Real-time Feedback in Pay-for-Performance: Does More Information Lead to Improvement?
Pay-for-performance (P4P) has been used expansively to improve quality of care delivered by physicians. However, to what extent P4P works through the provision of information versus financial incentives is poorly understood. To determine whether an increase in information feedback without changes to financial incentives resulted in improved physician performance within an existing P4P program. Implementation of a new registry enabling real-time feedback to physicians on quality measure performance. Observational, predictive piecewise model at the physician-measure level to examine whether registry introduction associated with performance changes. We used detailed physician quality measure data 3 years prior to registry implementation (2010-2012) and 2 years after implementation (2014-2015). We also linked physician-level data including age, gender, and board certification; group-level data including registry click rates; and patient panel data including chronic conditions. Four hundred thirty-four physicians continuously affiliated with Advocate from 2010 to 2015. Physician performance on ten quality metrics. We found no consistent pattern of improvement associated with the availability of real-time information across ten measures. Relative to predicted performance without the registry, average performance increased for two measures (childhood immunization status-rotavirus (p < 0.001) and diabetes care-medical attention for nephropathy (p = 0.024)) and decreased for three measures (childhood immunization status-influenza (p < 0.001) and diabetes care-HbA1c testing (p < 0.001) and poor HbA1c control (p < 0.001)). Results were consistent for subgroup analysis on those most able to improve, i.e., physicians in the bottom tertile of performance prior to registry introduction. Physicians who improved most were in groups that accessed the registry more than those who improved least (8.0 vs 10.0 times per week, p = 0.010). More frequent provision of information, provided in real-time, was insufficient to improve physician performance in an existing P4P program with high baseline performance. Results suggest that electronic registries may not themselves drive performance improvement. Future work should consider testing information feedback enhancements with financial incentives.


Measuring teamwork in primary care: Triangulation of qualitative and quantitative data.
This article describes the triangulation of qualitative dimensions, reflecting high functioning teams, with the results of standardized teamwork measures. The study used a mixed methods design using qualitative and quantitative approaches to assess teamwork in 19 Family Health Teams in Ontario, Canada. This article describes dimensions from the qualitative phase using grounded theory to explore the issues and challenges to teamwork. Two quantitative measures were used in the study, the Team Climate Inventory (TCI) and the Providing Effective Resources and Knowledge (PERK) scale. For the triangulation analysis, the mean scores of these measures were compared with the qualitatively derived ratings for the dimensions. The final sample for the qualitative component was 107 participants. The qualitative analysis identified 9 dimensions related to high team functioning such as common philosophy, scope of practice, conflict resolution, change management, leadership, and team evolution. From these dimensions, teams were categorized numerically as high, moderate, or low functioning. Three hundred seventeen team members completed the survey measures. Mean site scores for the TCI and PERK were 3.87 and 3.88, respectively (of 5). The TCI was associated will all dimensions except for team location, space allocation, and executive director leadership. The PERK was associated with all dimensions except team location. Data triangulation provided qualitative and quantitative evidence of what constitutes teamwork. Leadership was pivotal in forging a common philosophy and encouraging team collaboration. Teams used conflict resolution strategies and adapted to the changes they encountered. These dimensions advanced the team's evolution toward a high functioning team.


Improving the sensitivity of confocal laser induced fluorescence detection to the sub-picomolar scale for round capillaries by laterally shifting the laser focus point.
This paper describes a simple and efficient approach to reduce the background level of confocal laser induced fluorescence (LIF) detection for round capillaries by laterally shifting the laser focus point. A phenomenon of spontaneous separation of the fluorescence and reflected laser beams at the pinhole of a confocal LIF system when the laser focus point deviates from the center of a capillary channel to the sides was observed for the first time. On the basis of this phenomenon, the reflected laser light from the capillary-air interfaces could be mostly eliminated with a spatial filtering pinhole. A comprehensive study on the phenomenon and optimization of the shift distance was carried out using both experimental and simulation methods. A best shift distance of ±20 μm was obtained, with which background intensity could be significantly reduced by 98.9%, while fluorescence intensity was only reduced by 25.7%, resulting in an improvement of signal-to-noise ratio of 8.3 times, compared with that at a shift distance of 0 μm usually used in most of the confocal LIF systems for round capillaries. A limit of detection of 66 fM was obtained for sodium fluorescein. To demonstrate its potential as an on-column sensitive detector for microscale separation systems, the present system was coupled with a capillary electrophoresis system for separation of four fluorescein isothiocyanate labeled amino acids with concentrations of 100 pM.


Expression of T cell receptor genes in human B cells.
We analyzed the transcription and rearrangement of the T cell antigen receptor (Ti) genes Ti alpha and Ti beta in human B cell, T cell, and myeloid cell lines, as well as in purified tonsillar B and T cells. All four B cell lines examined, as well as one of two myeloid cell lines, expressed low levels of truncated Ti beta transcripts, as did freshly purified tonsillar B cells. Two of the B cell lines and one of the myeloid lines also expressed truncated Ti alpha transcripts, while tonsillar B cells did not. Sequence analysis of cDNA clones from a B cell line demonstrated that these truncated Ti alpha and Ti beta transcripts were composed of unrearranged J and C gene segments. Comparison of cDNA clones from T and B cells suggests that D alpha genes or N regions contribute to the formation of Ti alpha transcripts in T cells but not in B cells. None of the B cell or myeloid cell lines in this study showed evidence of Ti beta gene rearrangements by Southern blotting. Our data, and other studies of gene rearrangements in human tumors, demonstrate that the level of Ti beta transcriptional activity and the frequency of Ti beta gene rearrangements are correlated in all cell types examined. Thus, our data support the accessibility model of antigen receptor gene rearrangement, whereby the susceptibility of gene segments to recombination enzymes is correlated with their transcriptional activity.


Prevalence of HBV infection among the healthy Nepalese males: a serological survey.
Sera from 478 healthy Nepalese male population, inhabiting various districts of five development regions of Nepal were collected from October 1996 to March 1997 and examined for the presence of HBsAg by third generation ELISA and Latex agglutination test in the laboratory of Central Department of Microbiology, Tribhuvan University, Kirtipur. The surface antigen was detected by ELISA in 4.0% (19/478) of subjects studied. However, different results were obtained in Latex agglutination test. The correlation between the results obtained from these two different tests is statistically significant (chi2=85.11, P<0.05). The results obtained from ELISA showed the probability of Nepal to fall in WHO category of intermediate endemicity zone for hepatitis B infection. The percent positivity of HBsAg was found to increase steadily from Eastern (2%) to Far Western (6.2%) development regions. Among the districts studied, Kailali district gave characteristically high prevalence followed by Rukum and Kaski. Other, districts representing for the prevalence are Sankhuwasabha, Jhapa, Ramechhap, Sarlahi, Dhanusa, Baglung, Gulmi, Palpa and Dang. None of the samples represented from Kathmandu valley were positive for HBsAg. The age groups of 16-20 years and 36-40 years were found to be associated with the hepatitis B infection. Furthermore, various percent prevalence of the infection were encountered from 16 to 40 years subjects and a single case was also observed from 63 years old man. All the samples recorded positive for HBsAg from ELISA were assayed for the amount of ALT as a liver function test. Where, 15.8% (3/19) of the infected subjects had impaired liver function, hence it showed that, the subjects with high ALT to be the possible carrier of the HBV. Conversely, the remaining 84.2% (16/19) of the total HBsAg positive subjects were concluded to have the infection either at incubation or at prodrome period.


Laboratory versus daily life gait characteristics in patients with multiple sclerosis, Parkinson's disease, and matched controls.
Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinson's Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring. We recruited 15 people with MS (age mean ± SD: 49 ± 10 years), 16 MS-Ctl (45 ± 11 years), 16 people with idiopathic PD (71 ± 5 years), and 15 PD-Ctl (69 ± 7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. Mann-Whitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life. Participants wore sensors for 60-68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI] = 0.80 [0.63-0.96]) whereas gait speed in daily life (AUC = 0.84 [0.69-1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUC = 0.78 [0.59-0.96]) whereas foot-strike angle in daily life (AUC = 0.84 [0.70-0.98]). AUCs were larger in daily life compared to the laboratory. Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures.


Genome-wide transcript profiling reveals the coevolution of plastid gene sequences and transcript processing pathways in the fucoxanthin dinoflagellate Karlodinium veneficum.
Plastids utilize a complex gene expression machinery, which has coevolved with the underlying genome sequence. Relatively, little is known about the genome-wide evolution of transcript processing in algal plastids that have undergone complex endosymbiotic events. We present the first genome-wide study of transcript processing in a plastid acquired through serial endosymbiosis, in the fucoxanthin-containing dinoflagellate Karlodinium veneficum. The fucoxanthin dinoflagellate plastid has an extremely divergent genome and utilizes two unusual transcript processing pathways, 3'-poly(U) tail addition and sequence editing, which were acquired following the serial endosymbiosis event. We demonstrate that poly(U) addition and sequence editing are widespread features across the Karl. veneficum plastid transcriptome, whereas other dinoflagellate plastid lineages that have arisen through independent serial endosymbiosis events do not utilize either RNA processing pathway. These pathways constrain the effects of divergent sequence evolution in fucoxanthin plastids, for example by correcting mutations in the genomic sequence that would otherwise be deleterious, and are specifically associated with transcripts that encode functional plastid proteins over transcripts of recently generated pseudogenes. These pathways may have additionally facilitated divergent evolution within the Karl. veneficum plastid. Transcript editing, for example, has contributed to the evolution of a novel C-terminal sequence extension on the Karl. veneficum AtpA protein. We furthermore provide the first complete sequence of an episomal minicircle in a fucoxanthin dinoflagellate plastid, which contains the dnaK gene, and gives rise to polyuridylylated and edited transcripts. Our results indicate that RNA processing in fucoxanthin dinoflagellate plastids is evolutionarily dynamic, coevolving with the underlying genome sequence.


Non-steady-state, non-uniform transpiration rate and leaf anatomy effects on the progressive stable isotope enrichment of leaf water along monocot leaves.
This study focuses on the spatial patterns of transpiration-driven water isotope enrichment (Delta(lw)) along monocot leaves. It has been suggested that these spatial patterns are the result of competing effects of advection and (back-)diffusion of water isotopes along leaf veins and in the mesophyll, but also reflect leaf geometry (e.g. leaf length, interveinal distance) and non-uniform gas-exchange parameters. We therefore developed a two-dimensional model of isotopic leaf water enrichment that incorporates new features, compared with previous models, such as radial diffusion in the xylem, longitudinal diffusion in the mesophyll, non-uniform gas-exchange parameters and non-steady-state effects. The model reproduces well all published measurements of Delta(lw) along monocot leaf blades, except at the leaf tip and given the uncertainties on measurements and model parameters. We show that the longitudinal diffusion in the mesophyll cannot explain the observed reduction in the isotope gradient at the leaf tip. Our results also suggest that the observed differences in Delta(lw) between C(3) and C(4) plants reflect more differences in mesophyll tortuosity rather than in leaf length or interveinal distance. Mesophyll tortuosity is by far the most sensitive parameter and different values are required for different experiments on the same plant species. Finally, using new measurements of non-steady-state, spatially varying leaf water enrichment we show that spatial patterns are in steady state around midday only, just as observed for bulk leaf water enrichment, but can be easily upscaled to the whole leaf level, regardless of their degree of heterogeneity along the leaf.


Mechanism of CRP-mediated cya suppression in Escherichia coli.
Escherichia coli strain NCR30 contains a cya lesion and a second-site cya suppressor mutation that lies in the crp gene. NCR30 shows a pleiotropic phenotypic reversion to the wild-type state in expressing many operons that require the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex for positive control. In vivo beta-galactosidase synthesis in NCR30 was sensitive to glucose-mediated repression, which was relieved not only by cAMP but also by cyclic GMP and cyclic CMP. The CRP isolated from NCR30 differed from the protein isolated from wild-type E. coli in many respects. The mutant protein bound cAMP with four to five times greater affinity than wild-type CRP. Protease digestion studies indicated that native NCR30 CRP exists in the cAMP-CRP complex-like conformation. The protein conferred a degree of cAMP independence on the in vitro synthesis of beta-galactosidase. In addition, the inherent positive control activity of the mutant protein in vitro was enhanced by those nucleotides that stimulate in vivo beta-galactosidase synthesis in NCR30. The results of this study supported the conclusion that the crp allele of NCR30 codes for a protein having altered effector specificity yet capable of promoting positive control over catabolite-sensitive operons in the absence of an effector molecule.


Serine protease activity contributes to control of Mycobacterium tuberculosis in hypoxic lung granulomas in mice.
The hallmark of human Mycobacterium tuberculosis infection is the presence of lung granulomas. Lung granulomas can have different phenotypes, with caseous necrosis and hypoxia present within these structures during active tuberculosis. Production of NO by the inducible host enzyme NOS2 is a key antimycobacterial defense mechanism that requires oxygen as a substrate; it is therefore likely to perform inefficiently in hypoxic regions of granulomas in which M. tuberculosis persists. Here we have used Nos2-/- mice to investigate host-protective mechanisms within hypoxic granulomas and identified a role for host serine proteases in hypoxic granulomas in determining outcome of disease. Nos2-/- mice reproduced human-like granulomas in the lung when infected with M. tuberculosis in the ear dermis. The granulomas were hypoxic and contained large amounts of the serine protease cathepsin G and clade B serine protease inhibitors (serpins). Extrinsic inhibition of serine protease activity in vivo resulted in distorted granuloma structure, extensive hypoxia, and increased bacterial growth in this model. These data suggest that serine protease activity acts as a protective mechanism within hypoxic regions of lung granulomas and present a potential new strategy for the treatment of tuberculosis.


Structural requirements for key residues and auxiliary portions of a BLUF domain.
BlrB in Rhodobacter sphaeroides is a single domain, flavin-based blue light sensor protein in the BLUF family of photoreceptors. Consistent with other members of this family, blue light excitation induces a putative signaling state characterized by a 10 nm red shift in the UV-visible absorbance spectrum. Structural and spectroscopic characterization of truncated BlrB constructs establishes that the C-terminal 50 amino acids of this protein are essential to its structural integrity despite not being part of the canonical BLUF domain architecture. Mutagenesis studies support the critical roles of Tyr9, Asn33, and Gln51 for flavin binding and the integrity of the BLUF domain fold. Comparison of solution NMR spectra of BlrB acquired under dark and light conditions indicates very limited light-dependent conformational changes except for a few interesting residues: Trp92, Met94, and Ile127. Notably, the Ile127 side chain experiences significant chemical shift changes despite the fact that it is far ( approximately 15 A) from the flavin chromophore in the C-terminal extension. These data suggest that the light-induced signal is propagated from the flavin through the beta sheet to the last two alpha helices in the C-terminal extension, potentially providing a mechanism to transmit this change to initiate a cellular response to blue light.


Biotechnological applications of functional metagenomics in the food and pharmaceutical industries.
Microorganisms are found throughout nature, thriving in a vast range of environmental conditions. The majority of them are unculturable or difficult to culture by traditional methods. Metagenomics enables the study of all microorganisms, regardless of whether they can be cultured or not, through the analysis of genomic data obtained directly from an environmental sample, providing knowledge of the species present, and allowing the extraction of information regarding the functionality of microbial communities in their natural habitat. Function-based screenings, following the cloning and expression of metagenomic DNA in a heterologous host, can be applied to the discovery of novel proteins of industrial interest encoded by the genes of previously inaccessible microorganisms. Functional metagenomics has considerable potential in the food and pharmaceutical industries, where it can, for instance, aid (i) the identification of enzymes with desirable technological properties, capable of catalyzing novel reactions or replacing existing chemically synthesized catalysts which may be difficult or expensive to produce, and able to work under a wide range of environmental conditions encountered in food and pharmaceutical processing cycles including extreme conditions of temperature, pH, osmolarity, etc; (ii) the discovery of novel bioactives including antimicrobials active against microorganisms of concern both in food and medical settings; (iii) the investigation of industrial and societal issues such as antibiotic resistance development. This review article summarizes the state-of-the-art functional metagenomic methods available and discusses the potential of functional metagenomic approaches to mine as yet unexplored environments to discover novel genes with biotechnological application in the food and pharmaceutical industries.


Japanese Reverse Compasses: Grounding Cognition in History and Society.
ArgumentAn unusual compass, on which east and west are reversed, provides insight into the dynamics guiding our understanding of artifacts. By examining how such compasses were used in Tokugawa Japan (1600-1868), the benefits they brought, and how users knew how to read them, this article uncovers the cognitive factors that shape our interaction with technology. Building on the methodological approach of the distributed cognition theory, the article claims that reverse compasses allowed the user to conserve cognitive effort, which was particularly advantageous to Tokugawa-period mariners. Moreover, the article shows that even non-professional Tokugawa Japanese had a relatively easy time reading reverse compasses due to similarity between the compasses' orientation and Tokugawa timekeeping practices. Building on the bodily and cognitive habits they had developed through the practices of keeping time, users could identify and interpret cultural cues embedded in the structure of reverse compasses.


Cubic versus hexagonal - phase, size and morphology effects on the photoluminescence quantum yield of NaGdF4:Er3+/Yb3+ upconverting nanoparticles.
Upconverting nanoparticles (UCNPs) are well-known for their capacity to convert near-infrared light into UV/visible light, benefitting various applications where light triggering is required. At the nanoscale, loss of luminescence intensity is observed and thus, a decrease in photoluminescence quantum yield (PLQY), usually ascribed to surface quenching. We evaluate this by measuring the PLQY of NaGdF4:Er3+,Yb3+ UCNPs as a function of size (ca. 15 to 100 nm) and shape (spheres, cubes, hexagons). Our results show that the PLQY of α-phase NaGdF4 Er3+,Yb3+ surpasses that of β-NaGdF4 for sizes below 20 nm, an observation related to distortion of the crystal lattice when the UCNPs become smaller. The present study also underlines that particle shape must not be neglected as a relevant parameter for PLQY. In fact, based on a mathematical nucleus/hull volumetric model, shape was found to be particularly relevant in the 20 to 60 nm size range of the investigated UCNPs.


Safe positioning for neurosurgical patients.
Positioning the patient for surgery is an important part of perioperative nursing care that should not be underemphasized. The combined factors of time, mechanical pressure, and immobility increase the risk of tissue damage. The objectives of perioperative positioning activities are to balance optimal surgical exposure with the prevention of any injury related to position and to maintain normal body alignment without excess flexion, extension, or rotation. General principles of positioning and specific considerations with surgical rationale are presented in this article for each of the commonly used neurosurgical positions (eg, supine, knee-chest, prone, lateral, park-bench, sitting).


