preferentially in cortical areas, caused by panoply of structural and neurochemical dysfunctions. Recent advances in the field have focused on the molecular mechanisms involved in the epileptogenic process. In the present review, we describe the main genetic alterations associated to the process of epileptogenesis and discuss the new findings that are shedding light on the molecular substrates of monogenic idiopathic epilepsies (MIE) and on genetically complex epilepsies (GCE). Linkage and association studies have shown that mutations in ion channel genes are the main causes of MIE and of predisposition for GCE. Moreover, mutations in genes involved in neuronal migration, glycogen metabolism and respiratory chain are associated to other syndromes involving seizures. Therefore, different gene classes contribute to the epileptic trait. The identification of epilepsy-related gene families can help us understand the molecular mechanisms of neuronal hyperexcitability and recognize markers of early diagnosis as well as new treatments for these epilepsies.


Cytoarchitectonic Maps of the Human Metathalamus in 3D Space.
The human metathalamus plays an important role in processing visual and auditory information. Understanding its layers and subdivisions is important to gain insights in its function as a subcortical relay station and involvement in various pathologies. Yet, detailed histological references of the microanatomy in 3D space are still missing. We therefore aim at providing cytoarchitectonic maps of the medial geniculate body (MGB) and its subdivisions in the BigBrain - a high-resolution 3D-reconstructed histological model of the human brain, as well as probabilistic cytoarchitectonic maps of the MGB and lateral geniculate body (LGB). Therefore, histological sections of ten postmortem brains were studied. Three MGB subdivisions (MGBv, MGBd, MGBm) were identified on every 5th BigBrain section, and a deep-learning based tool was applied to map them on every remaining section. The maps were 3D-reconstructed to show the shape and extent of the MGB and its subdivisions with cellular precision. The LGB and MGB were additionally identified in nine other postmortem brains. Probabilistic cytoarchitectonic maps in the MNI "Colin27" and MNI ICBM152 reference spaces were computed which reveal an overall low interindividual variability in topography and extent. The probabilistic maps were included into the Julich-Brain atlas, and are freely available. They can be linked to other 3D data of human brain organization and serve as an anatomical reference for diagnostic, prognostic and therapeutic neuroimaging studies of healthy brains and patients. Furthermore, the high-resolution MGB BigBrain maps provide a basis for data integration, brain modeling and simulation to bridge the larger scale involvement of thalamocortical and local subcortical circuits.


Stimulation of amyloid precursor protein synthesis by adrenergic receptors coupled to cAMP formation.
Amyloid plaques in Alzheimer disease are primarily aggregates of Abeta peptides that are derived from the amyloid precursor protein (APP). Neurotransmitter agonists that activate phosphatidylinositol hydrolysis and protein kinase C stimulate APP processing and generate soluble, non-amyloidogenic APP (APPs). Elevations in cAMP oppose this stimulatory effect and lead to the accumulation of cell-associated APP holoprotein containing amyloidogenic Abeta peptides. We now report that cAMP signaling can also increase cellular levels of APP holoprotein by stimulating APP gene expression in astrocytes. Treatment of astrocytes with norepinephrine or isoproterenol for 24 h increased both APP mRNA and holoprotein levels, and these increases were blocked by the beta-adrenergic antagonist propranolol. Treatment with 8-bromo-adenosine 3',5'-cyclic monophosphate or forskolin for 24 h similarly increased APP holoprotein levels; astrocytes were also transformed into process-bearing cells expressing increased amounts of glial fibrillary acidic protein, suggesting that these cells resemble reactive astrocytes. The increases in APP mRNA and holoprotein in astrocytes caused by cAMP stimulation were inhibited by the immunosuppressant cyclosporin A. Our study suggests that APP overexpression by reactive astrocytes during neuronal injury may contribute to Alzheimer disease neuropathology, and that immunosuppressants can inhibit cAMP activation of APP gene transcription.


High-performance laser power converts for wireless information transmission applications.
Laser Power Converters (LPCs) are components of the laser wireless power transmission (LWPT) system receiving laser power. This paper proposes a comprehensive test method that employs continuous, pulse-pause, and short-time techniques to evaluate the performance of six-junction GaAs LPCs operating with an optical input at 808 nm. Additionally, we investigate the performance of LPCs with different areas and achieve a conversion efficiency over 60%. Furthermore, we apply LPCs with varying areas to wireless information transmission and successfully achieve a response time of 1.7 µs.


Highly selective hydroiodation of alkynes using an iodine-hydrophosphine binary system.
A novel hydroiodation of alkynes (1) using an iodine/hydrophosphine binary system takes place regioselectively to provide the corresponding Markovnikov-type adducts (2) in good yield. This hydroiodation is advantageous in terms of mild conditions, convenient operation, and tolerance to various functional groups.


PHLYCTENULOSIS IN THE ESKIMOS OF THE CANADIAN EASTERN ARCTIC.
During a recent ophthalmic survey of 780 Eskimos in the Canadian Eastern Arctic, 217 were found to have stigmata of phlyctenular keratoconjunctivitis, 198 of these being inactive and 19 active. Attention is drawn to the high incidence of pediculosis capitis in the Eskimos of this region, and it is suggested that there may be a relationship between this infestation and phlyctenulosis.


Persistence of the mini pivot shift after anatomically placed anterior cruciate ligament reconstruction.
We hypothesized that traces of pivot-shift instability (a minipivot) would persist after anterior cruciate ligament reconstruction in some knees despite objective restoration of anteroposterior laxity to normal. We tested intact cadaver knees after anterior cruciate ligament transection and then after anatomically placed single-bundle anterior cruciate ligament reconstructions. We measured the rotational laxities and pivot-shift kinematics over a range of graft tensions. Increasing graft tension decreased anteroposterior laxity; anteroposterior laxity was greater than normal at 0 and 10 N tensions but not different than normal at 20 to 60 N tensions. Anterior cruciate ligament deficiency had little effect on rotation laxity, and reconstruction had little effect on rotational laxity, which was not reduced by increasing graft tension. During the pivot-shift test, increasing graft tension reduced the anteroposterior subluxation-reduction events, but tibial rotational was not restored to normal. More sophisticated reconstruction methods may be required to control rotation. Objective restoration of anteroposterior laxity to normal does not necessarily return knee kinematics, especially rotational behavior, to normal.


