Personal versus therapist perioperative music intervention: a randomized controlled trial.

INTRODUCTION: Music interventions can alleviate patient anxiety and improve post-surgical satisfaction. However, it remains uncertain whether personal music preferences affect efficacy. The authors tested whether personal music intervention with patient-selected songs played ad libitum is more effective than standard therapist-designed treatment with classical music. METHODS: A prospective, parallel-group, single-blinded, randomized controlled trial with 229 participants (aged 18-60 years) previously scheduled for elective surgery. Data analyses followed a modified intention-to-treat principle. The patients were randomized into three groups: Standard care without music (Control), therapist-designed classic music treatment (TT), or personal music intervention with patient-selected songs played ad libitum by the patient (PI). All patients received standard post-anaesthesia care, and music intervention was started upon arrival at the post-anaesthesia care unit. Primary outcomes were anxiety and overall satisfaction at discharge. In contrast, secondary outcomes were systolic blood pressure during music intervention, the sleep quality of the night after surgery, and the occurrence of postoperative nausea and vomiting within the first 24 h after surgery. RESULTS: Compared with therapist-designed music treatment, personal intervention decreased systolic blood pressure (T 0 : 124.3±13.7, 95% CI:121-127.7; T 20min : 117.6±10.4, 95% CI:115-120.1; T 30min : 116.9±10.6, 95% CI:114.3-119.4), prevented postoperative nausea and vomiting (Control: 55.9%, TT: 64.6%, PI: 77.6%), including severe postoperative nausea (VAS score>4; Control: 44.1%; TT: 33.8%; PI: 20.9%) and severe emesis (Frequency≥3, Control: 13.2%; TT: 7.7%; PI: 4.5%). None of the treatments affected sleep quality at night after surgery (Median, Q1-Q3, Control: 3, 1-3; TT: 3, 1-4; PI: 3, 1-3.5). Personal, but not therapist, music intervention significantly prevented anxiety (Control: 36.4±5.9, 95% CI:35.0-37.9; TT: 36.2±7.1, 95% CI: 34.4-37.9; PI: 33.8±5.6, 95% CI: 32.4-35.2) and emesis (Control: 23.9%; TT: 23.4%; PI: 13.2%) and improved patient satisfaction (Median, Q1-Q3, C: 8, 6-8; TT: 8, 7-9; PI: 8, 7-9). CONCLUSIONS: Personal music intervention improved postoperative systolic blood pressure, anxiety, nausea, emesis, and overall satisfaction, but not sleep quality, as compared to therapist-designed classic intervention.

Atypical perianal and buttocks epidermal-dermal necrosis in Human Monkeypox. Histopathological study of the lesion in Peru

We report the histopathological study of a large, black, crusted lesion with symmetrical distribution in both buttocks and perineum, never described, in a man who has sex with men (MSM) and proctitis associated with Human Monkey Pox Virus (hMPXV) and HIV-AIDS infection never treated. A 39-year-old male, homosexual, HIV-AIDS without Highly Active Antiretroviral Therapy (HAART), was admitted to a hospital in Lima, Peru, with papulopustular lesions on the body and perianal area. Days later, a large, crusty, black lesion with a symmetrical distribution appeared on the buttocks and perineum. The tissue culture was negative. Wedge biopsy of the lesion showed typical MPXV cytopathogenics lesions in addition to fibrin micro thrombosis in the underlying papillary dermis. The histopathological findings of the scabby and black lesion are the classic ones described by Stagles, except for the phenomenon of fibrin micro thrombosis in the papillary dermis, a novel cytopathogenic effect of MPXV with clinical relevance (epidermal-dermal necrosis).

Reportamos el estudio histopatológico de una gran lesión costrosa, negra, de distribución simétrica en ambas nalgas y periné, nunca descrito, en un hombre que tiene sexo con hombres (HSH) y proctitis asociado a Viruela del Mono Humana (hMPXV) e infección por VIH-SIDA nunca tratado. Un varón de 39 años, homosexual, VIH-SIDA sin Terapia Antirretroviral de Gran Actividad (TARGA), ingresó en un hospital de Lima, Perú, con lesiones papulopustulosas en el cuerpo y el area perianal. Días después apareció una gran lesión negra, costrosa de distribución simétrica en las nalgas y periné. El cultivo de tejidos fue negativo. La biopsia en cuña de la lesión mostró lesiones citopatogénicas típicas de MPXV, además de microtrombosis de fibrina en la dermis papilar subyacente. Los hallazgos histopatológicos de la lesión costrosa y negra que reportamos son los clásicos descritos por Stagles, a excepción del fenómeno de microtrombosis de fibrina en la dermis papilar, un efecto citopatogénico novedoso de MPXV con relevancia clínica (necrosis epidermo-dérmico).

Splenic SUMO1 controls systemic inflammation in experimental sepsis.

Introduction: The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting. Methods: We used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis. Results and discussion: Here, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia. Conclusion: These results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.

Minocycline protects against neuronal mitochondrial dysfunction and cognition impairment.

The potential of minocycline to protect against methylphenidate­induced neurodegeneration has been extensively reported in the literature but the mechanism of action is still unknown. This study aims to determine the role of mitochondrial chain enzymes and redox homeostasis on the neuroprotective effects of minocycline in methylphenidate­induced neurodegeneration. Wistar adult male rats were randomly assigned to the seven experimental groups: Group 1 received saline solution; Group 2 received methylphenidate (10 mg/kg, i.p.); Groups 3, 4, 5, and 6 received methylphenidate and minocycline for 21 days; Group 7 received minocycline alone. Cognition was evaluated with the Morris water maze test. Activity of the hippocampal mitochondrial quadruple complexes I, II, III and IV, mitochondrial membrane potential, adenosine triphosphate (ATP) levels, total antioxidant capacity, and reactive oxygen species were determined. Treatment with minocycline inhibited methylphenidate­induced cognitive dysfunction. Minocycline treatment increased mitochondrial quadruple complex activities, mitochondrial membrane potential, total antioxidant capacity, and ATP levels in the dentate gyrus and cornu ammonis­1 (CA1) areas of the hippocampus. Minocycline is likely to confer neuroprotection against methylphenidate­induced neurodegeneration and cognition impairment by regulating mitochondrial activity and oxidative stress.

Is lithium neuroprotective? An updated mechanistic illustrated review.

Neurodegeneration is a pathological process characterized by progressive neuronal impairment, dysfunction, and loss due to mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Many studies have shown that lithium protects against neurodegeneration. Herein, we summarize recent clinical and laboratory studies on the neuroprotective effects of lithium against neurodegeneration and its potential to modulate mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Recent findings indicate that lithium regulates critical intracellular pathways such as phosphatidylinositol-3 (PI3)/protein kinase B (Akt)/glycogen synthase kinase-3 (GSK3ß) and PI3/Akt/response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF). We queried PubMed, Web of Science, Scopus, Elsevier, and other related databases using search terms related to lithium and its neuroprotective effect in various neurodegenerative diseases and events from January 2000 to May 2022. We reviewed the major findings and mechanisms proposed for the effects of lithium. Lithium's neuroprotective potential against neural cell degeneration is mediated by inducing anti-inflammatory factors, antioxidant enzymes, and free radical scavengers to prevent mitochondrial dysfunction. Lithium effects are regulated by two essential pathways: PI3/Akt/GSK3ß and PI3/Akt/CREB/BDNF. Lithium acts as a neuroprotective agent against neurodegeneration by preventing inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction using PI3/Akt/GSK3ß and PI3/Akt/CREB/BDNF signaling pathways.

