The N-terminal extensions of Deinococcus radiodurans Dps-1 mediate DNA major groove interactions as well as assembly of the dodecamer.
Dps (DNA protection during starvation) proteins play an important role in the protection of prokaryotic macromolecules from damage by reactive oxygen species. Previous studies have suggested that the lysine-rich N-terminal tail of Dps proteins participates in DNA binding. In comparison with other Dps proteins, Dps-1 from Deinococcus radiodurans has an extended N terminus comprising 55 amino acids preceding the first helix of the 4-helix bundle monomer. In the crystal structure of Dps-1, the first approximately 30 N-terminal residues are invisible, and the remaining 25 residues form a loop that harbors a novel metal-binding site. We show here that deletion of the flexible N-terminal tail obliterates DNA/Dps-1 interaction. Surprisingly, deletion of the entire N terminus also abolishes dodecameric assembly of the protein. Retention of the N-terminal metal site is necessary for formation of the dodecamer, and metal binding at this site facilitates oligomerization of the protein. Electrophoretic mobility shift assays using DNA modified with specific major/minor groove reagents further show that Dps-1 interacts through the DNA major groove. DNA cyclization assays suggest that dodecameric Dps-1 does not wrap DNA about itself. A significant decrease in DNA binding affinity accompanies a reduction in duplex length from 22 to 18 bp, but only for dodecameric Dps-1. Our data further suggest that high affinity DNA binding depends on occupancy of the N-terminal metal site. Taken together, the mode of DNA interaction by dodecameric Dps-1 suggests interaction of two metal-anchored N-terminal tails in successive DNA major grooves, leading to DNA compaction by formation of stacked protein-DNA layers.


Differential attachment to and subsequent contamination of agricultural crops by Salmonella enterica.
U.S. salmonellosis outbreaks have occurred following consumption of tomato and cantaloupe but not lettuce. We report differential contamination among agricultural seedlings by Salmonella enterica via soil. Members of the family Brassicaceae had a higher incidence of outbreak than carrot, lettuce, and tomato. Once they were contaminated, phyllosphere populations were similar, except for tomato. Contamination differences exist among tomato cultivars.


In vitro lysis of islet cells by lymphocytes from diabetic BB/Wor rats is not antibody mediated.
The role of pancreatic islet cell directed, antibody dependent cell mediated cytotoxicity (ADCC) in the development of diabetes was investigated in the spontaneously diabetic BB/Wor rat. Specific lysis of BB/Wor rat islet cells by effector splenic lymphocytes from acutely diabetic (AD) BB/Wor and control Wistar Furth (WF) rats in a 51Cr release assay was evaluated using four different ADCC assay protocols: two involved the pre-incubation, in the assay wells, of effector or target cells with heat inactivated sera from diabetic or control rats (1:10 dilution) prior to the addition of target or effector cells, respectively. The other two protocols involved the pre-incubation of effector or target cells with a 1:10 dilution of sera from diabetic or control rats, followed by two washes, prior to their addition into serum-free assay wells containing target or effector cells, respectively. The antibodies most likely to be involved in islet directed ADCC are the islet cell surface antibodies (ICSA), which have previously been demonstrated in the sera of diabetic rats; their presence in the diabetic sera used in these assays was confirmed. In the absence of serum pretreatment of either effector or target cells, specific lysis of islet cell targets by AD effector cells was 32.0 +/- 1.4% (n = 34), while specific lysis by control WF effector cells was 9 +/- 1.4% (n = 19), p less than 0.001. In no instance in any of the ADCC assays did the pre-treatment with AD (or WF) sera significantly increase target cell lysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Binding of the unorthodox transcription activator, Crl, to the components of the transcription machinery.
The small regulatory protein Crl binds to sigmaS, the RNA polymerase stationary phase sigma factor. Crl facilitates the formation of the sigmaS-associated holoenzyme (EsigmaS) and thereby activates sigmaS-dependent genes. Using a real time surface plasmon resonance biosensor, we characterized in greater detail the specificity and mode of action of Crl. Crl specifically forms a 1:1 complex with sigmaS, which results in an increase of the association rate of sigmaS to core RNA polymerase without any effect on the dissociation rate of EsigmaS. Crl is also able to associate with preformed EsigmaS with a higher affinity than with sigmaS alone. Furthermore, even at saturating sigmaS concentrations, Crl significantly increases EsigmaS association with the katN promoter and the productive isomerization of the EsigmaS-katN complex, supporting a direct role of Crl in transcription initiation. Finally, we show that Crl does not bind to sigma70 itself but is able at high concentrations to form a weak and transient 1:1 complex with both core RNA polymerase and the sigma70-associated holoenzyme, leaving open the possibility that Crl might also exert a side regulatory role in the transcriptional activity of additional non-sigmaS holoenzymes.


A comparative study of clinical symptoms and treatment outcomes of acute bacterial prostatitis according to urine culture.
Because acute bacterial prostatitis (ABP) is an urgent condition of the prostate but prostatic massage is contraindicated at the onset of ABP, clinical symptoms and urine tests are used for diagnosis. In this study, we compared the clinical symptoms and treatment outcomes of patients with negative urine culture results, to whom only empirical antibiotics were administered, with those of patients with positive urine culture results. Patients were divided into two groups according to the results of urine culture. Then, the clinical symptoms and course of each group were analyzed. In addition, age, symptoms, antibiotics, mean inpatient and outpatient length of treatment, and the treatment outcome of each group were also analyzed. Of the total 144 patients, the positive urine culture group consisted of 51 patients (35.4%) and the most frequent bacterial strain causing ABP was reported to be Escherichia coli. Fever and storage symptoms were significantly more common in the positive urine culture group than in the negative urine culture group (p=0.031 and 0.047, respectively). Only inpatient treatment was significant longer in the positive urine culture group than in the negative urine culture group (p<0.05). The mean length of treatment of inpatients was 4.8±2.6 days and 6.2±2.9 days in the two groups, respectively. No sequelae such as prostatic abscess or chronic prostatitis were found in either group. In the treatment of ABP, the use of empirical antibiotics can be expected to have sufficient effects regardless of bacterial culture. However, it is hard to determine the causative bacteria of ABP by urine culture results only.


Evaluation of Central Auditory Processing in Musicians and Non-Musicians.
Auditory processing is the analysis of sounds' attributions such as localization, lateralization, temporality, frequency, loudness, phase, auditory memory and auditory attention through primer and secondar central auditory paths. This study aims to show that music contributes on auditory processing by applying central auditory tests on two groups who are musicians and nonmusicians. The participants in this study are aged between 20 and 40. The mean age of the musician participants is 24.40±3.811, when the mean age of non-musician participants is 26.07±4.525. Each group has 30 participants. All participants got examined for otorhinolaryngology and they were tested for pure tone audiometry and immitansmetric measurement. For musician participants, this study included people who have professional music career for at least 5 years and for non-musician participants, it has been included those who are capable of normal hearing. All participants tested for Frequency Patterns Test (FPT), Duration Patterns Test (DPT), Random Gap Detection Test (RGDT) and Staggered Spondaic Word Test (SSWT). The results of the FPT, DPT, RGDT and SSWT tests applied to musician and non-musician participants indicate that there is a statistical significance on auditory processing between these two groups (p<0.05). It is founded that there is a considerable difference as a result of statistical significance between the tests from right to left and from left to right (p<0.05). In addition, it is founded that musician participants have much more comprehension ability in the tests from left to right than the tests from right to lefts. This study indicates that people who are interested in music professionally have developed auditory processing skills and senses than people who does not show any professional interest in music.


Screening HIV-positive men who have sex with men for hepatitis C re-infection risk: is a single question on condom-use enough? A sensitivity analysis.
Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection. Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours. Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7-88.2%). Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment. Clinical Trial Number: NCT02785666 , 30.05.2016.


Enhanced Recovery After Surgery Interactive Audit System: 10 Years' Experience with an International Web-Based Clinical and Research Perioperative Care Database.
The Enhanced Recovery After Surgery (ERAS) is a managed care program that has shown the ability to reduce complications following elective colorectal surgery. In 2006, the ERAS ® Society developed the ERAS ® Interactive Audit System (EIAS), which has allowed centers in over 20 countries to enter perioperative patient data to benchmark against international practice within the audit system and act as a stimulus for quality improvement. The de-identified patient data are coded in SQL (a relational database), stored on secure servers, and data governance aspects have been secured in all involved countries. A collaborative approach is undertaken within involved units toward research questions with published cohort data from the audit system having demonstrated the importance of overall compliance on improving patient outcomes and less cost of care. The EIAS has shown that collaborative clinical effort can drive quality improvement in a short time frame in an international context.


Southern blot and PCR analyses of dystrophin gene deletions in Japanese patients with Duchenne muscular dystrophy.
We have analyzed 34 Japanese patients of 31 families with Duchenne muscular dystrophy (DMD) by Southern blot and PCR (polymerase chain reaction) to detect large deletions in the genomic dystrophin gene on the X chromosome. Fifteen families (48%) had various deletions in the dystrophin gene by Southern blot analysis using the dystrophin cDNA probes 1-2a, 2b-3 and 8 which effectively covers the high-risk regions of deletion. Lengths and positions of the gene deletions detected were variable. Although there were no common deletions of exons in the gene of the DMD patients examined with the above cDNA probes, the deletion frequency of each exon was almost the same as the result previously reported in Caucasian DMD patients. The PCR method was also applied to confirm gene deletions in 9 cases from the above 15 families by amplifying 6 different regions of the dystrophin gene. Eight out of 9 DMD cases had gene deletions at the same genomic regions as found by Southern blot analysis. In a single DMD case, the Southern blot analysis indicated the exon 12 deletion, but PCR successfully amplified a 331 bp DNA fragment containing exon 12 and flanking introns. This difference may arise by a large deletion except for the above small 331 bp sequence in the HindIII digests of dystrophin gene.


