[E-learning : an effective and necessary complement to the postgraduate training].
The evolution of modern medicine largely influenced the development of new postgraduate training programs, which requirements are more engaging and constraining. Time dedicated to education more and more often comes into competition with the resident's clinical and administrative activities. In this context, E-learning could be an interesting solution, if used complementary to the classical training which does not further overload the clinical activity. By focusing on the recognition of clinical images, and interpretation of functional tests, we target some well known knowledge gaps of our trainees. Our program allows every participant to be exposed to some important, prototypical or rare situations, independent of the clinical exposure. The quality of our program is ensured by the collaboration with several specialty departments of our hospital.


Thalidomide-based treatment for HIV-associated multiple myeloma: a case report.
The spectrum of hematologic and immunologic abnormalities induced by HIV infection is broad. Although the incidence of HIV-associated B-cell neoplasms has increased, relatively few cases of multiple myeloma have been reported, and even fewer cases have detailed treatment outcome. The case of an HIV-infected man in whom multiple myeloma was diagnosed following progressive anemia and fatigue is described. The patient began treatment consisting of thalidomide, dexamethasone, and clarithromycin, which led to a rapid and dramatic antitumor response. He experienced modest regimen-related toxicities while retaining a normal CD4+ T-lymphocyte count and a nondetectable HIV viral load. The immunologic and antitumor effects of thalidomide in the context of multiple myeloma and HIV infection are also briefly reviewed. Given thalidomide's relatively favorable side-effect profile and purported immunologic benefit, further studies of this drug in the treatment of HIV-associated multiple myeloma should be pursued.


Time-resolved radiation chemistry: dynamics of electron attachment to uracil following UV excitation of iodide-uracil complexes.
Electron attachment to uracil was investigated by applying time-resolved photoelectron imaging to iodide-uracil (I(-)U) complexes. In these studies, an ultraviolet pump pulse initiated charge transfer from the iodide to the uracil, and the resulting dynamics of the uracil temporary negative ion were probed. Five different excitation energies were used, 4.00 eV, 4.07 eV, 4.14 eV, 4.21 eV, and 4.66 eV. At the four lowest excitation energies, which lie near the vertical detachment energy of the I(-)U complex (4.11 eV), signatures of both the dipole bound (DB) as well as the valence bound (VB) anion of uracil were observed. In contrast, only the VB anion was observed at 4.66 eV, in agreement with previous experiments in this higher energy range. The early-time dynamics of both states were highly excitation energy dependent. The rise time of the DB anion signal was ∼250 fs at 4.00 eV and 4.07 eV, ∼120 fs at 4.14 eV and cross-correlation limited at 4.21 eV. The VB anion rise time also changed with excitation energy, ranging from 200 to 300 fs for excitation energies 4.00-4.21 eV, to a cross-correlation limited time at 4.66 eV. The results suggest that the DB state acts as a "doorway" state to the VB anion at 4.00-4.21 eV, while direct attachment to the VB anion occurs at 4.66 eV.


Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study.
Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.


Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins.
The energy landscape theory provides a general framework for describing protein folding reactions. Because a large number of studies, however, have focused on two-state proteins with single well-defined folding pathways and without detectable intermediates, the extent to which free energy landscapes are shaped up by the native topology at the early stages of the folding process has not been fully characterized experimentally. To this end, we have investigated the folding mechanisms of two homologous three-state proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the early and late transition states on their folding pathways. Through a combination of Phi value analysis and molecular dynamics simulations we obtained atomic-level structures of the transition states of these homologous three-state proteins and found that the late transition states are much more structurally similar than the early ones. Our findings thus reveal that, while the native state topology defines essentially in a unique way the late stages of folding, it leaves significant freedom to the early events, a result that reflects the funneling of the free energy landscape toward the native state.


Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline.
Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (P<0.01). No significant differences in the expression of MMP-2, TIMP-1 or TIMP-2 mRNA were observed between the experimental and control groups. Using an MMP-9 activity assay, the levels of MMP-9 activity in the experimental group were demonstrated to be significantly higher than in the control group (P<0.05). To investigate associated cellular signaling pathways, PDTC [a nuclear factor (NF)-κB/inhibitor of NF-κB (IκB) inhibitor], PD98059 [a mitogen-activated protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK inhibitor) and 5,15-DPP [a signal transduction and activator of transcription (STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP-9 upregulation induced by stimulation with arecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.


The National Programme for IT in England.
The National Programme for IT in England has been designed to support the modernisation of the National Health Service, and the Government aims of delivering a high-quality service designed around the needs of the patient. This article describes the architecture for the core component of the NHS Care Record Service including the application, information and security architectures and the requirements for supporting standards and technologies.


Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes.
(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein (alpha SYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express alpha SYN, so MSA pathology may arise from aberrant expression of alpha SYN in OLs. To study pathological deposition of alpha SYN in OLs, transgenic mice were generated in which human wild-type alpha SYN was driven by a proteolipid protein promoter. Transgenic alpha SYN was detected in OLs but no other brain cell type. At the light microscopic level, the transgenic alpha SYN profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic hyperphosphorylation at S129 of alpha SYN was reproduced in the transgenic mice. A significant proportion of the transgenic alpha SYN was detergent insoluble, as in MSA patients. The histological and biochemical abnormalities were specific for the disease-relevant alpha SYN because control green fluorescent protein was fully soluble and evenly distributed throughout OL cell bodies and processes. Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology.


Removal of arsenate from aqueous solution by nanocrystalline Mg/Al layered double hydroxide: sorption characteristics, prospects, and challenges.
Removal of arsenate (As(V)) from aqueous solution using both nanocrystalline and coprecipitated Mg/Al layered double hydroxides (LDHs) was examined under different sorption/desorption conditions. The surface area, pore volume, and pore size of the nanocrystalline LDH were significantly higher than those of the coprecipitated LDH, thus resulting in a higher As(V) sorption maximum than the coprecipitated LDH. The calculated activation energy (E(a)) value was 24.7 kJ/mol, suggesting the occurrence of anion exchange process for As(V) removal by the nanocrystalline LDH. The predominance of anion exchange process was further supported by the investigation of ionic strength effect, and XRD and FTIR analyses. The effect of aqueous matrix on As(V) sorption by the nanocrystalline LDH was found to increase in the order of nitrate < silica < sulfate < carbonate < phosphate. Regeneration study showed that a secondary sorption mechanism might occur concurrently for the As(V) sorption by nanocrystalline LDH besides the predominant anion exchange process. Prospects and challenges for practical application of the nanocrystalline LDH were also discussed in the latter part of this study.


Randomized Controlled Trials on Chronic Obstructive Pulmonary Disease in Africa: A Systematic Review.
The rising burden of chronic obstructive pulmonary disease (COPD) in African countries is attributed to the growing and aging of the populations, lifestyles, and environmental changes. This systematic review aims to map the available evidence on COPD interventions in Africa. We performed a systematic search in 6 databases (including local African databases) and registries with updates through January 2022. We included randomized controlled trials (RCTs) that included patients diagnosed with COPD and were conducted in Africa, studying outcomes on acute respiratory episodes and rates, physical and functional abilities, and adverse events. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study quality was assessed using the Cochrane risk of bias tool. We primarily summarized the results in narrative form. Out of 1594 identified publications, we included 18 studies with a total of 1504 participants, conducted in Egypt, South Africa, and Tunisia. Eight studies investigated interventions for patients in stable phases treated in outpatient settings, and 10 included patients with acute COPD exacerbations treated in emergency or intensive care settings. The interventions mainly included ventilatory support and pharmacological and rehabilitative interventions. Reported treatment effects were heterogeneous, ranging from no beneficial effects to clinically relevant benefits. The included studies were conducted in countries with high infrastructural development and half of them were set in intensive care units. Despite the paucity of RCTs on COPD management, research activities have been increasing over the last several years.


Encapsulated transgene cells attenuate hypertension, cardiac hypertrophy and enhance renal function in Goldblatt hypertensive rats.
The success of any gene-therapy approach depends on the survival of the genetically engineered cells that are implanted in the patient to deliver the therapeutic product. Immunoisolation of nonautologous cells within a microcapsule is a unique approach for gene therapy. We employed an immunoisolation device that protects nonautologous cells from destruction, to implant human atrial natriuretic peptide (hANP)-producing Chinese hamster ovary (CHO) cells in two-kidney, one-clip (2K1C) hypertensive rats. CHO cells transfected with the plasmid CMV-cANP were encapsulated in biocompatible polycaprolactone (PCL) capsules, and then the PCL capsules were implanted into 2K1C hypertensive rats intraperitoneally. The implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase 2 weeks post-implantation and the effect lasted for more than 5 months. The implantation of encapsulated hANP-producing cells also caused significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), sodium output, urine excretion, and urinary cGMP levels. These beneficial effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, reduction in cardiomyocyte size, tubular injury and renal arterial thickening. Immunoreactive hANP can be detected in the blood of 2K1C rats after implantation of the PCL capsules containing hANP-producing cells. This study demonstrates the usefulness of encapsulated ANP gene transfected cells as a new tool for ANP gene delivery in studying renovascular hypertension and cardiovascular diseases. Thus, our results may have important implications for clinical use of transgene cells as therapeutic agents in the treatment of cardiovascular diseases.


