Acute brachial plexopathy secondary to surgical management of an atrophic nonunion of a clavicle fracture.

We report the case of a 28-year-old patient who developed acute transient brachial plexopathy secondary to surgical management of an atrophic clavicle nonunion. The treatment was conservative, with symptom resolution at 4 months after surgery. This is the first reported case with electromyographic and neuroconduction follow-up, demonstrating complete and spontaneous resolution of axonal damage. The limited number of cases reported in the scientific literature allows for exploring some underlying causes of the acute plexopathy depending on the nature of the non-union (hypertrophic or atrophic).

Infratentorial Cerebral Cavernous Malformation May be a Risk Factor for Symptomatic Bleeding and Precocity of Symptoms: A Multicenter, Propensity Score Matched, Case-Control Study.

BACKGROUND: Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable. OBJECTIVE: Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease. METHODS: We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life. RESULTS: The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03). CONCLUSION: Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.

The Influence of Genetic Polymorphisms on the Expression of Interleukin-1beta, Prostaglandin E2 and Tumor Necrosis Factor Alpha in Peri-Implant Crevicular Fluid: A Cross-Sectional Study.

The aim of this study was to evaluate the possible relationships between polymorphisms in the interleukin-1 (IL-1) A, IL-1B, and IL-1RN genes and concentrations of the inflammatory mediators IL-1ß, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) in peri-implant crevicular fluid (PICF). A cross-sectional analytical study was conducted on 51 patients with dental implants. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR and restriction fragment length polymorphism analysis for IL-1RN. For the biochemical analysis, the concentrations of IL-1ß and TNF-α were analyzed using multiplexed fluorescent sphere immunoassays, and PGE2 by enzyme-linked immunosorbent assay. In patients with detected IL-1RN polymorphism, there was an increase in the concentration of the three mediators with statistically significant differences in the mean values of TNF-α and PGE2, regardless of peri-implant health status (p = 0.002 and p = 0.049, respectively). The concentrations of all three mediators were positively and significantly correlated (IL-1ß vs. TNF-α Rho = 0.480, p < 0.001; IL-1ß vs. PGE2 Rho = 0.382, p = 0.006; and TNF-α vs. PGE2 Rho = 0.528, p < 0.001). We can conclude that the IL-1RN polymorphism exerts an influence on the PICF immune response, which may explain the influence of this genetic polymorphism on the occurrence of peri-implantitis.

Self-Management Ability Questionnaire Validation in Portuguese Adults With Periodontitis.

OBJECTIVES: We aimed to test the psychometric validity of the adapted and translated Self-Management Ability Questionnaire-Short Form (SMAQ-12) to Portuguese. METHODS: The translation and adaptation of the SMAQ-12 followed international guidelines. We included 280 participants with chronic periodontitis from the Department of Periodontology of the Egas Moniz Dental Clinic. Participants completed the Portuguese version of the SMAQ-12 (SMAQ-12-PT), a 12-item scale with 3 conceptual domains (Role Management, Medical Management, and Emotional Management). The validity of the content, its construct and internal consistency, as well as test-retest reliability were used to estimate psychometric properties. RESULTS: The SMAQ-12-PT showed an interclass correlation coefficient value of 0.90, with a 95% confidence interval (0.79-0.95; P < .001) and high reliability (Cronbach alpha coefficient ranging between 0.78 and 0.94). Confirmatory factor analysis revealed adequate model fit, with comparative fit index of 0.853, goodness-of-fit of 0.947, and a 0.052 value of root mean squared error of approximation. CONCLUSIONS: The SMAQ-12-PT was found to be a valid and reliable instrument in the Portuguese population. Disease management representation for the specialty of periodontology and its impact on periodontal schedules and practices should be evaluated in future studies.

Revisiting Standard and Novel Therapeutic Approaches in Halitosis: A Review.

