Design and Evaluation of a Novel Venturi-Based Spirometer for Home Respiratory Monitoring.

The high cost and limited availability of home spirometers pose a significant barrier to effective respiratory disease management and monitoring. To address this challenge, this paper introduces a novel Venturi-based spirometer designed for home use, leveraging the Bernoulli principle. The device features a 3D-printed Venturi tube that narrows to create a pressure differential, which is measured by a differential pressure sensor and converted into airflow rate. The airflow is then integrated over time to calculate parameters such as the Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). The system also includes a bacterial filter for hygienic use and a circuit board for data acquisition and streaming. Evaluation with eight healthy individuals demonstrated excellent test-retest reliability, with intraclass correlation coefficients (ICCs) of 0.955 for FVC and 0.853 for FEV1. Furthermore, when compared to standard Pulmonary Function Test (PFT) equipment, the spirometer exhibited strong correlation, with Pearson correlation coefficients of 0.992 for FVC and 0.968 for FEV1, and high reliability, with ICCs of 0.987 for FVC and 0.907 for FEV1. These findings suggest that the Venturi-based spirometer could significantly enhance access to spirometry at home. However, further large-scale validation and reliability studies are necessary to confirm its efficacy and reliability for widespread use.

Protocol for CRISPR-Cas12a genome editing of protein tyrosine phosphatases in human pluripotent stem cells and functional ß-like cell generation.

Gene editing of human pluripotent stem cells is a promising approach for developing targeted gene therapies for metabolic diseases. Here, we present a protocol for generating a CRISPR-Cas12a gene knockout of protein tyrosine phosphatases in human embryonic stem cells. We describe steps for differentiating the edited clones into pancreatic islet-like spheroids rich in ß-like cells. We then detail procedures for implanting these spheroids under the murine kidney capsule for in vivo maturation.

Origem aberrante da artéria subclávia direita: um diagnóstico a ser considerado / Aberrant origin of the right subclavian artery: a diagnosis to be considered

APRESENTAÇÃO DO CASO: Paciente do sexo masculino, 5 anos, encaminhado ao nosso serviço devido quadro de refluxo gastresofágico (RGE) iniciado aos 4 meses de idade, evoluindo com disfagia, vômitos intensos, déficit pôndero-estatural e episódios recorrentes de broncoespasmo. Fez uso contínuo de corticóide inalatório, broncodilatadores e inibidores de bomba de prótons (IBP), sem resposta adequada. Devido à persistência dos sintomas, realizado endoscopia digestiva alta (EDA), a qual evidenciou quadro de Esofagite Erosiva Distal de leve intensidade e compressão extrínseca esofágica pulsátil, sugestiva de artéria subclávia anômala. Confirmado diagnóstico por ecodopplercardiograma transtorácico que demonstrou a presença de artéria subclávia direita aberrante com trajeto retroaórtico e realizado angiotomografia dos vasos da base que corroborou com achado ecocardiográfico. Paciente evoluiu clinicamente estável, sendo mantido em seguimento clínico devido exames subsequentes como EDA e estudo contrastado do esôfago-estômago-duodeno (EED) sem sinais de compressão extrínseca naquele momento. DISCUSSÃO: A anomalia da artéria subclávia direita é a malformação vascular mais comum do arco aórtico, apesar de ser considerada uma condição rara na população de modo geral, estando presente em apenas 0,05% a 1%, em paciente com Síndrome de Down, a incidência encontra-se em cerca de 40%. Tal condição ocorre quando a artéria subclávia direita se origina diretamente da aorta descendente, e sua causa pode estar relacionada à regressão anormal do quarto arco aórtico primitivo, durante o desenvolvimento embriológico. O trajeto posterior ao esôfago e à traqueia é uma característica importante dessa anomalia, pois, apesar de raros, são descritos sintomas consequentes à compressão posterior dessas estruturas, tais como disfagia, RGE, estridor e dispneia, além de degeneração aneurismática ou doença aterosclerótica oclusiva. COMENTÁRIOS FINAIS: Por mais que a artéria subclávia com origem aberrante seja uma malformação rara, geralmente um achado acidental e embora dificilmente perpetue com sintomas, a suspeita sempre deve ser levantada diante de quadro de sintomas relacionados à compressão traqueal ou esofageana, como crises de broncoespasmo recorrentes e sintomas digestivos como refluxo e disfagia. Dessa forma, seu diagnóstico precoce é essencial para melhora da qualidade de vida, bem como evitar repercussões clínicas ao paciente.

Origem anômala da coronária esquerda do tronco pulmonar (ALCAPA): uma série de casos / Anomalous origin of the left coronary artery from the pulmonary trunk (ALCAPA): a case series

APRESENTAÇÃO DOS CASOS: Caso 1: Paciente sexo feminino, 11 meses, encaminhada devido quadro de insuficiência cardíaca congestiva (ICC) e diagnóstico de miocardiopatia dilatada aos 4 meses de idade. À admissão, eletrocardiograma (ECG) com sinais de sobrecarga biventricular e presença de onda Q em parede anterior-média. Ecocardiograma transtorácico (ECOTT) confirmou ALCAPA, cursando com disfunção importante do ventrículo esquerdo com FEVE pelo método de Simpson (Biplanar) de 14%. Realizado angiotomografia de coronárias e ressonância nuclear magnética, a qual identificou defeito de perfusão transmural na parede septal e anterior lateral (sugestivo de isquemia miocárdica) e presença de realce tardio de padrão coronariano nos segmentos médiobasal, anterior e lateral. Paciente submetida a cirurgia de Takeuchi, evoluindo com melhora clínica e recuperação gradual da função ventricular. Caso 2: Paciente sexo feminino, 12 anos, portadora de síndrome de Down, encaminhada devido queixa de dispneia aos grandes esforços. ECG sem sinais de isquemia. ECOTT evidenciou ALCAPA com função sistólica biventricular preservada, justificada pela presença de suprimento vascular através de colaterais entre as coronárias direita e esquerda. Devido estabilidade clínica e cardiopatia sem repercussão, mantida em seguimento ambulatorial. DISCUSSÃO: A síndrome de ALCAPA é uma cardiopatia congênita rara. Expressa nos primeiros meses de vida, em 85% dos casos, por quadro de ICC e disfunção ventricular esquerda, podendo englobar arritmias, síncope e morte súbita. Em cerca de 15%, o desenvolvimento de rede de colaterais coronárias garante o suprimento arterial miocárdico, evoluindo oligossintomáticos até a fase adulta. O diagnóstico baseia-se na suspeição clínica, associada a ECG compatível com isquemia segmentar e imagem ecocardiográfica característica. Embora o exame padrão-ouro seja a angiografia invasiva coronariana, esse exame tem sido reservado para os raros casos de dúvida diagnóstica. Assim, a correção cirúrgica garante o reestabelecimento da função cardíaca quanto mais precoce for realizado, com taxas de recuperação em até 98% dos pacientes. CONSIDERAÇÕES FINAIS: Trata-se da comparação de 2 casos clínicos demonstrando as variantes da síndrome de ALCAPA, na qual, a presença ou não de rede de colaterais gerando suprimento miocárdico, pode alterar o curso clínico da doença. Assim, o diagnóstico preciso em qualquer faixa etária é essencial para garantir um bom prognóstico da síndrome.

Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression.