Las donaciones de sangre en Cuba desde una perspectiva histórica / Blood donations in Cuba from a historical perspective

Introducción: Las donaciones de sangre constituyen una actividad sanitaria de importancia estratégica, su historia ha evolucionado junto a la del sistema de salud cubano. Objetivo: Describir el comportamiento de las donaciones de sangre desde una perspectiva histórica, según las etapas del desarrollo del sistema sanitario cubano. Métodos: Se realizó una investigación por el método histórico-lógico sobre los antecedentes históricos y la actualidad de las donaciones de sangre. La información se obtuvo mediante la entrevista y las revisiones bibliográfica y documental. Resultados: Durante la seudorepública se fundaron las primeras instituciones de salud para las donaciones y transfusiones de sangre, su administración se fundamentaba en las recolecciones provenientes de los donantes remunerados y familiares. En el período revolucionario se logró un programa de sangre organizado e integrado al sistema de salud, por primera vez unificado y de alcance nacional, con la participación coordinada entre el personal del nivel primario de atención y las organizaciones sociales. Esto permitió el creciente y considerable incremento de la disponibilidad de sangre y el desarrollo de la medicina transfusional, las especialidades médico-quirúrgicas y la industria médico-farmacéutica cubanas. Además, se consolidó la práctica de donar sangre como un acto voluntario. Conclusiones: La donación de sangre en Cuba constituye una actividad trazadora que muestra el desarrollo del sistema sanitario cubano en sus diferentes etapas y es reflejo de la voluntad política del gobierno, el pueblo y sus instituciones(AU)

Introduction: Blood donations are health care activity of a strategic importance. Their history has evolved together with the Cuban health system. Objective: To describe the behaviour of blood donations from a historical perspective according to the development stages of the Cuban health system. Method: It was carried out a research by the logic-historical method on the historical background and the current data on blood donations. The information was collected through interviews and the bibliographic and documentary reviews. Results: During the pseudo-republic times, the first institutions for blood donations and transfusions were created, and their managements was supported with the collections of paid donors and relatives. In the Revolution period, it was achieved an organized blood donation program which was integrated to the health system and for the fist time unified and of national scope, with coordinated participation between the staff of the first level of care and the social organizations. This allowed the significant increase of the availability of blood and the development of the Cuban transfusion medicine, medical-surgical specialties and medical-pharmaceutical industry. In addition, it was strengthen the practice of blood donation as a voluntary act. Conclusions: Blood donation in Cuba is a trace activity that shows the development of the Cuban health system in its different stages and it is a reflection of the political will of the Government, the people and the institutions(AU)

Review of Perioperative Music Medicine: Mechanisms of Pain and Stress Reduction Around Surgery.

Clinical-experimental considerations and an approach to understanding the autonomic basis of improved surgical outcomes using Perioperative Music Medicine (PMM) are reviewed. Combined surgical, psycho-physiological, and experimental perspectives on Music Medicine (MM) and its relationship to autonomic nervous system (ANS) function are discussed. Considerations are given to the inter-related perioperative effects of MM on ANS, pain, and underlying vagal and other neural circuits involved in emotional regulation and dysregulation. Many surgical procedures are associated with significant pain, which is routinely treated with post-operative opioid medications, which cause detrimental side effects and delay recovery. Surgical trauma shifts the sympathetic ANS to a sustained activation impairing physiological homeostasis and causing psychological stress, as well as metabolic and immune dysfunction that contribute to postoperative mortality and morbidity. In this article, we propose a plan to operationalize the study of mechanisms mediating the effects of MM in perioperative settings of orthopedic surgery. These studies will be critical for the implementation of PMM as a routine clinical practice and to determine the potential limitations of MM in specific cohorts of patients and how to improve the treatment.

Cervical Vagus Nerve Stimulation Improves Neurologic Outcome After Cardiac Arrest in Mice by Attenuating Oxidative Stress and Excessive Autophagy.

