Locked Stem Reverse Total Shoulder Arthroplasty for Complex Proximal Humerus Fracture in the Elderly: Clinical and Radiological Short-Term Results.

Purpose: To evaluate both the short-term clinical and radiological results of reverse shoulder arthroplasty (RSA) with uncemented locked stem in the management of a proximal humerus fracture (PHFs) in the elderly. Methods: Retrospective study including 40 consecutive 3-4 part proximal humerus fractures treated with reverse shoulder arthroplasty with a minimum of 24 months follow-up. In all the cases, the greater tuberosity (GT) was reattached with a standardized suture technique and a local horseshoe bone graft. All the patients were assessed at the 24-month follow-up with Constant-Murley Score (CMS) and Visual Analog Score (VAS). Radiographic healing of the greater tuberosity was noted in addition to stem locking screws radiographic changes. Complications and revision rates were reported. Results: Mean final CMS for this cohort was 80 points. The greater tuberosity healed in the anatomic position in 90% of the cases (N = 36), obtaining an average CMS of 80 in these patients. Healing of the greater tuberosity did not occur in 10% of the cases (N = 4), obtaining an average CMS of 60. All patients scored above 100° in forward elevation with a mean of 140°. Mean active external rotation was 30°. Low-grade scapular notching was reported in <1% of the cases. Major complications were reported in one patient with an acromial fracture. No complications or loosening of stem locking screws were noted. There were no reoperations. Conclusion: In the elderly population, reverse shoulder arthroplasty utilizing a fracture-specific locking stem, low-profile metaphysis, suture-friendly groove, meticulous suture technique, and local bone grafting allows adequate fixation, variable prosthesis height adjustment, and enhances greater tuberosity healing. This approach yields positive short-term clinical outcomes without complications related to the stem's locking screws. Level of Evidence: Level IV Retrospective Case Series.

Light regulates widespread plant alternative polyadenylation through the chloroplast.

Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage, and polyadenylation (CPA), and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3' untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover, and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways, and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial and TOR kinase activities are necessary for the effect of light. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by histone deacetylase inhibition. Instead, regulation seems to correlate with changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.

Oxigenoterapia hiperbárica. Sus aplicaciones en Cirugía Plástica / Hyperbaric oxygen therapy. Its applications in Plastic Surgery

La oxigenoterapia hiperbárica (OHB) puede mejorar la cicatrización de las heridas. La hipoxia, la alteración de la angiogénesis y la inflamación prolongada son condiciones constantes que la OHB favorece su reversibilidad; hace ya muchos años que, en el listado de indicaciones reconocidas por Sociedades Científicas que rigen esta práctica, se encuentra como indicación aceptada para el tratamiento coadyuvante en injertos o colgajos en riesgo isquémico, como también en heridas refractarias; en la última década, paulatinamente, con la difusión y el aumento de las facilidades para acceder a equipos hiperbáricos, las indicaciones se extendieron al área de la cirugía plástica, para tratamiento de complicaciones posoperatorias en tejidos isquémicos o necrosados y también para preacodicionamiento preoperatorio y sostén posoperatorio de cierto grupo de pacientes con mayor riesgo de sufrir una complicación, en las lipotransferencias como coadyuvante para aumento de la preservación de una mayor cantidad de tejido graso. Las publicaciones al respecto son cada día más frecuentes, algunas presentan un pequeño número de casos, otras son estudios de cohorte retrospectivos, con un nivel de evidencia elevado. El objetivo de este artículo es presentar el concepto básico de los efectos de la OHB, referencia al estado actual de las distintas indicaciones en uso en cirugía plástica y medicina cosmética y la experiencia personal al respecto.

Hyperbaric oxygen therapy (HOT) can improve wound healing, hypoxia, alteration of angiogenesis and prolonged infl ammation are constant conditions that HOT favors its reversibility for many years now, in the list of indications recognized by Scientifi c Societies. that govern this practice, is a recognized indication for adjuvant treatment in grafts or fl aps at ischemic risk, as well as in refractory wounds; In the last decade, gradually, with the dissemination and increase in the facilities to access hyperbaric equipment, the indications were extended to the area of plastic surgery, for the treatment of post-operative complications in ischemic or necrotic tissues as well as for preconditioning. operative and post-operative support of a certain group of patients with a higher risk of suff ering a complication, in lipotransferences as an adjuvant to increase the preservation of a greater amount of fatty tissue. Publications in this regard are becoming more frequent every day, some present a small number of cases, others are retrospective cohort studies, with a high level of evidence. The objective of this article is to present the basic concept of the eff ects of HOT, reference to the current state of the diff erent indications in use in plastic surgery, and cosmetic medicine and personal experience in this regard

Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of São Paulo, Brazil.

Friedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians. Prevalence was estimated dividing the number of patients by the population of the state as reported in the last census. Patients were invited to answer an online survey to describe clinical data and diagnostic journey of the disease. FRDA estimated prevalence was 0.367:100,000, with a slight predominance of women (58.2% vs 41.7%). One hundred and four patients answered the survey (mean age of 37.3 ± 13.8 years; 75.9% classical and 24.0% late onset). On average, 6.2 ± 4.1 physicians were visited before reaching the diagnosis. Mean diagnostic delay was 7.8 ± 6.7 years; no difference between classical and LOFA groups was found. Most of the patients reported unsteadiness and gait abnormalities as the first symptom. Neurologists and orthopedical surgeons were the main specialties first sought by patients. We found a prevalence of 0.36:100,000 for FRDA in the state of São Paulo, Brazil. The disease is characterized by remarkable diagnostic delay, with no relevant differences between classical and LOFA patients.

Distribution of gamma-ray elements in Cerro do Jarau impact structure and a proposal of geothermal modeling.

Large meteorite impacts release kinetic energy that induces rock deformation, high temperatures and fluid circulation during the cratering process. To understand the correlation between rock deformation and fluid circulation, it is relevant to investigate post-impact hydrothermal flux and its relation to the local geology. The Cerro do Jarau impact structure is a ~13.5 km diameter impact structure located in southern Brazil and formed on Cretaceous continental flood basalts of the Serra Geral Formation and underlying sedimentary strata. This study collected ground gamma-ray data over the structure and produced K, eTh and eU concentrations, eTh/K ratio and F-factor maps to characterize it in terms of its radiometric signatures and their respective spatial distribution. A general decrease in the concentration of the three elements was observed from the outer-rim towards the center of the crater. The central area is defined by very low radiometric values, with relatively high K values, thus indicating the occurrence of K-bearing rocks. Numerical simulations using the HYDROTHERM 3 code showed the fluid circulation pattern over the impact structure. Data interpretation resulted in a scenery consistent with potential fluid remobilization within the impact structure related to hydrothermal processes in the late stages of the crater formation process.

Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.

BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

Cranial Nerve Thinning Distinguishes RFC1-Related Disorder from Other Late-Onset Ataxias.

BACKGROUND: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. OBJECTIVES: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. METHODS: Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. RESULTS: Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). CONCLUSION: MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.

Reverse total shoulder arthroplasty for complex proximal humerus fracture in the elderly: clinical and radiological results.

Background: The use of reverse total shoulder arthroplasty (RSA) for the treatment of proximal humeral fractures (PHFs) is steadily increasing. Better clinical outcomes of RSA have been correlated with tuberosity reattachment and healing. The purpose of this study was to evaluate both the clinical and radiological results of reverse shoulder arthroplasty in the management of a proximal humerus fracture in the elderly. Methods: Retrospective study including 400 consecutive 3-4 part proximal humerus fractures treated with reverse shoulder arthroplasty with a minimum of 12-month follow-up. In all the cases, the greater tuberosity was reattached with a standardized suture technique and a local bone graft. All the patients were assessed at the 12-month follow-up with Constant-Murley Score (CMS). Radiographic healing of the greater tuberosity was noted. Complications and revision rates were reported. Results: Mean final CMS for this cohort was 82 points. The greater tuberosity healed in anatomic position in 85% of the cases (N = 340), obtaining an average CMS of 85 in these patients. Healing of the greater tuberosity did not occur in 13% of the cases (N = 52) and displacement more than 5 mm occurred in 2% (N = 8) of the patients for an average CMS of 60. All patients scored above 120° in forward elevation with a mean of 150°. Mean active external rotation was 35°. The lateralization shoulder angle had a mean of 91° and the distalization shoulder angle had a mean of 54°. Low-grade scapular notching was reported in <1% of the cases. A total of 60 patients presented failure of healing or displacement of the greater tuberosity. Major complications were reported in nine patients. Of these nine patients, two acquired superficial wound infections, while two had deep shoulder prosthetic infection. Two other patients developed hematomas, one sustained an acromial stress fracture, and two had a stem loosening. There were 4 reoperations. Conclusion: Reverse shoulder arthroplasty, with the use of a fracture-specific stem, allows an improved rate of greater tuberosity healing and short-term clinical outcomes in the elderly population.

Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia.

BACKGROUND: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. OBJECTIVE: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. METHODS: We performed a cross-sectional analysis of cervical spinal cord (C1-C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. RESULTS: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < -0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. CONCLUSIONS: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Beyond transcription: compelling open questions in plant RNA biology.

The study of RNAs has become one of the most influential research fields in contemporary biology and biomedicine. In the last few years, new sequencing technologies have produced an explosion of new and exciting discoveries in the field but have also given rise to many open questions. Defining these questions, together with old, long-standing gaps in our knowledge, is the spirit of this article. The breadth of topics within RNA biology research is vast, and every aspect of the biology of these molecules contains countless exciting open questions. Here, we asked 12 groups to discuss their most compelling question among some plant RNA biology topics. The following vignettes cover RNA alternative splicing; RNA dynamics; RNA translation; RNA structures; R-loops; epitranscriptomics; long non-coding RNAs; small RNA production and their functions in crops; small RNAs during gametogenesis and in cross-kingdom RNA interference; and RNA-directed DNA methylation. In each section, we will present the current state-of-the-art in plant RNA biology research before asking the questions that will surely motivate future discoveries in the field. We hope this article will spark a debate about the future perspective on RNA biology and provoke novel reflections in the reader.

The physiology of alternative splicing.

Alternative splicing is a substantial contributor to the high complexity of transcriptomes of multicellular eukaryotes. In this Review, we discuss the accumulated evidence that most of this complexity is reflected at the protein level and fundamentally shapes the physiology and pathology of organisms. This notion is supported not only by genome-wide analyses but, mainly, by detailed studies showing that global and gene-specific modulations of alternative splicing regulate highly diverse processes such as tissue-specific and species-specific cell differentiation, thermal regulation, neuron self-avoidance, infrared sensing, the Warburg effect, maintenance of telomere length, cancer and autism spectrum disorders (ASD). We also discuss how mastering the control of alternative splicing paved the way to clinically approved therapies for hereditary diseases.

Creatine supplementation protects against diet-induced non-alcoholic fatty liver but exacerbates alcoholic fatty liver.

AIMS: This work investigated the effects of creatine supplementation on different pathways related to the pathogenesis of non-alcoholic fatty liver disease and alcoholic liver disease. MAIN METHODS: To induce alcoholic liver disease, male Swiss mice were divided into three groups: control, ethanol and ethanol supplemented with creatine. To induce non-alcoholic fatty liver disease, mice were divided into three groups: control, high-fat diet and high-fat diet supplemented with creatine. Each group consisted of eight animals. In both cases, creatine monohydrate was added to the diets (1 %; weight/vol). KEY FINDINGS: Creatine supplementation prevented high-fat diet-induced non-alcoholic fatty liver disease progression, demonstrated by attenuated liver fat accumulation and liver damage. On the other hand, when combined with ethanol, creatine supplementation up-regulated key genes related to ethanol metabolism, oxidative stress, inflammation and lipid synthesis, and exacerbated ethanol-induced liver steatosis and damage, demonstrated by increased liver fat accumulation and histopathological score, as well as elevated oxidative damage markers and inflammatory mediators. SIGNIFICANCE: Our results clearly demonstrated creatine supplementation exerts different outcomes in relation to non-alcoholic fatty liver disease and alcoholic liver disease, namely it protects against high-fat diet-induced non-alcoholic fatty liver disease but exacerbates ethanol-induced alcoholic liver disease. The exacerbating effects of the creatine and ethanol combination appear to be related to oxidative stress and inflammation-mediated up-regulation of ethanol metabolism.

Pharmacotherapy for the management of the symptoms of Machado-Joseph Disease.

