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BACKGROUND: Currently no consensus guidelines on the evaluation and therapy of chronic cough in children have been published in German. Aim of this study was therefore, after a literature search on all relevant publications and guidelines concerning chronic cough in children, to publish a Statement of the Austrian Society of Pediatrics and The Austrian Society of Pneumology on the evaluation and therapy of chronic childhood cough and to publish a practice based approach. Aim was also to differentiate cough clearly from obstructive airway diseases and to summarize all relevant differential diagnosis using relevant patient history and clinical characteristics and give an overview of therapeutical approaches. The subjective component of cough and the difficulty to assess cough in an objective manner is discussed. METHODS: A Cochrane and Medline Search were performed on all relevant literature until Mai 2013. RESULTS: Chronic cough in children is defined as daily cough for more than 4 weeks. Duration of 3 to 8 weeks is sometimes called prolonged or sub-acute cough. Chronic cough may have specific cause and may be a symptom of an underling disease, which needs to be found and treated adequately. Unspecific cough may only be diagnosed after exclusion of all other causes. Any therapeutical approach needs to be re- evaluated and efficacy needs to be reviewed. Parental understanding of the etiology of cough in general and the influence of environmental exposures is essential for diagnosis. CONCLUSION: Chronic cough needs a detailed history and various differential diagnoses need to be taken in consideration. Children with persistent complaints without a proper diagnosis need to be seen in a center specialized in Pediatric Respiratory Medicine. | Cough |
Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation. The cooperation of spliced XBP1 and STAT3 reinforced the pro-tumorigenic phenotype and expression of immunosuppressive genes. Ablation of XBP1 expression with genetic manipulation or ameliorating ER stress responses by facilitating LPCAT3-mediated incorporation of unsaturated lipids to the phosphatidylcholine hampered pro-tumorigenic phenotype and survival in TAMs. Together, we uncover the unexpected roles of tumor-cell-produced lipids that simultaneously orchestrate macrophage polarization and survival in tumors via induction of ER stress responses and reveal therapeutic targets for sustaining host antitumor immunity. | X-Box Binding Protein 1 |
Most of antisense oligonucleotides (ASOs) subjected to current clinical evaluation belong to phosphorothioate (PS) analogues. Although PS has great advantage in DNase resistance, it can induce nonspecific side-effects. Thus it is important to investigate the influence of ASOs with different PS contents. In this paper, we prepared the complex consisting of schizophyllan (SPG) and ASOs attached a dA(4)(0) tail with different PS contents to the 3' end of the ODN, which is introduced to stabilize the complex with SPG. With increase of PS content in the dA(4)(0), its complexation ability with SPG was improved and the complex showed high thermal stability. The thermal stability of the fully phosphorothioated ASOs was obtained by only replacing 20% of the oxygen of the phosphodiester moiety. The ability of gene suppression between PS and phosphodiester for antisense sequences was almost the same, indicating that the antisense sequences need not to be PS backbone. These data may provide new insight for the interaction between beta-1,3-glucan and DNA and help to deliver therapeutic ODNs. | Sizofiran |
AIM OF THE STUDY: San-bai-tang (SBT), a Chinese herbal formula, is traditionally used as a skin whitener in China. In our previous screening assays, SBT was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the anti-melanogenic effect and mechanisms of SBT in B16 cells. MATERIALS AND METHODS: Cell viability was examined by the MTT assay. Cellular tyrosinase activity and melanin content were determined using spectrophotographic methods. Protein expression was analyzed by immunoblotting. RESULTS: SBT inhibited tyrosinase activity with an IC(50) of 215.6 +/- 10.3 mug/ml, and decreased cellular melanin content with an IC(50) of 254.8 +/- 14.5 mug/ml at 48 h. MTT assay demonstrated that 48-h SBT (50-400 mug/ml) treatment did not show obvious cytotoxicity. Immunoblot analysis showed that SBT (100, 200 or 400 mug/ml) treatment for 48 h down-regulated the expression levels of phosphorylated-p38, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. CONCLUSIONS: SBT inhibited melanogenesis in B16 cells, and suppression of p38 MAPK signaling pathway contributed to the anti-melanogenic effect of SBT by down-regulating the expression of MITF and melanogenic enzymes. These novel findings demonstrated the anti-melanogenic effect and mechanisms of SBT, and provide pharmacological basis for the traditional use of SBT. | Smilax |
The level of serum angiopoietin-like protein 8 (ANGPTL8), a novel hepatokine, is associated with obesity and type 2 diabetes mellitus (T2DM). The aims of this study were to investigate whether serum ANGPTL8 level in patients with T2DM was affected by treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, and to determine whether and how GLP-1R agonists regulated ANGPTL8 production in hepatocytes. A multiple-center trial was conducted in China. Among 240 patients with T2DM enrolled in this trial, 195 patients adhered to a 16-week exenatide treatment and follow-up. Human liver cell line HepG2 cells were incubated for 24â¯h with either exendin-4 (a native form of exenatide) or liraglutide in the presence or absence of GLP-1R antagonist exendin (9-39) and PI3K inhibitor LY294002. Change of serum ANGPTL8 level in patients with T2DM and regulation of ANGPTL8 production by the GLP-1R agonists in HepG2 cells were evaluated. Results showed that compared with baseline, exenatide treatment significantly increased serum ANGPTL8 level, and lowered body weight, fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) in patients with T2DM (all Pâ¯<⯠0.05). The exenatide treatment-mediated upregulation of serum ANGPTL8 level was not associated with the levels of its lowering effects on body weight, FBG and HbA1c stratified by the median. Moreover, exendin-4 or liraglutide dose-dependently upregulated the level of ANGPTL8 expression and secretion in HepG2 cells, which was eliminated by adding exendin (9-39) and LY294002. In conclusion, GLP-1R agonists enhance ANGPTL8 production in vivo and in vitro, which is mediated via the PI3K/Akt pathway in a GLP-1R-dependent manner. | Angiopoietin-Like Protein 8 |
Poloxamer 188, a commonly used emulsifying and solubilizing agent, was found to be the cause of crystallization of an investigational drug, AMG 579, from its amorphous solid dispersion at accelerated storage conditions. Investigation of this physical stability issue included thorough characterization of poloxamer 188 at non-ambient conditions. At 40 degrees C, poloxamer 188 becomes deliquescent above relative humidity of 75%. Upon returning to ambient conditions, the deliquescent poloxamer 188 loses water and re-solidifies. The reversible phase transformation of poloxamer 188 may cause physical and chemical stability issues and this risk should be assessed when selecting it as an excipient for formulation development. | Poloxamer |
Apoptosis is a genetically in-built process whereby organisms remove unwanted cells. Apoptosis can serve as a regulatory and defense mechanism in the formation of the shape and size of the human body and also to eradicate surplus amount of cells. The regulation of apoptosis is relevant and differentiates between a normal cells of body and cancer cells by loss of control. Apoptosis being an intricate process regulated by much more than just a biological mechanism. The induction of the apoptosis manifests the control on the tumour size and number of tumour cells hence establishing the application of apoptotic inducers as vital components in the treatment of cancer. During apoptosis, cells die in a controlled and regulated fashion which makes apoptosis distinct from necrosis (uncontrolled cell death). Protein components and regulators for apoptosis signaling pathways can involve the mitochondria (intrinsic pathway) or signal through death receptors (extrinsic pathway). Many different drug and gene therapy approaches are being tested for initiating apoptosis. Resistance to apoptosis is considered a hallmark of cancer. Therapeutic approaches attempted to date include traditional small molecules, antisense oligonucleotides, monoclonal antibodies, recombinant proteins and several classes of chemical compounds discussed in this review. These compounds may serve as precursor molecules for more effective drugs, all aimed at developing clinically effective therapeutics, targeting key apoptosis regulatory mechanism. This review will discuss the current understanding of apoptosis induced by various chemical agents and highlighting the role of apoptosis inducing agents as emerging opportunities for cancer therapy. | Receptors, Death Domain |
We compared the characteristics of seeds within faeces between semi-terrestrial Japanese macaques (Macaca fuscata) and sympatric arboreal Japanese martens (Martes melampus) in Shiga Heights, central Japan. We collected faecal samples of the two mammalian species for 1 year (n = 229 for macaques and n = 22 for martens). We then compared the proportion of seed occurrence, life-form composition, number of seeds and species richness within single faecal samples, and the seed intact ratio between the two mammalian species. We detected seeds from 20 and 7 species from macaque and marten faeces, respectively. Macaque faeces contained seeds of multiple strata, while marten faeces contained no herbaceous plant seeds. Seed sizes within faeces showed no interspecific difference. For macaques, seeds were found within faecal samples collected in late spring to late fall, while for martens, seeds were found between summer and winter. The proportion of seed occurrence was greater in summer (both species) and fall (macaques), which implied that the seed dispersal roles of macaques and martens was greater in these seasons. The mean seed number (across species), intact ratio of seeds (high for both species) and seed species richness within single faecal samples of macaques and martens showed no significant differences, but for several species, martens defecated more seeds than macaques and showed higher intact ratio. Our study indicates that sympatric mammals in the temperate regions of Japan contribute differently to seed dispersal in forest ecosystems. | Macaca fuscata |
Fifty-eight encopretic children were placed on a habit training regimen consisting of initial disimpaction followed by attempts to defecate after a specific meal, and use of enemas contingent on failure to defecate for 2 successive days. All patients had gross incontinence of long duration. After an average of less than four visits in 5 months, 83% had an excellent outcome, 60% were completely continent, and 23% had only staining. Patients not achieving continence averaged a 90% decrease in frequency of incontinence. The mean frequency of incontinent episodes decreased from 13.2 to 0.52 per week, while appropriate bowel movements increased from 3.8 to 5.9 per week. At follow-up (average of 3 years), 61% of 43 patients contacted had excellent outcomes, 51% were continent, and 10% had only staining. Patients still incontinent at follow-up averaged 89% fewer episodes than they had prior to treatment. These findings show habit training to be a rapidly effective and long-lasting treatment for encopresis secondary to chronic constipation. | Elimination Disorders |
Parkinson's disease (PD) is the second most unconcealed neurodegenerative disorder labelled with motor impairments. Two pesticides, manganese ethylene-1,2-bisdithiocarbamate (maneb) and 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat), together, are reported to increase the incidence of PD in humans and Parkinsonism in mice. Conversely, silymarin and melatonin, two naturally occurring antioxidants, rescue from maneb- and paraquat-induced Parkinsonism. The study examined silymarin- and melatonin-mediated changes in the expression of selected genes in maneb- and paraquat-induced Parkinsonism employing mouse discover chips microarrays. The mice were treated intraperitoneally (i.p.), daily, with silymarin (40 mg/kg) or melatonin (30 mg/kg) for 9 weeks along with vehicles. Subsets of animals were also treated with maneb (30 mg/kg; i.p.) and paraquat (10 mg/kg; i.p.), twice a week, for 9 weeks. Whilst the expression of genes in the striatum was determined by microarray, the expression of randomly selected transcripts was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Combined maneb- and paraquat-treatment altered the expression of several genes associated with apoptosis, inflammation, cell cycle, cell-signalling, etc. pathways. Silymarin and melatonin significantly resisted the changes in the expression of a few genes related to apoptosis, inflammation, cell cycle, cell-signalling, etc. The expression patterns of seven randomly selected genes were analyzed by qRT-PCR, which were found to follow the similar trends, as observed with microarray. The results obtained from the study thus demonstrate that despite resemblances, silymarin and melatonin differentially offset maneb- and paraquat-induced changes in transcriptome. | Maneb |
