Carbon turnover in the water-soluble protein of the adult human lens.

PurposeHuman eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the (14)C bomb pulse.MethodsAdult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The (14)C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the (14)C bomb pulse.ResultsThe water-insoluble fractions possessed (14)C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction.ConclusionsAs the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining homeostasis in part due to intricate protein transport mechanisms and possibly protein repair. This finding implies that the lens plays an active role in the aversion of age-related nuclear (ARN) cataract

Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

Cancer frequency in muscle-specific kinase myasthenia gravis (MuSK-MG) has not yet been explored and the mechanisms leading to the formation of MuSK IgG remain elusive. We aimed to explore cancer frequency in MuSK-MG patients and to assess MuSK expression in cancer cells from 2 tumors occurred in this cohort. Immunohistochemistry on tumor specimens revealed the expression of MuSK in the cancer cells from primary mediastinal B cell lymphoma and endometrial carcinoma. Twenty-one males and 73 females were enrolled. Fifteen cancers occurred in 13 of 94 patients (13.8%). Patients with cancer were significantly older at time of MuSK-MG onset

Study of the D^0 \to pi^-pi^+pi^-pi^+ decay

Using data from the FOCUS (E831) experiment at Fermilab, we present new measurements for the Cabibbo-suppressed decay mode $D^0 \to \pi^-\pi^+\pi^-\pi^+$. We measure the branching ratio $\Gamma(D^0 \to\pi^+\pi^- \pi^+\pi^-)/\Gamma(D^0 \to K^-\pi^+\pi^-\pi^+) = 0.0914 \pm 0.0018 \pm 0.0022$. An amplitude analysis has been performed, a first for this channel, in order to determine the resonant substructure of this decay mode. The dominant component is the decay $D^0 \to a_1(1260)^+ \pi^-$, accounting for 60% of the decay rate. The second most dominant contribution comes from the decay $D^0 \to \rho(770)^0\rho(770)^0$, with a fraction of 25%. We also study the $a_1(1260)$ line shape and resonant substructure. Using the helicity formalism for the angular distribution of the decay $D^0 \to \rho(770)^0\rho(770)^0$, we measure a longitudinal polarization of $P_L = (71 \pm 4\pm 2)$%.Comment: 38 pages, 8 figures. accepted for publication in Physical Review

evaluation of botulinum toxin therapy of spastic equinus in paediatric patients with cerebral palsy

Objective: To develop a clinical and instrumental protocol to assess the postural and dynamic effects following treatment with botulinum neurotoxin A in children with cerebral palsy affected by spastic equinus. Design: Open study, in which every patient served as his or her own control. Patients: Ten sequential children with cerebral palsy and spastic dynamic equinus foot. Methods: Botulinum neurotoxin A was injected in the gastrocnemius, soleus and tibialis posterior muscles. The main measures were: pedobarometry, dynamic surface electromyography, video gait analysis scale, and the modified As hworth Scale. Results: After treatment with botulinum neurotoxin A, pedobarometric evaluation revealed a significant change in all parameters, including a decrease in the modified Ashworth Scale and an increase in the range of motion. All children showed significant improvement in initial foot contact, as documented by the video gait analysis scale. The calf muscle electromyography pattern showed a decrease in co-contraction during gait in all children. These modifications were sta tistically significant for all parameters considered ( p < 0.05). Conclusion: This pilot study suggests that dynamic electr

Comparison of Fixed and Live Cell-Based Assay for the Detection of AChR and MuSK Antibodies in Myasthenia Gravis

