The polyunsaturated fatty acid docosahexaenoic affects mitochondrial function in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) shows a rewired metabolism featuring increased fatty acid uptake and synthesis via de novo lipogenesis, both sharply related to mitochondrial physiology. The docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that exerts its antitumoral properties via different mechanisms, but its specific action on mitochondria in PCa is not clear. Therefore, we investigated whether the DHA modulates mitochondrial function in PCa cell lines. METHODS: Here, we evaluated mitochondrial function of non-malignant PNT1A and the castration-resistant (CRPC) prostate 22Rv1 and PC3 cell lines in response to DHA incubation. For this purpose, we used Seahorse extracellular flux assay to assess mitochondria function, [14C]-glucose to evaluate its oxidation as well as its contribution to fatty acid synthesis, 1H-NMR for metabolite profile determination, MitoSOX for superoxide anion production, JC-1 for mitochondrial membrane polarization, mass spectrometry for determination of phosphatidylglycerol levels and composition, staining with MitoTracker dye to assess mitochondrial morphology under super-resolution in addition to Transmission Electron Microscopy, In-Cell ELISA for COX-I and SDH-A protein expression and flow cytometry (Annexin V and 7-AAD) for cell death estimation. RESULTS: In all cell lines DHA decreased basal respiratory activity, ATP production, and the spare capacity in mitochondria. Also, the omega-3 induced mitochondrial hyperpolarization, ROS overproduction and changes in membrane phosphatidylglycerol composition. In PNT1A, DHA led to mitochondrial fragmentation and it increased glycolysis while in cancer cells it stimulated glucose oxidation, but decreased de novo lipogenesis specifically in 22Rv1, indicating a metabolic shift. In all cell lines, DHA modulated several metabolites related to energy metabolism and it was incorporated in phosphatidylglycerol, a precursor of cardiolipin, increasing the unsaturation index in the mitochondrial membrane. Accordingly, DHA triggered cell death mainly in PNT1A and 22Rv1. CONCLUSION: In conclusion, mitochondrial metabolism is significantly affected by the PUFA supplementation to the point that cells are not able to proliferate or survive under DHA-enriched condition. Moreover, combination of DHA supplementation with inhibition of metabolism-related pathways, such as de novo lipogenesis, may be synergistic in castration-resistant prostate cancer.

Red Nodule on the Scalp in a Healthy Young Man.

A man in his 40s was referred for an 8-mm red, firm, mobile nodule with irregular red lacunae and vessels and an absence of septa. What is your diagnosis?

Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Machine learning-based soil quality assessment for enhancing environmental monitoring in iron ore mining-impacted ecosystems.

In November 2015, a catastrophic rupture of the Fundão dam in Mariana (Brazil), resulted in extensive socio-economic and environmental repercussions that persist to this day. In response, several reforestation programs were initiated to remediate the impacted regions. However, accurately assessing soil health in these areas is a complex endeavor. This study employs machine learning techniques to predict soil quality indicators that effectively differentiate between the stages of recovery in these areas. For this, a comprehensive set of soil parameters, encompassing 3 biological, 16 chemical, and 3 physical parameters, were evaluated for samples exposed to mining tailings and those unaffected, totaling 81 and 6 samples, respectively, which were evaluated over 2 years. The most robust model was the decision tree with a restriction of fewer levels to simplify the tree structure. In this model, Cation Exchange Capacity (CEC), Microbial Biomass Carbon (MBC), Base Saturation (BS), and Effective Cation Exchange Capacity (eCEC) emerged as the most pivotal factors influencing model fitting. This model achieved an accuracy score of 92% during training and 93% during testing for determining stages of recovery. The model developed in this study has the potential to revolutionize the monitoring efforts conducted by regulatory agencies in these regions. By reducing the number of parameters that necessitate evaluation, this enhanced efficiency promises to expedite recovery monitoring, simultaneously enhancing cost-effectiveness while upholding the analytical rigor of assessments.

Extranodal Follicular Dendritic Cell Sarcoma Presenting on the Skin.

ABSTRACT: Follicular dendritic cell sarcoma is a rare intermediate-grade malignancy characterized by a proliferation of ovoid to spindle-shaped cells with morphologic and immunophenotypic features similar to normal follicular dendritic cells. It may develop in lymph nodes or extranodal sites. Its presentation in extranodal tissues is a diagnostic challenge. It requires a high index of suspicion because follicular dendritic cell markers are not included in the routine immunohistochemical panels used for differential diagnosis. In an extensive review of the English literature, we found 3 cases of follicular dendritic cell sarcoma developing on the skin. We report a case of a primary cutaneous follicular dendritic cell sarcoma in a 28-year-old man, which presented as a 6-mm skin-colored nodule on the right forearm. We describe the morphologic and immunohistochemical features and a review of the literature.

Herniated superficial lipomas in gluteal and thigh support areas: a special clinical ultrasound presentation.