Physicochemical characteristics of SAPO-34 molecular sieves synthesized with mixed templates as MTO catalysts.
In the present work, a variety of SAPO-34 catalysts have been prepared using various templates such as a single or mixtures of tetraethylammonium hydroxide (TEAOH), morpholine, diethylamine (DEA), triethylamine (TEA), dipropylamine (DPA), isopropylamine (IPA) and Diethanolamine (DEtA). It is shown that crystal morphology and physicochemical properties were affected by the kinds of templates and mixture contents. Especially, inexpensive SAPO-34 catalyst with good crystal properties and catalytic performance was obtained by using mixed template of DEA and TEAOH. Through N2 isotherm, XRD, SEM, NH3 TPD and 29Si-NMR techniques, the effect of mixed template on the crystal morphology, acidity and Si distribution were investigated. Catalytic activity and life stability of SAPO-34 in MTO reaction was improved by using mixed template because of the distinction of the crystal size, acidity and Si distribution.


Malignant mesenchymoma of the prostate: immunohistochemical and ultrastructural observations.
A case of malignant mesenchymoma of the prostate is reported. Immunohistochemical and ultrastructural examination revealed malignant chondro-osteoblastic and rhabdomyoblastic features. A separate incidental prostatic adenocarcinoma was also seen. These lesions should be differentiated from carcinosarcoma in which adenocarcinoma is intermingled with malignant mesenchymal components.


Interaction of Uranium with Bacterial Cell Surfaces: Inferences from Phosphatase-Mediated Uranium Precipitation.
Deinococcus radiodurans and Escherichia coli expressing either PhoN, a periplasmic acid phosphatase, or PhoK, an extracellular alkaline phosphatase, were evaluated for uranium (U) bioprecipitation under two specific geochemical conditions (GCs): (i) a carbonate-deficient condition at near-neutral pH (GC1), and (ii) a carbonate-abundant condition at alkaline pH (GC2). Transmission electron microscopy revealed that recombinant cells expressing PhoN/PhoK formed cell-associated uranyl phosphate precipitate under GC1, whereas the same cells displayed extracellular precipitation under GC2. These results implied that the cell-bound or extracellular location of the precipitate was governed by the uranyl species prevalent at that particular GC, rather than the location of phosphatase. MINTEQ modeling predicted the formation of predominantly positively charged uranium hydroxide ions under GC1 and negatively charged uranyl carbonate-hydroxide complexes under GC2. Both microbes adsorbed 6- to 10-fold more U under GC1 than under GC2, suggesting that higher biosorption of U to the bacterial cell surface under GC1 may lead to cell-associated U precipitation. In contrast, at alkaline pH and in the presence of excess carbonate under GC2, poor biosorption of negatively charged uranyl carbonate complexes on the cell surface might have resulted in extracellular precipitation. The toxicity of U observed under GC1 being higher than that under GC2 could also be attributed to the preferential adsorption of U on cell surfaces under GC1. This work provides a vivid description of the interaction of U complexes with bacterial cells. The findings have implications for the toxicity of various U species and for developing biological aqueous effluent waste treatment strategies. The present study provides illustrative insights into the interaction of uranium (U) complexes with recombinant bacterial cells overexpressing phosphatases. This work demonstrates the effects of aqueous speciation of U on the biosorption of U and the localization pattern of uranyl phosphate precipitated as a result of phosphatase action. Transmission electron microscopy revealed that location of uranyl phosphate (cell associated or extracellular) was primarily influenced by aqueous uranyl species present under the given geochemical conditions. The data would be useful for understanding the toxicity of U under different geochemical conditions. Since cell-associated precipitation of metal facilitates easy downstream processing by simple gravity-based settling down of metal-loaded cells, compared to cumbersome separation techniques, the results from this study are of considerable relevance to effluent treatment using such cells.


The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: structure, quantum-theoretical analysis, and simultaneity principles.
Six stable dimer models for 7-azaindole (including the classic C(2h) doubly hydrogen-bonded, coplanar, centrosymmetric dimer) are considered to be observable in adiabatic nozzle jet molecular beams. They are analyzed by hybrid density functional theory (DFT), the MP2 ab initio method for the ground electronic state, and the single-excitation configuration interaction (CIS) (over frozen ground state optimized geometries obtained from DFT) excited state calculations, for global potential minima and proton-transfer potential energy curves. Three simultaneity principles are stated: (i) intermolecular coherent excitation molecular exciton simultaneity, (ii) intramolecular acid-base change simultaneity at the pyrrolo-N-H and aza-N proton-donor, proton-acceptor sites, and (iii) intermolecular simultaneity of catalytic proton-donor, proton-acceptor action. It is suggested that the formation of the classic C(2h) dimer of 7-azaindole, which is considered exclusively by previous researchers, can be formed from at least one of the several card-pack hydrogen-bonded dimers in a secondary slower step approaching a microsecond scale, instead of the picosecond events at the supersonic nozzle. It is proposed that the complexity of dimerization modes is the basis of the postexcitation, postionization diverse kinetic isotope results.


Three-wavelength optical sensor for measuring distributed mass concentrations of aerosols from stationary sources.
Stationary source emissions of key industries, such as thermal power plants, have become the central consideration in environmental protection programs. Existing photoelectric sensors at stationary sources usually use a single wavelength laser to measure the total mass concentration of the particulate matter, bearing inherent errors due to the changing particle size distribution (PSD). However, the total mass concentration cannot comprehensively estimate the air pollution caused by the stationary sources. Therefore, it is required to measure both the mass concentration and PSD of the aerosols emitted by the stationary sources, based on which we can get a distributed mass concentration. To implement this, in this study, we designed a novel three-wavelength photoelectric sensor and tested its performance. Results showed that the prototype correctly determines the mean particle size and standard deviation of the PSDs and consequently adjusts the coefficient for measuring the mass concentration from light intensity, providing a comprehensive assessment of the pollutants.


Multi-Surface Cartilage Defects about the Knee Treated with Cartilage Restoration Procedures Show Good Outcomes and Survivorship at Minimum 2-Year Follow-Up.
We aimed to evaluate the outcomes, survivorship, and complications following multi-surface cartilage procedures at minimum 2-year follow-up. Patients with either (1) single-surface osteochondral allograft transplantation (OCAT) with third-generation matrix-induced autologous cultured chondrocyte implantation (MACI) or particulated juvenile cartilage implantation (DeNovo), or (2) multiple-surface OCAT ± associated MACI/DeNovo procedures for grade IV chondral or osteochondral defects about the knee with minimum 2-year follow-up were analyzed. Patient-reported outcome measures (PROMs), including International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, were obtained preoperatively and at minimum 2 years postoperatively. The percentage of patients who met the minimal clinically important difference (MCID) for each PROM was reported. Failure was defined as revision OCAT, conversion to patellofemoral/total/unicompartmental joint arthroplasty, or Arthrosurface HemiCAP placement. Of 257 patients identified, 35 were included. There was a significant increase in IKDC, KOOS-pain, KOOS-symptom, KOOS-sport, and KOOS-quality of life scores from preoperative to postoperative evaluation (P < 0.03 for all). More than 50% of patients met the MCID for each PROM. There were 2 failures, 1 of the patella and 1 of the medial femoral condyle, at 39.7 and 38.6 months postoperatively, respectively. Multi-surface cartilage procedures are a safe, efficacious treatment option for multifocal cartilage defects about the knee at short-term follow-up.


[FROM THEORY TO PRACTICE - IMPLEMENTING THE BIO-PSYCHO-SOCIAL MODEL IN CLINICAL AND RESEARCH ACTIVITIES IN THE BEER-SHEVA MENTAL HEALTH CENTER].
The Beer Sheva Mental Health Center is the second largest mental health hospital in Israel and provides acute and chronic in-patient services for the entire population of the Southern District of Israel, from Ashdod to Eilat (about 1.2 million people) from adolescence to the elderly. The outpatient services include a variety of regional specialty services such as bipolar, eating disorders, anxiety, neuromodulation, gender-oriented, attention deficit hyperactivity disorder, sleep, dual diagnosis, geronto-psychiatry and post-traumatic stress disorder clinics and various rehabilitation day-care services. The emergency department provides 24 hour services with a 30-bed intensive care ward alongside it. The center offers up to date bio-psycho-social treatment and rehabilitation care, provided by academically-approved clinical social workers, psychologists, nursing staff and psychiatrists, all of whom are involved in under-graduate Mental Health Education (affiliated to Ben-Gurion University) and post-graduate Residency Training Programs (for each of the above disciplines). Despite the routine workload vis-a-vis patients and families and the busy teaching schedule, the center regards research as a lynch-pin of health care provision. In this issue of "Harefuah", clinical research and study reports by physicians, psychologists, clinical social workers and basic scientists from the Mental Health Center are presented. The manuscripts relate to quantitative and qualitative studies with patients and animal models, therapeutic approaches and scientific theories, which represent a sample of the ongoing clinical research activities.


Evidence that tissue mast cells derive from mononuclear phagocytes.
A new method has been developed that allows in vitro differentiation of rat mast cells from precursor cells in the absence of feeder layers. In the present investigation, the precursor cells are further characterized as to their nature, state of activation and distribution in different organs of the rat. The data support our previously published evidence, based on morphology and enzyme-cytochemical reaction patterns that the precursor cells are mononuclear phagocytes. Peritoneal macrophages elicited by mineral oil, thioglycollate or proteose-peptone have lost the ability to differentiate into mast cells. Single cell suspensions of spleen and bone marrow contain mast cell precursors, while cells from mesenteric lymph nodes and thymus or purified lymphocytes never yield mast cells in this culture system.