Ovarian cancer (OC) patients develop ascites, an accumulation of ascitic fluid in the peritoneal cavity anda sign of tumour dissemination within the peritoneal cavity. This body fluid is under-researched, mainly regarding the ascites formed during tumour progression that have no diagnostic value and, therefore, are discarded. We performed a discovery proteomics study to identify new biomarkers in the ascites supernatant of OC patients. In this preliminary study, we analyzed a small amount of OC ascites to highlight the importance of not discarding such biological material during treatment, which could be valuable for OC management. Our findings reveal that OC malignant ascitic fluid (MAF) displays a proliferative environment that promotes the growth of OC cells that shift the metabolic pathway using alternative sources of nutrients, such as the cholesterol pathway. Also, OC ascites drained from patients during treatment showed an immunosuppressive environment, with up-regulation of proteins from the signaling pathways of IL-4 and IL-13 and down-regulation from the MHC-II. This preliminary study pinpointed a new protein (Transmembrane Protein 132A) in the OC context that deserves to be better explored in a more extensive cohort of patients' samples. The proteomic profile of MAF from OC patients provides a unique insight into the metabolic kinetics of cancer cells during disease progression, and this information can be used to develop more effective treatment strategies.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

OBJECTIVE: To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). METHODS: We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. RESULTS: Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). CONCLUSIONS: The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

All-on-4 Hybrid with Extra-Long Transnasal Implants: Descriptions of the Technique and Short-Term Outcomes in Three Cases.

Background/Objectives: There is a need for alternative approaches to full-arch rehabilitation of atrophic maxillae. The aim of this short case series was to describe the technique and assess the short term-outcomes of atrophic maxillae rehabilitation using transnasal implants in conjunction with zygomatic implants. Methods: Three female patients (average age: 62 years) presenting comorbidities and atrophic maxillae preventing the insertion of standard maxillary anchored implants received a full-arch fixed prosthesis supported by transnasal implants together with zygomatic implants, using the ad modum all-on-4 concept. Patients were followed during the functional osseointegration period. Primary outcome measures were prosthetic and implant survival based on function. Secondary outcome measures were complication parameters (biological and mechanical), plaque and bleeding levels, and probing pocket depths > 4 mm. Results: No implant failures were registered, and all prostheses remained in function. The only complication was a fracture of a provisional crown that was resolved. Plaque and bleeding scores were mild during the follow-up period. Conclusions: The present manuscript describes the use of extra-long transnasal implants in combination with zygomatic implants in immediate function for full-arch fixed prosthetic rehabilitation of atrophic maxillae, with the objective of promoting more research into this relatively recent technique. More studies are needed to validate the technique.

Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options.

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

Orbitostriatal encoding of reward delayed gratification and impulsivity in chronic pain.

Central robust network functional rearrangement is a characteristic of several neurological conditions, including chronic pain. Preclinical and clinical studies have shown the importance of pain-induced dysfunction in both orbitofrontal cortex (OFC) and nucleus accumbens (NAc) brain regions for the emergence of cognitive deficits. Outcome information processing recruits the orbitostriatal circuitry, a pivotal pathway regarding context-dependent reward value encoding. The current literature reveals the existence of structural and functional changes in the orbitostriatal crosstalk in chronic pain conditions, which have emerged as a possible underlying cause for reward and time discrimination impairments observed in individuals affected by such disturbances. However, more comprehensive investigations are needed to elucidate the underlying disturbances that underpin disease development. In this review article, we aim to provide a comprehensive view of the orbitostriatal mechanisms underlying time-reward dependent behaviors, and integrate previous findings on local and network malplasticity under the framework of the chronic pain sphere.

A New Full Digital Workflow for Fixed Prosthetic Rehabilitation of Full-Arch Edentulism Using the All-on-4 Concept.

(1) Background: Recent digital workflows are being developed for full-arch rehabilitations supported by implants with immediate function. The purpose of this case series is to describe a new digital workflow for the All-on-4 concept. (2) Methods: The patients were rehabilitated using the All-on-4 concept with a digital workflow including computerized tomography scanning, intra-oral scanning, and CAD-CAM production of the temporary prosthesis, with the 3D printing of stackable guides (base guide, implant guide, and prosthetic guide). The passive fit of the prostheses and the time to perform the rehabilitations were evaluated. (3) Results: The digital workflow allowed for predictable bone reduction, the insertion of implants with immediate function, and the connection of an implant-supported prosthesis with immediate loading. The time registered to perform the full-arch rehabilitations (implant insertion, abutment connection, prosthesis connection) was below 2 hours and 30 min. No passive fit issues were noted. (4) Conclusions: within the limitation of this case series, the digital workflow applied to the All-on-4 concept using stackable base-, implant-, and prosthetic guides constitutes a potential alternative with decreased time for the procedure without prejudice of the outcome.