Development of a ZnOS+C Composite as a Potential Adsorbent for the Effective Removal of Fast Green Dye from Real Wastewater.
Wastewater treatment is becoming increasingly important due to the potential shortage of pure drinking water in many parts of the world. Adsorption offers a potential technique for the uptake of contaminants and wastewater purification. In the last two decades, several efforts have been made to remove fast green (FG) dye from wastewater via different adsorbent materials. However, adsorption capacity shown by these adsorbents is low and time-consuming. Herein, we have synthesized for the first time a new powdered adsorbent ZnOS+C, modified zinc peroxide with sulfur and activated carbon to effectively remove FG dye from wastewater. Results of batch adsorption experiments have suggested that ZnOS+C has the maximum adsorption potential of 238.28 mg/g for FG dye within 120 min of adsorption equilibrium for a wide range of pH ranging from 2 to 10 pH. The adsorption process conforms to the Freundlich isotherm model, suggesting a multilayered adsorption process on the outer surface of ZnOS+C. The adsorption kinetics study indicates that the kinetics of the reaction are the intraparticle diffusion model. Briefly, this study shows proof of the application of ZnOS+C powder as a new eco-friendly adsorbent with extremely high efficiency and high surface area for removing FG dye.


[The organization of preventive examinations in the system of medical support of industrial enterprises].
The article presents the results of analysis of actual system of medical support of industrial enterprises and consumer estimate of accessibility o and quality of organization of medical examinations during dispensarization. The new form of complex medical examinations is proposed combining capacity of programs of examination of periodical medical check-ups of workers of enterprises and the first stage of dispensarization implemented on the basis of of integrated medical organization according to developed regulations. On the basis of increasing coverage of workers with measures of dispensarization the economic efficiency of complex medical examinations at the expense of decreasing of economic burden of chronic non-infectious diseases is substantiated.


Ambulatory heart rate and target organ damage in never-treated essential hypertensives.
Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (<or= 1 year) grade 1 and 2 hypertension, categorized by tertiles of HR levels, assessed by two 24-h ambulatory blood pressure monitoring at 1- to 4-week interval, sex and the presence or absence of TOD were considered for this analysis. All subjects also underwent laboratory and ultrasonographic investigations searching for microalbuminuria (MA), left ventricular hypertrophy (LVH) and carotid atherosclerosis (carotid thickening/plaque). In the whole population, as well as in both genders, LVH, carotid atherosclerosis and MA prevalence rates did not significantly increase with 48-h HR tertiles. When patients were categorized according to the presence or absence of TOD (that is, LVH, carotid atherosclerosis or MA) no significant intergroup differences in 48-h HR were found. Furthermore, average 48-h HR was similar in patients without organ involvement as in those with one, two or three TOD signs. Finally, in a multivariate analysis age, 48-h systolic blood pressure and metabolic syndrome assessed by ATP III criteria, but not HR were independently associated with TOD. Our findings showing that 48-h ambulatory HR is not associated with markers of TOD do not support the view that a faster HR may have an additive value in predicting organ damage in the early phases of essential hypertension.


Osteopetrosis in the IA rat cured by spleen cells from a normal littermate.
Osteopetrosis in ia rats has been cured by combining whole-body irradiation with infusion of spleen cells from a normal littermate. The cure, first seen radiographically and histologically as areas of resorption below the epiphyseal plates of long bones, progressed to produce marrow cavities of normal proportions. Treatment of ia rats with either radiation or normal spleen cells alone was not successful. Furthermore, osteopetrosis was induced in normal littermates when radiation was combined with infusion of mutant (ia) spleen cells. These results show that spleen cells contribute to the resorbing capacity of the skeleton and suggest that osteoclasts might have a hematogenous origin.


A comparative neuropsychological test battery differentiates cognitive signatures of Fragile X and Down syndrome.
Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and weaknesses as well as the affected brain areas. To evaluate the utility and feasibility of six non-verbal comparative neuropsychological (CN) tasks administered in a modified version of the Wisconsin General Test Apparatus (WGTA) to confirm and extend our knowledge of unique cognitive signatures of Fragile X syndrome (FXS) and Down syndrome (DS). A test battery of CN tasks adapted from the animal literature was administered in a modified WGTA. Tasks were selected that have established or emerging brain-behaviour relationships in the domains of visual-perceptual, visual-spatial, working memory and inhibition. Despite the fact that these tasks revealed cognitive signatures for the two ID groups, only some hypotheses were supported. Results suggest that whereas individuals with DS were relatively impaired on visual-perceptual and visual-spatial reversal learning tasks they showed strengths in egocentric spatial learning and object discrimination tasks. Individuals with FXS were relatively impaired on object discrimination learning and reversal tasks, which was attributable to side preferences. In contrast, these same individuals exhibited strengths in egocentric spatial learning and reversal tasks as well as on an object recognition memory task. Both ID groups demonstrated relatively poor performance for a visual-spatial working memory task. Performance on the modified WGTA tasks differentiated cognitive signatures between two of the most common forms of ID. Results are discussed in the context of the literature on the cognitive and neurobiological features of FXS and DS.


