Toxic factors of Vibrio strains pathogenic to shrimp.
Vibriosis is a major disease problem in shrimp aquaculture. 'Syndrome 93' is a seasonal juvenile vibriosis caused by Vibrio penaeicida which affects Litopenaeus stylirostris in grow-out ponds in New Caledonia. This study assessed the toxic activities of extracellular products (ECPs) from V. penaeicida, V. alginolyticus and V. nigripulchritudo using in vivo injections in healthy juvenile L. stylirostris (= Penaeus stylirostris) and in vitro assays on shrimp primary cell cultures and the fish cell line epithelioma papulosum cyprini (EPC). Toxic effects of ECPs were demonstrated for all pathogenic Vibrio strains tested both in vivo and in vitro, but for shrimp only; no effect was observed on the fish cell line. ECP toxicity for New Caledonian V. penaeicida was found only after cultivation at low temperature (20 degrees C) and not at higher temperature (30 degrees C). This points to the fact that 'Syndrome 93' episodes are triggered by temperature drops. The assays used here demonstrate the usefulness of primary shrimp cell cultures to study virulence mechanisms of shrimp pathogenic bacteria.


[Acute myeloid leukemia diagnosed with soft tissue mass in the right thigh].
Myeloid sarcoma is a very rare solid tumor which frequently accompanies myeloproliferative disorders and consists of immature myeloid cells. A 47-year-old male patient admitted to our clinic with complaints of swelling and pain in the right thigh. After diagnosis of myeloid sarcoma was made with tru-cut biopsy, acute myeloid leukemia was diagnosed by hematology clinic as a result of peripheral smear and bone marrow biopsy. No surgical intervention was performed. Patient was treated with chemotherapy for acute myeloid leukemia, and allogeneic bone marrow transplantation. In the follow-up period, patient was asymptomatic at 14 months and magnetic resonance imaging showed almost complete regression of the tumor.


Psychological effects of bed bug attacks (Cimex lectularius L.).
In some individuals, psychological sequelae resulting from bed bug biting events include nightmares, flashbacks, hypervigilance (to keep the bugs away), insomnia, anxiety, avoidance behaviors, and personal dysfunction. These symptoms are suggestive of posttraumatic stress disorder (PTSD). We used a previously published PTSD checklist to analyze online blogs and other Internet sites where bed bug postings occur to assess postings for evidence of emotional trauma. One hundred thirty-five postings were read and analyzed, and 110 (81%) of those postings reported psychological effects from bed bug infestations. Scoring with the PTSD checklist revealed a range of 0-52 (mean 13.25; SD 9.38); one met the criteria (≥50) considered positive for PTSD. Based upon our survey of online postings concerning such effects, an as-yet-to-be-determined proportion of individuals who experience bed bug bites develop moderate-to-severe negative emotional symptoms after infestations. These individuals should be identified in the course of their interactions with health professionals so that appropriate mental health care may be provided.


Age differences in spatial memory for mediated environments.
Compared with younger adults, older adults have more difficulty with navigation and spatial memory in both familiar and unfamiliar domains. However, the cognitive mechanisms underlying these effects have been little explored. We examined three potential factors: (a) use of and coordination across spatial reference frames, (b) nonspatial cognitive abilities, and (c) the ability to segment a route into effective chunks. In two experiments, healthy young and older adults watched videos of navigation in a novel environment and had to remember the placement of landmarks along the route. Participants completed three spatial memory tasks-a virtual pointing task, a distance estimation task, and sketch map drawing-for each route. The pointing task depends on updating and accessing the updated egocentric reference frame relative to other frames. Map drawing may rely more on environment-centered processing. The distance estimation task could be solved using either frame of reference. Last, participants segmented each route. In a separate session, working memory, processing speed, and verbal memory were assessed. Older adults performed less well on all spatial tasks compared with younger adults; aging had a stronger negative effect on pointing performance. This may point to impairments in older adults' ability to update and coordinate information across reference frames. Performance on all spatial tasks was predicted by nonspatial task performance. Segmentation did not predict spatial memory. These results underline the importance of situating age differences in navigation in the context of basic transformations of spatial reference frames, and also in the context of nonspatial cognitive abilities. (PsycINFO Database Record


Random geometric graphs with general connection functions.
In the original (1961) Gilbert model of random geometric graphs, nodes are placed according to a Poisson point process, and links formed between those within a fixed range. Motivated by wireless ad hoc networks "soft" or "probabilistic" connection models have recently been introduced, involving a "connection function" H(r) that gives the probability that two nodes at distance r are linked (directly connect). In many applications (not only wireless networks), it is desirable that the graph is connected; that is, every node is linked to every other node in a multihop fashion. Here the connection probability of a dense network in a convex domain in two or three dimensions is expressed in terms of contributions from boundary components for a very general class of connection functions. It turns out that only a few quantities such as moments of the connection function appear. Good agreement is found with special cases from previous studies and with numerical simulations.


Diagnosing ASD in Adults Without ID: Accuracy of the ADOS-2 and the ADI-R.
Diagnosing autism spectrum disorder (ASD) in adulthood often represents a challenge in clinical practice. The aim of the present study was to evaluate the sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults. 113 subjects with an IQ of 70 or above were assessed through an extensive clinical evaluation. The ADOS-2 Module 4 and the ADI-R were separately administered by staff members blind to clinical judgment. Our results cautiously confirm the accuracy of ADOS-2 Module 4, while suggest that ADI-R might not be reliable in adults without intellectual disability. Clinicians' training and experience remains of primary importance while assessing adults who could potentially belong to the autism spectrum.


[Morpho-functional characteristics of hemoglobinopathies].
The approaches to the problems of primary diagnostics of the hereditary hematoglobinopathias caused by unbalanced synthesis of alpha and beta chains, as well as modern state of screening of hereditary thalassemic hematoglobinopathias are considered. The result of the available information analysis takes into account numerous peculiarities of this problem, including economic ones. Experience of an estimation of the displays of unbalanced synthesis of globin chains concerning the morphology of red blood cells is presented in the generalized form. The latter is a very important for preliminary diagnostics the hematoglobinopathias because, for the first, it may be realized at primary units of public health system service, for the second, it allows to narrow to an acceptable level the group of persons whose blood requires more complex and expensive researches.


Gamma-herpesvirus latency requires T cell evasion during episome maintenance.
The gamma-herpesviruses persist as latent episomes in a dynamic lymphocyte pool. Their consequent need to express a viral episome maintenance protein presents a potential immune target. The glycine-alanine repeat of the Epstein-Barr virus episome maintenance protein, EBNA-1, limits EBNA-1 epitope presentation to CD8(+) T lymphocytes (CTLs). However, CTL recognition occurs in vitro, so the significance of such evasion for viral fitness is unclear. We used the murine gamma-herpesvirus-68 (MHV-68) to define the in vivo contribution of cis-acting CTL evasion to host colonisation. Although the ORF73 episome maintenance protein of MHV-68 lacks a glycine-alanine repeat, it was equivalent to EBNA-1 in conferring limited presentation on linked epitopes. This was associated with reduced protein synthesis and reduced protein degradation. We bypassed the cis-acting evasion of ORF73 by using an internal ribosome entry site to express in trans-a CTL target from the same mRNA. This led to a severe, MHC class I-restricted and CTL-dependent reduction in viral latency. Thus, despite MHV-68 encoding at least two trans-acting CTL evasion proteins, cis-acting evasion during episome maintenance was essential for normal host colonisation.


[Novel antiviral agents for the treatment of HCV among renal transplant recipients].
The frequency of hepatitis C virus infection remains high in renal transplant recipients and plays a detrimental role on survival in this population. According to the latest evidence, the adjusted relative risk of mortality and graft loss for anti-HCV seropositive versus anti-HCV negative renal transplant recipients was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P < 0.0001) and 1.76 (95% CI, 1.46 ; 2.11) (P < 0.0001), respectively. Interferon-based regimens have been recommended for the treatment of hepatitis C after renal transplantation only in selected circumstances because of an increased risk of acute rejection due to the immuno-stimulatory properties of interferon. Limited data exist on the treatment of HCV with direct-acting antiviral agents among kidney transplant recipients. To date, the most important evidence comes from the European multicenter study where a large cohort (n=114) of patients with glomerular filtration rate of 40 mL/min/1.73m² received an interferon-free, ribavirin-free combination of direct-acting antivirals (Ledipasvir/Sofosbuvir) for 12 or 24 weeks. A high efficacy [SVR12 rate, 100% (114/114) ] was found even if three serious adverse were observed ; all were determined to be treatment related, one patient interrupted permanently treatment. Also, single-center single-arm observational studies have reported high efficacy and safety of sofosbuvir-based combinations for the treatment of HCV after renal transplant. A decline in through levels of calcineurin inhibitors after completion of antiviral therapy has been found in many patients; an enhanced metabolism of calcineurin inhibitors associated with resolution of liver injury has been suggested. An effective and safe therapy for HCV in kidney transplant recipients might improve the current suboptimal utilization of HCV-positive kidney donors and provide many patients with end-stage renal disease access to HCV-infected donor kidneys.


The Gene Regulatory Roles of Herbal Extracts on the Growth, Immune System, and Reproduction of Fish.
The crucial need for safe and healthy aquatic animals obligates researchers in aquaculture to investigate alternative and beneficial additives. Medicinal herbals and their extracts are compromised with diverse effects on the performances of aquatic animals. These compounds can affect growth performance and stimulate the immune system when used in fish diet. In addition, the use of medicinal herbs and their extracts can reduce oxidative stress induced by several stressors during fish culture. Correspondingly, aquatic animals could gain increased resistance against infectious pathogens and environmental stressors. Nevertheless, the exact mode of action where these additives can affect aquatic animals' performances is still not well documented. Understanding the mechanistic role of herbal supplements and their derivatives is a vital tool to develop further the strategies and application of these additives for feasible and sustainable aquaculture. Gene-related studies have clarified the detailed information on the herbal supplements' mode of action when administered orally in aquafeed. Several review articles have presented the potential roles of medicinal herbs on the performances of aquatic animals. However, this review article discusses the outputs of studies conducted on aquatic animals fed dietary, medicinal herbs, focusing on the gene expression related to growth and immune performances. Furthermore, a particular focus is directed to the expected influence of herbal supplements on the reproduction of aquatic animals.


Carbon-13 NMR chemical shifts in columnar liquid crystals.
In this article, we present quantum chemical density functional theory (DFT) calculations of the NMR (13)C chemical shift (CS) tensors in 2,3,6,7,10,11-hexahexylthiotriphenylene (HHTT). The DFT calculations are performed on a smaller model molecule where the hexyl chains were reduced to methyl groups (HMTT). These tensors are compared with our previously reported experimental results carried out under magic-angle spinning (MAS) conditions. The phase diagram of HHTT is K ↔ H ↔ D(hd) ↔ I, where H is a helical phase and D(hd) is a columnar liquid crystal. The motivation for the present study was to explain experimentally observed and puzzling thermal history effects, which resulted in different behavior in the helical phase upon cooling and heating. In particular, the CS tensors for the aromatic carbons measured in the helical phase upon heating from the solid phase were essentially unaffected, while the cooling from the columnar liquid crystal resulted in a significant averaging. We investigate the effect on the CS tensors of (i) conformational transitions, and (ii) relative molecular orientations within the columns for dimer and trimer configurations. Finally a motional wobbling (PIZZA) model for the dynamic averaging of the CS tensor in the helical phase is suggested.


Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer.
Protein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy. PRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed. PRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P<0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P<0.001). These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.


Clinical evaluation of extended-wear lidofilcon B contact lenses in aphakia.
A total of 138 aphakic eyes in 109 patients were fitted with lidofilcon B contact lenses for extended wear. These patients were observed for six months to more than three years. Their problems with fit, comfort, infection, lens loss, and visual acuity were reviewed. A comparison between patients in whom the lenses were used successfully and patients in whom the lenses were used unsuccessfully was made, and the causes of failure discussed.


Reconstructing past ecological networks: the reconfiguration of seed-dispersal interactions after megafaunal extinction.
The late Quaternary megafaunal extinction impacted ecological communities worldwide, and affected key ecological processes such as seed dispersal. The traits of several species of large-seeded plants are thought to have evolved in response to interactions with extinct megafauna, but how these extinctions affected the organization of interactions in seed-dispersal systems is poorly understood. Here, we combined ecological and paleontological data and network analyses to investigate how the structure of a species-rich seed-dispersal network could have changed from the Pleistocene to the present and examine the possible consequences of such changes. Our results indicate that the seed-dispersal network was organized into modules across the different time periods but has been reconfigured in different ways over time. The episode of megafaunal extinction and the arrival of humans changed how seed dispersers were distributed among network modules. However, the recent introduction of livestock into the seed-dispersal system partially restored the original network organization by strengthening the modular configuration. Moreover, after megafaunal extinctions, introduced species and some smaller native mammals became key components for the structure of the seed-dispersal network. We hypothesize that such changes in network structure affected both animal and plant assemblages, potentially contributing to the shaping of modern ecological communities. The ongoing extinction of key large vertebrates will lead to a variety of context-dependent rearranged ecological networks, most certainly affecting ecological and evolutionary processes.


The "Begin Exploring Fertility Options, Risks and Expectations" (BEFORE) decision aid: development and alpha testing of a fertility tool for premenopausal breast cancer patients.
Premenopausal breast cancer patients are at risk of treatment-related infertility. Many patients do not receive sufficient fertility information before treatment. As such, our team developed and alpha tested the Begin Exploring Fertility Options, Risks, and Expectations decision aid (BEFORE DA). The BEFORE DA development process was guided by the International Patient Decision Aids Standards and the Ottawa Decision Support Framework. Our team used integrated knowledge translation by collaborating with multiple stakeholders throughout the development process including breast cancer survivors, multi-disciplinary health care providers (HCPs), advocates, and cancer organization representatives. Based on previously conducted literature reviews and a needs assessment by our team - we developed a paper prototype. The paper prototype was finalized at an engagement meeting with stakeholders and created into a graphically designed paper and mirrored online decision aid. Alpha testing was conducted with new and previously engaged stakeholders through a questionnaire, telephone interviews, or focus group. Iterative reviews followed each step in the development process to ensure a wide range of stakeholder input. Our team developed an 18-page paper prototype containing information deemed valuable by stakeholders for fertility decision-making. The engagement meeting brought together 28 stakeholders to finalize the prototype. Alpha testing of the paper and online BEFORE DA occurred with 17 participants. Participants found the BEFORE DA usable, acceptable, and most provided enthusiastic support for its use with premenopausal breast cancer patients facing a fertility decision. Participants also identified areas for improvement including clarifying content/messages and modifying the design/photos. The final BEFORE DA is a 32-page paper and mirrored online decision aid ( https://fertilityaid.rethinkbreastcancer.com ). The BEFORE DA includes information on fertility, fertility options before/after treatment, values clarification, question list, next steps, glossary and reference list, and tailored information on the cost of fertility preservation and additional resources by geographic location. The BEFORE DA, designed in collaboration with stakeholders, is a new tool for premenopausal breast cancer patients and HCPs to assist with fertility discussions and decision-making. The BEFORE DA helps to fill the information gap as it is a tool that HCPs can refer patients to for supplementary information surrounding fertility.


Effects of luminance and stimulus distance on accommodation and visual resolution.
Measurements of accommodation and visual resolution were obtained at a number of luminance levels and stimulus distances. With reductions in luminance the eye approached a "fixed-focus" condition of accommodation for intermediate distances, resulting in successively larger errors in accommodation for both near and far stimuli. The visual resolution values were initially affected by both the luminance and distance of the stimulus. Subsequent measurements of resolution, following the correction of accommodative errors, were found to be independent of the stimulus distance. The findings are discussed with regard to the problems of "night myopia" and variations in visual resolution with stimulus distance.


Transmembrane communication: general principles and lessons from the structure and function of the M2 proton channel, K⁺ channels, and integrin receptors.
Signal transduction across biological membranes is central to life. This process generally happens through communication between different domains and hierarchical coupling of information. Here, we review structural and thermodynamic principles behind transmembrane (TM) signal transduction and discuss common themes. Communication between signaling domains can be understood in terms of thermodynamic and kinetic principles, and complex signaling patterns can arise from simple wiring of thermodynamically coupled domains. We relate this to functions of several signal transduction systems: the M2 proton channel from influenza A virus, potassium channels, integrin receptors, and bacterial kinases. We also discuss key features in the structural rearrangements responsible for signal transduction in these systems.


Best Practices in CD30 Immunohistochemistry Testing, Interpretation, and Reporting: An Expert Panel Consensus.
Although CD30 testing is an established tool in the diagnostic workup of lymphomas, it is also emerging as a predictive biomarker that informs treatment. The current definition of CD30 positivity by immunohistochemistry is descriptive and based on reactivity in lymphomas that are defined by their universal strong expression of CD30, rather than any established threshold. Challenges include inconsistencies with preanalytic variables, tissue processing, pathologist readout, and with the pathologist and oncologist interpretation of reported results. To develop and propose general best practice recommendations for reporting CD30 expression by immunohistochemistry in lymphoma biopsies to harmonize practices across institutions and facilitate assessment of its significance in clinical decision-making. Following literature review and group discussion, the panel of 14 academic hematopathologists and 2 clinical/academic hematologists/oncologists divided into 3 working groups. Each working group was tasked with assessing CD30 testing by immunohistochemistry, CD30 expression readout, or CD30 expression interpretation. Panel recommendations were reviewed and discussed. An online survey was conducted to confirm the consensus recommendations. CD30 immunohistochemistry is required for all patients in whom classic Hodgkin lymphoma and any lymphoma within the spectrum of peripheral T-cell lymphoma are differential diagnostic considerations. The panel reinforced and summarized that immunohistochemistry is the preferred methodology and any degree of CD30 expression should be reported. For diagnostic purposes, the interpretation of CD30 expression should follow published guidelines. To inform therapeutic decisions, report estimated percent positive expression in tumor cells (or total cells where applicable) and record descriptively if nontumor cells are positive.


Utilizing drug repurposing against COVID-19 - Efficacy, limitations, and challenges.
The recent outbreak of Coronavirus disease (COVID-19), first in Eastern Asia and then essentially across the world has been declared a pandemic by the WHO. COVID-19 is caused by a novel virus SARS-CoV2 (2019-nCoV), against which there is currently no vaccine available; and current antiviral therapies have failed, causing a very high mortality rate. Drug repurposing i.e. utilizing an approved drug for different indication, offers a time- and cost-efficient alternative for making new therapies available to patients. Although there are several reports presenting novel approaches to treat COVID-19, still an attentive review of previous scientific literature is essential to overcome their failure to exhibit efficacy. There is an urgent need to provide a comprehensive outlook toward utilizing drug repurposing as a tool for discovery of new therapies against COVID-19. In this article, we aim to provide a to-the-point review of current literature regarding efficacy of repurposed drugs against COVID-19 and other respiratory infections caused by coronaviruses. We have briefly discussed COVID-19 epidemiology, and then have discussed drug repurposing approaches and examples, specific to respiratory viruses. Limitations of utilization of repurposed drug molecules such as dosage regimen and associated challenges such as localized delivery in respiratory tract have also been discussed in detail.