Asociación entre niveles de ansiedad y depresión en adultos con obesidad / Associação entre níveis de ansiedade e depressão em adultos com obesidade / Association between anxiety levels and depression in adults with obesity

Objetivo: Verificar la asociación entre los niveles de ansiedad y depresión en participantes de un Programa Multidisciplinario para el Tratamiento de la Obesidad, con variables antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y aptitud física relacionada con la salud. Método: Estudio cuantitativo, correlacional, transversal, realizado con adultos participantes del Programa Multidisciplinario de Tratamiento de la Obesidad en un municipio del Noroeste de Paraná. Para la recolección de datos se aplicaron medidas antropométricas en julio de 2021; composición corporal; parámetros bioquímicos y hemodinámicos; pruebas de aptitud física relacionadas con la salud; y escala para evaluar los niveles de ansiedad y depresión. Resultados: Participaron del estudio 116 individuos, 87,94% mujeres, 12,06% hombres, con una edad media de 40 años. Hubo una correlación positiva considerable entre la hemoglobina y el hematocrito; colesterol total y LDL; glucosa y HbA1C1; peso e IMC; peso y perímetro abdominal; peso y circunferencia de la cintura; IMC y perímetro abdominal; IMC y perímetro de cintura; así como ansiedad y depresión. Conclusión: Los niveles de ansiedad y depresión de los participantes de Programa Multidisciplinario para el Tratamiento de la Obesidad no se correlacionaron significativamente con las variables de medición antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y pruebas de evaluación de la aptitud física relacionadas con la salud. (AU)

Objetivo: Verificar associação entre níveis de ansiedade e depressão de participantes de um Programa Multiprofissional de Tratamento da Obesidade, com variáveis antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; e aptidão física relacionada à saúde. Método: Estudo transversal, realizado com adultos que participaram do programa em município do Noroeste do Paraná. Para a coleta de dados, aplicou-se em julho de 2021, avaliações de medidas antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; testes de aptidão física relacionada à saúde; e escala para avaliar os níveis de ansiedade e depressão. Resultados: Participaram do estudo 116 indivíduos, sendo 87,94% do sexo feminino, 12,06% do sexo masculino, com média de idade de 40 anos. Houve correlação positiva entre hemoglobinas e hematócritos; colesterol total e LDL; glicose e HbA1C1; peso, IMC e circunferências abdominal e de cintura; além de ansiedade e depressão. Conclusão: Os níveis de ansiedade e depressão não apresentaram correlação significativa com as variáveis estudadas. (AU)

Objective: To verify the association between levels of anxiety and depression of participants in a Multidisciplinary Program for the Treatment of Obesity, with anthropometric variables; body composition; biochemical and hemodynamic parameters; and health-related physical fitness. Method: Quantitative, correlational, cross-sectional study carried out with adults who participated in the Multidisciplinary Program for the Treatment of Obesity in a municipality in the Northwest of Paraná. For data collection, anthropometric measurements were applied in July 2021; body composition; biochemical and hemodynamic parameters; health-related physical fitness tests; and scale to assess levels of anxiety and depression. Results: 116 individuals participated in the study, 87.94% female, 12.06% male, with a mean age of 40 years. There was a considerable positive correlation between hemoglobin and hematocrit; total and LDL cholesterol; glucose and HbA1C1; weight and BMI; weight and abdominal circumference; weight and waist circumference; BMI and abdominal circumference; BMI and waist circumference; as well as anxiety and depression. Conclusion:The levels of anxiety and depression of the participants of the Multidisciplinary Program for the Treatment of Obesity did not present a significant correlation with the variables of anthropometric measurements; body composition; biochemical and hemodynamic parameters; and health-related physical fitness assessment tests. (AU)

Concern about the risk of aerosol contamination from ultrasonic scaler: a systematic review and meta-analysis.

