miR-1 Targeted Downregulation of Bcl-2 Increases Chemosensitivity of Lung Cancer Cells.
Objective: To investigate the expression of B cell lymphoma-2 (Bcl-2) in lung cancer cells and the effect of the miR-1/Bcl-2 axis on the chemosensitivity of lung cancer. Materials and Methods: Real-time quantitative PCR and western blotting were used to detect the expression of Bcl-2 in human embryonic lung fibroblasts and lung cancer cells. The effects of siRNA directed against Bcl-2, in lung cancer tissue samples was detected by immunohistochemistry; these results were used to develop prognostic models. Bioinformatic analyses, dual luciferase reporter gene technology, and western blotting technology were used to explore the targeted regulation of miR-1 on bcl-2. The effect of miR-1 on the chemosensitivity of lung cancer cells was measured using the MTT assay. Results: Compared with human embryonic lung fibroblasts, Bcl-2 was highly expressed in the lung cancer cells, especially in H460 cells. After silencing Bcl-2 with siRNA, the sensitivity of the cells to cisplatin (CDDP) increased. Immunohistochemical results and prognostic analysis revealed that high Bcl-2 expression in lung cancer tissues was negatively correlated with prognosis of lung cancer patients; A dual luciferase reporter assay combined with western blotting confirmed that miR-1 can bind to the Bcl-23' UTR region and regulate its expression. Overexpression of miR-1 in lung cancer cells (H460 and A549) increased the sensitivity of these cells to CDDP. Conclusion: Bcl-2 is upregulated in lung cancer cells, which is negatively correlated with the patient prognosis. miR-1 affects the chemosensitivity of lung cancer cells by targeting Bcl-2. These data should provide a theoretical basis for refining the molecular mechanisms of chemoresistance in lung cancer.


Tearing down or fixing up institutional care for abandoned children? Comment on Rygaard (2020).
Typical large-group institutions for abandoned children or orphans are known to be bad for the development of children, but what about small-group care? Rygaard (2020) presents SOS Children's Villages (SOSCV) as a natural and nondetrimental setting for abandoned children. In a random effects meta-analysis, we combined the scientific evidence on the physical and mental health of children growing up in SOSCV compared with peers growing up in typical institutions and in biological and foster families (N = 1,567). Results showed substantial developmental delays of SOSCV children compared with their peers in family care. Compared with children in typical institutions SOSCV children do better on mental health but even worse on physical growth. All efforts should be directed not to improving group care, but to the transition to family based care and the prevention of separation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Laser flash photolysis formation and direct kinetic studies of manganese(V)-oxo porphyrin intermediates.
Irradiation of porphyrin-manganese(III) perchlorate complexes in acetonitrile with 355 nm laser light gave MnV-oxo intermediates that were characterized by their UV-vis spectra and reactivities. The MnV-oxo species of tetrakis(pentafluorophenyl)porphyrin (2), tetraphenylporphyrin (4), and tetra-(4-(N-methylpyridiniumyl))porphyrin (6) were generated. Second-order rate constants for reactions of 2 with substrates were as follows: 6.1 x 105 M-1 s-1 (cis-stilbene), 1.3 x 105 M-1 s-1 (diphenylmethane), 1.3 x 105 M-1 s-1 (ethylbenzene), and 0.55 x 105 M-1 s-1 (ethylbenzene-d10). In oxidations of cis-stilbene and diphenylmethane, the order of reactivity of the MnV-oxo species was 2 > 6 > 4.


Nonadditive gene expression in polyploids.
Allopolyploidy involves hybridization and duplication of divergent parental genomes and provides new avenues for gene expression. The expression levels of duplicated genes in polyploids can show deviation from parental additivity (the arithmetic average of the parental expression levels). Nonadditive expression has been widely observed in diverse polyploids and comprises at least three possible scenarios: (a) The total gene expression level in a polyploid is similar to that of one of its parents (expression-level dominance); (b) total gene expression is lower or higher than in both parents (transgressive expression); and (c) the relative contribution of the parental copies (homeologs) to the total gene expression is unequal (homeolog expression bias). Several factors may result in expression nonadditivity in polyploids, including maternal-paternal influence, gene dosage balance, cis- and/or trans-regulatory networks, and epigenetic regulation. As our understanding of nonadditive gene expression in polyploids remains limited, a new generation of investigators should explore additional phenomena (i.e., alternative splicing) and use other high-throughput "omics" technologies to measure the impact of nonadditive expression on phenotype, proteome, and metabolome.


Outcomes of Late-Onset Bleb-Related Endophthalmitis Treated with Pars Plana Vitrectomy.
Purpose. To investigate clinical results on bleb-related endophthalmitis (BRE) after trabeculectomy treated with pars plana vitrectomy (PPV) and to evaluate influence factors for visual prognosis. Methods. Investigating medical records retrospectively, BRE was defined as an endophthalmitis induced by bleb infection. A total of 2018 eyes of 1225 patients who had trabeculectomy between December 2000 and July 2013 were included in this study. Eleven eyes of 11 patients with BRE were performed with PPV. Results. The mean age was 56.6 years. The mean period between trabeculectomy and BRE onset was 7.4 years. The mean period from starting symptom to initiation of treatment for endophthalmitis (PSITE) was 2.3 days. Bleb leakages were observed in 7 eyes (64%). On culture examinations, highly pathogenic bacteria (HPB) were identified in 6 cases (55%). HPB infection was influence factors on visual disturbance (P = .0337). Number of HPB infections is significantly higher in poor visual outcome than without poor visual outcome (P = .0310). Conclusion. Visual prognosis of BRE treated by PPV is significantly better when the pathogenic bacteria are not HPB. Severe visual loss occurred with HPB infection even though patients had appropriate treatments. Physicians need to have careful consideration to prevent bleb infection after trabeculectomy with MMC.


[IL-18 expression in whole blood cell cultures from active lupus nephritis and the inhibitory effects of FK506, cyclosporin A and dexamethasone].
To explore the expression of IL-18 in patients with active lupus nephritis(LN) and the inhibitory effects of immunosupressive agents FK506, cyclosporin A (CsA) and dexamethasone(DEX). Peripheral blood samples were collected from 16 LN patients and 10 health volunteers and cultured with or without PHA/LPS, PHA/LPS+FK506, PHA/LPS+CsA and PHA/LPS+DEX for 24 hours. The IL-18 level in cultured supernatants and the IL-18 mRNA expression in cultured whole blood cells were detected by ELISA and semi-quantitative RT-PCR respectively, and the inhibitory effects of FK506, CsA and DEX on IL-18 expression were investigated. The expression levels of IL-18 mRNA and its protein in whole blood cell cultures from LN patients were higher than those in normal control group (P<0.01) either spontaneously or after stimulation with LPS/PHA. FK506, CsA and DEX suppressed significantly the expressions of IL-18 mRNA and its protein (P<0.001) in LPS/PHA-stimulated whole blood cell from LN patients. The inhibitory effects of FK506, CsA and DEX on the IL-18 protein expression in LN patients were stronger than that in normal control group (P<0.01 or P<0.05). IL-18 may play an important role in the pathogenesis of LN and inhibition of IL-18 production may be an useful way to treat LN.


miRCancer: a microRNA-cancer association database constructed by text mining on literature.
Research interests in microRNAs have increased rapidly in the past decade. Many studies have showed that microRNAs have close relationships with various human cancers, and they potentially could be used as cancer indicators in diagnosis or as a suppressor for treatment purposes. There are several databases that contain microRNA-cancer associations predicted by computational methods but few from empirical results. Despite the fact that abundant experiments investigating microRNA expressions in cancer cells have been carried out, the results have remain scattered in the literature. We propose to extract microRNA-cancer associations by text mining and store them in a database called miRCancer. The text mining is based on 75 rules we have constructed, which represent the common sentence structures typically used to state microRNA expressions in cancers. The microRNA-cancer association database, miRCancer, is updated regularly by running the text mining algorithm against PubMed. All miRNA-cancer associations are confirmed manually after automatic extraction. miRCancer currently documents 878 relationships between 236 microRNAs and 79 human cancers through the processing of >26 000 published articles. miRCancer is freely available on the web at http://mircancer.ecu.edu/


All New Faces of Diatoms: Potential Source of Nanomaterials and Beyond.
Nature's silicon marvel, the diatoms have lately astounded the scientific community with its intricate designs and lasting durability. Diatoms are a major group of phytoplanktons involved in the biogeochemical cycling of silica and are virtually inherent in every environment ranging from water to ice to soil. The usage of diatoms has proved prudently cost effective and its handling neither requires costly materials nor sophisticated instruments. Diatoms can easily be acquired from the environment, their culture requires ambient condition and does not involve any costly media or expensive instruments, besides, they can be transported in small quantities and proliferated to a desirable confluence from that scratch, thus are excellent cost effective industrial raw material. Naturally occurring diatom frustules are a source of nanomaterials. Their silica bio-shells have raised curiosity among nanotechnologists who hope that diatoms will facilitate tailoring minuscule structures which are beyond the capabilities of material scientists. Additionally, there is a colossal diversity in the dimensions of diatoms as the frustule shape differs from species to species; this provides a scope for the choice of a particular species of diatom to be tailored to an exacting requisite, thus paving the way to create desired three dimensional nanocomposites. The present article explores the use of diatoms in various arenas of science, may it be in nanotechnology, biotechnology, environmental science, biophysics or biochemistry and summarizes facets of diatom biology under one umbrella. Special emphasis has been given to biosilicification, biomineralization and use of diatoms as nanomaterials', drug delivery vehicles, optical and immune-biosensors, filters, immunodiagnostics, aquaculture feeds, lab-on-a-chip, metabolites, and biofuels.