Pressures to publish, perverse incentives, financial interest and gender are amongst the most commonly discussed risk factors for scientific misconduct. However, evidence of their association with actual data fabrication and falsification is inconclusive. A recent case-controlled analysis of articles containing problematic image duplications suggested that country of affiliation of first and last authors is a significant predictor of scientific misconduct. The same analysis found null or negative associations with individual proxies of publication rate, impact and gender. The latter findings, in line with previous evidence, failed to support common hypotheses about the prevalence and causes of misconduct, but country-level effects may have confounded these results. Here we extend and complete previous results by comparing, via matched-controls analysis, articles from authors in the same country. We found that evidence for individual-level risk factors may be significant in some countries, and null or opposite in others. In particular, in countries where publications are rewarded with cash incentives, and especially China, the risk of problematic image duplication was higher for more productive, more frequently cited, earlier-career researchers working in lower-ranking institutions, in accordance with a misaligned incentives" explanation for scientific misconduct. However, a null or opposite pattern was observed in all other countries, and especially the USA, UK and Canada, countries where concerns for misaligned incentives are commonly expressed. In line with previous results, we failed to observe a statistically significant association with industry funding and with gender. This is the first direct evidence of a link between publication performance and risk of misconduct and between university ranking and risk of misconduct. Commonly hypothesised individual risk factors for scientific misconduct, including career status and productivity, might be relevant in countries where cash-reward policies generate perverse incentives. In most scientifically active countries, however, where other incentives systems are in place, these patterns are not observed, and other risk factors might be more relevant. Policies to prevent and correct scientific misconduct may need to be tailored to a countries' or institutions' specific context." | Professional Misconduct |
BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA-approved medications is an evidence-based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention treatment. METHODS: Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone. RESULTS: Emerging practices for extended-release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended-release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. ((c) 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177-187). | Opioid-Related Disorders |
Connections of motor areas in the frontal cortex of prosimian galagos (Otolemur garnetti) were determined by injecting tracers into sites identified by microstimulation in the primary motor area (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), frontal eye field (FEF), and granular frontal cortex. Retrogradely labeled neurons for each injection were related to architectonically defined thalamic nuclei. Nissl, acetylcholinesterase, cytochrome oxidase, myelin, parvalbumin, calbindin, and Cat 301 preparations allowed the ventral anterior and ventral lateral thalamic regions, parvocellular and magnocellular subdivisions of ventral anterior nucleus, and anterior and posterior subdivisions of ventral lateral nucleus of monkeys to be identified. The results indicate that each cortical area receives inputs from several thalamic nuclei, but the proportions differ. M1 receives major inputs from the posterior subdivision of ventral lateral nucleus while premotor areas receive major inputs from anterior parts of ventral lateral nucleus (the anterior subdivision of ventral lateral nucleus and the anterior portion of posterior subdivision of ventral lateral nucleus). PMD and SMA have connections with more dorsal parts of the ventral lateral nucleus than PMV. The results suggest that galagos share many subdivisions of the motor thalamus and thalamocortical connection patterns with simian primates, while having less clearly differentiated subdivisions of the motor thalamus. | Ventral Thalamic Nuclei |
Hemifacial spasm (HFS) is a movement disorder characterized by involuntary contractions of the facial muscles innervated by the seventh cranial nerve. Generally, it is associated with a poor quality of life due to social embarrassment and can lead to functional blindness. Moreover, it is a chronic condition, and spontaneous recovery is rare. Intramuscular injections of Botulinum Toxin (BoNT) are routinely used as HFS treatment. METHODS: We reviewed published articles between 1991 and 2021 regarding the effectiveness and safety of BoNT in HFS as well as any reported differences among BoNT formulations. RESULTS: The efficacy of BoNT for HFS treatment ranged from 73% to 98.4%. The mean duration of the effect was around 12 weeks. Effectiveness did not decrease over time. Adverse effects were usually mild and transient. The efficacy and tolerability of the different preparations appeared to be similar. Among the studies, dosage, injected muscles, intervals of treatment, and rating scales were variable, thus leading to challenges in comparing the results. CONCLUSIONS: BoNT was the treatment of choice for HFS due to its efficacy and safety profile. Further studies are needed to investigate the factors that influence the outcome, including the optimal timing of treatment, injection techniques, dosage, and the best selection criteria for formulations. | Botulinum Toxins, Type A |
As respiratory difficulty may accompany nipple feeding in preterm neonates, we studied the effect of oral feeding on ventilation in 23 preterm infants. The infants composed two groups based on their postconceptional age at the time of study: Group A comprised 12 infants 34 to 35.9 weeks of age, and group B, 11 infants 36 to 38 weeks. Ventilation was measured via a nasal mask pneumotachometer, and sucking pressure via a nipple that also permitted milk delivery; transcutaneous PO2 and PCO2 were continuously monitored. The feeding pattern comprised an initial period of continuous sucking of at least 30 seconds, followed by intermittent sucking bursts for the remainder of the feed. When compared with an initial semi-upright control period, minute ventilation (V1) during continuous sucking fell by 52 +/- 6% (P less than 0.001) and 40 +/- 2% (P less than 0.001) in groups A and B, respectively. This was the result of a decrease in respiratory frequency and tidal volume and was associated with a fall in TcPO2 of 13 +/- 4 mm Hg (P less than 0.01) in group A and 10 +/- 2 mm Hg (P less than 0.01) in group B. During intermittent sucking, V1 and TcPO2 recovered partially only in the more mature infants (group B). At the end of the feed, TcPCO2 have risen by 3 +/- 1 mm Hg (P less than 0.001) in group A and by 2 +/- 2 mm Hg (P less than 0.05) in group B. Thus oral feeding results in an impairment of ventilation during continuous sucking and the subsequent recovery during intermittent sucking is dependent on postconceptional age. | Total Lung Capacity |
The advancement of science and technology has led to the recent development of highly sensitive pathogen biosensing techniques. The effective treatment of pathogen infections requires sensing technologies to not only be sensitive but also render results in real-time. This review thus summarises the recent advances in optical surface plasmon resonance (SPR) sensor technology, which possesses the aforementioned advantages. Specifically, this technology allows for the detection of specific pathogens by applying nano-sized materials. This review focuses on various nanomaterials that are used to ensure the performance and high selectivity of SPR sensors. This review will undoubtedly accelerate the development of optical biosensing technology, thus allowing for real-time diagnosis and the timely delivery of appropriate treatments as well as preventing the spread of highly contagious pathogens. | Surface Plasmon Resonance |
Replication provides verification and disconfirmation functions for the scholarly fields. Relatively few replications were found in a survey of studies in JSHD and JSHR over a recent decade. Based on the probabilities of Type I and Type II errors, there are likely to be approximately 50 to 250 false findings in this literature. Because many studies had relatively small sample sizes, replication would be helpful for extending the generalization of their results. These data underscore the urgency for more replications in the field. | Allied Health Occupations |
RPL10 encodes ribosomal protein L10 (uL16), a highly conserved multifunctional component of the large ribosomal subunit, involved in ribosome biogenesis and function. Using X-exome resequencing, we identified a novel missense mutation (c.191C>T; p.(A64V)) in the N-terminal domain of the protein, in a family with two affected cousins presenting with X-linked intellectual disability, cerebellar hypoplasia, and spondylo-epiphyseal dysplasia (SED). We assessed the impact of the mutation on the translational capacity of the cell using yeast as model system. The mutation generates a functional ribosomal protein, able to complement the translational defects of a conditional lethal mutation of yeast rpl10. However, unlike previously reported mutations, this novel RPL10 missense mutation results in an increase in the actively translating ribosome population. Our results expand the mutational and clinical spectrum of RPL10 identifying a new genetic cause of SED and highlight the emerging role of ribosomal proteins in the pathogenesis of neurodevelopmental disorders. | Ribosomal Protein L10 |
We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild." | Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
Cord blood T lymphocytes proliferated in vitro in response to mycobacterial organisms but did not proliferate in the presence of tuberculin purified protein derivative. Components recognized by cord blood T cells were resistant to protease digestion. In contrast, T lymphocytes derived from tuberculin-positive adult peripheral blood proliferated when stimulated by the protease-sensitive component of mycobacterial organisms or purified protein derivative, confirming that adult T cells respond to protein components whereas cord blood T cells respond to the nonpeptide component of mycobacteria. In vitro culture of cord blood lymphocytes stimulated by either mycobacterial lysates or the lipid fraction showed increases in the numbers of T-cell receptor (TcR) gamma/delta T lymphocytes with no changes in the numbers of TcR alpha/beta T lymphocytes in contrast to the in vitro cultures of adult blood lymphocytes stimulated with mycobacterial ligands in which no increase of TcR gamma/delta cells was observed. Interleukin-2 receptor (CD25) and Ia antigen (HLA-DR) analyses evidenced the activation of a large proportion of cord blood gamma/delta T cells which had increased after stimulation with mycobacteria in vitro. Further characterization of mycobacterial ligand suggested that the lipid fraction of mycobacterial lysate or trehalose dimycolate-cord factor was the most plausible cause for T-cell proliferation in cord blood. These results suggest that when the gamma/delta T cells in a newborn infant not yet sensitized to any pathogenic organisms are confronted by a mycobacterium, they respond nonspecifically to the mycobacterial organism or its lipid component (cord factor). gamma/delta T cells may therefore play a distinct role in forming the first line of the host defense system against certain microorganisms. | Cord Factors |
Glutamate amidation, a secondary modification of the peptidoglycan, was first identified in Staphylococcus aureus It is catalyzed by the protein products of the murT and gatD genes, which are conserved and colocalized in the genomes of most sequenced Gram-positive bacterial species. The MurT-GatD complex is required for cell viability, full resistance to beta-lactam antibiotics, and resistance to human lysozyme and is recognized as an attractive target for new antimicrobials. Great effort has been invested in the study of this step, culminating recently in three independent reports addressing the structural elucidation of the MurT-GatD complex. In this work, we demonstrate through the use of nonstructural approaches the critical and multiple roles of the C-terminal domain of MurT, annotated as DUF1727, in the MurT-GatD enzymatic complex. This domain provides the physical link between the two enzymatic activities and is essential for the amidation reaction. Copurification of recombinant MurT and GatD proteins and bacterial two-hybrid assays support the observation that the MurT-GatD interaction occurs through this domain. Most importantly, we provide in vivo evidence of the effect of substitutions at specific residues in DUF1727 on cell wall peptidoglycan amidation and on the phenotypes of oxacillin resistance and bacterial growth." | Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor |
Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case-control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n = 18; RR = 0.85; 95% CI = 0.78-0.92) and liver cancers (n = 10; RR = 0.55; 95% CI = 0.46-0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n = 6; RR = 0.87; 95% CI = 0.80-0.95), lung (n = 6; RR = 0.77; 95% CI = 0.61-0.96) and liver (n = 8; RR = 0.83; 95% CI = 0.72-0.95) cancers. Insulins were negatively associated with breast (n = 15; RR = 0.90; 95% CI = 0.82-0.98) and prostate cancer risks (n = 7; RR = 0.74; 95% CI = 0.56-0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n = 5; RR = 1.26; 95% CI = 1.01-1.57), and between insulins and liver (n = 7; RR = 1.74; 95% CI = 1.08-2.80) and pancreatic cancers (n = 8; RR = 2.41; 95% CI = 1.08-5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk. | Insulin Secretagogues |
