Plasma lipidomics analysis reveals altered profile of triglycerides and phospholipids in children with Medium-Chain Acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid ß-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography-mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.

Influence of contextual factors and reliability of ultrasound skin measures in persons with systemic sclerosis and healthy controls.

OBJECTIVES: To examine the influence of contextual factors upon the evaluation of skin thickness and stiffness by ultrasound and to assess the reliability of these parameters. METHODS: Ultrasound dermal thickness (by B-mode, 18MHz) and skin stiffness (by shear-wave elastography, 9MHz) were assessed in persons with systemic sclerosis (SSc) and in healthy controls. The influence of contextual factors upon repeated measures was evaluated: (i) room temperature (16-17ºC vs. 22-24ºC); (ii) time of day (morning vs. afternoon), and (iii) menstrual cycle phase (menstrual vs. ovulatory). Differences were analysed using the related-samples Wilcoxon signed-rank test. Inter- and intra-rater reliability of ultrasound skin thickness and stiffness were evaluated in the 17 skin Rodnan sites of 20 persons with SSc and 20 healthy controls, under stable contextual conditions. RESULTS: A significant increase in ultrasound dermal thickness was observed at the leg in the afternoon vs morning, in both patients and controls. Similar observations were made for skin stiffness at the leg (in SSc) and at the foot (in SSc and controls) in the afternoon. No significant changes were observed in association with room temperature and menstrual cycle. Intra- and inter-rater-reliability was good to excellent for ultrasound dermal thickness and stiffness, both in SSc and healthy controls. CONCLUSIONS: The timing of the ultrasound procedure within each day seems to influence the ultrasound measures at the legs and feet. Our study corroborates that ultrasound dermal thickness and skin stiffness are reliable domains to quantify skin involvement in SSc.

Mitochondrial Fatty Acid ß-Oxidation Disorders: From Disease to Lipidomic Studies-A Critical Review.

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial ß-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.

Rare manifestations of refractory extrapulmonary sarcoidosis.

Sarcoidosis is a multisystemic disease, characterised by histopathologic presence of non-necrotising granulomas, primarily affecting the lungs (>90%). We present three cases predominantly characterised by uncommon extrapulmonary manifestations of sarcoidosis, where only one had pulmonary involvement. We describe three female patients, between the second and third decades of life, whose sarcoidosis was a diagnostic challenge due to their atypical extrapulmonary manifestations, from which we highlight: livedo reticularis and painful subcutaneous nodules with uncommon localisation, size and histology, being the first reported case of extensive subcutaneous nodules triggered by intramuscular penicillin; extensive symptomatic and refractory osseous involvement; and dispersed erythema nodosum affecting the entire body surface. All three patients required third-line treatment (antitumour necrosis factor agents) to achieve significant clinical and imagiological improvement. Through this case series, we highlight the importance of considering the rare and atypical presentations of sarcoidosis to avoid diagnostic delays and serious repercussions on the patient's prognosis.

Deep Vein Thrombosis in the Humeral Vein After Implantable Cardioverter-Defibrillator Implantation: A Family Physician's Perspective.

Upper extremity deep vein thrombosis (DVT) is an uncommon, under-reported, and difficult-to-diagnose condition. Although the strong provoking risk factors of venous thromboembolism are well described in the literature, the majority of cases are provoked by weak risk factors or are even considered unprovoked. In this case report, we describe a rare case of a brachial DVT in a woman in her 40s following implantable cardioverter-defibrillator (ICD) implantation. In her first evaluation, slight left arm edema and brachialgia were noted, and physiotherapy was prescribed. One month later, the patient was reevaluated because her complaints did not resolve, and an upper extremity venous ultrasound was done to exclude complications due to ICD implantation. The ultrasound identified an old DVT, which had been completely recanalized. The patient was then referred to a vascular surgery specialty consultation, which confirmed the diagnosis, and an anticoagulant was prescribed for three months. The symptoms resolved, and the patient did not report any more pain.

Solvent-Induced Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is a vasospastic disorder characterized by an exaggerated vasoconstrictive response to cold or emotional stress. It can be classified as primary (PRP) or secondary (SRP) depending on its association with an underlying condition. We present a case of a young female with severe RP, with trophic changes and abnormal capillaroscopy. After a detailed investigation, a diagnosis of secondary RP due to solvent exposure was made. The patient was treated with calcium channel blocker in low doses, due to hypotension, without improvement of symptoms. Vitamin C and pentoxifylline were added with an unsatisfactory response. Given the progressive worsening of RP and the appearance of trophic lesions, the patient's treatment was reviewed, and continuous intravenous iloprost infusion through an elastomeric pump was started. This resulted in significant symptom improvement and normalization on the capillaroscopic examination.

Portuguese Consensus on Acute Porphyrias: Diagnosis, Treatment, Monitoring and Patient Referral.

Acute porphyrias are a group of rare genetic metabolic disorders, caused by a defect in one of the enzymes involved in the heme biosynthesis, which results in an abnormally high accumulation of toxic intermediates. Acute porphyrias are characterized by potentially life-threatening attacks and, for some patients, by chronic manifestations that negatively impact daily functioning and quality of life. Clinical manifestations include a nonspecific set of gastrointestinal, neuropsychiatric, and/or cutaneous symptoms. Effective diagnostic methods are widely available, but due to their clinical heterogeneity and non-specificity, many years often elapse from symptom onset to diagnosis of acute porphyrias, delaying the treatment and increasing morbidity. Therefore, increased awareness of acute porphyrias among healthcare professionals is paramount to reducing disease burden. Treatment of acute porphyrias is centered on eliminating the potential precipitants, symptomatic treatment, and suppressing the hepatic heme pathway, through the administration of hemin or givosiran. Moreover, properly monitoring patients with acute porphyrias and their relatives is fundamental to preventing acute attacks, hospitalization, and long-term complications. Considering this, a multidisciplinary panel elaborated a consensus paper, aiming to provide guidance for an efficient and timely diagnosis of acute porphyrias, and evidence-based recommendations for treating and monitoring patients and their families in Portugal. To this end, all authors exhaustively reviewed and discussed the current scientific evidence on acute porphyrias available in the literature, between November 2022 and May 2023.

Effects of the COVID-19 pandemic on nurses' psychological well being in an emergency room.

OBJECTIVES: to assess the level of anxiety of nurses in an emergency room in view of the new Coronavirus and describe the relationship between the degrees of anxiety and their sociodemographic variables. METHODS: quantitative descriptive-correlational study with a sample of 60 nurses. A questionnaire was used as a data collection instrument based on the Hamilton Anxiety Assessment Scale. RESULTS: the nurses' average anxiety is mild. A statistically significant relationship was found between anxiety and the variables "sex" and "children", with women having higher levels of anxiety than men, and nurses who do not have children showing mild, moderate, or severe anxiety. CONCLUSIONS: COVID-19 triggers anxiety in nurses, sometimes at pathological levels. Being female and not having children increase the anxiety experienced. Sex can be considered the determining factor for the level of anxiety experienced.

Impact of age in critically Ill infected patients: a post-hoc analysis of the INFAUCI study.

PURPOSE: Older patients are the fastest expanding subgroup of intensive care units (ICU) and are particularly susceptible to bacterial infections and sepsis. The aim of this study was to address the epidemiology and the main determinants of outcome of infection in old and very old patients admitted to ICU. METHODS: We performed a post hoc analysis of all infected patients admitted to ICU enrolled in a 1-year prospective, observational, multipurpose study. Patients aged < 65, 65-74 and ≥ 75 years were compared. RESULTS: Of the 1652 patients included, 50% were older than 65 years. There were no significant differences between young, old and very old patients in either ICU, hospital length of stay, or nosocomial infection. All-cause mortality was significantly higher in participants aged ≥ 75. Increased Gram-negative microorganisms' isolates occurred in > 65 years (25% versus 31%; p = 0.034). Multidrug-resistant (MDR) microorganisms were directly associated to inappropriate empiric antibiotic therapy (OR 4.73; 95% CI 2.99-7.47) and inversely associated with community-acquired infection (OR 0.39; 95% CI 0.19-0.83). Age (65-74 years: OR 1.10; 95% CI 0.64-1.90 and ≥ 75 years: OR 1.52; 95% CI 0.89-2.59) and sepsis severity (sepsis: OR 0.67; 95% CI 0.18-2.46; severe sepsis: OR 1.17; 95% CI 0.40-3.44; septic shock: OR 0.77; 95% CI 0.27-2.24) were not associated to MDR bacteria. CONCLUSION: Patients > 65 years accounted for 50% of infected patients admitted to an ICU. ICU and hospital length of stay, and nosocomial infection did not increase with age. Age did predispose to increased risk for infection by Gram-negatives. These findings may optimize strategies for infection management in older patients.

Effects of age and optical blur on real depth stereoacuity.

