Estrogens as a Possible Therapeutic Strategy for the Management of Neuroinflammation and Neuroprotection in COVID-19.

The Coronavirus disease 2019 (COVID-19) affects several tissues, including the central and peripheral nervous system. It has also been related to signs and symptoms that suggest neuroinflammation with possible effects in the short, medium, and long term. Estrogens could have a positive impact on the management of the disease, not only due to its already known immunomodulator effect, but also activating other pathways that may be important in the pathophysiology of COVID-19, such as the regulation of the virus receptor and its metabolites. In addition, they can have a positive effect on neuroinflammation secondary to pathologies other than COVID-19. The aim of this study is to analyze the molecular mechanisms that link estrogens with their possible therapeutic effect for neuroinflammation related to COVID-19. Advanced searches were performed in scientific databases as Pub- Med, ProQuest, EBSCO, the Science Citation index, and clinical trials. Estrogens have been shown to participate in the immune modulation of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to this mechanism, we propose that estrogens can regulate the expression and activity of the Angiotensin-converting enzyme 2 (ACE2), reestablishing its cytoprotective function, which may be limited by its interaction with SARS-CoV-2. In this proposal, estrogens and estrogenic compounds could increase the synthesis of Angiotensin-(1-7) (Ang-(1-7)) that acts through the Mas receptor (MasR) in cells that are being attacked by the virus. Estrogens can be a promising, accessible, and low-cost treatment for neuroprotection and neuroinflammation in patients with COVID-19, due to its direct immunomodulatory capacity in decreasing cytokine storm and increasing cytoprotective capacity of the axis ACE2/Ang (1-7)/MasR.

Correction: Long, S. SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives. Viruses 2020, 13, 1923.

The author is no longer affiliated with the original institution "AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA", so the author wishes to change the affiliation to "Independent Researcher, Clarksburg, MD 20871, USA" [...].

Comparing intraoperative parathyroid identification based on surgeon experience versus near infrared autofluorescence detection - A surgeon-blinded multi-centric study.

BACKGROUND: Near infrared autofluorescence (NIRAF) detection has previously demonstrated significant potential for real-time parathyroid gland identification. However, the performance of a NIRAF detection device - PTeye® - remains to be evaluated relative to a surgeon's own ability to identify parathyroid glands. METHODS: Patients eligible for thyroidectomy and/or parathyroidectomy were enrolled under 6 endocrine surgeons at 3 high-volume institutions. Participating surgeons were categorized based on years of experience. All surgeons were blinded to output of PTeye® when identifying tissues. The surgeon's performance for parathyroid discrimination was then compared with PTeye®. Histology served as gold standard for excised specimens, while expert surgeon's opinion was used to validate in-situ tissues. RESULTS: PTeye® achieved 92.7% accuracy across 167 patients recruited. Junior surgeons (<5 years of experience) were found to have lower confidence in parathyroid identification and higher tissue misclassification rate per specimen when compared to PTeye® and senior surgeons (>10 years of experience). CONCLUSIONS: NIRAF detection with PTeye® can be a valuable intraoperative adjunct technology to aid in parathyroid identification for surgeons.

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BACKGROUND: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field. AIM: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors. METHODS: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors. RESULTS: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients. CONCLUSION: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

The Mechanisms of Action of Botulinum Toxin Type A in Nociceptive and Neuropathic Pathways in Cancer Pain.

BACKGROUND: Botulinum toxin type A (BoNT-A) is widely employed for cosmetic purposes and in the treatment of certain diseases such as strabismus, hemifacial spasm and focal dystonia among others. BoNT-A effect mainly acts at the muscular level by inhibiting the release of acetylcholine at presynaptic levels consequently blocking the action potential in the neuromuscular junction. Despite the great progress in approval and pharmaceutical usage, improvement in displacing BoNT-A to other pathologies has remained very limited. Patients under diagnosis of several types of cancer experience pain in a myriad of ways; it can be experienced as hyperalgesia or allodynia, and the severity of the pain depends, to some degree, on the place where the tumor is located. Pain relief in patients diagnosed with cancer is not always optimal, and as the disease progresses, transition to more aggressive drugs, like opioids is sometimes unavoidable. In recent years BoNT-A employment in cancer has been explored, as well as an antinociceptive drug; experiments in neuropathic, inflammatory and acute pain have been carried out in animal models and humans. Although its mechanism has not been fully known, evidence has shown that BoNT-A inhibits the secretion of pain mediators (substance P, Glutamate, and calcitonin gene related protein) from the nerve endings and dorsal root ganglion, impacting directly on the nociceptive transmission through the anterolateral and trigeminothalamic systems. AIM: The study aimed to collect available literature regarding molecular, physiological and neurobiological evidence of BoNT-A in cancer patients suffering from acute, neuropathic and inflammatory pain in order to identify possible mechanisms of action in which the BoNT-A could impact positively in pain treatment. CONCLUSION: BoNT-A could be an important neo-adjuvant and coadjuvant in the treatment of several types of cancer, to diminish pro-tumor activity and secondary pain.