[Prehospital analgesia by emergency physicians and paramedics : Comparison of effectiveness].
In some German emergency medical service districts, analgesia is performed by paramedics without support of emergency physicians on scene. With regard to safety and effectiveness, paramedics should not be overshadowed by emergency physicians. Is prehospital analgesia performed by paramedics under medical supervision or emergency physicians comparable regarding processes and effectiveness in the case of isolated limb injury? As a retrospective analysis of patients with isolated limb injury, analgesia performed by paramedics and by emergency physicians was analyzed. In addition to pain reduction, prescribed monitoring, and further airway maneuvers, vital parameters (Glasgow coma scale, systolic blood pressure, heartrate and respiratory rate, oxygen saturation) were recorded at the beginning and end of prehospital treatment. Pain was reduced from NRS 8 ± 1 to NRS 2 ± 1 in the paramedic group, and from NRS 8 ± 2 to NRS 2 ± 2 in the physician group, so the mean pain reduction was 6 ± 2 in the paramedic-group and 5 ± 2 in the physician group (p < 0.001). Adequate analgesia was found in 96.9% in the physician group and 91.7% in the paramedic group (p = 0.113). ECG monitoring and oxygen administration according to SOP was significantly more frequent in the paramedic group than in the physician group (p < 0.001). Respiratory frequency was significantly more frequent in the physician group than in the paramedic group (p < 0.001). The study shows, with a given indication, that German paramedics can independently perform safe and successful analgesia under medical supervision.


Comparison of regulative functions between dietary soy isoflavones aglycone and glucoside on lipid metabolism in rats fed cholesterol.
The effects of dietary soy isoflavones aglycone and glucoside on lipid metabolism were compared in male Sprague-Dawley rats (4 weeks old) given purified diets containing 0.3% cholesterol. The rats were fed a diet supplemented with either isoflavone aglycone-rich powder (IF-A group) or isoflavone glucoside-rich powder (IF-G group) or isoflavone-free diet (control group) for 40 days. The additional level of isoflavone aglycone moiety in the diet was prepared to the same level (approximately 0.096 g/100 g: approximately 0.1% in diet). The activity of hepatic cholesterol 7alpha-hydroxylase tended to be slightly higher in the rats fed isoflavones than in those fed the isoflavone-free diet. On the other hand, the activity of hepatic Delta6 desaturase in the IF-A group was lower than that of the control group. Reflecting this effect, the Delta6 desaturation indices [(20:3n-6+20:4n-6)/18:2n-6] in liver phospholipids of the IF-A group were lower than those in the control group. Liver and serum total cholesterol levels and liver TG level were also reduced by consumption of isoflavone aglycone. Moreover, serum TG level was lowered by consumption of both isoflavones aglycone and glucoside. The level of serum total isoflavones in the IF-A group was significantly higher than that in the IF-G group. Therefore, we speculate that the absorption speed of isoflavone aglycones might be faster than that of isoflavone glucosides in rats. This study suggests that dietary soy isoflavones, particularly their aglycone form, may exert a beneficial effect on lipid metabolism in rats fed cholesterol.


A rare case describing catastrophic destruction of the whole skeleton caused by severe hyperparathyroidism.
Osteitis fibrosa cystica is a skeletal disorder seen in advanced stages of persistent hyperparathyroidism. Although the measurement of serum Ca and intact-parathormone levels provides early diagnosis and decreases the incidence of radiographic bone involvement, progressive major bone lesions may still be seen in developing countries even in the modern era. We aimed to share, by writing up this report, our astonishment after observing how the skeletal system can be ruined by persistent hyperparathyroidism.


The Association between Self-Reported Grocery Store Access, Fruit and Vegetable Intake, Sugar-Sweetened Beverage Consumption, and Obesity in a Racially Diverse, Low-Income Population.
This study sought to examine the relationship between self-reported time and distance to the nearest retail grocery store, healthy and unhealthy food consumption, and objectively measured body mass index (BMI). We conducted a survey with 1,503 racially diverse, low-income residents at five public health centers in Los Angeles County. Most participants reported shopping at a supermarket (86.7%) and driving (59.9%) to their usual source for groceries. Over half reported living less than a mile from (58.9%) and traveling 5 min or less to reach (50.3%) the nearest grocery store. In the multivariable regression models, neither self-reported distance nor time to the nearest grocery store was consistently associated with fruit and vegetable intake, sugar-sweetened beverage consumption, or BMI. Results suggest that the need to consider access and quality as well as urban planning and transportation, when examining the relationship between the retail food environment and health outcomes.


Ni-Catalyzed Amination Reactions: An Overview.
Nitrogen-containing organic compounds are valuable in many fields of science and industry. The most reliable method for the construction of C(sp(2) )-N bonds is undoubtedly palladium-catalyzed amination. In spite of the great achievements made in this area, the use of expensive Pd-based catalysts constitutes an important limitation for large-scale applications. Since nickel is the least expensive and most abundant among the group 10 metals, the interest in Ni-based catalysts for processes typically catalyzed by palladium has grown considerably over the last few years. Herein, we revise the development of Ni-catalyzed amination reactions, emphasizing the most relevant and recent advances in the field.


Impact of formate on the growth and productivity of Clostridium ljungdahlii PETC and Clostridium carboxidivorans P7 grown on syngas.
The current energy model based on fossil fuels is coming to an end due to the increase in global energy demand. Biofuels such as ethanol and butanol can be produced through the syngas fermentation by acetogenic bacteria. The present work hypothesizes that formate addition would positively impact kinetic parameters for growth and alcohol production in Clostridium ljungdahlii PETC and Clostridium carboxidivorans P7 by diminishing the need for reducing equivalents. Fermentation experiments were conducted using completely anaerobic batch cultures at different pH values and formate concentrations. PETC cultures were more tolerant to formate concentrations than P7, specially at pH 5.0 and 6.0. Complete growth inhibition of PETC occurred at sodium formate concentrations of 30.0 mM; however, no differences in growth rates were observed at pH 7.0 for the two strains. Incubation at formate concentrations lower than 2.0 mM resulted in increased growth rates for both strains. The most recognizable effects of formate addition on the fermentation products were the increase in the total carbon fixed into acids and alcohols at pH 5.0 and pH 6.0, as well as, a higher ethanol to total products ratio at pH 7.0. Taken all together, these results show the ability of acetogens to use formate diminishing the energy demand for growth, and enhancing strain productivity.


