313 research outputs found
Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy
No full textOculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease caused by an abnormal (GCN) triplet expansion within the polyadenylate-binding protein nuclear 1 gene and consequent mRNA processing impairment and myogenic defects. Because a reduced cell proliferation potential and the consequent regeneration failure of aging muscle have been shown to be governed by lethal-7 (let-7) microRNA-mediated mechanisms, in the present study, we evaluated the role of let-7 in the pathogenesis of OPMD. By a multidisciplinary approach, including conf ocal microscopy, Western blot, and quantitative PCR analyses on muscle biopsies from patients and unaffected individuals, we found a significant increase in let-7 expression in OPMD muscles associated with an unusual high percentage of paired box 7–positive satellite cells. Furthermore, IL-6, a cytokine involved in the regulation of satellite cell proliferation and differentiation and a potential target of let-7, was found strongly down-regulated in OPMD compared with control muscles. The decrease in IL-6 transcript levels and protein content was also confirmed in vitro during differentiation of patients' and controls' muscle cells. Overall, our data suggest a key role of let-7 in the regeneration and degeneration process in OPMD muscle and pointed to IL-6 as a potential target molecule for new therapeutic approaches for this disorder.—Cappelletti, C., Galbardi, B., Bruttini, M., Salerno, F., Canioni, E., Pasanisi, M. B., Rodolico, C., Brizzi, T., Mora, M., Renieri, A., Maggi, L., Bernasconi, P., Mantegazza, R. Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy. FASEB J. 33, 7155–7167 (2019). www.fasebj.org
Utilità dell'immunoistochimica nel differenziare un carcinoma papillare della tiroide insorto su tessuto ectopico da una metastasi laterocervicale
No full textEffect of Vocalization on Static Handgrip Force Output
No full textRodolico, C., Oberholzer, R., Smith, S. Drexel University, Health Science Department, Philadelphia, PA
Purpose: This study examined differences in maximal static handgrip force between three conditions: passive breathing, forced exhalation, and vocalized exhalation. We hypothesized that handgrip force would be greater during vocalized exhalation compared to passive breathing and forced exhalation. Methods: Eighteen women and 12 men (24.9+ 5.9 years) performed maximal-effort, two-second static handgrip exercise during a passive breathing, forced exhalation, and vocalized exhalation condition. Three trials were conducted, each with a different condition order. There were twenty-second rest intervals between each condition and ninety-second intervals between each trial. A handgrip dynamometer and chest ventilation strap were used to measure force (N) and relative chest expansion during trials (AD Instruments, Powerlab 26T). A two-way repeated measures ANOVA was used to determine differences across conditions and trials with a 0.05 significance level (mean + SD). Results: The average handgrip force during vocalization (251.2 + 76.0 N) was greater than both passive breathing (201.2 + 118.4 N; pConclusion: Vocalized exhalation increased average static handgrip force by 25% compared to passive breathing and by 11% compared to forced exhalation. We hypothesize that vocalization increases sympathetic drive which may enhance overall motor unit activation increasing muscle force production. Further study investigating the effect of vocalization on muscle potentiation and sympathetic drive is suggested
Candida spp. infections after abdominal urgent surgery: comparative analysis of histologic data for which microbiological results were positive for Candida spp.
No full textEV0515
ePoster Viewing
Diagnostic/laboratory methods other than molecular
Candida spp. infections after abdominal urgent surgery: comparative analysis of histologic data for which microbiological results were positive for Candida spp.
V. Rodolico1, G. Gulotta1, L. Montana1, G. Salamone1, D.C. Paola1
1Department of Sciences for Health Promotion and Mother Child Care, Palermo, Italy
Objectives: Microbiological identification is justified when the yeast is isolated from a sterile site, the potential clinical impact of identified
isolates from non sterile sites such as intra- abdominal organs don’t help the clinicians to determine whether the strain isolate represents
contamination, colonization, or true infection. To investigate the contribute of hystopathological investigations in surgical patients who survive
the initial postoperative period we compare histological and microbiological results positive for Candida spp. Methods: A retrospective study
of abdominal intraoperative tissue or biopsy specimens obtained from patients admitted for acute abdomen with post-operative
microbiological samples positive for Candida spp was performed for the years January 2008 to December 2012. Specimens obtained from
autopsy cases were excluded. For each case, demographic data, mortality, comorbidity conditions, antimicrobial therapy, specimen type,
the use of special histologic stains, any reported suggestion to correlate with or defer to microbiology, and the individual surgical pathologist
were recorded. Results: we evaluated 66 positive candida spp culture reports of which 56 had a concurrent surgical pathology specimen; of
the 56 cases 5 were excluded because of a known history of fungal infection, among the remaining we selected 23 (15%) histological
results because in these patients clinical, microbiological and enventual other histopathological follow-up data were available. Table 1
showed microbiological and hystopathological data. When other than blood culture specimens such as drainage were positive for candida
infection the result was suitable with histological picture. On the other hand, when the blood culture was positive the hystopathological
results (proliferative and granulomatous inflammation accompanied by numerous macrophages, lymphocytes, plasma cells and
neutrophils) were compatible with the patients’ complications to confirm that Candida spp. is a frequent opportunistic pathogen especially in
cancer disease. In table we showed comparative analysis of 23 histologic data for which microbiological results were positive for Candida
spp.
Microbiological Specimen
Positive for Candida spp (n) Concorde
Histological features Candida specie Comorbidity Outcome
(Died)
Blood 6 1 C. albicans=3C. nonalbicans=
3 Cancer=5; Cholecistitis=1 3 (c.
albican=2)
Bile 4 / C. albicans=1C. non
albicans=3
Cancer=2Chronic gastritis plus
cholecystitis =2
Drainage 6 6 C. albicans=4C. non
albicans=2 Cancer= 4Fistula=2 3 ( c.
albicans)
Biopsy 4 4 C. albicans=4C. non
albicans= Cancer=2Fistula=2 1 (c. non
albicans)
Urine 1 1 C. albicans
Bile plus blood 2 2 C. albicans
Conclusions: Post- operative Candida spp infection is an important cause of morbidity and is frequently associated with poor prognosis,
particularly in higher risk patients. Complicated intra-abdominal infections diagnosis is mainly a clinical diagnosis, therefore, low expansive
supplemental procedures for diagnosis, such as histopathology examination provide insight into the diagnostic significance of Candida spp
isolated from surgical specimens other than blood samples
Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
No full textA few patients with Hashimoto's thyroiditis or Graves' disease develop a multiform syndrome of the central nervous system (CNS) termed Hashimoto's encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroid disease (HE/SREAT). They have high levels of thyroid autoantibodies (TgAb, TPOAb and/or TSH-R-Ab) in blood and cerebrospinal fluid. Autoantibodies against alpha-enolase, aldehyde reductase-I (AKRIA) and/or dimethylargininase-I (DDAHI), proteins expressed in the CNS among other tissues, were detected in the blood and, when searched, in the cerebrospinal fluid of HE/SREAT patients. Recently, we reported that alpha-enolase, AKRIA and DDAHI share local sequence homology with each of the three autoantigens (TgAb, TPOAb, TSH-R-Ab), often in epitope-containing segments of the thyroid autoantigens. We hypothesized that there might be additional CNS-expressed proteins homologous to thyroid autoantigens, possibly overlapping known epitopes of the thyroid autoantigens. We used bioinformatic methods to address this hypothesis. Six, 27 and 47 of 46,809 CNS-expressed proteins share homology with TSH-R, Tg and TPO, respectively. The homologous regions often contain epitopes, and some match regions of thyroid autoantigens which have homology with alpha-enolase, AKRIA and/or DDAHI. Several of the aforementioned proteins are present in CNS areas that show abnormalities at neuroimaging in HE/SREAT patients. Furthermore, autoantibodies against some of the said six, 27 and 47 proteins were reported to be associated with a number of autoimmune diseases. Not only we validated our hypothesis, but we think that such a variety of potential CNS targets for thyroid Ab against epitopes contained in regions that have local homology with CNS proteins may explain the polymorphic phenotypes of HE/SREAT. Only when elevated amounts of these Ab are synthesized and trespass the blood-brain barrier, HE/SREAT appears. This might explain why HE/SREAT is so relatively rare
The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.
No full textAims
To assess whether host metabolic factors influence the degree of hepatic
steatosis and fibrosis in patients infected with hepatitis C virus, and to
evaluate the impact of anti-viral therapy on insulin resistance and
serum levels of adipocytokines.
Methods
Clinical and biochemical features, anthropometrical characteristics, and
levels of fasting insulin, leptin, adiponectin and resistin were measured
in ‘naı ̈ve’ patients with chronic hepatitis C, before, during and after
therapy with Peg-Interferon-alpha 2a plus Ribavirin.
Results
Forty-eightpatientswereincluded(M/F28/20;meanage50.0 12.6years;
62.5% genotype-1). Body mass index was 26.4 4.0 kg/m2
, and visceral
obesity was present in 24 patients. At multivariate analysis (RR; 95% CI),
steatosis was associated to older age (1.08; 1–1.18), necroinflammatory
activity (17.67; 1.6–194.46), and raised insulin levels (1.39; 1.1–1.77).
Fibrosis was related to necroinflammatory activity (25.73; 2.54–261.11),
and steatosis (6.47; 1.09–38.29). Sustained viral response was achieved by
62.5% of patients and was associated with younger age (0.92; 0.85–0.99),
genotype non-1 (10.61; 1.52–73.76) and absence of visceral obesity (13.78;
2.36–80.29). At the end of follow-up, insulin and the homeostasis model
assesment for insulin resistance were reduced and adiponectin increased
whencompared withbaseline,all unrelatedtotheoutcome oftreatment.
Conclusions
Visceral obesity correlates with the degree of steatosis and fibrosis, and
it negatively affects treatment response. Significant changes of insulin
resistance and adipocytokines occur under treatment, irrespective of virological
outcome
Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression
No full textThe nuclear gene TK2 encodes the mitochondrial thymidine kinase, an enzyme involved in the phosphorylation of deoxycytidine and deoxythymidine nucleosides. Biallelic TK2 mutations are associated with a spectrum of clinical presentations mainly affecting skeletal muscle and featuring muscle mitochondrial DNA (mtDNA) instability. Current classification includes infantile- (≤ 1 year), childhood- (1–12 years), and late-onset (≥12 years) forms. In addition to age at onset, these forms differ for progression, life expectancy, and signs of mtDNA instability (mtDNA depletion vs. accumulation of multiple mtDNA deletions). Childhood-onset TK2 deficiency typically causes a rapidly progressive proximal myopathy, which leads to wheelchair-bound status within 10 years of disease onset, and severe respiratory impairment. Muscle biopsy usually reveals a combination of mitochondrial myopathy and dystrophic features with reduced mtDNA content. Here we report the case of an Italian patient presenting childhood-onset, slowly progressive mitochondrial myopathy, ptosis, hypoacusis, dysphonia, and dysphagia, harboring the TK2 variants c.278A>G and c.543del, the latter unreported so far. Compared to other childhood-onset TK2-patients, our case displays atypical features, including slowly progressive muscle weakness and absence of respiratory failure, which are usually observed in late-onset forms. This report extends the genetic background of TK2-related myopathy, highlighting the clinical overlap among different forms
Intra-abdominal Candida spp infection in acute abdomen in a quality assurance (QA)-certified academic setting
No full textAims To evaluate the contribution of light microscopy to detecting Candida spp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward. Methods We conducted a retrospective study (2008-2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive for Candida spp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved. Results Sixty-six patients with complicated IAIs due to Candida spp were identified (39 male, 27 female, mean±SD age 75±20...years). Candida albicans was isolated in 35 cases and Candida non-albicans spp in 31 cases. Candida spp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according to Candida spp (albicans vs non-albicans), underlying cancer disease and no previous antimicrobial administration, and a positive correlation with C. albicans isolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative of Candida spp, in 23. Identification of Candida spp in histological specimens was higher in C. albicans cases than in C. non-albicans cases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients. Conclusions Light microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer
Rituximab in AChR subtype of myasthenia gravis: Systematic review
No full textMyasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999-2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients' evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment
PathVisio Analysis: An Application Targeting the miRNA Network Associated with the p53 Signaling Pathway in Osteosarcoma
No full textMicroRNAs (miRNAs) are small single-stranded, non-coding RNA molecules involved in the pathogenesis and progression of cancer, including osteosarcoma. We aimed to clarify the pathways involving miRNAs using new bioinformatics tools. We applied WikiPathways and PathVisio, two open-source platforms, to analyze miRNAs in osteosarcoma using miRTar and ONCO.IO as integration tools. We found 1298 records of osteosarcoma papers associated with the word "miRNA". In osteosarcoma patients with good response to chemotherapy, miR-92a, miR- 99b, miR-193a-5p, and miR-422a expression is increased, while miR-132 is decreased. All identified miRNAs seem to be centered on the TP53 network. This is the first application of PathVisio to determine miRNA pathways in osteosarcoma. MiRNAs have the potential to become a useful diagnostic and prognostic tool in the management of osteosarcoma. PathVisio is a full pathway editor with the potentiality to illustrate the biological events, augment graphical elements, and elucidate all the physical structures and interactions with standard external database identifiers
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