Kingella kingae keratitis.
We present the first two cases of Kingella kingae keratitis in adults. This species is a rare isolate from ophthalmic samples for which final identification was obtained with matrix-assisted laser desorption ionization-time of flight mass spectrometry. One of the patients recovered uneventfully with topical therapy. Results from the second patient cannot be confirmed as he was lost to follow-up.


Parameter estimation of dynamical systems via a chaotic ant swarm.
Through the construction of suitable objective function, the parameter estimation of the dynamical system could be converted to the problem of parameter optimization. Based on the chaotic ant swarm optimization approach, we investigate the problem of parameter optimization for the dynamical systems in the presence of noise. We systematically analyze the basic relationships among the complexity of objective function, the length of time series, and the performance of the searching algorithm. Furthermore, we consider the effect of measurable additive noise on the objective function. Numerical simulations are also provided to show the effectiveness and feasibility of the proposed methods.


Hydrated Zinc Borates and Their Industrial Use.
Zinc borates are important chemical products having industrial applications as functional additives in polymers, bio-composites, paints and ceramics. Of the thirteen well documented hydrated binary zinc borates, Zn[B3O4(OH)3] (2ZnO∙3B2O3∙3H2O) is manufactured in the largest quantity and is known as an article of commerce as 2ZnO∙3B2O3∙3.5H2O. Other hydrated zinc borates in commercial use include 4ZnO∙B2O3∙H2O, 3ZnO∙3B2O3∙5H2O and 2ZnO∙3B2O3∙7H2O. The history, chemistry, and applications of these and other hydrated zinc borate phases are briefly reviewed, and outstanding problems in the field are highlighted.


Cytogenetic studies on the malaria vector mosquito Anopheles arabiensis Patton in the Awash Valley, Ethiopia.
Blood fed female mosquitoes were collected from human dwellings in the Awash Valley, Ethiopia. Those identified morphologically as A. gambiae s.l. were preserved in Carnoy's fixative for later ovarian polytene chromosomes examination. Only one member of the A. gambiae complex, A. arabiensis, was found by such examination. The polymorphic inversions identified were 2Rb and 3Ra. The frequencies of these inversions were variable in different localities and the former inversion was found to form an altitudinal cline.


Virus-induced gene silencing of the RPC5-like subunit of RNA polymerase III caused pleiotropic effects in Nicotiana benthamiana.
In eukaryotic cells, RNA polymerase III is highly conserved and transcribes housekeeping genes such as ribosomal 5S rRNA, tRNA and other small RNAs. The RPC5-like subunit is one of the 17 subunits forming RNAPIII and its exact functional roles in the transcription are poorly understood. In this work, we report that virus-induced gene silencing of transcripts encoding a putative RPC5-like subunit of the RNA Polymerase III in a model species Nicotiana benthamiana had pleiotropic effects, including but not limited to severe dwarfing appearance, chlorosis, nearly complete reduction of internodes and abnormal leaf shape. Using transcriptomic analysis, we identified genes and pathways affected by RPC5 silencing and thus presumably related to the cellular roles of the subunit as well as to the downstream cascade of reactions in response to partial loss of RNA Polymerase III function. Our results suggest that silencing of the RPC5L in N. benthamiana disrupted not only functions commonly associated with the core RNA Polymerase III transcripts, but also more diverse cellular processes, including responses to stress. We believe this is the first demonstration that activity of the RPC5 subunit is critical for proper functionality of RNA Polymerase III and normal plant development.


ECONOMIC ISSUES IN THERAPEUTIC DRUG MONITORING.
The fact that resources for health care are limited has been found as a rationale for the development of pharmacoeconomics. Pharmacoeconomic analysis identifies, measures and compares the costs and the economic, clinical and humanistic outcomes of diseases, drug therapies and programmes directed to these diseases. As health care expenditures have escalated over the past decades, the number of its applications has increased. Taking into consideration outcome and economic issues and establishing their mutual relationship helps proper resource allocation. In the case of some effective and toxic drugs therapeutic drug monitoring has been proven to allow obtaining the desired clinical effects safely and thus to improve outcome. However, it requires the presence of clinical pharmacology or clinical pharmacy service within a hospital, which in turn is associated with some additional costs. This review sums up the results of pharmacoeconomic studies relevant to the use of therapeutic drug monitoring in case of the medicines for which it has been commonly performed so far.


Current management options for liposarcoma and challenges for the future.
Liposarcoma (LS) represents one of the most common soft tissue sarcomas. There are three major subtypes, namely, well/dedifferentiated, myxoid/round cell and pleomorphic LS. In general, LS is known to be a relatively chemo-resistant sarcoma subtype with the exception of the myxoid variant. Conventional chemotherapy with doxorubicin and ifosfamide represents the mainstay of systemic treatment in the first line. Other active cytotoxic agents include gemcitabine and docetaxel and the marine-derived compounds trabectedin. Recent progress in molecular diagnostics of each single LS subtype has improved the knowledge of the molecular characteristics and has led to two recent treatment targets: the amplification of mouse double minute 2 homolog and cyclin-dependent kinase-4 in well- and dedifferentiated LS. Thus far, only early-phase trials are reported and no new drugs have been introduced in daily clinical practice. The focus of this review is on current systemic treatment options, including novel strategies.


Upper Airway Obstruction Secondary to Anticoagulant Rodenticide Toxicosis in Five Dogs.
Five dogs were presented with clinical signs compatible with upper airway obstruction, including stridor, stertor, coughing, gagging, and varying degrees of respiratory distress. All dogs had radiographic findings of soft tissue opacity in the area of the pharynx, larynx, or trachea, and several had narrowing of the tracheal lumen. Coagulation abnormalities (prolonged prothrombin time, activated partial thromboplastin time) were present in the four dogs that underwent testing. Four of five dogs were treated for the coagulopathy, presumably due to anticoagulant rodenticide toxicosis, and survived to discharge.Upper airway obstruction is an unusual presentation for anticoagulant rodenticide toxicosis in dogs. Raising the index of suspicion for this treatable condition may help clinicians to identify this sooner.


Platelet Dysfunction and Its Role in the Pathogenesis of Psoriasis.
Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of cardiovascular disease events, especially in severe cases. The hemostatic balance is disrupted due to the prothrombotic bias in psoriasis, which might be mainly preserved by platelet hyperactivity. Platelets are also immune cells that initiate and regulate immune and inflammatory processes, except as the principal mediator of hemostasis and thrombosis, and platelet dysfunction is deeply involved in the pathogenesis of psoriasis. The aim of this study is to perform a review that expounds abnormal platelet function in psoriasis and explains the important role of platelets in the pathogenic mechanism of psoriasis in order to provide new targets for comprehensive medical treatment.


Policies influencing the provision of healthy food and drinks in local government-owned sport and recreation facilities in Victoria, Australia.
Sporting facilities owned or managed by local governments (LGs) can promote health by selling healthy food and drinks. This study assessed the policies, attitudes and practices of LGs in Victoria, Australia, relating to obesity prevention and the provision of healthy food in their sporting facilities. An online survey was e-mailed to all Victorian LGs (n=79) in July 2018. Questions assessed LGs' healthy food policies relating to sport and recreation facilities and the priority LGs give to obesity prevention. Forty-nine LGs (62%) completed the survey from July to November 2018. Obesity prevention and promotion of healthy food and drink were a moderate to high priority for councils. The priority LGs give to healthy food promotion was reported to have increased over the previous year in 55% of LGs. Those LGs in areas of higher socioeconomic position and located in major cities had made more healthy changes at their facilities. Obesity prevention is a priority for LGs, and they are making changes to improve the food environments in their sporting facilities. Greater support may be required for smaller LGs and those in socioeconomically disadvantaged areas to create healthier food environments. Implications for public health: Monitoring changes to healthy eating policies within council facilities is essential to understand how local government actions are contributing to obesity prevention.


Volatile profiles of Italian monovarietal extra virgin olive oils via HS-SPME-GC-MS: newly identified compounds, flavors molecular markers, and terpenic profile.
This study aims to contribute to the knowledge of the commercial, sensory, and analytical characteristics of extra virgin olive oil (EVOO) from Italy (Marche region), renowned since ancient times. Headspace solid-phase micro-extraction (HS-SPME) was applied for the very first time to the sampling of volatile compounds of eleven typical Italian monocultivar EVOOs. Forty-eight compounds were characterised by GC-MS, some of them were only occasionally found in other EVOOs and some other were never detected before in any EVOO. Compounds belonging mainly to alcohols, esters, aldehydes, ketones and hydrocarbons chemical classes characterised the volatile profiles. The main volatile compounds detected in the EVOOs were the C6 compounds derived from polyunsaturated fatty acids, through the lipoxygenase pathway, in different proportion according to the specific cultivar. The results suggest that genetic factors strongly influence volatile formation and terpene hydrocarbons are claimed to be suitable markers of the geographic origin and genotype of the EVOO. Correlations among sensory attributes evaluated by a panel test and the presence of specific volatile compounds were highlighted for the very first time. The significance of the presence of some newly identified volatile compounds was discussed.