BACKGROUND: Cerebral ischemia and reperfusion (I/R) induces oxidative stress and activates autophagy, leading to brain injury and neurologic deficits. Cervical vagus nerve stimulation (VNS) increases cerebral blood flow (CBF). In this study, we investigate the effect of VNS-induced CBF increase on neurologic outcomes after cardiac arrest (CA). MATERIALS AND METHODS: A total of 40 male C57Bl/6 mice were subjected to ten minutes of asphyxia CA and randomized to vagus nerve isolation (VNI) or VNS treatment group. Eight mice received sham surgery and VNI. Immediately after resuscitation, 20 minutes of electrical stimulation (1 mA, 1 ms, and 10 Hz) was started in the VNS group. Electrocardiogram, blood pressure, and CBF were monitored. Neurologic and histologic outcomes were evaluated at 72 hours. Oxidative stress and autophagy were assessed at 3 hours and 24 hours after CA. RESULTS: Baseline characteristics were not different among groups. VNS mice had better behavioral performance (ie, open field, rotarod, and neurologic score) and less neuronal death (p < 0.05, vs VNI) in the hippocampus. CBF was significantly increased in VNS-treated mice at 20 minutes after return of spontaneous circulation (ROSC) (p < 0.05). Furthermore, levels of 8-hydroxy-2'-deoxyguanosine in the blood and autophagy-related proteins (ie, LC-3Ⅱ/Ⅰ, Beclin-1, and p62) in the brain were significantly decreased in VNS mice. Aconitase activity was also reduced, and the p-mTOR/mTOR ratio was increased in VNS mice. CONCLUSIONS: Oxidative stress induced by global brain I/R following CA/ROSC leads to early excessive autophagy and impaired autophagic flux. VNS promoted CBF recovery, ameliorating these changes. Neurologic and histologic outcomes were also improved.

[Portrayal of cancer prevalence and mortality in Chilean digital media]. / Representación de la incidencia y de la mortalidad por cáncer en los medios de comunicación chilenos.

BACKGROUND: Cancer is the second death cause in Chile. The Chilean National Cancer Act will secure treatment and labor protection for people diagnosed with cancer. AIM: To answer questions regarding the media portrayal of cancer. MATERIAL AND METHODS: Through data-mining and the conduction of content analysis, 2,523 news titles about cancer were analysed. The news titles were obtained from 345 Chilean digital media which published cancer related news on Twitter between January and December 2019. An attempt was made to answer two research questions, namely are cancer incidence and mortality rates portrayed in a corresponding magnitude in the Chilean digital media? and what words are commonly used for this purpose? RESULTS: There is not a coherence between the incidence and mortality of the main cancer types in Chile and the amount of content published in communication media. CONCLUSIONS: Our results are consistent with international studies. We should expect the delivery of complete, timely and effective information about cancer in communication media, aiming to educate the population and reinforce prevention.

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.

Annexin A1 Tripeptide Mimetic Increases Sirtuin-3 and Augments Mitochondrial Function to Limit Ischemic Kidney Injury.

Background: Acute kidney injury (AKI) is one of the most common organ failures following surgery. We have developed a tripeptide mimetic (ANXA1sp) of the parent annexin A1 molecule that shows promise as an organ protectant limiting cellular stress; however, its potential as a kidney protective agent remains unexplored, and its mechanism of action is poorly understood. Our hypothesis was that ANXA1sp would limit kidney injury following surgical ischemic kidney injury. Methods: In a blinded fashion, wildtype mice were assigned to receive vehicle control or ANXA1sp one hour prior to and one hour after kidney vascular clamping. Our primary outcomes were markers of kidney injury and function as measured by serum creatinine and histologic injury scoring of kidney tissue sections. Immunofluorescence microscopy, real-time PCR, and Western blot were used to assess cell death, oxidative stress, and mitochondrial biomarkers. An in vitro model of oxygen-glucose deprivation in immortalized kidney tubule cells was used. Results: ANXA1sp given prior to and after ischemic kidney injury abrogated ischemic kidney injury. ANXA1sp limited cell death both in vivo and in vitro and abrogated oxidative stress following ischemia. ANXA1sp significantly increased the expression of markers associated with protective mitophagy and limited the expression of markers associated with detrimental mitochondrial fission. ANXA1sp upregulated the expression of the mitochondrial protectant sirtuin-3 (SIRT3) in the mitochondria of kidney tubular cells. Silencing of SIRT3 reversed ANXA1sp-mediated protection against hypoxic cell death. Conclusions: ANXA1sp limits kidney injury, upregulates SIRT3, and preserves mitochondrial integrity following ischemic kidney injury. ANXA1sp holds considerable promise as a perioperative kidney protectant prior to ischemia inducing surgery and kidney transplantation.

Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats.

The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3+ and CD4+ lymphocytes, and CD68+ and CD206+ macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4+ lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.

Representación de la incidencia y de la mortalidad por cáncer en los medios de comunicación chilenos / Portrayal of cancer prevalence and mortality in Chilean digital media

Background: Cancer is the second death cause in Chile. The Chilean National Cancer Act will secure treatment and labor protection for people diagnosed with cancer. Aim: To answer questions regarding the media portrayal of cancer. Material and Methods: Through data-mining and the conduction of content analysis, 2,523 news titles about cancer were analysed. The news titles were obtained from 345 Chilean digital media which published cancer related news on Twitter between January and December 2019. An attempt was made to answer two research questions, namely are cancer incidence and mortality rates portrayed in a corresponding magnitude in the Chilean digital media? and what words are commonly used for this purpose? Results: There is not a coherence between the incidence and mortality of the main cancer types in Chile and the amount of content published in communication media. Conclusions: Our results are consistent with international studies. We should expect the delivery of complete, timely and effective information about cancer in communication media, aiming to educate the population and reinforce prevention.

SUMOylation Connects Cell Stress Responses and Inflammatory Control: Lessons From the Gut as a Model Organ.

Conjugation with the small ubiquitin-like modifier (SUMO) constitutes a key post-translational modification regulating the stability, activity, and subcellular localization of its target proteins. However, the vast numbers of identified SUMO substrates obscure a clear view on the function of SUMOylation in health and disease. This article presents a comprehensive review on the physiological relevance of SUMOylation by discussing how global SUMOylation levels-rather than specific protein SUMOylation-shapes the immune response. In particular, we highlight the growing body of work on SUMOylation in intestinal pathologies, because of the unique metabolic, infectious, and inflammatory challenges of this organ. Recent studies show that global SUMOylation can help restrain detrimental inflammation while maintaining immune defenses and tissue integrity. These results warrant further efforts to develop new therapeutic tools and strategies to control SUMOylation in infectious and inflammatory disorders.

Association of CARD8 Activating Polymorphism With Bone Erosion in Cholesteatoma Patients.

OBJECTIVES: We compared the incidence of polymorphisms activating the NLRP3 inflammasome between controls and patients with cholesteatoma and its potential association with bone erosion in patients with cholesteatoma. METHODS: This is a case-control study assessing the mutation rates in genes of interest in patients with and without cholesteatoma. A total of 133 saliva samples from control (n = 65) and cholesteatoma (n = 68) patients were collected for DNA extraction. Caspase recruitment domain family member 8 (CARD8) (AA: homozygous wild type, AT: heterozygous, TT: homozygous mutant polymorphism) and NLRP3 (CC: homozygous wild type, CA: heterozygous, AA: homozygous mutant) polymorphisms were analyzed with TaqMan single-nucleotide polymorphism (SNP) quantitative polymerase chain reaction (ThermoFisher Scientific, Waltham, MA). Mutation status was correlated with a novel bone erosion scoring model developed as a part of this study. Summary statistics, including frequencies (%) and median (Q1, Q3) were used to describe the sample. RESULTS: The presence of CARD8 and NLRP3 homozygous wild-type polymorphisms were generally similar for the control and cholesteatoma patient groups. CARD8 homozygous TT polymorphisms were an exception, occurring more frequently in patients who developed a cholesteatoma compared to the control group (29% vs. 10%, P = .009). Those patients with CARD8 homozygous TT polymorphism had higher median scores of bone erosion as compared to subjects with nonhomozygous mutant genotypes (median [interquartile range]: 4.0 [3.0, 5.5] vs. 2.5 [1.0, 3.5], P = .0142). CONCLUSION: Cholesteatoma patients have a significant, twofold higher incidence of CARD8 homozygous TT polymorphism. Furthermore, cholesteatoma patients with this homozygous polymorphism had greater bone erosion rates than controls. These findings suggest that genetic mutations may increase host susceptibility to cholesteatomas. Specifically, the CARD8 TT polymorphism may influence the severity of cholesteatoma-induced bone erosion. LEVEL OF EVIDENCE: 3B.