Compressed and distributed sensing of neuronal activity for real time spike train decoding.
Multivariate point processes are increasingly being used to model neuronal response properties in the cortex. Estimating the conditional intensity functions underlying these processes is important to characterize and decode the firing patterns of cortical neurons. This paper proposes a new approach for estimating these intensity functions directly from a compressed representation of the neurons' extracellular recordings. The approach is based on exploiting a sparse representation of the extracellular spike waveforms, previously demonstrated to yield near-optimal denoising and compression properties. We show that by restricting this sparse representation to a subset of projections that simultaneously preserve features of the spike waveforms in addition to the temporal characteristics of the underlying intensity functions, we can reasonably approximate the instantaneous firing rates of the recorded neurons with variable tuning characteristics across a multitude of time scales. Such feature is highly desirable to detect subtle temporal differences in neuronal firing characteristics from single-trial data. An added advantage of this approach is that it eliminates multiple steps from the typical processing path of neural signals that are customarily performed for instantaneous neural decoding. We demonstrate the decoding performance of the approach using a stochastic cosine tuning model of motor cortical activity during a natural, nongoal-directed 2-D arm movement.


Modular porous metal augments for treatment of severe acetabular bone loss during revision hip arthroplasty.
Modular acetabular augments were implanted in 16 patients (16 hips) for support of an uncemented hemispheric acetabular component during revision acetabular reconstruction. Based on the classification of Paprosky, acetabular bone defects were classified as 2A in one hip, 2B in three hips, 2C in one hip, 3A in five hips, and 3B in six hips. Preoperatively, the prosthetic femoral head centers were located at a mean horizontal distance of 18.6 mm (range, -3-46 mm), and a mean vertical distance of 27.6 mm (range, -16-52 mm) from the approximate femoral head center. Postoperatively, the prosthetic femoral head centers were located at a mean horizontal distance of 10.4 mm (range, 1-25 mm), and a mean vertical distance of 7.4 mm (range, -15-25 mm). At final followup, no implant had evidence of migration or loosening. At early clinical followup, this modular acetabular augment system seems helpful in acetabular reconstructions that cannot be treated with an uncemented hemispheric cup that would have required other forms of treatment such as structural allografts, acetabular cages, bilobed acetabular components, or custom acetabular components. Longer term followup is required to determine whether there are untoward effects of using a modular acetabular reconstructive system.


Biological constraints simplify the recognition of hand shapes.
This study sought to identify constraints that might lead to a concise system of recognizing fingerspelling hand shapes. Previous studies of grasping suggested that hand shape is controlled using combinations of a small number of neuromuscular synergies, but fingerspelling shapes appear to be more highly individuated and, therefore, might require a larger number of degrees of freedom. Static hand postures of the American Sign Language manual alphabet were recorded by measuring 17 joint angles. Principal components (PCs) analysis was compared to the use of subsets of individual variables (i.e., joint angles) for reduction in degrees of freedom. The first four PCs were similar across subjects. Classification using weightings from these four components was 86.6% accurate, while classification using four individual variables was 88.5% accurate (thumb abduction, as well as flexion at the index and middle finger proximal interphalangeal joints and the ring finger metacarpalphalangeal joint). When chosen for each subject, particular four-variable subsets yielded correct rates above 95%. This superior performance of variable subsets over PC weighting vectors suggests that the reduction in degrees of freedom is due to biomechanical and neuromuscular constraints rather than synergistic control. Thus, in future application to dynamic fingerspelling, reasonable recognition accuracy might be achieved with a significant reduction in both computational and measured degrees of freedom.


Advantages of a Photodiode Detector Endoscopy System in Fluorescence-Guided Percutaneous Liver Biopsies.
Image-guided liver biopsies can improve their success rate when combined with the optical detection of Indocyanine Green (ICG) fluorescence accumulated in tumors. Previous works used a camera coupled to a thin borescope to capture and quantify images from fluorescence emission during procedures; however, light-scattering prevented the formation of sharp images, and the time response for weakly fluorescent tumors was very low. Instead, replacing the camera with a photodiode detector shows an improved temporal resolution in a more compact and lighter device. This work presents the new design in a comparative study between both detection technologies, including an assessment of the temporal response and sensitivity to the presence of background fluorescence.


Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection.
Initiation of the innate immune response requires agonist recognition by pathogen-recognition receptors such as the Toll-like receptors (TLRs). Toll/interleukin-1 receptor (TIR) domain-containing adaptors are critical in orchestrating the signal transduction pathways after TLR and interleukin-1 receptor activation. Myeloid differentiation primary response gene 88 (MyD88) adaptor-like (MAL)/TIR domain-containing adaptor protein (TIRAP) is involved in bridging MyD88 to TLR2 and TLR4 in response to bacterial infection. Genetic studies have associated a number of unique single-nucleotide polymorphisms in MAL with protection against invasive microbial infection, but a molecular understanding has been hampered by a lack of structural information. The present study describes the crystal structure of MAL TIR domain. Significant structural differences exist in the overall fold of MAL compared with other TIR domain structures: A sequence motif comprising a β-strand in other TIR domains instead corresponds to a long loop, placing the functionally important "BB loop" proline motif in a unique surface position in MAL. The structure suggests possible dimerization and MyD88-interacting interfaces, and we confirm the key interface residues by coimmunoprecipitation using site-directed mutants. Jointly, our results provide a molecular and structural basis for the role of MAL in TLR signaling and disease protection.


Atrous spatial pyramid pooling and multi-image data fusion for smooth muscle segmentation in upper gastrointestinal sphincters.
Gastrointestinal (GI) sphincters provide critical roles in regulating the transport of contents along the GI tract. Dysfunctions of GI sphincters are associated with a range of major digestive disorders. Despite their importance, the microstructures of GI sphincters are not well investigated. While micro-computed tomography (μ-CT) provides detailed 3D images, conventional segmentation methods rely on manual correction, which is both time-consuming and prone to human error. This study proposes a segmentation method using atrous spatial pyramid pooling (ASPP), which helps in capturing different effective fields of view from a given input feature map, thereof providing finer local and global information for a given pixel. Additionally, we explored the use of multi-species data fusion to make the model more generalized. The proposed segmentation network incorporating ASPP and multi-species data fusion improved the segmentation of sphincter muscle images. Specifically, it increased the dice score and Jaccard index by 3.7% and 5.8%, respectively, while reducing the variance compared to conventional methods.Clinical relevance- Techniques developed in this study will inform μ-CT segmentation of human upper GI sphincters for detailed structural analysis of muscular dysfunction.


At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products.
The interaction of advanced glycation end products (AGEs) with their main receptor RAGE in endothelial cells induces intracellular generation of reactive oxygen species (ROS) and the expression of vascular cell adhesion molecule (VCAM)-1. We investigated the role of distinct sources of ROS, including the mitochondrial electron transport chain, NAD(P)H oxidase, xanthine oxidase, and arachidonic acid metabolism, in AGE-induced VCAM-1 expression. The induction of ROS and VCAM-1 by AGEs in cultured human umbilical vein endothelial cells was specifically blocked by an anti-RAGE antibody. The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. The inhibition of Cu/Zn superoxide dismutase inhibited both ROS and VCAM-1 induction, indicating that H2O2 by this source is involved as a mediator of VCAM-1 expression by AGEs. Altogether, these results demonstrate that ROS generated by both NAD(P)H-oxidase and the mitochondrial electron transport system are involved in AGE signaling through RAGE, and indicate potential targets for the inhibition of the atherogenic signals triggered by AGE-RAGE interaction.


Molecular signature of erythroblast enucleation in human embryonic stem cells.
While enucleation is a critical step in the terminal differentiation of human red blood cells, the molecular mechanisms underlying this unique process remain unclear. To investigate erythroblast enucleation, we studied the erythroid differentiation of human embryonic stem cells (hESCs), which provide a unique model for deeper understanding of the development and differentiation of multiple cell types. First, using a two-step protocol, we demonstrated that terminal erythroid differentiation from hESCs is directly dependent on the age of the embryoid bodies. Second, by choosing hESCs in two extreme conditions of erythroid culture, we obtained an original differentiation model which allows one to study the mechanisms underlying the enucleation of erythroid cells by analyzing the gene and miRNA (miR) expression profiles of cells from these two culture conditions. Third, using an integrated analysis of mRNA and miR expression profiles, we identified five miRs potentially involved in erythroblast enucleation. Finally, by selective knockdown of these five miRs we found miR-30a to be a regulator of erythroblast enucleation in hESCs.