Background and ObjectivesLive cell-based assay (CBA) can detect acetylcholine receptors (AChRs) or muscle-specific tyrosine kinase (MuSK) antibodies (Abs) in a proportion of patients with radioimmunoassay (RIA)-double seronegative myasthenia gravis (dSN-MG). A commercial fixed CBA for AChR and MuSK Abs has recently become available; however, comparative studies on fixed and live CBAs are lacking. In this study, we compared the performance of fixed and live CBAs in patients with RIA-dSN MG and assessed their sensitivity in RIA-positive MG samples and their specificity.MethodsAChR and MuSK Abs were tested in 292 serum samples from 2 Italian MG referral centers by live and fixed CBAs: 192 from patients with MG and 100 from controls. All samples had been previously assessed by RIA: 66 were AChR positive, 40 MuSK positive, and 86 dSN. All controls were negative. Two independent raters assessed the CBA results. Fixed and live CBAs were compared with the McNemar test; interrater and interlaboratory agreement were assessed with Cohen's kappa or interclass correlation coefficient (ICC), as appropriate.ResultsIn 86 RIA-dSN samples, fixed CBA detected Abs in 10 cases (11.6%, 95% CI 5.7-20.3), whereas live CBA detected Abs in 16 (18.6%, 95% CI 11.0-28.5) (p = 0.0143). Of these sera, those positive by fixed CBA were also positive by live CBA. In addition, live CBA could detect MuSK Abs in 4 and AChR Abs in 2 samples that were negative by fixed CBA, providing an 8% (95% CI 2.9-16.6) further increase in the Ab detection rate. These results were confirmed by flow cytometry. In the RIA-positive cohort, the sensitivity for AChR Abs was 98.5% (95% CI 91.9%-99.9%) for fixed CBA and 100% (95% CI 94.6-100) for live CBA (p = 0.1573). For both assays, the sensitivity for MuSK Abs was 100% (95% CI 91.2-100), and the specificity was 100% (95% CI 96.4-100). Interrater agreement was almost perfect for live and fixed CBAs (Cohen's kappa 0.972 and 0.978, respectively), alike interlaboratory agreement. Interrater agreement for the CBA score ranged from good to excellent (ICC: 0.832-0.973).DiscussionFixed CBA represents a valuable alternative to RIA for AChR and MuSK Ab detection in patients with MG and could be considered as a first-step diagnostic test. Live CBA can be useful in the serologic evaluation of RIA- and fixed CBA-negative samples

Complement inhibitor therapy in thymoma-associated myasthenia gravis: a real-world experience

Introduction: Thymoma-associated myasthenia gravis (TAMG) accounts for 15-20% of all myasthenia gravis (MG) cases and is typically characterized by severe clinical manifestations and suboptimal response to conventional therapies. However, TAMG patients are underrepresented in clinical trials, leaving gaps in evidence for optimal treatment strategies. This study assessed the efficacy of complement inhibitors (CI) in TAMG population. Methods: We retrospectively reviewed 23 TAMG patients who received CI, with a minimum follow-up of six months. Additionally, we randomly included 22 MG patients without thymoma, treated with CI, in the control group. Clinical outcomes were measured using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores at baseline, three, and six months. Results: Among the 23 TAMG patients, 21 initiated CI after thymectomy, with a median interval of eight years (IQR:2.5-15) post-surgery. Two patients achieved sufficient stabilization on CI to undergo thymectomy thereafter. The most frequent thymoma histological subtype was WHO type B2, detected in 43.5% of cases. Median MG-ADL score decreased from 11 (IQR:8-15) to 3 (IQR:2-5) and 4 (IQR:1-5) at three and six months, respectively (both p&lt;0.001). Median QMG score decreased from 16 (IQR:14-22) to 10 (IQR: 5-11) at three and six months (both p&lt;0.001). Prednisone dosage was tapered in 20 patients. No significant differences were observed between TAMG and MG patients without thymoma in MG-ADL, QMG and steroid reduction. Conclusion: CI demonstrated significant improvements in MG-ADL and QMG scores, along with a steroid-sparing effect, suggesting its potential as an effective treatment for this challenging subpopulation

O impacto da implementação da tabela salarial única na motivação dos funcionários públicos: casos dos docentes de ensino secundário geral em Caia- Moçambique

O presente artigo analisa o impacto da implementação da Tabela Salarial Única (TSU) na motivação dos funcionários públicos, com foco nos docentes do ensino secundário geral em Murraça-Caia. O estudo tem como objetivos avaliar os efeitos dessa política na motivação dos professores, descrever o processo de implementação da TSU na função pública, identificar fatores que influenciam a motivação e produtividade docente e propor estratégias de gestão e incentivo para melhorar o desempenho profissional. Com a implementação da TSU e a eliminação da remuneração por horas extras, observou-se uma queda significativa na motivação dos docentes, refletindo diretamente na produtividade das instituições de ensino. A ausência de incentivos financeiros e o baixo reconhecimento profissional resultaram em uma desmotivação generalizada, comprometendo o desempenho pedagógico e a qualidade da educação. O estudo, de caráter exploratório, adotou uma abordagem mista, combinando a coleta de dados primários (entrevistas e questionários) e secundários (pesquisa bibliográfica e análise documental). A amostra foi composta por 18 docentes, com idades entre 35 e 40 anos, e os dados foram analisados por meio de métodos estatísticos. Os resultados indicam que a implementação da TSU não representou um aumento real nos salários da função pública. Além disso, o processo de implementação revelou-se complexo, sendo influenciado por diversos fatores socioeconômicos e políticos. Embora a pesquisa tenha abrangência limitada, seus achados podem contribuir para o debate sobre políticas públicas que afetam a motivação dos servidores e, consequentemente, sua produtividade