Central angiotensin-(1-7) attenuates systemic inflammation via activation of sympathetic signaling in endotoxemic rats.

Angiotensin-(1-7) [Ang-(1-7)] is an angiotensin-derived neuropeptide with potential anti-hypertensive and anti-inflammatory properties. However, a possible action of Ang-(1-7) in neuroimmune interactions to regulate inflammatory response has not been explored. Thus, the aim of this study was to determine whether the intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation via sympathetic efferent circuits. Wistar male rats received systemic administration of lipopolysaccharide (LPS) (1.5 mg/Kg). Ang-(1-7) (0.3 nmol in 2 µL) promoted the release of splenic norepinephrine and attenuated tumor necrosis factor (TNF) and nitric oxide (NO), but increased interleukin-10 (IL-10), levels in the serum, spleen, and liver in endotoxemic rats. Furthermore, 6-hydroxydopamine-induced chemical sympathectomy (100 mg/Kg, intravenous) or i.c.v. administration of Mas receptor antagonist A779 (3 nmol in 2 µL) abolished the anti-inflammatory effects of central Ang-(1-7) injection. Moreover, this treatment did not alter the plasmatic LPS-induced corticosterone and vasopressin. The administration of Ang-(1-7) reverted the low resistance in response to catecholamines of rings of thoracic aorta isolated from endotoxemic rats, treated or not, with this peptide by a mechanism dependent on the regulation of NO released from perivascular adipose tissue. Together, our results indicate that Ang-(1-7) regulates systemic inflammation and vascular hyporesponsiveness in endotoxemia via activation of a central Mas receptors/sympathetic circuits/norepinephrine axis and provide novel mechanistic insights into the anti-inflammatory Ang-(1-7) properties.

Transgelin-2: Biochemical and Clinical Implications in Cancer and Asthma.

Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders.

Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice.

Neuroendocrine changes are essential factors contributing to the progression and development of rheumatoid arthritis. However, the role of estrogen in the innate immunity during arthritis development is still controversial. Here, we evaluated the effect of estrous cycle, ovariectomy, estradiol replacement therapy and treatment with estrogen receptor (ER)α and ERß specific agonists on joint edema formation, neutrophil recruitment, and articular levels of cytokines/chemokines in murine zymosan-induced arthritis. Our results showed that articular inflammation of proestus/estrus was similar to metaestus/diestrus animals indicating that the inflammatory response in acute arthritis is not affected by the estrous cycle. However, ovariectomy increased joint swelling, neutrophil migration, and TNF-α level. Treatment for six consecutive days with estradiol cypionate re-established the acute inflammation in ovariectomized arthritic mice to responses similar to those in SHAM-proestrus/estrus or naive mice. Moreover, treatment with propylpyrazoletriol and diarylpropionitrile, two ERα and ERß selective agonists, respectively, inhibited both edema and neutrophil recruitment. Finally, the non-genomic properties of estradiol were analyzed with an acute treatment with ß-estradiol-water soluble, which reduced the edema only. In the present study, estradiol replacement therapy improves the innate immune responses in ovariectomized arthritic mice by activating nuclear estrogen receptors. These results suggest that estradiol can induce a protective anti-inflammatory effect in arthritis during ovaries failure, as observed in the menopause.