Low-voltage ride-through capability in a DFIG using FO-PID and RCO techniques under symmetrical and asymmetrical faults.
The power grid faults study is crucial for maintaining grid reliability and stability. Understanding these faults enables rapid detection, prevention, and mitigation, ensuring uninterrupted electricity supply, safeguarding equipment, and preventing potential cascading failures, ultimately supporting the efficient functioning of modern society. This paper delves into the intricate challenge of ensuring the robust operation of wind turbines (WTs) in the face of fault conditions, a matter of substantial concern for power system experts. To navigate this challenge effectively, the implementation of symmetrical fault ride-through (SFRT) and asymmetrical fault ride-through (AFRT) control techniques becomes imperative, as these techniques play a pivotal role in upholding the stability and dependability of the power system during adverse scenarios. This study addresses this formidable challenge by introducing an innovative SFRT-AFRT control methodology based on rotor components optimization called RCO tailored for the rotor side converter (RSC) within a doubly-fed induction generator (DFIG) utilized in wind turbine systems. The proposed control strategy encompasses a two-fold approach: firstly, the attenuation of both positive and negative components is achieved through the strategic application of boundary constraints and the establishment of reference values. Subsequently, the optimization of the control characteristic '[Formula: see text]' is accomplished through the utilization of a particle swarm optimization (PSO) algorithm integrated within an optimization loop. This intricate interplay of mechanisms aims to optimize the performance of the RSC under fault conditions. To measure the efficacy of the proposed control technique, a comparative analysis is conducted. Fractional-order (FO) proportional-integral-derivative (PID) controllers are employed as an additional method to complement the novel approach. By systematically juxtaposing the performance of the proposed SFRT-AFRT control technique with the FO-PID controllers, a comprehensive evaluation of the proposed approach's effectiveness is attained. This comparative assessment lends valuable insights into the potential advantages and limitations of the novel control technique, thereby contributing to the advancement of fault mitigation strategies in WT systems. Finally, the paper highlights the economic viability of the proposed control method, suggesting its suitability for addressing broader power network issues, such as power quality, in future wind farm research.


Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to amphotericin B and miconazole.
Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO4)2 6H2O and [Cu(phendio)3](ClO4)2 4H2O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC90 whereas pre-growth in AgClO4 and [Ag(phendio)2]ClO4 resulted in a small decrease in the relevant MIC90 values. The copper complexes reduce the oxygen consumption of C. albicans while the silver complexes increase oxygen consumption. In addition, pre-growth of cells in the copper complexes resulted in a lower ergosterol content while the silver complexes induced an elevation in ergosterol synthesis. The ability of copper and silver complexes to alter the susceptibility of C. albicans to miconazole and amphotericin B may be influenced by their action on respiration, since reduced respiration rates correlate with reduced cellular ergosterol which is the target for amphotericin B. Lower levels of ergosterol have previously been associated with elevated tolerance to this drug. In the case of reduced sensitivity to miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise to fewer toxic side products once biosynthesis is inhibited by miconazole.


Metastable chimera states in community-structured oscillator networks.
A system of symmetrically coupled identical oscillators with phase lag is presented, which is capable of generating a large repertoire of transient (metastable) "chimera" states in which synchronization and desynchronization coexist. The oscillators are organized into communities, such that each oscillator is connected to all its peers in the same community and to a subset of the oscillators in other communities. Measures are introduced for quantifying metastability, the prevalence of chimera states, and the variety of such states a system generates. By simulation, it is shown that each of these measures is maximized when the phase lag of the model is close, but not equal, to pi/2. The relevance of the model to a number of fields is briefly discussed with particular emphasis on brain dynamics.


Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties.
The mammalian heart contains two cardiac myosin isoforms: beta-myosin heavy chain (MHC) is found predominantly in the ventricles of large mammals, and alpha-MHC is expressed in the atria. The sequence identity between these isoforms is approximately 93%, with nonidentical residues clustered in discrete, functionally important domains associated with actin binding and ATPase activity. It is well-established that rabbit alpha-cardiac myosin has a 2-fold greater unloaded shortening velocity than beta-cardiac myosin but a 2-fold lower average isometric force. Here, we test the generality of these relationships for another large mammal, the pig, as well as for a small rodent, the mouse, which expresses alpha-MHC in its ventricles throughout adulthood. Hydrophobic interaction chromatography (HIC) was used to purify myosin from mouse, rabbit, and pig hearts. The superior resolving power of HIC made it possible to prepare highly homogeneous, enzymatically active myosin from small amounts of tissue. The movement of actin filaments by myosin was measured in an in vitro motility assay. The same assay could be used to determine average isometric force by loading the actin filaments with increasing concentrations of alpha-actinin to stop filament motion. We conclude that myosin from the mouse has significantly higher velocities for both alpha and beta isoforms than myosin from rabbits and pigs, even though the 2-fold difference in velocity between isoforms is maintained. Unlike the larger mammals, however, the small rodent generates the same high isometric force for both alpha and beta isoforms. Thus, nature has adapted the function of cardiac myosin isoforms to optimize power output for hearts of a given species.


Shedding Light on the Formation and Structure of Kombucha Biofilm Using Two-Photon Fluorescence Microscopy.
Kombucha pellicles are often used as inoculum to produce this beverage and have become a signature feature. This cellulosic biofilm produced by acetic acid bacteria (AAB) involves yeasts, which are also part of the kombucha consortia. The role of microbial interactions in the de novo formation and structure of kombucha pellicles was investigated during the 3 days following inoculation, using two-photon microscopy coupled with fluorescent staining. Aggregated yeast cells appear to serve as scaffolding to which bacterial cellulose accumulates. This initial foundation leads to a layered structure characterized by a top cellulose-rich layer and a biomass-rich sublayer. This sublayer is expected to be the microbiologically active site for cellulose production and spatial optimization of yeast-AAB metabolic interactions. The pellicles then grow in thickness while expanding their layered organization. A comparison with pellicles grown from pure AAB cultures shows differences in consistency and structure that highlight the impact of yeasts on the structure and properties of kombucha pellicles.


A Federated Attention-Based Multimodal Biometric Recognition Approach in IoT.
The rise of artificial intelligence applications has led to a surge in Internet of Things (IoT) research. Biometric recognition methods are extensively used in IoT access control due to their convenience. To address the limitations of unimodal biometric recognition systems, we propose an attention-based multimodal biometric recognition (AMBR) network that incorporates attention mechanisms to extract biometric features and fuse the modalities effectively. Additionally, to overcome issues of data privacy and regulation associated with collecting training data in IoT systems, we utilize Federated Learning (FL) to train our model This collaborative machine-learning approach enables data parties to train models while preserving data privacy. Our proposed approach achieves 0.68%, 0.47%, and 0.80% Equal Error Rate (EER) on the three VoxCeleb1 official trial lists, performs favorably against the current methods, and the experimental results in FL settings illustrate the potential of AMBR with an FL approach in the multimodal biometric recognition scenario.


Morbidity and Mortality Associated with Surgery of Traumatic C2 Fractures in Octogenarians.
Management of axis fractures in the elderly remains controversial. As the US population increasingly lives past 80 years, published C2 fracture morbidity/mortality profiles in younger cohorts (55+) have become less applicable to octogenarians. To report associations between surgery and mortality, hospital length of stay and discharge disposition in octogenarians with traumatic C2 fractures. Retrospective cohort study of 3847 patients age ≥ 80 years representing 17 702 incidents nationwide, divided into surgery/nonsurgery cohorts, using the National Sample Program of the National Trauma Data Bank from 2003 to 2012. Inpatient complications, mortality, length of stay, and discharge disposition are characterized; multivariable regression was utilized to determine associations between surgery and outcomes. The National Sample Program dataset from the National Trauma Data Bank is fully deidentified and does not contain Health Insurance Portability and Accountability Act identifiers; therefore, this study is exempt from IRB review at the University of California, San Francisco. Incidence of surgery was 10.3%. Surgery was associated with increased pneumonia, acute respiratory distress syndrome, and decubitus ulcer risks ( P < .001). Inpatient mortality was 12.8% (nonsurgery-13.0%; surgery-10.3%; P = .120). Length of stay was 8.31 ± 9.32 days (nonsurgery 7.78 ± 9.21; surgery 12.86 ± 9.07; P < .001) and showed an adjusted mean increase of 5.68 days with surgery (95% confidence interval [4.74-6.61]). Of patients surviving to discharge, 26% returned home (nonsurgery-26.8%; surgery-18.8%; P = .001); surgery patients were less likely to return home (odds ratio 0.59 [0.44-0.78]). The present study confirms that surgery of traumatic C2 fractures in octogenarians does not significantly affect inpatient mortality and increases discharge to institutionalized care. Patients undergoing surgery are more likely to require longer hospitalization and suffer increased medical complications during their stay. Given the retrospective nature of this study, it is unclear whether these conclusions reflect differences in injury severity between surgery cohorts. This question may be considered in a future prospective study.