BACKGROUND: Mycetoma is a pathological process in which eumycotic (fungal) or actinomycotic causative agents from exogenous source produce grains. It follows penetrating injury inoculating soil organisms, occurring preferentially in rural areas usually among labourers who work barefoot. Mycetoma is a localized chronic, and deforming infectious disease of subcutaneous tissues, skin and bones. We report 130 cases of mycetoma in Senegal from 1983 to 2000. PATIENTS AND METHODS: There were 130 patients with mycetoma. Clinical diagnosis of mycetoma was based on open tract sinuses, tumefaction or discharge of grain. Diagnosis confirmation was based on mycology and histology. An X-ray was preformed to detect bone lesions. Treatment was medical for actinomycetoma and surgical for eumycetoma. RESULTS: We observed 76 actinomycetoma and 54 eumycetoma (Sex ratio M/F=6.6; mean age=34.7 +/- 14.8 years). The mean duration before the first medical evaluation was 4.8 +/- 5.6 years. Actinomycetoma was due to Actinomadura pelletieri, (54 cases), Actinomadura madurae (17 cases) and Streptomyces somaliensis (5 cases). Eumycetoma was due to Madurella mycetomatis (38 cases), Leptospahria senegalensis (9 cases), Pseudoallescheria boydii (6 cases) and Rhinoclediella atrovirens (1 case). Clinical inflammatory features significantly associated with actinomyces (p<0.001 OR=2.64) were predominant (85 cases). Tumoral and cystic features were found in the others forms. Lesions were located on the foot in 81 patients. Bone lesions, depending on the duration, were observed in 68 patients. Neurological damage occurred in 3 patients with dorsolumbar actinomycetoma. Sixty-six patients with actinomycetoma were cured by medical treatment. DISCUSSION: The 130 cases of mycetoma were remarkable by the long duration of the disease before the first medical evaluation. Pain and tumor were the two main symptoms which brought the patients to the hospital and had appeared after 5 years duration and the predominance of actinomadura pelletieri actinomycetoma was responsible for 41.3 p. 100 of our cases. In Niger and Mauritania, mycetoma were actinomycetoma in respectively 71.2 p. 100 and 25 p. 100 of cases. The geographic distribution of pathogenic mycetoma agents was determined by the annual rainfall. Distinction between eumycetoma and actinomycetoma is very important for the treatment. | Mycetoma |
This study involved 331 individuals who were without clinical evidence of gingival inflammation. The width of the keratinized gingiva and the depth of the gingival sulcus were measured on the mid-facial aspect of all teeth in each patient, using a calibrated, flat periodontal probe. The mean width of the attached gingiva did not show an increase from the deciduous to the permanent dentition. However, the width of the attached gingiva in the case of newly erupted permanent teeth was narrower than in the corresponding primary teeth. The widest zone of attached gingiva was found over the central and lateral incisors. The width of the attached gingiva decreased over the canine and the first premolar (and first primary molar). It then increased over the second premolar (and second primary molar) and the first molar. These variations were approximately the same in both the maxilla and the mandible, although there was a greater over-all width of attached gingiva in the maxilla than in the mandible. The tendency, in the permanent dentition, for the attached gingiva to increase in width with age was related to a concomitant decrease in sulcus depth. | Mouth |
This study investigated whether ramipril treatment has a beneficial effect on left atrial appendage (LAA) function in patients with systemic hypertension in sinus rhythm. Patients with untreated systemic hypertension and normal left ventricular systolic function in sinus rhythm (n = 20; six males/14 females; age 35 - 69 years, mean +/- SD 52.8 +/- 8.9 years) were evaluated using transthoracic and transoesophageal echocardiography at baseline and after 6 months of treatment with 5 mg/day ramipril. Mean systolic and diastolic blood pressures decreased significantly after ramipril therapy. Baseline LAA emptying velocity was below the age-related reference value for this parameter, indicating abnormal LAA function. There were significant increases in the LAA filling and emptying velocities after ramipril treatment. It is concluded that the decrease in blood pressure and haemodynamic improvements brought about by ramipril therapy resulted in improved LAA function in hypertensive patients with normal left ventricular systolic function in sinus rhythm. | Ramipril |
Cerebral venous thrombosis shows remarkable clinical polymorphism: isolated intracranial hypertension, cerebrovascular accident or focal, subacute cerebral lesion. Magnetic resonance imaging permits easy identification of the thrombosis and its tissular consequences as well as long-term follow-up. Search for the cause should be meticulous, given the multiple possibilities, presently dominated by prothrombotic states (postpartum, haemostasis anomalies, systemic affections, haematologic diseases, birth control pill, etc.). The development of neuro-imaging is changing the classic severity of cerebral venous thrombosis. Anti-coagulant treatment is widely used, including during haemorrhagic infarction. This treatment probably contributes to improving the survival and functional prognosis." | Intracranial Embolism and Thrombosis |
In Western Europe the most frequent cause of multiple injuries is blunt trauma. Only few of us have experience with penetrating trauma, without exception far less than in the USA or South-Africa. In Rotterdam, the Erasmus Medical Centre is a level I trauma centre, situated directly in the town centre. All penetrating traumas are directly presented to our emergency department by a well organized ambulance service supported by a mobile medical team if necessary. The delay with scoop and run principles is very short for these cases, resulting in severely injured reaching the hospital alive in increasing frequency. Although the basic principles of trauma care according to the guidelines of the Advanced Trauma Life Support (ATLS) (1-2) are the same for blunt and penetrating trauma with regard to priorities, diagnostics and primary therapy, there are some pitfalls in the strategy of management in penetrating trauma one should be aware of. Simple algorithms can be helpful, especially in case of limited experience (3). In case of life-saving procedures, the principles of Damage Control Surgery (DCS) must be followed (4-5). This approach is somewhat different from traditional" surgical treatment. In the Ist phase prompt interventions by emergency thoracotomy and laparotomy are carried out, with only two goals to achieve: surgical control of haemorrhage and contamination. After temporary life-saving procedures, the 2nd phase is characterized by intensive care treatment, dealing with hypothermia, metabolic acidosis and clotting disturbances. Finally in the 3rd phase, within 6-24 hours, definitive surgical care takes place. In this overview, penetrating injuries of neck, thorax, abdomen and extremities will be outlined. Penetrating cranial injuries, as a neurosurgical emergency with poor prognosis, are not discussed. History and physical examination remain the corner stones of good medical praxis. In a work-up according to ATLS principles airway, breathing and circulation should be evaluated with great care. Neurovascular examination related to trauma of the spinal cord, peripheral nerves as well as vascular involvement should be carried out also in extremity injuries. Physical examination should be completed by localization of all stabwounds, in- and outshot openings as well as recto-vaginal examination and inspection of the oropharynx." | Wounds, Penetrating |
Among patients with cat-scratch disease, the oculoglandular form is the most common unusual manifestation. This condition, seen in 14 of 585 patients with the infection encountered in a private pediatric practice over a span of 23 years, belongs in the syndrome of the oculoglandular disease of Parinaud. Most of the 14 patients described were only mildly ill and had but little discomfort. All patients recovered without residuals. Diagnosis is based on four criteria: exposure to a cat, usually an immature one; the presence of a localized granuloma of the eye; the presence of preauricular lymphadenopathy; and a positive skin test to cat-scratch antigen of known potency. Several unusual features, never before described, of oculoglandular disease due to cat-scratch disease are submitted. | Cat-Scratch Disease |
Emodin (1) is the major bioactive compound of several herb species, which belongs to anthraquinone class of compound. As a part of our drug discovery program, large quantities of emodin (1) was isolated from the roots of Rheum emodi and a library of novel emodin derivatives 2-15 were prepared to evaluate their antiproliferative activities against HepG2, MDA-MB-231 and NIH/3T3 cells lines. The derivatives 3 and 12 strongly inhibited the proliferation of HepG2 and MDA-MB-231 cancer cell line with an IC(5)(0) of 5.6, 13.03 and 10.44, 5.027, respectively, which is comparable to marketed drug epirubicin (III). The compounds 3 and 12 were also capable of inducing cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines and exhibit DNA intercalating activity. These emodin derivatives hold promise for developing safer alternatives to the marketed epirubicin. | Emodin |
Iron-containing ligands targeting the human histamine H(3) receptor (hH(3)R) were prepared. The compounds contain ferrocene sandwich complexes coupled via different linkers to a basic hH(3)R antagonist/inverse agonist pharmacophore. In a click chemistry approach, a triazole was successfully inserted as a new linking element. Two ferrocenylmethylamines and a ferrocenyltriazole were the most affine hH(3)R ligands within this series, showing receptor binding in the nano- and subnanomolar concentration range. | Receptors, Histamine H3 |
Infantile and classical late infantile neuronal ceroid lipofuscinoses (NCL) are two recent additions to the expanding spectrum of lysosomal storage disorders caused by deficiencies in lysosomal hydrolases. They are latecomers to the lysosomal storage disorders, probably because of the heterogeneous nature of the storage material, which precluded meaningful biochemical analysis. Infantile NCL is caused by deficiency in palmitoyl-protein thioesterase, an enzyme that hydrolyzes fatty acids from cysteine residues in lipid-modified proteins. Classical late-infantile NCL is caused by a deficiency in tripeptidyl amino peptidase-I, a lysosomal peptidase that removes three amino acids from the free amino terminus of peptides or small proteins. Late-onset forms of these disorders have been described. The clinical, biochemical, and molecular genetic aspects of these two latest lysosomal storage disorders are discussed in this review. In addition, approaches to treatment and future directions for research are examined." | Neuronal Ceroid-Lipofuscinoses |
Method development and validation studies have been completed on an assay that will allow the determination of 2,4-dichlorophenoxyacetic acid (2,4-D) in human urine. The accurate determination of 2,4-D in urine is an important factor in monitoring worker and population exposure. These studies successfully validated a method for the detection of 2,4-D in urine at a limit of quantitation (LOQ) of 5.00 ppb (parts per billion) using gas chromatography with mass selective detection (GC/MSD). The first study involved the determination of 2,4-D in control human urine and urine samples fortified with 2,4-D. Due to chromatographic interference, a second study was conducted using 14C-2,4-D to verify the recoverability of 2,4-D from human urine at low levels using the GC/MSD method. The second study supports the results of the original data. The 2,4-D was extracted from human urine using a procedure involving hydrolysis using potassium hydroxide, followed by a liquid-liquid extraction into methylene chloride. The extracted samples were derivatized with diazomethane. The methylated fraction was analyzed by GC/MSD. Quantitation was made by comparison to methylated reference standards of 2,4-D. Aliquots fortified at 5-, 50-, and 500-ppb levels were analyzed. The overall mean recovery for all fortified samples was 90.3% with a relative standard deviation of 14.31%." | 2,4-Dichlorophenoxyacetic Acid |
To summarize, it should be realized that acceptance of surgicenters has happened. Surgery centers expect heightened awareness of their services as patients, in conjunction with their own physicians, make decisions based on cost, service, and convenience of the care provided. As copayments and deductibles increase, consumers have become better educated, taking a more active role in selecting their health care providers. This activity has given rise to joint ventures between physicians and hospitals offering new ambulatory care packages previously based in hospitals alone. The net effect will divide the health care industry into two markets, one that will manage high-intensity surgical procedures and one that will promote outpatient surgical procedures. | Surgicenters |
INTRODUCTION: Imported diseases pose a diagnostic challenge for the physician, epidemiologists, and the local health care authorities, implying a risk for the community in some cases. METHOD: We report the case of a patient with Chikungunya virus infection in Spain and describe the clinical and epidemiological characteristics of this condition. RESULTS: Diagnosis was confirmed by specific tests in paired samples. CONCLUSIONS: The vector for the disease (Aedes albopictus) now exists in Spain. There is a danger that local outbreaks may occur where there are patients with viremia in areas with a prevalence of the vector. | Alphavirus Infections |
Thermolysin, a thermophilic metalloproteinase, is markedly activated in the presence of high concentrations (1-5 M) of neutral salts. The activity increases in an exponential fashion with increasing salt concentration, and is enhanced 13-15 times with 4 M NaCl at pH 7.0 and 25 degreesC (K. Inouye, Effects of salts on thermolysin: activation of hydrolysis and synthesis of N-carbobenzoxy-l-aspartyl-l-phenylalanine methyl ester, and a unique change in the absorption spectrum of thermolysin, J. Biochem. 112 (1992) 335-340). In this study, the effect of NaCl on the thermal stability of thermolysin has been examined at 60-85 degreesC. The activation energy, Ea, for the thermal inactivation is 15 kcal/mol at 0 M NaCl, and increases up to 30-33 kcal/mol by the addition of 0. 5-1.5 M NaCl. Further increase in [NaCl] decreases the Ea value, and at 4 M NaCl it is almost the same as that at 0 M NaCl. Thermolysin at 0.5-1.5 M NaCl is twice as heat-stable as in the absence of NaCl. The NaCl dependence of the stability is different from that of the activity, suggesting that the effects of NaCl on activity and stability are independent. Thermolysin has been demonstrated to be not only a thermophilic enzyme but also a highly halophilic one. | Thermolysin |
The Subaru Telescope(a)) is an 8.2 m optical/infrared telescope constructed during 1991-1999 and has been operational since 2000 on the summit area of Maunakea, Hawaii, by the National Astronomical Observatory of Japan (NAOJ). This paper reviews the history, key engineering issues, and selected scientific achievements of the Subaru Telescope. The active optics for a thin primary mirror was the design backbone of the telescope to deliver a high-imaging performance. Adaptive optics with a laser-facility to generate an artificial guide-star improved the telescope vision to its diffraction limit by cancelling any atmospheric turbulence effect in real time. Various observational instruments, especially the wide-field camera, have enabled unique observational studies. Selected scientific topics include studies on cosmic reionization, weak/strong gravitational lensing, cosmological parameters, primordial black holes, the dynamical/chemical evolution/interactions of galaxies, neutron star mergers, supernovae, exoplanets, proto-planetary disks, and outliers of the solar system. The last described are operational statistics, plans and a note concerning the culture-and-science issues in Hawaii. | Telescopes |
Skin is a complex organ covering the entire surface of the body. Aged skin is characterized by appearance of wrinkles, laxity, and pigmentary irregularities. These changes occur under the influence of intrinsic and extrinsic factors, with sun exposure being the most deleterious to the skin. Skin changes associated with aging are the focus of many surgical and nonsurgical procedures aimed to improve the appearance of skin. Knowledge of skin histology and physiology will deepen the understanding of cutaneous changes associated with aging and will promote optimal cosmetic and functional patient outcomes. | Skin Aging |
Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered. | Valine |
Intravenously administered ketorolac tromethamine provided complete pain relief to a 54-year-old man with right-sided testicular pain and nausea and vomiting. The patient had a ureteral calculus documented by computed tomography. This patient's pain initially failed to respond to intravenously administered hydromorphone hydrochloride. Subsequently, he was admitted to the hospital and had operative removal of his ureteral calculus and placement of a ureteral stent. Based on their findings and review of the literature, the authors recommend that intravenous ketorolac be used as the first-line treatment for acute renal colic in patients in whom the medication is not contraindicated. | Ketorolac |
Panfolliculoma is a rare follicular neoplasm with differentiation toward both upper (infundibulum and isthmus) and lower (stem, hair matrix, and bulb) segments of a hair follicle. We present an unusual case of cystic panfolliculoma. A 33-year-old Hispanic woman presented with an 8-month history of a 3.0-cm cystic scalp mass. The lesion was excised, and the histologic sections showed a cystic follicular neoplasm that contained corneocytes in basket-woven and laminated array, trichohyalin granules of the inner root sheath, germinative cells, papillae, matrical cells, and shadow" cells. Cytokeratin 903 and cytokeratin 5/6 immunostains uniformly highlight the tumor cells. Ber-EP4 strongly labels the germinative cells but not the follicular papillae. CD34 labels the surrounding fibrotic stroma and focally the epithelial component." | Follicular Cyst |
BACKGROUND: Myocardial strain-change in myocardial fibre length over the cardiac cycle-is a measure of cardiac muscle function. It is obtained using conventional techniques such as echocardiography and magnetic resonance imaging, adding additional clinical information to augment the current techniques. METHODS: A narrative review of the current relevant literature with respect to myocardial strain, with a focus on strain measured by echocardiography. RESULTS: Myocardial strain identifies global and regional abnormalities in myocardial function and differentiates types of cardiomyopathy. It is an earlier marker of myocardial disease than ejection fraction and is predictive of cardiovascular adverse events. Accurate measurement requires high-quality images and experienced practitioners. CONCLUSION: This review explains advantages and disadvantages of myocardial strain imaging and explains why, through adding increased precision without additional burden, it should be a standard part of cardiac assessment." | Magnetic Resonance Imaging, Cine |
Schisandra chinensis is a medicinal and edible plant that contains various bioactive compounds. Among these, lignans are the major functional compounds. Nevertheless, detailed information about lignans in Schisandra chinensis oil remains scarce. A powerful UPLC-Q/TOF-MS method was established for the rapid identification of the lignan constituents of Schisandra chinensis oils. The results showed that 21 lignans have been unambiguously identified, and four lignans have been tentatively identified in the Schisandra chinensis oils. In addition, semi-quantitative analysis indicated that the total lignan content in the Schisandra chinensis oils was distributed from 67.73 +/- 0.06 to 87.61 +/- 1.83 mg/g. Schisandrin and schisandrin B were the most abundant lignans in the Schisandra chinensis oils, their content ranging from 15.85 +/- 0.09 to 20.57 +/- 0.38 mg/g. Additionally, this study provided a systematic characterization of lignans in Schisandra chinensis oil and indicated that the oil might be used as lignan-related functional foods. | Austrobaileyales |
Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with unclear pathogenesis. The gut microbiota and intestinal barrier play an essential role in AIH. Polymeric immunoglobulin receptor (pIgR) is a central component of mucosal immunity. Herein, we aimed to test the hypothesis that pIgR plays a pivotal role in maintaining gut microbiota homeostasis and gut barrier integrity in an AIH mouse model. The expression of intestinal pIgR shows the variation tendency of falling after rising with the aggravation of experimental AIH (EAH). The deletion of Pigr exacerbates liver damage in EAH. Furthermore, we identified a distinct microbiota profile of Pigr-deficient EAH mice, with a significant increased aboundance in the Oscillospiraceae family, particularly the Anaeromassilibacillus genus. Such a situation occurs because the loss of Pigr inhibits MEK/ERK, a key signal pathway whereby pIgR transports immunoglobulin A (IgA), resulting in reduced IgA secretion, which leads to the destruction of intestinal epithelial tight junction proteins and intestinal flora disturbance. Increased intestinal leakage causes increased translocation of bacteria to the liver, thus aggravating liver inflammation in EAH. Treatment with the Lactobacillus rhamnosus GG supernatant reverses liver damage in EAH mice but loses its protective effect without pIgR. Our study identifies that intestinal pIgR is a critical regulator of the adaptive response to S100-induced alterations in gut flora and the gut barrier function, which closely correlates with liver injury. Intestinal upregulation of pIgR could be a novel approach for treating AIH." | Receptors, Polymeric Immunoglobulin |
The activity of the 5-nitrovinylfuran, SQ 18 506, is compared in vivo and in vitro with lampit (a 5-nitrofuran), Ro 7-1051 (a 2-nitroimidazole) and metronidazole (a 5-nitroimidazole). The order of activities on a weight basis was: SQ 18 506 greater than lampit greater than Ro 7-1051 greater than metronidazole. Concern about possible mutagenicity and carcinogenicity, however, has precluded the use of SQ 18 506 in clinical trials." | 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole |
This paper investigates the design of a single-chip, 100-channel wireless neural-signal acquisition, processing, and communications device. Design approaches for realizing front-end neural-signal amplifier, data conversion, microprocessor, and transceiver circuitry have been outlined. | Telemetry |
In the present study, we applied a novel high-throughput in vitro gastrointestinal digestion model to phenotype bioaccessibility of phenolics in a diverse germplasm collection representing cultivated highbush blueberries. Results revealed significant (P < 0.05) differences between accessions, years, and accession by year interaction for relative and absolute bioaccessibility of flavonoids and phenolic acids. Broad sense heritability estimates revealed low to moderate inheritances of relative and absolute bioaccessibility, suggesting that besides environmental variables, genetics factors could control bioaccessibility of phenolics. Acylated anthocyanins had significantly higher relative bioaccessibility than non-acylated anthocyanins. Correlation analysis indicated that relative bioaccessibility did not show significant association with fruit quality or raw concentration of metabolites. The study also identified accessions that have high relative and absolute bioaccessibility values. Overall, combining the bioaccessibility of phenolics with genetic and genomic approaches will enable the identification of genotypes and genetic factors influencing these traits in blueberry. | Vaccinium |
The effectiveness of a simple PCR protocol performed on paraffin-embedded tissues, obtained from histopathologically and culturally diagnosed cases of dermatophytic pseudomycetoma DPM was tested. The specimens were investigated using previously described primers (DH1L and DH1R) targeting the 18S rDNA gene and amplifying a 183-bp fragment. Microsporum canis was identified from all samples. The PCR protocol described in the present work demonstrated a 100% concordant result comparing the molecular characterisation with phenotypic characterisation of dermatophytes. Molecular biology could represent a valid identification tool in dermatophytic deep infections, when diagnosis cannot be achieved by cultural methods. | Microsporum |
AIM: Primary mesenteric fibromatosis is a rare, locally invasive, non-metastasizing type of intra-abdominal fibromatoses with a very high rate of recurrence. In this study, we aimed to present our surgical approach, tumor characteristics, clinical presentation and long-term follow-up results in cases of primary mesenteric fibromatosis. MATERIAL AND METODS: The data collected from 11 patients who underwent surgery due to primary mesenteric fibromatosis in our clinic between 2010 and 2019 were analyzed retrospectively. RESULTS: Abdominal ipain, abdominal distention, and two patients (18.2%) were operated on with a diagnosis of acute abdomen in the emergency setting due to mechanical bowel obstruction in one patient There were 11 patients in our study. Six patients were female and 5 were male. The mean age was 44.2+/-15.8 years. Abdominal mass was detected in 5 patients (45.5%) who had complaints of mechanical bowel obstruction such as nausea and vomitingand gastrointestinal perforation in other patient. Mesenteric mass was detected in 3 patients (27.3%) with vague abdominal pain. One patient (9.1%) presented with abdominal pain and swelling of the right leg. After a mean follow-up period of 43.4+/-28.4 months, only 1 patient (9.1%) had recurrence and required reoperation approximately 80 months after the first operation. One patient (9.1%) died of anastomotic leakage and sepsis in the first 30 days postoperatively, and other patient (9.1%) idied of other reasons 1 year later postoperatively. CONCLUSIONS: Although mesenteric fibromatosis is a benign tumor pathologically, the main principle in the treatment of this tumor which is clinically aggressive and has high recurrence rate is wide surgical resection. Mesenteric fibromatoses have a varied clinical presentation. Radiological imaging methods helps diagnosis and planning the surgical treatment. Immunohistochemical characteristics confirms the diagnosis and differentiates from other similar tumors. KEY WORDS: Desmoid tumor, Fibromatosis, Mesentery, Mesenteric tumor,Mesenteric fibromatosis. | Fibromatosis, Abdominal |
PURPOSE: To evaluate whether the gentian violet staining of the anterior lens capsule during the cataract surgery is cytotoxic for the human lens epithelial cells, as an indirect indication of possible toxicity towards the corneal endothelium and the safety of gentian violet application. MATERIALS AND METHODS: Two groups of anterior lens capsules obtained during the cataract surgery, gentian violet stained and non-stained, were incubated with fluorescent dye Fura-2. Their fluorescence, upon excitation at 360 and 380 nm, was imaged to monitor changes in free intracellular calcium concentration ([Ca(2+)]i) in response to pharmacological stimulation by acetylcholine. The [Ca(2+)]i homeostasis is the indicator of cellular function. The changes in [Ca(2+)]i were compared between the two groups. RESULTS: Epithelial cells responded to acetylcholine in both groups of capsules - gentian violet stained (n = 17) and non-stained ones (n = 33). No significant differences of the elicited responses were found in rise time (p = 0.89), decay time (p = 0.61) or amplitude of [Ca(2+)]i (p = 0.96 for 63x and p = 0.26 for 40x objectives) between the two groups of capsules (Student t test). CONCLUSIONS: The staining of the anterior lens capsule with gentian violet during phacoemulsification in concentration of 0.01%, does not have detectable cytotoxic effects, which would affect the [Ca(2+)]i homeostasis in lens epithelial cells. The data, if extrapolated to corneal endothelium, exposed to the same concentration, suggest that gentian violet in concentration of 0.01% is safe as an adjunct for capsule visualization in cataract surgery. | Anterior Capsule of the Lens |
Idiopathic hypereosinophilic syndrome (IHES) is a rare clinical disorder associated with blood and tissue infiltration by eosinophils. Cardiac involvement in patients with IHES can have varied presentations, and is often associated with significant morbidity and mortality. On the other hand, cardiac tamponade is a very rare presentation of IHES, and few anecdotal cases exist in literature. We report on IHES in a patient who presented with cardiac tamponade. | Cardiac Tamponade |
We report a case of a 13-year old girl with pectus excavatum who had a Nuss procedure and two years later a new cardiac murmur appeared which on investigation was diagnosed as supravalvular pulmonary artery stenosis. Following removal of the Nuss bar the stenosis resolved." | Pulmonary Subvalvular Stenosis |
Tyrosyl-tRNA synthetase (TyrRS) has been studied extensively by mutational and structural analyses to elucidate its catalytic mechanism. TyrRS has the HIGH and KMSKS motifs that catalyze the amino acid activation with ATP. In the present study, the crystal structures of the Escherichia coli TyrRS catalytic domain, in complexes with l-tyrosine and a l-tyrosyladenylate analogue, Tyr-AMS, were solved at 2.0A and 2.7A resolution, respectively. In the Tyr-AMS-bound structure, the 2'-OH group and adenine ring of the Tyr-AMS are strictly recognized by hydrogen bonds. This manner of hydrogen-bond recognition is conserved among the class I synthetases. Moreover, a comparison between the two structures revealed that the KMSKS loop is rearranged in response to adenine moiety binding and hydrogen-bond formation, and the KMSKS loop adopts the more compact (semi-open") form, rather than the flexible, open form. The HIGH motif initially recognizes the gamma-phosphate, and then the alpha and gamma-phosphates of ATP, with a slight rearrangement of the residues. The other residues around the substrate also accommodate the Tyr-AMS. This induced-fit form presents a novel "snapshot" of the amino acid activation step in the aminoacylation reaction by TyrRS. The present structures and the T.thermophilus TyrRS ATP-free and bound structures revealed that the extensive induced-fit conformational changes of the KMSKS loop and the local conformational changes within the substrate binding site form the basis for driving the amino acid activation step: the KMSKS loop adopts the open form, transiently shifts to the semi-open conformation according to the adenosyl moiety binding, and finally assumes the rigid ATP-bound, closed form. After the amino acid activation, the KMSKS loop adopts the semi-open form again to accept the CCA end of tRNA for the aminoacyl transfer reaction." | Tyrosine-tRNA Ligase |
The relationship between type 2 diabetes mellitus and pancreatic cancer (PC) is not clear. It has been reported that the increased release of islet amyloid polypeptides (IAPPs) is responsible for the impaired glucose tolerance in PC patients. However, no information exists on the patterns of IAPP expression in PC tissue in comparison with tissue from the normal pancreas and that of a patient with type 2 diabetes. Therefore, we performed a morphometric study and compared the patterns of IAPP expression in 5 normal pancreases (as a control), 6 pancreases from patients with type 2 diabetes, and 11 surgical PC specimens, which were processed for immunohistochemistry using anti-insulin and an anti-IAPP antibody. From the cancer tissue, sections were taken from the tumor (T) and from adjacent tumor-free areas (TF). The size of islets and the number of immunostained cells in these islets were recorded. In diabetes and PC, the size of islets and the number of beta-cells was significantly lower than in the controls. Also, the number of IAPP-expressing cells was significantly lower in diabetes and in the T area but not in the TF region. In addition, no characteristic changes found in diabetic pancreases were observed in the TF area, indicating that PC patients had no prior diabetic diseases. The reduction in the number of IAPP in the T area seems to argue against the role of IAPP in glucose abnormality in PC patients. The primary endocrine alteration in the tumor area suggests that cancer cells produce diabetogenic substances, the nature of which awaits further research." | Pancreatic Polypeptide-Secreting Cells |
There is a growing body of evidence that the formation and accumulation of advanced glycation end products (AGE) have been known to progress under diabetic conditions, thereby being involved in diabetic vascular complications. Further, we, along with others, have recently found AGE could disturb insulin actions in cultured adipocytes and skeletal muscles. However, the pathological role of AGE in insulin resistance in vivo is not fully understood. Therefore, in this study, we examined whether pyridoxamine, an inhibitor of AGE formation could ameliorate insulin resistance in KK-A(y) mice, a model animal of obese, type 2 diabetes. Fasting blood glucose, serum levels of insulin and AGE in KK-A(y) mice were elevated as the mice got older (from 5 weeks old to 15 weeks old). Serum levels of AGE were positively correlated with insulin (R(2)=0.3956, P=0.002) in KK-A(y) mice. Administration of pyridoxamine dose-dependently decreased fasting insulin levels and improved insulin sensitivity in KK-A(y) mice of 10 weeks old, although it did not affect fasting blood glucose levels. Our present study suggests the involvement of AGE in insulin resistance in KK-A(y) mice. Inhibition of AGE formation may be a novel therapeutic target for improving insulin resistance in diabetes with obesity. | Pyridoxamine |
Diatoms are unicellular algae that possess cell wall made of silica. These diatoms play a pivotal role in synthesis of variety of silica nanostructures and have adorning morphology in nature. In the present study, we have used field emission scanning electron microscopy (FE-SEM) to investigate their morphological features like pore size, shape, and porous pattern in various diatoms isolated from Kurichi and Sulur fresh water lakes, Coimbatore, Tamil Nadu, India. Diatoms were identified as Nitzschia sp., Cyclotella meneghiniana, Coscinodiscus sp. and Cyclotella atomus based on their morphological features. The arrangement of porous nanostructures in these diatoms have been characterized. The change in the nanostructures present in the diatoms have been correlated to the contamination of water bodies. | Diatoms |
On-line monitoring biomass concentration in mycelial fed-batch cultivations of Streptomyces clavuligerus grown with soluble and partially insoluble complex media, was investigated with an in-situ capacitance probe fitted to an industrial pilot-plant tank. Standard off-line and on-line biomass determinations, including cell dry weight, packed mycelial volume, viscosity, DNA concentration and total CO(2) evolution in the exhaust gases, were performed throughout the experiments and compared to on-line capacitance measurements. Linear relations between capacitance and all other measurements were developed for both media that hold only in defined process phases, depending on the biomass state and the amount of insoluble matter present. For the industrial complex culture media good linear relations were obtained in the fast growth phase between capacitance and DNA concentration and total CO(2) evolution, while in the subsequent transition and stationary phases only with apparent viscosity was a reasonable correlation found. The capacitance probe was shown to be a valuable tool for real-time monitoring biomass concentration in industrial-like cultivation of mycelial streptomycetes. | Industrial Microbiology |
The likelihood that ovum transport is altered after fallopian tube surgery for infertility is suggested by the high ectopic pregnancy rate that follows such surgery. To test the hypothesis that a primary (although undefined) disturbance of ovum transport may lead to faulty uterine implantation and so to abortion, the author examined the case records of 273 patients who underwent nonmicrosurgical bilateral tubal surgery for infertility at King George V Memorial Hospital, Sydney, between 1966 and 1975. An analysis of the nature of the first pregnancy in the 71 patients in whom conception occurred indicates an ectopic pregnancy rate of 8.5% and a spontaneous abortion rate among uterine pregnancies of 20.0%, both of which are higher than would be expected normally. It is suggested that the 3 specific reproductive difficulties that can follow technically successful tubal surgery are lasting infertility despite tubal patency, ectopic pregnancy, and abortion. | Ovum Transport |
Adenosine is a physiologically important nucleoside in the cardiovascular system where it can act as a cardioprotectant and modulator of energy usage. Adenosine transporters (ATs) modulate cellular adenosine levels, which, in turn, can affect a number of processes such as receptor activation and glucose uptake, but their role in cardiac physiology is poorly understood. Therefore, we have developed a new cell model by determining various adenosine-related characteristics of HL-1, an immortalized atrial cardiomyocyte murine cell line. Adenosine uptake in HL-1 cells is sodium independent, saturable, and inhibitable by nucleoside transport inhibitors (nitrobenzylthioinosine (NBTI), dipyridamole, dilazep). Reverse transcription--polymerase chain reaction analysis confirmed that HL-1 cells possess mouse equilibrative nucleoside transporters 1 and 2 (mENT1, mENT2) and kinetic analyses indicate moderate-affinity (Km = 51.3 +/- 12.9 microM), NBTI-sensitive adenosine transport. NBTI binds at a high-affinity single site (B(max) = 520 +/- 10 fmol/mg protein, Kd = 0.11 +/- 0.04 nM, 1.6 x 10(5) NBTI-binding sites/cell). HL-1 cells possess adenosine receptor, metabolic enzyme, protein kinase C isoform, and insulin-stimulated glucose transport profiles that match normal mouse heart. Therefore, HL-1 is an excellent model to study ATs within cardiomyocytes and the first model for evaluating in detail the role of the ATs in modulating effects of adenosine." | Equilibrative-Nucleoside Transporter 2 |
5-methyltetrahydrofolate (5MTHF) absorbs UV radiation and has an absorption coefficient of 24250+/-1170 M(-1) cm(-1) at 290 nm. It has a weak fluorescence emission in the wavelength region around 360 nm. Our data demonstrated induction of 5-methyldihydrofolate by exposure to UVB and, after continues irradiation, p-aminobenzoyl-L-glutamic acid was found. The photodegradation of 5MTHF follows a first order kinetic with a degradation rate constant of 9.2 x 10(-3) min(-1) under our conditions (fluence rate of 2.15 mW cm(-2), exposure wavelengths from 280 to 350 nm). Our results indicate that a direct degradation of 5MTHF by UV exposure in humans in vivo is rather unlikely. 5MTHF mainly absorbs, and is degraded by, UVB and UVC, radiation that does not penetrate the earth's atmosphere and the human skin well. | Pterins |
The stronger antioxidant capacity of the flavonoid quercetin (Q) compared with taxifolin (dihydroquercetin, T) has been the subject of previous experimental and theoretical studies. Theoretical work has focused on the analysis of hydrogen bond dissociation energies (BDE) of the OH phenolic groups, but consider mechanisms that only involve the transfer of one hydrogen atom. In the present work we consider other mechanisms involving a second hydrogen transfer in reactions with free radicals. The relative stability of the radicals formed after the first hydrogen transfer reaction is considered in discussing the antioxidant activity of Q and T. In terms of global and local theoretical reactivity descriptors, we propose that the radical arising from Q should be more persistent in the environment and with the capability to react with a second radical by hydrogen transfer, proton transfer and electron transfer mechanisms. These mechanisms could be responsible of the stronger antioxidant capacity of Q. | Quercetin |
N6-methyladenosine (m6A) modification is the most extensively studied epigenetic modification due to its crucial role in regulating an array of biological processes. Herein, Bsu06560, formerly annotated as an adenine deaminase derived from Bacillus subtilis 168, was recognized as the first enzyme capable of metabolizing the epigenetic nucleoside N6-methyladenosine. A model of Bsu06560 was constructed, and several critical residues were putatively identified via mutational screening. Two mutants, F91L and Q150W, provided a superiorly enhanced conversion ratio of adenosine and N6-methyladenosine. The CRISPR-Cas9 system generated Bsu06560-knockout, F91L, and Q150W mutations from the B. subtilis 168 genome. Transcriptional profiling revealed a higher global gene expression level in BS-F91L and BS-Q150W strains with enhanced N6-methyladenosine deaminase activity. The differentially expressed genes were categorized using GO, COG, KEGG and verified through RT-qPCR. This study assessed the crucial roles of Bsu06560 in regulating adenosine and N6-methyladenosine metabolism, which influence a myriad of biological processes. This is the first systematic research to identify and functionally annotate an enzyme capable of metabolizing N6-methyladenosine and highlight its significant roles in regulation of bacterial metabolism. Besides, this study provides a novel method for controlling gene expression through the mutations of critical residues. | Deamination |
OBJECTIVE: Rhinolith is a hard nasal mass formed in time by the mineral salts around an endogenous or exogenous-originating nidus. Rhinolith, which is seen rarely, has been reported in the literature as case reports. In this study, we are presenting the demographic and clinical features together with accompanying sinonasal pathologies of 23 rhinolith cases. METHODS: The medical records and radiological findings of 23 cases, who were operated for rhinolith between January 2010 and June 2018 in Tokat State Hospital, were analyzed retrospectively. The age, gender, the side where rhinolith exists, nidus presence, type of surgery and sinonasal pathologies that accompany rhinolith, and accompanying secondary sinonasal surgeries were examined. RESULTS: A total of 17 (73.2%) of the 23 cases were female, and 6 (26.8%) were male. The mean age was 24.9 years. The symptoms that were seen in the patients were nasal obstruction (100%), rhinorrhea (82.6%), nasal malodor (78.2%), oral malodor (26%), headache (26%), epistaxis (17.3%), face pain (4,3%), respectively. Nidus could be detected in 6 patients. The most frequent localization of rhinolith was between the inferior concha and the nasal septum (n=21). The most common concomitant sinonasal pathology in rhinolith was septum deviation (43.4%); and the second most common pathology was mucosal thickening (30.4%) in the maxillary sinus. The surgery type that accompanied rhinolith at the highest frequency was septoplasty (n=5). Other surgeries were septorhinoplasty (n=1), antrochoanal polyp excision (n=1), adenoidectomy (n=1). CONCLUSION: The most common symptoms of rhinolith, which is a rare nasal pathology, are nasal obstruction and rhinorrhea. Radiological imaging together with a rigid endoscopy is important especially to evaluate the placement of rhinolith. In addition to this, radiological imaging, evaluation of the sinuses that are not sufficiently evaluated with rigid endoscope are important for planning the type of the operation and secondary surgical procedures which may accompany. | Lithiasis |
A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1beta/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D(3), metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited." | Coronavirus Nucleocapsid Proteins |
From the petroleum ether extract of the rhizomes of Tamus communis, the 7-hydroxy-2,3,4,8-tetramethoxyphenanthrene (1) was isolated, together with the known 2,3,4-trimethoxy-7,8-methylenedioxyphenanthrene (2), 3-hydroxy-2,4,-dimethoxy-7,8-methylenedioxyphenanthrene (3), 2-hydroxy-3,5,7-trimethoxyphenanthrene (4) and 2-hydroxy-3,5,7-trimethoxy-9,10-dihydrophenanthrene (5), through cytotoxic assay guidance. The structures were determined by means of HREIMS, (1)H NMR, JMOD and NOESY experiments. The cytotoxic effects of the isolated compounds were tested on cervix adenocarcinoma (HeLa) cells, with the MTT assay. The results demonstrated that, with the exception of 2, all these compounds displayed pronounced cytotoxic activity; especially 1 and 3 exhibited significant cell growth inhibitory effects, with IC(50)=8.52+/-0.70 and 3.64+/-0.12 microM, respectively. | Phenanthrenes |
Long-term travelers to areas where malaria is endemic are at risk for this potentially fatal disease; however, malaria can be prevented through the use of insecticide-treated bednets, mosquito repellents, and chemoprophylaxis. Three options for chemoprophylaxis are available in the Africa region: mefloquine, doxycycline, and atovaquone-proguanil. These options differ by dosing regimen, cost, and side effect profile. Long-term adverse effects of these drugs have been reported rarely. | Atovaquone |
A comparison is made between results recently reported on the induction of free radicals in irradiated alanine and studies previously published on irradiated amino acids. It is shown that there is good qualitative agreement between the old and the new measurements although several quantitative inconsistencies are noted. A query is raised as to whether the new data can truly be interpreted in terms of the theory of track structure when some of the effects observed are not fully taken into account." | Dose-Response Relationship, Radiation |
Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal syndrome of pathologic immune dysregulation characterized by clinical signs and symptoms of extreme inflammation. HLH can occur as a genetic or sporadic disorder and, though seen as an inherited condition affecting primarily a pediatric population, can occur at any age and can be encountered in association with a variety of underlying diseases. Clinically the syndrome, whether genetic or acquired, is characterized by fever, hepatosplenomegaly, cytopenias, and activated macrophages in hematopoietic organs. Therapy centers on suppression of this hyperinflammatory state with cytotoxic, immunosuppressive therapy and treatment of any existing HLH triggers." | Lymphohistiocytosis, Hemophagocytic |
Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research. In addition, we identify inconsistencies in the evidence implicating a strong effect of increased adiposity and suggest that certain behaviours (such as diet and stress) might place nonobese and otherwise healthy people at risk of this disease. Key risk factors are reviewed, including the global westernization of diets (usually involving a high intake of red and processed meats, high-fructose corn syrup and unhealthy cooking methods), stress, antibiotics, synthetic food dyes, monosodium glutamate, titanium dioxide, and physical inactivity and/or sedentary behaviour. The gut microbiota is probably at the crossroads of these risk factors and EOCRC. The time course of the disease and the fact that relevant exposures probably occur in childhood raise important methodological issues that are also discussed. | Exposome |
Embryogenic cultures of Panax ginseng were established without using phytohormones. Somatic embryos developed from the roots of an in vitro seedling and from excised leaf and petiole segments cultured in half-macro-salt strength Murashige and Skoog medium. Excised leaf and petiole segments were obtained from in vitro germinated seedlings. Plantlets were subsequently obtained from developing somatic embryos in phytohormone-free media. Shoot formation from somatic embryos was influenced by light intensity. The rate of growth and frequency of embryogenesis were improved when cut-up embryogenic tissues were inoculated into liquid media in the dark. The ginsenoside contents of a 4 year-old field-cultivated root, seedlings from zygotic embryos, somatic embryos and embryogenic tissues were determined and compared. Somatic embryos contained 1.7 times the amount of ginsenoside Rb1 and 2.3 times the amount of ginsenoside Re compared to seedlings from zygotic embryos. Ginsenoside Rd, which was absent in the seedlings derived from zygotic embryos, was detected in somatic embryos. Higher ginsenosides Rd and Rg1 levels were found in embryogenic tissues grown on solid media than in tissues grown in liquid media. The total ginsenoside yields, including the ginsenosides Rb1 and Rg1 levels, of cut-up embryogenic tissues, were higher than those of clump tissues. | Araliaceae |
It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation. | Citrates |
Two patients who developed massive pulmonary oedema, profound vasoconstriction and hypertension followed by hypotension after Atrax Robustus envenomation are described. The pulmonary oedema is due to increased pulmonary capillary membrane permeability which may be due to neurogenic or toxic causes. Use of artificial ventilation with high level PEEP, isoprenaline and high dose steroids allowed support of the patients during volume replacement with albumin. When the circulation was stable and airway frothing ceased, conventional dehydration therapy further improved lung function. Both patients were discharged well. | Spider Bites |
Cardiac device infections are a rare complication of pacing and defibrillator therapy. The number of implanted devices will likely continue to rise with increasing implantation of the cardioverter defibrillator and cardiac resynchronization devices. This report describes a case of an uncommon pathogen for device-associated endocarditis. | Haemophilus Infections |
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. Although the HIPEC procedure is adopted throughout the world, major differences exist between treatment protocols regarding the carrier solution, perfusate volume, use of an open or closed technique, duration of the perfusion and application of additional flushing. These differences can influence the pharmacokinetics and pharmacodynamics of oxaliplatin and might thereby have an impact on the efficacy and/or safety of the treatment. Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure. | Oxaliplatin |
Over the last several years, thrombectomy for large vessel occlusions (LVOs) has emerged as a standard of care for acute stroke patients. Furthermore, the time to reperfusion has been identified as a predictor of overall patient outcomes, and much effort has been made to identify potential areas to target in enhancing preintervention workflow. As medical technology and stroke devices improve, nearly all time points can be affected, from field stroke triage to automated imaging interpretation to mass mobile stroke code communications. In this article, we review the preintervention stroke workflow with specific regard to emerging technologies in improving time to reperfusion and overall patient outcomes. | Time-to-Treatment |
Previously, we showed that the Vpu protein from HIV-1 subtype C is more efficiently transported to the cell surface than the well studied subtype B Vpu (Pacyniak et al., 2005) and that a SHIV expressing the subtype C Vpu exhibited a decreased rate of CD4+ T cell loss following inoculation in macaques (Hill et al., 2008). In this study, we examined the role of overlapping tyrosine-based (YXXPhi) and dileucine-based ([D/E]XXXL[L/I]) motifs in the membrane proximal region of the subtype C Vpu (EYRKLL) in Vpu intracellular transport, CD4 surface expression and virus release from the cell surface. We constructed three site-directed mutants of the subtype C vpu and fused these genes to the gene for enhanced green fluorescent protein (EGFP). The first mutation made altered the tyrosine (EARKLL; VpuSCEGFPY35A), the second altered the dileucine motif (EYRKLG; VpuSCEGFPL39G), and the third contained both amino acid substitutions (EARKLG; VpuSCEGFPYL35,39AG) in this region of the Vpu protein. The VpuSCEGFPY35A protein was transported to the cell surface similar to the unmodified VpuSCEGFP1 while VpuSCEGFPL39G was expressed at the cell surface at significantly reduced levels. The VpuSCEGFPYL35,39AG was found to have an intermediate level of cell surface expression. All three mutant Vpu proteins were analyzed for the ability to prevent cell surface expression of CD4. We found that both single mutants did not significantly effect CD4 surface expression while the double mutant (VpuSCEGFPYL35,39AG) was significantly less efficient at preventing cell surface CD4 expression. Chimeric simian human immunodeficiency viruses were constructed with these mutations in vpu (SHIVSCVpuY35A, SHIVSCVpuL39G and SHIVSCVpuYL35,39AG). Our results indicate that SHIVSCVpuL39G replicated much more efficiently and was much more cytopathic than SHIVSCVpu. In contrast, SHIVSCVpuY35A and SHIVSCVpuYL35,39AG replicated less efficiently when compared to the parental SHIVSCVpu. Taken together, these results show for the first time that the membrane proximal tyrosine-based sorting motif in the cytoplasmic domain of Vpu is essential for efficient virus release. These results also indicate that the dileucine-based sorting motif affects the intracellular trafficking of subtype C Vpu proteins, virus replication, and release. | Genes, vpu |
Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization." | Central Nervous System Sensitization |
The use of total parenteral nutrition (TPN) in patients with gastrointestinal cancers is a well-established practice, yet there is substantial variability in its use across institutions. Decision-making around the initiation of TPN is complex. An interdisciplinary team can help identify patient factors and clinical situations that influence whether a patient is likely to benefit from parenteral nutrition. We present the case of a woman with a gastrointestinal cancer who benefited from the initiation of TPN as a bridge therapy to further cancer treatment. This case highlights the importance of establishing a plan for nutrition with specific goals in mind, such as optimizing patients for more cancer-directed therapy. Although patients with gastrointestinal cancers may be candidates for TPN, many patient-specific factors, such as functional status and opportunities for future treatments, must be considered prior to the initiation of parenteral nutrition. An interdisciplinary approach should be used to make recommendations based on patient goals, with a focus on patient and cancer characteristics that are associated with positive outcomes after initiation of TPN. These characteristics include functional status, nutritional status, degree of symptom control, and ability to safely administer nutrition. It is important to continually assess whether parenteral nutrition is beneficial in respect to a patient's preferences and prognosis. | Parenteral Nutrition, Total |
One of the potential adverse effects of anti-arrhythmic agents is an impairment of cardiac function as a result of their intrinsic negative inotropic properties. Amiodarone, in animals, also induces dose-related negative inotropic effects, in addition to coronary and systemic vasodilatation and slowing of the heart. Likewise, in most human studies, intravenous amiodarone gives rise to early systemic and coronary vasodilatation, followed by a reduction in contractility. Depending on the relative impact of these opposing effects on the left ventricle, the changes in heart rate, cardiac output and left ventricular filling pressure are variable. Particularly in patients with pre-existing ventricular dysfunction, cardiac pump function is impaired further when relatively high dosages of amiodarone are used without its solvent Tween 80. In contrast, fast bolus administrations, eg. 5 mg/kg amiodarone in 5 minutes, result in an improvement of cardiac output, albeit at the expense of an increase in left ventricular filling pressure. The latter observation suggests that intravenous amiodarone should be given with caution in patients with heart failure and elevated left ventricular filling pressures. When given by mouth, amiodarone does not have significant hemodynamic effects, other than a moderate reduction in heart rate and, occasionally, in diastolic blood pressure. Cardiac pump function is not affected, even in patients with ventricular dysfunction or heart failure, in whom chronic oral administration of the drug is well tolerated. | Amiodarone |
PURPOSE OF REVIEW: Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes angiotensin II (AngII). AngII levels can be modulated by ACE2 in tissues where the enzyme is highly expressed, such as the kidney. In the kidney, ACE2 has the potential to regulate the intrarenal renin-angiotensin system (RAS), which can impact blood pressure and renal injury. Thus, in disease states where the RAS is often upregulated, the function of ACE2 plays a particularly important role. This review highlights the results of recent studies that demonstrate the interplay between ACE2 and the kidney under normal and pathological conditions. RECENT FINDINGS: ACE2 has been reported to play a key role in renal and cardiovascular function. Recent studies have implicated shedding of the membrane-bound ectodomain of ACE2 as one way in which the enzyme can be regulated and enzymatic activity altered. This posttranslational modification releases a fragment which retains enzymatic activity, and thus provides a novel mechanism by which the RAS can be altered in response to physiological stimuli. Decreased ACE2 activity is associated with increased blood pressure, diabetes, and oxidative stress, whereas, increased levels of ACE2 appear to be renoprotective. SUMMARY: A growing body of evidence, involving both experimental and human studies, points out the crucial role that ACE2 plays on the modulation of renal injury. Thus, therapeutic targets aiming to increase ACE2 activity and the ACE2-Ang(1-7)-MasR axis could potentially become clinically relevant, especially in disease states where the renal RAS is upregulated. | Peptidyl-Dipeptidase A |
OBJECTIVE: To investigate the effects on the blink reflex (BR) of single stimuli applied to the pedunculopontine tegmental nucleus (PPTg). METHODS: The BR was evoked by stimulating the supraorbital nerve (SON) in fifteen patients suffering from idiopathic Parkinson's disease (PD) who had electrodes monolaterally or bilaterally implanted in the PPTg for deep brain stimulation (DBS). Single stimuli were delivered to the PPTg through externalized electrode connection wires 3-4 days following PPTg implantation. RESULTS: PPTg stimuli increased the latency and reduced duration, amplitude and area of the R2 component of the BR in comparison to the response recorded in the absence of PPTg stimulation. These effects were independent of the side of SON stimulation and were stable for interstimulus interval (ISI) between PPTg prepulse and SON stimulus from 0 to 110 ms. The PPTg-induced prepulse inhibition of the BR was bilaterally present in the brainstem. The R1 component was unaffected. CONCLUSIONS: The prepulse inhibition of the R2 component may be modulated by the PPTg. SIGNIFICANCE: These findings suggest that abnormalities of BR occurring in PD may be ascribed to a reduction of basal ganglia-mediated inhibition of brainstem excitability. | Midbrain Reticular Formation |
OBJECTIVE: To identify the determinants of operative time for thyroidectomy and quantify the relative influence of preoperative and intra-operative factors. BACKGROUND: Anticipation of operative time is key to avoid both waste of hospital resources and dissatisfaction of the surgical staff. Having an accurate and anticipated planning would allow a rationalized operating room use and may improve patient flow and staffing level. METHODS: We conducted a prospective, cross-sectional study between April 2008 and December 2009. The operative time of 3454 patients who underwent thyroidectomy performed by 28 surgeons in five academic hospitals was monitored. We used multilevel linear regression to model determinants of operative time while accounting for the interplay of characteristics specific to surgeons, patients, and surgical procedures. The relative impact of each variable on operative time was estimated. RESULTS: Overall, 86% (99% CI 83 to 89) of operative time variation was related to preoperative variables. Surgeon characteristics accounted for 32% (99% CI 29 to 35) of variation, center location for 29% (99% CI 25 to 33), and surgical procedure or patient variables for 24% (99% CI 20 to 27). Operative time was significantly lower among experienced surgeons having practiced from 5-19 years (-21.8 min, P<0.05), performing at least 300 thyroidectomies per year (-28.8 min, P<0.05), and with increasing number of thyroidectomies performed the same day (-11.7min, P<0.001). Conversely, operative time increased in cases of procedure supervision by a more experienced surgeon (+20.0 min, P<0.001). The remaining 13.0% of variability was attributable to unanticipated technical difficulties at the time of surgery. CONCLUSIONS: Variation in thyroidectomy duration is largely explained by preoperative factors, suggesting that it can be accurately anticipated. Prediction tools allowing better regulation of patient flow in operating rooms appears feasible for both working conditions and cost management. | Operative Time |
AIMS/HYPOTHESIS: N(6)-methyladenosine (m(6)A) mRNA methylation and m(6)A-related proteins (methyltransferase-like 3 [METTL3], methyltransferase-like 14 [METTL14] and YTH domain containing 1 [YTHDC1]) have been shown to regulate islet beta cell function and the pathogenesis of diabetes. However, whether Wilms' tumour 1-associating protein (WTAP), a key regulator of the m(6)A RNA methyltransferase complex, regulates islet beta cell failure during pathogenesis of diabetes is largely unknown. The present study aimed to investigate the role of WTAP in the regulation of islet beta cell failure and diabetes. METHODS: Islet beta cell-specific Wtap-knockout and beta cell-specific Mettl3-overexpressing mice were generated for this study. Blood glucose, glucose tolerance, serum insulin, glucose-stimulated insulin secretion (both in vivo and in vitro), insulin levels, glucagon levels and beta cell apoptosis were examined. RNA-seq and MeRIP-seq were performed, and the data were well analysed. RESULTS: WTAP was downregulated in islet beta cells in type 2 diabetes, due to lipotoxicity and chronic inflammation, and islet beta cell-specific deletion of Wtap (Wtap-betaKO) induced beta cell failure and diabetes. Wtap-betaKO mice showed severe hyperglycaemia (above 20 mmol/l [360 mg/dl]) from 8 weeks of age onwards. Mechanistically, WTAP deficiency decreased m(6)A mRNA modification and reduced the expression of islet beta cell-specific transcription factors and insulin secretion-related genes by reducing METTL3 protein levels. Islet beta cell-specific overexpression of Mettl3 partially reversed the abnormalities observed in Wtap-betaKO mice. CONCLUSIONS/INTERPRETATION: WTAP plays a key role in maintaining beta cell function by regulating m(6)A mRNA modification depending on METTL3, and the downregulation of WTAP leads to beta cell failure and diabetes. DATA AVAILABILITY: The RNA-seq and MeRIP-seq datasets generated during the current study are available in the Gene Expression Omnibus database repository ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215156 ; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215360 ). | Methyltransferases |
High expression of the E26 transforming sequence related gene (ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling cascades in acute leukemia. Herein, we further expand those studies by identifying a consensus of biological targets in primary blasts of newly diagnosed acute leukemia patients. Our findings of chromatin immunoprecipitation-on-chip of primary samples revealed 48 significantly enriched single genes including DAAM1 and NUMB. Significantly enriched signaling pathways included WNT/beta-catenin, p53, and PI3K/AKT with ERG overexpression inducing dephosphorylation of AKT(Ser473) relative to non ERG expressing K562 cells. Cell based ERG overexpression studies also revealed drug resistance to multi-kinase inhibitor, BAY 43-9006 (Sorafenib) and to the tyrosine kinase inhibitor TKI258. Thus in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors. | Transcriptional Regulator ERG |
Hypertension is a major public health problem and one of the most important causes of premature morbidity and mortality. Yoga is a traditional Indian practice that has been adapted for use in complementary and alternative medicine and mainly includes physical postures, breathing techniques, and meditation. The impact of yoga as a complementary intervention for hypertension has been investigated in a number of randomized controlled trials; with an overall effect of about 10 mmHg reduction in systolic and about 8 mmHg reduction in diastolic blood pressure. Yoga seems to be effective only for hypertension but not for prehypertension; and only as an adjunct to antihypertensive pharmacological treatment but not as an alternative therapy. Breathing and meditation rather than physical activity seem to be the active part of yoga interventions for hypertensive patients. These practices can increase parasympathic activity and decrease sympathetic activity, arguably mainly by increasing GABA activity; thus counteracting excess activity of the sympathetic nervous system which has been associated with hypertension. Although yoga has been associated with serious adverse events in single case reports, population-based surveys as well as clinical trials indicate that yoga is a relatively safe intervention that is not associated with more adverse events than other forms of physical activity. Yoga can thus be considered a safe and effective intervention for managing hypertension. Given the possibly better risk/benefit ratio, it may be advisable to focus on yogic meditation and/or breathing techniques. | Breathing Exercises |
Postnatal development of the cerebellar cortex in the mouse is characterised by proliferation of cells of the external granular cell layer, migration of the granule cells across the molecular layer and simultaneous maturation of the Purkinje cells. At the same time, there is elaboration of the folia and fissures of the cerebellum. These features were studied postnatally in relation to the age and weight of the animal in the inbred strain of C3HeB/FeJ mice fed on standard diet. In every litter there was a difference in body weight of the various pups, and for the present study, the lowest and highest weighing animals from each litter were used. The observations presented here are on animals at the 1st, 7th, 13th and 24th days postnatum. It appears that the size of the cerebellum and the degree of the development of the cerebellar cortex are directly proportional to the weight of the animal for that age period. | Cerebellar Cortex |
Sleep and sleep deprivation have become major health issues in our modern society. Impaired sleep can negatively affect physical and psychological well-being, and conversely, certain common conditions can impair sleep. Furthermore, insufficient or disrupted sleep can contribute to functional impairments. As health care professionals, physical therapists are singularly concerned with function and well-being. To understand the role of sleep and sleep deprivation on health, this article describes sleep, our contemporary culture of sleeplessness, insomnia, sleep needs, the physical cost of inadequate sleep, the psychological cost of sleep deprivation, and the effects of sleep debt on safety. How to assess an individual's sleep debt is then described, and a sleep inventory questionnaire and scoring scale are presented. Evidence-based recommendations for optimizing sleep are outlined, and these can be readily implemented by the busy clinician. The sleep inventory questionnaire can be used to evaluate the outcome of these recommendations or other interventions as well as serve as an assessment tool. Based on the literature, the assessment and evaluation of sleep and basic sleep recommendations need to be considered as fundamental clinical competencies in contemporary physical therapy care. | Sleep Deprivation |
BACKGROUND/PURPOSE: Hirschsprung disease (HSCR; megacolon, congenital aganglionosis) is a congenital disorder characterized by the absence of ganglion cells along variable segments of the gut. Both rare (RV) and common variants of the RET gene are associated with HSCR. The aim of this study is to assess, for the first time, the variation in the RET gene of Vietnamese HSCR patients. METHODS: We used Sanger sequencing to screen the coding sequence of the RET gene of 97 Vietnamese HSCR patients of Southern Chinese ancestry. The healthy population consisted of 250 Southern Chinese individuals with no diagnosis of HSCR. RESULTS: We detected 8 heterozygous RVs distributed among 13 patients (13.40%) and that were not present in healthy individuals. Among those variants, there were 2 novel and deleterious (R133C [c.397 C>T]; R144C [c.430 C>T]) missense amino acid substitutions, 2 novel silent variants (P667P [c.2001 A>T]; Y809Y [c.2427 C>T]), and 4 previously described missense substitutions (R114H [c.341 G>A]; V292M [c.874 G>A]; G533S [c.1597 G>A]; R982C [c.2944 C>T]). As expected, the common RET coding sequence variants rs1800858 (A45A [c.135 G>A]) and rs1800861 (L769L [c.2307 T>G]) were highly associated with the disease. CONCLUSIONS: The identification of novel deleterious variants together with the fact RET RVs are virtually unique to HSCR patients indicates that the RET gene is a target for mutations among Hirschsprung patients of any population. | Proto-Oncogene Proteins c-ret |
A total of 28 pregnant women with growth-retarded fetuses were studied to examine the antepartum fetal heart rate patterns between 30 and 39 weeks of gestation. Sonicaid Computer System 8000 was used to analyze on line 200 cardiotocograms. We found that there is an increase in the number of accelerations, an increase in variation assessed in beats per minute and in milliseconds, an increase in duration of high episode and a decrease in the number of decelerations. | Fetal Monitoring |
Barringtonia racemosa presents a wide range of therapeutic applications. In the course of identifying bioactives from Indian medicinal plants it was observed that the hexane, ethanol and methanol extracts of B. racemosa seeds displayed potent yeast and intestinal alpha-glucosidase inhibitory activities. The methanol extract was found to be superior among them. However, none of the extracts exhibited pancreatic alpha-amylase inhibitory activity, rather the ethanol and methanol extracts accelerated the alpha-amylase enzyme activity. Interestingly, however, bartogenic acid isolated from the methanol extract inhibited alpha-amylase also. This is the first report identifying alpha-glucosidase inhibitory activity in B. racemosa seed extracts and assigning to bartogenic acid an alpha-glucosidase and amylase inhibitory property. The presence of bartogenic acid in B. racemosa seeds as a major compound is also reported for the first time in this communication. | Barringtonia |
A combination of stereological and physicochemical data was used to estimate the oxygen-diffusing capacity of the human term placenta. The effects on this morphometric diffusing capacity of isolated changes in placental structure were investigated by permitting volumes, surface areas and harmonic mean diffusion distances to deviate from normal baseline (term) values. Diffusion performance could be monitored effectively by estimating only three structural quantities. The most influential variable was the harmonic mean thickness of the villous membrane followed by the surface areas of villi and of fetal capillaries. Blood space volumes and plasma diffusion distances had negligible effects on diffusing capacity. Conclusions are discussed in the context of published findings on changes in placental anatomy which occur during gestation, abnormal pregnancies and pregnancies at high altitude. | Placenta |
Micro-organisms are increasingly used in a variety of products for commercial uses, including cleaning products. Such microbial-based cleaning products (MBCP) are represented as a more environmentally-friendly alternative to chemically based cleaning products. The identity of the micro-organisms formulated into these products is often considered confidential business information and is not revealed or it is only partly revealed (i.e., identification to the genus, not to the species). That paucity of information complicates the evaluation of the risk associated with their use. The accurate taxonomic identification of those micro-organisms is important so that a suitable risk assessment of the products can be conducted. To alleviate difficulties associated with adequate identification of micro-organisms in MBCP and other products containing micro-organisms, a microbial identification framework for risk assessment (MIFRA) has been elaborated. It serves to provide guidance on a polyphasic tiered approach, combining the data obtained from the use of various methods (i.e., polyphasic approach) combined with the sequential selection of the methods (i.e., tiered) to achieve a satisfactory identity of the micro-organism to an acceptable taxonomic level. The MIFRA is suitable in various risk assessment contexts for micro-organisms used in any commercial product. | Detergents |
Education is a common strategy used to prevent occupational injuries. However, its effectiveness is often measured using surrogate measures instead of true injury outcomes. To evaluate the effectiveness of workplace educational interventions, we selectively analyzed studies that reported injury outcomes (PROSPERO ID: CRD42019140631). We searched databases for peer-reviewed journal articles and sources of grey literature such as abstracts, registered trials, and theses published between 2000 and 2019. Studies on educational interventions that reported fatal or non-fatal occupational injury outcomes were selected. Two reviewers independently and in duplicate screened the studies, extracted data, and assessed risk of bias. Heterogeneity in the data precluded meta-analysis, and the results were reviewed narratively. In total, 35 studies were included. Of which, 17 found a significant reduction in injuries, most of which featured a multifaceted approach or non-didactic education. The remaining studies either described equivocal results or did not report statistical significance. Overall, interventions in the manufacturing industry were more effective than those in the construction sector. Risk of bias among included studies was moderate to high. In conclusion, educational interventions could be an effective part of multifaceted injury prevention programs. However, over-reliance on didactic education alone is not advised. | Occupational Injuries |
The contamination of oats with Fusarium toxins poses a high risk for food safety. Among them, trichothecenes are the most frequently reported in European oats, especially in northern countries. The environmental conditions related to the climate change scenario might favour a distribution shift in Fusarium species and the presence of these toxins in Southern European countries. In this paper, we present an ambitious work to determine the species responsible for trichothecene contamination in Spanish oats and to compare the results in the United Kingdom (UK) using a metataxonomic approach applied to both oat grains and soil samples collected from both countries. Regarding T-2 and HT-2 toxin producers, F. langsethiae was detected in 38% and 25% of the oat samples from the UK and Spain, respectively, and to the best of our knowledge, this is the first report of the detection of this fungus in oats from Spain. The relevant type B trichothecene producer, F. poae, was the most frequently detected Fusarium species in oats from both origins. Other important trichothecene producers, such as the Fusarium tricinctum species complex or Fusarium cerealis, were also frequently detected in oat fields. Many Fusarium toxins, including T-2 and HT-2 toxins, deoxynivalenol, or nivalenol, were detected in oat samples. The results obtained in this work revealed a clear change in the distribution of trichothecene producers and the necessity to establish the potential of these species to colonize oats and their ability to produce mycotoxins. | Trichothecenes, Type B |
Developing specific probes that distinguishes types and subtypes of viruses by a single probe will have a great impact not only in developing specific diagnostic reagents but also in developing tailor-made drugs and dosage requirements depending upon the genotype that cause the infection. We have selected aptamers specific for hemagglutinin protein of human influenza virus B/Johannesburg/05/1999. The selected aptamer, Class A-20, bind specifically to hemagglutinin of B/Johannesburg/05/1999 and able to discriminate it from hemagglutinin of human influenza A virus. | Influenza B virus |
Amniocentesis through an ultrasound aspiration biopsy transducer was performed 156 times. The technique is described and our results are presented. By closely monitoring the fetus and the needle entry into the amniotic cavity, we have avoided serious complications. The importance of adequate genetic counselling for the procedure is stressed, as most cases fall into the second trimester group, and the procedure is indicated in order to try to prevent inheritable disorders. The importance of continual monitoring of the fetus before, during and after the procedure is pointed out, and recommendations are made to avoid difficulties and complications in amniocentesis. | Amniocentesis |
OBJECTIVE: A commercially available medication containing homeopathic ingredients showed first signs of success in atopic dermatitis in dogs. The aim of this case series was to evaluate the effect of the preparation in a larger number of dogs with atopic dermatitis. MATERIAL AND METHODS: Ten atopic dogs received the oral homoeopathic combination preparation daily for 3 weeks according to the manufacturer's specifications. The diagnosis of atopic dermatitis was made previously by medical history, clinical examination and exclusion of differential diagnoses. Skin infections with bacteria and yeasts were excluded by clinical examination and cytological evaluation of impression smears. In food-allergic dogs, an elimination diet was fed at least 2 months prior and during the entire study period. Patients with suspected or confirmed flea allergy received flea control for at least 1 month prior to and during the study. The clinical signs were evaluated before and after therapy using a validated Pruritus Visual Analogue Acale (PVAS) and the Canine Atopic Dermatitis Lesion Index (CADLI). The coat quality was assessed by the owners. Possible adverse effects were recorded at the recheck. RESULTS: There were no significant changes in the lesion score (Wilcoxon test, p = 1.0), pruritus score (paired t test, p = 0.34) and coat quality (paired t test, p = 0.34) over the duration of treatment. Only one patient showed a slight improvement in itching and coat quality. No side effects were observed. CONCLUSION AND CLINICAL RELEVANCE: In this case series, the tested homoeopathic preparation did not show a positive effect on the clinical signs of canine atopic dermatitis. | Animal Fur |
The acquisition of an optimal peptide ligand by MHC class I molecules is crucial for the generation of immunity to viruses and tumors. This process is orchestrated by a molecular machine known as the peptide loading complex (PLC) that consists of specialized and general ER-resident molecules. These proteins collaborate to ensure the loading of an optimal peptide ligand into the antigen binding cleft of class I molecules. The surprising diversity of peptides bound to MHC class I molecules and recapitulation of class I assembly in vitro have provided new insights into the molecular machinations of peptide loading. Coupled with the extraordinary polymorphism of class I molecules and their differential dependence on various components of the PLC for cell surface expression, a picture of peptide loading at the molecular level has recently emerged and will be discussed herein." | Histocompatibility Antigens Class I |
PURPOSE OF REVIEW: The aim of this review was to present and comment on recent data published on palliative sedation in palliative and end-of-life care. Palliative sedation is a medical procedure used to deal with the refractory symptoms occurring in the advanced stages of cancer. It has clinical, nursing, relational and ethical implications, making it a highly sensitive issue. RECENT FINDINGS: Over the last 12 months, a number of authors have published interesting new findings on different areas of palliative sedation, that is prevalence, indications, monitoring, duration and choice of drugs. In particular, a clear definition of palliative sedation and of its more pronounced form, deep continuous sedation (DCS), has emerged. It has been confirmed that, when performed in the correct way and with the right aims, palliative sedation does not have a detrimental impact on survival. SUMMARY: Recent findings confirm that palliative sedation is an integral part of a medical palliative care approach and is needed in certain clinical situations. It is a legitimate clinical practice from any ethical point of view. While oncologists should have a basic knowledge of the procedure, its in depth study is a core competency for palliative care physicians. | Deep Sedation |
A growing number of professional associations and occupational groups are creating codes of ethics with the goal of guiding their members, protecting service users, and safeguarding the reputation of the profession. There is a great deal of literature dealing with the question to what extent ethical codes can achieve their desired objectives. The present paper does not contribute to this debate. Its aim is rather to investigate how rational it is to comply with codes of conduct. It is natural and virtually inevitable for a reflective person to ask why one should pay any attention to ethical codes, in particular if following a code is not in one's own interest. In order to achieve the aim of this paper, I shall (in Quasi-reasons for complying with an ethical code" section) discuss reasons that only appear to be reasons for complying with a code. In "Code-independent reasons" section, I shall present genuine practical reasons that, however, turn out to be reasons of the wrong kind. In "Code-dependent reasons" section finally presents the most important reasons for complying with ethical codes. The paper argues that while ethical codes do not necessarily yield reasons for action, professionals can have genuine reasons for complying with a code, which may, however, be rather weak and easily overridden by reasons for deviating from the code." | Codes of Ethics |
The objective of this article is to review the available studies regarding mold immunotherapy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to mold immunotherapy using the following keywords: mold, allergy, asthma, and immunotherapy. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic. Allergic responses to inhaled mold antigens are a recognized factor in allergic rhinitis and asthma. There are significant problems with respect to the production of relevant allergen material for the diagnosis and treatment of mold allergy with immunotherapy. Mold allergens contain proteases and should not be mixed with other allergens for immunotherapy. Most of the immunotherapy studies focus on two molds, Alternaria and Cladosporium. There is a lack of randomized placebo-controlled trials when evaluating the efficacy of mold immunotherapy with trials only focusing on immunotherapy to Alternaria and Cladosporium. Additional studies are needed regarding mold allergy and immunotherapy focusing on which molds are important for causing allergic disease. | Desensitization, Immunologic |
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