Modes of retrotransposition of long interspersed element-1 by environmental factors.
Approximately 42% of the human genome is composed of endogenous retroelements, and the major retroelement component, long interspersed element-1 (L1), comprises ∼17% of the total genome. A single human cell has more than 5 × 10(5) copies of L1, 80∼100 copies of which are competent for retrotransposition (RTP). Notably, L1 can induce RTP of other retroelements, such as Alu and SVA, and is believed to function as a driving force of evolution. Although L1-RTP during early embryogenesis has been highlighted in the literature, recent observations revealed that L1-RTP also occurs in somatic cells. However, little is known about how environmental factors induce L1-RTP. Here, we summarize our current understanding of the mechanism of L1-RTP in somatic cells. We have focused on the mode of L1-RTP that is dependent on the basic helix-loop-helix/per-arnt-sim (bHLH/PAS) family of transcription factors. Along with the proposed function of bHLH/PAS proteins in environmental adaptation, we discuss the functional linking of L1-RTP and bHLH/PAS proteins for environmental adaptation and evolution.


[Significance of hepatic biopsy specimens in the diagnosis of liver disease in babies of the first year of life].
The paper gives the results of a histological study of 21 liver biopsy specimens from babies of the first year of life, who had clinical manifestations of neonatal hepatitis with cholestasis syndrome. The major morphological variants of hepatic lesion, such as giant-cell hepatitis, chronic active hepatitis, congenital cystic fibrosis with extensive intrahepatic cholestasis and a high hepatic inflammatory-necrotic activity have been found to result in the early development of severe hepatic fibrosis and cirrhosis, which is of great prognostic value. It is necessary to enhance the efficiency of a histological assessment of an etiological factor in the hepatic biopsy specimen in order to optimize treatment for liver diseases in this category of patients.


Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population.
To determine the prevalence and incidence of trichomoniasis, risk factors for infection, and the prevalence of metronidazole and tinidazole-resistant Trichomonas vaginalis (T. vaginalis) in female adolescents. Nonpregnant, HIV-seronegative, sexually active females (13-19 years) visiting an inner city public primary care clinic were tested for T. vaginalis by wet mount and culture, and interviewed about risk-taking behavior every 6 months. Infected patients were treated with a 2 g oral dose of metronidazole. Isolates from positive T. vaginalis cultures were tested for in vitro resistance to metronidazole and tinidazole. Among 467 study participants, 67 (14.4%; 95% confidence interval, 11.3-17.5) were diagnosed with trichomoniasis at first T. vaginalis culture. Significant risk factors for T. vaginalis infection were having an older sex partner and concurrent Neisseria gonorrhoeae infection. The incidence was 22.1 cases per 100 person-years. Among 42 participants who had a prevalent infection and returned for followup, 13 (31.0%) had at least 1 more episode of trichomoniasis. Resistance testing was completed for 78 isolates: 37 at first visit and 41 during follow-up. One (2.7%; 95% confidence interval, 0.07-14.2) of the 37 first-visit isolates was moderately resistant to metronidazole (minimal lethal concentration = 200 microg/mL). Of the 41 follow-up visit isolates, 1 was moderately resistant to metronidazole and 2 had borderline resistance (minimal lethal concentration = 50 microg/mL). The prevalence of tinidazole resistance was 0% (0.0%-9.5%). The study population had high prevalence and incidence of trichomoniasis. The prevalence of antibiotic-resistant T. vaginalis among female adolescents was low.


[Orbito-fronto-temporal approach to tumors at the base of the skull. Our experience in the creation of orbito-zygomatic-malar flap].
The authors describe the technique of mobilization of the osseous orbito-zygomatico-malar complex pedicled to the masseter muscle. In some affections it is justiciable to use this approach which provides an excellent view of the lateral region of the medial cranial fossa and orbit and permits the access to the base of the tumor by a intra- and extracranial approach without traumatic injury for the brain and easy reconstruction.


Adenosine usage during AF ablation in Europe and selected long-term findings from the ESC-EHRA EORP Atrial Fibrillation Ablation Long-Term registry.
Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety. The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared. Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p < 0.001). Adenosine was associated with better rhythm outcome in RF ablation procedures, but not in cryo-ablation procedures (freedom from AF: RF: AG: 70.9%, NAG: 58.1%, p < 0.001, cryo: AG: 63.9%, NAG: 63.8%, p = 0.991). The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.


Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice.
To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging. A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance. Infected cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD) of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was 11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose. The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector.


Analysis of antimicrobial sales data of the main distributor in Quebec from 2016 to 2019: An estimate of usage in dairy cattle, horses, and small animals.
Because antimicrobial usage (AMU) data are crucial in understanding and dealing with the threat that antimicrobial resistance (AMR) poses to global health, data of the sale of antimicrobials from 2016 to 2019 of CDMV Inc. - a major distributor of veterinary products in Canada - were collected and analyzed for the province of Quebec. The primary objective was to describe the evolution of AMU sales data for dairy cattle, small animals, and horses; a secondary objective was to determine effects of a new provincial regulation on antimicrobials of very high importance (in Quebec) on sales for dairy cattle. Results are described in milligrams of antimicrobials per kilogram of animal biomass (mg/PCU) for dairy cattle, small animals, and horses; intramammary products were analyzed for number of treatments per 100 cow-years; and results for dairy cattle were compared in Canadian-defined course doses for cattle (DCDbovCA) per 100 cow-years to a recent study for this species in Quebec. Between 2016 and 2019, there were decreased sales of Category 1 antimicrobials for all species included in the study (Category 1-VI for small animals). This reduction was even more apparent for dairy cattle, for which a 76% decrease occurred from 2018 to 2019 (1.7 to 0.4 mg/PCU). This marked reduction was attributed to the new regulation implemented in February 2019. Since a farm- and clinic-level AMU monitoring system has not yet been implemented in Quebec, analysis of CDMV Inc. sales enabled observations of temporal trends in AMU for dairy cattle, horses, and small animals. These temporal trends based on CDMV Inc. sales will be useful for making comparisons and validating trends derived from farm- and clinic-level data generated by a monitoring system.


Oxa-di-pi-methane photochemical rearrangement of quinuclidinones. Synthesis of pyrrolizidinones.
[reaction: see text] The oxa-di-pi-methane (ODPM) photochemical rearrangement, a triplet-sensitized sigmatropic 1,2-acyl shift of beta,gamma-enones, was successful utilizing methyl and heptyl 1-aza-3-carboalkoxybicyclo[2.2.2]oct-2-en-5-ones (quinuclidinones) as the photoprecursors. The cyclopropane of the heptyl ester tricyclic photoproduct could be opened with lithium dimethylcuprate or via hydrogenolysis to produce the corresponding pyrrolizidinone skeletons.


Pregnancy outcomes after maternal exposure to simvastatin and lovastatin.
Our objective was to determine the frequency of adverse outcomes after maternal exposure to simvastatin and/or lovastatin during pregnancy in postmarketing experience. We reviewed the Merck & Co., Inc. (West Point, PA) pharmacovigilance database for reports of exposure to simvastatin or lovastatin during pregnancy. The reports were classified as prospective (reported prior to pregnancy outcome) or retrospective (reported after pregnancy outcome) and were evaluated for timing of exposure, outcome, congenital anomalies, and other events. Outcome rates were calculated for prospective pregnancies. We identified 477 reports (386 prospective and 91 retrospective) with 225 prospective outcomes reported: 154 live born infants, 49 elective abortions, 18 spontaneous abortions, and 4 fetal deaths. Six congenital anomalies were reported: chromosomal translocation, trisomy 18, hypospadias, duodenal atresia, cleft lip, and skin tag. The rate of congenital anomalies (congenital anomalies/live births plus fetal deaths) was 3.8%, which is similar to the background population rate (3.2%; relative ratio, 1.21; 95% 1-sided upper confidence interval [CI], 2.02). There were 13 retrospective reports describing a range of congenital anomalies. No specific pattern of anomalies was identified in either the prospective or retrospective reports. Rates for other outcomes were similar to background rates. Although the number of reports was relatively small, there was no evidence of a notable increase in congenital anomalies in women exposed to simvastatin or lovastatin versus the general population. Greater reporting of congenital abnormalities in the retrospective cohort is not unexpected and may reflect a reporting bias. Drugs should be used during pregnancy only if the benefits outweigh the risks. Simvastatin and lovastatin remain contraindicated during pregnancy.


An integrative approach to the assessment of narcissism.
Narcissism research is poorly calibrated across fields of study in part due to confusion over how to integrate normal and pathological descriptions of narcissism. We argue that pathological and normal narcissism can be integrated in a single model that organizes around self-regulation mechanisms. We present theoretical and empirical support for this interpretation, and demonstrate that modeling pathological and normal narcissism as 2 dimensions underlying the narcissistic character can help to resolve some of the inconsistencies in the field regarding how to best assess adaptive and maladaptive expressions of narcissism.


Evaluation of celiac disease with uniphasic and multiphasic dynamic MDCT imaging.
An analysis of dynamic contrast MRI has been shown to provide valuable information about disease activity in Crohn's disease and Celiac disease (CD). However, there are no reports of dynamic multi-detector computer tomography use in patients with CD. The aim of this study is to determine and compare the perfusion dynamics of the patients treated with control subjects and the perfusion dynamics in patients with untreated CD, using dynamic contrast in MDCT and compare studying contrast dynamics in Marsh types as well. In this retrospective study, uniphasic and multiphasic MDCT, untreated, treated, incompatible CD patients and healthy control group duodenum wall thickness and HU values were compared in terms of patient groups and modified Marsh types. In dynamic CT, the highest contrast curve was observed in the untreated group and Marsh type 1. While the contrast curve of the untreated and non-compliant patients increased rapidly and showed wash out, the type 4 contrast curve was observed, whereas the treated and control group slowly increased type 5 contrast curve. In the contrast-enhanced CT in the venous phase, in the ROC analysis between Marsh 1-2 and Marsh 3a-c, the sensitivity was 97% and the specificity was 87% when the cut off was taken as 4.45 mm for wall thickness (p: 0.005). Contrast-enhanced single-phase and dynamic MDCT imaging in CD patients may be useful in evaluating the inflammatory and pathological process in the small intestine.