Halitosis, or bad breath, is an oral health problem characterized by an unpleasant malodor emanating from the oral cavity. This condition can have different origins and causes a negative burden in social interactions, communication and quality of life, and can in uncommon cases be indicative of underlying non-oral non-communicable diseases. Most cases of halitosis are due to inadequate oral hygiene, periodontitis and tongue coating, yet the remaining proportion of cases are due to ear-nose-throat-associated (10%) or gastrointestinal/endocrine (5%) disorders. For this reason, the diagnosis, treatment and clinical management of halitosis often require a multidisciplinary team approach. This comprehensive review revisits the etiology of halitosis as well as standard and novel treatment that may contribute to higher clinical success.

Association between IL-1A and IL-1B gene polymorphisms with peri-implantitis in a Portuguese population-a pilot study.

Background: Scientific evidence indicates that biological complications in dental implants tend to be concentrated in a subset of individuals, which seems to imply that the host response may play a determining role in implant success. Over the last few decades, several polymorphisms have been studied. Polymorphisms in the interleukin (IL) 1 gene cluster have been associated with periodontitis. There are some similar features in the sequence of immunopathological events in peri-implant and periodontal infections. We aimed to investigate if individuals carrying the genetic single nucleotide polymorphism (SNP) in the IL-1A (rs1800587) and IL-1B (rs1143634) genes are more susceptible to develop peri-implantitis. Methods: A cross-sectional analytic pilot study was conducted in 20 Caucasian Portuguese subjects divided into two groups: 10 subjects with peri-implantitis and 10 subjects with peri-implant health (control group). Samples containing cells from the buccal mucosa were stored at -20 °C and later submitted to the DNA extraction process. Genetic analysis was performed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Data were analyzed by using descriptive and inferential statistical methodologies. Results: For the IL-1A (-889) gene polymorphism, it was observed that the mutated allele was present in a higher percentage in the peri-implantitis group compared to the control group (30% vs 15% respectively, Fisher's exact test, p = 0.45). For the IL-1B (+3954) gene polymorphism, it was also observed that the altered allele was present in a higher percentage in the disease group compared to the control group (35% vs 10% respectively, Fisher's exact test, p = 0.13). The positive genotype (at least one allele with nucleotide sequence changed in both genes) was detected in six patients, five belonging to the disease group and one to the health group. Conclusions: Regarding IL-1 gene polymorphisms, there was no statistically significant difference between the health and disease group, however a trend should be highlighted, showing a potential link between the IL-1 genotype and peri-implantitis. More studies are needed to clarify the role of genetic polymorphisms in the development of peri-implantitis.

CASP4/11 contributes to pulmonary inflammation and disease exacerbation in COVID-19

Infection with SARS-CoV-2 induces COVID-19, an inflammatory disease that is usually self-limited, but depending on patient conditions may culminate with critical illness and patient death. The virus triggers activation of intracellular sensors, such as the NLRP3 inflammasome, which promotes inflammation and aggravates the disease. Thus, identification of host components associated with NLRP3 inflammasome is key for understanding the physiopathology of the disease. Here, we reported that SARS-CoV-2 induces upregulation and activation of human Caspase-4/CASP4 (mouse Caspase-11/CASP11) and this process contributes to inflammasome activation in response to SARS-CoV-2. CASP4 was expressed in lung autopsy of lethal cases of COVID-19 and CASP4 expression correlates with expression of inflammasome components and inflammatory mediators such as CASP1, IL1B, IL18 and IL6. In vivo infections performed in transgenic hACE2 humanized mouse, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with reduced body weight loss, reduced temperature variation, increased pulmonary parenchymal area, reduced clinical score of the disease and reduced mortality. Collectively, our data establishes that CASP4/11 contributes to disease pathology and contributes for future immunomodulatory therapeutic interventions to COVID-19.

Payment for environmental services for flood control analysis and method of economic viability.

