Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.

Femoral bone mineral density at the time of hip fracture is higher in women with versus without type 2 diabetes mellitus: a cross-sectional study.

PURPOSE: To compare femoral bone mineral density (BMD) levels in hip-fracture women with versus without type 2 diabetes mellitus (T2DM). We hypothesized that BMD levels could be higher in the women with T2DM than in controls and we aimed to quantify the BMD discrepancy associated with the presence of T2DM. METHODS: At a median of 20 days after the occurrence of an original hip fracture due to fragility we measured BMD by dual-energy x-ray absorptiometry at the non-fractured femur. RESULTS: We studied 751 women with subacute hip fracture. Femoral BMD was significantly higher in the 111 women with T2DM than in the 640 without diabetes: mean T-score between-group difference was 0.50, (95% CI from 0.30 to 0.69, P < 0.001). The association between the presence of T2DM and femoral BMD persisted after adjustment for age, body mass index, hip-fracture type, neurologic diseases, parathyroid hormone, 25-hydroxyvitamin D and estimated glomerular filtration rate (P < 0.001). For a woman without versus with T2DM, the adjusted odds ratio to have a femoral BMD T-score below the threshold of - 2.5 was 2.13 (95% CI from 1.33 to 3.42, P = 0.002). CONCLUSIONS: Fragility fractures of the hip occurred in women with T2DM at a femoral BMD level higher than in control women. In the clinical assessment of fracture risk, we support the adjustment based on the 0.5 BMD T-score difference between women with and without T2DM, although further data from robust longitudinal studies is needed to validate the BMD-based adjustment of fracture risk estimation.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.

BACKGROUND: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. INTRODUCTION: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. MATERIAL AND METHODS: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. RESULTS: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. CONCLUSION: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Perfil clínico e incidência de eventos cardiovasculares em 36 meses em pacientes com Minoca: registro de 126 pacientes em um hospital terciário de cardiologia / Clinical profile and incidence of cardiovascular events at 36 months in patients with Minoca: registry of 126 patients in a tertiary cardiology hospital

INTRODUÇÃO: Em 5% a 6% dos IAM não são observadas lesões obstrutivas maiores que 50%, sendo estes classificados como MINOCA (Infarto do Miocárdio com Artérias Coronárias não Obstrutivas). Estudos maiores de longo prazo demonstraram que o prognóstico desses pacientes não é benigno com risco aumentado de morte e novos eventos cardiovasculares. MÉTODOS: Nesta coorte de centro único, todos os pacientes que preencheram os critérios diagnósticos para MINOCA com (1) IAM (2) ausência de estenose coronária ≥ 50% na artéria relacionada ao infarto e (3) nenhuma outra causa específica clinicamente evidente entre março de 2000 e junho de 2022 foram incluídos com um acompanhamento médio de 30 (9,5-67,3) meses. As características da amostra foram descritas em frequências e valores medianos (p25%-p75%). A incidência de um novo evento cardiovascular (CV) em 36 meses após a MINOCA foi estimada pelo método de Kaplan-Meier e o teste de log-rank aplicado para comparar os grupos, acompanhado de intervalos de confiança de 95% e alfa de 5% (R 3,6,1 para MacOS). RESULTADOS: Dos 126 pacientes, 57,1% eram mulheres com cerca de 50 anos de idade (42,0-57,8). 20,6% tinham diabetes, 47,6% dislipidemia, 60,3% hipertensão e 20% IAM prévio. A apresentação clínica predominante foi IAMSSST (55,6%) e 7 pacientes tiveram um episódio de morte súbita abortada durante a internação. 38,1% dos pacientes não tiveram uma etiologia identificada. O mecanismo fisiopatológico mais prevalente foi ruptura da placa < 50% (16,7%), seguido de tromboembolismo (13,5%) e dissecção espontânea de coronária (13,5%). Apenas 3,2% realizaram tomografia de coerência óptica (OCT) ou ultrassom intravascular (IVUS). Nenhum teste provocativo foi realizado. 44,4% realizaram ressonância magnética cardíaca (RMC), com mediana de tempo para realização de 180,0 (60,0-707,5) dias após o evento. Em relação à medicação prescrita na alta hospitalar, 79,4% tiveram betabloqueador e IECA/BRA prescritos, 14,3% iniciaram anticoagulação e apenas 34,1% receberam dupla antiagregação plaquetária (DAP). A incidência do desfecho composto (morte CV, novo IAM, AVC e internação CV) em 36 meses foi de 15% (IC95% 8,9%-24,6%). A incidência de novo IAM foi de 6,3% (N=8), de AVC 2,4% (N=3), de hospitalização CV 17,5% (N=22) e apenas um óbito. CONCLUSÃO: Chama a atenção o risco do desfecho primário em 36 meses. Notavelmente, a maior parte da incidência foi atribuída à hospitalização CV. Um número importante de pacientes recebeu alta sem etiologia conhecida para sua apresentação clínica e, consequentemente, sem tratamento individualizado.

Strengthening preparedness against global health threats: A paradigm shift based on One Health approaches.

The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

Polypharmacy is a determinant of hospitalization in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease (PD) are at a higher risk of hospitalization and recurrent hospitalizations, with consequent complications. Polypharmacy is associated with several adverse outcomes, including hospitalization, increased length of hospital stay, and mortality. The aim of this study was to evaluate among patients with PD the association between the number of medications and incident hospitalizations. PATIENTS AND METHODS: We analysed the data of 165 patients with Parkinson's disease attending a geriatric Day Hospital who were enrolled in a cohort study and followed for a median of two years. RESULTS: Over the follow-up, 46 participants (46%) were hospitalized at least one time; multiple admissions were observed in 12 subjects (7%). The median number of agents was 5 (4-7). In Cox regression, the number of drugs was associated with increased hospitalization rates (HR=1.23; 95% CI=1.06-1.43), also after excluding non-neurological medications (HR=1.18; 95% CI=1.01-1.38). Using Poisson regression, polypharmacy (i.e., use of >5 drugs) predicted the number of repeated hospitalizations (IRR=2.62; 95% CI=1.28-5.36; p=.008). CONCLUSIONS: Among patients with PD, the number of daily medications is associated with increased risk of hospitalization; an increasing number of drugs is associated with increasing number of hospitalizations.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.

BACKGROUND: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. INTRODUCTION: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. MATERIAL AND METHODS: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. RESULTS: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. CONCLUSION: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Assessment of neurological manifestations in hospitalized patients with COVID-19.

BACKGROUND AND PURPOSE: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. METHODS: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. RESULTS: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. CONCLUSIONS: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

The anti-proliferative effects of adiponectin on human lung adenocarcinoma A549 cells and oxidative stress involvement.

Adiponectin (Acrp30) plays an important role in energy metabolism and inflammation. Recently, in vivo serum Acrp30 levels have been reported to be correlated to risk of developing several types of cancers such as lung cancer, and in vitro studies have demonstrated a role for Acrp30 in the control of cell proliferation and survival. However, the molecular effects of Acrp30 on lung cancer have not yet been clearly defined. In the present study, we investigated the effects of different concentrations of Acrp30 on the A549 human alveolar epithelial cell line, an in vitro model of lung adenocarcinoma. A549 cells were exposed to various concentrations of Acrp30 and successively, proliferation, apoptosis and oxidative stress were evaluated by MTT test, caspase activity assay, flow-cytometry and western blotting analysis. Our results demonstrated that Acrp30 causes, in a time- and dose-dependent manner, a reduction of cell viability and duplication together with an increase in cell apoptosis rate. In addition, we found that Acrp30 induces an increase of lipid peroxidation evaluated by TBARS assay and a concomitant reduction of nitric oxide release, both markers of cellular oxidative stress. Taken together, our data on A549 cells provides new insight into potential involvement of Acrp30 on physio-pathologic mechanisms of lung diseases through interference with proliferation, apoptosis and oxidative status.

Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy.

OBJECTIVES: A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. METHODS: Between 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. RESULTS: Of 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor-recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-ß-lactamase (VIM)-producing Enterobacter aerogenes. CONCLUSIONS: This study showed a low risk of donor-recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

Adiponectin profile at baseline is correlated to progression and severity of multiple sclerosis.

BACKGROUND AND PURPOSE: Adiponectin is a cytokine linking energy metabolism and immune system. After being assembled, adiponectin circulates as oligomers of different molecular weight, i.e. low, medium and high (HMW) molecular weight. These have the most potent biological effects. Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system. The aim of this study was to characterize the expression levels of both total adiponectin and its oligomerization state in the serum from 99 patients with MS at baseline (i.e. not influenced by therapies). We also investigated the potential relationships between adiponectin and disease progression and severity. METHODS: Adiponectin was quantified and visualized by enzyme-linked immunosorbent assay, western blotting and fast protein liquid chromatography. During the follow-up (3.6 ± 2.20 years), the patients were evaluated using total annualized relapse rate and Expanded Disability Status Scale score. RESULTS: Total adiponectin is statistically higher in patients with MS compared with matched controls (12.18 vs. 10.02 µg/mL, P = 0.001). Interestingly, the adiponectin oligomerization state is altered in MS, with an increase of HMW oligomers. In addition, patients with MS with higher levels of adiponectin at baseline have significantly higher risk of progression and severity (Multiple Sclerosis Severity Score, 3.84 vs. 2.44, P = 0.001). No statistical difference in adiponectin expression was found between active and inactive patients with MS and among the different forms of disease. CONCLUSIONS: This study demonstrated that adiponectin and its HMW oligomers are greatly involved in MS autoimmune disorder representing a potential biomarker to predict worse MS prognosis and severity. Further studies are required to clarify the molecular mechanisms underlying the properties of adiponectin and HMW oligomers in MS.

Laterality in Parkinson's disease may predict motor and visual imagery abilities.

Experimental evidence suggests that motor imagery (MI) engages the same neural substrates supporting actual motor activities and is likely impaired when such substrates are damaged, as in Parkinson's disease (PD). MI intuitively relies on visual imagery (VI), because mental simulations of physical movements depend on the visual retrieval of these movements. Although VI is generally considered a right hemispheric function, the hemispheric dominance of MI is still in dispute. Disparities in sidedness of motor disturbances are a distinctive feature of PD, and recent findings indicate that such disparities may similarly characterize cognition. Specifically, the deficits observed may depend upon which hemisphere is principally involved. Essentially, MI and VI are cognitive tasks subject to differential impairment and reflecting the prevalence of hemispheric impairment in PD. Motor imagery (assessed by the Vividness of Motor Imagery Questionnaire [VMIQ]) and VI (assessed by the Vividness of Visual Imagery Questionnaire [VVIQ] and Test of Visual Imagery Control [TVIC]) were examined in patients with asymmetric PD and in healthy elderly control subjects (HC group). VMIQ scores were similar in PD laterality subsets and the HC group, but VVIQ scores were significantly lower in both PD groups compared with the HC group. TVIC scores were significantly lower in the presence of left motor (right hemispheric) impairment and were predictive of left motor (right hemispheric) impairment. We suspect that MI is strongly reliant on VI and that language may mediate these two functions, to the extent that both are evoked through verbal stimuli. Working memory, both visual and verbal, is also involved in MI and VI tasks. Without due attention to laterality of symptoms, any training incorporating MI and VI may not deliver expected outcomes in the setting of asymmetric PD symptomatology.

Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines.

Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic and anti-inflammatory properties. Colorectal cancer is among the most common cancers worldwide. The aim of present study was to explore the effects of Acrp30 on both CaCo-2 and HCT116 colorectal cancer cells in terms of viability, oxidative stress, and apoptosis. In addition, since colorectal cancer represents a typical inflammation-related cancer, we investigated whether Acrp30 treatment modifies the migration and the expression of crucial proteins in the EMT transition. Finally, we analyzed the expression of cytokines in CaCo-2 cells. We found that Acrp30 reduces the survival rate of both CaCo-2 and HCT116 cells through induction of apoptosis and oxidative stress already after 24 h of treatment. In addition, wound-healing assay indicated that Acrp30 exposure statistically inhibits CaCo-2 and HCT116 cell migration. Western blot analysis performed on E-cadherin and vimentin, two EMT crucial markers in carcinogenesis, indicated that Acrp30 does not influence EMT transition. Finally, we found a reduction of mRNA levels corresponding to the anti-inflammatory IL-10 cytokine together with an increase of the pro-inflammatory IL-6 and IL-8 cytokines. This study provides new insight into Acrp30 molecular effects on colorectal cancer cells. Indeed, even if further studies are necessary to clarify the precise role of Acrp30 in colorectal cancer, our data strongly suggest that Acrp30 negatively regulates cell survival and migration in association with induction of oxidative stress and regulation of cytokines expression in both CaCo-2 and HCT116 colorectal cells.

Colonization by multidrug-resistant organisms in long-term care facilities in Italy: a point-prevalence study.

OBJECTIVES: To determine prevalence and risk factors for colonization by multidrug-resistant organisms (MDROs) in long-term care facility (LTCF) residents in Italy. Genotypes of MDRO isolates were investigated. METHODS: A point-prevalence study was conducted at 12 LTCFs located in four Italian cities (2 February to 14 March 2015). Rectal swabs, faeces and nasal/auxiliary swabs were cultured for extended-spectrum ß-lactamase (ESBL)- and/or carbapenemase-producing Enterobacteriaceae, Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) respectively. Antimicrobial susceptibility testing, detection of ESBL and/or carbapenemase genes and molecular typing of MDROs were performed. Risk factors for colonization were determined by univariate and multivariate analysis. RESULTS: A total of 489 LTCF residents aged ≥65 years were enrolled. The prevalence of colonization by ESBL-producing Enterobacteriaceae, MRSA and C. difficile was 57.3% (279/487), 17.2% (84/487) and 5.1% (21/409) respectively. Carriage rate of carbapenemase-producing Enterobacteriaceae was 1% (5/487). Being bedridden was a common independent risk factor for colonization by all MDROs, although risk factors specific for each MDRO were identified. ESBL-producing Escherichia coli carriage was associated with the sequence type (ST) 131-H30 subclone, but other minor STs predominated in individual LTCF or in LTCFs located in the same city, suggesting a role for intrafacility or local transmission. Similarly, MRSA from LTCF residents belonged to the same spa types/ST clones (t008/ST8 and t032/ST22) commonly found in Italian acute-care hospitals, but infrequent spa types were recovered in individual LTCFs. The prevalent C. difficile PCR ribotypes were 356/607 and 018, both common in Italian acute-care hospitals. CONCLUSIONS: MDRO colonization is common among residents in Italian LTCFs.

Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience.

BACKGROUND AND PURPOSE: Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. METHODS: To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. RESULTS: A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. CONCLUSIONS: In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis.

Differentially expressed and activated proteins associated with non small cell lung cancer tissues.

BACKGROUND: Lung cancer is a leading cause of mortality. The most common cancer subtype, non small cell lung cancer (NSCLC), accounts for 85-90% all cases and is mainly caused by environmental and genetic factors. Mechanisms involved in lung carcinogenesis include deregulation of several kinases and molecular pathways affecting cell proliferation, apoptosis and differentiation. Despite advances in lung cancer detection, diagnosis and staging, survival rate still remains poor and novel biomarkers for both diagnosis and therapy need to be identified. In the present study, we have explored the potential of novel specific biomarkers in the diagnosis of NSCLC, and the over-expression/activation of several kinases involved in disease development and progression. METHOD: Lung tumor tissue specimens and adjacent cancer-free tissues from 8 NSCLC patients undergoing surgery were collected. The differential activation status of ERK1/2, AKT and IKBα/NF-κß was analyzed. Subsequently, protein expression profile of NSCLC vs normal surrounding tissue was compared by a proteomic approach using LC-MS MS. Subsequently, MS/MS outputs were analyzed by the Protein Discoverer platform for label-free quantitation analysis. Finally, results were confirmed by western blotting analysis. RESULTS: This study confirms the involvement of ERK1/2, AKT, IKBα and NF-κß proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Furthermore, we found significant differential expression of 20 proteins (Rsc ≥ 1.50 or ≤ -1.50) of which 7 are under-expressed and 13 over-expressed in NSCLC lung tissues. Finally, we validated, by western blotting, the two most under-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms. CONCLUSION: Our data further support the possibility of developing both diagnostic tests and innovative targeted therapy in NSCLC. In addition to selective inhibitors of ERK1/2, AKT, IKBα and NF-κß, as therapeutic options, our data, for the first time, indicates carbonic anhydrase I and II as attractive targets for development of diagnostic tools enabling selection of patients for a more specific therapy in NSCLC.

[Prevalence of genital anomalies in young football players]. / Prevalencia de anomalías genitales en futbolistas jóvenes.

The purpose of genital examination (GE) during the Pre-participation Physical Examination (PPE) is to identify the state of maturity, and rule out any genital pathology. To describe genital anomalies (GA) and estimate the awareness of GE in young football players. A descriptive, cross-sectional study was conducted in 280 elite football players from the results of PPE over two seasons. There was a detection rate of 5.4% GA, with varicocele being 3.2%, and of which only 13% were aware of their condition. Although this study shows a low incidence of genital abnormality in the study population, only 13% were aware of the GE prior to assessment. These findings demonstrate a low incidence of GA in this population. While GE is recommended during PPE, it is not a routine practice performed by family doctors or sports medicine specialists. This article attempts to raise awareness of the importance of GE in PPE as a preventive health strategy.