BACKGROUND: Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments can carry, in addition to water, droplets of saliva, blood, and microorganisms, which can pose a risk of infections for healthcare professionals and patients. Due to the COVID-19 pandemic, this gained attention. OBJECTIVE: The aim was to carry out a systematic review of the evidence of the scope of the aerosol produced by ultrasonic scaler in environmental contamination and the influence of the use of intraoral suction reduction devices. DESIGN: Scientific literature was searched until June 19, 2021 in 6 databases: Pubmed, EMBASE, Web of science, Scopus, Virtual Health Library and Cochrane Library, without restrictions on language or publication date. Studies that evaluated the range of the aerosol produced by ultrasonic scaler during scaling/prophylaxis and the control of environmental contamination generated by it with the use of low (LVE) and high (HVE) volume evacuation systems were included. RESULTS: Of the 1893 potentially relevant articles, 5 of which were randomized controlled trials (RCTs). The meta-analysis of 3 RCTs showed that, even at different distances from the patient's oral cavity, there was a significant increase in airborne bacteria in the dental environment with the use of ultrasonic scaler. In contrast, when meta-analysis compared the use of HVE with LVE, there was no significant difference (P = 0.40/CI -0.71[-2.37, 0.95]) for aerosol produced in the environment. CONCLUSIONS: There is an increase in the concentration of bioaerosol in the dental environment during the use of ultrasonic scaler in scaling/prophylaxis, reaching up to 2 m away from the patient's mouth and the use of LVE, HVE or a combination of different devices, can be effective in reducing air contamination in the dental environment, with no important difference between different types of suction devices.

Partial Implant Rehabilitations in the Posterior Regions of the Jaws Supported by Short Dental Implants (7.0 mm): A 7-Year Clinical and 5-Year Radiographical Prospective Study.

Background: Short implants have been used in the restoration of edentulous jaws in the past several years. However, some studies have suggested that short implants are less successful than standard implants. The aim of this study is to investigate the outcome of short implants placed in the posterior maxilla or mandible following one-stage or immediate-function protocols with a follow-up of 7 years (clinically) and 5 years (radiographically). Methods: This study included 127 patients rehabilitated with 217 implants measuring 7 mm and supporting 157 fixed prostheses in the posterior segments of both jaws. Final abutments were delivered at the surgery stage and were loaded after 4 months in 116 patients (199 implants). The primary outcome measure was implant survival measured through life tables. Secondary outcome measures were marginal bone loss and the incidence of biological and mechanical complications at the patient level and implant level (evaluated through descriptive statistics). Results: Twenty-four patients (18.9%) with 45 implants (20.7%) were lost to the follow-up. In total, 32 implants failed (14.8%) in 22 patients (17.3%), resulting in a cumulative survival rate at 7 years of 81.2% for 7 mm implants in the rehabilitation of the posterior regions of the maxilla and mandible. The average (standard deviation) marginal bone loss was 1.47 mm (0.99 mm) at 5 years. The incidence rate of biological complications was 12.6% and 10.6% at the patient and implant levels, respectively. The incidence rate of mechanical complications was 21.3% for patients and 16.1% for implants. A higher failure rate was registered in smokers and in implant arrangements with a sequence of three fixtures in proximity. Conclusions: Within the limitations of this study, it can be concluded that the placement of 7 mm long implants for the partial implant-supported rehabilitation of atrophic posterior jaws is possible in the long term, judging by the survival rate and stable average marginal bone loss. Nevertheless, strict case selection should be performed, especially in smokers and with implant arrangements that provide a minimum of one unit in inter-implant distance.

Cdc42 activation is necessary for heterosynaptic cooperation and competition.

Synapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that modulation of actin cytoskeleton by Cdc42 activation is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated.

Epidemiological, immunological, and treatment response profile of patients with lupus nephritis in Brazil.

BACKGROUND AND HYPOTHESIS: Brazil has the largest number of individuals of African descent outside Africa and a very admixed population. Among cases of lupus nephritis (LN) in the country, there are differences in incidence, and even in severity, depending on the location and characteristics of the population studied. The aim of this study was to describe the clinical and epidemiological characteristics of LN in Brazil, as well as to determine which of those characteristics would be risk factors for a poor renal prognosis. METHODS: This was a retrospective, descriptive observational study of patients diagnosed with LN who underwent kidney biopsy between 1999 and 2015 in the Nephrology Department of the Hospital das Clínicas, in São Paulo, Brazil. Data were collected from electronic medical records. RESULTS: We evaluated 398 patients, among who 94.1% and 77.7% tested positive for antinuclear antibodies and anti-DNA antibodies, respectively, whereas 33.7% showed the full-house pattern. The time from LN symptom onset to biopsy was <6 months in 47.5% (early biopsy group) and ≥6 months in 52.5% (late biopsy group). In the early biopsy group, the chronicity index was lower and the activity index was higher. Multivariate analysis showed that a higher chronicity index was the only independent risk factor for progression to requiring kidney replacement therapy. CONCLUSION: Late biopsy seems to be associated with negative renal outcomes in LN. However, it seems that a higher chronicity index is the main predictor of a poor renal outcome among patients with LN in Brazil.

The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Allopurinol-Induced Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a rare and life-threatening cutaneous disease, frequently triggered by drugs. Allopurinol is one of the most frequent drugs associated with TEN, which implies detachment of a significant amount of the body surface area (BSA) and has a high morbidity and mortality associated with it. We present the case of a 68-year-old female with a recent diagnosis of hyperuricemia who started treatment with allopurinol. A week later, she presented to the emergency department with an extensive maculopapular exanthema with blisters and skin detachment. After the exclusion of other etiologies, the diagnosis of allopurinol-induced TEN was made, with 35% of BSA involvement. Due to the severity of the clinical condition, she was admitted to intensive care and treated with corticoids that had no response. So, she was started on immunoglobulins and transferred to a burn unit. She developed sepsis with multiorgan failure and required supportive treatment. She was discharged after a month, and physical rehabilitation was needed. This clinical case highlights the severity of allopurinol hypersensitivity that may happen and the importance of an accurate diagnosis and treatment for this rare disease.

Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions.

Chronic pain is a health problem that affects the ability to work and perform other activities, and it generally worsens over time. Understanding the complex pain interaction with brain circuits could help predict which patients are at risk of developing central dysfunctions. Increasing evidence from preclinical and clinical studies suggests that aberrant activity of the lateral habenula (LHb) is associated with depressive symptoms characterized by excessive negative focus, leading to high-level cognitive dysfunctions. The primary output region of the LHb is the ventral tegmental area (VTA), through a bidirectional connection. Recently, there has been growing interest in the complex interactions between the LHb and VTA, particularly regarding their crucial roles in behavior regulation and their potential involvement in the pathological impact of chronic pain on cognitive functions. In this review, we briefly discuss the structural and functional roles of the LHb-VTA microcircuit and their impact on cognition and mood disorders in order to support future studies addressing brain plasticity during chronic pain conditions.

Faunistic Analysis of Calliphoridae and Mesembrinellidae (Diptera: Oestroidea) at Different Stages of Bovine Liver Decomposition in the State of Rio de Janeiro.