Hollow Cathode Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride Using Pentachlorodisilane.
In this work, a novel chlorodisilane precursor, pentachlorodisilane (PCDS, HSi2Cl5), was investigated for the growth of silicon nitride (SiN x) via hollow cathode plasma-enhanced atomic layer deposition (PEALD). A well-defined self-limiting growth behavior was successfully demonstrated over the growth temperature range of 270-360 °C. At identical process conditions, PCDS not only demonstrated approximately >20% higher growth per cycle than that of a commercially available chlorodisilane precursor, hexachlorodisilane (Si2Cl6), but also delivered a better or at least comparable film quality determined by characterizing the refractive index, wet etch rate, and density of the films. The composition of the SiN x films grown at 360 °C using PCDS, as determined by X-ray photoelectron spectroscopy, showed low O content (∼2 at. %) and Cl content (<1 at. %; below the detection limit). Fourier transform infrared spectroscopy spectra suggested that N-H bonds were the dominant hydrogen-containing bonds in the SiN x films without a significant amount of Si-H bonds originating from the precursor molecules. The possible surface reaction pathways of the PEALD SiN x using PCDS on the surface terminated with amine groups (-NH2 and -NH-) are proposed. The PEALD SiN x films grown using PCDS also exhibited a leakage current density as low as 1-2 nA/cm2 at 2 MV/cm and a breakdown electric field as high as ∼12 MV/cm.


Helper T-cell type 17 cytokines and immunity in the lung.
The HIV epidemic has clearly demonstrated the critical role CD4(+) T cells play in preventing opportunistic infections in the lung. The types of CD4(+) effector T-cell populations in the lung have significantly expanded over the last 8-10 years with the discovery of helper T type 17 cells, and this review summarizes the field and discusses how these effector cells may be exploited to augment mucosal immunity in the lung.


Mucosa associated lymphoma of the lung.
Two cases of mucosa associated lymphoma (pseudolymphoma) of the lung are described which highlight the varied clinical and radiological features of this rare pulmonary condition. Following chemotherapy with prednisolone and chlorambucil, both patients are disease free three years later.


Two New Mylagaulid Rodents from the Early Miocene of China.
Mylagaulid fossorial rodents are a common component of North American Miocene fossil faunas. However outside of North America, only three species are known from Asia. Here we report two new mylagaulids, Irtyshogaulus minor gen. et sp. nov. and Irtyshogaulus major gen. et sp. nov., recovered from early Miocene sediments in the Junggar Basin in northwestern China. The two new taxa are small-sized, high-crowned promylagauline rodents. Their lower molars possess high metastylid crests, small mesostylids, broad and posterolingually expanded labial inflections, and transversely extending metalophid IIs. The mesoconid is absent in both species. The anterior and posterior fossettids are large and equally developed. Their upper M1-2s possess a square occlusal surface with five deep fossettes. The two new taxa are distinguished from each other mainly by their size, the morphology of fossettes and fossettids, development of mesial and distal lophs, posterior reduction of M3, and the orientation of m2 hypolophid. Our phylogenetic analysis indicates that Irtyshogaulus and Lamugaulus (another early Miocene Asian mylagaulid) are sister taxa. The two genera are nested among the North American promylagaulines, and share a common ancestor from North America, indicating early Miocene intercontinental dispersal within this clade of rodents.


In vivo confocal microscopy of polymorphic amyloid degeneration and posterior crocodile shagreen.
To report the in vivo confocal microscopic findings of combined polymorphic amyloid degeneration and posterior crocodile shagreen and correlate these findings with clinical presentations and previous histopathologic analysis. Case reports with confocal microscopic analysis and literature review. Three patients with bilateral corneal opacities presented to the Emory Eye Center Cornea Clinic for evaluation. The first patient, a 65-year-old woman, was noted to have bilateral, discrete, punctate, and filamentous refractile stromal opacifications that appeared to be concentrated in the deep stroma. The second patient, a 50-year-old man, had bilateral deep central stromal haze in a mosaic pattern with intervening cracklike clear zones. The third patient, an 80-year-old woman, had bilateral deep stromal deposits similar to patient 1 in addition to bilateral deep central stromal haze in a mosaic pattern with intervening cracklike clear zones similar to patient 2. Confocal microscopy showed bright, enhancing punctate lesions in the deep stroma and anterior stroma, with unaffected areas between these regions in patients 1 and 3, and central acellular opacification of irregular intensity with intermittent linear clear zones within the normal posterior stromal bed in cases 2 and 3. The first patient was diagnosed with isolated polymorphic amyloid degeneration, the second patient was diagnosed with isolated posterior crocodile shagreen, and the third patient was diagnosed with combined polymorphic amyloid degeneration and posterior crocodile shagreen. These cases are, to our knowledge, the first to report confocal microscopic findings in isolated polymorphic amyloid degeneration and combined polymorphic amyloid degeneration with posterior crocodile shagreen.


A constitutively nuclear form of NFATx shows efficient transactivation activity and induces differentiation of CD4(+)CD8(+) T cells.
The Ca(2+) signal facilitates nuclear translocation of NFAT through the dephosphorylation of clustered serine residues in the calcium regulatory domain by the Ca(2+)/calmodulin-dependent phosphatase calcineurin. The conformation of dephosphorylated NFAT exposes the nuclear localization signal for translocation into the nucleus and masks the nuclear export sequence to keep the protein in the nucleus. It has been reported that deletion of some serine-rich motifs masking the nuclear localization signal results in the translocation of NFAT into the nucleus, but that the nuclear export sequence located at the N terminus also needs to be deleted for NFATx (NFAT4/NFATc3) to exert efficient transactivation function. Here, we report that deletion of the critical serine-rich motifs of NFATx leads to a conformation that efficiently exposes the nuclear localization signal and that has stronger transcription activity compared with the fully activated wild-type protein in the presence of the nuclear export sequence. This also suggests that the regulation of the transactivation domain by phosphorylation observed in NFAT1 may not contribute significantly to the transcription activity of NFATx. The expression of this constitutively nuclear form of NFATx in the CD4(+)CD8(+) T cell line facilitates differentiation into the CD4 single-positive stage upon stimulation with phorbol ester. Our data suggest that NFATx is involved in the regulation of co-receptor expression during differentiation into the CD4 single-positive stage.


Invasive pneumococcal disease and socioeconomic deprivation: a population study from the North East of England.
Some communicable diseases disproportionately affect poor and vulnerable groups. Invasive pneumococcal disease (IPD) is an important cause of morbidity and mortality; however, the relationship between IPD and deprivation has not been well described. Population based study assessing the relationship between incidence of IPD and deprivation in the North East of England using data from an enhanced IPD surveillance system and the 2010 Indices of Multiple Deprivation and the Rural and Urban Area Classification. The incidence of IPD increased linearly with increasing deprivation from 7.0 per 100 000 population to 13.6 per 100 000 population. This association was demonstrated for the 16-64 and ≥65 year age groups, but not the <16 year age group. IPD incidence was strongly associated with all individual domains of deprivation except for the 'barriers to housing and services' domain. IPD incidence was higher in urban than rural areas. The risk of IPD is strongly associated with deprivation in adults, but not children. The mechanisms producing the associations observed remain unclear and require further investigation. Findings from this study reinforce the need to address social inequalities to reduce the burden of disease. Targeting vaccination at adults living in deprived areas could reduce the burden of IPD.


Complete versus partial excision of infected arteriovenous grafts: Does remnant graft material impact outcomes?
Infected arteriovenous grafts necessitate intervention to obtain source control. However, excising the graft material can be challenging and can lead to complications. Leaving a cuff of graft at the sites of anastomosis allows for the avoidance of potential risks. However, it is unclear whether doing so places patients at risk of recurrent graft infection. The purpose of the present study was to investigate the effect of complete vs partial excision of infected arteriovenous prosthetic dialysis access grafts. The data from all patients who had undergone surgical intervention for infected arteriovenous grafts at a single institution were retrospectively reviewed. The patients were grouped according to intervention type: complete excision and partial excision of arteriovenous prosthetic grafts. Partial excisions were further substratified based on whether flow had been restored through the arteriovenous access. The primary outcome was freedom from subsequent intervention for infection, defined as the number of days from excision to subsequent reoperation for reinfection. Freedom from infection was analyzed using the Kaplan-Meier method. A total of 117 patients had undergone surgical intervention for 122 infected arteriovenous grafts from 2003 to 2016. Of these 117 patients, 79 (64.8%) had undergone partial excision of infected arteriovenous grafts, and 43 (35.2%) had undergone complete excision with vascular repair. Within the partial excision cohort, 71 infected arteriovenous grafts (58.2%) were not flow restored and 8 (6.6%) were flow restored using either prosthetic or autogenous interpositions. The median follow-up time was 2.4 years (interquartile range, 0.6-4.5 years). The most common causative organisms included methicillin-resistant Staphylococcus aureus (n = 34; 27.9%), methicillin-sensitive S. aureus (n = 17; 13.9%), and S. epidermidis (n = 15; 12.3%). The recurrent infection rate in the partial excision group was 16.5% (n = 13) compared with 2.3% (n = 1) in the complete excision group. In the flow-restored subcohorts, those with restoration using prosthetic interposition grafts had the greatest reinfection rate at 57.1% (n = 4), and those with restoration using autogenous conduits did not experience reinfection (P = .033). Incomplete excision of infected arteriovenous prosthetic grafts was associated with a higher rate of reinfection compared with complete graft excision. Complete excision presents technical challenges but could provide superior source control in managing infected dialysis access. Complete excision with vascular reconstruction should be performed when possible to avoid leaving remnant prosthetic material.


Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles.
Polymorphonuclear leukocyte (PMN)-derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A(4) receptor or ALX. Intravenous delivery of human PMN-derived microparticles markedly inhibited PMN recruitment to an air pouch inflamed with IL-1beta. This anti-inflammatory effect was also dependent on endogenous AnxA1, since injection of microparticles produced from wild-type PMNs (bone marrow derived), but not from AnxA1-null PMNs, inhibited IL-1beta-induced leukocyte trafficking. In conclusion, PMN-derived microparticles contain functionally active AnxA1 that confers them anti-inflammatory properties; generation of these microparticles in the microcirculation could promote inflammatory resolution by time-dependent dampening of cell recruitment.


Socio-economic and health characteristics of HIV-infected patients seeking care in relation to access to the Drug Access Initiative and to antiretroviral treatment in Côte d'Ivoire.
To compare socio-economic and health characteristics of HIV-infected patients in Côte d'Ivoire whether or not they had access to the Drug Access Initiative (DAI) and to antiretroviral drug (ARV) treatment. Cross-sectional survey using medical files, blood sampling for CD4 cell counts and face-to-face interviews among all patients, informed of their HIV status, who attended during a 6-week period in the five DAI referral centres and three additional centres in charge of HIV care in Abidjan and Bouaké (participation rate = 65.4%). Multiple logistic regression using generalized estimating equations (GEE) to identify factors related to non-access to DAI and to ARV treatment. Among the 711 respondents, 23.0% were ARV-treated, 14.2% had been included in the DAI but were still waiting for initiation of ARV, and 62.7% were neither part of the DAI nor ARV-treated. In this latter group, less than one-third (29.6%) declared that they knew about the existence of the DAI. Among the 164 ARV-treated patients, 59.1% had benefited from DAI public subsidies partially covering the costs of drugs. In the non-DAI-non-ARV-treated group, 86% could have qualified for ARV treatment according to the DAI medical criteria (CD4 cell counts < 500 x 10(6) cells/l), and only 32.9% of those medically eligible were prescribed cotrimoxazole prophylaxis. In multivariate analysis, not being in the DAI and not being ARV-treated was related to: being a male, not having health care insurance, having a low level of education, living in poor housing conditions (absence of refrigerator in the household, absence of ventilation in patient's bedroom), and not being under cotrimoxazole prophylaxis. The Ivoirian DAI has facilitated access to ARV treatment for a significant number of patients with limited ability to pay. The majority of HIV-infected patients seeking care however face persisting socio-economic and informational barriers to access to these treatments.


Inhibition evaluation for a 20-min endotoxin limit test on FDG.
In chemical quality control tests for 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG), gel time is inversely related to endotoxin concentration. Solutions for positive product control (PPC) and positive water control (PWC) should contain a highly concentrated endotoxin level. The aims of our study were to derive an endotoxin concentration that causes PPC and PWC to gel and to evaluate inhibitory effects caused by FDG on gel formation in PPC and PWC test solutions. At expiration, the maximum administered total dose (in millilitres) of FDG should contain fewer than 175 endotoxin units (EU). Our average batch volume of FDG is 15 ml; thus, the minimum endotoxin limit should be 12 EU x ml(-1) . Twelve tubes were tested for each of four concentrations. Inhibition was assessed using Limulus amoebocyte lysate reagent, depyrogenated vials, and pyrogen-free sterile micropipette tips. Each study was performed with four groups of solutions: decayed 18F-FDG, negative control, PPC and PWC. In the study of undiluted FDG, seven of 50 PPC vials at 12 EU x ml(-1) did not gel. The lowest endotoxin concentration that consistently gelled at 20 min was 4 EU x ml(-1) . In the sample tested for inhibition using PPC tubes at 4 EU x ml(-1) , 49 tubes gelled at 20 min, and one did not. The inhibition rate improved between undiluted (i.e., 7/50 (14%)) and diluted (i.e., 1/50 (2%)) FDG PPC trials (P=0.03). However, given that 1 of 50 trials failed for diluted FDG PPC, we conclude that inhibition still occurs and there is a 95% chance that the inhibition rate could be as high as 11% or as low as 0% on repetition of the experiment.


Carnosic acid ameliorated Aβ-mediated (amyloid-β peptide) toxicity, cholinergic dysfunction and mitochondrial defect in Caenorhabditis elegans of Alzheimer's Model.
Amyloid-β peptide (Aβ)-induced cholinergic system and mitochondrial dysfunction are major risk factors for Alzheimer's disease (AD). Our previous studies found that carnosic acid (CA), an important polyphenol antioxidant, could significantly delay Aβ1-42-mediated acute paralysis. However, many details and underlying mechanisms of CA's neuroprotection against Aβ-induced cholinergic system defects and mitochondrial dysfunction remain unclear. Herein, we deeply investigated the effects and the possible mechanisms of CA-mediated protection against Aβ toxicity in vivo through several AD Caenorhabditis elegans strains. The results showed CA delayed age-related paralysis and Aβ deposition, and significantly protected neurons from Aβ-induced toxicity. CA might downgrade the expression of ace-1 and ace-2 genes, and upregulate cha-1 and unc-17 genes to inhibit acetylcholinesterase activity and relieve Aβ-caused cholinergic system defects. Furthermore, CA might also ameliorate Aβ-induced mitochondrial imbalance and oxidative stress through up-regulating the expression of phb-1, phb-2, eat-3, and drp-1 genes. The enhancements of the cholinergic system and mitochondrial function might be the reasons for the amelioration of Aβ-mediated toxicity and Aβ aggregation mediated by CA. These findings have helped us to understand the CA anti-Aβ activity in C. elegans and the potential mechanism of action.


Running power: lab based vs. portable devices measurements and its relationship with aerobic power.
In recent years, different companies have developed devices that estimate "running power". The main objective of this paper is to evaluate the effect of running speed on aerobic and running powers measured using force plates and by different devices. The second objective is to evaluate the relationship between aerobic power and running powers measured using force plates and by different devices. We enrolled 11 subjects in the study, they performed 5-min running trials at 2.22, 2.78, 3.33, 3.89 and 4.44 m/s respectively on a force-measuring treadmill while we collected metabolic data. We calculated running power as the dot product of ground reaction force and velocity of the centre of mass and compared it to the running power estimates of three devices: Skillrun (Technogym), Stryd Summit Powermeter (Stryd) and Garmin HRM-Run (Garmin). We found statistically significant linear correlations with running powers measured by all devices and running speed. Although absolute running power measurements were different among devices, an increase of 1 m/s in running speed translated to an increase of 0.944 W/kg in running power (p < 0.001). We found statistically significant linear correlations with running powers measured by all devices and aerobic power, in particular: as aerobic power increases by 1 W/kg, running power increases by 0.218 W/kg for all devices (p < 0.001). For level treadmill running, across speeds, running power measured by commercially available devices reflects force-based measurements and it can be a valuable metric, providing quasi real-time feedback during training sessions and competitions.HighlightsWe evaluated the effect of running speed on aerobic and running powers measured using force plates and by different devices.We also compared the relationship between aerobic power and running powers measured using force plates and by different devices.We found statistically significant linear correlations with running powers measured by all devices and aerobic power, in particular: as aerobic power increases by 1 W/kg, running power increases by 0.218 W/kg for all devices.For level treadmill running, across speeds, running power measured by commercially available devices reflects force-based measurements and it can be a valuable metric, providing quasi real-time feedback during training sessions and competitions.


[CONNECTIVE TISSUE METABOLIC FEATURES IN CLIMACTERIC SYNDROME'S PATIENTS WITH VARIOUS TYPES OF MENOPAUSE].
The purpose of the study was investigation of the connective tissue metabolic features among women with menopausal syndrome (MS) and MS, in which the arthropathic syndrome is leading and comparative analysis of the connective tissue indicators exchange during menopause caused in a surgical and natural way. We examined 70 women in total, menopause duration they accounted for 1,95±1,1 years, it came both as natural, and as a result of a surgery. The main group included 40 women with MS with leading arthropathic syndrome. The patients' modified menopausal index was calculated (MMI), the functional condition of the joints was assessed on a scale-questionnaire with the calculation of the clinical-functional index of WOMAC; the quantitative content and qualitative composition of glycosaminoglycans in the serum, the urinary excretion of hydroxyproline and uronic acids were determined. To determine the degree of deviation from the control (standard) indicators was used non-parametric Mann-Whitney criterion and factor analysis (main components method). It was revealed that all patients have an increased content of glycosaminoglycans and glycoprotein in the blood, which corresponds to the general age-related rearrangement of connective tissue metabolism, but the patients of the main group have more expressed indictors, which corresponds to more severe dystrophic changes and the severity of clinical symptoms. Redistribution of the fractional composition of glycosaminoglycans towards the increase of chondroitin-6 sulfate in patients of the main group indicates the presence of pre-emptive destruction of cartilage. The arthropathic syndrome availability also confirms the significant reduction CI-6s / CI-4s ratio and an increased content of chondroitin sulfates. Patients with a natural type of menopause showed more pronounced changes in connective tissue metabolites, in contrast to patients with surgical menopause еhat indicates a longer and more invasive pathologic course of natural menopause.