My Mind is Working Overtime-Towards an Integrative Perspective of Psychological Detachment, Work-Related Rumination, and Work Reflection.
In the literature on occupational stress and recovery from work, several facets of thinking about work during off-job time have been conceptualized. However, research on the focal concepts is currently rather diffuse. In this study we take a closer look at the five most well-established concepts: (1) psychological detachment, (2) affective rumination, (3) problem-solving pondering, (4) positive work reflection, and (5) negative work reflection. More specifically, we scrutinized (1) whether the five facets of work-related rumination are empirically distinct, (2) whether they yield differential associations with different facets of employee well-being (burnout, work engagement, thriving, satisfaction with life, and flourishing), and (3) to what extent the five facets can be distinguished from and relate to conceptually similar constructs, such as irritation, worry, and neuroticism. We applied structural equation modeling techniques to cross-sectional survey data from 474 employees. Our results provide evidence for (1) five correlated, yet empirically distinct facets of work-related rumination. (2) Each facet yields a unique pattern of association with the eight aspects of employee well-being. For instance, detachment is strongly linked to satisfaction with life and flourishing. Affective rumination is linked particularly to burnout. Problem-solving pondering and positive work reflection yield the strongest links to work engagement. (3) The five facets of work-related rumination are distinct from related concepts, although there is a high overlap between (lower levels of) psychological detachment and cognitive irritation. Our study contributes to clarifying the structure of work-related rumination and extends the nomological network around different types of thinking about work during off-job time and employee well-being.


Nursing handover of vital signs at the transition of care from the emergency department to the inpatient ward: An integrative review.
To examine nursing handover of vital signs during patient care transition from the emergency department (ED) to inpatient wards. Communication failures are a leading cause of patient harm making communication through clinical handover an international healthcare priority. The transition of care from ED to ward settings is informed by nursing handover. Vital sign abnormalities in the ED are associated with clinical deterioration following hospital admission. Understanding the role and perceived value of vital sign content in clinical handover is important for patient safety. An integrative design was used. A search of electronic databases was undertaken using MEDLINE, CINAHL, EMBASE, Cochrane, Web of Science and SCOPUS. Identified records were screened to elicit further studies for inclusion. A comprehensive peer-review screening process was performed. Studies were included that described the surrounding issues of handover, vital signs, ED, transition of care and ward. Five studies were included in the final review, one specific to nursing and four specific to emergency medicine. Vital signs were perceived to be an important inclusion in clinical handover, and the communication of vital signs in handover was perceived to be indicators for patient safety and risk factors for future clinical deterioration. The ED environment had an influence on effective communication within handover. Vital signs were an important inclusion for clinical handover. Deficiencies in vital sign content were perceived to be risk factors for patient adverse events following hospital admission. The quality of vital sign information in clinical handover may be important for accurate decision-making. Vital signs are an important component of clinical handover and are perceived to be indicators for patient safety and risk of future adverse events.


Affective empathy in schizophrenia: a meta-analysis.
Affective empathy, or the emotional response one has to the experiences or emotional states of others, contributes to relationship-maintaining behaviors and is key in fostering social connections, yet no work has synthesized the body of literature for people with schizophrenia. The aim of the present meta-analysis was to determine the extent to which those diagnosed with schizophrenia experience deficits in affective empathy. A literature search was conducted of studies examining empathy. Data were analyzed using a random effects meta-analytic model with Hedges' g standardized mean difference effect size. Individuals with schizophrenia exhibited significant, medium deficits in affective empathy (k=37). Measurement type moderated the affective empathy deficit such that performance-based measures showed larger schizophrenia group deficits than self-report measures. Consistent, significant deficits in affective empathy were found comparing people with schizophrenia to healthy controls, especially when using performance-based assessments. The medium effect suggests an important role for empathy in the realm of social cognitive research, and points to the need for further investigation of measurement techniques and associations with functional outcomes.


[Therapeutic Effect and Adverse Events of Ramucirumab in Patients with Gastric Cancer in Our Hospital].
From January 2016 through December 2017, 18 patients received paclitaxel plus ramucirumab combination therapy and 1 patient received ramucirumab monotherapy. Thus, a total of 19 patients were analyzed in terms of both therapeutic effect and adverse events. The response evaluation of the targeted lesion was as follows; CR: 0, PR: 1, SD: 16, PD: 2. The median of overall survival and progression-free survival of the combination therapy was 9.9 months and 4.2 months, respectively. Although more than half of the patients were enforced after tertiary therapy in our department, the therapeutic effect of paclitaxel plus ramucirumab combination therapy was considerably satisfactory. Neutropenia as an adverse event was observed in 13(68.4%)out of 19 patients, and 8 patients(42.1%)had neutropenia greater than Grade 3. Non -hematologic toxicity was observed in 17 cases(89.5%), and anorexia, nausea, diarrhea, dysgeusia, peripheral neuropathy, hair loss, and fatigue were determined to be either Grade 1 or 2. Alternatively, 1 patient developed Grade 3 interstitial pneumonia, and 3 patients(15.8%)had complicated Grade 3 high blood pressure. Only 2 patients who had severe adverse events, one was interstitial pneumonia and the other was high blood pressure, discontinued paclitaxel plus ramucirumab combination therapy.


Genetic variations in the leptin gene associated with growth and carcass traits in Nellore cattle.
The aim of the study was to detect polymorphisms in the leptin gene and to determine the association of these polymorphisms with growth and carcass traits in Nellore cattle. The single nucleotide polymorphisms (SNPs) -1457 (AJ571671:g.-1457A>G) and A59V (AF536174.1:g. 321C>T), as well as the microsatellite BM1500 (3.9 kb downstream), were genotyped. The measures of body weight and ultrasound examinations (rib eye area, back, and rump fat thickness) were performed in 3 different periods of animal management. During the first period, the animals were fed with grass and mineralized salt ad libitum. In the second period, they received grass and concentrate, and in the third, only concentrate. After the slaughter of animals, data were collected for classification and typification of carcasses. No significant association was found between the variables assessed and SNP -1457. Conversely, SNP A59V was associated with rump fat thickness and muscle color post-slaughter. BM1500 was associated with rump fat thickness in the first period (pre-slaughter), subcutaneous fat thickness in the second, weight of the animals in the third, and length of the carcass after slaughter. These results suggest that SNP A59V and the microsatellite BM1500 might be useful for marker-assisted selection in Nellore cattle.


Perivascular epithelioid cell tumor (PEC-ome) of the prostate: ultrasound feature in case report.
We describe a rare tumor arising from the prostate gland: Perivascular Epithelioid Cells tumor (PEC-ome). A 54-years old was treated for acute urinary retention with alpha-blockers at presentation due to benign prostate enlargement (65 cc) with asymmetric middle lobe and regular PSA (0.92 ng/ml). After 5 months, patient developed a second acute urinary retention episode and nodules in the left lung; he was treated with transurethral resection of the prostate and left lobectomy. Histological examination of prostate and lung tissue gave the same diagnosis: leiomyosarcoma with atypical morphological features and patient was observed for 4 months. Considering the uncommon diagnosis, pathological review by the uro-pathologist at our Hospital was done. Additional immunohistochemistry was done and both tumors showed similar and typical features of metastatic PEC-ome (T1b N0 M1). Therefore a new staging showed local and distant progression with prostatic mass and small lung metastasis. Three cycles of Gemcitabine and Pazopanib were administered, but 2 months later a new urinary retention occurred, despite chemotherapy. Patient referred to our Hospital for salvage pelvic surgery with lymph node dissection. Final pathological diagnosis was PEC-ome of the prostate stage pT4 pN0 R0 M1. PEC-ome is a rare but rapidly invasive mesothelial tumor with early metastatic potential. When this tumors originates from the fibromuscular stroma of the prostate it mimics benign prostatic enlargement and causes LUTS. Expert pathology aided by immunoisthochemistry is the cornerstone of diagnosis. There are no pathognomonic imaging on ultrasound or symptoms suggesting the presence of PEC-ome in early stage. A multidisciplinary approach is necessary and radical surgery should be done to treat this aggressive cancer.


Iterated conformal dynamics and Laplacian growth.
The method of iterated conformal maps for the study of diffusion limited aggregates (DLA) is generalized to the study of Laplacian growth patterns and related processes. We emphasize the fundamental difference between these processes: DLA is grown serially with constant size particles, while Laplacian patterns are grown by advancing each boundary point in parallel, proportional to the gradient of the Laplacian field. We introduce a two-parameter family of growth patterns that interpolates between DLA and a discrete version of Laplacian growth. The ultraviolet putative finite-time singularities are regularized here by a minimal tip size, equivalently for all the models in this family. With this we stress that the difference between DLA and Laplacian growth is not in the manner of ultraviolet regularization, but rather in their deeply different growth rules. The fractal dimensions of the asymptotic patterns depend continuously on the two parameters of the family, giving rise to a "phase diagram" in which DLA and discretized Laplacian growth are at the extreme ends. In particular, we show that the fractal dimension of Laplacian growth patterns is higher than the fractal dimension of DLA, with the possibility of dimension 2 for the former not excluded.


Essential Oils and Gastroparesis: Power for Transforming Health, Hope, and Quality of Life.
This study explored how essential oils for persons with gastroparesis symptoms affect the quality of life. Gastroparesis is a chronic delayed gastric motility disorder characterized by postprandial fullness, early satiety, nausea, vomiting, abdominal discomfort, bloating, depression, and anxiety. The aim of this study was to determine how essential oils support digestion and eliminate inflammation in the body as evidenced by self-reporting a decrease in symptoms, thereby improving quality of life. A qualitative descriptive methodology using Barrette's Theory of Power as Knowing Participation in Change thematic framework was used. Three main themes were extracted from the data: awareness of quality of life possibilities, freedom to make choices, and transforming health and hope. The constitutive theme that was synthesized became essential oils transform health, hope, and increase quality-of-life possibilities.