BACKGROUND: Lipomas are the most frequent benign tumor. They have been described as soft, well-defined, slow-growing palpable masses, and classified as deep or superficial. PURPOSE: To present the clinical and ultrasound findings of herniated superficial subcutaneous lipoma (HSL), located in pressure/support areas, not previously described. MATERIAL AND METHODS: A seven-year retrospective review was performed. Patients with a preoperative high-resolution ultrasound (HRUS) diagnosis of HSL archived in the computational system and histological study information were selected. RESULTS: A total of 37 patients (mean age = 46 years) were recruited. The clinical diagnoses were "lipoma" or "suspected lipoma" in just 46% of the cases. This was three times more frequent in women. Tumors were located mainly in the gluteal (38%) and proximal thigh areas (35%). Clinically, all patients showed small, soft, rounded skin nodules. On HRUS, they appear as lipomatous tumors that protruded, compressed, and thinned the covering dermal layer. The subcutaneous portion was bigger than the herniated part, with an iceberg image. CONCLUSION: HSL in support areas have a special clinical ultrasound presentation, not previously described. It is important to recognize them for a proper diagnosis and treatment, especially because they clinically may present as small superficial lesions; however, they are associated with a larger subcutaneous portion (iceberg image). It is probable that an estrogen influence on the adipose tissue can be suspected because of the female predominance.

Darier disease: the use of dermoscopy in monitoring acitretin treatment

Abstract Darier disease is an uncommon autosomal dominant inherited disease, caused by a mutation in the ATP2A2 gene. The clinical findings are hyperkeratotic papules on the trunk, scalp, face, and neck, maceration of intertriginous areas, palmar pits, whitish papules on the oral mucosa and nail abnormalities. The main histopathologic findings are acantholysis and dyskeratotic keratinocytes. Dermatoscopic features are comedo-like openings with a central polygonal yellowish/brownish structure, surrounded by a whitish halo. First-line treatment includes acitretin. Five reports have been published describing Darier disease dermatoscopic findings. Herein, we report for the first time a patient under acitretin treatment and dermatoscopic follow-up.

Darier disease: the use of dermoscopy in monitoring acitretin treatment.

Darier disease is an uncommon autosomal dominant inherited disease, caused by a mutation in the ATP2A2 gene. The clinical findings are hyperkeratotic papules on the trunk, scalp, face, and neck, maceration of intertriginous areas, palmar pits, whitish papules on the oral mucosa and nail abnormalities. The main histopathologic findings are acantholysis and dyskeratotic keratinocytes. Dermatoscopic features are comedo-like openings with a central polygonal yellowish/brownish structure, surrounded by a whitish halo. First-line treatment includes acitretin. Five reports have been published describing Darier disease dermatoscopic findings. Herein, we report for the first time a patient under acitretin treatment and dermatoscopic follow-up.

Skin collision tumour and dermoscopic diagnosis of melanoma in situ and dilated pore of Winer.

Collision tumours are a random association of two or more neoplasms arising in the same anatomical site. Dilated pore of Winer (DPW) - an adnexal tumour of pilar origin - has been described in collisions with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and trichoblastoma. We present a literature review of melanoma-associated skin lesions and describe the first collision of a DPW with a melanoma in situ (MIS) and the sequential dermoscopic examination for diagnosis.

Understanding the Relationship between Intrinsic Cardiorespiratory Fitness and Serum and Skeletal Muscle Metabolomics Profile.

Intrinsic cardiorespiratory fitness (iCRF) indicates the CRF level in the sedentary state. However, even among sedentary individuals, a wide interindividual variability is observed in the iCRF levels, whose associated molecular characteristics are little understood. This study aimed to investigate whether serum and skeletal muscle metabolomics profiles are associated with iCRF, measured by maximal power output (MPO). Seventy sedentary young adults were submitted to venous blood sampling, a biopsy of the vastus lateralis muscle and iCRF assessment. Blood serum and muscle tissue samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Metabolites related to iCRF were those supported by three levels of evidence: (1) correlation with iCRF, (2) significant difference between individuals with low and high iCRF, and (3) metabolite contribution to significant pathways associated with iCRF. From 43 serum and 70 skeletal muscle analyzed metabolites, iCRF was positively associated with levels of betaine, threonine, proline, ornithine, and glutamine in serum and lactate, fumarate, NADP+, and formate in skeletal muscle. Serum betaine and ornithine and skeletal muscle lactate metabolites explained 31.2 and 16.8%, respectively, of the iCRF variability in addition to body mass. The results suggest that iCRF in young adults is positively associated with serum and skeletal muscle metabolic levels, indicative of the amino acid and carbohydrate metabolism.

Auricular Pseudocyst: Sonographic Appearance in 17 Patients.