In situ detection of protein-hydrolysing microorganisms in activated sludge.
Protein hydrolysis plays an important role in the transformation of organic matter in activated sludge wastewater treatment plants, but no information is currently available regarding the identity and ecophysiology of protein-hydrolysing organisms (PHOs). In this study, fluorescence in situ enzyme staining with casein and bovine serum albumin conjugated with BODIPY dye was applied and optimized to label PHOs in activated sludge plants. A strong fluorescent labeling of the surface of microorganisms expressing protease activity was achieved. Metabolic inhibitors were applied to inhibit the metabolic activity to prevent uptake of the fluorescent hydrolysates by oligopeptide-consuming bacteria. In five full-scale, nutrient-removing activated sludge plants examined, the dominant PHOs were always different morphotypes of filamentous bacteria and the epiflora attached to many of these. The PHOs were identified by FISH using a range of available oligonucleotide probes. The filamentous PHOs belonged to the candidate phylum TM7, the phylum Chloroflexi and the class Betaproteobacteria. In total they comprised 1-5% of the bacterial biovolume. Most of the epiflora-PHOs hybridized with probe SAP-309 targeting Saprospiraceae in the phylum Bacteroidetes and accounted for 8-12% of the total bacterial biovolume in most plants and were thus an important and dominant part of the microbial communities.


In vitro glycation of articular cartilage alters the biomechanical response of chondrocytes in a depth-dependent manner.
To determine if increasing cartilage cross-links through in vitro glycation of cartilage explants can alter the biomechanical response of chondrocytes to compressive deformation. Bovine osteochondral explants were either incubated with cell culture solution supplemented with (n = 7) or without (n = 7) ribose for 42 h in order to induce glycation. Deformation-induced changes in cell volume, dimensions and local tissue strains were determined through confocal laser scanning microscopy (CLSM) and the use of a custom built micro-compression device. Osteochondral explants were also utilized to demonstrate changes in depth-wise tissue properties, biomechanical tissue properties and cross-links such as pentosidine (Pent), hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP). The ribose treated osteochondral samples experienced reduced cell volume deformation in the upper tissue zone by ∼ 8% (P = 0.005), as compared the control samples, through restricting cell expansion. In the deeper tissue zone, cell volume deformation was increased by ∼ 12% (P < 0.001) via the transmission of mechanical signals further into the tissue depth. Biomechanical testing of the ribose treated osteochondral samples demonstrated an increase in the equilibrium and dynamic strain dependent moduli (P < 0.001 and P = 0.008, respectively). The biochemical analysis revealed an increase in Pent cross-links (P < 0.001). Depth-wise tissue property analyses revealed increased levels of carbohydrate content, greater levels of fixed charge density and an increased carbohydrate to protein ratio from 6 to 16%, 55-100% and 72-79% of the normalized tissue thickness (from the surface), respectively, in the ribose-treated group (P < 0.05). In vitro glycation alters the biomechanical response of chondrocytes in cartilage differently in upper and deeper zones, offering possible insights into how aging could alter cell deformation behavior in cartilage.


Transcriptome analysis provides insights into the responses of sweet potato to sweet potato virus disease (SPVD).
Sweet potato (Ipomoea batatas) ranks among the most important crops in the world and provides nutritional and economic sustainability for subsistence farmers in sub-Saharan Africa. Its production is mainly constrained by sweet potato virus disease (SPVD) caused by the coinfection of two positive-sense single-stranded RNA viruses, sweet potato chlorotic stunt virus (SPCSV) and sweet potato feathery mottle virus (SPFMV). Current understanding of sweet potato responses to SPCSV and SPFMV at the molecular level remains very limited. In this study, we performed deep sequencing of both messenger RNA (mRNA) and small RNA (sRNA) populations in an SPVD-susceptible cultivar 'Beauregard' upon viral infection, to identify biological pathways that contribute to both general and specific host responses to these important viral pathogens. We found that pathways related to stress response and signaling were significantly affected by viral infection. sRNA components of these pathways were predominantly affected in late stages of the coinfection by SPCSV and SPFMV. We identified several novel microRNAs that were responsive to viral infection, some of which were predicted to target nucleotide-binding site leucine-rich repeat (NBS-LRR) disease resistance genes. The downregulation of the salicylic acid-mediated defense response pathway in particular seems to be a result of the viral infection process, and can in part explain the susceptible nature of the 'Beauregard' cultivar.


[Clinical and morphological characterizations of first detected cases of caseous pneumonia and its outcomes under conditions of current antibacterial therapy].
The paper provides a clinical and X-ray picture of first detected caseous pneumonia. It shows the potentialities of currently available antibiotic therapy used in patients with this diagnosis. At the same time closure of decay cavities and eradication of bacteria can be achieved only in 29% of cases. The major outcome of caseous pneumonia is fibrocavernous tuberculosis. Thus, surgical methods must play an important role in curing such patients. A detailed morphological characterization of surgical materials has demonstrated that active chemotherapy may result in 3 types of caseous pneumonia outcomes: acute progression, chronicity tended to progression, and the development of fibrocavernous tuberculosis. The morphological studies have provided evidence for the validity of the clinical and X-ray dynamics of the disease and for the correctness of choice of surgical policy.


Aflatoxins contamination of maize in Serbia: the impact of weather conditions in 2015.
In recent years climate changes recorded in temperate regions of Europe have led to aflatoxin (AF) contamination of maize. Thus, the aim of this study was to investigate the influence of weather conditions on levels of aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) in 180 maize samples collected from the main maize-growing regions (Western Bačka, North Banat, South Banat and Central Serbia) in Serbia after harvest in 2015. The concentrations of AFs were determined by a validated HPLC method with post-column derivatisation and fluorescence detection (HPLC-FLD). The presence of AFB1, AFB2, AFG1 and AFG2 was detected in 57.2%, 13.9%, 5.6% and 2.8% of maize samples in the concentration ranges of 1.3-88.8 µg kg-1, 0.60-2.8 µg kg-1, 1.8-28.5 µg kg-1 and 2.1-7.5 µg kg-1 respectively. The recorded smaller amount of precipitation and especially higher air temperatures during the summer of 2015 were favourable for AF production, which resulted in 32.2% and 21.1% of samples being unsuitable for human consumption, since AFB1 and the sum of AFs concentrations were above 5.0 and 10.0 µg kg-1 respectively. Furthermore, the findings in this study indicate that the microclimate conditions in the investigated regions had a great influence on the contamination frequency of maize with AFs. The highest percentage of samples unsuitable for human consumption, considering both AFB1 and total AFs content were 72.5% and 51.5% respectively from Central Serbia, whilst the lowest percentages of 15.6% and 6.2% respectively were found in Western Bačka. These findings confirmed that maize should be continuously monitored in order to protect human and animal health from the harmful effects caused by AFs contamination.


Does Obstructive Sleep Apnea Influence Perioperative Outcome? A Qualitative Systematic Review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing.
Obstructive sleep apnea (OSA) is a commonly encountered problem in the perioperative setting even though many patients remain undiagnosed at the time of surgery. The objective of this systematic review was to evaluate whether the diagnosis of OSA has an impact on postoperative outcomes. We performed a systematic review of studies published in PubMed-MEDLINE, MEDLINE In-Process, and other nonindexed citations, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Health Technology Assessment up to November 2014. Studies of adult patients with a diagnosis of OSA or high risk thereof, published in the English language, undergoing surgery or procedures under anesthesia care, and reporting ≥1 postoperative outcome were included. Overall, the included studies reported on 413,304 OSA and 8,556,279 control patients. The majority reported worse outcomes for a number of events, including pulmonary and combined complications, among patients with OSA versus the reference group. The association between OSA and in-hospital mortality varied among studies; 9 studies showed no impact of OSA on mortality, 3 studies suggested a decrease in mortality, and 1 study reported increased mortality. In summary, the majority of studies suggest that the presence of OSA is associated with an increased risk of postoperative complications.


Biochemical and immunocytological localization of the neuropeptides FMRFamide, SCPA, SCPB, to neurons involved in the regulation of feeding in Aplysia.
The localization of the neuropeptide FMRFamide in the buccal ganglia and buccal muscles of Aplysia was studied by immunocytology and high-pressure liquid chromatography (HPLC) combined with either a sensitive bioassay or 35S-methionine labeling. Immunocytology with an antiserum directed to FMRFamide stained a large number of fibers, varicosities, and neuronal somata. Two groups of stained neurons were of particular interest. One was the S cells, a group comprised of many small neurons, the majority of which were stained. HPLC of pooled labeled S cells confirmed that at least some of these neurons synthesize FMRFamide. The other group of stained neurons were in the ventral cluster, a group comprised of a small number of large neurons, many of which are motor neurons that innervate the buccal muscles involved in producing biting and swallowing movements. Several of the ventral neurons were previously shown to contain 2 other neuropeptides, the small cardioactive peptides SCPA and SCPB. These neurons are sufficiently large to permit HPLC analyses of the neuropeptides synthesized by individual neurons. This procedure confirmed that individual ventral neurons synthesized FMRFamide, or the SCPs, or all 3 peptides. The coexistence of FMRFamide and the SCPs in the same neuron was confirmed by simultaneous staining of sections from the buccal ganglia with a monoclonal antibody to the SCPs and an antiserum to FMRFamide. The coexistence of the 3 peptides in the same neuron was surprising in light of the observations that these peptides often have opposite biological activity. The ventral neurons are large and potentially identifiable as individuals. Thus, these neurons may be particularly useful for studying the physiological and behavioral roles of neuropeptides in generating complex behaviors.


Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis.
Tumour angiogenesis, as assayed by microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) have become established as important prognostic indicators for many tumour types. In this study, MVD and the expression of VEGF and PD-ECGF were examined by immunohistochemical staining of 50 pancreatic cancer tissues, and the relationships between either MVD or the expression of these two angiogenic factors and the clinicopathological features, including survival, were analysed. The expression of VEGF and PD-ECGF proteins were confirmed by Western blot analysis and VEGF mRNA isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in five pancreatic cancer cell lines. Twenty-eight (56%) of 50 pancreatic cancers were positive for VEGF protein in cancer cells, and 16 (32%) showed strong PD-ECGF staining in cancer and infiltrating cells. VEGF121 and VEGF165 were identified as the predominant species produced in pancreatic cancer cells. The overexpression of VEGF and PD-ECGF protein significantly correlated with high MVD (P = 0.002, 0.044, respectively). Advanced stage of disease was significantly more frequent in patients with high MVD (P = 0.025). No significant association was found between the expression of VEGF or PD-ECGF and clinicopathological features, except for tumour histology. The expression of PD-ECGF correlated with poor survival (P = 0.011), but MVD and VEGF expression were not found to be useful for the prediction of overall survival. This study suggests that VEGF and PD-ECGF may play an important role in tumour angiogenesis, and that PD-ECGF expression seems to be useful for establishing prognoses for pancreatic cancer.


Rapid response of protein synthesis to insulin in 3T3 cells: effects of protein kinase C depletion and differences from the response to serum repletion.
Quiescent 3T3 cells grown in media containing 4% foetal calf serum showed different responses to insulin and to serum repletion (to 12%). Insulin stimulated protein synthesis within 1 h and this early response was insensitive to actinomycin D. The later insulin response showed progressive sensitivity to actinomycin D. The serum response was slower, not occurring until 1 h, and was inhibited by actinomycin D. Depletion of cell protein kinase C by pre-treatment with phorbol ester caused a total block of the immediate response to insulin but had little effect on the response to serum or the later response to insulin. Acute phorbol ester treatment stimulated protein synthesis.


Split Scores: A Tool to Quantify Phylogenetic Signal in Genome-Scale Data.
Detecting variation in the evolutionary process along chromosomes is increasingly important as whole-genome data become more widely available. For example, factors such as incomplete lineage sorting, horizontal gene transfer, and chromosomal inversion are expected to result in changes in the underlying gene trees along a chromosome, while changes in selective pressure and mutational rates for different genomic regions may lead to shifts in the underlying mutational process. We propose the split score as a general method for quantifying support for a particular phylogenetic relationship within a genomic data set. Because the split score is based on algebraic properties of a matrix of site pattern frequencies, it can be rapidly computed, even for data sets that are large in the number of taxa and/or in the length of the alignment, providing an advantage over other methods (e.g., maximum likelihood) that are often used to assess such support. Using simulation, we explore the properties of the split score, including its dependence on sequence length, branch length, size of a split and its ability to detect true splits in the underlying tree. Using a sliding window analysis, we show that split scores can be used to detect changes in the underlying evolutionary process for genome-scale data from primates, mosquitoes, and viruses in a computationally efficient manner. Computation of the split score has been implemented in the software package SplitSup.


Pre-exposure prophylaxis use among female sex workers in Gulu city, Uganda: a community-based cross-sectional study.
Pre-exposure prophylaxis (PrEP) is an important intervention for reducing the risk of HIV transmission among high-risk populations such as female sex workers in Africa, where HIV prevalence remains high. We aimed to assess the use of PrEP among female sex workers in Gulu, Uganda. In this community-based cross-sectional study, we included HIV-negative female sex workers purposely selected from hotspots within Gulu city, Uganda between February and March 2023. A semi-structured questionnaire was administered to collect data on sociodemographic characteristics, reproductive data, sexual practices, and self-reported PrEP use in the past 3 months. Symptoms of depression were screened using Patient Health Questionnaire-2 tool. Predictors of PrEP use was determined using modified Poisson regression analysis model. p < 0.05 was considered statistically significant. We enrolled 273 female sex workers with a median age of 27 (interquartile range: 24-32) years. Overall, 181 (66.3%) participants used PrEP. PrEP use was associated with; regular source of income beside sex work [adjusted prevalence ratio (aPR): 3.7, 95% confidence interval (CI): 2.11-6.35, p < 0.001], being in a polygamous marriage (aPR: 6.9, 95% CI: 1.32-35.77, p = 0.022), practicing sex work in both rural and urban areas (aPR: 2.5, 95% CI: 1.49-4.35, p < 0.001), having symptoms of depression (aPR: 3.3, 95% CI: 1.43-7.74, p = 0.005), and use of postexposure prophylaxis (PEP) in the past 12 months (aPR: 0.31, 95% CI: 0.17-0.59, p < 0.001). Almost two in three of the female sex workers in Gulu city were currently using PrEP. Previous use of PEP was associated with lower use of PrEP. These findings suggest the need for targeted interventions to increase PrEP uptake and decrease HIV acquisition in this high-risk population among female sex workers, especially those with low income and limited access to healthcare.


Understanding and retention of the informed consent process among parents in rural northern Ghana.
The individual informed consent model remains critical to the ethical conduct and regulation of research involving human beings. Parental informed consent process in a rural setting of northern Ghana was studied to describe comprehension and retention among parents as part of the evaluation of the existing informed consent process. The study involved 270 female parents who gave consent for their children to participate in a prospective cohort study that evaluated immune correlates of protection against childhood malaria in northern Ghana. A semi-structured interview with questions based on the informed consent themes was administered. Parents were interviewed on their comprehension and retention of the process and also on ways to improve upon the existing process. The average parental age was 33.3 years (range 18-62), married women constituted a majority (91.9%), Christians (71.9%), farmers (62.2%) and those with no formal education (53.7%). Only 3% had ever taken part in a research and 54% had at least one relation ever participate in a research. About 90% of parents knew their children were involved in a research study that was not related to medical care, and 66% said the study procedures were thoroughly explained to them. Approximately, 70% recalled the study involved direct benefits compared with 20% for direct risks. The majority (95%) understood study participation was completely voluntary but only 21% recalled they could withdraw from the study without giving reasons. Younger parents had more consistent comprehension than older ones. Maternal reasons for allowing their children to take part in the research were free medical care (36.5%), better medical care (18.8%), general benefits (29.4%), contribution to research in the area (8.8%) and benefit to the community (1.8%). Parental suggestions for improving the consent process included devoting more time for explanations (46.9%), use of the local languages (15.9%) and obtaining consent at home (10.3%). Significant but varied comprehension of the informed consent process exists among parents who participate in research activities in northern Ghana and it appears the existing practices are fairly effective in informing research participants in the study area.


Let's get hyper! Interactive multimedia in EMS.
What's all this hoopla about interactive multimedia? You may have seen the headlines in the Wall Street Journal, Time, Newsweek or U.S. News and World Report. Their message: Brace yourself for the future--multimedia is going to change the world! And, while technology is ever-changing, here's an update on the EMS training products currently available, what they do and how they can be a part of your training program.


Protective Effect of the Hydroalcoholic Extract of Pelargonium Graveolens L. on Rats with Acetaminophen- Induced Nephrotoxicity.
Geranium has various antioxidant, anti-inflammatory, and anti-microbial effects. Prescribing glutathione probably enhances the protective mechanisms of nephrons against oxidative stresses. This study aimed to evaluate the protective effect of geranium on acetaminophen-induced nephrotoxic rats. In the present study, 70 mice were divided into seven groups. In five groups (T1, T2, T3, T4, and T5), different doses of geranium were given by gavage to the mice for seven days, then on the 8th day, a high dose of acetaminophen was administered intraperitoneally. Group T5 only received geranium extract. The control group received neither acetaminophen nor the extract while the last group received only a toxic dose of acetaminophen. Twenty-four hours after the last drug administration, blood samples were taken to check the levels of uric acid, blood nitrogen, and creatinine. The data were analyzed in SPSS version 25. To investigate the between-group factors' effects, one-way ANOVA with Tukey's post hoc test was performed at the alpha level of < 0.05. The differences between the levels of blood creatinine, urea, and uric acid were significant (P < .001) among the groups. The mean blood urea for groups T3 and T4 were similar, and they had a significant difference in comparison with the control group (P < .05). The mean creatinine levels were similar between T4, T5, and the control groups and were significantly different from the other groups (P < .05). Blood uric acid for groups T1 and T2 were similar to Group B and higher than the other groups (P < .05). The results showed that by strengthening cell protection mechanisms against oxidative stress, geranium extract reduces the toxic effects of acetaminophen on mice's kidney function and thus ameliorates the damage. As a result, the geranium extract has no adverse effects on kidney function. DOI: 10.52547/ijkd.6679.


Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas.
The efficacy of novel targeted therapies is often tested at the time of tumor recurrence. However, for glioblastoma (GBM) patients, surgical resections at recurrence are performed only in a minority of patients; therefore, molecular data are predominantly derived from the initial tumor. Molecular data of the initial tumor for patient selection into personalized medicine trials can therefore be used only when the specific genetic change is retained in the recurrent tumor. In this study we determined whether EGFR amplification and expression of the most common mutation in GBMs (EGFRvIII) is retained at tumor recurrence. Because retention of genetic changes may be dependent on the initial treatment, we only used a cohort of GBM samples that were uniformly treated according to the current standard of care (ie, chemo-irradiation with temozolomide). Our data show that, in spite of some quantitative differences, the EGFR amplification status remains stable in the majority (84%) of tumors evaluated. EGFRvIII expression remained similar in 79% of GBMs. However, within the tumors expressing EGFRvIII at initial diagnosis, approximately one-half lose their EGFRvIII expression at tumor recurrence. The relative stability of EGFR amplification indicates that molecular data obtained in the primary tumor can be used to predict the EGFR status of the recurrent tumor, but care should be taken in extrapolating EGFRvIII expression from the primary tumor, particularly when expressed at first diagnosis.


Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide synthase and intestinal transit.
The disrupted intestinal transit during endotoxemia may be mediated by nitric oxide (NO). We hypothesized that the isoforms of nitric oxide synthase (NOS) are up-regulated in intestinal smooth muscle during endotoxemia and that the scavenging of NO will normalize transit. Rats were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg intravenously and were killed 4 hours later. To determine the activity of NOS isoforms in the jejunum and ileum, the conversion of tritiated L-arginine to tritiated L-citrulline was measured. Western immunoblots were performed by incubating the extracted protein with specific polyclonal antibodies. To determine intestinal transit, rats were divided into 4 groups: 0.9% sodium chloride 1 mL/h intravenously for 5 hours, LPS 10 mg/kg intravenous bolus plus 1 mL/h 0.9% sodium chloride intravenously, LPS plus oxyhemoglobin 0.5 g/kg/h intravenously, and oxyhemoglobin 0.5 g/kg/h intravenously. LPS increased the constitutive and inducible NOS enzyme activities in the jejunum and ileum. Western blots demonstrated that LPS up-regulates both the NOS1 and NOS2 isoforms in jejunal and ileal smooth muscle. Oxyhemoglobin alone increased intestinal transit compared with controls, whereas endotoxemia increased intestinal transit, which was ameliorated with infusions of oxyhemoglobin. NO may play a major role in mediating the rapid intestinal transit induced by endotoxemia.


IL-7R α polymorphisms in 60 Iranian multiple sclerosis patients.
Multiple sclerosis (MS), a chronic inflammatory demyelinating disorder with neurodegenerative aspects, is more common among young adults, particularly women. This molecular study was designed to investigate the IL-7R α chain gene in Iranian MS patients. We studied 60 MS patients, diagnosed based on 2005 R-McDonald criteria and 60 apparently healthy individuals as the control group. DNA was extracted from whole blood cells using MBST/IRAN Extraction kit and all samples were screened for possible sequence variation in three regions including promoter, exon 2 and exon 4 with single strand conformation polymorphism (SSCP). The alterations were confirmed with direct sequencing by ABI 3730XL. Although no mutation was detected in the studied regions, eight single nucleotide polymorphisms (SNPs) consisting of rs71617734 in promoter; rs35967524, rs11567704, rs1494558, rs11567705 and rs969128 in exon 2 as well as rs1494555 and rs2228141 in exon 4 were observed. The rs1494558 in exon 2 and rs1494555 in exon 4 were missense variations. Our results also showed the substitution of isoleucine with threonine in rs1494558 (P.I66T) with this accession number, FR863587 submitted in EMBL bank. The study of exon4 areas revealed two SNPs and two sequence variations, where [p.V138I] Valine substituted with isoleucine (FR863588), as well as a silent nucleotide substitution [P. H165H] in the absence of amino acid alteration. The analysis of the SNP genotype in the controls and the patients, using χ(2) showed no significant association with multiple sclerosis in this group. Our study demonstrated the effects of some SNPs on the IL-7R α protein in MS. Further studies are required to reveal the effects of these SNPs on the IL-7R α protein in multiple sclerosis.


Cost-effectiveness of clopidogrel in acute coronary syndromes in Canada: a long-term analysis based on the CURE trial.
Cardiovascular diseases account for nearly 20% of all hospitalizations in Canada and consume 12% of the total cost of all illnesses. With increasing trends of cardiovascular disease and increasing costs of care, development of cost-effective strategies is vital. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial demonstrated the effectiveness of clopidogrel plus acetylsalicylic acid (ASA) compared with ASA alone in reducing cardiovascular events in patients with acute coronary syndromes and, in addition, patients undergoing percutaneous coronary intervention in the Percutaneous Coronary Intervention in CURE (PCI-CURE) trial. To assess the cost-effectiveness of clopidogrel in the Canadian health care system. Estimates of hospitalization costs were based on the 2003 cost schedules released by the Health Funding and Costing Branch of the Alberta Health and Wellness, as well as on the Case Mix Group classification system. Life expectancy beyond the trial was estimated from the Saskatchewan Health Database. Cost-effectiveness was expressed as the incremental cost-effectiveness ratio, and bootstrap methods were used to estimate the joint distribution of costs and effectiveness. Clopidogrel was shown to be cost-effective, with incremental cost-effectiveness ratios less than $10,000 per event prevented and less than $4,000 per life-year gained. The probability of clopidogrel resulting in cost per life-year gained of less than $20,000 was 0.975 for CURE patients and 0.904 for PCI-CURE patients. The economic analysis demonstrated that clopidogrel combination therapy is not only cost-effective as antiplatelet therapy compared with ASA alone, but it is also cost-effective compared with other commonly used and openly reimbursed cardiovascular therapies in the Canadian health care system.


Hello, Who is Calling?: Can Words Reveal the Social Nature of Conversations?
This study aims to infer the social nature of conversations from their content automatically. To place this work in context, our motivation stems from the need to understand how social disengagement affects cognitive decline or depression among older adults. For this purpose, we collected a comprehensive and naturalistic corpus comprising of all the incoming and outgoing telephone calls from 10 subjects over the duration of a year. As a first step, we learned a binary classifier to filter out business related conversation, achieving an accuracy of about 85%. This classification task provides a convenient tool to probe the nature of telephone conversations. We evaluated the utility of openings and closing in differentiating personal calls, and find that empirical results on a large corpus do not support the hypotheses by Schegloff and Sacks that personal conversations are marked by unique closing structures. For classifying different types of social relationships such as family vs other, we investigated features related to language use (entropy), hand-crafted dictionary (LIWC) and topics learned using unsupervised latent Dirichlet models (LDA). Our results show that the posteriors over topics from LDA provide consistently higher accuracy (60-81%) compared to LIWC or language use features in distinguishing different types of conversations.


Development of a training model for small animal thoracocentesis and chest tube thoracostomy.
Training veterinary students to perform emergency procedures, such as thoracocentesis and chest tube thoracostomy, poses challenges in terms of providing adequate hands-on experience without compromising animal welfare. A small animal thoracocentesis and chest tube thoracostomy model has been developed, that allows repetitive practice in a safe, standardised environment. The model has been incorporated into a clinical skills laboratory, where students work through computerised case studies in small groups, performing thoracocentesis or chest tube thoracostomy where indicated during the case. Student feedback indicated a high degree of satisfaction with the model and the laboratory experience, high perceived value of the case studies in improving learning, and increased confidence to perform the procedures under supervision. This model can replace the use of live animals while students are practising these procedures, improving their technique, and learning the appropriate safeguards used to prevent injuries such as pulmonary trauma.


Purine synthesis promotes maintenance of brain tumor initiating cells in glioma.
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. In contrast, differentiated glioma cells were unaffected by the targeting of purine biosynthetic enzymes, suggesting selective dependence of BTICs. MYC coordinated the control of purine synthetic enzymes, supporting its role in metabolic reprogramming. Elevated expression of purine synthetic enzymes correlated with poor prognosis in glioblastoma patients. Collectively, our results suggest that stem-like glioma cells reprogram their metabolism to self-renew and fuel the tumor hierarchy, revealing potential BTIC cancer dependencies amenable to targeted therapy.


N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits.
The sulfonylurea receptor (SUR), an ATP-binding cassette (ABC) protein, assembles with a potassium channel subunit (Kir6) to form the ATP-sensitive potassium channel (K(ATP)) complex. Although SUR is an important regulator of Kir6, the specific SUR domain that associates with Kir6 is still unknown. All functional ABC proteins contain two transmembrane domains but some, including SUR and MRP1 (multidrug resistance protein 1), contain an extra N-terminal transmembrane domain called TMD0. The functions of any TMD0s are largely unclear. Using Xenopus oocytes to coexpress truncated SUR constructs with Kir6, we demonstrated by immunoprecipitation, single-oocyte chemiluminescence and electrophysiological measurements that the TMD0 of SUR1 strongly associated with Kir6.2 and modulated its trafficking and gating. Two TMD0 mutations, A116P and V187D, previously correlated with persistent hyperinsulinemic hypoglycemia of infancy, were found to disrupt the association between TMD0 and Kir6.2. These results underscore the importance of TMD0 in K(ATP) channel function, explaining how specific mutations within this domain result in disease, and suggest how an ABC protein has evolved to regulate a potassium channel.


