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1.
Eur J Orthop Surg Traumatol ; 34(1): 433-440, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37573541

ABSTRACT

PURPOSE: The management of isolated SLAP lesions is still debated especially in athletes. Aims of the study were: 1. to analyse our algorithm to treat SLAP lesions starting from the selection of patients for surgery and 2. to correlate the familiarity for diabetes and hypothyroid disorders with post-operative results. METHODS: Seventy-eight patients with isolated SLAP lesion were arthroscopically treated using knotless anchors and microfractures. All patients had a pre-operative and post-operative clinical examination according to Walch-Duplay, Constant, Rowe and Dash scores and interviewed for familiarity to diabetes and hypothyroid disorders. RESULTS: About 68.8% of patients solved pain with rehabilitation. About 29% of patients returned to the sports activities. About 32% of patients were no responder to physiotherapy and were arthroscopically treated. About 53.9% of patients responded excellent, 34.7% good, 3.8% medium and 7.6% poor results according to Walch-Duplay score. The Constant score increased from 64 to 95, the Rowe score from 48 to 96. The outcomes were significantly worse in patients with familiarity for diabetes. CONCLUSIONS: Microfractures and knotless anchor give long-term good results for the treatment of SLAP lesions in athletes. The familiarity for diabetes is an important risk factor that can lead to decreased outcomes.


Subject(s)
Diabetes Mellitus , Fractures, Stress , Shoulder Injuries , Shoulder Joint , Tendon Injuries , Humans , Fractures, Stress/etiology , Tendon Injuries/surgery , Arthroscopy/adverse effects , Arthroscopy/methods , Suture Anchors , Risk Factors , Shoulder Joint/surgery , Shoulder Injuries/surgery
2.
J Endocrinol Invest ; 45(4): 753-762, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34792796

ABSTRACT

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.


Subject(s)
COVID-19/complications , Respiratory Insufficiency/etiology , Testosterone/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/mortality , Survival Rate
3.
J Endocrinol Invest ; 44(10): 2285-2293, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33666876

ABSTRACT

PURPOSE: Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. METHODS: Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. RESULTS: In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). CONCLUSION: This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.


Subject(s)
COVID-19/complications , Hyperparathyroidism/complications , Respiratory Insufficiency/complications , Vitamin D Deficiency/complications , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/therapy , Female , Humans , Hyperparathyroidism/blood , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Retrospective Studies , Treatment Outcome , Vitamin D Deficiency/blood
4.
J Hum Hypertens ; 31(1): 37-42, 2017 01.
Article in English | MEDLINE | ID: mdl-26911533

ABSTRACT

Familiarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67-3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66-3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01-2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87-4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype.


Subject(s)
Chromosomes, Human, X , Hypertension/genetics , Female , Humans , Male , Maternal Inheritance , Middle Aged , Phenotype , Polymorphism, Single Nucleotide
5.
Musculoskelet Surg ; 101(1): 75-83, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28004306

ABSTRACT

PURPOSE: The treatment of chronic anterior shoulder instability with glenoid bone loss is still debated. The purpose of this study is to compare short-term results of two techniques treating chronic shoulder instability with moderate glenoid bone loss: bone block according to open Latarjet-Patte procedure and arthroscopic Bankart repair in association with subscapularis augmentation. METHODS: Ninety-one patients with moderate anterior glenoid bone loss underwent from 2011 to 2015. From these patients, two groups of 20 individuals each have been selected. The groups were homogeneous in terms of age, gender, dominance and glenoid bone loss. In group A, an open Latarjet procedure has been performed, and in group B, an arthroscopic Bankart repair associated with subscapularis augmentation has been performed. The mean follow-up in group A was 21 months (20-39 months), while in group B was 20 months (15-36 months). QuickDash score, Constant and Rowe shoulder scores, were used for evaluations of results. RESULTS: The mean preoperative rate of QuickDash score was 3.6 for group A and 4.0 for group B; Rowe Score was 50.0 for group A and 50.0 for group B. Preoperative mean Constant score was 56.2 for Latarjet-Patte and 55.2 for Bankart plus ASA. Postoperative mean QuickDash score was in group A 1.8 and 1.7 in group B; Rowe Score was 89.8 and 91.6; Constant Score was 93.3 and 93.8. No complications related to surgery have been observed for both procedures. Not statistically significant difference was reported between the two groups (p > .05). Postoperatively, the mean deficit of external rotation in ER1 was -9° in group A and -8 in group B; In ER2, the mean deficit was -5° in both groups (p = .0942). CONCLUSIONS: Arthroscopic subscapularis augmentation of Bankart repair is an effective procedure for the treatment of recurrent anterior shoulder instability with glenoid bone loss without any significant difference in comparison with the well-known open Latarjet procedure.


Subject(s)
Arthroplasty/methods , Arthroscopy/methods , Glenoid Cavity/surgery , Shoulder Dislocation/surgery , Adolescent , Adult , Female , Follow-Up Studies , Humans , Joint Instability/surgery , Male , Range of Motion, Articular , Retrospective Studies , Rotator Cuff/surgery , Scapula/surgery , Shoulder Dislocation/diagnosis , Treatment Outcome
6.
Transl Med UniSa ; 14: 28-37, 2016 May.
Article in English | MEDLINE | ID: mdl-27326393

ABSTRACT

GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechanisms by which GRK5 exerts its effects, and the potential therapeutic strategies to modulate them.

7.
Transl Med UniSa ; 14: 42-53, 2016 May.
Article in English | MEDLINE | ID: mdl-27326395

ABSTRACT

High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

8.
J Endocrinol Invest ; 39(10): 1095-103, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27180180

ABSTRACT

Type 2 diabetes (T2D) and obesity are the major public health problems. Substantial efforts have been made to define loci and variants contributing to the individual risk of these disorders. However, the overall risk explained by genetic variation is very modest. Epigenetics is one of the fastest growing research areas in biomedicine as changes in the epigenome are involved in many biological processes, impact on the risk for several complex diseases including diabetes and may explain susceptibility. In this review, we focus on the role of DNA methylation in contributing to the risk of T2D and obesity.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Epigenesis, Genetic/genetics , Obesity/genetics , Humans
9.
Osteoporos Int ; 27(7): 2355-2365, 2016 07.
Article in English | MEDLINE | ID: mdl-26856585

ABSTRACT

UNLABELLED: In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. INTRODUCTION: Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. METHODS: Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. RESULTS: DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients.


Subject(s)
Bone Remodeling , Diphosphonates/therapeutic use , Osteogenesis Imperfecta/drug therapy , Osteogenesis Imperfecta/physiopathology , Adaptor Proteins, Signal Transducing , Bone Morphogenetic Proteins/blood , Child , Female , Genetic Markers , Glycoproteins , Humans , Intercellular Signaling Peptides and Proteins/blood , Male , Osteoclasts/cytology , Osteogenesis , Osteoprotegerin/blood , RANK Ligand/blood , Tumor Necrosis Factor-alpha/blood
10.
Musculoskelet Surg ; 99 Suppl 1: S17-23, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25962807

ABSTRACT

PURPOSE: The aim of this study is to report the clinical and radiological results of reverse total shoulder arthroplasty (rTSA) in elderly patients who have been treated for complex humeral fractures. MATERIALS AND METHODS: From January 2005 to December 2014, we have implanted rTSA for proximal humeral fractures in 95 patients (80 women, 15 men) about 75 years old on average (range 62-95 years). All rates and results on intraoperative and postoperative complications have been collected in a specific database. In all cases we have used a modular implant prosthesis (Lima Corporate, San Daniele del Friuli, Italy). The prosthesis was implanted cementless in 92 cases. Because of the presence of a high percentage of comorbidities in the elderly patients, we have retrospectively analyzed the necessity of a secondary hospitalization, from a week to a 6-month time after the discharge, due to general health problems and specific postoperative shoulder complications. The mean follow-up was 5 years (range 1-9 years) for 70 of 95 patients, 50 of whom had adequate radiographic controls. RESULTS: None of 95 patients has required a reoperation or a hospitalization for general health problems from 1 week to 6 months postoperative. No early or late infection of prosthesis has been observed. There were seven cases of perioperative complications, three humeral vertical bone fissuring, two glenoid fractures and two cases of deltoid muscle damage. We have had three cases of postoperative hematoma and one case of ulnar nerve neuropathy. The mean constant score was 85.4, and the mean simple shoulder test was 7.4. We have observed a grade 1 scapular notching in 15 cases (30 %). In the remaining 35 reviewed cases, there was no notching. Peri-articular heterotopic ossifications were found in 11 cases (22 %). CONCLUSION: Reverse shoulder prosthesis in complex humeral fractures in the elderly can be considered as a reliable surgical procedure, which leads to very good clinical and radiological results in case of cementless prosthesis, as well.


Subject(s)
Arthroplasty, Replacement, Shoulder/methods , Shoulder Fractures/surgery , Shoulder Prosthesis , Aged , Aged, 80 and over , Arthroplasty, Replacement, Shoulder/instrumentation , Female , Humans , Length of Stay , Male , Middle Aged , Postoperative Complications , Radiography , Reoperation , Shoulder Fractures/diagnostic imaging , Shoulder Fractures/rehabilitation , Shoulder Joint/diagnostic imaging , Time Factors , Treatment Outcome
11.
Br J Cancer ; 112(1): 77-85, 2015 Jan 06.
Article in English | MEDLINE | ID: mdl-25422906

ABSTRACT

BACKGROUND: p53 is a transcription factor with tumour suppressor properties, which is able to induce mitochondrial apoptosis independently of its transcriptional activity. We recently synthesised two new compounds (ISA27 and SM13), which block p53-MDM2 interaction and induce apoptosis in p53 wild-type (WT) tumour cells. The aim of this study was to verify the effectiveness of these compounds in tumours carrying a mutated form of p53 gene with no transcriptional activity. METHODS: In vitro we evaluated the effectiveness of our compounds in cancer cell lines carrying WT, mutated and null p53 gene. In vivo study was performed in Balb/c nude mice and the mitochondrial-dependent apoptotic signalling was evaluated by western blot. RESULTS: Both ISA27 and SM13 reduced cell proliferation and induced apoptosis in vitro in cells carrying either p53 WT or mutated gene, suggesting that its effect is independent from p53 transcriptional activity. On the contrary, SM13 had no effect in a p53 null cell line. In vivo, ISA27 and SM13 induced cancer cell death in a dose-dependent manner through the activation of the mitochondrial-dependent death signalling in p53-mutated cells. In vivo, SM13 reduced tumour growth. CONCLUSIONS: Our study proposes SM13 as anticancer compound to use for the treatment of p53-dependent tumours, even in the absence of p53 transcriptional activity.


Subject(s)
Indoles/pharmacology , Mitochondria/drug effects , Neoplasms/drug therapy , Spiro Compounds/pharmacology , Animals , Apoptosis/drug effects , Cell Growth Processes/drug effects , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Mitochondria/metabolism , Mitochondria/pathology , Neoplasms/genetics , Neoplasms/metabolism , Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors , Proto-Oncogene Proteins c-mdm2/metabolism , Small Molecule Libraries/pharmacology , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays
12.
FEBS Lett ; 587(21): 3487-94, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24036448

ABSTRACT

G-protein-coupled receptor kinase 2 (GRK2) levels are elevated in inflammation but its role is not clear yet. Here we show that GRK2 expression is dependent on NFκB transcriptional activity. In macrophages, LPS induces GRK2 accumulation in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal domain of GRK2 (ßARK-ct), known to displace GRK2 from plasma membranes, induces earlier localization of GRK2 to mitochondria in response to LPS leading to increased mt-DNA transcription and reduced ROS production and cytokine expression. Our study shows the relevance of GRK2 subcellular localization in macrophage biology and its potential therapeutic properties in inflammation.


Subject(s)
G-Protein-Coupled Receptor Kinase 2/metabolism , Inflammation/metabolism , Macrophages/metabolism , Mitochondria/enzymology , Animals , Humans , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Mice , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction
13.
Work ; 41 Suppl 1: 863-8, 2012.
Article in English | MEDLINE | ID: mdl-22316830

ABSTRACT

BACKGROUND: Australian children as young as five years are using computers in the home and school environments with increased frequency and longer duration as they age. Consequently, they may be exposed to risk factors for the development of physical health problems described in studies of adult computer users. To date schools have focused on providing children with the latest computer technologies; with far less attention given to appropriate workstations, ergonomics education and incorporating safe computing practices. By better understanding children's attitudes and knowledge, a directional approach to the development of an ergonomics education program may be established using a health promotion framework to encourage healthy computing behaviors. OBJECTIVE: The purpose of this study was to identify children's knowledge of, and attitudes towards healthy computing. METHOD: A cross-sectional inferential study of 537 Australian school children (aged 9 to 11 years) from Catholic Education Schools across Western Australia was conducted. Multiple logistic regression analyses identified that children's beliefs and attitudes about the negative health effects of computers were found to be most associated with unhealthy computing behaviors. RESULTS: Children lacked sufficient knowledge about the importance of postural and task variation, but had sufficient knowledge about adjusting workstation furniture specific to healthy computer use.


Subject(s)
Ergonomics , Health Knowledge, Attitudes, Practice , Microcomputers , Students , Australia , Biomechanical Phenomena , Child , Cross-Sectional Studies , Female , Humans , Interior Design and Furnishings , Male , Posture
14.
Work ; 41 Suppl 1: 869-75, 2012.
Article in English | MEDLINE | ID: mdl-22316831

ABSTRACT

BACKGROUND: Information and communication technologies (ICT), including computers, are becoming commonplace tools for learning by school children in Australia and around the world. Teachers are responsible for integrating ICT into the school learning environment; however, they may not recognize how and when ICT use may compromise their students' physical health. Children's exposure to physical harm through the unhealthy use of ICT may have liability implications for the education sector. OBJECTIVES: To determine (i) whether teachers consider it their responsibility to promote healthy ICT use among their students; (ii) teachers' self-perceived competence to do so; and (iii) what teachers perceive are the barriers and enablers to promoting healthy ICT use among their students. METHOD: An online survey was developed for the study. All Catholic Education school principals in Western Australia (n=157) were sent an email link to the survey for distribution to teachers at their respective schools. Over the three week survey period, 95 teachers completed the survey. Descriptive and inferential statistics were used to analyze the data and summarize participants' responses. RESULTS: Fifty-five percent of teachers agreed they were concerned about their students' physical health when using ICT. Only 19% of teachers reported they frequently or always provided their students with information on how to use computers in their class in a way, so as to promote physical health. Teachers identified barriers to promoting healthy computing use among students including; insufficient time (47%), non-adjustable furniture (46%), and insufficient knowledge (41%). Male teachers reported more confidence in their ability to promote healthy ICT use among students than female teachers. CONCLUSION: Just over half of the teachers in this study were concerned for the physical health of their students when using ICT in the classroom. Respondents identified barriers that limit their ability to promote healthy practices to their students. Designing and implementing school-based computer ergonomics education programmes may assist teachers fulfil their duty of care in regard to the physical health and well-being of their students.


Subject(s)
Faculty , Health Knowledge, Attitudes, Practice , Musculoskeletal Diseases/prevention & control , Professional Competence , Self Efficacy , Adult , Ergonomics , Female , Humans , Interior Design and Furnishings , Male , Microcomputers , Middle Aged , Posture , Time Factors , Western Australia
15.
Diabetologia ; 53(7): 1482-92, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20396999

ABSTRACT

AIMS/HYPOTHESIS: Overexpression of PED (also known as PEA15) determines insulin resistance and impaired insulin secretion and may contribute to progression toward type 2 diabetes. Recently, we found that the transcription factor hepatocyte nuclear factor (HNF)-4alpha binds to PED promoter and represses its transcription. However, the molecular details responsible for regulation of PED gene remain unclear. METHODS: Here we used gain and loss of function approaches to investigate the hypothesis that HNF-4alpha controls chromatin remodelling at the PED promoter in human cell lines. RESULTS: HNF-4alpha production and binding induce chromatin remodelling at the -250 to 50 region of PED, indicating that remodelling is limited to two nucleosomes located at the proximal promoter. Chromatin immunoprecipitation assays also revealed concomitant HNF-4alpha-induced deacetylation of histone H3 at Lys9 and Lys14, and increased dimethylation of histone H3 at Lys9. The latter was followed by reduction of histone H3 Lys4 dimethylation. HNF-4alpha was also shown to target the histone deacetylase complex associated with silencing mediator of retinoic acid and thyroid hormone receptor, both at the PED promoter, and at GRB14 and USP21 regulatory regions, leading to a reduction of mRNA levels. Moreover, HNF-4alpha silencing and PED overexpression were accompanied by a significant reduction of hepatic glycogen content. CONCLUSIONS/INTERPRETATION: These results show that HNF-4alpha serves as a scaffold protein for histone deacetylase activities, thereby inhibiting liver expression of genes including PED. Dysregulation of these mechanisms may lead to upregulation of the PED gene in type 2 diabetes.


Subject(s)
Epigenesis, Genetic/physiology , Hepatocyte Nuclear Factor 4/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Phosphoproteins/metabolism , Acetylation , Animals , Apoptosis Regulatory Proteins , Blotting, Western , Chromatin Assembly and Disassembly/genetics , Chromatin Assembly and Disassembly/physiology , Chromatin Immunoprecipitation , Epigenesis, Genetic/genetics , Hep G2 Cells , Hepatocyte Nuclear Factor 4/genetics , Histones/metabolism , Humans , Intracellular Signaling Peptides and Proteins/genetics , Mice , Mice, Transgenic , Nucleosomes/genetics , Phosphoproteins/genetics , Promoter Regions, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction
16.
Br J Pharmacol ; 153(5): 936-46, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18084315

ABSTRACT

BACKGROUND AND PURPOSE: Intact endothelium plays a pivotal role in post-ischaemic angiogenesis. It is a phenomenon finely tuned by activation and inhibition of several endothelial receptors. The presence of alpha(1)-adrenoceptors on the endothelium suggests that these receptors may participate in regenerative phenomena by regulating the responses of endothelial cells involved in neo-angiogenesis. EXPERIMENTAL APPROACH: We evaluated the expression of the subtypes of the alpha(1)-adrenoceptor in isolated endothelial cells harvested from Wistar-Kyoto (WKY) rats. We explored the possibility these alpha(1)-adrenoceptors may influence the pro-angiogenic phenotype of endothelial cells in vitro. In vivo, we used a model of hindlimb ischaemia in WKY rats, to assess the effects of alpha(1) adrenoceptor agonist or antagonist on angiogenesis in the ischaemic hindlimb by laser Doppler blood flow measurements, digital angiographies, hindlimb perfusion with dyed beads and histological evaluation. KEY RESULTS: In vitro, pharmacological antagonism of alpha(1)-adrenoceptors in endothelial cells from WKY rats by doxazosin enhanced, while stimulation of these adrenoceptors with phenylephrine, inhibited endothelial cell proliferation and DNA synthesis, ERK and retinoblastoma protein (Rb) phosphorylation, cell migration and tubule formation. In vivo, we found increased alpha(1)-adrenoceptor density in the ischaemic hindlimb, compared to non-ischaemic hindlimb, suggesting an enhanced alpha(1)-adrenoceptor tone in the ischaemic tissue. Treatment with doxazosin (0.06 mg kg(-1) day(-1) for 14 days) did not alter systemic blood pressure but enhanced neo-angiogenesis in the ischaemic hindlimb, as measured by all our assays. CONCLUSIONS: Our findings support the hypothesis that the alpha(1)-adrenoceptors in endothelial cells provide a negative regulation of angiogenesis.


Subject(s)
Ischemia/physiopathology , Neovascularization, Physiologic , Receptors, Adrenergic, alpha-1/metabolism , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Blood Pressure/drug effects , Cell Proliferation/drug effects , Doxazosin/pharmacology , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Gene Expression , Hindlimb/blood supply , Hindlimb/pathology , In Vitro Techniques , Phenylephrine/pharmacology , Rats , Rats, Inbred WKY
17.
Chir Organi Mov ; 90(2): 159-69, 2005.
Article in English, Italian | MEDLINE | ID: mdl-16422242

ABSTRACT

Between 1996 and 2003 a total of 19 humeral head osteotomies were performed to treat post-traumatic malunion of the proximal humerus. Mean age was 46 years, ranging from 17 to 71 years. The period of time between traumas and surgeries ranged from 6 to 22 months. Osteotomy procedure was as follows: one after two-part fracture of the greater tuberosity, three after two-part fracture of the surgical neck, five after three-part fracture of the greater tuberosity, eight after four-part fracture, two after complex head splitting fracture, one after two-part fracture with anterior dislocation. Three different types of osteotomies were performed: osteotomy of the humeral neck for varus deformity, isolated osteotomy of the greater tuberosity, and a new osteotomy technique (two-plane and three-plane osteotomy) for three- and four-fragment fracture sequelae. At the time of follow-up evaluation, all 19 patients were questioned regarding pain and function. Excellent results in 14 patients and satisfactory results in 5 were obtained. None of the patients required revision surgery. Findings were recorded using the Constant rating scale. All patients had had significant pain relief after shoulder osteotomy. Range of motion was increased in all patients treated by osteotomy. The success of osteotomy in these cases was based on: patient selection, extensive preoperative evaluation, surgical technique and postoperative rehabilitation.


Subject(s)
Fractures, Malunited/surgery , Osteotomy , Shoulder Fractures/surgery , Adolescent , Adult , Aged , Female , Fractures, Malunited/pathology , Fractures, Malunited/physiopathology , Humans , Male , Middle Aged , Osteotomy/methods , Pain/etiology , Range of Motion, Articular , Retrospective Studies , Shoulder Fractures/pathology , Shoulder Fractures/physiopathology , Treatment Outcome
18.
Chir Organi Mov ; 90(2): 137-43, 2005.
Article in English, Italian | MEDLINE | ID: mdl-16422239

ABSTRACT

Purpose of this study is to analyze the results of a consecutive series of 139 patients affected with anterior-inferior shoulder instability and treated by arthroscopic capsuloplasty using the Thal method with absorbable and non-absorbable Mitek knotless anchors. Much attention was paid to the preoperative and intraoperative selection of patients, excluding from the arthroscopic procedure those with bony Bankart lesions measuring more than 25%, with an inverted-pear glenoid, with engaged Hill-Sachs lesions and patients with HAGL lesions. Pre- and postoperative clinical evaluation was carried out using the Rowe scale. Scores rose from 45-55 to 96 postoperatively. Intra-articular mobilization of the anchors did not occur and peri-metallic lysis was not manifested. Areas of bone resorption were observed in 7 cases (7/38, 18.4%) with the presence of peri-insertional geodes with biological anchors, but this had no effect on the clinical results.


Subject(s)
Joint Instability/surgery , Shoulder Joint/surgery , Suture Techniques , Adolescent , Adult , Arthroscopy/methods , Female , Follow-Up Studies , Humans , Joint Instability/classification , Joint Instability/diagnostic imaging , Male , Radiography , Retrospective Studies , Shoulder Injuries , Shoulder Joint/diagnostic imaging , Suture Techniques/instrumentation
19.
G Ital Nefrol ; 21(4): 371-3, 2004.
Article in Italian | MEDLINE | ID: mdl-15470663

ABSTRACT

With few exceptions renal volume is markedly reduced in patients with end-stage renal disease, a phenomenon which is almost always accompanied by a progressive loss of renal compliance secondary to renal structure fibrosis. We have observed a remarkable renal compliance during an episode of acute pyelonephritis in a patient on long-term dialysis.


Subject(s)
Kidney Failure, Chronic/pathology , Kidney/pathology , Adult , Humans , Male
20.
G Ital Nefrol ; 20(1): 61-4, 2003.
Article in Italian | MEDLINE | ID: mdl-12647288

ABSTRACT

A 26-year-old patient with chronic renal failure presented a spinal cord infarction during haemodialysis. This is the first case of a patient with chronic renal failure maintained on chronic haemodialysis described in literature. In this case, the severity of vascular lesions documented by widespread vascular calcifications were particularly striking.


Subject(s)
Calcinosis/complications , Cardiovascular Diseases/complications , Infarction/etiology , Kidney Failure, Chronic/complications , Spinal Cord/blood supply , Adult , Humans , Kidney Failure, Chronic/therapy , Male , Renal Dialysis
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