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Brucellosis is an infection that affects mammals’ cells caused by a species from the genus Brucella, a gram-negative, immobile, facultative, intracellular, and microaerophilic coccobacillus. In humans, the pathogen species are Brucella melitensis, B. abortus, B. suis and B. canis. We are presenting the case of a 62-year-old man with confirmed brucellosis and his consequent cardiovascular, cutaneous, gastrointestinal, hepatic, osteomuscular, renal and hematological complications. It is necessary to be highly suspicious of this infection, since its non-specific nature can be challenging for the physician.

Introduction: There are numerous studies appraising the variables that may influence the clinical outcomes after lumbar thermal radiofrequency ablation (RFA). Expanding the lesion size may increase the likelihood of capturing the target nerves in the lesion, thereby increasing the technical success rate of RFA. However, our literature search has failed to identify a consensus on the optimal target temperature. A retrospective study demonstrated that there seems to be significant functional improvement associated with the temperature of 90°C compared with 80°C. The authors prospectively studied the subject in a double-blinded randomized fashion., Methods: Patients undergoing RFA for lumbar facetogenic pain were randomized in two cohorts (80°C and 90°C). Physicians and patients were blinded to the temperature used. The primary outcome was self-reported pain scores up to 12 months. Secondary outcomes included: self-reported functional improvement, duration of relief as measured by the time before repeat ablation of the same medial branches nerves, opioids' consumption, and patient satisfaction., Results: Both groups reported pain improvement in all follow-up time points. Overall, both groups achieved statistically significant pain reduction (p<0.05). The median time to repeat RFA in the 80°C group was 112 (49-252) days, while it was 217 (198-348) days in the 90°C group (p<0.04). The univariate analysis emphasized that the RFA temperature is a statistically significant factor for pain improvement of more than 50%, OR 2.7 (1.1 to 6.6) p value=0.031., Conclusion: RFA has been demonstrated as an effective therapeutic modality for lumbar facetogenic back pain. Yet, the several factors involved in determining a favorable outcome of this procedure require further research and optimization. This prospective double-blinded randomized trial demonstrated that RFA at both temperatures (80°C, 90°C) provided significance at all the time periods examined. However, RFA at 90°C was superior to 80°C in regard to the duration of relief., Competing Interests: Competing interests: NM: Research Support: Avanos “Halyard”; Mesoblast; Neuros Medical. Independent Medical Monitor for: Accurate Trial, Abbott; HF-10 for PDN, Nevro Inc; EVOKE Trial, Saluda; MOTION Trial, Vertos; RESTORE Trial, Mainstay Medical; ViaDisc-NP Trial, Vivex; Therapeutics. SC: Research Support: ECAP Trial, Saluda; MOTION Trial, Vertos; RESTORE Trial, Mainstay Medical; ViaDisc-NP Trial, Vivex Therapeutics. The rest of the authors have no competing conflict of interest., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Obesity is associated with low-grade inflammation and oxidative stress, leading to insulin resistance and type II diabetes. Caryocar brasiliense pulp oil (pequi oil - PO) is rich in oleic acid and carotenoids and positively implicated in regulating inflammation and oxidative stress. This study investigated PO's antioxidant and anti-inflammatory effects in a diet-induced obesity model. Male Wistar rats were allocated into three experimental groups: Control (CD), Western Diet (WD), and Western Diet, with 27% of lard switched by PO (WDP). Metabolic, inflammatory, and oxidative stress biomarkers were evaluated after 12 weeks of diet protocols in liver and adipose tissue. WDP rats gained less body mass and epididymal fat, had less hepatic fat infiltration, and were more glucose-tolerant and insulin-sensitive than WD (p < 0.05). In the liver, the WDP group had the highest non-enzymatic antioxidant capacity, SOD and GPx activities, CAT, SOD II, and HSP72 expression compared to WD (p < 0.05). Adipose tissue IL-6 and TNF were reduced, and IL-10 was increased in WDP compared to WD (p < 0.05). Our data suggest that the partial replacement of lard by PO in a Western diet prevented visceral fat accumulation and contributed to reducing inflammation in adipose tissue and liver oxidative stress, improving obesity-related insulin resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