Questions about the numerical value and quantitative data transfer of tooth preparation-from experience guidance to digital guidance.
Tooth preparation is a common operation in dental clinical practice. This procedure is irreversible and invasive from the point of view of tooth preservation. Conditions of the abutment tooth, treatment methods, and restoration materials for target restoration affect tooth preparation. To achieve the goals of tooth tissue preservation, dental pulp protection, and periodontal health, dentistry professionals agreed on the importance of minimizing the amount of tooth reduction. The foundations for realizing this consensus are as follows. First, the available restoration materials with improved comprehensive performance need less target restoration space. Next, teeth can be prepared under a digital guide, and the real-time measurement of restoration space can be verified due to the invention of digital technologies for the analysis of the quantity and shape of the prepared tooth and tooth measurement. Moreover, guiding methods for preparation have been developed from freehand operation under the naked eye based on accumulated personal experience to digital-guidance jointing microscope. These innovations indicate the creation of a prototype of guided prosthodontics that is precise and applies real-time measurement throughout the process of tooth preparation. From the perspective of the evolution of digital, guided, and micro prosthodontics, this article raised seven questions about the numerical value and quantitative data transfer of tooth preparation and evaluated the authenticity of existing numerical requirements from the perspective of the four elements of measurement. Identifying unified measuring methods and developing measuring tools with a precision of hundred or ten microns will be the key to solving the problem about the authenticity of numerical measurement. Furthermore, this paper summarizes the methods of how to control tooth reduction and explains in depth why the currently dominant tooth preparation technology, which is based on empiricism, cannot effectively achieve the goals in digital prosthodontics. Therefore, we strongly call for rebuilding the digital foundation of prosthodontic treatment immediately.


GPU-enabled FREALIGN: accelerating single particle 3D reconstruction and refinement in Fourier space on graphics processors.
Among all the factors that determine the resolution of a 3D reconstruction by single particle electron cryo-microscopy (cryoEM), the number of particle images used in the dataset plays a major role. More images generally yield better resolution, assuming the imaged protein complex is conformationally and compositionally homogeneous. To facilitate processing of very large datasets, we modified the computer program, FREALIGN, to execute the computationally most intensive procedures on Graphics Processing Units (GPUs). Using the modified program, the execution speed increased between 10 and 240-fold depending on the task performed by FREALIGN. Here we report the steps necessary to parallelize critical FREALIGN subroutines and evaluate its performance on computers with multiple GPUs.


National cost of trauma care by payer status.
Several studies have described the burden of trauma care, but few have explored the economic burden of trauma inpatient costs from a payer's perspective or highlighted the differences in the average costs per person by payer status. The present study provides a conservative inpatient national trauma cost estimate and describes the variation in average inpatient trauma cost by payer status. A retrospective analysis of patients who had received trauma care at hospitals in the Nationwide Inpatient Sample from 2005-2010 was conducted. Our sample patients were selected using the appropriate "International Classification of Diseases, Ninth Revision, Clinical Modification" codes to identify admissions due to traumatic injury. The data were weighted to provide national population estimates, and all cost and charges were converted to 2010 US dollar equivalents. Generalized linear models were used to describe the costs by payer status, adjusting for patient characteristics, such as age, gender, and race, and hospital characteristics, such as location, teaching status, and patient case mix. A total of 2,542,551 patients were eligible for the present study, with the payer status as follows: 672,960 patients (26.47%) with private insurance, 1,244,817 (48.96%) with Medicare, 262,256 (10.31%) with Medicaid, 195,056 (7.67%) with self-pay, 18,506 (0.73%) with no charge, and 150,956 (5.94%) with other types of insurance. The estimated yearly trauma inpatient cost burden was highest for Medicare at $17,551,393,082 (46.79%), followed by private insurance ($10,772,025,421 [28.72%]), Medicaid ($3,711,686,012 [9.89%], self-pay ($2,831,438,460 [7.55%]), and other payer types ($2,370,187,494 [6.32%]. The estimated yearly trauma inpatient cost burden was $274,598,190 (0.73%) for patients who were not charged for their inpatient trauma treatment. Our adjusted national inpatient trauma yearly costs were estimated at $37,511,328,659 US dollars. Privately insured patients had a significantly higher mean cost per person than did the Medicare, Medicaid, self-pay, or no charge patients. The results of the present study have demonstrated that the distribution of trauma burden across payers is significantly different from that of the overall healthcare system and suggest that although the burden of trauma is high, the burden of self-pay or nonreimbursed inpatient services is actually lower than that of overall medical care.


Enterococcus faecalis sufCDSUB complements Escherichia coli sufABCDSE.
Iron-sulfur [Fe-S] clusters are inorganic prosthetic groups that play essential roles in all living organisms. Iron and sulfur mobilization, formation of [Fe-S] clusters, and delivery to its final protein targets involves a complex set of specific protein machinery. Proteobacteria has three systems of [Fe-S] biogenesis, designated NIF, ISC, and SUF. In contrast, the Firmicutes system is not well characterized and has only one system, formed mostly by SUF homologs. The Firmicutes phylum corresponds to a group of pathological bacteria, of which Enterococcus faecalis is a clinically relevant representative. Recently, the E. faecalis sufCDSUB [Fe-S] cluster biosynthetic machinery has been identified, although there is no further information available about the similarities and/or variations of Proteobacteria and Firmicutes systems. The aim of the present work was to compare the ability of the different Proteobacteria and Firmicutes systems to complement the Azotobacter vinelandii and Escherichia coli ISC and SUF systems. Indeed, E. faecalis sufCDSUB is able to complement the E. coli SUF system, allowing viable mutants of both sufABCDSE and iscRSU-hscBA-fdx systems. The presence of all E. faecalis SUF factors enables proper functional interactions, which would not otherwise occur in proteins from different systems.


SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-β receptor stability.
Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr249 (SMURF2Thr249) activates its E3 ubiquitin ligase activity. Here, we demonstrate that SMURF2Thr249 phosphorylation plays an essential role in maintaining GSC stemness and tumorigenicity. SMURF2 silencing augmented the self-renewal potential and tumorigenicity of patient-derived GSCs. The SMURF2Thr249 phosphorylation level was low in human glioblastoma pathology specimens. Introduction of the SMURF2T249A mutant resulted in increased stemness and tumorigenicity of GSCs, recapitulating the SMURF2 silencing. Moreover, the inactivation of SMURF2Thr249 phosphorylation increases TGF-β receptor (TGFBR) protein stability. Indeed, TGFBR1 knockdown markedly counteracted the GSC phenotypes by SMURF2T249A mutant. These findings highlight the importance of SMURF2Thr249 phosphorylation in maintaining GSC phenotypes, thereby demonstrating a potential target for GSC-directed therapy.


Pathology: A Satisfying Medical Profession.
Medical students are often unsure about the viability of a career as a physician in pathology. In particular, they are concerned that pathologists may not have a gratifying lifestyle or be well compensated. These worries may cause angst among medical students considering pathology and among junior pathology residents wondering if they made the correct career choice. A 2016 survey of nearly 20 000 physicians including nearly 400 pathologists provides reassuring data about compensation and career choice. This survey showed that 52% of pathologists are satisfied with their career choice and 63% are satisfied with their compensation. Among the 26 specialties that were surveyed, pathologists ranked 2 in believing that they were fairly compensated. Moreover, 66% of pathologists find that making diagnostic decisions, a core aspect of our discipline, is the most rewarding aspect of their career. Pathologists also ranked among the highest groups of physicians in reporting happiness at work and among the lowest groups reporting burnout. Overall, these 2016 surveys show that the majority of pathologists find deep satisfaction in their careers as pathologists.


Xenobiotic-metabolizing cytochromes P450 convert prostaglandin endoperoxide to hydroxyheptadecatrienoic acid and the mutagen, malondialdehyde.
Cyclooxygenases catalyze the oxygenation of arachidonic acid to prostaglandin endoperoxides. Cyclooxygenase-2- and the xenobiotic-metabolizing cytochrome P450s 1A and 3A are all aberrantly expressed during colorectal carcinogenesis. To probe for a role of P450s in prostaglandin endoperoxide metabolism, we studied the 12-hydroxyheptadecatrienoate (HHT)/malondialdehyde (MDA) synthase activity of human liver microsomes and purified P450s. We found that human liver microsomes have HHT/MDA synthase activity that is concentration-dependent and inhibited by the P450 inhibitors, ketoconazole and clotrimazole with IC(50) values of 1 and 0.4 microM, respectively. This activity does not require P450 reductase. HHT/MDA synthase activity was present in purified P450s but not in heme alone or other heme proteins. The catalytic activities of various purified P450s were determined by measuring rates of MDA production from prostaglandin endoperoxide. At 50 microM substrate, the catalytic activities of purified human P450s varied from 10 +/- 1 to 0.62 +/- 0.02 min(-1), 3A4 >> 2E1 > 1A2. Oxabicycloheptane analogs of prostaglandin endoperoxide, U-44069 and U-46619, induced spectral changes in human P450 3A4 with K(s) values of 240 +/- 20 and 130 +/- 10 microM, respectively. These results suggest that co-expression of cyclooxygenase-2 and P450s in developing cancers may contribute to genomic instability due to production of the endogenous mutagen, MDA.


Lower extremity kinematics in runners with patellofemoral pain during a prolonged run.
Investigate lower extremity kinematics in runners with patellofemoral pain (PFP) syndrome during a prolonged run. For this study, 20 runners with PFP and 20 uninjured controls performed a prolonged run on a treadmill at a self-selected pace. The run ended based on HR, perceived exertion, or level of knee pain. Kinematic data were analyzed at the beginning and at the end of the run. The PFP group demonstrated less peak knee flexion, peak hip adduction, eversion excursion, peak knee flexion velocity, peak hip adduction velocity, and peak hip internal rotation velocity compared with controls. A significant main effect for time indicated that increases in most kinematic variables occurred at the end of the run. Interestingly, five runners with PFP displayed atypical motions of knee valgus and eight displayed hip abduction during the first half of stance. The PFP group as a whole displayed less overall motion compared with controls. This may be indicative of a strategy aimed at limiting lower extremity movement to reduce pain. However, increases in joint motion occurred at the end of the run where pain levels were greatest. Three distinct PFP subgroups were noted, and each demonstrated unique kinematic mechanisms that may be associated with PFP. In the knee valgus subgroup, increased knee valgus and decreased peak motions were noted in other joints. In the hip abduction subgroup, less knee flexion and motion overall was noted. In the subgroup that displayed typical first half patterns (knee and hip adduction), increased hip internal rotation and decreased knee internal rotation were observed. These results suggest that several different kinematic mechanisms related to PFP may exist.