La donación y la transfusión de sangre en función del envejecimiento poblacional de Cienfuegos, 2010-2016 / Blood donation and transfusion according to the population aging of Cienfuegos, 2010-2016

Introducción: La provincia de Cienfuegos es autosuficiente para satisfacer su demanda transfusional actual. Sin embargo, esta situación podría modificarse por los efectos que sobre la asistencia sanitaria ejerce el envejecimiento poblacional. Objetivos: Identificar la relación entre donaciones y transfusiones de sangre en función de los cambios en la dinámica poblacional. Métodos: Estudio descriptivo transversal desarrollado mediante revisión documental. Se incluyó como variables el número de habitantes agrupados según la edad regulada en Cuba para donar sangre, la cantidad de donaciones y de pacientes transfundidos durante el periodo de estudio. se utilizó el coeficiente de correlación de Spearman ( ρ)para establecer el grado de relación entre ellas. Se calcularon tasas, porcientos y el cambio relativo entre años extremos de las series. Resultados: La composición de los grupos de edades de la población mostró preferencia hacia el envejecimiento con una disminución del 5 por ciento en el número de habitantes de 0 a 19 años junto a un incremento del doble de ese valor en los adultos mayores. Las donaciones decrecen en cerca del 8 por ciento, mientras que el número de pacientes transfundidos aumentan en el 33 por ciento. Se comprueba la existencia de correlaciones directas e inversas, estadísticamente significativas, entre los indicadores estudiados. Conclusiones: Los resultados de la investigación son sugerentes a una relación entre los indicadores de donaciones, transfusiones de sangre y los cambios en la estructura por edad de la población que, de mantenerse la tendencia actual, podrían conducir a periodos de escasez de sangre para transfusiones(AU)

Introduction: The province of Cienfuegos is self-sufficient to satisfy the actual transfusion demand. However, this situation could be modified due to the effects of population aging on health care service. Objective: To identify the relationship between donations and blood transfusions based on changes in population dynamics. Methods: Transversal descriptive study developed through documentary review. The number of inhabitants grouped according to the regulated age in Cuba to donate blood, the number of donations and transfused patients during the study period were included as variables, using the Spearman correlation coefficient ( ρ) to establish the degree of relationship between them. The rates, percent and relative change between the extreme years of the series were calculated. Results: The composition of the age groups of the population was inclined towards aging with a 5 percent decrease in the number of inhabitants from 0 to 19 years, together with an increase of twice that value in the elderly. Donations decrease by about 8 percent, while the number of patients transfused increases by 33 percent. The existence of statistically significant direct and inverse correlations between the indicators studied is verified. Conclusions. The results of the research are suggestive of a relationship between the blood donationand blood transfusion indicators and the changes in the age structure of the population observed which, if the current trend continues, lead to periods of blood shortage for transfusions(AU)

Exercise activates vagal induction of dopamine and attenuates systemic inflammation.

Physical exercise is one of the most important factors improving quality of life, but it is not feasible for patients with morbidity or limited mobility. Most previous studies focused on high-intensity or long-term exercise that causes metabolic stress or physiological adaption, respectively. Here, we studied how moderate-intensity swimming affects systemic inflammation in 6-8 week old C57BL/6J male mice during endotoxemia. One-hour swimming prevented hypokalemia, hypocalcemia, attenuated serum levels of inflammatory cytokines, increased anti-inflammatory cytokines but affected neither IL6 nor glycemia before or after the endotoxic challenge. Exercise attenuated serum TNF levels by inhibiting its production in the spleen through a mechanism mediated by the subdiaphragmatic vagus nerve but independent of the splenic nerve. Exercise increased serum levels of dopamine, and adrenalectomy prevented the potential of exercise to induce dopamine and to attenuate serum TNF levels. Dopaminergic agonist type-1, fenoldopam, inhibited TNF production in splenocytes. Conversely, dopaminergic antagonist type-1, butaclamol, attenuated exercise control of serum TNF levels. These results suggest that vagal induction of dopamine may contribute to the anti-inflammatory potential of physical exercise.