Disorganized urban growth, deforestation, and the occupation of floodplains and riverside areas significantly alter land-use patterns and social and environmental wellbeing. This work aims to present the analysis of the feasibility of the proposal for the implementation of a Payment for Environmental Services (PES) project for flood control. It is related to the recovery and conservation of areas of environmental interest in a hydrographic basin and considering the river channel as a reference and its buffer areas. For the implementation of a PES project aiming at the reduction of floods downstream through the recovery of riparian forests, including their subsequent maintenance, this work proposes a flowchart of the applicable steps, develops a formulation for the definition of payment for the service, and defines a set of measures necessary for its management. Through a case study, it was possible to simulate different scenarios for different recurrence time (RT) in the study area, and thus assess the damage caused by these different events. The innovation of this work comes from the use of PES for the control of floods, with the use of an integral formula to calculate the costs of PES and to evaluate the expected damages. The application of the Poisson distribution was used to estimate the losses for different RT events expected in 50 years, estimating the losses overtime for the scenario with the implementation of the PES project and without it. The damage when reduced or avoided becomes a useful resource for the establishment of other public policies.

COVID-19 Management in Clinical Dental Care Part II: Personal Protective Equipment for the Dental Care Professional.

BACKGROUND: Facing the coronavirus disease 2019 (COVID-19) challenge on a global level, dental care professionals are encouraged to optimize universal precautions and adopt measures that ensure protection against infection by contaminated aerosols and droplets. Although aerosol transmission is possible, direct contact through large droplets is probably responsible for the vast majority of transmissions. METHODS: This paper is the second of a series of 3 on the management of COVID-19 in clinical dental care settings and aims to describe the selection and use of personal protection equipment (PPE) by dental care professionals (DCP), with consideration of the level of risk associated with the planned procedures. PPE selection depends directly on the local epidemiological setting, the patient's characteristics, and the level of risk of the planned procedures. The procedures performed in the office environment are classified as low-, moderate-, or high-risk. Moderate risk includes 2 further sublevels associated with the cleaning, disinfection, and sterilization of materials for clinical procedures that do not generate aerosols. The training of DCP on how to properly don (put on) and doff (remove) PPE is as important as choosing the appropriate PPE because it can be associated with a risk of infection. DISCUSSION: When there is limited availability of PPE, measures should be adjusted to the risk associated with the intervention. Assuming that an effective COVID-19 vaccine will be developed, once it becomes widely available for DCP, PPE requirements will likely be different. CONCLUSION: The proper use of PPE, together with the adoption of other operational procedures, can provide effective protection against microorganisms being transmitted via body fluids or in the air.

Nasopharyngeal microbial communities of patients infected with SARS-COV-2 that developed COVID-19.

BackgroundSARS-CoV-2 is an RNA virus causing COVID-19. The clinical characteristics and epidemiology of COVID-19 have been extensively investigated, however studies focused on the patients microbiota are still lacking. In this study, we investigated the nasopharyngeal microbiome composition of patients who developed different severity levels of COVID-19. We performed Rdna-SSU (16S) sequencing from nasopharyngeal swab samples obtained from SARS-CoV-2 positive (56) and negative (18) patients in the province of Alicante (Spain) in their first visit to the hospital. Positive SARS-CoV-2 patients were observed and later categorized in mild (symptomatic without hospitalization), moderate (hospitalization) and severe (admission to ICU). We compared the microbiome diversity and OTU composition among severity groups using Similarity Percentage (SIMPER) analysis and Maaslin2. We also built bacterial co-abundance networks for each group using Fastpar. ResultsStatistical analysis indicated differences in the nasopharyngeal microbiome of COVID19 patients. 62 OTUs were found exclusively in SARS-CoV-2 positive patients, mostly classified as members of the phylum Bacteroidetes (18) and Firmicutes (25). OTUs classified as Prevotella were found to be significantly more abundant in patients that developed more severe COVID-19. Furthemore, co-abundance analysis indicated a loss of network complexity among samples from patients that later developed more severe symptoms. ConclusionsOur preliminary study shows that the nasopharyngeal microbiome of COVID-19 patients showed differences in the composition of specific OTUs and complexity of co-abundance networks. These microbes with differential abundances among groups could serve as biomarkers for COVID-19 severity. Nevertheless, further studies with larger sample sizes should be conducted to validate these results. IMPORTANCEThis work has studied the microbiota of the nasopharyngeal tract in COVID19 patients using advanced techniques of molecular microbiology. Diverse microorganisms, most of which are harmless or even beneficial to the host, colonize the nasopharyngeal tract. These microorganisms are the microbiota, and they are present in every people. However, changes in this microbiota could be related to different diseases as cancer, gastrointestinal pathologies or even COVID19. This study has been performed to investigate the microbiota from patients with COVID19, in order to determinate its implication in the pathology severity. The results obtained showed that it is possible that several specific microorganisms are present only in patients with severe COVID19. These data, could be used as a prognostic biomarker to early detect whose patients will develop a severe COVID19 and improve their clinical management.

Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

Inflammasome activation in COVID-19 patients

Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1{beta} and IL-18. Although the participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease is unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and it is active in COVID-19, influencing the clinical outcome of the disease. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of post-mortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that the inflammasome is key in the pathophysiology of the disease, indicating this platform as a marker of disease severity and a potential therapeutic target for COVID-19.

First Report of Concomitant Pathogenic Mutations Within MGC4607/CCM2 and KRIT1/CCM1 in a Familial Cerebral Cavernous Malformation Patient.

BACKGROUND: Familial cerebral cavernous malformations (CCM) are among the most common vascular malformations of the central nervous system (CNS) and are linked to mutations on the specific genes CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. We present the first report in the literature of a pharmaco-resistant epileptic patient harboring co-occurring pathogenic mutations within CCM2/MGC4607 and CCM1/KRIT1. CASE DESCRIPTION: A 51-year-old patient first presented at age of 33 years with episodes of seizures. Magnetic resonance imaging including a susceptibility-weighted imaging sequence had shown multiple cerebral cavernous malformation lesions. She had partial response of symptoms and remained in routine follow-up needing progressive pharmacological improvement. Direct sequencing allowed the detection of 1 nonsense pathogenic mutation in CCM2/MGC4607 (c.118C>T; p.Arg40Ter) and 1 unclassified frameshift insertion variant in CCM1/KRIT1 (c.1687_1688insT; p.Tyr563LeufsTer5). CONCLUSIONS: Although the CCM2/MGC460 variant seems to be the major contributor for the patient's CCM phenotype, the mutated CCM1/KRIT1 seems to act as a booster to CCM overall pathogenicity.

Single application of 0.8% hyaluronic acid as a coadjuvant of nonsurgical treatment in nonsmoking patients with periodontitis: A split-mouth, randomized, controlled pilot clinical trial.

BACKGROUND: Topical coadjuvants might be indicated to increase the results of nonsurgical periodontal treatment and overcome some of its limitations. The aim of this study was to evaluate the clinical benefits of a single topical application of 0.8% hyaluronic acid (HA) as a coadjuvant to scaling and root planing (SRP) in periodontal patients. MATERIALS AND METHODS: Sixteen patients diagnosed with periodontitis were recruited to participate in this split-mouth randomized controlled trial. At baseline, oral hygiene instructions, prophylaxis, and SRP were performed in both sides; additionally, a subgingival application of HA at 0.8% was made in the test side. Several clinical parameters were assessed at baseline, 6, and 12 weeks later: full mouth plaque score, gingival score, bleeding on probing (BoP), probing depth (PD), and clinical attachment level (CAL). RESULTS: At the end of 12 weeks, there was a overall improvement in all periodontal parameters in both sides (P < 0.05). Test sides showed less BoP when compared to the control sides (9.4 ± 4.0 vs. 14.9 ± 8.9, P < 0.05). Other periodontal parameters such as PD and CAL showed a slight improvement in comparison with the control sides, but the difference was not statistically significant (P > 0.05). CONCLUSION: Results from this study indicate that a single subgingival application of 0.8% HA seems to reduce gingival inflammation and improve clinical parameters, particularly BoP. Further studies are needed to evaluate the effect of repeated application of HA and long-term results.

Redescription of Naineris aurantiaca (Müller, 1858) and designation of a neotype from the Brazilian coast (Annelida: Orbiniidae).

The genus Naineris differs from other genera of the Orbiniidae in that all its species possess a rounded prostomium and one or two achaetous rings. Currently, 21 species of this genus have been described worldwide, five of which are recorded from Brazil. Naineris aurantiaca is the only species originally described from the Brazilian coast and the original description is the only record of this species. The description is short and vague, making identification difficult. From recent samples obtained in the type locality of Florianópolis, Brazil, we were able to study specimens of Naineris aurantiaca and redescribe the species. Diagnostic characters for this species are the presence of pre- and post-branchial papillae, anterior branchiae in thoracic segments considerably smaller than those of the rest of the body, distinct dorsal sensory organ from chaetiger 12 onwards, the chaetal arrangement of the thoracic neuropodia (crenulated capillaries in a lower oblique row, uncini in an upper oblique row, subuluncini in two anterior transverse rows, and acicular spines in a posterior row), interramal papillae only present on abdominal parapodia, and the presence of furcate chaetae in the abdominal notopodia. Here, we designate a neotype for the species and discuss the morphological variations we observed among specimens.

Functional capacity, renal function and vitamin D in community-dwelling oldest old.

PURPOSE: The aim of this study was to evaluate the association between the decline in estimated glomerular filtration rate (eGFR) and serum 25(OH)D with the physical and mental functional capacity of elderly individuals aged 80 years or older. METHODS: We evaluated the functional capacity in its multidomain aspects: Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL), Mental State Mini-Exam (MMSE), Verbal Fluency Test (VF), handgrip strength and time to sit and rise from a chair five times, combined creatinine and cystatin C-based eGFR and 25(OH)D levels in 205 independent asymptomatic and community-dwelling elderly subjects in a cross-sectional study. RESULTS: Every 1 year of life, there was reduction of about 10% chance of adequate performance in functional capacity. Each 1 ml/min/m2 in eGFR was associated with 2% better chance of adequate performance in the IADL. We found no association between eGFR and cognition. Serum 25(OH)D between 15.00 and 22.29 ng/ml increased the chance of better performance in VF, IADL, handgrip strength and sit and rise from the chair compared to the lower level of serum vitamin D. CONCLUSIONS: Decreased renal function associated with age compromises the ability to perform activities for independent life in the community, but we did not observe influence in specific domains of cognition and physical performance. Low serum level of 25(OH)D appears to be a marker of greater risk of functional decline than eGFR measurement in independent oldest old dwelling in the community.

Prevalence of chronic kidney disease and comorbidities in isolated African descent communities (PREVRENAL): methodological design of a cohort study.