INTRODUCTION: Machado-Joseph disease or spinocerebellar ataxia type 3 (SCA3/MJD) is the leading cause of autosomal dominant ataxia worldwide. This is a slowly progressive, but very disabling disorder. Ataxia is the main clinical feature, but additional motor and non-motor manifestations may be found. Many of these manifestations are amenable to pharmacological treatments, which may impact the quality of life of affected subjects. AREAS COVERED: Authors review available literature on both disease-modifying and symptomatic pharmacological therapies for SCA3/MJD. Discussion is stratified into motor (ataxic and non-ataxic syndromes) and non-motor manifestations. Ongoing clinical trials and future perspectives are also discussed in the manuscript. EXPERT OPINION: Symptomatic treatment is the mainstay of clinical care and should be tailored for each patient with SCA3/MJD. Management of ataxia is still a challenging task, but relief (at least partial) of dystonia, pain/cramps, fatigue, and sleep disorders is an achievable goal for many patients. Even though there are no disease-modifying treatments so far, recent advances in understanding the biology of disease and international collaborations of clinical researchers are now paving the way for a new era where more clinical trials will be available for this devastating disorder.

Dysautonomia in RFC1-related disorder: Clinical and neurophysiological evaluation.

OBJECTIVE: To characterize and quantify autonomic involvement in patients with RFC1-related disorder of adult-onset cerebellar ataxia and idiopathic sensory neuropathy. METHODS: We enrolled 16 subjects with biallelic RFC1 (AAGGG)n expansions and 16 age and sex-matched healthy controls that underwent comprehensive clinical and neurophysiological evaluation. Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction (SCOPA-AUT) score was used to assess autonomic symptoms. Electrophysiological testing included assessment of heart rate variability and quantitative sudomotor axon reflex test (QSART). Between-group comparisons were assessed using non-parametric tests. RESULTS: In the patient group, there were 9 men/7 women and the median age was 60.5 years. SCOPA-AUT scores were significantly higher in the RFC1 group compared to controls (22 vs 10, p < 0.001). Half of patients had cardiac autonomic neuropathy. In neurophysiology, there was resting tachycardia combined with abnormal responses during Valsalva maneuver and deep breathing among patients. QSART responses were also significantly reduced in the RFC1 group, especially in the lower limbs. CONCLUSIONS: Autonomic dysfunction is frequent, clinically relevant and involves multiple domains in RFC1-related disorder. Patients have both sympathetic and parasympathetic involvement. From a topographical perspective, this condition is characterized by a small fiber autonomic axonopathy. SIGNIFICANCE: Dysautonomia is frequent, severe and related to peripheral damage in RFC1-related disorder.

RFC1-Related Disorder: In Vivo Evaluation of Spinal Cord Damage.

BACKGROUND: RFC1-related disorder is a novel heredodegenerative condition with a broad phenotypic spectrum. Its neuropathological bases are not yet fully understood, particularly regarding the pattern, extent, and clinical relevance of spinal cord (SC) damage. OBJECTIVES: The objectives were to determine the SC structural signature in RFC1-related disorder in vivo and to identify potential clinical correlates for these imaging abnormalities. METHODS: We enrolled 17 subjects with biallelic RFC1 (AAGGG)n expansions and 11 age- and sex-matched healthy controls that underwent multimodal magnetic resonance imaging SC acquisitions in a 3T Philips Achieva scanner. Both global morphometry and tract-specific analyses were then performed across all cervical levels. Between-group comparisons were assessed using nonparametric tests. RESULTS: In the patient group, mean age and disease duration were 62.9 ± 9.3 and 9.3 ± 4.0, respectively. Compared to controls, patients had remarkable SC cross-sectional area reduction along all cervical levels but anteroposterior flattening only in the lower cervical levels. There was also prominent SC gray matter atrophy. Diffusivity abnormalities were identified in the dorsal columns but not in the lateral corticospinal tracts. Disease severity did not correlate with these imaging parameters. CONCLUSION: SC damage is a hallmark of RFC1-related disorder and characterized by gray as well as white matter involvement. In particular, dorsal columns are severely and diffusely affected. The clinical correlates of these imaging abnormalities still deserve additional investigations. © 2022 International Parkinson and Movement Disorder Society.