Introduction: The worldwide incidence of melanoma has been increasing rapidly in recent decades with Switzerland having one of the highest rates in Europe. Ultraviolet (UV) radiation is one of the main risk factors for skin cancer. Our objective was to investigate UV protective behavior and melanoma awareness in a high-risk cohort for melanoma., Methods: In this prospective monocentric study, we assessed general melanoma awareness and UV protection habits in at-risk patients (≥100 nevi, ≥5 dysplastic nevi, known CDKN2A mutation, and/or positive family history) and melanoma patients using questionnaires., Results: Between 01/2021 and 03/ 2022, a total of 269 patients (53.5% at-risk patients, 46.5% melanoma patients) were included. We observed a significant trend toward using a higher sun protection factor (SPF) in melanoma patients compared with at-risk patients (SPF 50+: 48% [n=60] vs. 26% [n=37]; p=0.0016). Those with a college or university degree used a high SPF significantly more often than patients with lower education levels (p=0.0007). However, higher educational levels correlated with increased annual sun exposure (p=0.041). Neither a positive family history for melanoma, nor gender or Fitzpatrick skin type influenced sun protection behavior. An age of ≥ 50 years presented as a significant risk factor for melanoma development with an odd's ratio of 2.32. Study participation resulted in improved sun protection behavior with 51% reporting more frequent sunscreen use after study inclusion., Discussion: UV protection remains a critical factor in melanoma prevention. We suggest that melanoma awareness should continue to be raised through public skin cancer prevention campaigns with a particular focus on individuals with low levels of education., Competing Interests: AM has received support for conference attendance from ALK, Bencard and Galderma. LK has received speaking fees in a presentation sponsored by Boehringer Ingelheim. ML has project-specific research funding from Roche, Novartis, Molecular Partners, and Oncobit AG and has received speaking fees from Danaher. J-TM is and has served as advisor and/or received speaking fees and/ or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB. AN declares being a consultant and advisor and/or receiving speaking fees and/or grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, Biomed, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Regeneron, Sandoz, Sanofi, and UCB. LM has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by Almirall, Amgen, BMS, Celgene, Eli Lilly, MSD, Novartis, Pierre Fabre, Roche and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mueller, Goessinger, Cerminara, Kostner, Amaral, Huber, Passweg, Moreno, Bodenmann, Kunz, Levesque, Maul, Cheng, Navarini and Maul.)

Introduction: Intraoperative hypotension (IH) is an independent predictor of mortality. Some experts have suggested that ultrasound measurement of the inferior vena cava (IVC) in spontaneous ventilation can predict IH., Objective: To evaluate the capacity of ultrasound measures of IVC in spontaneous ventilation to predict episodes of IH after anaesthesia induction., Patients and Methods: We studied 55 high-risk cardiac patients undergoing vascular surgery. The maximum (dIVCmax) and minimum (dIVCmin) diameter of the IVC were measured and the collapsibility index CI = (dIVCmax-dIVCmin)/dIVCmax was calculated prior to anaesthesia induction. Three definitions of IH were used: systolic blood pressure (SBP) less than 100 mmHg, mean arterial pressure (MAP) less than 60 mmHg, and a decrease in MAP greater than or equal to 30% compared to baseline., Results: There were no significant differences in dIVCmax or in CI between patients presenting IH after anaesthesia induction and those who did not. ROC curves for dIVCmax showed an area under the curve of 0.55 (0.39-0.70), 0.69 (0.48-0.90), and 0.57 (0.42-0.73) and ROC curves for the CI were 0.62 (0.47-0.78), 0.60 (0.41-0.78) and 0.62 (0.47-0.78) for the 3 definitions of IH (<100 mmHg, MAP < 60 mmHg, and MAP ≥30% baseline), respectively., Conclusions: Ultrasound measurements of IVC in spontaneous ventilation are not good predictors of IH after anaesthesia induction in these patients. The optimal cut-off points show low specificity and moderate sensitivity for predicting IH., (Copyright © 2021 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: Intestinal nutrient absorption plays a vital role in developing obesity, and nutrient transporters expressed in the enterocytes facilitate this process. Moreover, previous studies have shown that specific foods and diets can affect their cell levels. Herein, we investigated the effects of pequi oil (PO), which is high in several bioactive compounds, on intestinal nutrient transporter levels as well as on intestinal morphology and metabolic biomarkers., Main Methods: Groups of male C57BL/6 mice were fed either a standard (C) or a high-fat diet (HFD) and pequi oil (CP and HFDP with PO by gavage at 150 mg/day) for eight weeks. Food intake and body weight were monitored, serum metabolic biomarkers, intestinal transporter levels and histological analyses were performed., Key Findings: PO increased caloric intake without increasing body or fat mass regardless of diet. The HFD group treated with