Performing quantitative sampling and determining faunistic analyses of dipterans is of fundamental importance in the analysis of ecological behavior, such as population dynamics and diversity, among other factors, for exotic and native species of necrophagous dipterans, so it is important to observe the type of bait used in traps to capture these dipteran species. This work aims to study structural parameters and faunistic indices of the diversity of Calliphoridae and Mesembrinellidae species as well as the abundance and diversity of species attracted to liver in two stages of decomposition: fresh liver and liver at 48 h of putrefaction. A total of 2826 dipterans were collected during the period from May 2021 to February 2022. We observed that liver in decomposition for 48 h was more attractive in the forest and rural environments, while fresh liver showed greater attractiveness in the urban environment; however, no statistical difference was evidenced between the attractiveness in the different environments. The Mesembrinellidae family and the species Lucilia eximia (Wiedemann, 1819) were collected mostly from deteriorated liver, while Cochliomyia macellaria (Fabricius, 1775) showed no preference for any liver decomposition stage. The Wilcoxon test indicated that there is a significant difference between the preferences for putrefied bait in Mesembrinellidae, while in Calliphoridae, there was no preference for type of bait. The faunistic analysis showed that richness in the forest area was always higher when compared to the urban and rural areas. Laneela nigripes (Guimarães, 1977) and Mesembrinella bellardiana (Aldrich, 1922) were abundant and exclusive in the preserved environment, showing themselves to be good environmental bioindicators.

Associação de métodos de imagem no desafio diagnóstico da drenagem anômala total das veias pulmonares do tipo mista / Association of imaging methods in the diagnostic challenge of mixed total anomalous pulmonary vein drainage

APRESENTAÇÃO DO CASO: Lactente sem diagnósticos prévios, internado com dispneia e baixo débito cardíaco aos dois meses de vida. Transferido para serviço de referência em cardiopatias congênitas em ventilação mecânica e em uso de drogas vasoativas. Realizado ecocardiograma que demonstrou drenagem anômala total das veias pulmonares (DATVP) do tipo mista, com as veias pulmonares esquerdas drenando em veia vertical ascendente, que desemboca na veia inominada, e então na veia cava superior (VCS) e as veias pulmonares direitas drenando no seio coronário, que desemboca no átrio direito. O exame também demonstrou comunicações interatriais tipo ostium secundum não restritivas com fluxo do átrio direito para o esquerdo, dilatação importante das cavidades direitas, ventrículo direito com hipertrofia importante e disfunção sistólica, além de hipertensão pulmonar. Submetido a angiotomografia de coração corroborando o diagnóstico, com melhor visualização de todo o trajeto da veia vertical. Realizada cirurgia com redirecionamento das veias pulmonares e ligadura da veia vertical, com sucesso. DISCUSSÃO: A DATVP é uma cardiopatia congênita cianótica rara na qual todas as veias pulmonares se conectam com o sistema venoso sistêmico. Resulta da persistência das conexões embrionárias do plexo venoso pulmonar. O tipo IV da classificação de Darling e colaboradores ou drenagem mista é a associação entre duas ou mais dentre as formas supracardíaca, infracardíaca ou intracardíaca. Neste caso, houve combinação da drenagem supracardíaca das veias pulmonares esquerdas (que por meio da veia vertical drenavam na VCS), com a drenagem intracardíaca das veias pulmonares direitas (que drenavam no átrio direito através do seio coronário). Esta associação é uma variante rara com apenas alguns relatos. O ecocardiograma realizado por profissional experiente em cardiopatias congênitas dá o diagnóstico, mas a associação com outros métodos de imagem como a tomografia é especialmente importante nas variantes mistas para permitir um plano cirúrgico adequado e o redirecionamento completo, evitando lesões residuais. COMENTÁRIOS FINAIS: Apresentamos um caso de DATVP com drenagem cardíaca e supracardíaca, forma rara e de diagnóstico desafiador, definido pelo ecocardiograma e confirmado por tomografia computadorizada com reconstrução 3D. Devido à grande variabilidade da DATVP, é essencial detalhar bem o trajeto, as conexões dos vasos e o local de drenagem de cada um deles para um manejo adequado.