Highly-coherent stimulated phonon oscillations in a multi-core optical fiber.
Opto-mechanical oscillators that generate coherent acoustic waves are drawing much interest, in both fundamental research and applications. Narrowband oscillations can be obtained through the introduction of feedback to the acoustic wave. Most previous realizations of this concept, sometimes referred to as "phonon lasers", relied on radiation pressure and moving boundary effects in micro- or nano-structured media. Demonstrations in bulk crystals required cryogenic temperatures. In this work, stimulated emission of highly-coherent acoustic waves is achieved in a commercially-available multi-core fiber, at room temperature. The fiber is connected within an opto-electronic cavity loop. Pump light in one core is driving acoustic waves via electrostriction, whereas an optical probe wave at a different physical core undergoes photo-elastic modulation by the stimulated acoustic waves. Coupling between pump and probe is based entirely on inter-core, opto-mechanical cross-phase modulation: no direct optical feedback is provided. Single-frequency mechanical oscillations at hundreds of MHz frequencies are obtained, with side-mode suppression that is better than 55 dB. A sharp threshold and rapid collapse of the linewidth above threshold are observed. The linewidths of the acoustic oscillations are on the order of 100 Hz, orders of magnitude narrower than those of the pump and probe light sources. The relative Allan's deviation of the frequency is between 0.1-1 ppm. The frequency may be switched among several values by propagating the pump or probe waves in different cores. The results may be used in sensing, metrology and microwave-photonic information processing applications.


Arterial stiffness measured as pulse wave velocity is highly correlated with coronary atherosclerosis in asymptomatic patients.
Carotid-femoral pulse wave velocity is a well-known predictor of all-cause and cardiovascular mortality. Few studies have evaluated the relationship between brachial-ankle pulse wave velocity (ba-PWV) and coronary artery disease. We conducted this study to elucidate the relationship between arterial stiffness measured by ba-PWV and coronary atherosclerosis. An automatic waveform analyzer was used to measure the ba-PWV. Multidetector computed tomography coronary angiography was used to assess the coronary artery calcium (CAC) score and to detect coronary stenosis. A total of 654 patients, including 358 women and 296 men (mean age, 54.5 ± 9.4 years), were recruited during the period March 2005 to June 2008. One hundred and twenty-seven patients (19.4%) had at least one stenotic coronary vessel. Mean ba-PWV and mean CAC scores were significantly higher in the stenotic group than in the normal control (15.94 ± 3.07 m/s vs. 14.39 ± 0.98 m/s; 293.1 ± 435.9 vs. 29.8 ± 110.8, respectively; both p < 0.001). The adjusted OR for coronary stenosis increased as ba-PWV increased (p for trend = 0.0001). Using ba-PWV < 14.0 m/s as the reference group, we found that ba-PWV between 14.0-18.0 m/s and ba-PWV > 18.0 m/s were significantly associated with coronary stenosis (OR, 2.48; CI, 1.56-3.93 and OR, 3.16; CI, 1.68-5.95, respectively). The cutoff point at 15.64 m/s using the ROC curve showed a sensitivity of 64.5%, specificity of 65.6%, and an AUC of 0.662 in predicting coronary artery stenosis. Ba-PWV had an additional power for correlating coronary artery disease with the Framingham risk score. Ba-PWV correlated well with coronary atherosclerosis. Lifestyle modification is an efficacious therapeutic intervention for preventing the progression of arterial stiffness. This non-invasive technique can assist in the early detection of cardiovascular disease and should be included in community screening programs.


c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells.
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, but little is known about the role of the c-Rel subunit in solid cancer and PDAC apoptosis control. In the present study, by analysis of genome-wide patterns of c-Rel-dependent gene expression, we were able to establish c-Rel as a critical regulator of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in PDAC. TRAIL-resistant cells exhibited a strong TRAIL-inducible NF-κB activity, whereas TRAIL-sensitive cells displayed only a small increase in NF-κB-binding activity. Transfection with siRNA against c-Rel sensitized the TRAIL-resistant cells in a manner comparable to siRNA targeting the p65/RelA subunit. Gel-shift analysis revealed that c-Rel is part of the TRAIL-inducible NF-κB complex in PDAC. Array analysis identified NFATc2 as a c-Rel target gene among the 12 strongest TRAIL-inducible genes in apoptosis-resistant cells. In line, siRNA targeting c-Rel strongly reduced TRAIL-induced NFATc2 activity in TRAIL-resistant PDAC cells. Furthermore, siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL-induced apoptosis. Finally, TRAIL-induced expression of COX-2 was diminished through siRNA targeting c-Rel or NFATc2 and pharmacologic inhibition of COX-2 with celecoxib or siRNA targeting COX-2, enhanced TRAIL apoptosis. In conclusion, we were able to delineate a novel c-Rel-, NFATc2- and COX-2-dependent antiapoptotic signalling pathway in PDAC with broad clinical implications for pharmaceutical intervention strategies.


Comparative Cost of Virtual Reality Training and Live Exercises for Training Hospital Workers for Evacuation.
Adoption of virtual reality technology may be delayed due to high up-front costs with unknown returns on that investment. In this article, we present a cost analysis of using virtual reality as a training tool. Virtual reality was used to train neonatal intensive care workers in hospital evacuation. A live disaster exercise with mannequins was also conducted that approximated the virtual experience. Comparative costs are presented for the planning, development, and implementation of both interventions. Initially, virtual reality is more expensive, with a cost of $229.79 per participant (total cost $18 617.54 per exercise) for the live drill versus $327.78 (total cost $106 951.14) for virtual reality. When development costs are extrapolated to repeated training over 3 years, however, the virtual exercise becomes less expensive with a cost of $115.43 per participant, while the cost of live exercises remains fixed. The larger initial investment in virtual reality can be spread across a large number of trainees and a longer time period with little additional cost, while each live drill requires additional costs that scale with the number of participants.


Hamstring strain injuries: recommendations for diagnosis, rehabilitation, and injury prevention.
Hamstring strain injuries remain a challenge for both athletes and clinicians, given their high incidence rate, slow healing, and persistent symptoms. Moreover, nearly one third of these injuries recur within the first year following a return to sport, with subsequent injuries often being more severe than the original. This high reinjury rate suggests that commonly utilized rehabilitation programs may be inadequate at resolving possible muscular weakness, reduced tissue extensibility, and/or altered movement patterns associated with the injury. Further, the traditional criteria used to determine the readiness of the athlete to return to sport may be insensitive to these persistent deficits, resulting in a premature return. There is mounting evidence that the risk of reinjury can be minimized by utilizing rehabilitation strategies that incorporate neuromuscular control exercises and eccentric strength training, combined with objective measures to assess musculotendon recovery and readiness to return to sport. In this paper, we first describe the diagnostic examination of an acute hamstring strain injury, including discussion of the value of determining injury location in estimating the duration of the convalescent period. Based on the current available evidence, we then propose a clinical guide for the rehabilitation of acute hamstring injuries, including specific criteria for treatment progression and return to sport. Finally, we describe directions for future research, including injury-specific rehabilitation programs, objective measures to assess reinjury risk, and strategies to prevent injury occurrence. Diagnosis/therapy/prevention, level 5.


From Their Voices: Barriers to HIV Testing among Black Men Who Have Sex with Men Remain.
HIV testing continues to be a major priority for addressing the epidemic among young Black men who have sex with men (BMSM). This study explored barriers to HIV testing uptake, and recommendations for motivating HIV testing uptake among Black men who have sex with men (BMSM) aged 18 to 30. BMSM (N = 36) were recruited through flyers and social media for six focus groups. From the perspectives and experiences of young BMSM, participants recommended that information be included in HIV testing messages that would help young BMSM do self HIV-risk appraisals. Particularly, participants recommended that more knowledge about Pre-Exposure Prophylaxis (PrEP) and the role of PrEP in safer-sex practices be provided. This information is important to help those untested, or who infrequently test, better understand their risk and need for testing. Likewise, participants recommended that more information about a person being undetectable and the risk of condomless sex with an HIV negative sex partner; this information will be helpful for both the HIV negative and HIV positive sex partner for making safer sex decisions. Participants also recommended that interventions should focus on more than drug use as risk; the risk posed by the use of alcohol before and during sex deserves attention among young BMSM. These findings may inform new HIV testing interventions being tailored for young BMSM. The interventions should also consider revisiting street-based peer-outreach approaches for those young BMSM with limited access to social media campaigns due to limited access or infrequent use of social media.


Trust, Punishment, and Cooperation Across 18 Societies: A Meta-Analysis.
Punishment promotes contributions to public goods, but recent evidence suggests that its effectiveness varies across societies. Prior theorizing suggests that cross-societal differences in trust play a key role in determining the effectiveness of punishment, as a form of social norm enforcement, to promote cooperation. One line of reasoning is that punishment promotes cooperation in low-trust societies, primarily because people in such societies expect their fellow members to contribute only if there are strong incentives to do so. Yet another line of reasoning is that high trust makes punishment work, presumably because in high-trust societies people may count on each other to make contributions to public goods and also enforce norm violations by punishing free riders. This poses a puzzle of punishment: Is punishment more effective in promoting cooperation in high- or low-trust societies? In the present article, we examine this puzzle of punishment in a quantitative review of 83 studies involving 7,361 participants across 18 societies that examine the impact of punishment on cooperation in a public goods dilemma. The findings provide a clear answer: Punishment more strongly promotes cooperation in societies with high trust rather than low trust.