PO reduced fasting blood glucose and villus width. PO did not affect GLUT2, L-FABP, FATP4, NPC1L1, NHE3 or PEPT1 content in CP or HFDP groups. GLUT5 and FAT/CD36 levels were reduced in both CP and HFDP., Significance: Our data suggest that PO attenuated monosaccharide and fatty acid absorption, contributing to lower fasting glycemia and higher food intake without affecting body weight or visceral fat of high-fat feed mice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The popular recreational drug MDMA (3,4-methylenedioxy-methamphetamine) has a documented potential as a psychopharmacological clinical and research tool. This is due to its unique ability to promote reprocessing of traumatic memories, empathetic and pro-social states. Although it is established that MDMA exerts its behavioural effects via the serotonin transporter (SERT), the ligand-protein molecular interplay remains elusive. In order to shed light on the binding of MDMA and its primary congeneric entactogens (MDA, MBDB and MDAI), we first combined induced fit with Monte Carlo simulations. The computed interaction energies of the models correlated well with experimental activities ( adj R 2 = 0.78). Then we carried out 'ensemble binding space docking' on trajectories generated by interpolation of experimentally derived structures of the hSERT from the outward-open, and the occluded, to the inward-open states. This approach revealed low-energy alternative binding modes, suggesting high occupancy of the central site, yet considerable MDMA mobility within it, favouring the paroxetine-like orientation. Finally, we designed a pharmacophore that may be used to recognise hSERT-mediated serotonin releasers and uptake inhibitors of diverse chemical structure, identifying their active conformations and interacting residues. We conclude that the conserved amine-Asp98 ionic and edge-to-face π-π interactions are crucial to the mode of action of MDMA on the hSERT, underscoring the contributions of Tyr95 and gating residues Phe341, Tyr176 and Phe335. Amenable to experimental testing, our modelling may aid the rational design of novel entactogenic compounds and contribute to the understanding of an action mechanism, common and typical of psychotropic agents., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Introduction and Objectives: Severe tricuspid regurgitation (TR) is a prevalent valve disease with a high mortality rate. Current guidelines do not define specific thresholds at which patients should be considered for surgery or percutaneous procedures. Thus, patients are usually referred for intervention at a late stage of the disease. This study aimed to assess predictors of cardiovascular outcomes in a prospective cohort of patients with severe TR referred for surgery., Methods: This was an observational, prospective, nonrandomized study. All patients underwent surgery for severe TR based on current clinical guidelines. Complete anamnesis, blood test, echocardiogram, cardiovascular magnetic resonance and right and left catheterization were performed. Patients were followed up in the outpatient department and a combined endpoint (hospitalization for heart failure and cardiovascular mortality) was registered., Results: Forty-three consecutive patients were included (age: 66.9 ± 9.6 years, 67.4% female). Tricuspid annuloplasty was performed in all patients. After a median follow-up of 38 months, 12 patients (27.9%) showed the combined endpoint and 7 (16.3%) died. Above all clinical, blood and imaging data, the indexed right ventricular end-diastolic volume constituted the best predictor of the combined endpoint (HR, 1.1; P = .02) and cardiovascular mortality (HR, 1.1; P = .05). Furthermore, indexed right ventricular end-diastolic volume was associated with TR recurrence after surgery, with no impact on clinical outcomes., Conclusions: In patients with severe TR referred for surgery, right ventricular remodeling assessed by cardiovascular magnetic resonance constituted the best independent predictor of cardiovascular outcomes at follow-up., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: We describe the efficacy of lateral transorbital canthopexy using a silicone tube in managing severe paralytic ectropion., Methods: Patients with paralytic ectropion involving at least two-third of lower eyelid length and scleral exposure of 3 mm or more were considered. A silicone prosthetic was inserted during canthopexy., Results: Lateral transorbital canthopexy using a silicone tube was performed on 10 eyelids in nine patients. All patients had corneal surface abnormalities. Scleral exposure resolved completely in three cases. At 8-month follow-up, residual scleral exposure of 1 mm and 2 mm persisted in n  = 6 and n  = 1 cases, respectively., Conclusions: Lateral transorbital canthopexy using a silicone tube is an effective therapeutic option for paralytic ectropion, facilitating both functional and cosmetic results that proved durable over time.