Effect of postictal process in motor deficit and monoaminergic concentration in hippocampus, cerebellum, and cortex / Efecto del proceso postictal en el déficit motor y la concentración monoaminérgica en el hipocampo, el cerebelo y la corteza

Abstract Introduction Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process.

Resumen Introducción La administración sistémica de pentilentetrazol (PTZ) causa daño cerebral y desencadena una serie de cambios morfológicos y neuroquímicos que a su vez provocan déficits conductuales, cognitivos y motores. Los niveles de serotonina (5-HT), dopamina (DA) y noradrenalina (NA) son modulados por varias estructuras cerebrales y sus concentraciones se relacionan con la actividad motora; sin embargo, se desconoce la concentración de estos neurotransmisores durante el proceso postictal. Objetivo Evaluar la manera en que la concentración de 5-HT, NA y DA en el hipocampo, el cerebelo y la corteza influye en el déficit motor durante la etapa postictal. Método Se utilizaron 18 ratas macho Wistar (300 g), divididas en dos grupos: control (n = 9, solución salina) y experimental (n = 9, PTZ). Se registraron las sacudidas mioclónicas y se evaluó el comportamiento motor durante tres horas después de la inyección de PTZ (90 mg/kg). Se extrajeron la corteza, el cerebelo y el hipocampo de cada rata para determinar la concentración de 5-HT, DA y NA mediante cromatografía líquida de alta resolución. Resultados La administración de PTZ indujo un aumento significativo en los niveles totales de 5-HT y DA en el hipocampo y la corteza; en el cerebelo hubo un aumento significativo en la concentración de 5-HT y NA. Se encontró una diferencia significativa entre el grupo experimental y control con respecto a las sacudidas mioclónicas; asimismo, los animales del grupo experimental mostraron un marcado déficit motor. Discusión y conclusión La 5-HT modula la concentración de otras monoaminas involucradas directamente en aspectos motores tal como NA y DA en el hipocampo, el cerebelo y la corteza durante el proceso postictal.

Adrenocortical Cancer Treatment.

Adrenocortical cancer is a rare disease. Prognosis remains poor but is improving. In this article, initial presentation, biochemical and imaging evaluation, surgical approach to resection, and postoperative care are reviewed. Prognosis, patterns of recurrence, treatment of metastatic disease using medical therapy and other surgical and nonsurgical therapies are discussed.

Chyle Leak Following Autologous Breast Reconstruction: A Rare Complication of a Deep Inferior Epigastric Artery Perforator Flap.

BACKGROUND: While complications of deep inferior epigastric artery perforator flaps are known and well documented, a thorough literature review revealed no other reports of a patient developing a chyle leak following the use of the internal mammary vessels for recipient vessels in autologous breast reconstruction. CASE: A 55-year-old woman underwent free autologous breast reconstruction. She developed a chyle leak during the postoperative period. This was verified through a computed tomography scan and fluid analysis demonstrating a high triglyceride count and the presence of chylomicrons. The leak resolved with conservative measures including compression and a low-fat, high-protein diet. DISCUSSION: The presence of chyle leak following dissection of the internal mammary vessels is a unique complication of autologous breast reconstruction. There have been reports of lymph leaks following mastectomy, but these are mostly reported in the axilla. A history of radiation to the contralateral breast and aberrant anatomy may have contributed to the complication. Treatment of chyle leaks ranges from conservative management to the use of total parenteral nutrition and somatostatin analogs to surgical intervention. CONCLUSION: While altering practice patterns based on a single case is not usually suggested, this complication does intimate that dealing with lymphatic vessels and lymph nodes in the chest should be done deliberately to prevent lymphatic leaks.

Comparative mutational landscape analysis of patient-derived tumour xenografts.

BACKGROUND: Screening of patients for cancer-driving mutations is now used for cancer prognosis, remission scoring and treatment selection. Although recently emerged targeted next-generation sequencing-based approaches offer promising diagnostic capabilities, there are still limitations. There is a pressing clinical need for a well-validated, rapid, cost-effective mutation profiling system in patient specimens. Given their speed and cost-effectiveness, quantitative PCR mutation detection techniques are well suited for the clinical environment. The qBiomarker mutation PCR array has high sensitivity and shorter turnaround times compared with other methods. However, a direct comparison with existing viable alternatives are required to assess its true potential and limitations. METHODS: In this study, we evaluated a panel of 117 patient-derived tumour xenografts by the qBiomarker array and compared with other methods for mutation detection, including Ion AmpliSeq sequencing, whole-exome sequencing and droplet digital PCR. RESULTS: Our broad analysis demonstrates that the qBiomarker's performance is on par with that of other labour-intensive and expensive methods of cancer mutation detection of frequently altered cancer-associated genes, and provides a foundation for supporting its consideration as an option for molecular diagnostics. CONCLUSIONS: This large-scale direct comparison and validation of currently available mutation detection approaches is extremely relevant for the current scenario of precision medicine and will lead to informed choice of screening methodologies, especially in lower budget conditions or time frame limitations.