[The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging].
To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats. Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis. It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.


Prolonged Linear Amplification of qPCR for the Correction of Amplification Variation and the Absolute Quantification without Standard Curves.
The variable amplification efficiency of each thermal cycle of qPCR obeys the Poisson distribution, and the qPCR system dynamically changes, so there must be a detection error in its quantitative analysis. Here, more than 20 cycles of the linear amplification of qPCR can be produced as the BSA hydrogel is introduced to achieve the controlled release of Taq DNA polymerase. There is a significant negative correlation between the slope of linear amplification and Ct values (r = -0.9455), and it is well evident that the slope can reflect the amplification efficiency and a linear positive correlation exists between them. Through the change in the concentration of primers in the qPCR system, an exponential equation between Ct values and the slopes can be fitted (R2 = 0.9995). The slopes and Ct values of each qPCR system can be corrected by using this equation to guarantee that there will be significant consistency in their amplification efficiency because the degree of linear fitting (R2) between Ct values and the logarithm of their corresponding concentration of the DNA template increased significantly. By this time, the accurate amplification efficiency can be calculated in a known multiple of two initial concentrations of DNA templates. With the aid of the relationship between the known primer concentration and the fluorescence intensity at the end of PCR (End RFU), the initial concentrations of DNA templates can be reversely calculated in the absence of standard curves.


Urinary 6-sulfatoxymelatonin excretion and aging: new results and a critical review of the literature.
The apparent age-related decline in melatonin production has been thought to continue in a secular manner across the lifespan. While it is clear that melatonin levels in children and adolescents are elevated compared to older individuals, the question of whether there is a sudden or gradual change has not been adequately addressed. In this study, we report the excretion of the melatonin metabolite, 6-sulfatoxymelatonin in 253 subjects aged between 21 and 82 yr. The correlation with age was significant (r = -0.24; P < 0.05). When the data was analysed by ANOVA using 5-yr age spans, there was a significant effect of age, but post hoc analysis indicated that after 25 yr of age there was no significant decline in excretion of the metabolite. Thus, although the oldest subjects excreted 36% less melatonin metabolite than the youngest, the decrease occurred at a very early age. In the second part of the study, we re-evaluated the data from seven previous studies that measured plasma melatonin levels or metabolite excretion across a wide range of ages and 11 studies comparing young versus older subjects. Statistical analysis by ANOVA again suggested that the changes in melatonin occurring with age were essentially complete before 30 yr of age. The youngest subjects produced at the most twice the amount of melatonin as the oldest subjects. Finally, we evaluated the mean plasma melatonin levels in 144 groups of normal subjects reported in 137 separate publications with respect to age. Again, whereas there was a significant correlation with age, ANOVA showed that there was no difference between groups after 35 yr of age, and the oldest groups had levels that were only 43% of the youngest groups. We conclude that melatonin production is lower in older people, but that the change occurs very early in life, around 20-30 yr of age.


Retroviral vector infection and transplantation in rats of primary fetal rat hepatocytes.
Retroviral vectors were used to transduce recombinant DNA encoding firefly luciferase, Escherichia coli beta-galactosidase or human factor IX into fetal rat hepatocytes in primary culture. Hepatocytes were transduced optimally during a restricted time interval, 2-4 days post-plating. Although efficient and stable expression of reporter gene products was observed in vitro, it was affected differentially by culture conditions (plating density, media constituents) and chemical modulators of hepatocyte growth and differentiation (gelatin, hydrocortisone, isobutylmethylxanthine). Cultured cells, mock-infected or infected with a luciferase-expressing vector, were harvested non-enzymatically and injected subcutaneously into the dorsal neck fascia of neonatal syngeneic rats. Tissue isolated from injection sites one week later contained hepatocyte foci. In animals transplanted with infected cells, the preliminary results suggest that luciferase activity was present at these sites in proportion to the numbers of injected cells. These findings and previous observations made with hepatocytes from neonatal and adult primary cultures, indicate that from day 19 in utero through maturity the transient temporal 'period of susceptibility' to infection in vitro is independent of the developmental state of starting tissue. Transplantability of cultured fetal hepatocytes infected with retroviral vectors and stably expressing reporter gene products suggests that such cells might provide promising models for liver gene therapy.


Hybrid ancestry of an island subspecies of Galápagos mockingbird explains discordant gene trees.
Introgression of genes through hybridization has been proposed to be an important driver of speciation, but in animals this has been shown only in relatively few cases until recently. Additionally, introgressive hybridization among non-sister species leads to a change in the gene tree topology of the concerned loci and thus complicates phylogenetic reconstruction. However, such cases of ancient introgression have been very difficult to demonstrate in birds. Here, we present such an example in an island bird subspecies, the Genovesa mockingbird (Mimus parvulus bauri). We assessed phylogenetic relationships and population structure among mockingbirds of the Galápagos archipelago using mitochondrial and nuclear DNA sequences, autosomal microsatellites, and morphological measurements. Mitochondrial haplotypes of Genovesa mockingbirds clustered closely with the haplotypes from two different species, San Cristóbal (M. melanotis) and Española (M. macdonaldi) mockingbirds. The same pattern was found for some haplotypes of two nuclear gene introns, while the majority of nuclear haplotypes of Genovesa mockingbirds were shared with other populations of the same species (M. parvulus). At 26 autosomal microsatellites, Genovesa mockingbirds grouped with other M. parvulus populations. This pattern shows that Genovesa mockingbirds contain mitochondria and some autosomal alleles that have most likely introgressed from M. melanotis into a largely M. parvulus background, making Genovesa mockingbirds a lineage of mixed ancestry, possibly undergoing speciation. Consistent with this hypothesis, mockingbirds on Genovesa are more clearly differentiated morphologically from other M. parvulus populations than M. melanotis is from M. parvulus.


Effects of destrin pathway mutations on the gene expression profile.
This study aimed to explore the interaction and crosstalk between pathways in response to destrin mutations. All the pathways from the MINT database were downloaded, a protein-protein interaction network was then constructed, and the crosstalk between pathways was investigated, in particular, the overlap of 2 significant pathway analysis results. As expected, the results showed that regulation of the actin cytoskeleton was the significant pathway of destrin mutations in mice. Further analysis indicated that 28 significant pathways cross-talked with the pathway regulating the actin cytoskeleton. Importantly, 3 pathways, including regulation of actin cytoskeleton pathway, pathways in cancer, and the B cell receptor signaling pathway were linked by inositol phosphate metabolism based on crosstalk analysis of Gene Ontology relationships among pathways. All of these pathways have been demonstrated to participate in cytoskeleton dynamics. These findings might provide valuable insights into cytoskeleton dynamic abnormalities in destrin mutations of corneal diseases.