Global Muscle Coactivation of the Sound Limb in Gait of People with Transfemoral and Transtibial Amputation.
The aim of this study was to analyze the effect of the level of amputation and various prosthetic devices on the muscle activation of the sound limb in people with unilateral transfemoral and transtibial amputation. We calculated the global coactivation of 12 muscles using the time-varying multimuscle coactivation function method in 37 subjects with unilateral transfemoral amputation (10, 16, and 11 with mechanical, electronic, and bionic prostheses, respectively), 11 subjects with transtibial amputation, and 22 healthy subjects representing the control group. The results highlighted that people with amputation had a global coactivation temporal profile similar to that of healthy subjects. However, amputation increased the level of the simultaneous activation of many muscles during the loading response and push-off phases of the gait cycle and decreased it in the midstance and swing subphases. This increased coactivation probably plays a role in prosthetic gait asymmetry and energy consumption. Furthermore, people with amputation and wearing electronic prosthesis showed lower global coactivation when compared with people wearing mechanical and bionic prostheses. These findings suggest that the global lower limb coactivation behavior can be a useful tool to analyze the motor control strategies adopted and the ability to adapt to the prosthetic device.


The Effect of Daily Sedation-Weaning Application on Morbidity and Mortality in Intensive Care Unit Patients.
Background/aims Sedation is one of the most important components of intensive care unit (ICU) in patients who are mechanically ventilated at intensive care conditions. As a result of sedation and analgesia in the intensive care unit, the patient is to be awakened a comfortable and easy process. The aim of the study is to demonstrate the effects of day-time sedation interruptions in intensive care patients. Material and methods We made a retrospective review of 100 patients who were monitored, mechanically ventilated and treated at our intensive care unit between January 2008 and January 2013. Patients were divided into two groups, including Group P (continuous infusion of sedative agent) and Group D (daily sedation interruptions - daily recovery). Demographics, mechanical ventilation time, stay at intensive care unit, hospitalization period, time of first weaning, success of weaning, ventilator-related pneumonia (VRP), total doses of drugs, re-intubation frequency, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) scores and mortality rates of patients were compared. Ramsay Sedation Score (RSS) was used to evaluate the level of sedation. Considering that ideal sedation level is "3" with RSS, RSS < 3 is considered as mild sedation, while RSS > 3 is considered as deep sedation. Results There was no difference between demographics of patients. Mechanical ventilation period was significantly longer in Group P than Group D (p < 0.001). When stay at ICU unit was considered, ICU stay was significantly longer in Group P than Group D (p < 0.001). No statistically significant difference was found between two groups with respect to hospitalization period. In inter-group comparison, time to start first weaning was significantly late in Group P than Group D (p < 0.05). There was no difference between groups in terms of frequency of success of weaning and mortality rate (p > 0.05). In inter-group comparison the frequency of reintubation viewed in Group D was significantly less than in Group P (p < 0.05). Considering development of VRP, it was significantly more common in Group P in comparison with Group D (p < 0.05). No statistically significant difference was found between groups in terms of doses of sedative agents (p > 0.05). Considering doses of opioid analgesics, the total dose of fentanyl was significantly higher in Group P than Group D (p = 0.04), while no difference was found for doses of morphine (p > 0.05). Again, no statistical difference was found in doses of muscle relaxant agents (p > 0.05). Conclusion It was observed that the sedation technique with daily interruption is superior to continuous infusion of sedatives. Accordingly, we believe that daily weaning will make positive contributions to patients who are mechanically ventilated at intensive care unit.


Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage.
CCN2 is best known as a promoter of chondrocyte differentiation among the CCN family members, and its null mice display skeletal dysmorphisms. However, little is known concerning roles of the other CCN members in chondrocytes. Using both in vivo and in vitro approaches, we conducted a comparative analysis of CCN2-null and wildtype mice to study the roles of CCN2 and the other CCN proteins in cartilage development. Immunohistochemistry was used to evaluate the localization of CCN proteins and other chondrocyte-associated molecules in the two types of mice. Moreover, gene expression levels and the effects of exogenous CCN proteins on chondrocyte proliferation, differentiation, and the expression of chondrocyte-associated genes in their primary chondrocytes were evaluated. Ccn3 was dramatically upregulated in CCN2-null cartilage and chondrocytes. This upregulation was associated with diminished cell proliferation and delayed differentiation. Consistent with the in vivo findings, CCN2 deletion entirely retarded chondrocyte terminal differentiation and decreased the expression of several chondrocyte-associated genes in vitro, whereas Ccn3 expression drastically increased. In contrast, the addition of exogenous CCN2 promoted differentiation strongly and induced the expression of the associated genes, whereas decreasing the Ccn3 expression. These findings collectively indicate that CCN2 induces chondrocyte differentiation by regulating the expression of chondrocyte-associated genes but that these effects are counteracted by CCN3. The lack of CCN2 caused upregulation of CCN3 in CCN2-null mice, which resulted in the observed phenotypes, such as the resultant delay of terminal differentiation. The involvement of the PTHrP-Ihh loop in the regulation of CCN3 expression is also suggested.


Impact of caring for persons with Alzheimer's disease or dementia on caregivers' health outcomes: findings from a community based survey in Japan.
This study assessed how family caregivers for patients with Alzheimer's disease (AD) or dementia in Japan differed from non-caregivers in characteristics and health outcomes (i.e., comorbidities, health-related quality of life [HRQoL], productivity, and resource use). Caregivers were hypothesized to experience significantly poorer outcomes than non-caregivers. Data were combined from the 2012 and 2013 National Health and Wellness Survey in Japan (n = 60000). Caregivers for adult relatives with AD or dementia were compared with non-caregivers on: comorbidities (including Patient Health Questionnaire (PHQ-9) cutoff scores suggesting presence/absence of major depressive disorder (MDD)), Work Productivity and Activity Impairment (WPAI), SF-36v2-based HRQoL, and healthcare resource utilization. Sociodemographic characteristics, health characteristics and behaviors, and Charlson comorbidity index (CCI) scores were compared across groups. Propensity matching, based on scores generated from a logistic regression predicting caregiving, was used to match caregivers with non-caregivers with similar likelihood of being caregivers. Bivariate comparisons across matched groups served to estimate outcomes differences due to caregiving. Among 55060 respondents, compared with non-caregivers (n = 53758), caregivers (n = 1302) were older (52.6 vs. 47.5 years), more frequently female (53 % vs. 49 %), married/partnered, frequent alcohol drinkers, current smokers, exercisers, and not employed, and they averaged higher CCI scores (0.37 vs. 0.14), all p < 0.05. Propensity scores incorporated sex, age, body mass index (BMI), exercise, alcohol, smoking, marital status, CCI, insured status, education, employment, income, and children in household. A greedy matching algorithm produced 1297 exact matches, excluding 5 non-matched caregivers. Health utilities scores were significantly lower among caregivers (0.724) vs. non-caregivers (0.764), as were SF-36v2 Physical and Mental Component Summary scores. Caregivers vs. non-caregivers had significantly higher absenteeism, presenteeism-related impairment, overall work impairment (25.8 % vs. 20.4 %, respectively), and activity impairment (25.4 % vs. 21.8 %), more emergency room and traditional provider visits (7.70 vs. 5.35) in the past six months, and more frequent MDD (14 % vs. 9 %), depression, insomnia, anxiety, and pain. Those providing care for patients with AD or dementia in Japan experienced significantly poorer HRQoL and greater comorbid risk, productivity impairment, and resource use. These findings inform the need for greater support for caregivers and their patients.


Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis.
Five to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the central nervous system, these treatments can be limiting for subsets of patients due to adverse effects and expense. To circumvent these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE), a model of autoimmune-mediated demyelination that induces visual and motor pathologies similar to those experienced by people with multiple sclerosis (MS). EAE was induced in female and male mice and the impact of limiting dietary carbohydrates by feeding a ketogenic diet (KD) enriched in medium chain triglycerides (MCTs), alpha-linolenic acid (an omega-3 fatty acid), and fiber was evaluated in both a preventive regimen (prior to immunization with MOG antigen) and an interventional regimen (following the onset of symptoms). Motor scores were assigned daily and visual acuity was measured using optokinetic tracking. Immunohistochemical analyses of optic nerves were done to assess inflammatory infiltrates and myelination status. Fatty acid and cytokine profiling from blood were performed to evaluate systemic inflammatory status. The KD was efficacious when fed as a preventive regimen as well as when initiated as an interventional regimen following symptom onset. The KD minimally impacted body weight during the experimental time course, increased circulating ketones, prevented motor and ocular deficits, preserved myelination of the optic nerve, and reduced infiltration of immune cells to optic nerves. The KD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with EAE-mediated pathological inflammation. In light of ongoing clinical trials using dietary strategies to treat people with MS, these findings support that a KD enriched in MCTs, omega-3 fatty acids, and fiber promotes a systemic anti-inflammatory milieu and ameliorates autoimmune-induced demyelinating visual and motor deficits.


Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery.
Slices of human cortical tissue from epilepsy surgery were investigated with intracellular recordings to elucidate the mechanisms contributing to augmented synaptic excitation and to repetitive activity. The analysis of single synaptic potentials revealed, amongst other differences to rodent cortex, a disturbance of GABAA inhibition, namely depolarizing responses. A tentative ionic mechanism, impaired KCl outward-transport (KCC2), was evaluated in a rat model (0-Mg hyperexcitability). The observed down-regulation of KCC2 mRNA after 0-Mg-ACSF exposure of slices may contribute to the depolarizations by GABA. The factors enabling repetitive activity were addressed with a paired-pulse paradigm. In slices from epilepsy surgery, synaptic responses were virtually constant with interstimulus intervals between 100 and 1000 ms. Tiagabine markedly prolonged the effects of released GABA at GABAA receptors, but paired-pulse behaviour was only slightly affected. We demonstrate that bicuculline-induced paroxysmal activity of rat cortex is frequency-limited (to about <1 Hz) by presynaptic GABAB receptors. The lack of frequency limitation of synaptic events suggests an impaired GABAB receptor function in the human epileptogenic cortex. The data are discussed regarding the pivotal role of KCl transport in epileptic disorders of various origins and the role of GABAB receptors in the frequency limitation of paroxysmal activity.


Vitamin D regulates glucose metabolism in zebrafish (Danio rerio) by maintaining intestinal homeostasis.
Vitamin D (VD) is a steroid hormone that is widely known to play an important role in maintaining mineral homeostasis, and regulating various physiological functions. Our previous results demonstrated that the interruption of VD metabolism caused hyperglycemia in zebrafish. In the present study we further explored the mechanism that VD regulates glucose metabolism by maintaining intestinal homeostasis in zebrafish. Our results showed that the expression of several peptide hormones including gastric inhibitory peptide, peptide YY, and fibroblast growth factor 19 in the intestine decreased, while the expression of sodium glucose cotransporter-1 and gcg was increased in the intestine of the zebrafish fed with the VD3-deficient diet. Consistently, similar results were obtained in cyp2r1-/- zebrafish, in which endogenous VD metabolism is blocked. Furthermore, the results obtained from germ-free zebrafish exhibited that VD-regulated glucose metabolism was partly dependent on the microbiota in zebrafish. Importantly, the transplantation of gut microbiota collected from cyp2r1-/- zebrafish to germ-free zebrafish led to hyperglycemic symptoms in the fish, which were associated with the altered structure and functions of the microbiota in cyp2r1-/- zebrafish. Interestingly, the treatments with acetate or Cetobacterium somerae, a potent acetate producer, lowered the glucose contents whereas augmented insulin expression in zebrafish larvae. Notably, acetate supplementation alleviated hyperglycemia in cyp2r1-/- zebrafish and other diabetic zebrafish. In conclusion, our study has demonstrated that VD modulates the gut microbiota-SCFAs-gastrointestinal hormone axis, contributing to the maintenance of glucose homeostasis.


T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease.
Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T-suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T-cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.


Knowledge, attitude and practice of modern contraception among single women in a rural and urban community in southeast Nigeria.
The contraceptive information and services offered to single women in most developing countries is compromised by stigma attached to premarital sex. This study was to ascertain the knowledge, attitude and practice of contraception among single women in a rural and urban community in southeast Nigeria, using a cross-sectional survey of 279 and 295 single women in Ngwo (rural) and Enugu (urban) community. The mean age of the population was 21.3 years. Contraceptive awareness was more among the urban than rural respondents (90.2% vs 34.1%). The major sources of contraceptive knowledge were mass media (68%) and peer groups (86.3%) for the urban and rural respondents, respectively. Most respondents in both groups had positive attitude towards contraception. More urban than rural respondents (68.3% vs 12.5%) began sexual activity during adolescence and the level of contraceptive use during first coitus were 48.4% and 13.7%, respectively. Of the currently sexually active respondents, 32.5% (rural) and 59.7% (urban) were using a form of modern contraception. Condoms, followed by oral pills were the most popular contraceptive method because they can easily procure them over the counter. Poor contraceptive information, highly critical behavior of family planning providers towards unmarried women seeking contraception and attitude of male partners militate against contraceptive practice. There is need to promote information and education on contraception among single women, their male partners and family planning providers.


Bone mineral density in Crohn's disease: a longitudinal study of budesonide, prednisone, and nonsteroid therapy.
Corticosteroids may contribute to the bone loss associated with Crohn's disease (CD). We investigated the effect on bone mineral density (BMD) of treatment with budesonide, a steroid with low systemic activity, and compared the outcome with prednisone and nonsteroid therapy in patients with CD. Prospective annual BMDs of the lumbar spine (LS) and femoral neck (FN) were measured for 2 yr in 138 patients with quiescent CD treated with mean daily doses of 8.5 mg of budesonide (n = 48), 10.5 mg of prednisone (n = 45), or nonsteroid drugs (n = 45). Between baseline and 1 yr, the mean LS BMD decreased 2.36% in the budesonide group (p < 0.001), 0.61% in the prednisone group (ns), and 0.09% in the nonsteroid group (ns). The difference between budesonide and nonsteroid groups was significant (p = 0.003). In the 2nd yr, LS BMD did not change in the three groups. After 2 yr, FN BMD decreased 2.94% in the budesonide group (p < 0.01), 0.36% in the prednisone group (ns), and 1.05% in the nonsteroid group (ns); the differences among groups were not significant. The proportion of patients with bone loss of >2% per annum at the LS and FN was higher in the budesonide group than in the nonsteroid group (p < 0.001) and prednisone group (p < 0.05). Patients with CD receiving maintenance treatment for 2 yr with prednisone show little change in BMD, whereas treatment with budesonide may be associated with LS and FN bone loss. Budesonide does not confer an advantage over low-dose prednisone for the preservation of BMD.


Effects of copper on A-type potassium currents in acutely dissociated rat hippocampal CA1 neurons.
The effects of copper on voltage-gated A-type potassium currents were investigated in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp technique. Extracellular application of various concentrations of copper (1-1000 microM) reversibly reduced the amplitude of voltage-gated A-type potassium currents in a dose-dependent manner with a 50% inhibitory concentration value of 130 microM. Copper (300 microM) increased the V1/2 of the activation curve and state-inactivation curve by 17.2 and 9.0 mV, respectively. Thus, copper slowed down the activation and inactivation process of voltage-gated A-type potassium currents. This study indicated that copper reversibly inhibits the hippocampal CA1 neuronal voltage-gated A-type potassium current in a dose-dependent and voltage-dependent manner, and such actions are likely involved in the regulation of the neuronal excitability and the pathophysiology of Wilson's disease.


Advance modern medicine with clinical case reports.
Randomized clinical trial (RCT) can fail to demonstrate the richness of individual patient characteristics. Given the unpredictable nature of medicine, a patient may present in an unusual way, have a strange new pathology, or react to a medical intervention in a manner not seen before. The publication of these novelties as case reports is a fundamental way of conveying medical knowledge. Throughout history there have been famous case studies that shaped the way we view health and disease. Case reports can have the following functions: (I) descriptions of new diseases; (II) study of mechanisms; (III) discovery new therapies; (IV) recognition of side effects; and (V) education. Before submitting a case report, it is worthwhile to refer to the Case Report Check Sheet described by Green and Johnson [2006].


Past experience modulates the neural mechanisms of episodic memory formation.
Neuroscientists have observed the "birth" of memories, but have not explored how an organism's past experience with materials interacts with the neural mechanisms of episodic memory formation. Using functional neuroimaging, we searched for such an interaction by examining brain activity during memory encoding that predicted participants' subsequent episodic memory for novel and repeated scenes. Memory for both scene types was predicted by a common posterior network in occipital and parietal cortices. Medial temporal memory predictors were modulated by scene repetition: the right anterior hippocampus and right amygdala predicted memory for novel scenes only, whereas posterior hippocampi predicted memory for repeated scenes only. There was also greater functional connectivity between the temporal pole and anterior versus posterior hippocampus, and this link predicted memory for novel but not repeated scenes. In contrast, there was greater functional connectivity between the precuneus and posterior versus anterior hippocampus, and this link predicted memory for repeated but not novel scenes. Together, these results reveal a functional specialization within the hippocampus for the encoding of novel and previously experienced materials, and suggest that the topography of this specialization might be related to local variations in connectivity. Because episodic memory for repeated scenes was superior, our results also support traditional views of encoding emphasizing the role of prior representations, and illuminate one way in which humans use existing memories to help form new ones. In so doing, our results challenge recent novelty-encoding hypotheses.


Topologic Analysis of Plasma Mitochondrial DNA Reveals the Coexistence of Both Linear and Circular Molecules.
Cellular mitochondrial DNA (mtDNA) is organized as circular, covalently closed and double-stranded DNA. Studies have demonstrated the presence of short mtDNA fragments in plasma. It is not known whether circular mtDNA might concurrently exist with linear mtDNA in plasma. We elucidated the topology of plasma mtDNA using restriction enzyme BfaI cleavage signatures on mtDNA fragment ends to differentiate linear and circular mtDNA. mtDNA fragments with both ends carrying BfaI cleavage signatures were defined as circular-derived mtDNA, whereas those with no cleavage signature or with 1 cleavage signature were defined as linear-derived mtDNA. An independent assay using exonuclease V to remove linear DNA followed by restriction enzyme MspI digestion was used for confirming the conclusions based on BfaI cleavage analysis. We analyzed the presence of BfaI cleavage signatures on plasma DNA ends in nonhematopoietically and hematopoietically derived DNA molecules by sequencing plasma DNA of patients with liver transplantation and bone marrow transplantation. Both linear and circular mtDNA coexisted in plasma. In patients with liver transplantation, donor-derived (i.e., liver) mtDNA molecules were mainly linear (median fraction, 91%; range, 75%-97%), whereas recipient-derived (i.e., hematopoietic) mtDNA molecules were mainly circular (median fraction, 88%; range, 77%-93%). The proportion of linear mtDNA was well correlated with liver DNA contribution in the plasma DNA pool (r = 0.83; P value = 0.0008). Consistent data were obtained from a bone marrow transplantation recipient in whom the donor-derived (i.e., hematopoietic) mtDNA molecules were predominantly circular. Linear and circular mtDNA molecules coexist in plasma and may have different tissue origins.


Mycobacterium goodii: An Emerging Nosocomial Pathogen: A Case Report and Review of the Literature.
Mycobacterium goodii, a rapidly growing nontuberculous mycobacterium, is an emerging pathogen in nosocomial infections. Its inherent resistance patterns make it a challenging organism to treat, and delays in identification can lead to poor outcomes. We present a case of cardiac device pocket infection with M. goodii, complicated by both antibiotic resistance and drug reactions that highlight the challenges faced by clinicians trying to eradicate these infections. We also present a brief review of the English literature surrounding this disease, including a table of all reported cases of M. goodii infections and their outcomes to act as guide for clinicians formulating treatment plans for these infections. A clear understanding of diagnostic methods and treatment caveats is essential to curing infections caused by these organisms.


Preparation of hyaluronan polyaldehyde-a precursor of biopolymer conjugates.
Native hyaluronan (HA) has been oxidized to polyaldehyde polymers with a degree of substitution (DS) of up to 50%. Two different procedures enabling the control of the degree of substitution were followed in this study. Selective oxidation of primary hydroxyl groups of N-acetyl-D-glucosamine of hyaluronan was performed either in an aqueous solution containing AcNH-TEMPO/NaBr/NaOCl or in an aprotic solvent containing Dess-Martin periodinane (DMP). It was found that a change of reaction parameters (reaction time and temperature, type of catalyst, oxidant-to-HA ratio, presence of nitrogen, buffer type, and concentration) had an influence on the degree of substitution and molecular weight. The derivatives were characterized by MS, NMR spectroscopy, and SEC-MALLS. Degradation of hyaluronic acid by the oxidant was observed and confirmed by SEC. The effect of oxidized derivatives of hyaluronan on cells was studied by means of NIH 3T3 fibroblast viability, which indicates that prepared hyaluronan polyaldehydes are biocompatible and suitable for medical applications and tissue engineering. The function of polyaldehyde as precursor for other modification was illustrated in the reaction with lysine.


Clinical utility of the mBIAS and NSI validity-10 to detect symptom over-reporting following mild TBI: A multicenter investigation with military service members.
Self-report measures are commonly relied upon in military healthcare environments to assess service members following a mild traumatic brain injury (mTBI). However, such instruments are susceptible to over-reporting and rarely include validity scales. This study evaluated the utility of the mild Brain Injury Atypical Symptoms scale (mBIAS) and the Neurobehavioral Symptom Inventory Validity-10 scale to detect symptom over-reporting. A total of 359 service members with a reported history of mTBI were separated into two symptom reporting groups based on MMPI-2-RF validity scales (i.e., non-over-reporting versus symptom over-reporting). The clinical utility of the mBIAS and Validity-10 as diagnostic indicators and screens of symptom over-reporting were evaluated by calculating sensitivity, specificity, positive test rate, positive predictive power (PPP), and negative predictive power (NPP) values. An mBIAS cut score of ≥10 was optimal as a diagnostic indicator, which resulted in high specificity and PPP; however, sensitivity was low. The utility of the mBIAS as a screening instrument was limited. A Validity-10 cut score of ≥33 was optimal as a diagnostic indicator. This resulted in very high specificity and PPP, but low sensitivity. A Validity-10 cut score of ≥7 was considered optimal as a screener, which resulted in moderate sensitivity, specificity, NPP, but relatively low PPP. Owing to low sensitivity, the current data suggests that both the mBIAS and Validity-10 are insufficient as stand-alone measures of symptom over-reporting. However, Validity-10 scores above the identified cut-off of ≥7should be taken as an indication that further evaluation to rule out symptom over-reporting is necessary.