Stereoscopic depth perception utilizes the disparity cues between the images that fall on the retinae of the two eyes. The purpose of this study was to determine what role aging and optical blur play in stereoscopic disparity sensitivity for real depth stimuli. Forty-six volunteers were tested ranging in age from 15 to 60 years. Crossed and uncrossed disparity thresholds were measured using white light under conditions of best optical correction. The uncrossed disparity thresholds were also measured with optical blur (from +1.0D to +5.0D added to the best correction). Stereothresholds were measured using the Frisby Stereo Test, which utilizes a four-alternative forced-choice staircase procedure. The threshold disparities measured for young adults were frequently lower than 10 arcsec, a value considerably lower than the clinical estimates commonly obtained using Random Dot Stereograms (20 arcsec) or Titmus Fly Test (40 arcsec) tests. Contrary to previous reports, disparity thresholds increased between the ages of 31 and 45 years. This finding should be taken into account in clinical evaluation of visual function of older patients. Optical blur degrades visual acuity and stereoacuity similarly under white-light conditions, indicating that both functions are affected proportionally by optical defocus.

Continuous renal replacement therapy in the treatment of severe hyperkalemia: An in vitro study.

INTRODUCTION: Continuous renal replacement therapy is not presently recommended in the treatment of life-threatening hyperkalemia. There are no specific recommendations in hemodialysis to treat hyperkalemia. We hypothesized an in vitro model may provide valuable information on the usefulness of continuous renal replacement therapy to treat severe hyperkalemia. METHODS: A potassium-free solute was used instead of diluted blood for continuous renal replacement therapy with a simulated blood flowrate set at 200 mL/min. The mode of elimination included continuous filtration, continuous dialysis, and continuous diafiltration using a flowrate of 4000 mL/min for continuous filtration and continuous dialysis modes, and a ratio of 2500/1500 in the continuous diafiltration mode. RESULTS: The mean initial potassium in the central compartment was 10.1 ± 0.4 mmol/L. The clearances in the continuous diafiltration, continuous filtration, and continuous dialysis were 3.4 ± 0.5, 3.6 ± 0.1, and 3.7 ± 0.1 L/h, respectively, not significantly different. Continuous dialysis resulted in the lowest workload for staff. Increasing the continuous dialysis flowrates from 2000 to 8000 mL/h increased clearance from 2.3 ± 0.3 to 6.2 ± 0.8 L/h. The delays in decreasing the potassium concentration to 5.5 mmol/L dropped from 120 to 45 min, respectively. Potassium eliminated in the first hour increased from 18 to 38 mmol that compared favorably with hemodialysis. Decrease in simulated blood flowrate from 200 to 50 mL/min moderately but significantly decreased the clearance from 3.7 to 3.0 L/h. CONCLUSION: Hyperkalemia is efficiently treated by continuous renal replacement therapy using the dialysis mode. Caution is needed to prevent the onset of severe hypokalemia within 40 min after initiation of the session.

Lymphedema secondary to limited cutaneous systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by vascular abnormalities, immune system activation and fibrosis. Lymphatic involvement in SSc was described more recently and starts in early stages. This report describes a 46-year-old patient who developed over the last 2 years asymmetric lymphedema in lower extremities. Compromise in lymphatic drainage was confirmed by lymphoscintigraphy. She also presented Raynaud's phenomenon, a scleroderma pattern in nailfold capillaroscopy, cutaneous thickening and anticentromere antibodies, which together resulted in a new diagnosis of limited cutaneous SSc. Treatment with methotrexate, prednisolone and lymphatic drainage resulted in lymphedema improvement. To our knowledge, this is the first case of grade 2 lymphedema in the setting of anticentromere-positive limited cutaneous SSc. We highlight the importance of considering rheumatic diseases in the differential diagnosis of lymphedema.

Rare case of otomastoiditis due to Coxiella burnetii chronic infection.

Q fever is a zoonotic disease caused by Coxiella burnetii that usually presents with non-specific or benign constitutional symptoms. Diagnosis is often challenging and, after acute Q fever, 1%-5% of patients can develop chronic disease. We present an 80-year-old male patient who was admitted due to a 3 months history of fever, productive cough, myalgia, weight loss, headache and hearing loss. Chronic Q fever was confirmed by positive antiphase I immunoglobulin G. Frequent locations of chronic infection was discarded, and ear CT revealed a right mastoid infection. He was treated with doxycycline and hydroxychloroquine for 18 months with significant improvement. This is a rare case of chronic Q fever presenting with otomastoiditis that has never been described.

Effects of the COVID-19 pandemic on nurses' psychological well being in an emergency room / Efeitos da pandemia de COVID-19 no bem-estar psicológico dos enfermeiros de um serviço de urgência / Efectos de la pandemia de COVID-19 en el bienestar psicológico de los enfermeros de un servicio de urgencia

ABSTRACT Objectives: to assess the level of anxiety of nurses in an emergency room in view of the new Coronavirus and describe the relationship between the degrees of anxiety and their sociodemographic variables. Methods: quantitative descriptive-correlational study with a sample of 60 nurses. A questionnaire was used as a data collection instrument based on the Hamilton Anxiety Assessment Scale. Results: the nurses' average anxiety is mild. A statistically significant relationship was found between anxiety and the variables "sex" and "children", with women having higher levels of anxiety than men, and nurses who do not have children showing mild, moderate, or severe anxiety. Conclusions: COVID-19 triggers anxiety in nurses, sometimes at pathological levels. Being female and not having children increase the anxiety experienced. Sex can be considered the determining factor for the level of anxiety experienced.

