The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review.

Aging is characterized by significant physiological changes, with the degree of decline varying significantly among individuals. The preservation of intrinsic capacity over the course of an individual's lifespan is fundamental for healthy aging. Locomotion, which entails the capacity for independent movement, is intricately connected with various dimensions of human life, including cognition, vitality, sensory perception, and psychological well-being. Notably, skeletal muscle functions as a pivotal nexus within this intricate framework. Any perturbation in its functionality can manifest as compromised physical performance and an elevated susceptibility to frailty. Magnesium is an essential mineral that plays a central role in approximately 800 biochemical reactions within the human body. Its distinctive physical and chemical attributes render it an indispensable stabilizing factor in the orchestration of diverse cellular reactions and organelle functions, thereby rendering it irreplaceable in processes directly impacting muscle health. This narrative review offers a comprehensive exploration of the pivotal role played by magnesium in maintaining skeletal muscle integrity, emphasizing the critical importance of maintaining optimal magnesium levels for promoting healthy aging.

Vitamin D, zinc and glutamine: Synergistic action with OncoTherad immunomodulator in interferon signaling and COVID­19 (Review).

Coronavirus disease 2019 (COVID­19), caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS­CoV­2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non­muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID­19 in a case report that described the rapid recovery of a 78­year­old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID­19.

Antioxidant and anti­inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review).

Cardiovascular diseases are the most common cause of mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases; thus, anti­inflammatory and antioxidant agents that modulate redox balance have become research targets so as to evaluate their molecular mechanisms of action and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant properties due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also has prominent anti­inflammatory activity, possibly interrelated with its antioxidant effect, and is also involved in the modulation of lipid and glucose metabolism. Considering the potential beneficial effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, the aim of the present review was to describe the molecular and cellular mechanisms associated with the antioxidant and anti­inflammatory properties of this carotenoid in cardiovascular diseases, particularly atherosclerosis. The beneficial properties and safety profile of astaxanthin indicate that this compound may be used for preventing progression or as an adjuvant in the treatment of cardiovascular diseases.

Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity.

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans.

Caenorhabditiselegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candidaparapsilosis infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (C.parapsilosis (sensustricto), Candidaorthopsilosis and Candidametapsilosis) caused infection resulting in C. elegans killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in C. elegans-Candida infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall, the C. elegans-C. parapsilosis infection model can be used to model C. parapsilosis host-pathogen interactions.

Clinical impact of Candida spp. biofilm production in a cohort of patients with candidemia.

Persistent candidemia refers to the continued isolation of the same Candida species in the blood of a candidemic patient despite appropriate therapy. Despite the clinical importance of persistent candidemia, studies have superficially addressed the biological conditions behind this phenomenon. The aim of this study was to evaluate the correlation between the biofilm-forming ability by Candida bloodstream isolates and the persistence of infection. A total of 55 isolates of Candida were tested and characterized in two groups: (i) group I, which included seven patients with persistent candidemia, and (ii) group II, which included 18 patients with nonpersistent candidemia. Microorganisms were identified at the species level by sequencing the internal transcribed spacer (ITS) region of ribosomal DNA (rDNA). Biofilm quantification was evaluated by the crystal violet staining method and confocal scanning laser microscopy (CSLM). Molecular tests confirmed the identification of Candida albicans (92% group I and 94% group II) and Candida dubliniensis isolates (8% group I and 6% group II). All 55 isolates were able to form biofilms, but a higher biofilm mass was produced by C. albicans/C. dubliniensis strains cultured from the persistent group (P < .05). Our data suggest that Candida sp. biofilm production should be considered a relevant biologic variable in explaining patients who fail to clear a bloodstream infection despite adequate antifungal treatment with triazoles.

Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers.

The epidemiology of candidemia varies geographically, and there is still scarce data on the epidemiology of candidemia in Latin America (LA). After extensive revision of medical literature, we found reliable and robust information on the microbiological aspects of candidemia in patients from 11 out of 21 medical centers from LA countries and 1 out of 20 from Caribbean countries/territories. Based on 40 papers attending our search strategy, we noted that C. albicans remains the most common species causing candidemia in our region, followed by C. parapsilosis and C. tropicalis. In Argentina, Brazil, and Colombia, a trend towards an increase in frequency of C. glabrata candidemia was observed. Although resistance rates to fluconazole is under 3%, there was a slight increase in the resistance rates to C. albicans, C. parapsilosis and C. tropicalis isolates. Echinocandin resistance has been reported in a few surveys, but no single study confirmed the resistant phenotype reported by using molecular methods. We highlight the importance of conducting continuous surveillance studies to identify new trends in terms of species distribution of Candida and antifungal resistance related to episodes of candidemia in LA. This information is critical for helping clinicians to prevent and control Candida bloodstream infections in their medical centers.

Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit.

BACKGROUND: Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. METHODS: This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. RESULTS: We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. CONCLUSIONS: The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.