[Myocardial microcirculation in humans--new approaches using MRI].
One crucial goal of magnetic resonance imaging (MRI) in patients with coronary artery disease (CAD) is the characterization of myocardial microcirculation that reflects tissue supply much better than detection and quantification of a stenosis itself. PERFUSION: Myocardial perfusion is one important parameter of microcirculation and it is commonly detected by first-pass techniques using contrast agents (CA). Despite the quantification of perfusion it is an indispensable component of a comprehensive diagnosis to determine the perfusion reserve, which is believed a good indicator for viability of myocardium. However, most MRI techniques for perfusion imaging are Ca based and this implies a restricted reproducibility in humans. Beyond it, most first-pass techniques are qualitative and not quantitative. REGIONAL BLOOD VOLUME: Another parameter of microcirculation is the regional intracapillary myocardial blood volume (RBV) that almost represents the whole intramyocardial blood volume due to its dominating volume fraction. The RBV reflects the autoregulatory adaptation of microvessels, e.g., a severe stenosis may lead to an increase of the RBV by capillary recruitment, and the RBV is reduced in scar areas. The RBV may be quantified by first-pass techniques; however, this demands a definite relation between signal intensity and concentration of the CA, which is difficult to find for the range of concentrations present during the first pass. Until recently, no techniques existed for the exact and noninvasive assessment of the RBV. CAPILLARY RECRUITMENT: The evaluation of the relevance of a coronary artery stenosis is of paramount interest for the therapeutic decision. A severe stenosis implies the activation of compensation mechanisms, which includes poststenotic dilation of the microvascular system. This lowering of the vascular resistance aims to maintain sufficient blood supply at least under resting conditions. However, many obstacles hamper the noninvasive assessment of this autoregulatory response so far. Our laboratory recently developed different techniques for the assessment of myocardial perfusion, regional myocardial blood volume, and capillary recruitment. These techniques are based on theoretical and physiologic considerations and work mainly without CA. In this article, feasibility and reproducibility of these approaches are shown in volunteers and patients. MR exams were performed on a 1.5-T whole body scanner (SIEMENS Vision) and a 2-T system (BRUKER Tomikon). Stress examinations were done repeatedly under pharmacologically induced stress (dipyridamole or adenosine, infusion rate: 0.56 mg/kg body weight over 4 min via an antecubital vein). Heart rate and blood pressure were continuously monitored during stress exams. T1 Spin labeling used in this work is based on T1 measurements after global and slice-selective spin preparation using a fast ECG-gated saturation recovery FLASH sequence. Due to the inflow of unsaturated proton spins, T1 in tissue is shortened after slice-selective preparation case compared to global saturation. We showed that, assuming a two compartment model with fast proton exchange between the compartments, the absolute perfusion P (in [ml/g/min]) can be calculated as P = lambda/T1(blood) ([T1(global)/T1(selective)] - 1), where the blood tissue partition coefficient lambda represents the quotient of water content of capillary blood and perfused tissue, which is approximately 0.9 ml/g in myocardial tissue. T1(blood) is the longitudinal relaxation time T1 of the arterial blood, measured in the left ventricle (LV). T1(global) and T1(selective) are the myocardial T1 calculated after the respective spin preparation. Perfusion reserve is evaluated as the quotient of perfusion under adenosine-induced stress and perfusion at rest. In volunteers quantitative perfusion was determined as 2.5 +/- 0.7 ml/g/min (rest), perfusion reserve was about 2.0. Absolute perfusion decreased to 1.6 +/- 0.6 ml/g/min under oxygen breathing. In patients with CAD, myocardial regions with decreased perfusion reserve could be identified. perfusion reserve could be identified. Performing the described spin-labeling technique with an intravascular CA facilitates the determination of the intra-extracapillary water proton exchange frequency and the RBV. In a patient study, the effect of the intravascular CA Feruglose (Amersham) on relaxation rate in myocardium (R1(myo)) in the steady state was investigated (Figure 1). The dependence of R1(myo) on R1(blood) was characterized and compared with a theoretical model which allowed determination of the intra-extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9%). A linear response range of Delta R1(myo) on Delta R1(blood) was estimated which, in future studies, will allow the determination of RBV with intravascular CA (Figure 2). T2* We anticipated that poststenotic vasodilatation implies a capillary recruitment. Almost all (i.e., > 90%) of intramyocardial blood residues in that type of vessel. Due to their large arteriovenous oxygenation difference, myocardial capillaries contain considerable amounts of deoxyhemoglobin (Figure 3). Hence, in regions with autoregulatory capillary recruitment the tissue concentration of deoxyhemoglobin should be elevated when compared to myocardium supplied by a normal vessel (Figure 5b). Due to its paramagnetic property and its intravascular confinement, the natural CA deoxyhemoglobin may be assessed by susceptibility sensitive, or also called blood oxygenation level-dependent (BOLD) MRI. For T2* measurements, a segmented gradient echo pulse sequence was used, which acquired ten successive gradient echoes per rf excitation in a single breathhold. In volunteers, there was an increase in T2* of about 10% under dipyridamole-induced stress (Figure 4). This means a decrease of the intracapillary deoxyhemoglobin concentration, whereas the oxygen consumption under increased perfusion did not change. In myocardial regions of patients, associated with the stenotic artery T2* was significantly lower than in residual myocardium (p < 0.01; Figure 5a). This difference in T2* increased after application of the vasodilator dipyridamole (p < 0.001). In patients being reinvestigated after therapeutic interventions, the microvascular dilation was partly removed (Figure 5c). For the first time we could show that myocardial BOLD MRI detects poststenotic capillary recruitment dependent on a coronary artery stenosis.


A Preliminary Study of Clinical Abbreviation Disambiguation in Real Time.
To save time, healthcare providers frequently use abbreviations while authoring clinical documents. Nevertheless, abbreviations that authors deem unambiguous often confuse other readers, including clinicians, patients, and natural language processing (NLP) systems. Most current clinical NLP systems "post-process" notes long after clinicians enter them into electronic health record systems (EHRs). Such post-processing cannot guarantee 100% accuracy in abbreviation identification and disambiguation, since multiple alternative interpretations exist. Authors describe a prototype system for real-time Clinical Abbreviation Recognition and Disambiguation (rCARD) - i.e., a system that interacts with authors during note generation to verify correct abbreviation senses. The rCARD system design anticipates future integration with web-based clinical documentation systems to improve quality of healthcare records. When clinicians enter documents, rCARD will automatically recognize each abbreviation. For abbreviations with multiple possible senses, rCARD will show a ranked list of possible meanings with the best predicted sense at the top. The prototype application embodies three word sense disambiguation (WSD) methods to predict the correct senses of abbreviations. We then conducted three experments to evaluate rCARD, including 1) a performance evaluation of different WSD methods; 2) a time evaluation of real-time WSD methods; and 3) a user study of typing clinical sentences with abbreviations using rCARD. Using 4,721 sentences containing 25 commonly observed, highly ambiguous clinical abbreviations, our evaluation showed that the best profile-based method implemented in rCARD achieved a reasonable WSD accuracy of 88.8% (comparable to SVM - 89.5%) and the cost of time for the different WSD methods are also acceptable (ranging from 0.630 to 1.649 milliseconds within the same network). The preliminary user study also showed that the extra time costs by rCARD were about 5% of total document entry time and users did not feel a significant delay when using rCARD for clinical document entry. The study indicates that it is feasible to integrate a real-time, NLP-enabled abbreviation recognition and disambiguation module with clinical documentation systems.


Long-term use of cyclosporine A does not adversely impact on clinical outcomes following renal transplantation.
The present review summarizes thirteen selected studies addressing the impact of cyclosporin A (CsA) on long-term outcomes following successful renal transplantation. Together, the data reflect the clinical courses of over 4,000 CsA-treated renal allograft recipients followed from one to ten years from the time of transplantation. Seven of the studies provided historical control data from more than 10,000 patients treated with azathioprine and prednisone. Graft survival beyond one year in CsA-treated recipients was consistently as good as or better than that achieved in the pre-CsA era. Underscoring the graft survival data, severe forms of the afferent arteriolopathy described as pathognomonic for 'CsA nephropathy' have become very uncommon and highly unlikely to be a cause of early or late graft loss. Retrospective analyses of longitudinal changes in aggregate serum creatinine concentrations did not demonstrate any differences in the long-term rate of attrition of allograft function between CsA- and non-CsA-treated patients. Similarly, prospective studies of serial glomerular filtrate rates did not reflect accelerating loss of function in association with long-term CsA use. CsA may be used for up to 10 years following successful renal transplantation without jeopardizing clinical outcomes. Graft arteriopathy (that is, chronic rejection), not progressive nephrotoxicity, is the dominant obstacle to achieving more uniformly successful long-term graft survival in the CsA era.


Severe hypertriglyceridemia prevalence at a primary care setting in Catalonia, Spain.
Hypertriglyceridemia (HTG) increases the risk of cardiovascular disease and pancreatitis, and its prevalence varies across populations. To determine the prevalence of moderate-to-severe hypertriglyceridemia (msHTG, 500-879 mg/dl) and severe hypertriglyceridemia (sHTG, ≥ 880 mg/dl) in a primary care population in Catalonia, Spain, and to categorize them according to presence/absence of factors potentially causing HTG. Retrospective analysis of clinical and laboratory data in SIDIAP (Information System for the Development of Primary Care Research) from 2010, 2013, 2016, and 2019. We considered medications with hypolipidemic effects and those potentially increasing TG levels. We developed logistic regression models adjusted by age and sex to calculate the probability of having ms/sHTG according to covariates of interest. In the study years, 36.2‒42.0% of the >3.5 million active primary care users had ≥1 TG determination. Prevalence for msHTG was 0.7% and for sHTG 0.2% among those with recorded TG. In 2019, 54.7% were female; median (IQR) age was 62.5 (49.4‒73.7) years. Prevalence was higher in 36‒50-year-old persons (1.3% msHTG, 0.4% sHTG) and men (1.1% msHTG, 0.3% sHTG). Most cases were associated with secondary and <20% with non-secondary causes, the latter being most prevalent in young patients. The secondary causes more strongly associated with msHTG/sHTG were obesity, uncontrolled diabetes mellitus (DM) and gamma-glutamyl transferase >100 U/L. The prevalence of msHTG was 0.7% and that of sHTG was 0.2% between 2010 and 2019 among individuals with recorded TG. msHTG/sHTG most often affected men around their fifties and people with obesity and uncontrolled DM. Most msHTG and sHTG cases were associated with the presence of secondary causes.


Antioxidant and antipyretic studies on Pothos scandens L.
To investigate Pothos scandens for the in vitro antioxidant and antipyretic activity. Preliminary phytochemicals, total phenolics and flavonoid contents were analyzed in leaf, stem and root samples. In vitro antioxidant activity was evaluated by different assays such as 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2, 2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+) radical scavenging, ferric-reducing antioxidant power (FRAP) assay, phosphomolybdenum reduction assay, metal chelating activity, superoxide anion radical scavenging activity, hydrogen peroxide and nitric oxide scavenging assay. The antipyretic activity of root methanol extract was studied by pyrexia induced by brewer's yeast on Wistar albino rats at concentration of 200 and 400 mg/kg using paracetamol as standard drug. The total phenolics and tannin content were found to be higher in ethanol extract of stem, whereas total flavonoid content was higher in acetone extract of root. The methanol extract of root showed highest free radical scavenging activity in assays namely ABTS assay (8 221.5 μM TE/g extract), FRAP assay [514.4 mM Fe (II)/g extract], hydrogen peroxide (60.3%) and nitric oxide scavenging assays (58.7%). The DPPH assay and superoxide radical assay results revealed that the ethanol extract of root has remarkable free radical scavenging capacity (IC50 0.284 mg/mL and 70.84%). The antipyretic studies on methanol extract of root showed significant reduction of temperature in pyrexia induced rats at 200 and 400 mg/kg doses. These findings justify that Pothos scandens can be a valuable natural antioxidant and antipyretic source which seemed to provide potential nutraceuticals for human health.