Arginine for gestating sows and foetal development: A systematic review.
The use of functional amino acids during pregnancy has been linked to improved reproduction in mammals. In this context, arginine is a precursor in the synthesis of numerous molecules, such as nitric oxide and polyamines, which play an important role during reproduction. However, contradictory studies are found in the literature, particularly regarding the amount of supplementation and the period of pregnancy in which it is used. The objective of this study was to evaluate the effects of dietary arginine supplementation for pregnant sows on foetal development via a systematic review. The search for papers was performed during the month of December 2015, in the databases ISI Web of Science, Science Direct, Scopus, and SciELO. From a total of 5675 returned studies, only 13 papers were selected after applying selection criteria. Most (47%) of the studies that evaluated the effects of dietary arginine supplementation on foetal development in pigs used 1% arginine. Supplementation was initiated in the first third of pregnancy in 47% of tests, including in both primiparous and multiparous sows. These studies showed positive results for embryo survival and foetal development, evidenced by the increase in placental weight and the number and weight of piglets born alive. Of all evaluated studies, 53% showed benefits on foetal development. It is concluded that supplementing dietary arginine in gestating sows can benefit embryo survival and foetal development. However, to establish a supplementation plan with this amino acid, aspects related to the period of pregnancy, supplementation levels, and source of arginine must be well defined.


Impact of the Expression System on Recombinant Protein Production in Escherichia coli BL21.
Recombinant protein production for medical, academic, or industrial applications is essential for our current life. Recombinant proteins are obtained mainly through microbial fermentation, with Escherichia coli being the host most used. In spite of that, some problems are associated with the production of recombinant proteins in E. coli, such as the formation of inclusion bodies, the metabolic burden, or the inefficient translocation/transport system of expressed proteins. Optimizing transcription of heterologous genes is essential to avoid these drawbacks and develop competitive biotechnological processes. Here, expression of YFP reporter protein is evaluated under the control of four promoters of different strength (P T7 lac , Ptrc, Ptac, and PBAD) and two different replication origins (high copy number pMB1' and low copy number p15A). In addition, the study has been carried out with the E. coli BL21 wt and the ackA mutant strain growing in a rich medium with glucose or glycerol as carbon sources. Results showed that metabolic burden associated with transcription and translation of foreign genes involves a decrease in recombinant protein expression. It is necessary to find a balance between plasmid copy number and promoter strength to maximize soluble recombinant protein expression. The results obtained represent an important advance on the most suitable expression system to improve both the quantity and quality of recombinant proteins in bioproduction engineering.


Negative Poisson's ratio in graphene oxide.
We perform molecular dynamics simulations to investigate the Poisson's ratio of graphene oxide. We find that the Poisson's ratio can be effectively tuned by increasing the degree of oxidation of graphene oxide. More specifically, the Poisson's ratio decreases linearly from positive to negative with increasing oxidation, turning negative at room temperature for a degree of oxidation of 0.27, and reaching a value of -0.567 for fully oxidized graphene. The oxidation dependence of the Poisson's ratio is attributed to the tension-induced suppression of the ripples resulting from the oxidation, whose amplitude increases with increasing oxidation. Finally, we also demonstrate the temperature dependence of the Poisson's ratio in the graphene oxide.


A cognate tRNA specific conformational change in glutaminyl-tRNA synthetase and its implication for specificity.
Conformational changes that occur upon substrate binding are known to play crucial roles in the recognition and specific aminoacylation of cognate tRNA by glutaminyl-tRNA synthetase. In a previous study we had shown that glutaminyl-tRNA synthetase labeled selectively in a nonessential sulfhydryl residue by an environment sensitive probe, acrylodan, monitors many of the conformational changes that occur upon substrate binding. In this article we have shown that the conformational change that occurs upon tRNA(Gln) binding to glnRS/ATP complex is absent in a noncognate tRNA tRNA(Glu)-glnRS/ATP complex. CD spectroscopy indicates that this cognate tRNA(Gln)-induced conformational change may involve only a small change in secondary structure. The Van't Hoff plot of cognate and noncognate tRNA binding in the presence of ATP is similar, suggesting similar modes of interaction. It was concluded that the cognate tRNA induces a local conformational change in the synthetase that may be one of the critical elements that causes enhanced aminoacylation of the cognate tRNA over the noncognate ones.


Preoperative characteristics of auditory brainstem response in acoustic neuroma with useful hearing: importance as a preliminary investigation for intraoperative monitoring.
We classified the results of preoperative auditory brainstem response (ABR) in 121 patients with useful hearing and considered the utility of preoperative ABR as a preliminary assessment for intraoperative monitoring. Wave V was confirmed in 113 patients and was not confirmed in 8 patients. Intraoperative ABR could not detect wave V in these 8 patients. The 8 patients without wave V were classified into two groups (flat and wave I only), and the reason why wave V could not be detected may have differed between the groups. Because high-frequency hearing was impaired in flat patients, an alternative to click stimulation may be more effective. Monitoring cochlear nerve action potential (CNAP) may be useful because CNAP could be detected in 4 of 5 wave I only patients. Useful hearing was preserved after surgery in 1 patient in the flat group and 2 patients in wave I only group. Among patients with wave V, the mean interaural latency difference of wave V was 0.88 ms in Class A (n = 57) and 1.26 ms in Class B (n = 56). Because the latency of wave V is already prolonged before surgery, to estimate delay in wave V latency during surgery probably underestimates cochlear nerve damage. Recording intraoperative ABR is indispensable to avoid cochlear nerve damage and to provide information for surgical decisions. Confirming the condition of ABR before surgery helps to solve certain problems, such as choosing to monitor the interaural latency difference of wave V, CNAP, or alternative sound-evoked ABR.


Posterior mushroom keratoplasty in patients with Fuchs endothelial dystrophy and pseudophakic bullous keratopathy: transplant outcome.
To report the outcome of posterior mushroom or top-hat-shaped keratoplasty for patients with Fuchs endothelial dystrophy (FED) or pseudophakic bullous keratopathy (PBK), concerning postoperative astigmatism, visual improvement, and endothelial cell density. Twenty-two eyes of 21 patients who received a posterior mushroom keratoplasty for FED (n = 19) or PBK (n = 3) between March 2003 and January 2006 at the Erasmus MC, Rotterdam, The Netherlands, were included. Visual acuity, refraction, and keratometry were measured at 6, 12, 24, and 36 months. Specular microscopy was performed annually. Best-corrected visual acuity (BCVA) significantly (P < 0.05) improved from 0.25 preoperatively to 0.47 at 6 months and 0.64 at 1 year postoperatively. Visual acuity remained stable with a BCVA of 0.62 2 years and 0.69 3 years after keratoplasty. At the last follow-up, the BCVA measured 0.5 or more in all but 2 (91%) eyes. Mean postoperative astigmatism at 1, 2, and 3 years measured 2.72 +/- 1.48, 2.69 +/- 1.85, and 1.75 +/- 1.76 D. Endothelial cell density averaged 2143 +/- 428 cells/mm2 at 1 year, 1539 +/- 573 cells/mm2 at 2 years, and 1920 +/- 474 cells/mm2 at 3 years. All studied transplants remained functional and clear throughout the follow-up period. The posterior mushroom keratoplasty in FED and PBK results in a relatively good visual acuity, low astigmatism, and good endothelial cell density. The short-term results of our limited series of patients are encouraging.


Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria.
Intrinsic and acquired multidrug resistance in Gram-negative bacteria owes much to the synergy between limited outer membrane permeability and energy-dependent multidrug efflux. The importance of the outer membrane vis-a-vis resistance is aptly demonstrated by the impact of mutational changes in outer membrane constituents on drug susceptibility. Changes in lipopolysaccharide (LPS) that correlate with increased drug susceptibility confirm, for example, the significance of this macromolecule in the intrinsic antimicrobial resistance of Gram-negative bacteria. Alterations in LPS and porins correlating with increased resistance to a variety of antimicrobials are also known and highlight the significance of the outer membrane vis-a-vis acquired antimicrobial resistance. Efflux systems accommodating a range of structurally distinct antimicrobials, including antibiotics, detergents, dyes, biocides and aromatic hydrocarbons have been identified in a number of Gram-negative organisms. Mutational studies have confirmed the importance of these systems to intrinsic and acquired antimicrobial resistance in important disease-causing organisms. As such, strategies aimed at thwarting efflux and or the outer membrane barrier are effective at reversing antimicrobial resistance in these organisms.


Case Report: Diagnosis of hypogeusia after oral exposure to commercial cleaning agent and considerations for clinical taste testing.
Few reports in the literature document acute taste disturbance following exposure to toxic chemicals. We describe the case of a 54-year-old man who presented with primary complaint of tongue numbness and persistent problems with taste 1.5 years following oral exposure to a commercial cleaning agent. A test of olfaction revealed normosmia for age and gender. Lingual tactile two-point discrimination testing showed reduced somatosensation. Taste threshold testing using a 3-drop method demonstrated severe hypogeusia, though the patient was able to discriminate tastants at lower concentrations with a whole mouth swish and spit test. We conclude that clinical evaluation of dysgeusia can be performed using a number of previously published testing methods, however, determining causative factors may be confounded by duration since exposure, lack of knowledge of baseline taste function, and medications. Although many testing options exist, basic taste testing can be performed with minimal expertise or specialized equipment, depending on the patient history and goals of evaluation.