Cerebral infarctions with negative CT scans.
A selection of 181 stroke patients with a negative scan on computed tomography (CT) was studied. The CT scans were done at least 24 h after ictus. 39 of these cases were excluded because of a cortically located pathological uptake on a concomitant radionuclide scan. The 142 remaining cases were compared with patients who had CT-verified central and cortical infarctions. The CT-negative infarctions showed a profile of risk factors similar to the one in CT-verified central infarctions. It differed markedly, however, from the clinical picture of the cortically located infarctions. Thus, the subjects with a negative CT and isotope scan had a lower percentage of carotid lesions of hemodynamic significance (studied by isotope angiography) and a lower frequency of atrial fibrillation. There was also a much higher percentage of pure motor hemipareses among the CT-negative infarctions. This suggests that a great part of CT- and gamma camera-negative cerebrovascular infarctions may be suspected to be small lacunae, which are beyond the resolution capacity of the CT scan.


Immunocytochemical detection of cyclin, a proliferation-associated protein, in cytologic preparations.
Cyclin is a nuclear protein associated with DNA-polymerase delta, whose expression correlates with cell proliferation in vitro. To assess the value of cyclin staining in diagnostic cytology, an anticyclin monoclonal antibody was used to survey cyclin expression in cytologic preparations obtained as "bench top" aspirates from surgically resected specimens. The tissues assayed included carcinomas and normal and benign proliferative tissues of renal, mammary, prostatic and colonic origin. Staining was performed via the avidin-biotin-complex immunoperoxidase method. The staining of tumor cells was nuclear, with sparing of the nucleoli; the results were variable in different areas of a given tumor and varied significantly between tumors of the same histopathologic type. Benign proliferative tissues also showed staining. Nonproliferative tissues, such as renal tubules adjacent to a renal cell adenocarcinoma, were largely, but not entirely, nonstaining. The percentage of cyclin-positive nuclei was sometimes much higher than the typical percentages of tumor cells found in S phase. This observation was confirmed in two cases in which cyclin staining was much greater than the percentage of S-phase cells detected by flow cytometry. This suggests either stabilization of the protein beyond S phase in cells and/or dysregulation of cyclin expression in malignant cells. The viability of unfixed surgically resected tissue may also have affected the detection of cyclin, a problem that should not exist with clinically aspirated tissue fixed immediately after aspiration. These preliminary observations suggest that the selective use of cyclin staining may facilitate cytologic diagnoses. Furthermore, the wide range of cyclin expression within tumors of one histologic type suggests that cyclin expression may serve as a new parameter for investigating tumor behavior and prognosis.


Mast cell degranulation induces delayed rectal allodynia in rats: role of histamine and 5-HT.
Visceral hypersensitivity is a common feature of functional bowel disorders, where an increased number of mast cells have often been described. Thus, we investigated the effect of an experimental mast cell degranulation induced by BrX-537A on somatic (tail heating) and visceral (rectal distension) sensitivity in rats and the involvement of histamine and/or serotonin on this last response. After BrX-537A administration, the latency of tail withdrawal reflex was shortened within the 2- to 8-hr period. Moreover, BrX-537A reduced the distension volume threshold from 0.8 ml to 0.4 ml inducing allodynia, from 6 to 12 hr after its administration. This effect was suppressed by doxantrazole (mast cell stabilizing agent) and WAY 100635 (5-HT1A receptor antagonist), and reproduced by 5-HTP (5-HT precursor) and 8-OH-DPAT (5-HT1A receptor agonist). However, neither granisetron (5-HT3 receptor antagonist) nor H1, H2, or H3 histamine receptor antagonists modified the BrX-537A-induced allodynia. Consequently, mast cell degranulation initiates a delayed somatic and visceral allodynia, with the participation of serotonin, through 5-HT1A receptor activation, on the visceral response.


Marine-Derived Polymeric Materials and Biomimetics: An Overview.
The review covers recent literature on the ocean as both a source of biotechnological tools and as a source of bio-inspired materials. The emphasis is on marine biomacromolecules namely hyaluronic acid, chitin and chitosan, peptides, collagen, enzymes, polysaccharides from algae, and secondary metabolites like mycosporines. Their specific biological, physicochemical and structural properties together with relevant applications in biocomposite materials have been included. Additionally, it refers to the marine organisms as source of inspiration for the design and development of sustainable and functional (bio)materials. Marine biological functions that mimic reef fish mucus, marine adhesives and structural colouration are explained.


Intravenous thrombolysis in ischemic stroke patients with a prior intracranial hemorrhage: a meta-analysis.
The history of intracranial hemorrhage (ICrH) is considered a contraindication for intravenous thrombolysis (IVT) among patients with acute ischemic stroke (AIS). Objective: This study aimed at comparing the safety of IVT among patients with and without a history of ICrH. We performed a systematic review of the literature. Data regarding all AIS patients with prior ICrH who received IVT were retrieved. Meta-analysis was performed to compare the rate of symptomatic hemorrhagic transformation (sHT), death within 90 days, and favorable and unfavorable 90-day functional outcomes based on modified Rankin Scale (mRS) among stroke patients with and without prior ICrH. Out of 13,032 reviewed records, 7 studies were included in the systematic review and meta-analysis. Quantitative synthesis of data regarding the rate of sHT (5068 patients) revealed no significant difference between the two groups [odds ratio, OR: 1.55 (0.77, 3.12); p = 0.22]. However, a significantly higher risk of death within 90 days [OR: 3.91 (2.16, 7.08); p < 0.00001] and a significantly higher 90-day poor functional outcomes (mRS, 4-6) [OR: 1.57 (1.07, 2.30); p = 0.02] were observed among patients with prior ICrH. Likewise, the percentage of 90-day good functional outcomes (mRS, 0-1) was lower in the prior ICrH group [OR: 0.54 (0.35, 0.84); p = 0.06]. Subgroup analyses in patients with a history of ICrH (based on both patients' medical history and imaging confirmation) revealed no significant between-group differences in rates of sHT. Also, sensitivity analysis consisting of only studies using standard-dose IVT showed no difference in sHT rates and 90-day outcomes between the two groups. There was no evidence of heterogeneity (I 2 >50%) among included studies. The results of this study indicated that prior history of ICrH does not increase the risk of sHT post-IVT, but it is associated with a higher risk of death and poor functional outcomes in 90 days.