Condensation properties of stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

RNA regulation in mammalian cells requires complex physical compartmentalisation, using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic dystrophy type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures is a consequence of the presence of CUGexp RNA.</p

Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors

Trost E, Al-Dilaimi A, Papavasiliou P, et al. Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors. BMC Genomics. 2011;12(1): 383.ABSTRACT: Corynebacterium ulcerans has been detected as a commensal in domestic and wild animals that may serve as reservoirs for zoonotic infections. During the last decade, the frequency and severity of human infections associated with C. ulcerans appear to be increasing in various countries. As the knowledge of genes contributing to the virulence of this bacterium was very limited, the complete genome sequences of two C. ulcerans strains detected in the metropolitan area of Rio de Janeiro were determined and characterized by comparative genomics: C. ulcerans 809 was initially isolated from an elderly woman with fatal pulmonary infection and C. ulcerans BR-AD22 was recovered from a nasal sample of an asymptomatic dog. The circular chromosome of C. ulcerans 809 has a total size of 2,502,095 bp and encodes 2,182 predicted proteins, whereas the genome of C. ulcerans BR-AD22 is 104,279 bp larger and comprises 2,338 protein-coding regions. The minor difference in size of the two genomes is mainly caused by additional prophage-like elements in the C. ulcerans BR-AD22 chromosome. Both genomes show a highly similar order of orthologous coding regions; and both strains share a common set of 2,076 genes, demonstrating their very close relationship. A screening for prominent virulence factors revealed the presence of phospholipase D (Pld), neuraminidase H (NanH), endoglycosidase E (EndoE), and subunits of adhesive pili of the SpaDEF type that are encoded in both C. ulcerans genomes. The rbp gene coding for a putative ribosome-binding protein with striking structural similarity to Shiga-like toxins was additionally detected in the genome of the human isolate C. ulcerans 809. The molecular data deduced from the complete genome sequences provides considerable knowledge of virulence factors in C. ulcerans that is increasingly recognized as an emerging pathogen. This bacterium is apparently equipped with a broad and varying set of virulence factors, including a novel type of a ribosome-binding protein. Whether the respective protein contributes to the severity of human infections (and a fatal outcome) remains to be elucidated by genetic experiments with defined bacterial mutants and host model systems

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Case Series Treatment Outcome Report Following 5 Years of Implant Overdenture Treatment

Purpose: To assess clinical performance of bar-retained implant overdentures (IOs) with distally placed ERA attachments on four implants, and patient satisfaction after a follow-up period of 5 years in a convenience selection of 15 patients. Materials and Methods: Bar-retained IOs with distally placed ERA attachments were placed and clinically monitored. Encountered complications during a 5-year follow-up period were recorded; and a modified OHIP-14 questionnaire was used to assess patient satisfaction. Results: Implant and restoration survival rates of 97.5% and 100%, respectively, were recorded. The most common maintenance requirement was the replacement of ERA retentive elements. A high degree of patient satisfaction was reported. Conclusions: The proposed IO design is a reliable clinical treatment protocol associated with a high degree of patient satisfaction and minor prosthetic complications

A Chair-Based Music–Kinetic Combined Exercise Program as an Alternative Approach for Increasing Health, Functional Capacity, and Physical Fitness Indices in Middle-Aged Pre-Menopausal Women

Lately, chairs have been widely used as a cheap, easily accessible, safe, and effective training means in different settings (e.g., in gyms, the house, workplaces, and in rehabilitation). This study investigated the effectiveness of a 10-week chair-based music–kinetic integrated combined exercise program on health, functional capacity, and physical fitness indicators of middle-aged pre-menopausal women. A total of 40 healthy women (40–53 years) were assigned to two groups: exercise (EG) and control (CG). The EG followed a 10-week (3 times/weekly; 30 training sessions) chair-based exercise program including aerobic dance, flexibility, coordination, and strength exercises with body weight or auxiliary means. Selected indicators of health, functional capacity, and physical fitness were evaluated before and after the 10 weeks. Following the program, the EG significantly reduced their body fat (−2.5%), blood pressure (by −4.5 to −5.5%), the time during the timed up-and-go (TUG) test (by −10.27%), heart rate (by −6.35 to −13.78%), and the rate of perceived exertion (by −24.45 to −25.88%), while increasing respiratory function (3.5–4%), flexibility (12.17%), balance (50.38–51.07%), maximal handgrip strength (10–12.17%), and endurance strength (43.87–55.91%). The chair-based combined music–kinetic exercise program was effective and could be safely used in different settings to improve health, functional capacity, and physical fitness in middle-aged women

Safety of Botulinum Toxin A in Children and Adolescents with Cerebral Palsy in a Pragmatic Setting