[Epidural anesthesia in surgical interventions on the spine and spinal cord. II. Effects of epidural anesthesia on somatosensory evoked potentials].
Effects of epidural anesthesia (EA) on early components of somatosensory evoked potentials (SSEP) were studied and the objectiveness and efficiency of SSEP monitoring during interventions on the spine under EA were evaluated. Evoked potentials were studied in 21 patients operated on for vertebral disk hernias and extra-intradural tumors of the spine (lower thoracic and lumbar levels) under bupivacaine EA. Cortical SSEP were recorded and analyzed on a Viking IV neuroaverager (Nicolet, USA) stimulating n. tibialis posterior for obtaining a greater amplitude of evoked potentials. The following SSEP characteristics were measured: latency of PI (P37), NI (N45), and PII (P60) peaks, amplitude of PINI peak, and inter-peak latency of PI-NI and PI-PII. The major changes in cortical SSEP caused by EA (local anesthetic 0.5% bupivacaine) involve only PI and NI components which reflect the entry of information on an external stimulus into the cortex and objective physical parameters of this stimulus; this helps predict the onset of full-value epidural block and its duration. General anesthetic (propofol) affect mainly a later component of response, PII peak, which is responsible for processing of primary information about an external stimulus and reflects the activation of associative areas of the brain. Hence, SSEP regulation can be used together with traditional methods (pin prick test and Bromage scale) for evaluating epidural block in patients with spinal diseases.


Accelerated Sexual Maturation in Methoprene-Treated Sterile and Fertile Male Queensland Fruit Flies (Diptera: Tephritidae), and Mosquito Larvicide as an Economical and Effective Source of Methoprene.
Queensland fruit flies Bactrocera tryoni ('Q-fly') have long adult prereproductive development periods, which can present challenges for sterile insect technique (SIT) programs. Holding the sterile flies in release facilities is expensive for control programs. Alternatively, releases of sexually immature males can lead to substantial mortality of sterile males before they mature. Recent studies have reported effectiveness of dietary supplementation with a mosquito larvicide (NOMOZ) that contains S-methoprene, a juvenile hormone analogue, for accelerating sexual development of fertile Q-fly males. However, it is not known whether effects on sterile flies are comparable to effects on fertile flies, or whether effects of methoprene-containing larvicide are comparable to effects of analytical standard methoprene such has been used in most studies. Here we address both knowledge gaps, investigating the effects of analytical standard methoprene and NOMOZ mixed with food and provided for 48 h following emergence on sexual development and longevity of fertile and sterile Q-flies. Compared with controls, fertile and sterile male Q-flies that were provided diets supplemented with methoprene from either source exhibited substantially accelerated sexual development by 2-3 d and longer mating duration. Unlike males, females did not respond to methoprene treatment. Although fertile and sterile flies were generally similar in sexual development and response to methoprene treatment, sterile flies of both sexes tended to have shorter copula duration than fertile flies. Neither methoprene supplements nor sterilization affected longevity of flies. The present study confirms effectiveness of dietary methoprene supplements in accelerating sexual development of both fertile and sterile male (but not female) Q-flies, and also confirms that low-cost mosquito larvicides that contain methoprene can achieve effects similar to those for high-cost analytical grade methoprene as prerelease supplements for Q-fly SIT.


[Differentiated psychopharmacotherapy of anergic conditions and the search for predictors of its effectiveness].
A nosologically nonuniform group of patients with predominant anergy in the clinical symptomatology were examined and treated. During examination, use was made of the rating scale and of the "biological" tests: the dexamethasone test, response to a single intake of psychostimulants (methylphenidate or sydnocarb) and tranquilizers (the diazepam test). The treatment was carried out by means of different methods: with antidepressants (desipramine/petytyl) and incazane, with the "actoprotector" bemityl, the psychostimulant sydnocarb, the neuroleptic pimozide as well as with combinations of the two latter ones with incazane. Analysis of the correlations between the treatment results and the data of the clinico-nosological assessment and tests made it possible to reveal the efficacy predictors in 6 out of 7 methods employed. It should be noted that for three of them the correlations with the parameters of the tests offered turned out maximal, which supports advisability of the use of the given tests for differential diagnosis and choice of the treatment for patients with anergic conditions.


Repeated Hurricanes Reveal Risks and Opportunities for Social-Ecological Resilience to Flooding and Water Quality Problems.
Hurricanes that damage lives and property can also impact pollutant sources and trigger poor water quality. Yet, these water quality impacts that affect both human and natural communities are difficult to quantify. We developed an operational remote sensing-based hurricane flood extent mapping method, examined potential water quality implications of two "500-year" hurricanes in 2016 and 2018, and identified options to increase social-ecological resilience in North Carolina. Flooding detected with synthetic aperture radar (>91% accuracy) extended beyond state-mapped hazard zones. Furthermore, the legal floodplain underestimated impacts for communities with higher proportions of older adults, disabilities, unemployment, and mobile homes, as well as for headwater streams with restricted elevation gradients. Pollution sources were repeatedly affected, including ∼55% of wastewater treatment plant capacity and swine operations that generate ∼500 M tons/y manure. We identified ∼4.8 million km2 for possible forest and wetland conservation and ∼1.7 million km2 for restoration or altered management opportunities. The results suggest that current hazard mapping is inadequate for resilience planning; increased storm frequency and intensity necessitate modification of design standards, land-use policies, and infrastructure operation. Implementation of interventions can be guided by a greater understanding of social-ecological vulnerabilities within hazard and exposure areas.


Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator.
A modulator of the enzymatic activity of human thrombin, designated LY254603, was identified that enhances the thrombin-catalyzed generation of the anticoagulant factor activated protein C, yet inhibits thrombin-dependent fibrinogen clotting. By means of mutant substrates, it was shown that LY254603 mediates the change in enzymatic substrate specificity through an alteration in thrombin's S3 substrate recognition site, a mechanism that appeared to be independent of allosteric changes induced by either sodium ions or by thrombomodulin. This compound may represent the prototype of a class of agents that specifically modulates the balance between thrombin's procoagulant and anticoagulant functions.


A tetracycline-regulatable adeno-associated virus vector for double-gene transfer.
An increasing demand for polycistronic vectors that express multiple genes simultaneously has arisen in recent years to obtain an efficient gene therapy. Armed with the knowledge that the expression of transgene in mammalian cells often requires tight control, we constructed in this study a tetracycline-regulated double-gene adeno-associated virus (AAV) vector carrying green and red fluorescent protein genes and expressed it in PC12 cells. When detected by fluorescence microscope and fluorescence-activated cell sorting, gene expression was induced by 44-66-fold and could be reversibly controlled by doxycycline. This double-gene AAV vector may be useful for regulated expression of two genes or a marker to monitor transgene expression.


Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies.
Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 micrograms of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 micrograms/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 micrograms/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 micrograms/kg (10 times the recommended use level) to Collies known to be sensitive to this drug.


Work Productivity Loss After Minimally Displaced Complete Lateral Compression Pelvis Fractures.
To quantify work impairment and economic losses due to lost employment, lost work time (absenteeism), and lost productivity while working (presenteeism) after a lateral compression pelvic ring fracture. Secondarily, productivity loss of patients treated with surgical fixation versus nonoperative management was compared. Secondary analysis of a prospective, multicenter trial. Two level I academic trauma centers. Adult patients with a lateral compression pelvic fracture (OTA/AO 61-B1/B2) with a complete posterior pelvic ring fracture and less than 10 mm of initial displacement. Excluded were patients who were not working or non-ambulatory before their pelvis fracture or who had a concomitant spinal cord injury. Work impairment, including hours lost to unemployment, absenteeism, and presenteeism, measured by Work Productivity and Activity Impairment assessments in the year after injury. Results after non-operative and operative treatment were compared. Of the 64 included patients, forty-seven percent (30/64) were treated with surgical fixation, and 53% (30/64) with nonoperative management. 63% returned to work within 1 year of injury. Workers lost an average of 67% of a 2080-hour average work year, corresponding with $56,276 in lost economic productivity. Of the 1395 total hours lost, 87% was due to unemployment, 3% to absenteeism, and 10% to presenteeism. Surgical fixation was associated with 27% fewer lost hours (1155 vs. 1583, P = 0.005) and prevented $17,266 in average lost economic productivity per patient compared with nonoperative management. Lateral compression pelvic fractures are associated with a substantial economic impact on patients and society. Surgical fixation reduces work impairment and the corresponding economic burden. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Gingival microleakage of class V composite restorations with fiber inserts.
This study investigated the effect of different fiber inserts (glass and polyethylene), bonding agents, and resin composites on the gingival margin microleakage of class V composite restorations. Sixty premolars were sterilized and mounted in acrylic resin bases. Class V cavities were prepared buccally and lingually, 1 mm below the cementoenamel junction, comprising 12 groups (n = 10). In the experimental groups fiber inserts were cut and placed at the gingival seat, while the control groups had no inserts. Combinations of two composite materials, Filtek-Z250 and Filtek-LS (3M-ESPE), and four bonding agents, Clearfil SE bond (Kuraray) (C), Scotch Bond Multipurpose (3M-ESPE) (SB), Prime and Bond NT (Dentsply) (PB), and Filtek-LS (3M-ESPE) (LS) were used. Restorations were incrementally inserted and polymerized for 40s. Specimens were then stored in distilled water for 7 days and thermocycled for 500 cycles. Teeth surfaces were sealed with nail polish except for 1 mm around restoration margins and immersed in 2% red procion dye. Teeth were then sectioned buccolingually and dye penetration was assessed with five-point scale. Data were statistically-analyzed by Kruskal-Wallis, ANOVA and Tukey's tests (α = 5%). Mean microleakage scores varied from 0.40 (Groups C, C with polyethylene, LS, LS with polyethylene) to 1.50 (SB). Different bonding agents led to differences in microleakage scores where C and LS showed significantly lower microleakage than PB. SB had highest mean microleakage score, however, incorporation of fibers resulted in significant reduction in microleakage. Class V resin composite restorations bonded with a total-etch adhesive had a significant reduction in mean microleakage scores when glass or polyethylene fibers were placed at the gingival cavo-surface margin. In contrast, for two self-etch adhesive systems, the incorporation of fibers had no significant effect on mean microleakage scores.


Sharing health data for better outcomes on PatientsLikeMe.
PatientsLikeMe is an online quantitative personal research platform for patients with life-changing illnesses to share their experience using patient-reported outcomes, find other patients like them matched on demographic and clinical characteristics, and learn from the aggregated data reports of others to improve their outcomes. The goal of the website is to help patients answer the question: "Given my status, what is the best outcome I can hope to achieve, and how do I get there?" Using a cross-sectional online survey, we sought to describe the potential benefits of PatientsLikeMe in terms of treatment decisions, symptom management, clinical management, and outcomes. Almost 7,000 members from six PatientsLikeMe communities (amyotrophic lateral sclerosis [ALS], Multiple Sclerosis [MS], Parkinson's Disease, human immunodeficiency virus [HIV], fibromyalgia, and mood disorders) were sent a survey invitation using an internal survey tool (PatientsLikeMe Lens). Complete responses were received from 1323 participants (19% of invited members). Between-group demographics varied according to disease community. Users perceived the greatest benefit in learning about a symptom they had experienced; 72% (952 of 1323) rated the site "moderately" or "very helpful." Patients also found the site helpful for understanding the side effects of their treatments (n = 757, 57%). Nearly half of patients (n = 559, 42%) agreed that the site had helped them find another patient who had helped them understand what it was like to take a specific treatment for their condition. More patients found the site helpful with decisions to start a medication (n = 496, 37%) than to change a medication (n = 359, 27%), change a dosage (n = 336, 25%), or stop a medication (n = 290, 22%). Almost all participants (n = 1,249, 94%) were diagnosed when they joined the site. Most (n = 824, 62%) experienced no change in their confidence in that diagnosis or had an increased level of confidence (n = 456, 34%). Use of the site was associated with increasing levels of comfort in sharing personal health information among those who had initially been uncomfortable. Overall, 12% of patients (n = 151 of 1320) changed their physician as a result of using the site; this figure was doubled in patients with fibromyalgia (21%, n = 33 of 150). Patients reported community-specific benefits: 41% of HIV patients (n = 72 of 177) agreed they had reduced risky behaviors and 22% of mood disorders patients (n = 31 of 141) agreed they needed less inpatient care as a result of using the site. Analysis of the Web access logs showed that participants who used more features of the site (eg, posted in the online forum) perceived greater benefit. We have established that members of the community reported a range of benefits, and that these may be related to the extent of site use. Third party validation and longitudinal evaluation is an important next step in continuing to evaluate the potential of online data-sharing platforms.


Prophylaxis of acute respiratory virus infections using nucleic acid-based drugs.
Acute respiratory virus infections such as SARS and pandemic influenza are highly contagious diseases that cause global crisis, and inflict severe human mortality and morbidity. Vaccines against these viruses are either unavailable or do not provide adequate protection. In the absence of effective vaccines, nucleic acid-based immunomodulators have the potential to offer effective, broad-spectrum protection against these deadly pathogens. Poly ICLC and CpG oligonucleotides are promising gene-based drugs which have been shown in animal studies to protect against acute respiratory virus infections. Poly ICLC is a synthetic double-stranded RNA (dsRNA), and an effective interferon-inducer and natural killer cell activator. When encapsulated in liposomes, poly ICLC offers complete protection (100% survival rate in pretreated group versus 0% survival in control group) against a lethal respiratory challenge of influenza A virus in mice. This antiviral effect has been shown to persist for up to 3 weeks post-drug treatment. Poly ICLC pretreatment also protects mice against a respiratory challenge of western equine encephalitis (WEE) virus, at a level comparable to inactivated WEE vaccine. CpG oligos in liposomes also provided high level of protection against the lethal influenza challenge. Together, these studies suggest nucleic acid-based immunomodulators are promising antiviral agents which can offer effective and non-specific protection against acute respiratory virus infections.


From food to nutritional support to specific nutraceuticals: a journey across time in the treatment of disease.
Hospitalized patients who are unable to eat or cannot eat enough to meet their metabolic needs are given parenteral or enteral nutritional support. This form of therapy is now also given to patients at home. Nutritional support is a recent development, prior to which the value of food was recognized for its medicinal benefits as nutraceuticals. The value of such "alternative" therapy is now being rediscovered by many patients who enhance their dietary intake with these traditional remedies. In Western culture, conventional medicine until recently has largely rejected the use of such "alternative" therapeutic intervention. Based on an increasing database, though, insight has been gained concerning the scientific validity of many previously termed established nutraceuticals. We focus here on the effects of honey, green tea, ginseng, and vitamin supplementation on the immune system. Honey has proven antimicrobial activity. Green tea enhances humoral and cell-mediated immunity while decreasing the risk of certain cancers and the risk of cardiovascular disease. Ginseng enhances production of macrophages, B and T cells, natural killer cells, and colony-forming activity of bone marrow. Vitamin supplementation is associated with increased antibody titer response to both hepatitis B and tetanus vaccines as a result of macrophage and T cell stimulation. Because of these findings, nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing general well-being.


Muscle glycogen storage and its relationship with water.
This study examined the relationship between muscle glycogen and muscle water content. Exercise dietary manipulations were used to vary skeletal muscle glycogen levels in four groups of rodents: (1) eight animals were sedentary controls (SC); (2) ten animals were treadmill familiarized and allowed to recover 24 h before sacrifice (F); (3) ten animals were treadmill familiarized and exercised to exhaustion (E); (4) ten animals were treadmill familiarized, exercised to exhaustion, and allowed to recover with food and water ad libitum for 72 h (ER). All animals were sacrificed in a resting state to normalize intracellular, extracellular, and interstitial water compartments; thus, the E group was sacrificed 45 m in following their run. The treatments altered skeletal muscle glycogen to values ranging from 10.0 to 30.2 mumol glucosyl units/g wet tissue weight. Neither muscle triglyceride nor protein levels were affected by the treatments. Muscle water content expressed as mumol H2O lost/g wet tissue weight or made relative to protein content showed no consistent relationship to the glycogen content. These data, therefore, do not support the commonly accepted muscle glycogen-to-water ratio of 1.0:2.7 (g:g). Further work is necessary to quantify the exact amount of water that is actually associated with the glycogen complex.


Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature.
Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition.


Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human demyelinating disorder multiple sclerosis (MS). The immune cytokine interferon-gamma (IFN-gamma) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-gamma-oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-gamma. PLP/SOCS1 mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-gamma pretreatment of mature oligodendrocytes in vitro had a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 (IP10), CCL2 (MCP-1), CCL3 (MCP-1alpha), and CCL5 (RANTES). These results suggest that IFN-gamma-oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE.


Pronominal anaphora resolution in Polish: Investigating online sentence interpretation using eye-tracking.
The mechanism of anaphora resolution is subject to large cross-linguistic differences. The most likely reason for this is the different sensitivity of pronouns to the range of factors that determine their reference. In the current study, we explored the mechanism of anaphora resolution in Polish. First, we explored preferences in the interpretation of null and overt pronouns in ambiguous sentences. More specifically, we investigated whether Polish speakers prefer to relate overt pronouns to subject or object antecedents. Subsequently, we tested the consequences of violating this bias when tracing the online sentence-interpretation process using eye-tracking. Our results show that Polish speakers have a strong preference for interpreting null pronouns as referring to subject antecedents and interpreting overt pronouns as referring to object antecedents. However, in online sentence interpretation, only overt pronouns showed sensitivity to a violation of the speaker's preference for a pronoun-antecedent match. This suggests that null pronoun resolution is more flexible than overt pronoun resolution. Our results indicate that it is much easier for Polish speakers to shift the reference of a null pronoun than an overt one whenever a pronoun is forced to refer to a less-preferred antecedent. These results are supported by naturalness ratings, which showed that null pronouns are considered equally natural regardless of their reference, while overt pronouns referring to subject antecedents are rated as considerably less natural than those referring to object antecedents. To explain this effect, we propose that the interpretation of null and overt pronouns is sensitive to different factors which determine their reference.