We present a case of acute myocarditis with left ventricular dysfunction and intracavitary thrombosis in a 55-year-old man with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019) who was admitted with bilateral atypical pneumonia. The patient was treated with anticoagulation and optimal heart failure therapy and had an improvement of left ventricular function and thrombus resolution. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Caloric restriction (CR) reduces body weight and systemic inflammation, but the effects on adipose tissue under dietary lipid overload are controversial. We evaluated the effects of CR-induced weight loss with a high-fat diet on adipose tissue inflammation of obese mice. Male mice were assigned into low-fat diet (LF) and high-fat diet (HF) groups. After 8 weeks, the mice in the HF group were reassigned for another 7 weeks into the following 3 conditions: ( i ) kept in the HF condition; ( ii ) changed to low-fat diet ad libitum (LFAL); and ( iii ) changed to high-fat calorie-restricted (RHF) diet to reach LFAL body weight. Serum markers, adipocytokines, morphology, and inflammatory infiltrates in retroperitoneal adipose tissue (RAT) were accessed. The body weights of the LFAL and RHF groups were reduced, equaling the body weights of the LF group. The LFAL mice had restored almost all inflammatory markers as the LF mice, except tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and adiponectin. Compared with the HF group, the RHF group had lowered visceral adiposity, retroperitoneal adipocyte sizes, and RAT inflammatory cell infiltration, as well as TNF-α, interleukin-6, and hepatic and serum C-reactive protein, which were higher than that of the LFAL group; adiponectin and MCP-1 did not change. CR with high-fat diet reduced body weight and attenuated visceral adiposity but did not fully recover visceral tissue inflammation. Novelty Caloric restriction in a high-fat diet ameliorated visceral adiposity. Caloric restriction in a high-fat diet did not recover visceral adipose tissue inflammation.

Background: Caryocar brasiliense (pequi) oil is high in monounsaturated fat acids (MUFA), especially oleic, and in carotenoids, which have been associated with protection against cardiovascular disease. However, this food is poorly studied in this context, especially in the cardiac function. Therefore, we investigated the effects of a long-term intake of pequi oil in systemic cardiovascular risk factors and in the ex vivo cardiac function of rats., Methods: Previously, we determined fatty acids and carotenoids in pequi oil. Next, male rats were divided in C - control group feed a standard diet, and PO - pequi oil group fed the same diet added pequi oil (+2.25 g.100 g -1 ). After 15 weeks, plasma lipids, glucose, insulin, blood pressure, heart rate, hepatic lipids were accessed and visceral fat pads were harvested. Hearts were used for the ex vivo cardiac function, histologic assays, SERCA2a and phospholanban (PLB) determinations., Results: In agreement with scientific data, pequi oil had expressive amounts MUFA, especially oleic acid, and carotenoids. Hepatic triglycerides (TG) were reduced by pequi oil intake (p < 0.05). All others cardiovascular risk factors were not changed. The intrinsic heart rate was lower in PO group (p < 0.05). SERCA2a content was higher in this group (p < 0.05), without affecting PLB. Also, SERCA2a/PLB ratio increased in PO group (p < 0.05)., Conclusion: Pequi oil intake improved cardiac function ex vivo, despite no significant changes in systemic cardiovascular risk factors. The higher lipid offer in pequi oil diet, its composition in oleic acid and carotenoids could be related to those effects.

Lead intoxication is a worldwide health problem which frequently affects the kidney. In this work, we studied the effects of chronic lead intoxication (500 ppm of Pb in drinking water during seven months) on the structure, function and biochemical properties of rat proximal tubule cells. Lead-exposed animals showed increased lead concentration in kidney, reduction of calcium and amino acids uptake, oxidative damage and glucosuria, proteinuria, hematuria and reduced urinary pH. These biochemical and physiological alterations were related to striking morphological modifications in the structure of tubule epithelial cells and in the morphology of their mitochondria, nuclei, lysosomes, basal and apical membranes. Interestingly, in addition to the nuclei, inclusion bodies were found in the cytoplasm and in mitochondria. The epithelial cell structure modifications included an early loss of the apical microvillae, followed by a decrement of the luminal space and the respective apposition and proximity of apical membranes, resulting in the formation of atypical intercellular contacts and adhesion structures. Similar but less marked alterations were observed in subacute lead intoxication as well. Our work contributes in the understanding of the physiopathology of lead intoxication on the structure of renal tubular epithelial cell-cell contacts in vivo.