A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver.
Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver. Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter. ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group. These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field.


A reconsideration of the concept of regression.
Regression has been a useful psychoanalytic concept, linking present mental functioning with past experiences and levels of functioning. The concept originated as an extension of the evolutionary zeitgeist of the day as enunciated by H. Spencer and H. Jackson and applied by Freud to psychological phenomena. The value system implicit in the contrast of evolution/progression vs dissolution/regression has given rise to unfortunate and powerful assumptions of social, cultural, developmental and individual value as embodied in notions of "higher," "lower;" "primitive," "mature," "archaic," and "advanced." The unhelpful results of these assumptions are evident, for example, in attitudes concerning cultural, sexual, and social "correctness, " same-sex object choice, and goals of treatment. An alternative, a continuously constructed, continuously emerging mental life, in analogy to the ever changing, continuous physical body, is suggested. This view retains the fundamentals of psychoanalysis, for example, unconscious mental life, drive, defense, and psychic structure, but stresses a functional, ever changing, present oriented understanding of mental life as contrasted with a static, onion-layered view.


Hepatitis in clinical laboratories 1973-74.
The survey of laboratories in 1970-72 was continued by a questionnaire to members of the Association of Clinical Pathologists covering the next two years. Hepatitis B accounted for 14 of the 32 cases reported from 28 laboratories. A moderate excess of laboratories reporting hepatitis tested speciments from transplant units. The average attack rate for staff of all types was 143 per 100 000 with higher rates for science-biochemists (308), medical morbid anatomists (302), and haematology technicians (292). No case was fatal and only seven required hospital admission. The findings confirm the need for continued vigilance and precautions but do not justify alarm.


Frequency of underweight and stunting among children entering school in a small urban locality and their association with academic performance.
To determine the frequency of underweight and stunting among the children entering first year of school and to assess its associated factors. This descriptive, analytical study was conducted at 5 schools of Rabwah, Pakistan, from August to September 2015, and comprised all students who got admission in the selected schools during the study period. Name, father's name, gender, weight, height, status of height, and weight on Z-score charts, and marks obtained in the test were recorded. SPSS 20 was used for statistical analysis. Of the 478 participants, 212(44.4%) were boys and 266(55.6%) were girls. The overall mean age was 66.6±5.966 months (range: 41-129 months). Overall, 53(11.1%) were underweight, 22(4.6%) were severely underweight, 55(11.5%) had stunting and 12(2.5%) had severe stunting. Median marks (Interquartile Range [IQR]) in admission test for obese, overweight, normal, underweight and severely underweight children were 76.3%(37.2-84.7), 65.9%, 66.7%(56.4-72.3), 64.6%(47-71), and 67%(55.3-78), respectively. Median marks (IQR) in admission test for tall, normal height, stunted and severe stunted children were 24.1%, 67%(57.3-73), 57%(31.1-67.8), and 62.6%(49.7-68.3), respectively. Children with stunting scored significantly fewer marks compared to children of normal height (p<0.05). Stunting and underweight were common problems among children starting school. Stunting was found to be associated with lower marks in admission test.


A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension.
The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.


[Impact of systolic blood pressure on visit-to-visit blood pressure variability in middle-aged and elderly people].
To observe the impact of systolic blood pressure (SBP) on visit-to-visit blood pressure variability (BPV) in middle-aged and elderly people. Visit-to-visit BPV was determined in 5440 workers in the Kailuan study cohort from 2006 to 2007. The subjects were ≥ 40 years-old and had no history of stroke, transient ischemic attack or myocardial infarction. Participants were divided into five groups according to different levels of SBP. Linear regression was used to analyze the related factors which might affect BPV. Mean systolic BPV of all subjects was 10.35 mm Hg [coefficient of variation (CV 7.96%)]. The mean systolic BPV of males was 10.54 mm Hg (CV 7.90%) while the mean SBPV of females was 10.06 mm Hg (CV 7.90%). The BPV of males was significant higher than that of females (P < 0.001). CV of SBP was similar between males and females. Furthermore, higher SBP was associated with higher BPV. There were significant differences in BPV between different groups with different levels of SBP (P < 0.001). Linear regression analysis demonstrated that SBP, age, gender, high-sensitivity C-reactive protein (hsCRP) were affecting factors of BPV. Twenty mm Hg SBP increase was linked with 2.02 mm Hg BPV increase and 0.388%CV increase. Age increase of 1 year was associated with 0.044 mm Hg BPV increase and 0.029% CV increase. SBP, age, gender and hsCRP are important factors affecting BPV in middle-aged and elderly people. Higher SBP is closely related to greater BPV in this cohort.


Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis.
We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha and IFN-gamma in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1beta, IL-6, IL-8 and TNF-alpha; at the same time, they suppressed phytohemagglutinin (PHA)-induced production of IL-2, IL-4, IL-5, IFN-gamma and IL-12. As compared to cordycepin, CS displayed its regulatory effects on IL-2 and IL-10 in a similar dose-dependent manner even with higher efficiency. The binding activity of transcription factors in a human monocytic cell line THP-1 was tested by the trans-AM method, and a higher binding activity of SP1 and SP3 was observed in cordycepin or CS treated cells compared to the control. These results led to the opinion that cordycepin and CS pleiotropically affected the actions of immune cells and cytokine network in a similar fashion. Cordycepin could be an important immunoregulatory active ingredient in Cordyceps sinensis. In addition, CS may contain substances which possess synergism with cordycepin, as CS showed a higher efficiency in the production of IL-10 and IL-2 than cordycepin. However, merits of these effects in pharmacology and clinical medicine have yet to be proven and the precise mechanism of these immune regulatory actions should be researched.


Ultrathin single-channel fiberscopes for biomedical imaging.
Ultrathin flexible fiberscopes typically have separate illumination and imaging channels and are available in diameters ranging from 0.5 to 2.5 mm. Diameters can potentially be reduced by combining the illumination and imaging paths into a single fiberoptic channel. Single-channel fiberscopes must incorporate a system to minimize Fresnel reflections from air-glass interfaces within the common illumination and detection path. The Fresnel reflection at the proximal surface of the fiber bundle is particularly problematic. This paper describes and compares methods to reduce the background signal from the proximal surface of the fiber bundle. Three techniques are evaluated: (1) antireflective (AR)-coating the proximal face of the fiber, (2) incorporating crossed polarizers into the light path, and (3) a novel technique called numerical aperture sharing, whereby a portion of the image numerical aperture is devoted to illumination and a portion to detection.


Effect of inhibition of protein synthesis on lipid metabolism in Lactobacillus plantarum.
In Lactobacillus plantarum 17-5, lipid synthesis appears to be correlated with protein synthesis. Inhibition of protein synthesis by chloramphenicol (50 mug/ml) caused the nearly simultaneous inhibition of incorporation of radioactive oleic acid into polar lipids before the cessation of growth. In addition, de novo fatty acid synthesis, as determined by the incorporation of radioactive acetate into cellular lipids, was also inhibited. Removal of the antibiotic resulted in the resumption of growth, protein synthesis, and polar lipid synthesis. Inhibition of protein synthesis by leucine deprivation also produced a marked reduction in the incorporation of radioactive oleic acid into the total polar lipids at about the same time that growth stopped (30 to 60 min after the removal of leucine). However, the different classes of lipids behaved differently. For example, the incorporation of oleic acid into cardiolipin was inhibited immediately upon removal of leucine from the cultures, whereas incorporation into phosphatidyl-glycerol was maintained at near normal rates for 60 min after the removal of leucine and then ceased. In contrast, the accumulation of radioactive oleic acid in a neutral lipid identified as diglyceride occurred to a much greater extent in leucine-deprived cultures than in control (+ leucine) cultures. Upon addition of leucine to leucine-deprived cultures, the rates of synthesis of phosphatidyl-glycerol and cardiolipin returned to normal; the amount of radioactivity in the diglyceride fraction decreased to normal levels concomitantly with increased phospholipid synthesis.


Cost-effective choices of marine fuels in a carbon-constrained world: results from a global energy model.
The regionalized Global Energy Transition model has been modified to include a more detailed shipping sector in order to assess what marine fuels and propulsion technologies might be cost-effective by 2050 when achieving an atmospheric CO2 concentration of 400 or 500 ppm by the year 2100. The robustness of the results was examined in a Monte Carlo analysis, varying uncertain parameters and technology options, including the amount of primary energy resources, the availability of carbon capture and storage (CCS) technologies, and costs of different technologies and fuels. The four main findings are (i) it is cost-effective to start the phase out of fuel oil from the shipping sector in the next decade; (ii) natural gas-based fuels (liquefied natural gas and methanol) are the most probable substitutes during the study period; (iii) availability of CCS, the CO2 target, the liquefied natural gas tank cost and potential oil resources affect marine fuel choices significantly; and (iv) biofuels rarely play a major role in the shipping sector, due to limited supply and competition for bioenergy from other energy sectors.