Collaborative Virtual Reality Real-Time 3D Image Editing for Chest Wall Resections and Reconstruction Planning.
The integration of extended reality (XR) technologies into health care procedures presents transformative opportunities, particularly in surgical processes. This study delves into the utilization of virtual reality (VR) for preoperative planning related to chest wall resections in thoracic surgery. Leveraging the capabilities of 3-dimensional (3D) imaging, real-time visualization, and collaborative VR environments, surgeons gain enhanced anatomical insights and can develop predictive surgical strategies. Two clinical cases highlighted the effectiveness of this approach, showcasing the potential for personalized and intricate surgical planning. The setup provides an immersive, dynamic representation of real patient data, enabling collaboration among teams from separate locations. While VR offers enhanced interactive and visualization capabilities, preliminary evidence suggests it may support more refined preoperative strategies, potentially influence postoperative outcomes, and optimize resource management. However, its comparative advantage over traditional methods needs further empirical validation. Emphasizing the potential of XR, this exploration suggests its broad implications in thoracic surgery, especially when dealing with complex cases requiring multidisciplinary collaboration in the immersive virtual space, often referred to as the metaverse. This innovative approach necessitates further examination, marking a shift toward future surgical preparations. In this article, we sought to demonstrate the technique of an immersive real-time volume-rendered collaborative VR-planning tool using exemplary case studies in chest wall surgery.


Number density distribution of solvent molecules on a substrate: a transform theory for atomic force microscopy.
Atomic force microscopy (AFM) in liquids can measure a force curve between a probe and a buried substrate. The shape of the measured force curve is related to hydration structure on the substrate. However, until now, there has been no practical theory that can transform the force curve into the hydration structure, because treatment of the liquid confined between the probe and the substrate is a difficult problem. Here, we propose a robust and practical transform theory, which can generate the number density distribution of solvent molecules on a substrate from the force curve. As an example, we analyzed a force curve measured by using our high-resolution AFM with a newly fabricated ultrashort cantilever. It is demonstrated that the hydration structure on muscovite mica (001) surface can be reproduced from the force curve by using the transform theory. The transform theory will enhance AFM's ability and support structural analyses of solid/liquid interfaces. By using the transform theory, the effective diameter of a real probe apex is also obtained. This result will be important for designing a model probe of molecular scale simulations.


First worldwide clinical experience with a new dual chamber implantable cardioverter defibrillator. Advantages and complications. The Ventak AV II DR investigators.
The need for physiological pacing and for improving the ability to discriminate atrial from ventricular tachyarrhythmias has prompted the development of dual chamber implantable cardioverter/defibrillators (ICDs). Fifty-two patients were implanted with a newly developed dual-chamber ICD providing rate-responsive physiological pacing (Ventak AV II DR). The device possesses two new arrhythmia detection algorithms ('atrial fibrillation rate threshold' and 'ventricular to atrial rate relationship') in addition to commonly used features such as 'onset' and 'stability'. During implantation, the atrial and ventricular lead impedances and pacing thresholds were determined together with the defibrillation threshold. Prior to discharge, attempts were made to induce both atrial and ventricular tachyarrhythmias in order to test those new detection criteria. All patients were followed for at least 3 months. The device was successfully implanted in all 52 patients. Placement of the atrial lead was successful in 50/52 patients (96%; P-wave 3.2 +/- 1.4 mV; impedance 576 +/- 123 omega; atrial pacing threshold 1.2 +/- 0.9 V). Prior to discharge, 32 episodes of atrial fibrillation (AF) alone, 38 episodes of AF with ventricular fibrillation and 10 episodes of AF with monomorphic ventricular tachycardia were induced in 33/50 patients (66%) and all were appropriately classified by the detection algorithm. During the 3 months follow-up, 12 patients (23%) had appropriate and successful therapies for ventricular arrhythmias, while four patients (8%) experienced inappropriate ICD therapies. Although all these episodes were detected correctly as supraventricular arrhythmias by the device, therapy was delivered because of incorrect or incomplete programming. In all cases reprogramming of the device resolved the problem. Implantation of dual chamber ICDs is feasible and appears to improve discrimination of supraventricular from ventricular tachyarrhythmias. In addition, patients with tachyarrhythmias and concomitant bradyarrhythmias may benefit from simultaneous physiological pacing. However, implantation and follow-up of such patients should be performed at experienced centres since both surgical handling and programming of these devices is more difficult and complex than conventional ICDs.


Structure of ribosomal protein L30 from Thermus thermophilus at 1.9 A resolution: conformational flexibility of the molecule.
The crystal structure of ribosomal protein L30 from the extreme thermophilic bacterium Thermus thermophilus has been determined at 1. 9 A resolution. The crystals are trigonal and belong to space group P3(2)21, with unit-cell parameters a = b = 63.5, c = 77.8 A, alpha = beta = 90, gamma = 120 degrees and two molecules per asymmetric unit. The structure was solved by the molecular-replacement method with AMoRe and refined with X-PLOR to an R value of 20.3% and an R(free) of 25.3% in the resolution range 8-1.9 A. Detailed analyses of the structures of the two molecules in the asymmetric unit and comparison of T. thermophilus L30 structure with the structure of homologous L30 from Bacillus stearothermophilus reveal two flexible regions at opposite ends of the rather elongated molecule. Such flexibility could be important for the protein fitting in the ribosome. A comparison with B. stearothermophilus L30 shows a higher number of salt bridges and unbound positively charged residues and an increased accessible hydrophobic area on the surface of T. thermophilus L30. This could contribute to the stability of both the extreme thermophile protein and the ribosome as a whole.


Structure-based design of a parallel synthetic array directed toward the discovery of irreversible inhibitors of human rhinovirus 3C protease.
Utilizing the tools of parallel synthesis and structure-based design, a new class of Michael acceptor-containing, irreversible inhibitors of human rhinovirus 3C protease (HRV 3CP) was discovered. These inhibitors are shown to inhibit HRV-14 3CP with rates of inactivation ranging from 886 to 31 400 M(-1) sec(-1). These inhibitors exhibit antiviral activity when tested against HRV-14 infected H1-HeLa cells, with EC(50) values ranging from 1.94 to 0.15 microM. No cytotoxicity was observed at the limits of the assay concentration. A crystal structure of one of the more potent inhibitors covalently bound to HRV-2 3CP is detailed. These compounds were also tested against HRV serotypes other than type 14 and were found to have highly variable activities.


Microwave-induced plasma-promoted materials synthesis.
The discovery of new materials requires the development of a diversity of synthetic techniques. Microwave methods offer the opportunity to synthesise and modify the composition, structure and morphology of materials, particularly composites via differential heating. Microwave-induced plasmas (MIPs) allow any solid mixture to be heated, and can promote direct microwave heating at elevated temperature, greatly expanding the use of microwaves for reactions between solids and gas-solid mixtures.


The enzymic conversion of linoleic acid into 9-(nona-1',3'-dienoxy)non-8-enoic acid, a novel unsaturated ether derivative isolated from homogenates of Solanum tuberosum tubers.
1. A major component of the lipids in aqueous (pH7.5) homogenates of tuber tissue from Solanum tuberosum was isolated and characterized as 9-(nona-1',3'-dienoxy)non-8-enoic acid. 2. This novel unsaturated ether fatty acid derivative, which contains a butadienylvinyl ether function, has the structure: [Formula: see text] and is formed from linoleic acid by a sequence of enzymic reactions. 3. A precursor of the unsaturated ether derivative is 9-d-hydroperoxyoctadeca-10,12-dienoic acid, formed by the action of S. tuberosum lipoxygenase on linoleic acid. 4. An enzyme that converts the fatty acid hydroperoxide into the unsaturated ether derivative was isolated from S. tuberosum. The pH optimum of this enzyme is approx. 9, although the overall conversion of linoleic acid into the ether derivative is maximal at pH7.5. 5. An unusual feature of this pathway is the insertion of an oxygen atom into the alkyl chain of a fatty acid. 6. This novel mechanism may play a role in the breakdown of polyunsaturated fatty acids to volatile products in plants.


Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.
Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.


High valence 3p and transition metal based MOFs.
This article focuses on high valence 3p and transition metal based metal organic frameworks. In the first part we will discuss the complex solution chemistry of these metals which makes this sub-class of MOFs more of a challenge than the traditional low valence metal based MOFs. This is followed by a short review of the different classes of solids based on phosphonates, carboxylates and other linkers. Finally, we report some of the most relevant properties of these solids such as their chemical or thermal stability as well as their catalytic, redox- and photo-activities.


Steps that count: physical activity recommendations, brisk walking, and steps per minute--how do they relate?
Brisk walking is recommended as a form of health-enhancing physical activity. This study determines the steps/minute rate corresponding to self-paced brisk walking (SPBW); a predicted steps/minute rate for moderate physical activity (MPA) and a comparison of the 2 findings. A convenience sample (N = 58: 34 men, 24 women, 31.7 ± 7.7 yrs), wearing pedometers and a heart rate (HR) monitor, performed SPBW for 10 minutes and 5 indoor sessions, regulated by a metronome (ranging from 60-120 steps/minute). Using steps/minute and HR data of the trials, a steps/minute rate for MPA was predicted. Adjustments were subsequently made for aerobic fitness (using maximal oxygen uptake (VO2max) estimates), age, and sex as possible contributors to stepping rate differences. Average steps/minute rate for SPBW was 118 ± 9 (116 ± 9; 121 ± 8 for men/women, respectively; P = .022); predicted steps/minute rate for MPA was 122 ± 37 (127 ± 36; 116 ± 39 for men/women, respectively; P < .99) and was similar to steps/minute rate of SPBW (P = .452), even after adjusting for age, sex, and aerobic fitness. Steps/minute rates of SPBW correlates closely with targeted HR for MPA, independent of aerobic fitness; predicted steps/minute rate for MPA relates closely to steps/minute rates of SPBW. Findings support current PA messages that use the term brisk walking as a reference for MPA.