Imaging Flow Cytometry Protocols for Examining Phagocytosis of Microplastics and Bioparticles by Immune Cells of Aquatic Animals.
Imaging flow cytometry (IFC) is a powerful tool which combines flow cytometry with digital microscopy to generate quantitative high-throughput imaging data. Despite various advantages of IFC over standard flow cytometry, widespread adoption of this technology for studies in aquatic sciences is limited, probably due to the relatively high equipment cost, complexity of image analysis-based data interpretation and lack of core facilities with trained personnel. Here, we describe the application of IFC to examine phagocytosis of particles including microplastics by cells from aquatic animals. For this purpose, we studied (1) live/dead cell assays and identification of cell types, (2) phagocytosis of degradable and non-degradable particles by Atlantic salmon head kidney cells and (3) the effect of incubation temperature on phagocytosis of degradable particles in three aquatic animals-Atlantic salmon, Nile tilapia, and blue mussel. The usefulness of the developed method was assessed by evaluating the effect of incubation temperature on phagocytosis. Our studies demonstrate that IFC provides significant benefits over standard flow cytometry in phagocytosis measurement by allowing integration of morphometric parameters, especially while identifying cell populations and distinguishing between different types of fluorescent particles and detecting their localization.


Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin.
Mutations in the KCNQ2 gene, encoding for voltage-gated Kv7.2K(+) channel subunits, are responsible for early-onset epileptic diseases with widely-diverging phenotypic presentation, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy. In the present study, Kv7.2 BFNS-causing mutations (W344R, L351F, L351V, Y362C, and R553Q) have been investigated for their ability to interfere with calmodulin (CaM) binding and CaM-induced channel regulation. To this aim, semi-quantitative (Far-Western blotting) and quantitative (Surface Plasmon Resonance and dansylated CaM fluorescence) biochemical assays have been performed to investigate the interaction of CaM with wild-type or mutant Kv7.2 C-terminal fragments encompassing the CaM-binding domain; in parallel, mutation-induced changes in CaM-dependent Kv7.2 or Kv7.2/Kv7.3 current regulation were investigated by patch-clamp recordings in Chinese Hamster Ovary (CHO) cells co-expressing Kv7.2 or Kv7.2/Kv7.3 channels and CaM or CaM1234 (a CaM isoform unable to bind Ca(2+)). The results obtained suggest that each BFNS-causing mutation prompts specific biochemical and/or functional consequences; these range from slight alterations in CaM affinity which did not translate into functional changes (L351V), to a significant reduction in the affinity and functional modulation by CaM (L351F, Y362C or R553Q), to a complete functional loss without significant alteration in CaM affinity (W344R). CaM overexpression increased Kv7.2 and Kv7.2/Kv7.3 current levels, and partially (R553Q) or fully (L351F) restored normal channel function, providing a rationale pathogenetic mechanism for mutation-induced channel dysfunction in BFNS, and highlighting the potentiation of CaM-dependent Kv7.2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies.


Discerning biomimetic nanozyme electrodes based on g-C3N4 nanosheets and molecularly imprinted polythiophene nanofibers for detecting creatinine in microliter droplets of human saliva.
The growing risk of death associated with kidney dysfunction underlines the requirement for a cost-effective and precise point-of-care (POC) diagnostic tool to identify chronic kidney disease (CKD) at an early stage. This work reports the development of a non-invasive POC diagnostic based on cost-efficient, disposable electrodes and in situ-designed biomimetic nanozymes. The nanozymes are composed of graphitic carbon nitride nanosheets (gCN) and creatinine-imprinted polythiophene nanofibers (miPTh). Microscopic analyses reveal porous nanofibrous surface morphology of biomimetic miPTh/gCN nanozymes. Bulk imprinting and the inclusion of conductive gCN nanosheets drastically reduced the charge transfer resistance and improved the electron exchange kinetics at the nanozyme-electrolyte interface. The electrochemical oxidation of creatinine is studied via cyclic voltammetry (CV), and differential pulse voltammetry (DPV), which exhibit excellent creatinine recognition ability of biomimetic miPTh/gCN nanozyme sensors compared to pristine polymeric or non-imprinted nanozymes. The sensor reveals linear response toward 200-1000 nmol L-1 creatinine, high sensitivity (4.27 μA cm-2 nmol-1 L), sub-nanomolar detection limit (340 pmol L-1), and excellent selectivity over common salivary analytes. To corroborate its real-world utility, the miPTh/gCN nanozyme sensor shows an impressive 94.8% recovery of spiked creatinine concentrations in microliter droplets of human saliva samples. This disposable sensor reveals great potential in the realm of reliable and efficient non-invasive POC diagnostics for healthcare delivery.


Age-Related Changes in Thymic Central Tolerance.
Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance. In keeping with this possibility, there are age-associated changes in the cellular composition and function of T cells and Treg. This review summarizes changes in T cell and Treg function during the perinatal to adult transition and in the course of normal aging, and relates these changes to age-associated alterations in thymic HAPC and TEC subsets.


Redox potentials along the redox-active low-barrier H-bonds in electron transfer pathways.
Low-barrier H-bonds form when the pKa values of the H-bond donor and acceptor moieties are nearly equal. Here, we report redox potential (Em) values along two redox-active low-barrier H-bonds in the water-oxidizing enzyme photosystem II (PSII), using a quantum mechanical/molecular mechanical approach. The low-barrier H-bond between D1-Tyr161 (TyrZ) and D1-His190 is located in the middle of the electron transfer pathway. When the proton is at D1-His190, Em(TyrZ) is the lowest and can serve as an electron donor to the oxidized chlorophyll PD1˙+. Em(TyrZ) and Em(D1-His190) are equal, and the TyrZD1-His190 pair serves as an electron acceptor to Mn4CaO5 when the proton is at TyrZ. In the low-barrier H-bond between D1-His215 and plastoquinone QB, located at the terminus of the electron transfer pathway, the driving force of electron transfer and electronic coupling between QA and QB are maximized when the proton arrives at QB. It seems likely that local proton transfer along redox-active low-barrier H-bonds can alter the driving force or electronic coupling for electron transfer.


[Cardiologic assessment in candidates for non-cardiac surgery].
Cardiovascular complications are important causes of morbidity and mortality with major non cardiac procedures. The aim of preoperative cardiac evaluation is more appropriately the initiation of a process of communication between Cardiologist, Surgeon and Anesthesiologist, with the purpose of performing an evaluation of patient's clinical risk profile and of providing the more cost-effective strategy to reduce risk of cardiac complications. There is general agreement that an accurate clinical evaluation is necessary and often sufficient for preoperative cardiac risk assessment. Several indices for prediction of cardiac complications--based on the history and physical examination of the patient--have been proposed and many of them have been validated by following studies. An effective preoperative evaluation must focus four crucial data: clinical predictors and functional capacity of the patient and, on the other side, the specific risk of the type of surgical operation and its character of election or emergency. According to the integrated valuation of these four parameters we can identify the patients who need additional noninvasive testing from those who can directly undergo noncardiac surgery. Preoperative testing should be limited to circumstances in which the results will affect patient management and outcomes. Coronary angiography and following revascularization have the same indications as if performed in the non-operative setting.


Analyzing Reaction Rates with the Distortion/Interaction-Activation Strain Model.
The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the interaction energies between the two distorted molecules. The energy required to distort the molecules is called the activation strain or distortion energy. This energy is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by the stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions.


The protometabolic nature of prebiotic chemistry.
The field of prebiotic chemistry has been dedicated over decades to finding abiotic routes towards the molecular components of life. There is nowadays a handful of prebiotically plausible scenarios that enable the laboratory synthesis of most amino acids, fatty acids, simple sugars, nucleotides and core metabolites of extant living organisms. The major bottleneck then seems to be the self-organization of those building blocks into systems that can self-sustain. The purpose of this tutorial review is having a close look, guided by experimental research, into the main synthetic pathways of prebiotic chemistry, suggesting how they could be wired through common intermediates and catalytic cycles, as well as how recursively changing conditions could help them engage in self-organized and dissipative networks/assemblies (i.e., systems that consume chemical or physical energy from their environment to maintain their internal organization in a dynamic steady state out of equilibrium). In the article we also pay attention to the implications of this view for the emergence of homochirality. The revealed connectivity between those prebiotic routes should constitute the basis for a robust research program towards the bottom-up implementation of protometabolic systems, taken as a central part of the origins-of-life problem. In addition, this approach should foster further exploration of control mechanisms to tame the combinatorial explosion that typically occurs in mixtures of various reactive precursors, thus regulating the functional integration of their respective chemistries into self-sustaining protocellular assemblies.


Noninvasive imaging of the tree shrew eye: Wavefront analysis and retinal imaging with correlative histology.
Tree shrews are small mammals with excellent vision and are closely related to primates. They have been used extensively as a model for studying refractive development, myopia, and central visual processing and are becoming an important model for vision research. Their cone dominant retina (∼95% cones) provides a potential avenue to create new damage/disease models of human macular pathology and to monitor progression or treatment response. To continue the development of the tree shrew as an animal model, we provide here the first measurements of higher order aberrations along with adaptive optics scanning light ophthalmoscopy (AOSLO) images of the photoreceptor mosaic in the tree shrew retina. To compare intra-animal in vivo and ex vivo cone density measurements, the AOSLO images were matched to whole-mount immunofluorescence microscopy. Analysis of the tree shrew wavefront indicated that the optics are well-matched to the sampling of the cone mosaic and is consistent with the suggestion that juvenile tree shrews are nearly emmetropic (slightly hyperopic). Compared with in vivo measurements, consistently higher cone density was measured ex vivo, likely due to tissue shrinkage during histological processing. Tree shrews also possess massive mitochondria ("megamitochondria") in their cone inner segments, providing a natural model to assess how mitochondrial size affects in vivo retinal imagery. Intra-animal in vivo and ex vivo axial distance measurements were made in the outer retina with optical coherence tomography (OCT) and transmission electron microscopy (TEM), respectively, to determine the origin of sub-cellular cone reflectivity seen on OCT. These results demonstrate that these megamitochondria create an additional hyper-reflective outer retinal reflective band in OCT images. The ability to use noninvasive retinal imaging in tree shrews supports development of this species as a model of cone disorders.


[The role of immunological disorders in the infertile marriage].
The authors used modern immunological methods to investigate regulatory subpopulations of T-lymphocytes in 300 married couples. It was established that disorders of the immune status in females with infertility may develop according to two immune mechanisms--due to development of isoimmune response to ovocyte antigens. Development of antispermatic immunity is related to changes in the T- and B-system of immunity without involvement of the regulatory C-lymphocyte subpopulations while the C-suppressor deficit may be one of the links in the disorders of the immunological status leading to the development of antibodies to own ovarian antigens. Appearance of immunological disorders in the process of treatment of infertility is the reason for their correction.


Cost efficiency of reducing multiple births.
Reducing the frequency of multiple pregnancies would help to prevent prematurity associated with multiple births. Premature newborns may require extensive and costly medical interventions. Long-term disability also involves health, social and educational services during childhood, which may cost ten-fold more for twin than singleton births. On average, the known costs for twin births are four times higher than singleton births and triplet births are ten times higher than singleton births. Single embryo transfer (SET) can reduce the burden of illness due to multiple births. For good prognosis patients, the experimental evidence supports the transfer of a single embryo to reduce the burden of illness due to multiple birth and prematurity. Similar evidence suggests that the cost saving could support additional treatment cycles involving SET cycles. The findings have been confirmed by the beneficial outcome of a new health policy in Belgium, which allowed more reimbursement for assisted reproduction cycles in which transfer strategies aimed to reduce multiple birth rates.


Health status of seabirds and coastal birds found at the German North Sea coast.
Systematic pathological investigations to assess the health status of seabirds and coastal birds in Germany were performed. The investigation was conducted to obtain data on possible causes of decline in seabird and coastal bird populations. 48 individuals of 11 different species of seabirds and coastal birds were collected by the stranding network along the entire German North Sea coast from 1997 to 2008, including mainly waders such as Eurasian oystercatchers (Haematopus ostralegus) and red knots (Calidris canutus) as well as seabirds such as northern fulmars (Fulmaris glacialis) and common scoters (Melanitta nigra).For most birds (n = 31) found dead along the shore no obvious cause of death was evident, while 17 individuals were killed by collisions with lighthouses. Overall, the nutritional status of the investigated birds was very poor, and the body mass in most cases was significantly lower compared to masses of living birds caught during the same periods of the year. This is partly linked to chronic parasitic or bacterial infections in different organs or to septicaemia. In some cases infections with zoonotic tuberculosis caused by Mycobacterium spp. were found. Avian influenza was not found in any of the collected birds. The presented data contribute to the evaluation of the health status of birds in the German North Sea. Moreover, they present an important tool for the assessment of potential pathogens with an impact on the health status of seabirds and coastal birds.


Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion.
Metformin, a drug widely used in the treatment of type 2 diabetes, has recently been shown to act on skeletal muscle and liver in part through the activation of AMP-activated protein kinase (AMPK). Whether metformin or the satiety factor leptin, which also stimulates AMPK in muscle, regulates this enzyme in pancreatic islets is unknown. We have recently shown that forced increases in AMPK activity inhibit insulin secretion from MIN6 cells (da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, and Rutter GA. Biochem J 371: 761-774, 2003). Here, we explore whether 1) glucose, metformin, or leptin regulates AMPK activity in isolated islets from rodent and human and 2) whether changes in AMPK activity modulate insulin secretion from human islets. Increases in glucose concentration from 0 to 3 and from 3 to 17 mM inhibited AMPK activity in primary islets from mouse, rat, and human, confirming previous findings in insulinoma cells. Incubation with metformin (0.2-1 mM) activated AMPK in both human islets and MIN6 beta-cells in parallel with an inhibition of insulin secretion, whereas leptin (10-100 nM) was without effect in MIN6 cells. These studies demonstrate that AMPK activity is subject to regulation by both glucose and metformin in pancreatic islets and clonal beta-cells. The inhibitory effects of metformin on insulin secretion may therefore need to be considered with respect to the use of this drug for the treatment of type 2 diabetes.


DNA polymorphisms in new isolates of 'Deinococcus radiopugnans'.
Nineteen new Deinococcus isolates from soil, 18 of which were from samples immediately adjacent to a lake in Nottingham, UK, were characterized by conventional criteria, and found to be identical to each other and to conform most closely to the species D. radiopugnans. However, we detected three different restriction enzyme activities in three different isolates. Because of this suggestion of heterogeneity, we examined the isolates for restriction fragment length polymorphisms (RFLPs). RFLP analysis of the 19 original isolates, using three different probes, distinguished 17 divergent groups. This extraordinary diversity cannot be attributed to geographical differences, nor to the method of isolation, which employed UV-radiation selection.


Ultrastructural changes of photoreceptor synaptic ribbons in relation to time of day and illumination.
Electron microscopic sections through rod and cone ribbon synapses reveal mainly rodlike synaptic ribbon profiles, but a few unusual spherical and club-shaped profiles also occur. To elucidate the meaning of the latter two forms, the authors have investigated these ribbon synapses at different times during the 24-hour cycle and under various lighting conditions. The various types of ribbon profiles were counted, and their sizes were measured by means of transmission electron microscopy in retinas of male BALB/c mice exposed to 12 hours light (lights on at 6 AM) and 12 hours dark (LD 12:12), continuous light, or continuous darkness for 4 days. A 24-hour study of mice exposed to LD 12:12 showed that spherical and club-shaped profile numbers ranged from 0% to 29%, depending on the time of day. They reached a maximum at 3 hours after light onset, followed by a gradual decrease to approach zero at night and reappearing after light onset the next morning. After 4 days of continuous light, the spherical profiles were significantly decreased in number (examined at 9 AM). After continuous darkness, the spherical and club-shaped profiles were significantly reduced in number. Administration of 4 hours of light after 92 hours of continuous darkness restored the number of spherical and club-shaped profiles to normal values. The rodlike ribbon profiles were found to be longer in darkness than in light. In rod terminals containing spherical profiles, the rodlike ribbon profiles were shorter than in terminals without spherical profiles. CONCLUSIONS. The club-shaped and the spherical profiles were related to the turnover of the synaptic ribbons. Soon after light exposure in the morning, the synaptic ribbons formed distal swellings, giving rise to club-shaped profiles and a decrease in length. The swellings appeared to bud off, thus forming spherical synaptic bodies. This article discusses whether these changes are signs of degradation of spent ribbons, or whether they play a physiological role related to the inactivation of the ribbon synapses after light exposure.


Using Absorption Models for Insulin and Carbohydrates and Deep Leaning to Improve Glucose Level Predictions.
Diabetes is a chronic disease caused by the inability of the pancreas to produce insulin or problems in the body to use it efficiently. It is one of the fastest growing health challenges affecting more than 400 million people worldwide, according to the World Health Organization. Intensive research is being carried out on artificial intelligence methods to help people with diabetes to optimize the way in which they use insulin, carbohydrate intakes, or physical activity. By predicting upcoming levels of blood glucose concentrations, preventive actions can be taken. Previous research studies using machine learning methods for blood glucose level predictions have mainly focused on the machine learning model used. Little attention has been given to the pre-processing of insulin and carbohydrate signals in order to mimic the human absorption processes. In this manuscript, a recurrent neural network (RNN) based model for predicting upcoming blood glucose levels in people with type 1 diabetes is combined with several carbohydrate and insulin absorption curves in order to optimize the prediction results. The proposed method is applied to data from real patients suffering type 1 diabetes mellitus (T1DM). The achieved results are encouraging, obtaining accuracy levels around 0.510 mmol/L (9.2 mg/dl) in the best scenario.


Effects of accelerometer-based sedentary time and physical activity on DEXA-measured fat mass in 6059 children.
Globally, childhood obesity is on the rise and the effect of objectively measured movement behaviour on body composition remains unclear. Longitudinal and causal mediation relationships of accelerometer-based sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with dual-energy X-ray absorptiometry-measured fat mass were examined in 6059 children aged 11 years followed-up until age 24 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort. Over 13-year follow-up, each minute/day of ST was associated with 1.3 g increase in fat mass. However, each minute/day of LPA was associated with 3.6 g decrease in fat mass and each minute/day of MVPA was associated with 1.3 g decrease in fat mass. Persistently accruing ≥60 min/day of MVPA was associated with 2.8 g decrease in fat mass per each minute/day of MVPA, partly mediated by decrease insulin and low-density lipoprotein cholesterol. LPA elicited similar and potentially stronger fat mass-lowering effect than MVPA and thus may be targeted in obesity and ST prevention in children and adolescents, who are unable or unwilling to exercise.


Hesperidin as Radioprotector against Radiation-induced Lung Damage in Rat: A Histopathological Study.
Reactive oxygen species (ROS) are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT) of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES) against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham). G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg) for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05). Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05). Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05). HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05). Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats.


Experimental and Theoretical Evidence for Relativistic Catalytic Activity in C-H Activation of N-Phenylbenzamide Using a Cationic Iridium Complex.
This study elucidates that relativistic effect plays a key role in catalytic C-H activation using a cationic Ir complex. Experiments show that the cationic Ir(I)-diphosphine catalyst can be used for the deuterium substitution of N-phenylbenzamide, whereas a cationic Rh(I)-diphosphine catalyst is scarcely effective. Density functional theory calculations, including the relativistic effect, demonstrate a large difference in the reaction energy diagrams for the C-H activation of N-phenylbenzamide between the cationic Ir and Rh catalysts. In particular, the relatively low reaction barrier and considerably stabilized product obtained for the Ir catalysts are rationalized by strong Ir-C and Ir-H interactions, which originate from the relativistic self-consistent d-orbital expansion of Ir.