Power spectrum of the rectified EMG: when and why is rectification beneficial for identifying neural connectivity?
The identification of common oscillatory inputs to motor neurons in the electromyographic (EMG) signal power spectrum is often preceded by EMG rectification for enhancing the low-frequency oscillatory components. However, rectification is a nonlinear operator and its influence on the EMG signal spectrum is not fully understood. In this study, we aim at determining when EMG rectification is beneficial in the study of oscillatory inputs to motor neurons. We provide a full mathematical description of the power spectrum of the rectified EMG signal and the influence of the average shape of the motor unit action potentials on it. We also provide a validation of these theoretical results with both simulated and experimental EMG signals. Simulations using an advanced computational model and experimental results demonstrated the accuracy of the theoretical derivations on the effect of rectification on the EMG spectrum. These derivations proved that rectification is beneficial when assessing the strength of low-frequency (delta and alpha bands) common synaptic inputs to the motor neurons, when the duration of the action potentials is short, and when the level of cancellation is relatively low. On the other hand, rectification may distort the estimation of common synaptic inputs when studying higher frequencies (beta and gamma), in a way dependent on the duration of the action potentials, and may introduce peaks in the coherence function that do not correspond to physiological shared inputs. This study clarifies the conditions when rectifying the surface EMG is appropriate for studying neural connectivity.


Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography.
Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18 F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC.


Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats.
Spontaneous motor activity, rota-rod performance (motor co-ordination), body weight gain, food intake, activities of total cholinesterase (blood) and acetylcholinesterase (brain), and dental structure were determined in adult female rats treated with a very high dose of sodium fluoride (500 ppm in drinking water) alone and in combination with calcium carbonate (50 mg/kg body weight by oral intubation) for 60 days. The concentration of fluoride and calcium were measured in the serum of these animals. Administration of sodium fluoride with drinking water produced both behavioural and dental toxicities and not lethality in the present study. A suppression of spontaneous motor activity, a shortening of rota-rod endurance time, a decreased body weight gain and food intake, a suppression of total cholinesterase and acetylcholinesterase activities and dental lesion were observed in test animals. Serum fluoride concentration was raised markedly and that of calcium was decreased in these animals. The effects of sodium fluoride were prevented significantly when animals received calcium carbonate along with sodium fluoride. Serum fluoride content was decreased and that of calcium was restored to control level in these animals. These results indicate that calcium prevents not only fluoride-induced hypocalcemia but also the locomotor behavioral and dental toxicities of fluoride by decreasing bioavailability of fluoride.


Neuroprotective effects of GYKI 52466 on experimental spinal cord injury in rats.
The toxic effects of glutamate in the central nervous system are well known. This neurotoxicity occurs through metabotropic and ionotropic receptors, the latter group composed of N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and kainate receptors. The authors investigated the neuroprotective effects of GYKI 52466, a 2,3-benzodiazepine that is a selective and potent AMPA receptor antagonist, in a rat spinal cord trauma model. Sixty Wistar albino rats were studied in three groups of 20 animals each: sham-operated controls (Group 1); spinal cord-injured rats (Group 2); and spinal cord-injured plus GYKI 52466-treated rats (Group 3). In Groups 2 and 3, spinal cord injury (SCI) was induced at the thoracic level by applying an aneurysm clip to the cord for 1 minute. One minute after the clip was removed, the rats in Group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466. Responses to injury and treatment were evaluated based on biochemical parameters (lipid peroxidation and adenosine 5'-triphosphate [ATP] levels in tissue), and on light and transmission electron microscopy findings in cord tissue collected at different times post-SCI. Five rats from each group underwent assessment of functional recovery at 1, 3, and 5 days after SCI; evaluation was performed using the inclined-plane technique and Tarlov motor grading scale. The mean lipid peroxidation levels in Groups 1 and 2 were 21.73 +/- 4.35 and 35.53 +/- 2.99 nmol/g of wet tissue, respectively. The level in Group 3 was 27.98 +/- 3.93 nmol/g of wet tissue, which was significantly lower than that in Group 2 (p < 0.01). The mean ATP levels in Groups 1 and 2 were 166.21 +/- 25.57 and 41.72 +/- 12.28 nmol/g of wet tissue, respectively. The ATP level in Group 3 was 85.82 +/- 13.92 nmol/g of wet tissue, which was significantly higher than that in Group 2 (p < 0.01). Light microscopic examination of Group 2 tissues showed hemorrhage, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. In contrast, the examination of Group 3 tissues showed limited hemorrhage and no necrosis or vascular thrombi. The most prominent findings in Group 2 were hemorrhage and necrosis, whereas the most prominent findings in Group 3 were focal hemorrhage and leukocyte infiltration. Electron microscopy demonstrated that GYKI 52466 protected the neurons, myelin, axons, and intracellular organelles. The mean inclined-plane angles in Groups 1, 2, and 3 were 65 degrees, 40 to 45 degrees, and 55 degrees, respectively. Motor scale results in all groups showed a similar trend. The findings in this rat model suggest that GYKI 52466 may provide significant therapeutic protection from secondary damage after acute SCI. This agent may be a viable alternative treatment for SCI.


The Good Food Box Pilot Project as a Contribution to Addressing Food Accessibility in the Elderly.
The Good Food Box (GFB) is a program that offers fresh produce to community members. The implementation of a GFB pilot project targeting the elderly in Côte Saint-Luc (CSL) is described. Feasibility is evaluated in terms of partnerships necessary to realize the project and suitability of the GFB among seniors. Outcomes, lessons learned, and future directions are also discussed. GFBs were delivered biweekly for 10 weeks to 14 participants over the age of 65 years. Baseline and final surveys were administered to assess user satisfaction and effects of the project. Overall, participants were satisfied, finding the location convenient and the produce to be of excellent quality. Respondents also indicated an increased quantity of fresh fruits and vegetables in their home and an enhanced connection with the community. Many participants commented on excessive quantity and difficulty preparing certain products, demonstrating that the GFB may not be practical for all seniors. Smaller quantities and volunteer assistance could improve the program. Following the successful pilot project, the GFB was expanded to all members of the CSL community. Using the GFB as a major source of fresh produce will positively impact the health and quality of life for those who reside within the community.


[Intestinal placement of Miller-Abbott-tubes under endoscopic guidance (author's transl)].
Based on experiences with 9 treatments in 7 cases of intestinal obstruction, the technique of endoscopic transgastric guidance of Miller-Abbott-tubes is reported. On our service, the above mentioned method was applied in the treatment of intestinal obstruction observed in cases of advanced malignant lesions as well as in patients with intestinal obstruction in the early postoperative period. Apparative aids and technical guidelines are accentuated. The method requires a team consisting of at least one physician and three assistents with clearly defined competence. Success also depends on the selection of material used. Special problems arise in the treatment of patients following partial gastrectomy. Routine X-rays are important in order to control the course of treatment and to documentate the result. The inclusion of endoscopic aids resulted in successful intestinal intubation in all cases treated. The utilization of recommended guidelines seemingly rules out technical failure in the attempt of placing the tube in the desired anatomic position.


Models for Implant-Induced Capsular Contracture Post Breast Cancer Surgery.
Capsular contracture is a painful deformation of scar-tissue that may form around an implant in post-breast cancer reconstruction or cosmetic surgery. Inflammation due to surgical trauma or contamination in the tissue around the implant could account for recruitment of immune cells, and transdifferentiation of resident fibroblasts into cells that deposit abnormally thick collagen. Here we examine this hypothesis using a mathematical model for interacting macrophages, fibroblasts, myofibroblasts, and collagen. Our model demonstrates that cellular response can, together with inflammatory cell recruitment, account for prognoses.


[Hookworm discovered in a patient presenting with severe iron-deficiency anemia].
The purpose of this report is to describe a case involving severe anemia in a patient from New Caledonia. Endoscopic discovery of adult hematophagic hookworms in mainland France is novel because it is exceptional. However, this case also reminds us that hookworm disease is extremely widespread in the world. It often goes unrecognized causing progressive, insidious anemia that can be severe though long-term tolerance is good.


Novel DNA binding proteins highly specific to UV-damaged DNA sequences from embryos of Drosophila melanogaster.
Three new proteins which selectively bind to UV-damaged DNA were identified and purified to near homogeneity from UV-irradiated Drosophila melanogaster embryos through several column chromatographies. These proteins, tentatively designated as D-DDB P1, P2 and P3, can be identified as different complex bands in a gel shift assay by using UV-irradiated TC-31 probe DNA. Analysis of the purified D-DDB P1 fraction by native or SDS-polyacrylamide gel electrophoresis and FPLC-Superose 6 gel filtration demonstrated that it is a monomer protein which is a 30 kDa polypeptide. The D-DDB P2 protein is a monopolypeptide with a molecular mass of 14 kDa. Both D-DDB P1 and P2 highly prefer binding to UV-irradiated DNA, and have almost no affinity for non-irradiated DNA. Gel shift assays with either UV-irradiated DNA probes demonstrated that D-DDB P1 may show a preference for binding to (6-4) photoproducts, while D-DDB P2 may prefer binding to pyrimidine dimers. Both these proteins require magnesium ions for binding. D-DDB P1 is an ATP-preferent protein. These findings are discussed in relation to two recently described [Todo and Ryo (1991) Mutat. Res., 273, 85-93; Todo et al. (1993) Nature, 361, 371-374] DNA-binding factors from Drosophila cell extracts. A possible role for these DNA-binding proteins in lesion recognition and DNA-binding proteins in lesion recognition and DNA repair of UV-induced photo-products is discussed.