Antidiphtheria and antitetanus immunity of recruits in Romania.
The concern for maintaining a high antidiphtheria and antitetanus immunity level is permanent. The paper approaches the study of antidiphtheria and antitetanus immunity levels in a group of young recruits (who had been administered a DT booster 5-7 yrs before). The titres of antibodies were determined concomitantly by the neutralization test (NT) in vivo and by the passive hemagglutination assay (PHA) in vitro. The results obtained by the neutralization tests revealed (by the estimations shown by the geometrical means) a high antidiphtheria and antitetanus immunity level proved by an exceeding of the protection limits (0.03 IU/ml and 0.01 IU/ml) of 89 x and 953 x, respectively. The analysis of individual titres obtained by NT showed that of 540 subjects in whom diphtheria antitoxin was determined, 93.52% had protective titres, while of 619 subjects in whom the tetanus antitoxin was evaluated, 97.26% were immune. The results obtained by PHA were comparable with those obtained using the reference methods.


Chemotherapy in the treatment of prostate cancer--is there a role?
Prostate cancer is a common cancer in men. Traditional therapies are effective except in patients who progress to hormone refractory disease. Historically, chemotherapy has had a limited role in the treatment of prostate cancer. However, new agents are showing promise in patients with advanced disease. This article reviews and presents current evidence on the use of chemotherapy in the treatment of prostate cancer and attempts to aid general practitioners in their role in the multidisciplinary environment of current cancer care. Analysis of the literature suggests there is no clear role for chemotherapy in the neoadjuvant or adjuvant setting. Chemotherapy may provide a short survival benefit in men with androgen independent prostate cancer but more importantly, can improve quality of life, and reduce pain and prostate specific antigen thus providing effective palliation.


Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma.
Systemic inflammatory scores may aid prognostication and patient selection for trials. We compared five scores in advanced pancreatic adenocarcinoma (PDAC). Unresectable/metastatic PDAC patients enrolled in the Comprehensive Molecular Characterisation of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection trial (NCT02750657) were included. Patients had pre-treatment biopsies for whole genome and RNA sequencing. CD8 immunohistochemistry was available in a subset. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, Gustave Roussy Immune Score (GRIm-S), and Memorial Sloan Kettering Prognostic Score (MPS) were calculated. Overall survival (OS) was estimated using Kaplan-Meier methods. Associations between inflammatory scores, clinical/genomic characteristics, and OS were analysed. We analysed 263 patients. High-risk NLR, GRIm-S and MPS were poorly prognostic. The GRIm-S had the highest predictive ability: median OS 6.4 vs. 10 months for high risk vs. low-risk (P < 0.001); HR 2.26 (P < 0.001). ECOG ≥ 1, the basal-like subtype, and low-HRDetect were additional poor prognostic factors (P < 0.01). Inflammatory scores did not associate with RNA-based classifiers or homologous recombination repair deficiency genotypes. High-risk MPS (P = 0.04) and GRIm-S (P = 0.02) patients had lower median CD8 + tumour-infiltrating lymphocytes. Inflammatory scores incorporating NLR have prognostic value in advanced PDAC. Understanding immunophenotypes of poor-risk patients and using these scores in trials will advance the field.


Histomorphometric analysis of unilateral condylar hyperplasia in the temporomandibular joint: the value of the condylar layer and cartilage island.
This study aimed to describe the condylar layer and cartilage island in subjects with unilateral condylar hyperplasia (UCH). Five individuals (15-18 years old) with a diagnosis of UCH, treated in a university hospital in Temuco, Chile, were included. The analysis examined the presence, extension, and thickness of the layers on the condylar surface, the number, depth, and area of the cartilage islands, and the argyrophilic proteins of the nucleolar organizer region (AgNOR) score. Statistical significance was set at P<0.05. The fibrocartilaginous layer was thickest (0.13±0.05mm) and the joint layer was thinnest (0.07±0.01mm) (P<0.05). With respect to the number, depth, and area of the islands, case 1 presented the highest values, followed by case 2; the cartilage island was related to the fibrocartilaginous layer (P<0.05). All cases had AgNOR proteins in the proliferative and fibrocartilaginous layers, as well as the islands with the greatest presence of chondrocytes (P=0.245). A relationship was observed between the histopathological alterations in the different layers on the condylar surface and the thickness of the fibrocartilaginous layer, as well as the thickness of the latter and the number, depth, and area of the cartilage islands in the trabecular bone.


Transcriptomic and morphological profiling of Aspergillus fumigatus Af293 in response to antifungal activity produced by Lactobacillus plantarum 16.
The morphological effects of an antifungal activity produced by Lactobacillus plantarum 16, a malt-production steep water isolate, on two food-associated fungi were examined microscopically. Spore germination was completely inhibited in Aspergillus fumigatus and Rhizopus stolonifer upon treatment with concentrated cell-free supernatant (cCFS) of strain 16. Furthermore, addition of antifungal cCFS to germ tubes and hyphae halted further development compared to untreated controls. Transcriptome analysis of A. fumigatus Af293 following exposure to antifungal cCFS revealed a number of genes with altered transcription involved in a variety of cellular functions, most notably cell metabolism, suggesting a global metabolic shutdown and subsequent cell death. Increased transcription of the global regulator LaeA was also observed indicating that exposure to the antifungal activity caused a cellular stress response.


An update on data standards for gel electrophoresis.
The use of gel electrophoresis to separate and, in some instances, to quantify the abundance of large numbers of proteins from complex mixtures, has been well established for several decades. The quantity of publicly available data is still relatively modest due to a lack of community accepted data standards, tools to facilitate the data sharing process and controlled vocabularies to ensure that consistent terminology is used to describe the experimental methodology. It is becoming widely recognised that there are significant benefits in data sharing for proteomics, allowing results to be verified and new findings to be generated by re-analysis of published studies. We report on standards development by the Gel Analysis Workgroup of the Proteomics Standards Initiative. The workgroup develops reporting requirements, data formats and controlled vocabularies for experimental gel electrophoresis, and informatics performed on gel images. We present a tutorial on how such resources can be used and how the community should get involved with the on-going projects. Finally, we present a roadmap for future developments in this area.


Studying Staphylococcal Leukocidins: A Challenging Endeavor.
Staphylococcus aureus is a well-known colonizer of the human skin and nose, but also a human pathogen that causes a wide spectrum of diseases. It is well established that S. aureus secretes an arsenal of virulence factors that have evolved to circumvent the human immune system. A major group of S. aureus virulence factors is the bi-component β-barrel pore-forming toxins, also known as leukocidins. These pore-forming toxins target specific cells of the innate and adaptive immune system by interacting with specific receptors expressed on the cell membrane. Even though still heavily debated, clinical and epidemiological studies suggest the involvement of one of the bi-component toxin, Panton-Valentine Leukocidin (PVL), as an important factor contributing to the epidemic spread and increased virulence of CA-MRSA strains. However, the host- and cell-specificity of PVL and other leukocidins, and the lack of adequate in vivo models, fuels the controversy and impairs the appropriate assessment of their role in S. aureus pathophysiology. Currently, the mechanisms of pore-formation and the contribution of PVL and other leukocidins to S. aureus pathophysiology are incompletely understood. This review summarizes our current understanding of leukocidin pore-formation, knowledge gaps, and highlights recent findings identifying novel host-factors involved in the toxin-host interface. As a result, this review furthers emphasizes the complexity behind S. aureus leukocidin cytotoxicity and the challenges associated in the quest to study and understand these major virulence factors.


Characterization of siRNAs derived from cucumber mosaic virus in infected tobacco plants.
This study characterized the viral small interfering RNAs (vsiRNAs) from Nicotiana tabacum cv. Samsun infected with a cucumber mosaic virus (CMV) 2b-deficient mutant. Most vsiRNAs were 21 -22 nucleotides in length and the 5'-terminal ends were dominated by A and U, respectively. The observed vsiRNAs were heterogeneously distributed throughout the CMV genome; however, most of the vsiRNAs were derived from sense strands, as opposed to antisense strands. These results demonstrate the conserved and specific function of Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) proteins in tobacco. Finally, it was revealed that vsiRNAs target abundant host genes, indicating complex roles for CMV vsiRNAs during the development of symptoms.


A source to deliver mesoscopic particles for laser plasma studies.
Intense ultrashort laser produced plasmas are a source for high brightness, short burst of X-rays, electrons, and high energy ions. Laser energy absorption and its disbursement strongly depend on the laser parameters and also on the initial size and shape of the target. The ability to change the shape, size, and material composition of the matter that absorbs light is of paramount importance not only from a fundamental physics point of view but also for potentially developing laser plasma sources tailored for specific applications. The idea of preparing mesoscopic particles of desired size/shape and suspending them in vacuum for laser plasma acceleration is a sparsely explored domain. In the following report we outline the development of a delivery mechanism of microparticles into an effusive jet in vacuum for laser plasma studies. We characterise the device in terms of particle density, particle size distribution, and duration of operation under conditions suitable for laser plasma studies. We also present the first results of x-ray emission from micro crystals of boric acid that extends to 100 keV even under relatively mild intensities of 1016 W/cm2.


Control of fibrotic changes through the synergistic effects of anti-fibronectin antibody and an RGDS-tagged form of the same antibody.
TGF-β and myofibroblasts play a key role in fibrosis, characterized by aberrant synthesis and deposition of extracellular matrix (ECM) proteins, such as fibronectin (Fn) and collagen type I. There are two major roles played by integrins in the fibrotic pathology: (i) Fn-integrin interaction, coupled with cytokines like TGF-β, facilitates the self-polymerization of Fn and regulates cell-matrix fibrillar adhesions, thereby promoting fibrillogenesis; (ii) Integrin interaction with an RGD (arginine-glycine-aspartic) consensus sequence in the latent TGF-β, resulting in its activation. This study describes an anti-fibrotic strategy using a combination of two antibodies: Fn52 (targeted against the N-terminal 30 kDa region of fibronectin, a major site for Fn self-association), and its engineered form, Fn52RGDS (which binds to integrins). Interestingly, a synergistic effect of the cocktail in causing a decline in fibrotic features was confirmed in the context of fibrotic posterior capsular opacification (PCO), mediated by the lens epithelial cells (left behind after cataract surgery). Inclusion of Fn52RGDS to Fn52 aids in better diffusion of the antibodies; such combination therapies could be useful in the context of pathologies involving extensive remodeling of the fibronectin matrix, where the thick ECM offers a major challenge for efficient drug delivery.


Operating in the margins: Women's lived experience of training and working in orthopaedic surgery in South Africa.
Medicine in South Africa (SA), as in other parts of the world, is becoming an increasingly gender diverse profession, yet orthopaedic surgery continues to be dominated by men, with women constituting approximately 5% of the profession in SA. The aim of this descriptive qualitative study was to explore women's experiences of training and working as orthopaedic surgeons in SA and identify structures, practices, attitudes, and ideologies that may promote or impede the inclusion of women. Data were collected via focus group discussions with women orthopaedic surgeons (n=16). Grounded in phenomenology, data were analysed using thematic analysis following a data-driven inductive approach to making sense of participants' experiences. Five main themes emerged: i) dynamic working environments and the work of transformation; ii) negotiating competing roles of mother and surgeon; iii) belonging, exclusion and internalised sexism; iv) gaslighting and silencing; and v) acts of resistance - agency and pushing back. The findings highlight the dynamic process in which both men and women contribute to co-creating, re-producing, and challenging practices that make medicine more inclusive.


Risk/benefit profile of bevacizumab in metastatic colon cancer: a systematic review and meta-analysis.
Bevacizumab, an anti vascular endothelial growth factor antibody is licensed in several tumours and widely used in colorectal cancer. However, bevacizumab has several adverse effects which may appear unexpectedly and differ according to the tumour. The aim of this work is to quantify the overall risk of bevacizumab-related side effects in patients affected by advanced colorectal cancer and to compare them with its overall benefit. We performed a systematic review and meta-analysis investigating bevacizumab in metastatic colorectal cancer. Our primary endpoint was safety and secondary endpoints were overall survival and progression-free survival. The relative risks for side effects were calculated with their 95% confidence interval using the inverse of variance method. For statistically significant relative risks, number needed to harm were calculated. We retrieved six out of 17 eligible papers encompassing 3385 patients. Only hypertension (relative risk 2.98 95% confidence interval 2.32-3.84), gastrointestinal perforations (relative risk 5.04 95% confidence interval 1.72-14.79) and bleeding (relative risk 2.07 95% confidence interval 1.19-3.62) were significantly increased. Bevacizumab significantly improved both overall survival (HR 0.80 95% confidence interval 0.71-0.91) and progression-free survival (hazard ratio (HR) 0.62 95% confidence interval 0.52-0.74). Number needed to treat for overall survival is 12, whilst number needed to harms ranges from 2 to 14.286. These results show that the benefits of the treatment with bevacizumab outweigh the toxicity that may occur: enough to justify its use in advanced colorectal cancer.


Combination therapy as first-line treatment for hypertension.
With the cut-off point between "normal" and "high" blood pressure (BP) being pushed increasingly downward, especially for patients with multiple cardiovascular risk factors, most hypertensives need more than one antihypertensive agent to reach their target BP. In this article, we examine the rationale for combining drugs from different classes that have synergistic or additive effects and properties that might offset one another's adverse hemodynamic and/or metabolic reactions. We suggest circumstances in which the initiation of therapy with a fixed two-drug combination might be preferable to the usual practice of starting with monotherapy followed by upward titration and addition of other agents, and we briefly review the existing fixed drug combinations. We end with the intriguing and provocative notion of the future "polypill," a fixed combination of agents addressing various components of the metabolic syndrome as well as other coexisting common risk factors in both high-risk patients with conditions requiring polypharmacy and in healthy, asymptomatic individuals.


Plasmin Cleaves Von Willebrand Factor at K1491-R1492 in the A1-A2 Linker Region in a Shear- and Glycan-Dependent Manner In Vitro.
Previous studies have demonstrated a role for plasmin in regulating plasma von Willebrand factor (VWF) multimer composition. Moreover, emerging data have shown that plasmin-induced cleavage of VWF is of particular importance in specific pathological states. Interestingly, plasmin has been successfully used as an alternative to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif) in a mouse model of thrombotic thrombocytopenic purpura. Consequently, elucidating the molecular mechanisms through which plasmin binds and cleaves VWF is not only of basic scientific interest but also of direct clinical importance. Our aim was to investigate factors that modulate the susceptibility of human VWF to proteolysis by plasmin. We have adapted the VWF vortex proteolysis assay to allow for time-dependent shear exposure studies. We show that globular VWF is resistant to plasmin cleavage under static conditions, but is readily cleaved by plasmin under shear. Although both plasmin and ADAMTS13 cleave VWF in a shear-dependent manner, plasmin does not cleave at the Tyr1605-Met1606 ADAMTS13 proteolytic site in the A2 domain. Rather under shear stress conditions, or in the presence of denaturants, such as urea or ristocetin, plasmin cleaves the K1491-R1492 peptide bond within the VWF A1-A2 linker region. Finally, we demonstrate that VWF susceptibility to plasmin proteolysis at K1491-R1492 is modulated by local N-linked glycan expression within A1A2A3, and specifically inhibited by heparin binding to the A1 domain. Improved understanding of the plasmin-VWF interaction offers exciting opportunities to develop novel adjunctive therapies for the treatment of refractory thrombotic thrombocytopenic purpura.


Clinical value of epidermal growth factor receptor expression in primary breast cancer.
EGFR expression in primary breast cancer has been extensively investigated for its prognostic and predictive value. However overall there is no consensus on its potential to guide such prognostication. This is largely because of the great heterogeneity in study designs and methods used to assay the EGFR protein. The impetus to standardize such studies is much needed as there are now several tyrosine kinase inhibitors directed against the EGF receptor and phase II trials are showing significant promise.


Heterologous Matrix Metalloproteinase Gene Promoter Activity Allows In Vivo Real-time Imaging of Bleomycin-Induced Lung Fibrosis in Transiently Transgenized Mice.
Idiopathic pulmonary fibrosis is a very common interstitial lung disease derived from chronic inflammatory insults, characterized by massive scar tissue deposition that causes the progressive loss of lung function and subsequent death for respiratory failure. Bleomycin is used as the standard agent to induce experimental pulmonary fibrosis in animal models for the study of its pathogenesis. However, to visualize the establishment of lung fibrosis after treatment, the animal sacrifice is necessary. Thus, the aim of this study was to avoid this limitation by using an innovative approach based on a double bleomycin treatment protocol, along with the in vivo images analysis of bleomycin-treated mice. A reporter gene construct, containing the luciferase open reading frame under the matrix metalloproteinase-1 promoter control region, was tested on double bleomycin-treated mice to investigate, in real time, the correlation between bleomycin treatment, inflammation, tissue remodeling and fibrosis. Bioluminescence emitted by the lungs of bleomycin-treated mice, corroborated by fluorescent molecular tomography, successfully allowed real time monitoring of fibrosis establishment. The reporter gene technology experienced in this work could represent an advanced functional approach for real time non-invasive assessment of disease evolution during therapy, in a reliable and translational living animal model.


Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise?
Although there is evidence that sympathetic nerves release ATP as a neurotransmitter to produce vasoconstriction via P2X purinergic receptors, the role of these receptors in the regulation of blood flow to exercising skeletal muscle has yet to be determined. We hypothesized that there is tonic P2X receptor-mediated vasoconstriction in exercising skeletal muscle. To test this hypothesis, the effect of P2X receptor blockade on skeletal muscle blood flow was examined in six exercising mongrel dogs. P2X receptor antagonism was accomplished with pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid (PPADs). Animals were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. PPADs (40 mg) was infused as a bolus into the femoral artery catheter during steady-state exercise at 6 miles/h. Intra-arterial infusion of PPADs increased iliac blood flow from 542 +/- 55 to 677 +/- 69 ml/min (P < 0.05) and iliac vascular conductance from 5.17 +/- 0.62 to 6.53 +/- 0.80 ml.min(-1).mmHg(-1). The PPADs infusion did not affect blood flow in the contralateral iliac artery. These data support the hypothesis that P2X purinergic receptors produce vasoconstriction in exercising skeletal muscle.


Investigation of the efficacy of the GnRH agonist deslorelin in mitigating intraspecific aggression in captive male Amur leopards (Panthera pardus orientalis).
Housing bachelor groups is a necessary aspect of the care and husbandry of non-breeding individuals in zoological collections. Intraspecific aggressive behaviors may occur in this setting despite management strategies designed to mitigate these behaviors. Androgens (including testosterone) are associated with aggression in male species and interventional techniques to alter the animals' physiology to modify aggressive behavior are sometimes required. When agonistic behavior and physical aggression in two mature male Amur leopards housed together at Tayto Park escalated, despite all strategic management involvements, further intervention to moderate aggression was required. The gonadotropin-releasing hormone (GnRH) agonist, deslorelin, has been found to be effective in reducing androgens in domestic and non-domestic carnivores. We hypothesized that deslorelin's suppressive effect on hypothalamic-pituitary-gonadal axis would mitigate intraspecific aggression in two male intact leopards. Behavioral observations were carried out pre- and post-implant implantation of 9.4 mg deslorelin implant. The frequency of agonistic/aggressive behaviors for both leopards declined significantly (p < 0.05), as did marking behaviors post-implantation (p < 0.001). The insertion of deslorelin implants in two male intact leopards demonstrating increased frequency and severity of aggressive behaviors resulted in a reduction of the frequency of these behaviors. Deslorelin implantation should be considered for management of interspecific aggression of intact male leopards in bachelor groups.


[Prognostic significance of programmed dialysis in patients who initiate renal substitutive treatment. Multicenter study in Spain].
The aim of our study was to analyse patient characteristics, mortality and costs, all of them in relation to whether starting dialysis was planned or unplanned. A total of 362 patients (227 male and 135 female) from five hospitals of the National Health System, who were started on chronic renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who were started on RRT after acute renal failure were excluded. We carried out a retrospective analysis of the demographic characteristics, patients' conditions at the time of initiating dialysis and outcome and costs at six and thirty-six months of treatment. Patients were classified as planned (PL-D) or unplanned dialysis (UNPL-D), depending on whether or not the patient had a vascular or peritoneal access ready to use for initiating RRT. One hundred and eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176 (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis without previous nephrological follow-up. UNPL-D was associated with older age (p < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p = 0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main primary renal diseases were glomerular and polycystic disease, whereas interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005). Multivariate analysis showed that previous non nephrological follow-up, uraemic symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D was also associated with increased number of days of hospitalization at the initiation of dialysis, and during the first 6 months (p < 0.001), increase of hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%) (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006, log rank test). The costs of UNPL-D were fivefold that of the PL-D group. UNPL-D has been associated with worse overall clinical conditions at the initiation of chronic replacement therapy, choosing haemodialysis as first RRT, increased morbi-mortality and subsequent increase of costs.


Gordonia bacteremia.
Gordonia species are ubiquitous aerobic actinomycetes that rarely cause infection in humans. We report the second known case of Gordonia otitidis catheter-related bacteremia in an immunocompromised patient and review four additional cases of Gordonia bacteremia seen at our institution over the past 14 years. In addition, the existing literature on Gordonia infections is reviewed.


Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).
Recent years have seen a worldwide resurgence in serious infections caused by group A streptococci. This group includes Streptococcus pyogenes, one of the most common pathogens among children which causes diverse suppurative infections, such as pharyngitis, as well as nonsuppurative infections with sequelae, such as rheumatoid fever and rheumatic heart disease. S. pyogenes produces several superantigen-like erythrogenic toxins, which are believed to be associated with pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic effects. These toxins also can cause myocardial necrosis. In addition, recently reported streptococcal infections in obstetric human patients appear to be clinically different from classic puerperal sepsis. Here, we report a case of spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca mulatta). In addition to lesions consistent with bacteremia and toxic shock, this animal had severe cardiac lesions resembling those described in humans with rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver, placenta, and fetal tissues. This isolate also had a unique M protein gene.


Prevalence of premature loss of deciduous teeth and its relationship with gender among children from Acapulco, Guerrero: a cross-sectional study.
Premature loss of deciduous teeth is the exfoliation or extraction before physiological replacement with < 50% or < 75% of the root of the substitute tooth formed or if there is > 1 mm of alveolar bone covering the permanent successor tooth organ. This study aimed to estimate the prevalence of premature tooth loss in children and identify associated factors in a health center in Acapulco, Guerrero. We conducted a cross-sectional study in which we collected information from 109 clinical records of children examined from January 2019 to August 2021. Sociodemographic data of the children and parents were collected: socioeconomic level, non-pathological personal history, and the history of premature deciduous tooth loss. Multivariate analysis to identify factors associated with premature deciduous tooth loss was performed with CIETmap statistical software. Odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the association. The prevalence of premature loss of primary teeth was 40% (43/109). The leading cause was caries (84%, 36/43). The tooth organ with the highest loss occurrence was the lower right second molar (33%, 14/43). Gender was identified as an associated factor, with males having a higher risk of loss (ORa = 2.97; CI95% = 1.33-6.65). Our results were similar to those reported in other studies. Strategies aimed at health promotion directed at parents and children should be reinforced.


Stereotactic radiotherapy for the treatment of nonacoustic schwannomas.
Nonacoustic schwannomas are rare tumors in contrast to the most common neuromas of Cranial Nerve VIII. The current treatment of choice in these cases is microsurgical resection, but the risk of postoperative complications is high, especially in cavernous sinus-invading tumors. In many of these cases, it is not possible to achieve complete tumor removal, resulting in the probability of recurrences. For those patients, radiosurgery (RS) or stereotactic radiotherapy (SRT) can offer an alternate treatment. Within a 5-year period (2000-2005), 19 intracranial nonacoustic neuromas were treated with SRT-13 trigeminal neuromas, five neuromas of the lower cranial nerves (jugular foramen), and one located in the orbital region. Of these cases, there were nine women and 10 men who were, on average, 54 years of age (range, 33-83 yr). Eight patients had previously undergone surgery elsewhere and showed progressive tumor growth. All 19 patients were treated with SRT: 15 with normal fractions of 1.8-2 Gy single dose up to 54-59.4 Gy. Their irregular tumor volume ranged from 4.2 to 43.1 ccm (average: 14.1 ccm). Hypofractionation with 6 to 7 x 5 Gy was applied in four cases with an average tumor volume of 4.1 ccm (2.2-6.2 ccm). Clinical results and the efficacy for tumor control with an average follow-up of 35 months (11-63 mo) were evaluated. Local tumor control rate was 95% (18 of 19 cases): one patient previously operated on had a recurrence of tumor progression after SRT, followed by a second subtotal resection. A tumor regression was proved in 11 cases (one neuroma disappeared and four patients had tumor shrinkage of more than 50%, the other six experienced shrinkage between 20% and 40%). Within the first 6 months, two patients developed temporarily increased tumor volume as well as a confirmed reaction to irradiation. In one of these two cases, there were mild side effects according to CTC Grade I. No patient experienced a new or increased neurological deficit. Improvement of their cranial nerve disturbances was achieved in 11 of 19 patients and the other eight showed no clinical changes. The mostly moderate trigeminal pain decreased slowly. SRT is a low-risk and effective treatment option for intracranial neuromas. Particularly in cases of sinus cavernous-invading trigeminal and in jugular foramen tumors, SRT can be the treatment of choice. Concerning tumor regression, SRT is as effective as RS.


Nonclassical velocity statistics in a turbulent atomic Bose-Einstein condensate.
In a recent experiment Paoletti [Phys. Rev. Lett. 101, 154501 (2008)]10.1103/PhysRevLett.101.154501 monitored the motion of tracer particles in turbulent superfluid helium and inferred that the velocity components do not obey the Gaussian statistics observed in ordinary turbulence. Motivated by their experiment, we create a small 3D turbulent state in an atomic Bose-Einstein condensate, compute directly the velocity field, and find similar nonclassical power-law tails. We obtain similar results in 2D trapped and 3D homogeneous condensates, and in classical 2D vortex points systems. This suggests that non-Gaussian turbulent velocity statistics describe a fundamental property of quantum turbulence. We also track the decay of the vortex tangle in the presence of the thermal cloud.


A Memorable Moment During Laparoscopic Cholecystectomy: A Case Report.
Common bile duct (CBD) stones are encountered in 14%-15% of patients with symptomatic gall stone disease. Endoscopic retrograde cholangiopancreatography (ERCP) is a primary modality for the management of pancreaticobiliary disorders. We present a case of unintentional stent placement into the gall bladder discovered during surgery.


Giant congenital melanocytic nevi: 40 years of experience with the serial excision technique.
Although giant congenital melanocytic nevus is a rare lesion, it causes significant deformity and carries a risk of malignant degeneration. Different surgical techniques for the lesion removal are described, including serial resection, resection with skin grafting, and resection and coverage with expanded skin flap (skin expanders). The aim of this study is to report the author's 40 years of experience with cases requiring at least 4 serial excisions to complete the treatment. Serial resection is an effective, safe, and simple technique that requires a lot of patience. Treatment often results in a single linear scar, requires no donor sites, nor large flaps. It is not subject to potencial complications of expanders and avoid aesthetic deformities depending on the location.


[Recurrent goitre: our experience].
Recurrence after conservative thyroid surgery ranges from 7 to 40%. Risk factors for recurrence are female sex, multiple nodules in the resected lobe and lack of postoperative LT4 therapy. Indications for reoperation are suspected malignancy, recurrent thyrotoxicosis and recurrent uninodular or multinodulare goitre. From 2002 to 2008, 2149 total thyroidectomies were performed. Ninety-two patients had a completion thyroidectomy. The indication was recurrent multinodular goitre in 81, recurrent thyrotoxicosis in 3, and suspected malignancy in 8. Bilateral completion thyroidectomy was performed in 63 cases, lobectomy in 27 cases, removal of a mediastinal recurrence in 1 case and removal of a pyramidal remnant in 1 case. Histological examination revealed papillary cancer in 18 patients and follicular cancer in 1. Mean operative time was 140 minutes (range: 60-260). All patients were submitted to a minimum follow-up of 6 months. Temporary hypoparathyroidism occurred in 36 patients (39.1%) and definitive hypoparathyroidism in 7 patients (7.6%). Transient recurrent laryngeal nerve palsy occurred in 3 cases (3.2%) and permanent nerve palsy in 1 (1.1%). In 3 cases (3.2%) surgical revision of haemostasis was necessary for postoperative haemorrhage. Total thyroidectomy is the treatment of choice in multinodular goitre. In the cases in which reoperation is necessary, the intervention must be performed by an experienced surgeon.


[The role of computerized tomography in the staging of lung cancer].
Staging of lung cancer place significant role in the prognosis and treatment of the disease. Beside bronchoscopy, CT one of the important method for the tumor staging. 135 CT examinations with diagnosis of suspected lung cancer were evaluated and radiologic diagnosis was compared with the cyto-histological and surgical results. In 112 cases both CT and histological diagnosis were performed: both method revealed malignant tumors in 108 cases. Five lesions were regarded as tumour by CT but histological result proved aspergilloma, or specific processes. Abnormal lymph nodes were recognised at 98 tumours patients. There was a good correlation-regarding the number, size measurement-between CT and surgery. Histological diagnosis proved that all of the lymph nodes larger, then 2 cm of diameter contained metastic cells. In the 1-2 cm size almost all of the lymph nodes were metastatic. In addition tumour cells were found in some lymph nodes smaller, than 1 cm, too. This gives warning sign: smaller lymph nodes need more attention than we assumed. CT prove to be confident method for the evaluation, measurement and localisation of the tumours and lymph nodes in the chest.


Valacyclovir to expedite the clearance of recurrent herpes gladiatorum.
To determine if valacyclovir usage expedites the clearance of recurrent herpes gladiatorum (HG) in wrestlers. Double-blind, placebo-controlled, prospective study using valacyclovir from September 2001 through March 2003. Twenty-nine wrestlers were recruited from the Minneapolis-St. Paul, Minnesota area. They ranged in ages from 18 to 36, of whom 7 were coaches and 22 active wrestlers. All participants had greater than 2-year history of recurrent HG. Upon an outbreak, all participants would swab the area on a daily basis for 14 days. Swabs were analyzed for herpes simplex virus 1/2 via PCR. End point was determined as the last sample with measurable PCR detected. Individuals were randomly selected, yet equally distributed, to be in 1 of 3 groups: placebo x 7 days, valacyclovir 500 mg BID x 7 days, or valacyclovir 1,000 mg QD x 7 days. Twenty participants (3 coaches and 17 active wrestlers) experienced outbreaks. All participants were compliant and started medication within 24 hours of developing symptoms. Valacyclovir usage showed significant reduction in mean time until PCR clearance, 8.14 days with placebo versus 6.43 days with valacyclovir 500 mg BID. A 7-day regimen of valacyclovir 500 mg BID will reduce the length of time until clinical clearance of an outbreak of recurrent HG. Its usage reduced duration of viral presence by 21%.


Treatment of aniridia with Boston type I keratoprosthesis.
To report the outcomes of Boston keratoprosthesis (K-pro) type I implantation for congenital aniridia. A retrospective review of the medical records of every patient with congenital aniridia who underwent Boston K-pro type I implantation at the University of Iowa Hospitals and Clinics from January 1, 2009, through December 31, 2011 was performed. The main outcome measures were visual acuity, graft retention, and postoperative complications. A total of 7 eyes (7 patients) met the inclusion criteria. The mean patient age was 52 years (range, 12-85 years). The preoperative visual acuity was 20/1600 in 6 eyes (85.7%) and hand motions in 1 eye (14.3%). After a median follow-up period of 18 months (range, 3-30 months), the median final best spectacle-corrected visual acuity was 20/200 (range, 20/100 to light perception). This included 2 eyes (28.6%) that were 20/100 and 5 eyes (71.4%) that were better than 20/300. Compared with the preoperative best spectacle-corrected visual acuity, the final vision was improved in 6 eyes (85.7%) and worse in 1 eye (14.3%). The K-pro graft was retained in all 7 eyes (100%). The most common complication was the formation of a retroprosthetic membrane in 3 eyes (42.9%), none of which required either a YAG capsulotomy or a vitrectomy. One eye (14.3%) developed a wound dehiscence that required surgical repair. The Boston K-pro type I is a good option for the visual rehabilitation of eyes with congenital aniridia.


Retinoblastoma Protein Paralogs and Tumor Suppression.
The retinoblastoma susceptibility gene (RB1) is the first tumor suppressor gene discovered and a prototype for understanding regulatory networks that function in opposition to oncogenic stimuli. More than 3 decades of research has firmly established a widespread and prominent role for RB1 in human cancer. Yet, this gene encodes but one of three structurally and functionally related proteins that comprise the pocket protein family. A central question in the field is whether the additional genes in this family, RBL1 and RBL2, are important tumor suppressor genes. If so, how does their tumor suppressor activity overlap or differ from RB1. Here we revisit these questions by reviewing relevant data from human cancer genome sequencing studies that have been rapidly accumulating in recent years as well as pertinent functional studies in genetically engineered mice. We conclude that RBL1 and RBL2 do have important tumor suppressor activity in some contexts, but RB1 remains the dominant tumor suppressor in the family. Given their similarities, we speculate on why RB1 tumor suppressor activity is unique.


Metal-Free Photoinduced Electron Transfer-Atom Transfer Radical Polymerization Integrated with Bioinspired Polydopamine Chemistry as a Green Strategy for Surface Engineering of Magnetic Nanoparticles.
Developing green and efficient technologies for surface modification of magnetic nanoparticles (MNPs) is of crucial importance for their biomedical and environmental applications. This study reports, for the first time, a novel strategy by integrating metal-free photoinduced electron transfer-atom transfer radical polymerization (PET-ATRP) with the bioinspired polydopamine (PDA) chemistry for controlled architecture of functional polymer brushes from MNPs. Conformal PDA encapsulation layers were initially generated on the surfaces of MNPs, which served as the protective shells while providing an ideal platform for tethering 2-bromo-2-phenylacetic acid (BPA), a highly efficient initiator. Metal-free PET-ATRP technique was then employed for controlled architecture of poly(glycidyl methacrylate) (PGMA) brushes from the core-shell MNPs by using diverse organic dyes as photoredox catalysts. Impacts of light sources (including UV and visible lights), photoredox catalysts, and polymerization time on the composition and morphology of the PGMA brushes were investigated. Moreover, the versatility of the PGMA-functionalized core-shell MNPs was demonstrated by covalent attachment of ethylenediamine (EDA), a model functional molecule, which afforded the MNPs with improved hydrophilicity, dispersibility, and superior binding ability to uranyl ions. The green methodology by integrating metal-free PET-ATRP with facile PDA chemistry would provide better opportunities for surface modification of MNPs and miscellaneous nanomaterials for biomedical and electronic applications.


[International health research: priorities and commitment].
Of the global budget for health research, only 10% is spent on the disease burden of 90% of the world's population. Investments for international health research are lacking, hampering health for the poor. Effective vaccines against the world killers HIV, malaria and tuberculosis still do not exist. However, in order to understand the obstacles to implementing existing effective interventions, scaling up research for new drugs and vaccines must be accompanied by research in health systems, to understand the obstacles to implement existing effective interventions. The task demands political and private sector commitment.


Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart.
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart. Genetic disruption of the circadian clock in cardiomyocyte-specific Bmal1 knockout (CBK) and cardiomyocyte-specific Clock mutant (CCM) mice altered expression (gene and protein) of multiple insulin signaling components in the heart, including p85α and Akt. Both baseline and insulin-mediated Akt activation was augmented in CBK and CCM hearts (relative to littermate controls). However, insulin-mediated glucose utilization (both oxidative and non-oxidative) and AS160 phosphorylation were attenuated in CBK hearts, potentially secondary to decreased Inhibitor-1. Consistent with increased Akt activation in CBK hearts, mTOR signaling was persistently increased, which was associated with attenuation of autophagy, augmented rates of protein synthesis, and hypertrophy. Importantly, pharmacological inhibition of mTOR (rapamycin; 10days) normalized cardiac size in CBK mice. These data suggest that disruption of cardiomyocyte circadian clock differentially influences insulin-regulated processes, and provide new insights into potential pathologic mediators following circadian disruption.


Changes of kallikrein and serotonin in plasma during and after open-heart surgery.
Plasma kallikrein activity and plasma serotonin were studied during and after open-heart surgery in 15 patients with extracorporeal circulation and in 15 patients with surface-induced deep hypothermia. Following results were obtained: 1) Plasma kallikrein activity which reflects the activation of the kinin system, showed no significant change during extracorporeal circulation, and significantly increased three hours after the termination of perfusion. However, there was no significant difference in plasma kallikrein activity between the patients with and without low cardiac output syndrome (LOS). In surface-induced deep hypothermia, plasma kallikrein activity showed no significant change during and after operation. 2) Plasma serotonin significantly decreased during both extracorporeal circulation and hypothermia. Moreover, there was no significant difference in plasma serotonin between the patients with and without postoperative LOS or pulmonary hypertension. It is assumed that plasma serotonin may not play an important role in regulating blood pressure during or after open-heart surgery with either extracorporeal circulation or surface-induced deep hypothermia.


Widefield two laser interferometry.
A novel system has been developed that can capture the wide-field interference pattern generated by interfering two independent and incoherent laser sources. The interferograms are captured using a custom CMOS modulated light camera (MLC) which is capable of demodulating light in the megahertz region. Two stabilised HeNe lasers were constructed in order to keep the optical frequency difference (beat frequency) between the beams within the operational range of the camera.This system is based on previously reported work of an ultrastable heterodyne interferometer [Opt. Express 20, 17722 (2012)]. The system used an electronic feedback system to mix down the heterodyne signal captured at each pixel on the camera to cancel out the effects of time varying piston phase changes observed across the array. In this paper, a similar technique is used to track and negate the effects of beat frequency variations across the two laser pattern. This technique makes it possible to capture the full field interferogram caused by interfering two independent lasers even though the beat frequency is effectively random.As a demonstration of the system's widefield interferogram capture capability, an image of a phase shifting object is taken using a very simple two laser interferometer.