BACKGROUND: Chronic kidney disease (CKD) is considered a serious public health problem, both in Brazil and worldwide, with an increasing number of cases observed inrecent years. Especially, CKD has been reported to be highly prevalent in those of African descent. However, Brazil lacks data from early-stage CKD population studies, and the prevalence of CKD is unknown for both the overall and African descent populations. Hence, the present study aimsto estimate the prevalence of early-stage CKD and its associated risk factors in African-Brazilians from isolated African-descent communities. Herein, the detailed methodology design of the study is described. METHODS: This population-based, prospective, longitudinal, cohort study (PREVRENAL) is performed in three stages: first, clinical, nutritional, and anthropometric evaluations; measurements of serum and urinary markers; and examinations of comorbiditieswere performed. Second, repeated examinations of individuals with CKD, systemic arterial hypertension, and/or diabetes mellitus; image screening; and cardiac risk assessment were performed. Third, long-term monitoring of all selected individuals will be conducted (ongoing). Using probability sampling, 1539 individuals from 32 communities were selected. CKD was defined asaglomerular filtration rate (GFR) ≤60 mL/min/1.73m2 and albuminuria > 30 mg/day. DISCUSSION: This study proposes to identify and monitor individuals with and without reduced GFR and high albuminuria in isolated populations of African descendants in Brazil. As there are currently no specific recommendations for detecting CKD in African descendants, four equations for estimating the GFR based on serum creatinine and cystatin C were used and will be retrospectively compared. The present report describes the characteristics of the target population, selection of individuals, and detection of a population at risk, along with the imaging, clinical, and laboratory methodologies used. The first and second stages have been concluded and the results will be published in the near future. The subsequent (third) stage is the long-term, continuous monitoring of individuals diagnosed with renal abnormalities or with CKD risk factors. The entire study population will be re-evaluated five years after the study initiation. The expectation is to obtain information about CKD evolution among this population, including the progression rate, complication development, and cardiovascular events.

Doença de Creutzfeldt-Jakob: forma esporádica: relato de caso em paciente de 81 anos / Creutzfeldt-Jacob disease-sporadic form: case report of 81-year-old patient

As doenças priônicas são neurodegenerativas e possuem longo período de incubação, progredindo inexoravelmente, assim que os sintomas clínicos aparecem. A doença de Creutzfeldt-Jakob é a mais frequente das doenças priônicas, embora ainda seja rara. O quadro clínico dela é caracterizado por uma demência rapidamente progressiva, sintomas cerebelares e extrapiramidais, e a ressonância magnética, o eletroencefalograma e a análise do líquido cefalorraquidiano possuem achados típicos. Relatamos o caso de um paciente de 81 anos que se apresentou com declínio cognitivo rapidamente progressivo seguido, posteriormente, de mutismo acinético. Proteína 14-3-3 foi detectada no líquido cefalorraquidiano. A ressonância magnética revelou hipersinal do núcleo caudado e putâmen em imagem em difusão, T2 e FLAIR.(AU)

Prion diseases are neurodegenerative, and have long incubation periods, progressing inexorably once clinical symptoms appear. Creutzfeldt-Jakob disease (CJD) is the most frequent of the human prion diseases, although being still rare. The clinical picture of this disease is characterized by a rapidly progressing dementia, cerebellar and extrapyramidal symptoms, and rather specific magnetic resonance (MR), electroencephalography and cerebrospinal fluid (CSF) findings. We report the case of an 81-year-old patient who presented with rapidly progressive cognitive decline followed by akinetic mutism. Protein 14-3-3 in cerebrospinal fluid was detected. Magnetic resonance imaging findings revealed hyperintensity of the caudate and putamen in diffusion-weighted imaging, T2 Weighted sequences and FLAIR images. Patients who have progressive dementia should be evaluated by means of magnetic resonance imaging and cerebrospinal fluid analysis for Creutzfeldt-Jakob.(AU)

Paroxysmal Sympathetic Hyperactivity: An Old but Unrecognized Condition.

Patients who survive a traumatic brain injury (TBI) can sometimes experience symptoms of excessive sympathetic discharge. Despite being known about for more than 60 years, the diagnostic criteria for this condition have only recently been defined under the name "paroxysmal sympathetic hyperactivity". Failure to recognize this syndrome leads to excessive costs, prolonged hospital stays and delayed recovery for TBI patients. This case report describes a patient whose specific rehabilitation program was affected by a failure to identify this entity, even though he presented with many of the characteristics of this condition. LEARNING POINTS: Fever is a common sign in hospitalized patients and can result in expensive investigations and prolong length of stay.It is crucial to consider paroxysmal sympathetic hyperactivity (PSH) as a cause of fever in traumatic brain injury patients (TBI).A delay in diagnosing and treating PSH can have devastating consequences for these patients' recovery programs.

Papel da titina na modulação da função cardíaca e suas implicações fisiopatológicas / The role of titin in the modulation of cardiac function and its pathophysiological implications / Papel de la Titina en la Modulación de la Función Cardíaca y sus Implicaciones Fisiopatológicas

A titina é uma proteína sarcomérica gigante que se estende desde a linha Z até a linha M. Em razão de sua localização, representa um importante sensor biomecânico com um papel fundamental na manutenção da integridade estrutural do sarcômero. A titina funciona como uma "mola bidirecional" que regula o comprimento sarcomérico e realiza ajustes adequados da tensão passiva sempre que o comprimento varia. Dessa forma, não só determina a rigidez ventricular e a função diastólica, como também influencia a função cardíaca sistólica, modulando o mecanismo de Frank-Starling. O miocárdio expressa duas isoformas dessa macromolécula: a N2B, mais rígida, e a isoforma N2BA, mais complacente. As alterações na expressão relativa das duas isoformas da titina ou alterações do seu estado de fosforilação têm sido implicadas na fisiopatologia de várias doenças como a insuficiência cardíaca diastólica, a cardiomiopatia dilatada, a cardiomiopatia isquêmica e a estenose aórtica. Neste artigo pretende-se descrever sumariamente a estrutura e localização da titina, a sua relação com diferentes cardiomiopatias, e compreender de que forma as alterações dessa macromolécula influenciam a fisiopatologia da insuficiência cardíaca diastólica, salientando o potencial terapêutico da manipulação dessa macromolécula.

Titin is a giant sarcomeric protein that extends from the Z-line to the M-line. Due to its location, it represents an important biomechanical sensor, which has a crucial role in the maintenance of the sarcomere structural integrity. Titin works as a "bidireactional spring" that regulates the sarcomeric length and performs adequate adjustments of passive tension whenever the length varies. Therefore, it determines not only ventricular rigidity and diastolic function, but also systolic cardiac function, modulating the Frank-Starling mechanism. The myocardium expresses two isoforms of this macromolecule: the N2B, more rigid and the isoform N2BA, more compliant. The alterations in the relative expression of the two titin isoforms or alterations in their state of phosphorylation have been implicated in the pathophysiology of several diseases, such as diastolic heart failure, dilated cardiomyopathy, ischemic cardiomyopathy and aortic stenosis. The aim of this study is to describe, in brief, the structure and location of titin, its association with different cardiomyopathies and understand how alterations in this macromolecule influence the pathophysiology of diastolic heart failure, emphasizing the therapeutic potential of the manipulation of this macromolecule.

La titina es una proteína sarcomérica gigante que se extiende desde la línea Z hasta la línea M. En razón de su ubicación, representa un importante sensor biomecánico con un papel fundamental en la manutención de la integridad estructural del sarcómero. La titina funciona como un "resorte bidireccional" que regula el largo sarcomérico y realiza ajustes adecuados de la tensión pasiva siempre que ese largo varía. De esa forma, no sólo determina la rigidez ventricular y la función diastólica, sino también influye en la función cardíaca sistólica, modulando el mecanismo de Frank-Starling. El miocardio expresa dos isoformas de esa macromolécula: la N2B, más rígida, y la isoforma N2BA, más complaciente. Las alteraciones en la expresión relativa de las dos isoformas de la titina o alteraciones de su estado de fosforilación han sido implicadas en la fisiopatología de varias enfermedades como la insuficiencia cardíaca diastólica, la cardiomiopatía dilatada, la cardiomiopatía isquémica y la estenosis aórtica. Este artículo pretende describir sumariamente la estructura y ubicación de la titina, su relación con diferentes cardiomiopatías, y comprender de qué forma las alteraciones de esa macromolécula influyen en la fisiopatología de la insuficiencia cardíaca diastólica, destacando el potencial terapéutico de la manipulación de esa macromolécula.