Prevalence and associated risk factors of malaria among adults in East Shewa Zone of Oromia Regional State, Ethiopia: a cross-sectional study.
Malaria is one of the most important causes of morbidity and mortality in sub-Saharan Africa. The disease is prevalent in over 75% of the country's area making it the leading public health problems in the country. Information on the prevalence of malaria and its associated factors is vital to focus and improve malaria interventions. A cross-sectional study was carried out from October to November 2012 in East Shewa zone of Oromia Regional State, Ethiopia. Adults aged 16 or more years with suspected malaria attending five health centers were eligible for the study. Logistic regression models were used to examine the effect of each independent variable on risk of subsequent diagnosis of malaria. Of 810 suspected adult malaria patients who participated in the study, 204 (25%) had microscopically confirmed malaria parasites. The dominant Plasmodium species were P. vivax (54%) and P. falciparum (45%), with mixed infection of both species in one patient. A positive microscopic result was significantly associated with being in the age group of 16 to 24 years [Adjusted Odds Ratio aOR 6.7; 95% CI: 2.3 to 19.5], 25 to 34 years [aOR 4.2; 95% CI: 1.4 to 12.4], and 35 to 44 years [aOR 3.7; 95% CI: 1.2-11.4] compared to 45 years or older; being treated at Meki health center [aOR 4.1; 95% CI: 2.4 to 7.1], being in Shashemene health center [aOR = 2.3; 95% CI: 1.5 to 4.5], and living in a rural area compared to an urban area [aOR 1.7; 95% CI: 1.1 to 2.6)]. Malaria is an important public health problem among adults in the study area with a predominance of P. vivax and P. falciparum infection. Thus, appropriate health interventions should be implemented to prevent and control the disease.


Increased beta-oxidation and improved oocyte developmental competence in response to l-carnitine during ovarian in vitro follicle development in mice.
Oocyte developmental competence is acquired throughout folliculogenesis and is associated with appropriate differentiation and responsiveness to the luteinizing hormone (LH) surge. The recent development of a novel system for culturing ovarian follicles in a three-dimensional alginate matrix shows promise in phenocopying in vivo folliculogenesis. However, oocytes from follicles grown in vitro have a reduced capacity to complete nuclear maturation and be fertilized compared to oocytes matured in vivo. Oocyte metabolism is closely linked with oocyte quality, and we have recently shown that beta-oxidation of lipids is essential for oocyte developmental competence. Thus we investigated whether upregulation of beta-oxidation by treatment with the fatty acid transport cofactor l-carnitine could improve folliculogenesis and developmental competence of mouse follicles following three-dimensional culture. Ovarian hormones (androstenedione, estradiol, and progesterone) and the induction of cumulus matrix proteins (hyaluronan and ADAMTS1) were similar to in vivo follicles, indicating that appropriate differentiation of follicular cells occurs in cultured follicles after an LH/human chorionic gonadotropin (hCG) stimulus. l-carnitine did not alter survival, growth, or differentiation of follicles. However, l-carnitine supplementation significantly increased beta-oxidation, and markedly improved both fertilization rate and blastocyst development. Together, these results show that appropriate responsiveness of the follicle to the LH/hCG surge occurs following three-dimensional follicle culture but limitations on key metabolic requirements remain. l-carnitine supplementation during in vitro follicle culture increased lipid metabolism and improved oocyte developmental competence.


Health technology assessment use and dissemination by patient and consumer groups: why and how?
Although increasing effort is being devoted to developing strategies to increase knowledge transfer and the uptake of health technology assessment (HTA) by various stakeholders, very little is known about the utilization and dissemination of HTA findings by patient and consumer organizations. The goal of this study is to understand how and why patient and consumer organizations use HTA findings within their organizations, and what factors influence how and when they communicate their findings to members or other organizations. We examined the use and dissemination of four controversial HTA reports by sixteen patient and consumer organizations in Ontario and Quebec. We gathered data from semistructured interviews conducted between December 2006 and April 2007. Although HTA findings are often used by the patient and consumer organizations, key differences were observed in exactly how the four HTA reports were used. Three types of use (instrumental, conceptual, and symbolic) are reported and illustrated. We highlight the importance of the organization's mission and knowledge base in explaining the types of use observed. We contend that the use and dissemination of HTA reports by specific groups could help in widening the debate around controversial health technologies. The implications and opportunities for HTA agencies relate to the following: (i) identification of "lay" organizations that could help in disseminating results; (ii) acknowledgement of a "lay" audience for HTA findings; (iii) strategic inclusion of advocacy groups during the assessment process for highly controversial technologies; and (iv) contribution of these organizations to the push efforts of knowledge transfer.


Anterior identity is established in chick epiblast by hypoblast and anterior definitive endoderm.
Previous studies of head induction in the chick have failed to demonstrate a clear role for the hypoblast and anterior definitive endoderm (ADE) in patterning the overlying ectoderm, whereas data from both mouse and rabbit suggest patterning roles for anterior visceral endoderm (AVE) and ADE. Based on similarity of gene expression patterns, fate and a dual role in 'protecting' the prospective forebrain from caudalising influences of the organiser, the chick hypoblast has been suggested to be the homologue of the mouse anterior visceral endoderm. In support of this, when transplanted to chick embryos, the rabbit AVE induces anterior markers in the chick epiblast. To reevaluate the role of the hypoblast/ADE (lower layer) in patterning the chick ectoderm, we used rostral blastoderm isolates (RBIs) as an assay, that is, rostral regions of blastoderms transected at levels rostral to the node. RBIs are, therefore, free from the influences of Hensen's node and ingressing axial mesoderm - tissues that are able to induce Ganf, the earliest specific marker of anterior neural plate. We demonstrate, using such RBIs (or RBIs dissected to remove the lower layer with or without tissue replacement), that the hypoblast/ADE (lower layer) is required and sufficient for patterning anterior positional identity in the overlying ectoderm, leading to expression of Ganf in neuroectoderm. Our results suggest that patterning of anterior positional identity and specification of neural identity are separable events operating to pattern the rostral end of the early chick embryo. Based on this new evidence we propose a revised model for establishing anteroposterior polarity, neural specification and head patterning in the early chick that is consonant with that occurring in other vertebrates.


Spectrum-Effect Relationships Between the Bioactive Ingredient of Syringa oblata Lindl. Leaves and Its Role in Inhibiting the Biofilm Formation of Streptococcus suis.
Syringa oblata Lindl. (S. oblata) has been used in herbal medicines for treating bacterial diseases. It is also thought to inhibit Streptococcus suis (S. suis) biofilm formation. However, due to the inherent nature of the complexity in its chemical properties, it is difficult to understand the possible bioactive ingredients of S. oblata. The spectrum-effect relationships method was applied to screen the main active ingredients in S. oblata obtained from Heilongjiang Province based on gray relational analysis. The results revealed that Sub-MICs obtained from 10 batches of S. oblata could inhibit biofilm formation by S. suis. Gray relational analysis revealed variations in the contents of 15 main peaks and rutin was discovered to be the main active ingredient. Then, the function of rutin was further verified by inhibiting S. suis biofilm formation using crystal violet staining. Computational studies revealed that rutin may target the chloramphenicol acetyltransferase protein in the biofilm formation of S. suis. In conclusion, this study revealed that the spectrum-effect relationships and computational studies are useful tools to associate the active ingredient with the potential anti-biofilm effects of S. oblata. Here, our findings would provide foundation for the further understanding of the mechanism of S. oblata intervention in biofilm formation.


Transarticular pinning for repair of hip dislocation in the dog: a retrospective study of 40 cases.
Transarticular pinning was used for the repair of hip dislocation in 40 dogs. The mean follow-up period was 18.4 months. Satisfactory results were achieved in 80% of the cases. Body weight, ipsilateral femoral head fracture, and hip dysplasia appeared to affect long-term prognosis. The most frequent complication was pin breakage, but this did not affect final outcome and could be avoided by using pins of larger diameter. Osteonecrosis was observed in two cases.


Comparative Evaluation of the Effect of 0.2% Chlorhexidine, 2% LemonGrass Oil, and 2% Tea Tree Oil Mouth rinse on Salivary pH: An In vivo Study.
Mouthwashes containing essential oils are used in the prevention and treatment of periodontal diseases. Lemongrass oil (LGO) belongs to a section of andropogen called cymbogam of the family germineae and from it, the LGO is extracted. Tea tree oil (TTO) is extracted from Melaleuca alternifolia leaves (Myrtaceae family). The aim of the study is to evaluate the pH of saliva before and after using LGO and TTO mouth rinse and to determine its relevance to the oral health status. A purposive sample of 90 participants aged between 26 and 38 years were included in the study. The PH before and after the use of the chlorhexidine, LGO, and TTO mouthwashes are noted using the GC PH strips and a comparative study was made. Statistical analysis was performed using paired t-test. P < 0.05 was considered statistically significant. Comparative analysis was made with Wilcoxon signed-ranks test and found that the TTO gives a greater increase in salivary pH with a P = 0.001** (P < 0.05) which is found to be statistically significant. The study conducted shows beneficial effects of TTO and LGO mouth rinse. Further studies with larger samples may produce more reliable values.