A theoretical investigation of the excited states of OCLO radical, cation, and anion using the CASSCF/CASPT2 method.
Using the complete active space self-consistent field method with a large atomic natural orbital basis set, 10, 13, and 9 electronic states of the OClO radical, OClO(+) cation, and OClO(-) anion were calculated, respectively. Taking the further correlation effects into account, the second-order perturbation (CASPT2) calculations were carried out for the energetic calibration. The photoelectron spectroscopy of the OClO radical and OClO(-) anion were extensively studied in the both case of the adiabatic and vertical ionization energies. The calculated results presented the relatively complete assignment of the photoelectron bands of the experiments for OClO and its anion. Furthermore, the Rydberg states of the OClO radical were investigated by using multiconfigurational CASPT2 (MS-CASPT2) theory under the basis set of large atomic natural orbital functions augmented with an adapted 1s1p1d Rydberg functions that have specially been built for this study. Sixteen Rydberg states were obtained and the results were consistent with the experimental results.


Factors influencing the transition of foreign-educated nurses to the US healthcare setting: A systematic review.
This literature review examined the impact of the orientation or onboarding programs on the transition of foreign-educated nurses to a US healthcare setting and factors influencing their transition. Recruitment of foreign-educated nurses has been a solution to the ongoing nursing workforce shortage in the United States. However, they face various challenges in their transition to employment in the United States. Adequate orientation and continued support are needed for the successful transition of foreign-educated nurses. A systematic literature search was conducted in 2022 across PubMed, CINAHL, Academic Search Complete, Google Scholar, and MEDLINE databases. This review selected only articles published between 2015 and 2022 in English that addressed foreign-educated nurses' transition issues in US healthcare settings. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of the articles was appraised using the John Hopkins Evidence-based Practice tool. This review of 14 articles revealed that the quality of orientation and organizational support were positively associated with foreign-educated nurses' job satisfaction and turnover. Factors influencing foreign-educated nurses' transition included peer support, job assignment and workload, credentialing, communication and cultural adjustment, psychological factors, safety perceptions, work environment, and coping strategies. There was a lack of literature that evaluated orientation or onboarding programs for foreign-educated nurses. Further research is needed to explore the effectiveness of supportive programs in promoting their smooth transition. Efficient onboarding or orientation programs and policies for foreign-educated nurses are crucial, considering the factors influencing their transition. Good programs and policies that prioritize the support, integration, and professional development of FENs will help maximize their contributions to health care.


Coagulation and fibrinolytic responses to manual versus automated snow removal.
The purpose of this study was to assess coagulation and fibrinolytic responses to snow removal. Thirteen healthy male subjects (age = 26 +/- 5 yr, height = 179.0 +/- 7.0 cm, weight = 78.7 +/- 16.1 kg, .VO2max = 54.7 +/- 8.9 mL.kg-1.min-1) underwent maximal treadmill stress testing (TM), 10 min of snow shoveling (SS), and 10 min of snow removal using an automated snow thrower (ST). Blood was collected immediately before and after each test and analyzed for von Willebrand Factor antigen (vWF:ag), tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor-1 (PAI-1) activity. Data were analyzed using a two-factor repeated-measures analysis of variance. vWF:ag significantly increased during TM (84.7 +/- 21.7% normal preexercise, 149.0 +/- 45.6% normal postexercise) but not SS or ST. TM resulted in significant increases in tPA antigen (6.54 +/- 2.76 ng.mL-1 preexercise, 21.39 +/- 10.56 ng.mL-1 postexercise) and both SS and TM caused significant reductions in PAI-1 activity (SS = 15.1 +/- 3.8 AU.mL-1 preexercise, 13.2 +/- 4.3 AU.mL-1 postexercise; TM = 15.3 +/- 3.6 AU.mL-1 preexercise, 10.5 +/- 5.3 AU.mL-1 postexercise). Postexercise PAI-1 activity was significantly lower for TM versus SS. tPA antigen was unchanged after SS and ST, and PAI-1 activity was unchanged after ST. vWF:ag is unchanged after self-paced snow shoveling and automated snow removal in young, healthy males. Snow shoveling acutely increases fibrinolytic potential in this population, although not to the degree observed after maximal treadmill exercise.


Enzymatic N-methylation of phenelzine catalyzed by methyltransferases from adrenal and other tissues.
Phenelzine (2-phenylethylhydrazine) was found to be methylated by enzymes obtained from bovine adrenal and some rat tissues in the presence of S-adenosylmethionine as methyl group donor. The methylated product was chromatographically (TLC and HPLC) identical with chemically synthesized N-methylphenelzine and the structure of this methylated phenelzine has been confirmed by a GC/MS procedure. Methylation occurs at the terminal nitrogen of phenelzine. The phenelzine methyltransferase in the bovine adrenal has a molecular weight and isoelectric point identical with that of bovine adrenal phenylethanolamine N-methyltransferase. The affinity of phenelzine for the methyltransferase is quite high, i.e. KM = 6.5 x 10(-5) M. Methylated phenelzine possesses much weaker inhibitory activity toward monoamine oxidase (MAO). It can, however, be deaminated by MAO to produce phenylacetaldehyde, and subsequently phenylacetic acid. We have also observed that other hydrazine compounds, such as hydralazine, can be methylated by the adrenal enzyme. Our finding of enzymatic methylation of hydrazine compounds is novel and it may play a role in the metabolism of hydrazine drugs.


High-G stress and orientational stress: physiologic effects of aerial maneuvering.
G stress can readily incapacitate pilots of modern fighter aircraft and result in mishaps due to G-induced loss of consciousness (GLC). The physiologic effects of high-G stress, including decreased head-level blood pressure due to hydrostatic pressure drop and decreased cardiac output due to inadequate venous return, result in the symptoms of visual loss and GLC. The body's primary natural defenses against the effects of G stress in flight, i.e., the neural tissue energy reserve and the cardiovascular baroceptor reflexes, determine the characteristic shape of the G-time tolerance curve, which is presented. Means of raising G tolerance fall into three categories: mechanical, physiological, and educational. Mechanical means include anti-G suits and valves, assisted positive-pressure breathing (APPB) systems, and special seats in which the seatback is reclined and/or the pilot's legs are elevated. Physiological means include frequent exposure to G stress, physical conditioning (weight training and moderate aerobic conditioning), selection of pilots for high natural tolerance, and performance of a vigorous and efficient anti-G straining maneuver. Educational means include briefings on methods of enhancing tolerance, and high-G training in a centrifuge to allow the pilot to perfect his anti-G straining maneuver. An improved anti-G valve, physical conditioning, high-G awareness briefings, and centrifuge training are now being applied in efforts to prevent GLC in current fighter aircraft. Future generations of even more maneuverable aircraft will probably necessitate the use of APPB, pilot selection, and high-G seats for protection of pilots from the effect of sustained high G forces.


Successful Treatment of Cyst Infection in an Infant With Autosomal Dominant Polycystic Kidney Disease Using Trimethoprim/Sulfamethoxazole.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease causing renal cysts. Reports on kidney cyst infection in children are rare despite cyst infections being important complications of ADPKD. Here, we report a case of a child without any medical history who had a urinary tract infection with sepsis at 7 months. Leukocyturia persisted despite antibiotic therapy because the infection was treatment-resistant. Initial ultrasound and contrast computed tomography were inconclusive because cysts could not be detected clearly, and a family history of renal cysts was not determined. Subsequently, history of paternal renal cysts, thick walls in infectious cystic lesions on diffusion-weighted magnetic resonance imaging (MRI), and multiple small lesions with high signals on T2-weighted imaging in both kidneys became apparent. Upon diagnosis of ADPKD with cyst infection, antibiotic therapy was switched from cefotaxime to trimethoprim/sulfamethoxazole to achieve better cyst penetration, which successfully resolved the infection. In this patient, MRI was effective for clear visualization and diagnosis of infectious lesions and small cysts in undiagnosed ADPKD with cyst infection. Administering antibiotics with better cyst penetration is important. Trimethoprim/sulfamethoxazole is an option for use in children. This is the first case report that describes ADPKD with cyst infection in an infant in detail.


Diagnosis and management of acute and chronic prostatitis.
Prostatitis syndromes are some of the most poorly understood yet prevalent problems in urology. There is little controversy over acute prostatitis, a urinary tract infection with systemic symptoms and signs that typically responds to antimicrobial therapy. By contrast, the chronic prostatitis syndromes have so far eluded attempts to understand their pathophysiology and design effective therapies, resulting in great frustration among patients and health care providers. An accurate diagnosis and a multidisciplinary approach are essential to assist men with this often debilitating condition.


The molecular genetic basis of mitochondrial malfunction in bladder tissue following outlet obstruction.
Bladder dysfunction following partial outlet obstruction is a frequent consequence of benign prostatic hyperplasia and an increasingly common problem given the aging of the general population. Recent studies from this and other groups have begun to elucidate the molecular bases for the well described physiological malfunctions that characterize this clinical entity. We summarized and synthesized that information. Using modern methods of molecular genetics, including real-time polymerase chain reaction, real-time reverse transcriptase-polymerase chain reaction and others, as well as traditional experimental techniques such as electron microscopy we and others examined the transcriptional profile, morphology, etc of bladder smooth muscle mitochondria in experimental models of outlet obstruction. Data from many studies have demonstrated that aberrant gene expression in the mitochondrial and mitochondria related nuclear genetic systems underlies the loss of compliance and other attributes of bladder dysfunction following outlet obstruction. Such aberrant transcriptional characteristics engender loss of function in the electron transport and oxidative phosphorylation systems. Morphological studies of mitochondria in the animal model systems support this conclusion. In large part the loss of function in bladder smooth muscle following outlet obstruction results from the attenuation of mitochondrial energy production. In this article we reviewed and synthesized all available experimental observations relevant to this problem and we suggest future lines of inquiry that should prove fruitful in developing new strategies to treat the condition.