This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A) treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients). On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam) and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s) or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR) = 2.74 − p = 0.016 and OR = 2.35 − p = 0.046, respectively) but not with BoNT-A dose (either total or per kilogram). In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice

Cancer patients with large defects. Reconstructional options: a case study

Referimo-nos ao caso de um paciente masculino de setenta e cinco anos de idade, com um carcinoma espinocelular (SCC), que se originou na parte exterior da orelha direita há quatro anos. Sofreu uma remoção cirúrgica da parte lesionada combinada com dissecção modificada do pescoço e reconstrução com o uso de retalho peitoral maior. Além disso, teve radioterapia com 6000 rads na região temporal direita. Há dois meses o paciente mostrou urna recorrência expansiva no que diz respeito ao músculo temporal e ao osso, o osso litóide, os músculos masseter e os músculos pterigóideos, a parte direita da mandíbula, a glândula da parótida com o nervo facial, e o bulbo superior da veia jugular interna. Sofreu uma remoção cirúrgica da lesão afetada até as extremidades saudáveis e reconstrução estética e funcional com a utilização combinada de uma prótese de metal fixa do côndilo e da mandíbula direita e o uso de músculo-cutâneo trapezious flap. Apresentamos o relato de um caso sobre as opções de reconstrução que nós temos em nossos dias para proporcionar qualidade de vida a doentes que sofrem de cancro.We report a case of a seventy-five years old male patient with a squamous cell carcinoma (SCC) originated from the right external ear four years ago. He was undergone surgical removal of the lesion with a combination of modified neck dissection and reconstruction with the use of pectoralis major flap. Furthermore, he had radiotherapy with 6000 rads of the right temporal region. Two months ago the patient showed an extended recurrence concerning the temporal muscle and bone, the lithoid bone, the maseter and the pterygoids muscles, the right part of the mandible, the parotid gland with the facial nerve, and the superior bulb of the internal jugular vein. He had a surgical removal of the lesion in extended healthy margins and functional and esthetic reconstruction of the defect with a combination of metal fixed prosthesis of the condyle and the right mandible and the use of myocutaneous trapezious flap. This is a case report of the reconstruction options we have nowadays to provide quality of life in cancer patients

Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1

RNA regulation in mammalian cells requires complex physical compartmentalisation using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic Dystrophy Type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from a CTG expansion in the DM1 protein kinase gene (DMPK). The cellular hall-mark of DM1 is the formation of nuclear foci containing expanded DMPK RNA (CUGexp). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures may be a consequence of the presence of CUGexp RNA

Pacientes miológicos com defeitos extensos: opções de reconstrução. Relato de caso Cancer patients with large defects. Reconstructional options: a case study

Referimo-nos ao caso de um paciente masculino de setenta e cinco anos de idade, com um carcinoma espinocelular (SCC), que se originou na parte exterior da orelha direita há quatro anos. Sofreu uma remoção cirúrgica da parte lesionada combinada com dissecção modificada do pescoço e reconstrução com o uso de retalho peitoral maior. Além disso, teve radioterapia com 6000 rads na região temporal direita. Há dois meses o paciente mostrou urna recorrência expansiva no que diz respeito ao músculo temporal e ao osso, o osso litóide, os músculos masseter e os músculos pterigóideos, a parte direita da mandíbula, a glândula da parótida com o nervo facial, e o bulbo superior da veia jugular interna. Sofreu uma remoção cirúrgica da lesão afetada até as extremidades saudáveis e reconstrução estética e funcional com a utilização combinada de uma prótese de metal fixa do côndilo e da mandíbula direita e o uso de músculo-cutâneo trapezious flap. Apresentamos o relato de um caso sobre as opções de reconstrução que nós temos em nossos dias para proporcionar qualidade de vida a doentes que sofrem de cancro.<br>We report a case of a seventy-five years old male patient with a squamous cell carcinoma (SCC) originated from the right external ear four years ago. He was undergone surgical removal of the lesion with a combination of modified neck dissection and reconstruction with the use of pectoralis major flap. Furthermore, he had radiotherapy with 6000 rads of the right temporal region. Two months ago the patient showed an extended recurrence concerning the temporal muscle and bone, the lithoid bone, the maseter and the pterygoids muscles, the right part of the mandible, the parotid gland with the facial nerve, and the superior bulb of the internal jugular vein. He had a surgical removal of the lesion in extended healthy margins and functional and esthetic reconstruction of the defect with a combination of metal fixed prosthesis of the condyle and the right mandible and the use of myocutaneous trapezious flap. This is a case report of the reconstruction options we have nowadays to provide quality of life in cancer patients