Climate drives phenological reassembly of a mountain wildflower meadow community.
Spatial community reassembly driven by changes in species abundances or habitat occupancy is a well-documented response to anthropogenic global change, but communities can also reassemble temporally if the environment drives differential shifts in the timing of life events across community members. Much like spatial community reassembly, temporal reassembly could be particularly important when critical species interactions are temporally concentrated (e.g., plant-pollinator dynamics during flowering). Previous studies have documented species-specific shifts in phenology driven by climate change, implying that temporal reassembly, a process we term "phenological reassembly," is likely. However, few studies have documented changes in the temporal co-occurrence of community members driven by environmental change, likely because few datasets of entire communities exist. We addressed this gap by quantifying the relationship between flowering phenology and climate for 48 co-occurring subalpine wildflower species at Mount Rainier (Washington, USA) in a large network of plots distributed across Mt. Rainier's steep environmental gradients; large spatio-temporal variability in climate over the 6 yr of our study (including the earliest and latest snowmelt year on record) provided robust estimates of climate-phenology relationships for individual species. We used these relationships to examine changes to community co-flowering composition driven by 'climate change analog' conditions experienced at our sites in 2015. We found that both the timing and duration of flowering of focal species was strongly sensitive to multiple climatic factors (snowmelt, temperature, and soil moisture). Some consistent responses emerged, including earlier snowmelt and warmer growing seasons driving flowering phenology earlier for all focal species. However, variation among species in their phenological sensitivities to these climate drivers was large enough that phenological reassembly occurred in the climate change analog conditions of 2015. An unexpected driver of phenological reassembly was fine-scale variation in the direction and magnitude of climatic change, causing phenological reassembly to be most apparent early and late in the season and in topographic locations where snow duration was shortest (i.e., at low elevations and on ridges in the landscape). Because phenological reassembly may have implications for many types of ecological interactions, failing to monitor community-level repercussions of species-specific phenological shifts could underestimate climate change impacts.


Detection of Panton-Valentine leukocidin and MecA Genes in Staphylococcus aureus isolated from Iraqi Patients.
A gram-positive bacterium, Staphylococcus aureus, which is widely distributed is considered as a bacterial infection that commonly infects the skin and mucous membranes. Such infections can be the cause of death and illness. In the present study by using reverse transcription-polymerase chain reaction (rt-PCR) the Panton-Valentine leukocidin (PVL) and MecA genes of S. aureus which were isolated from skin and soft tissue infections (SSTIs) in Baghdad, Iraq were investigated. This study included 96 S. aureus isolated from SSTIs and identified by Vitek. The results showed that 61 (63.5%) and 48 (50%) of the isolates were positive for PVL and MecA genes, respectively. This work presented an effective real-time PCR technique for detecting PVL genes alone or in conjunction with MecA. The rt-PCR allows for easier reaction monitoring and eliminates the need for post-PCR processing, saving both resources and time. Moreover, it is ideal for diagnostic applications because of its high sensitivity, simplicity, and specificity. Besides, the rt-PCR has an option to do all the procedures in an automated mode of action.


Health literacy associations between Hispanic elderly patients and their caregivers.
Knowing health literacy levels of older patients and their caregivers is important because caregivers assist patients in the administration of medications, manage daily health care tasks, and help make health services utilization decisions. The authors examined the association of health literacy levels between older Hispanic patients and their caregivers among 174 patient-caregiver dyads enrolled from 3 community clinics and 28 senior centers in San Antonio, Texas. Health literacy was measured using English and Spanish versions of the Short-Test of Functional Health Literacy Assessment and categorized as "low" or "adequate." The largest dyad category (41%) consisted of a caregiver with adequate health literacy and patient with low health literacy. Among the dyads with the same health literacy levels, 28% had adequate health literacy and 24% had low health literacy. It is notable that 7% of dyads consisted of a caregiver with low health literacy and a patient with adequate health literacy. Low health literacy is a concern not only for older Hispanic patients but also for their caregivers. To provide optimal care, clinicians must ensure that information is given to both patients and their caregivers in clear effective ways as it may significantly affect patient health outcomes.


Locally Aggressive Rib Hemangioma With Glomeruloid and Papillary Features - Expanding the Clinicopathologic spectrum of Bone Hemangiomas.
Intra-osseous hemangiomas are uncommon tumors that can present diagnostic and treatment dilemmas. Bone hemangiomas with papillary and glomeruloid growth patterns are exceptionally rare. We present an example of an intra-osseous hemangioma of the rib displaying aggressive features on both radiology and histology. Morphologically, prominent papillary and glomeruloid architectural patterns were observed, in addition to features of cavernous and capillary hemangiomas. Extensive extra-osseous soft tissue involvement was seen. Awareness of the diverse histological features and locally aggressive behavior of bone hemangiomas is important in avoiding over-interpretation as a malignant lesion.


Induction of labor in breech presentation at term: a retrospective cohort study.
To compare the outcome of two methods of labor induction and spontaneous onset of labor in breech presentation at term. A retrospective study between 2003 and 2012. We compare obstetric (indication of induction, Bishop score, cesarean rate) and perinatal outcomes (Apgar score, umbilical artery pH, base excess ≤-12 mmol/L, admission to neonatal unit) between prostaglandins and oxytocin. We also compare labor induction versus spontaneous onset of labor. Of the 1684 breech deliveries, we carried out labor induction in 221 cases (76% with prostaglandins, 24% with oxytocin). The prostaglandins group had significantly lower Bishop scores and the time for induction phase was significantly higher. There were no differences in cesarean rate between both methods of induction or spontaneous onset of labor. The prostaglandins group had higher rates of base excess ≤-12 mmol/L. Compared with spontaneous onset of labor in breech presentation, induction had significant lower rates of newborn weight and higher rates of admission to the neonatal unit. Induction of labor in breech presentation at term is a reasonable and effective option after a careful selection of cases. It was not associated with an increase of perinatal morbidity or cesarean rate compared with spontaneous onset of labor.


Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia.
The combination of Venetoclax (VEN) and Azacitidine (AZA) increases survival outcomes and yields excellent responses in patients with acute myeloid leukemia (AML). However, dose reduction (or discontinuation) is commonly encountered due to therapy-related toxicity. Thus, this study aimed to investigate the efficiency and safety of a lower dosage of venetoclax for the treatment of AML. This observational study analyzed the characteristics and outcomes of newly diagnosed AML patients who received 100 mg VEN combined with AZA for 14 days at our institution. A total of 36 patients were enrolled, and the median age at diagnosis was 64 years. After a median follow-up of 15 (range 4-29) months, the median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 17 (4-29) months and 12 (1-28) months, respectively. Meanwhile, the overall response rate (ORR) was 69.4%, and the CRc rate was 66.7% in the whole cohort. Subgroup analysis revealed that NPM1 mutations and FAB-M5 subtype were associated with higher response rates, whereas the adverse ELN risk group was predictive of an inferior response. Moreover, ASXL1, NPM1, and IDH1/2 mutations negatively impacted PFS. Our study optimized the administration of venetoclax plus azacytidine for the treatment of AML patients. Response rates were favorable, with median survival in agreement with the findings of earlier reports, offering valuable insights for optimizing VEN-based regimens. In summary, the VEN combination regimen is effective for the treatment of newly diagnosed AML patients in the real world despite VEN dose reductions .


Antifungal properties of cathelicidin LL-37: current knowledge and future research directions.
The threat of fungal diseases is substantially underestimated worldwide, but they have serious consequences for humans, animals, and plants. Given the limited number of existing antifungal drugs together with the emergence of drug-resistant strains, many researchers have actively sought alternatives or adjuvants to antimycotics. The best way to tackle these issues is to unearth potential antifungal agents with new modes of action. Antimicrobial peptides are being hailed as a promising source of novel antimicrobials since they exhibit rapid and broad-spectrum microbicidal activities with a reduced likelihood of developing drug resistance. Recent years have witnessed an explosion in knowledge on microbicidal activity of LL-37, the sole human cathelicidin. Herein, we provide a summary of the current understanding about antifungal properties of LL-37, with particular emphasis on its molecular mechanisms. We further illustrate fruitful areas for future research. LL-37 is able to inhibit the growth of clinically and agronomically relevant fungi including Aspergillus, Candida, Colletotrichum, Fusarium, Malassezia, Pythium, and Trichophyton. Destruction of the cell wall integrity, membrane permeabilization, induction of oxidative stress, disruption of endoplasmic reticulum homeostasis, formation of autophagy-like structures, alterations in expression of numerous fungal genes, and inhibition of cell cycle progression are the key mechanisms underlying antifungal effects of LL-37. Burgeoning evidence also suggests that LL-37 may act as a potential anti-virulence peptide. It is hoped that this review will not only motivate researchers to conduct more detailed studies in this field, but also inspire further innovations in the design of LL-37-based drugs for the treatment of fungal infections.


The LIM domains of WLIM1 define a new class of actin bundling modules.
Actin filament bundling, i.e. the formation of actin cables, is an important process that relies on proteins able to directly bind and cross-link subunits of adjacent actin filaments. Animal cysteine-rich proteins and their plant counterparts are two LIM domain-containing proteins that were recently suggested to define a new family of actin cytoskeleton regulators involved in actin filament bundling. We here identified the LIM domains as responsible for F-actin binding and bundling activities of the tobacco WLIM1. The deletion of one of the two LIM domains reduced significantly, but did not entirely abolish, the ability of WLIM1 to bind actin filaments. Individual LIM domains were found to interact directly with actin filaments, although with a reduced affinity compared with the native protein. Variants lacking the C-terminal or the inter-LIM domain were only weakly affected in their F-actin stabilizing and bundling activities and trigger the formation of thick cables containing tightly packed actin filaments as does the native protein. In contrast, the deletion of one of the two LIM domains negatively impacted both activities and resulted in the formation of thinner and wavier cables. In conclusion, we demonstrate that the LIM domains of WLIM1 are new autonomous actin binding and bundling modules that cooperate to confer WLIM1 high actin binding and bundling activities.