Activated macrophages in congenitally athymic "nude mice" and in lethally irradiate mice.
Resistance to the facultative intracellular bacteria, Brucella abortus and Listeria monocytogenes, is principally the result of acquisition of enhanced antibacterial activity by host macrophages, probably in response to lymphokines released by T lymphocytes. However, the present paper describes a surprisingly high resistance on the part of both congenitally athymic "nude" mice and of lethally irradiated mice compared with normal controls. This enhanced bactericidal activity was evident 24 hr after infection, and could also be demonstrated in macrophages from nude mice cultured in vitro. It was concluded that the macrophages of these animals had been activated before infection.


Sustainability in the AAP Bronchiolitis Quality Improvement Project.
Adherence to American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline recommendations improved significantly through the AAP's multiinstitutional collaborative, the Bronchiolitis Quality Improvement Project (BQIP). We assessed sustainability of improvements at participating institutions for 1 year following completion of the collaborative. Twenty-one multidisciplinary hospital-based teams provided monthly data for key inpatient bronchiolitis measures during baseline and intervention bronchiolitis seasons. Nine sites provided data in the season following completion of the collaborative. Encounters included children younger than 24 months who were hospitalized for bronchiolitis without comorbid chronic illness, prematurity, or intensive care. Changes between baseline-, intervention-, and sustainability-season data were assessed using generalized linear mixed-effects models with site-specific random effects. Differences between hospital characteristics, baseline performance, and initial improvement between sites that did and did not participate in the sustainability season were compared. A total of 2275 discharges were reviewed, comprising 995 baseline, 877 intervention, and 403 sustainability- season encounters. Improvements in all key bronchiolitis quality measures achieved during the intervention season were maintained during the sustainability season, and orders for intermittent pulse oximetry increased from 40.6% (95% confidence interval [CI], 22.8-61.1) to 79.2% (95% CI, 58.0- 91.3). Sites that did and did not participate in the sustainability season had similar characteristics. BQIP participating sites maintained improvements in key bronchiolitis quality measures for 1 year following the project's completion. This approach, which provided an evidence-based best-practice toolkit while building the quality-improvement capacity of local interdisciplinary teams, may support performance gains that persist beyond the active phase of the collaborative.


Morbid Obesity: Increased Risk of Failure After Aseptic Revision TKA.
Patients with obesity are known to have a higher risk of complications after primary TKA; however, there is a paucity of data regarding the effects of obesity with revision TKAs. We asked the following questions : (1) Are patients with morbid obesity (BMI≥40 kg/m2) at greater risk for repeat revision, reoperation, or periprosthetic joint infection (PJI) compared with patients without obesity (BMI<30 kg/m2) after an index revision TKA performed for aseptic reasons? (2) Do patients who are not obese achieve higher Knee Society pain and function scores after revision TKA for aseptic reasons? We used a retrospective cohort study with 1:1 matching for sex, age (±3 years) and date of surgery (±1 year) to compare patients with morbid obesity with patients without obesity with respect to repeat revision, reoperation, and PJI. Using our institution's total joint registry, we identified 1291 index both-component (femoral and tibial) aseptic revision TKAs performed during a 15-year period (1992-2007). Of these, 120 revisions were in patients with morbid obesity (BMI≥40 kg/m2) and 624 were in patients with a BMI less than 30 kg/m2. We then considered only patients with a minimum 5-year followup, which was available for 77% of patients with morbid obesity and 76% of patients with a BMI less than 30 kg/m2 (p=0.84). All patients with morbid obesity who met criteria were included (morbid obesity group: n=93; average followup, 7.9 years) and compared with a matched cohort of patients with a BMI less than 30 kg/m2 (nonmorbid obesity group: n=93; average followup, 7.3 years). Medical records were reviewed to gather details regarding complications and clinical outcomes. Overall, patients with morbid obesity had an increased risk of repeat revision (hazard ratio [HR], 3.8; 95% CI, 1.2-16.5; p<0.02), reoperation (HR, 2.9; 95% CI, 1.3-7.4; p<0.02), and PJI (HR, 6.4; 95% CI, 1.2-119.7; p<0.03). Implant survival rates were 96% (95% CI, 92%-100%) and 100% at 5 years, and 81% (95% CI, 70%-92%) and 93% (95% CI, 86%-100%) at 10 years for the patients with morbid obesity and those without morbid obesity, respectively (p=0.02). At 10 years, The Knee Society pain (90 [95% CI, 88-92] vs 76 [95% CI, 71-81]; p<0.01) and function (61 [95% CI, 53-69] vs 57 [95% CI, 42-52]; p<0.01) scores were higher in patients with a BMI less than 30 kg/m2 compared with patients with morbid obesity. Morbid obesity is associated with increased rates of rerevision, reoperation, and PJI after aseptic revision TKA. As the time-sensitive nature of revision surgery may not always allow for patient or comorbidity optimization, these results emphasize the need for improving our care of patients with morbid obesity earlier on during the osteoarthritic process. Additional studies are needed to risk stratify patients in the morbidly obese population to better guide patient selection and effective optimization. Level III, therapeutic study.


Why are programmes for offenders with personality disorder not informed by the relevant scientific findings?
This paper examines the evidence to justify intervening in those with personality disorder, specifically antisocial personality disorder (ASPD) as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, American Psychiatric Association 1994). The evidence from randomized controlled trials in the mental health literature is reviewed and found to be deficient with only five trials satisfying Cochrane criteria, all of which had a reduction in substance misuse as their primary outcome, rather than a change in the personality disorder per se.Next, I consider the contribution of Thomas Kuhn to explain why it is difficult to develop a scientific basis in forensic mental health. I argue that, because forensic mental health is inclusive in its purpose (interacting with the law, social services and the penal system, all of which have different rules and agendas), it is difficult to develop a consensus on fundamentals, this consensus being a hallmark of a science.Finally, I argue that despite the absence of evidence from mental health, providers for ASPD are in a fortunate position in being able to draw upon the correctional literature. This is relevant, provided that we agree that a reduction in offending is the primary outcome. While mental health can learn much from correctional practice, it can also enhance the efficacy of the latter by, for instance, drawing attention to the specific vulnerabilities of the personality structure that might impede programme delivery in correctional settings. Means of achieving a conjunction of mental health and correctional practice are urgently required as this would be beneficial to both.


Dairy and Plant-Based Milks: Implications for Nutrition and Planetary Health.
Dairy milk products are dominant in the market; however, plant-based milks are gaining prominence among USA consumers. Many questions remain about how plant-based milk products compare to dairy milk from a nutrition, public health, and planetary health perspective. Here, we compare the retail sales, nutrient profiles, and known health and environmental impacts of the production and consumption of dairy and plant-based milks and identify knowledge gaps for future studies. For our plant-based milk comparisons, we reviewed almond, soy, oat, coconut, rice, pea, cashew, and other plant-based milks as data were available. The retail unit price of plant-based milks was generally higher than that of cow's milk, making it less accessible to lower-income groups. Many plant-based milks are fortified to match the micronutrient profile of dairy milk more closely. Notable differences remained, especially in protein, zinc, and potassium, depending on the base ingredient and individual product. Some plant-based milks contain added sugar to improve flavor. Plant-based milks were generally associated with lower environmental impacts (e.g., greenhouse gas emissions, water use) than cow's milk, with the notable exception of the higher water footprint of almond milk. This review of recent studies and consumer purchases confirmed that retail sales of plant-based milks are increasing and shifting among products. Further research is needed to better characterize the environmental impacts of newer plant-based milks, such as cashew, hemp, and pea milks; consumer attitudes and behavior towards plant-based milks; and the safety and potential health effects related to their long-term and more frequent consumption.


Effect of relative changes in anthropometry during childhood on muscular power production in pedaling: a biomechanical simulation.
When performing skillful movement muscular and nonmuscular forces act in concert to produce a resultant force that complies with the goal of the task. Nonmuscular forces are directly dependent on the anthropometry of the performer. The purpose of this study was to determine the effect of age-related changes in relative anthropometric characteristics between 5 and 10 years of age on muscular power production during pedaling. A secondary purpose was to determine the dependence of this effect on movement speed. A torque-driven model of two-legged pedaling was used to track experimental kinematics and forces obtained from 6 experienced adult cyclists pedaling at 60 and 120 rpm. Relative anthropometric characteristics were modified to simulate pedaling for children of 5, 7.5, and 10 years of age. Analyses of variance revealed that age-related differences in anthropometry did not affect the muscular contribution to crank power (p > .05), while they had a significant effect on the muscular contribution to limb power (p < .05). Adjustments by the proximal muscle groups (muscles spanning the hip and knee joints) were necessary to account for anthropometry-driven changes in nonmuscular power. These effects were independent of movement speed. Our results provide researchers with useful information to interpret age-related differences in muscular power production more accurately.


Cannabis use and risk of lung cancer: a case-control study.
The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking. A case-control study of lung cancer in adults <or=55 yrs of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-yr age groups and district health boards. Interviewer-administered questionnaires were used to assess possible risk factors, including cannabis use. The relative risk of lung cancer associated with cannabis smoking was estimated by logistic regression. In total, 79 cases of lung cancer and 324 controls were included in the study. The risk of lung cancer increased 8% (95% confidence interval (CI) 2-15) for each joint-yr of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5-9) for each pack-yr of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer (relative risk 5.7 (95% CI 1.5-21.6)), after adjustment for confounding variables including cigarette smoking. In conclusion, the results of the present study indicate that long-term cannabis use increases the risk of lung cancer in young adults.


Meiotic chromosome behavior influenced by mutation-altered disjunction in Drosophila melanogaster females.
The effects of a female-specific meiotic mutation, altered disjunction (ald: 3-61), are described. Although ald females show normal levels of meiotic exchange, sex- and 4th-chromosome nondisjunction occurs at an elevated level. A large proportion of the nondisjunction events is the result of nonhomologous disjunction of the sex and 4th chromosomes. These nonhomologous disjunction events, and probably all nondisjunction events occurring in ald females are the result of two anomalies in chromosome behavior: (1) X chromosomes derived from exchange tetrads undergo nonhomologous disjunction and (2) the 4th chromosomes nonhomologously disjoin from larger chromosomes. There is at best a marginal effect of ald on the meiotic behavior of chromosomes 2 or 3. The results suggest that the ald+ gene product acts to prevent the participation of exchange X chromosomes and all 4th chromosomes in nonhomologous disjunction events. The possible role of ald+ in current models of the disjunction process is considered.


An efficient synthesis of iminoquinones by a chemoselective domino ortho-hydroxylation/oxidation/imidation sequence of 2-aminoaryl ketones.
An efficient chemoselective domino oxidative homocoupling of 2-aminoaryl ketones in the presence of 2-iodoxybenzoic acid (IBX) for the synthesis of iminoquinone has been developed. The domino reaction proceeds via three consecutive steps, such as domino ortho-hydroxylation of 2-aminoaryl ketones, oxidation of a phenol derivative to benzoquinone and dimerization through imine formation to yield iminoquinone. Importantly, this reaction allows the recycling of the oxidant IBX by recovering the by-product iodosobenzoic acid (IBA) and oxidizing it back to IBX. A four step domino strategy for the synthesis of iminoquinone through in situ generation of 2-amino benzophenone from (2-amino phenyl)(phenyl)methanol was also developed.


[Experience with the early diagnosis and prevention of neuroendocrine diseases in an industrial enterprise].
The paper is concerned with a pressing problem of clinical endocrinology: diagnosis of diseases of the neuroendocrine system at early stages. Examination of workers in a large enterprise of a leading industrial branch was based on a special screening program. The results obtained lay in the basis of recommendations on the primary and secondary prevention of neuroendocrine diseases provided to workers in a sanatorium-preventorium without giving up their work. A complex of health-improving measures is aimed at the prevention of disease in persons having risk factors and at maintaining the working ability among patients with neuroendocrine disturbance.


Gender differences in mental health and substance use disorders and related healthcare services utilization.
Pathological gambling often co-occurs with other psychiatric disorders. Gender differences in treatment-seeking behaviors among patients with pathological gambling diagnosis remain poorly understood. This study assessed gender differences in healthcare services utilization in patients seeking treatment for pathological gambling, substance use, and mental health co-occurring conditions. Study data were derived from a representative sample of the Massachusetts All Payers Claims Database for the period 2009-2013. Descriptive analyses were performed by gender using group t-tests and Pearson's chi-square tests. Bootstrap analysis was used to account for skewed distribution of healthcare services utilization data. Multiple linear regressions were used to evaluate the association between healthcare services utilization and gender while controlling for patient's age, county, and ICD-9-CM diagnosis codes. Over two-thirds of the patients were males. Moreover, two in five patients seeking treatment had pathological gambling as principal or primary diagnosis. Females had a significantly greater number of three or more co-occurring psychiatric conditions than males. Having a diagnosis of episodic mood disorder, neurotic disorder, or adjustment reaction significantly increased the utilization of healthcare services for both genders. Females had a greater utilization of healthcare services than males for the same psychiatric diagnosis. Healthcare services utilization significantly varies by gender and type of mental health and substance use diagnosis. There are significant differences by gender in the utilization of healthcare services for the same psychiatric disorders. There is a need to address gender differences in psychiatric conditions and their related healthcare needs. (Am J Addict 2019;28:9-15).


Management of Primary Breast Cancer in Older Patients: Treatment Options.
Age-related differences occur in the biology of breast cancer. Elderly patients have breast cancers that are more likely to be well differentiated, to have slower growth rates, and to be endocrine responsive. In elderly patients, primary breast cancers can frequently be treated by breast conserving surgery. Radiation therapy may be necessary less often after breast conserving surgery, and there is less rationale for prophylactic axillary dissection. Since elderly patients have been systematically excluded from randomized clinical trials, our data on breast cancer management has a less firm scientific basis than for younger patients. The available data suggest age should be only one consideration in selection of treatment, and to determine optimum therapy, age should not be a criterion to exclude patients from trials.


The pyrethroid pesticide esfenvalerate suppresses the afternoon rise of luteinizing hormone and delays puberty in female rats.
One of the most widely used classes of insecticides is the synthetic pyrethroids. Although pyrethroids are less acutely toxic to humans than to insects, in vitro studies have suggested that pyrethroids may be estrogenic. We assessed pubertal effects by orally administering 0.5, 1.0, and 5.0 mg/kg/day of the type II pyrethroid esfenvalerate (ESF) to female rats beginning on postnatal day (PND) 22 until vaginal opening. ESF administration suppresses serum estradiol and delays pubertal onset. To assess possible hypothalamic and/or pituitary effects, animals received 0.5 or 1.0 mg/kg ESF or corn oil on PNDs 22-29. On PND30, we drew three blood samples (200 microL) from each rat at 15-min intervals beginning at 1000 hours, and again at 1500 hours. To test hypothalamic responsiveness, after the third afternoon sample, all animals received an intravenous injection of N-methyl-d,l-aspartic acid (NMA; 40 mg/kg), and then we drew two more samples. We performed a second experiment as above except that animals received luteinizing hormone-releasing hormone (LHRH; 25 ng/rat) to test pituitary responsiveness. Basal levels of luteinizing hormone (LH) in the afternoon hours were higher in control animals than in animals treated with 1.0 mg/kg ESF (p < 0.05). Furthermore, NMA- and LHRH-stimulated LH release was similar in control and ESF-treated animals, indicating that both hypothalamic and pituitary responsiveness, respectively, were unaffected. Although the hypothalamus is able to respond to exogenous stimuli, absence of a normal afternoon rise in LH would indicate a hypothalamic deficit in ESF-treated animals.


Unusual entrapment of deep peroneal nerve after femoral distal extension osteotomy.
The lateral exposure of the supracondylar femur includes the risk of damaging the neurovascular structures or tightening of the neurological structures within the popliteal fossa may occur as a complication of the osteotomy. Although different pathways of common peroneal nerve (CPN) have been reported throughout the literature, division of deep and superficial branches above the supracondylar femur level has not been reported. A 15-year-old boy with bilateral knee flexion contracture and spastic diplegic cerebral palsy underwent bilateral femoral distal extension osteotomy. The authors found an unusual higher division of CPN above the supracondylar femur level. This report is aimed at warning surgeons about the division of the CPN at a higher level and highlighting a need for a high-powered cadaveric research.


Will it never end? The narratives of incest victims on the termination of sexual abuse.
The aim of this study is to investigate how child sexual abuse is terminated. This study attempts to gain insight into how people exposed to incest narrate the termination of the incest relationship. Seven women and one man were recruited from the Incest Support Centre and from snowballing for a 1-2-hour-long in-depth interview using a narrative approach. The subjects' narratives varied according to how they perceived their own role in the termination process, their relationship with the offender, and how well they remembered the stage of termination. A common feature of the narratives was that the feeling of being a victim lasted after the abuse stopped. In this respect, the lack of support from family, friends, and healthcare personnel and the psychological power exercised by the offender were important issues in the narratives. It is suggested that the termination process is affected by the victims' ability to regulate influence and mentalization. Furthermore, a transfer of cultural meanings from the social environment to the individual must have taken place. Future research should focus on the significance of the termination process in terms of psychological functioning and the construction of self and identity.


Physiological variation in alpha-adrenoceptor-mediated arterial sensitivity: relation to agonist affinity.
Vascular smooth muscle from different arteries of the rabbit varies in sensitivity to norepinephrine, even when factors known to contribute to this variation are excluded. Sensitivity to norepinephrine mediated through the alpha-adrenoceptor is linearly related to the agonist dissociation constant, but is not significantly related to receptor reserve. These results suggest that agonist affinity is the primary determinant of sensitivity to norepinephrine, at least in these arteries, and that this is a locally regulated characteristic which may account for regional sensitivity changes.


Cytogenetics of Four Species of the Green Clade Aplastodiscus Lutz, 1950 (Anura: Cophomantinae): New Insights into the Chromosomal Evolution of the Genus.
The tree frog Aplastodiscus is a Neotropical taxon that encompasses 15 species in the Atlantic forest biome, with one isolated species in the Central Brazilian Cerrado. To date, only 8 species have been karyotyped, showing high levels of diploid number variation, which allowed clustering species in chromosome number groups: 2n = 24 (Aplastodiscus perviridis group), 2n = 22 (Aplastodiscus albofrenatus group), 2n = 20, and 2n = 18 (both within Aplastodiscus albosignatus group). This study aims to report karyotypic information on 4 species from the last 2 groups using classical and molecular cytogenetic techniques and hypothesize chromosomal evolutionary trends within the species groups. Aplastodiscus weygoldti showed 2n = 22; Ag-NOR and FISH 18S rDNA signals were located in the interstitial region of the short arms of chromosome pair 6. Aplastodiscus cavicola, Aplastodiscus sp. 4, and Aplastodiscus sp. 6 showed 2n = 18; Ag-NOR and FISH 18S rDNA bands were located in the terminal region of the long arm of chromosome pair 9. Our results support multiple and independent chromosome fusion events within Aplastodiscus, including a new chromosome fission event. Ag-NOR and FISH 18S rDNA patterns were restricted to the small chromosome pairs, similar to the other species within this genus, and confirm overall chromosome morphology conservation among the genera of Cophomantinae.