High rate of Candida deep-seated infection in patients under chronic hemodialysis with extended central venous catheter use / Altas tasas de infección profunda por Candida en pacientes en hemodiálisis crónica con catéter venoso central de uso prolongado

Background. Hemodialysis has been described as an important risk factor for the development of candidemia in patients suffering from chronic renal failure. Aims. The aim of this study was to evaluate the epidemiology of candidemia in outpatients with renal replacement therapy (RRT) by hemodialysis where the fungemia clearly represents a healthcare-associated infection. Methods. We retrospectively collected clinical and laboratory data from patients undergoing at least 3 months of RRT by hemodialysis who developed candidemia within 48 h of hospital admission. Results. We identified 14 patients with candidemia with central venous catheters (CVC) in place for 11-277 days before developing fungemia. Deep-seated infection was documented in 6 out of 14 candidiasis cases (43%), including 5 cases of endocarditis (36%). Conclusions. CVC in patients under RRT should be promptly replaced by fistulas and grafts to avoid bloodstream infections. Facing a case of candidemia, adequate source control and prompt initiation of antifungal therapy are mandatory to avoid morbidity and mortality (AU)

Antecedentes. La hemodiálisis se ha descrito como un importante factor de riesgo para el desarrollo de candidemia en pacientes con insuficiencia renal crónica. Objetivos. El objetivo de este estudio fue evaluar la epidemiología de la candidemia en pacientes en hemodiálisis con terapia renal sustitutiva (TRS), en la que la fungemia representa claramente una infección asociada a los cuidados hospitalarios. Métodos. Se recogieron retrospectivamente datos clínicos y microbiológicos de pacientes con, al menos, 3 meses de hemodiálisis con TRS que desarrollaron candidemia dentro de las primeras 48 horas tras la admisión hospitalaria. Resultados. Identificamos a 14 pacientes con candidemia asociada con el uso de catéter venoso central (CVC) durante períodos de 11 a 277 días previos al desarrollo de la fungemia. En 6 de los 14 casos de candidemia, el diagnóstico fue de candidiasis invasiva (43%), incluidos 5 casos de endocarditis (36%). Conclusiones. Los CVC en pacientes con TRS deberían ser sustituidos inmediatamente por fístulas o injertos arteriovenosos para evitar infecciones del torrente sanguíneo. Ante los casos de candidemia, un control adecuado de las posibles fuentes de infección y el comienzo inmediato de la terapia antifúngica deberían ser imperativos para reducir tanto la morbilidad como la mortalidad (AU)

High rate of Candida deep-seated infection in patients under chronic hemodialysis with extended central venous catheter use.

BACKGROUND: Hemodialysis has been described as an important risk factor for the development of candidemia in patients suffering from chronic renal failure. AIMS: The aim of this study was to evaluate the epidemiology of candidemia in outpatients with renal replacement therapy (RRT) by hemodialysis where the fungemia clearly represents a healthcare-associated infection. METHODS: We retrospectively collected clinical and laboratory data from patients undergoing at least 3 months of RRT by hemodialysis who developed candidemia within 48h of hospital admission. RESULTS: We identified 14 patients with candidemia with central venous catheters (CVC) in place for 11-277 days before developing fungemia. Deep-seated infection was documented in 6 out of 14 candidiasis cases (43%), including 5 cases of endocarditis (36%). CONCLUSIONS: CVC in patients under RRT should be promptly replaced by fistulas and grafts to avoid bloodstream infections. Facing a case of candidemia, adequate source control and prompt initiation of antifungal therapy are mandatory to avoid morbidity and mortality.

Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus.

The significant increase in the use of antifungal agents, both for the treatment of candidiasis and invasive aspergillosis and as azole fungicides in agricultural crop protection has resulted in the emergence of resistant clinical isolates, particularly to triazoles and echinocandins. Notably, among isolates that were primarily sensitive to fluconazole such as Candida parapsilosis and Candida tropicalis have witnessed an emerging resistance development. Also for echinocandins, the occurrence of Candida isolates with lower susceptibility to these drugs has been reported, which is possibly due to its broad clinical use. Triazole resistance among Aspergillus fumigatus and other Aspergillus species is commonly found in European and Asian countries. Specific mutations are associated with azole resistance in A. fumigatus and these mutations are now reported globally from six continents. Therefore, we highlight the need to conduct antifungal resistance surveillance studies using clinical isolates of Candida and Aspergillus in different geographical regions and monitoring of the infection rates in distinct population groups for early detection of resistance to these drugs and implementation of efficient policies for infection control and treatment.

Inhibition of bacterial and fungal pathogens by the orphaned drug auranofin.

BACKGROUND: We identified auranofin as an antimicrobial compound utilizing a high-throughput screen using a Caenorhabditis elegans-Staphylococcus aureus infection model. Results/methodology: Treatment of infected nematodes with auranofin resulted in a prolonged survival rate of 95%, reached with 0.78 µg/ml. Further investigation of the antimicrobial activity of auranofin found inhibition against S. aureus, Enterococcus faecium and Enterococcus faecalis. Importantly, the fungal pathogens Cryptococcus neoformans was also effectively inhibited with an MIC at 0.5 µg/ml. Auranofin appears to target the thioredoxin system. CONCLUSION: This work provides extensive additional data on the antibacterial effects of auranofin that includes both reference and clinical isolates and reports a novel inhibition of fungal pathogens by this compound.

Catheter-related infections in a northwestern São Paulo reference unit for burned patients care.

Despite improvements in care and rehabilitation of burned patients, infections still remain the main complication and death cause. Catheter-related infections are among the four most common infections and are associated with skin damage and insertion site colonization. There are few studies evaluating this kind of infection worldwide in this special group of patients. Padre Albino Hospital Burn Care Unit (PAHBCU) is the only reference center in the Northwestern São Paulo for treatment of burned patients. This paper presents the results of a retrospective study aiming at describing the epidemiological and clinical features of catheter-related infections at PAHBCU.

Catheter-related infections in a northwestern São Paulo reference unit for burned patients care

Despite improvements in care and rehabilitation of burned patients, infections still remain the main complication and death cause. Catheter-related infections are among the four most common infections and are associated with skin damage and insertion site colonization. There are few studies evaluating this kind of infection worldwide in this special group of patients. Padre Albino Hospital Burn Care Unit (PAHBCU) is the only reference center in the Northwestern São Paulo for treatment of burned patients. This paper presents the results of a retrospective study aiming at describing the epidemiological and clinical features of catheter-related infections at PAHBCU.