ABSTRACT: Auricular pseudocyst (AP) is a rare benign condition that corresponds to an intracartilaginous collection resulting in a noninflammatory cystic swelling of the ear.The objective is to describe ultrasound and clinical presentation of histologically proven AP.An Institutional Review Board (IRB) approved a 6-year retrospective study. Patients with an auricular pseudocyst were selected. Fifty-nine percent of the cases were referred with clinical suspicion of AP. One hundred percent were men, and in 76% of the cases, AP was located in the scaphoid fossa. The mean age was 35 years (76% from 20 to 50 years).Unilateral lesion was present in 94% of the cases. A single lesion was found in 88% and multiple lesions in 12%. On high-resolution ultrasound increased thickness of the cartilage was observed in all patients with a cystic lesion inside the cartilage. Fifty-nine percent of the cases were totally anechoic. The other presented echoes or septa inside the cystic lesion.In conclusion high-resolution ultrasound allows to study the exact anatomic involvement of the cartilage and the surrounding tissues. The auricular pseudocyst presented a characteristic ultrasound finding permitting an adequate early diagnosis and monitoring treatment. Knowledge of this pathology and the sonographic finding is important for a correct diagnosis.

Association between Lysholm score and muscular torque deficit after anterior cruciate ligament reconstruction.

PURPOSE: The asymmetry of muscular strength after anterior cruciate ligament reconstruction (ACLR) is associated with increase in the development of new lesions. This asymmetry is precisely assessed by isokinetic dynamometry which is a high-cost technique, limited to major centers and hospitals. Thus, the aim of this study was to test the accuracy of one of the most frequently used functional questionnaires, the Lysholm score, to diagnose the knee torque deficit. METHODS: In total, 115 patients were evaluated after ACLR. Knee symptoms were evaluated using the Lysholm questionnaire and knee extensor and flexor peak torque during maximal isokinetic concentric contractions at 60° s-1 (5 repetitions) and 180° s-1 (15 repetitions). Patients with <20% peak torque deficit were considered symmetric (normal). RESULTS: An increase in the Lysholm score was associated with a deficit reduction in the peak torque of knee extensors at 60° s-1 (r = -0.294) and 180° s-1 (r = -0.297) (p < 0.05 for both). Cutoff Lysholm scores of >90 points for 60° s-1 allowed the correct diagnosis of symmetry in 71% and of >89 points for 180º·s-1 allowed the correct diagnosis of symmetry in 73%, for knee extensors. Patients with a Lysholm score of >89 points presented an isokinetic deficit 36% lower than patients with a Lysholm score of ≤89 points (p < 0.05). CONCLUSION: A Lysholm score of >89 points has predictive value for deficits in the peak torque of knee extension (<20%). However, replacement of the isokinetic evaluation by this instrument must be performed with caution because of its accuracy.

Guía de práctica para el manejo de melanoma cutáneo primario de la Sociedad Chilena de Dermatología / Practice guideline for the management of melanoma primary skin cancer of the Chilean Society of Dermatology

Introducción: Desde el año 2011 a la fecha se han realizado grandes avances en el diagnóstico y el tratamiento del melanoma cutáneo. Las diferentes sociedades dermatológicas internacionales han actualizado sus recomendaciones y guías de manejo, tomando en consideración los nuevos avances científicos y resultados de ensayos clínicos. Objetivo: El objetivo de la presente revisión es proponer recomendaciones basadas en la evidencia sobre del rol del dermatólogo en el manejo del melanoma cutáneo en el sistema de salud de Chile. Diseño: Revisión sistemática de la literatura en cinco bases de datos: Pubmed/Medline, Embase, Web of Science, Lilacs/SciELO y Cochrane Library; desde julio del 2016 a julio del 2021. Resultados: 1306 registros fueron identificados y 153 cumplieron los criterios de inclusión. Se exponen recomendaciones actualizadas con respecto al diagnóstico y manejo del melanoma cutáneo en Chile. El panel de expertos presenta un diagrama de flujo del proceso de atención de una lesión sospechosa de melanoma, la participación global del equipo médico encargado del cuidado paciente y el rol del dermatólogo. Conclusión: El rol del dermatólogo es central e indispensable en todas las etapas de atención del melanoma cutáneo.

Introduction: Since 2011 great advances have been made in the diagnosis and treatment of cutaneous melanoma. The different international dermatological societies have updated their recommendations and clinical guidelines taking into account new scientific advances and the results of clinical trials. Objective: The aim of this review is to propose evidence-based recommendations on the role of the dermatologist in the diagnosis and management of cutaneous melanoma in the Chilean healthcare system. Design. Systematic review of the literature in five databases: Pubmed/Medline, Embase, Web of Science, Lilacs/SciELO and Cochrane Library; from July 2016 to July 2021. Results: 1306 records were identified and 153 met the inclusion criteria. Updated recommendations regarding the diagnosis and management of cutaneous melanoma in Chile are presented. The expert panel presents a flowchart of the process of care of a suspected melanoma lesion, the overall involvement of the medical team in charge of patient care, and the role of the dermatologist. Conclusion: The role of the dermatologist is central and critical in all stages of cutaneous melanoma care