RESUMO Objetivos: avaliar o nível de ansiedade dos enfermeiros de um serviço de urgência em face do novo coronavírus e descrever a relação entre os níveis de ansiedade e as variáveis sociodemográficas. Métodos: estudo quantitativo descritivo-correlacional com uma amostra de 60 enfermeiros. Recorreu-se à aplicação de um questionário como instrumento de coleta de dados baseando-se na Escala de Avaliação de Ansiedade de Hamilton. Resultados: o escore médio de ansiedade dos enfermeiros é leve. Verificou-se que existe uma relação estatisticamente significante entre a ansiedade e a variável "sexo" e "filhos", com as mulheres apresentando níveis de ansiedade superiores aos homens e os enfermeiros sem filhos apresentando níveis de ansiedade leve, moderada ou severa. Conclusões: a COVID-19 desencadeia ansiedade nos enfermeiros, por vezes a níveis patológicos; e ser do sexo feminino e não ter filhos a aumenta. É possível afirmar que o sexo foi o fator determinante para o nível de ansiedade experimentado.

RESUMEN Objetivos: evaluar nivel de ansiedad de enfermeros de un servicio de urgencia frente al nuevo coronavirus y describir la relación entre niveles de ansiedad y variables sociodemográficas. Métodos: estudio cuantitativo descriptivo-correlacional con una muestra de 60 enfermeros. Recorrido a la aplicación de una encuesta como instrumento de recolecta de datos basándose en la Escala de Evaluación de Ansiedad de Hamilton. Resultados: el escore mediano de ansiedad de los enfermeros es leve. Verificado que hay una relación estadísticamente significante entre la ansiedad y la variable "sexo" e "hijos", con mujeres presentando niveles de ansiedad superiores a los hombres y los enfermeros sin hijos presentando niveles de ansiedad leve, moderada o severa. Conclusiones: la COVID-19 desencadena ansiedad en los enfermeros, por veces a niveles patológicos; y ser del sexo femenino y no tener hijos la aumenta. Es posible afirmar que el sexo fue el factor determinante para el nivel de ansiedad experimentado.

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy.

Camurati-Engelmann disease (CED) is a rare disorder included in the group of craniotubular hyperostosis diseases. Corticosteroids are used for pain management in CED, but in refractory or corticosteroid-non-tolerant patients, pain management is limited. We report the case of a woman with CED diagnosed in early infancy whose initial complaints included persistent bone pain associated with progressive functional disability. She was treated with steroids but over time became dependent on higher doses with only mild pain relief. In her third decade, she was diagnosed with ulcerative colitis (UC) and was treated with mesalazine, azathioprine and prednisolone. Due to recurrent exacerbations of UC, treatment was changed to infliximab, an antitumour necrosis factor-alpha (TNFα). Remission of UC was achieved and CED-associated pain also improved with infliximab. This is the first report showing a possible role of anti-TNFα in pain management in CED with unsatisfactory response to steroids.

Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats.

AIMS: Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats. MAIN METHODS: Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant. KEY FINDINGS: The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed. SIGNIFICANCE: The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

Neuroinflammatory effects of tDCS in ovariectomized rats with chronic inflammation

Introduction: Postmenopausal women are more susceptible to chronic conditions, such as osteoporosis, arthritis, and other inflammatory diseases. We investigated the effects of transcranial direct current stimulation (tDCS) on biomarker levels in ovariectomized rats subjected to an inflammatory model. Methods: Twenty adult female Wistar rats underwent ovariectomy and complete Freund's adjuvant (CFA)-induced inflammation. We divided them into 2 groups: OAS (sham tDCS) and OAT (active tDCS). Fifteen days later, the rats underwent bimodal tDCS treatment (20 min, 0.5 mA, 8 days). After 24 h of the last tDCS session, we killed the rats and collected tissue samples (hypothalamus, cerebral cortex, and brainstem) for biomarker analysis by ELISA. We removed the paws for histological analysis. Results: Active tDCS increased hypothalamic and cortical TNF-α and NGF levels, hypothalamic and brainstem IL-1ß levels, and hypothalamic IL-10 levels. Histology of paws showed an inflammatory profile. We observed a small tDCS effect, not statistically significant. Discussion: Bimodal tDCS had an effect on the central inflammatory axis, with a small effect on the peripheral site as evaluated by histology in the current study. (AU)