Label image constrained multiatlas selection.
Multiatlas based method is commonly used in medical image segmentation. In multiatlas based image segmentation, atlas selection and combination are considered as two key factors affecting the performance. Recently, manifold learning based atlas selection methods have emerged as very promising methods. However, due to the complexity of prostate structures in raw images, it is difficult to get accurate atlas selection results by only measuring the distance between raw images on the manifolds. Although the distance between the regions to be segmented across images can be readily obtained by the label images, it is infeasible to directly compute the distance between the test image (gray) and the label images (binary). This paper tries to address this problem by proposing a label image constrained atlas selection method, which exploits the label images to constrain the manifold projection of raw images. Analyzing the data point distribution of the selected atlases in the manifold subspace, a novel weight computation method for atlas combination is proposed. Compared with other related existing methods, the experimental results on prostate segmentation from T2w MRI showed that the selected atlases are closer to the target structure and more accurate segmentation were obtained by using our proposed method.


A novel CRX frameshift mutation causing cone-rod dystrophy in a Chinese family: A case report.
Cone-rod dystrophy (CORD) is an inherited, progressive retinal disorder with genetic and phenotypic heterogeneity. Here, we aimed to identify the pathogenic mutation in affected individuals in a Chinese family with autosomal dominant cone-rod dystrophy (adCORD). Genomic DNA and clinical examination results were collected from a Chinese family presenting with adCORD. The candidate disease-causing mutations were screened with whole-exome sequencing (WES) and bioinformatics analyses. Sanger sequencing was used for validation and cosegregation analysis. A novel frameshift mutation (NM_000554.4; c.538dupG:p.Val180fs) in exon 4 of the CRX gene was identified in all affected individuals in the Chinese family with adCORD. Cosegregation analysis confirmed that this mutation was cosegregated with the disease. This variant, which results in premature termination of the protein, was absent from all public variant databases or internal exome databases. We used whole-exome sequencing to identify a novel CRX mutation causing adCORD in a Chinese family. This study broadens the known pathogenic mutation spectrum of the CRX gene and shows the potential of WES in identifying the pathogenic mutations of CORD disease.


Changes in Membrane Dielectric Properties of Porcine Kidney Cells Provide Insight into the Antiviral Activity of Glycine.
The ability to monitor the status and progression of viral infections is important for development and screening of new antiviral drugs. Previous research illustrated that the osmolyte glycine (Gly) reduced porcine parvovirus (PPV) infection in porcine kidney (PK-13) cells by stabilizing the capsid protein and preventing virus capsid assembly into viable virus particles. Dielectrophoresis (DEP) was examined herein as a noninvasive, electric field- and frequency-dependent tool for real-time monitoring of PK-13 cell responses to obtain information about membrane barrier functionality and polarization. DEP responses of PK-13 cells were compared to those of PPV-infected cells in the absence and presence of the osmolyte glycine. With infection progression, PK-13 DEP spectra shifted toward lower frequencies, reducing crossover frequencies (fCO). The spherical single-shell model was used to extract PK-13 cell dielectric properties. Upon PPV infection, specific membrane capacitance increased over the time progression of virus attachment, penetration, and capsid protein production and assembly. Following glycine treatment, the DEP spectra displayed attenuated fCO and specific membrane capacitance values shifted back toward uninfected PK-13 cell values. These results suggest that DEP can be used to noninvasively monitor the viral infection cycle and screen antiviral compounds. DEP can augment traditional tools by elucidating membrane polarization changes related to drug mechanisms that interrupt the virus infection cycle.


Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis.
Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8-15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation. NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.


Planar relationships of the semicircular canals in man.
Principal-component analyses were determined on a series of points measured from the dissected bony labyrinth of ten human skulls, resulting in planar equations for each of the six semicircular canals. Following this, angles were calculated between the ipsilateral canal planes, between opposite synergistically acting canal planes and between each canal and the Reid stereotaxic planes. Results indicated that pairs of ipsilateral canals were nearly perpendicular, with the excpetion of the angle formed between the anterior and horizontal canal (mean = 111 degrees). Pairs of contralateral synergistic canal planes formed angles of 19 degrees between right and left horizontal canal planes and 23-24 degrees between vertical canal pairs. The horizontal canals formed an angle of 25 degrees with the Reid horizontal plane. Mathematical equations of the semicircular canals were used to predict the optimal head position for rotational and caloric stimulation.


Evidence for a post-translational modification, aspartyl aldehyde, in a photosynthetic membrane protein.
In oxygenic photosynthesis, photosystem II (PSII) carries out the oxidation of water and reduction of plastoquinone. Three PSII subunits contain reactive groups that covalently bind amines and phenylhydrazine. It has been proposed that these reactive groups are carbonyl-containing, co- or post-translationally modified amino acids. To identify modified amino acid residues in one of the PSII subunits (CP47), tandem mass spectrometry was performed. Modified residues were affinity-tagged with either biotin-LC-hydrazide or biocytin hydrazide, which are known to label carbonyl groups. The affinity-tagged subunit was isolated by denaturing gel electrophoresis, and tryptic peptides were then subjected to affinity purification and tandem mass spectrometry. This procedure identified a hydrazide-labeled peptide, which has the sequence XKEGR. This result is supported by quantitative results acquired from peptide mapping and methylamine labeling. The gene sequence and these tandem data predict that the first amino acid, X, which is labeled with the hydrazide reagent, is a modified form of aspartic acid. On the basis of these data, we propose that D348 of the CP47 subunit is post- or co-translationally modified to give a novel amino acid side chain, aspartyl aldehyde.


Peroneal Tendon Dislocation: A Report of Two Cases.
Ankle injuries are a very common cause of patient visits to the primary care units and emergency departments. Although the most frequent ones are lateral ligament sprains, peroneal tendon subluxations have the same inversion mechanism and are described as one of the main causes of lateral ankle pain and instability. They are often missed during the acute phases as they are misdiagnosed as ankle sprains since both injuries share similar mechanisms and often occur in athletes and patients with high sports activity. We present two different cases of peroneal tendon dislocation that illustrate how this pathological condition may be present under different circumstances. We aim, through these cases, to provide clinical awareness and help improve earlier diagnosis of this condition; we also demonstrate the effectiveness of surgical reattachment of the upper retinaculum that two of our patients underwent.


Preoperative Music Listening in Pelvic Reconstructive Surgery: A Randomized Trial.
We aimed to investigate the effect of music listening on preoperative anxiety compared with usual care in patients undergoing pelvic reconstructive surgery. Patients scheduled for pelvic reconstructive surgery were enrolled on the day of surgery. Participants were randomized to either the usual care (control group) or to music listening on headphones (music group) before their surgery. Participants completed the Spielberg State-Trait Anxiety Inventory form Y1 to measure baseline state anxiety levels before surgery and again after 30 minutes of usual care or music listening. The primary outcome was the change in state anxiety score as measured by the State-Trait Anxiety Inventory form Y1. Sixty-nine women completed the study (35 assigned to the control group and 34 assigned to the music group). Analysis of the primary outcome included 66 participants (34 in the control group and 32 in the music group). Improvement in state anxiety was significantly better for patients assigned to music listening (-6.69; SD, 6.98) than for patients assigned to the control group (-1.32; SD, 8.03; P = 0.01). Six weeks postoperatively, patients in the music group (n = 29) reported higher overall satisfaction when compared with those in the control group (n = 31, P = 0.03). Patients undergoing pelvic reconstructive surgery present with moderate anxiety on the day of surgery. Allowing patients to listen to their preferred music is a simple intervention that may lower preoperative anxiety and improve satisfaction in this patient population.


Earlier winter/spring runoff and snowmelt during warmer winters lead to lower summer chlorophyll-a in north temperate lakes.
Winter conditions, such as ice cover and snow accumulation, are changing rapidly at northern latitudes and can have important implications for lake processes. For example, snowmelt in the watershed-a defining feature of lake hydrology because it delivers a large portion of annual nutrient inputs-is becoming earlier. Consequently, earlier and a shorter duration of snowmelt are expected to affect annual phytoplankton biomass. To test this hypothesis, we developed an index of runoff timing based on the date when 50% of cumulative runoff between January 1 and May 31 had occurred. The runoff index was computed using stream discharge for inflows, outflows, or for flows from nearby streams for 41 lakes in Europe and North America. The runoff index was then compared with summer chlorophyll-a (Chl-a) concentration (a proxy for phytoplankton biomass) across 5-53 years for each lake. Earlier runoff generally corresponded to lower summer Chl-a. Furthermore, years with earlier runoff also had lower winter/spring runoff magnitude, more protracted runoff, and earlier ice-out. We examined several lake characteristics that may regulate the strength of the relationship between runoff timing and summer Chl-a concentrations; however, our tested covariates had little effect on the relationship. Date of ice-out was not clearly related to summer Chl-a concentrations. Our results indicate that ongoing changes in winter conditions may have important consequences for summer phytoplankton biomass and production.


Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse.
Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins. We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4(+)CD8(+) double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus. Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells.