Time-Efficacy in SMA Type 1 and 2 Cases Treated with Nusinersen

Spinal muscular atrophy is a neuromuscular degenerative disorder characterized by progressive apoptosis of motor neurons, with severe weakness and bulbar dysfunction. The aim of the study was to analyze the correlations between the moment of initiation of treatment (nusinersen) and clinical evolution, and also the change of electrophysiological parameters and motor scales, fol-lowed up for 2 years. This study was carried out between 2018 and 2022 on 60 SMA children (29 girls, 31 boys), (29 type 1 and 31 type 2; 29 with 2 copies of SMN2, 29 with 3 copies, and 2 with 4 copies), aged between 3 weeks and 196 months, divided into 2 groups according type of SMA. For both types of SMA, statistically significant negative correlations were found between the elapsed interval from the onset of the disease to the initiation of treatment and upper motor acquisitions (type 1: p < 0.0001, r = -0.713, type 2: p<0.001, r = -0.560) and between age at the beginning of treatment and improvement in motor function (type 1: p <0.0001, r =-0.726, type 2: p<0.001, r=-0.553). For patients with type 2 SMA, a negative correlation was also identified between age at the time of onset and motor evolution (p<0.05, r = -0.378). Electrophysiological parameters were strongly positive correlated with motor improvement (p<0.0001, r=0.600). Our study established the necessity of early SMA diagnosis and therapy beginning, and demonstrated that Compound Motor Action Potential can be a predictive factor in the disease's progression

The dynamic of changes of pNFH levels in the CSF compared with the motor scales’ scores during three years of nusinersen treatment in children with spinal muscular atrophy types 2 and 3

Neurofilaments are crucial in neuronal cytoskeleton formation, influencing axonal growth and impulse modulation. This study focuses on understanding the dynamics of the phosphorylated neurofilament heavy subunit (pNFH) in pediatric spinal muscular atrophy (SMA) patients un-dergoing Nusinersen treatment. The presence of five neurofilament types, particularly pNFH, is explored as a potential biomarker. SMA, an autosomal recessive disease impacting motor neu-rons, is characterized by disease severity linked to the number of SMN2 gene copies. Approved drugs, including Nusinersen, have demonstrated efficacy in enhancing motor activity. Methods: A retrospective analysis was conducted on 18 pediatric SMA patients treated with Nusinersen from October 2018 to July 2023. Cerebrospinal fluid (CSF) samples were utilized to assess pNFH levels. Motor scales were employed to evaluate performance, focusing on patients with varying SMN2 gene copies. Results: Following the initiation of Nusinersen treatment, a substantial de-crease in pNFH levels was observed in CSF samples. Motor scales indicated improved perfor-mance, particularly in patients with more SMN2 copies. However, the correlation between pNFH levels and motor improvement was not strongly evident, suggesting a limited role as a prognostic indicator within this timeframe. Conclusion: Nusinersen effectively reduced pNFH levels in pediatric SMA patients, showcasing promising outcomes in motor function. However, the predictive value of pNFH remains inconclusive, emphasizing the need for further research. Study limitations, including the rarity of SMA, the absence of a control group, and the disease's dynamic nature over time, should be considered when interpreting these finding

Jetrena osteodistrofija: globalni pre(po)gled problema

Hepatic osteodystrophy is a common and frequently untreated complication, manifested as osteoporosis or osteopenia, encountered in the evolution of chronic liver diseases. Th is article provides a narrative review of hepatic osteodystrophy. Th e aim is to revise the prevalence, pathophysiology, diagnosis and management of hepatic osteodystrophy. We searched medical literature via PubMed, Google Scholar, Wiley, Science Direct, and Springer Link using respective keywords to obtain data on low bone mineral density connected to chronic liver diseases. Many studies have reported an increased prevalence of osteoporosis/osteopenia in patients with chronic liver diseases. Th e pathogenesis is multifactorial, involving genetic factors, vitamin defi ciencies, proinfl ammatory cytokines, hypogonadism, hyperbilirubinemia, antiviral therapy, corticosteroid drugs, and lifestyle factors. Th e management of patients should include individualized assessment for fracture risk factors and bone mineral density. Vitamin D and calcium supplementation should be recommended in all patients with chronic liver diseases and osteoporosis. Bisphosphonates are the most effi cient drugs used in the treatment of hepatic osteodystrophy. In the future, it is necessary to defi ne better the management and specifi c treatment of hepatic osteodystrophy for prevention of fragility fractures and to improve the patient quality of life.Jetrena osteodistrofi ja je česta i nerijetko neliječena komplikacija koja se manifestira kao osteoporoza ili osteopenija, a susreće se u bolesnika s kroničnim bolestima jetre. Ovaj narativni pregled jetrene osteodistrofi je preispituje učestalost, patofiziologiju, dijagnostiku i liječenje jetrene osteodistrofi je. Proveli smo pretragu medicinske literature u bazama podataka PubMed, Google Scholar, Wiley, Science Direct i Springer Link pomoću prikladnih ključnih riječi kako bismo dobili podatke o niskoj mineralnoj gustoći kosti povezanoj s kroničnim bolestima jetre. Mnoga istraživanja izvještavaju o povećanoj učestalosti osteoporoze/osteopenije u bolesnika s kroničnim jetrenim bolestima. Patogeneza je multifaktorijalna i uključuje genetske čimbenike, pomanjkanje raznih vitamina, proupalne citokine, hipogonadizam, hiperbilirubinemiju, protuvirusnu terapiju, kortikosteroidne lijekove te čimbenike povezane s načinom života. Liječenje ovih bolesnika treba obuhvatiti individualiziranu procjenu čimbenika rizika za prijelome te mineralnu gustoću kosti. Svim bolesnicima s kroničnim bolestima jetre i osteoporozom treba preporučiti uzimanje dodataka vitamina C i kalcija. Bisfosfonati su najučinkovitiji lijekovi za liječenje jetrene osteodistrofi je. Potrebno je bolje defi nirati zbrinjavanje i specifi čno liječenje jetrene osteodistrofi je kako bi se sprije čili prijelomi zbog krhkih kosti te poboljšala kvaliteta života ovih bolesnika

CEACAM1: Expression and Role in Melanocyte Transformation

Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe