Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice.

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis.

Role of parC Mutations at Position 84 on High-Level Delafloxacin Resistance in Methicillin-Resistant Staphylococcus aureus.

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1 mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present.

Effect of Melatonin on Herpesvirus Type 1 Replication.

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.

Respiratory syncytial virus incidence and typing in the last six seasons in the north of Spain (Asturias). Genetic characterization during the SARS-CoV-2 pandemic.

Respiratory syncytial virus is associated with lower respiratory tract infections. As several types and genotypes can circulate at the same time, genomic characterization is important for timely epidemiological control and treatment measures. In the last 6 seasons (2017-2023), 191 236 nasopharyngeal swabs were processed for respiratory viruses to determine the etiology of acute respiratory infections, describe the incidence and distribution of RSV types and enrich the data of epidemiological molecular studies on RSV in Spain. The incidence of RSV reached 7% in the pre-pandemic season. RSV was most frequent in children under 5 years of age (12.6%), but was also significant in those over 70 years of age (5.63%). The measures taken to control SARS-CoV-2 infection were useful for RSV control and the incidence decreased to 1.8%, but caused a change in the types. Pre-pandemic, the majority circulating types were RSV-B/RSV-B/RSV-A and in the pandemic it was RSV-B/RSV-B. In the last season, RSV-B and RSV-A were detected in the same proportion. Genetic characterization showed three new clades. This has been taken into account to understand the epidemiology as well as the development of therapeutic and preventive strategies.

NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Differential Cellular Interactome in Schizophrenia and Bipolar Disorder-Discriminatory Biomarker Role.

Schizophrenia (SCH) and bipolar disorder (BD) are two of the most important psychiatric pathologies due to their high population incidence and disabling power, but they also present, mainly in their debut, high clinical similarities that make their discrimination difficult. In this work, the differential oxidative stress, present in both disorders, is shown as a concatenator of the systemic alterations-both plasma and erythrocyte, and even at the level of peripheral blood mononuclear cells (PBMC)-in which, for the first time, the different affectations that both disorders cause at the level of the cellular interactome were observed. A marked erythrocyte antioxidant imbalance only present in SCH generalizes to oxidative damage at the plasma level and shows a clear impact on cellular involvement. From the alteration of protein synthesis to the induction of death by apoptosis, including proteasomal damage, mitochondrial imbalance, and autophagic alteration, all the data show a greater cellular affectation in SCH than in BD, which could be linked to increased oxidative stress. Thus, patients with SCH in our study show increased endoplasmic reticulum (ER)stress that induces increased proteasomal activity and a multifactorial response to misfolded proteins (UPR), which, together with altered mitochondrial activity, generating free radicals and leading to insufficient energy production, is associated with defective autophagy and ultimately leads the cell to a high apoptotic predisposition. In BD, however, oxidative damage is much milder and without significant activation of survival mechanisms or inhibition of apoptosis. These clear differences identified at the molecular and cellular level between the two disorders, resulting from progressive afflictions in which oxidative stress can be both a cause and a consequence, significantly improve the understanding of both disorders to date and are essential for the development of targeted and preventive treatments.

Phenotypic and Genotypic Antimicrobial Susceptibility Testing of Chlamydia trachomatis Isolates from Patients with Persistent or Clinical Treatment Failure in Spain.

The aim of this multicentre project (seven hospitals across the Spanish National Health Service) was to study the phenotypic and genotypic susceptibility of C. trachomatis to the main antimicrobials used (macrolides, doxycycline, and quinolones) in isolates from patients with clinical treatment failure in whom reinfection had been ruled out. During 2018-2019, 73 clinical isolates were selected. Sixty-nine clinical specimens were inoculated onto confluent McCoy cell monolayers for phenotypic susceptibility testing. The minimum inhibitory concentration for azithromycin and doxycycline was defined as the lowest concentration associated with an at least 95% reduction in inclusion-forming units after one passage in the presence of the antibiotic compared to the initial inoculum for each strain (control). Sequencing analysis was performed for the genotypic detection of resistance to macrolides, analysing mutations in the 23S rRNA gene (at positions 2057, 2058, 2059, and 2611), and quinolones, analysing a fragment of the gyrA gene, and searching for the G248T mutation (Ser83->Ile). For tetracyclines, in-house RT-PCR was used to test for the tet(C) gene. The phenotypic susceptibility testing was successful for 10 isolates. All the isolates had minimum inhibitory concentrations for azithromycin ≤ 0.125 mg/L and for doxycycline ≤ 0.064 mg/L and were considered sensitive. Of the 73 strains studied, no mutations were found at positions T2611C or G248T of the gyrA gene. We successfully sequenced 66 isolates. No macrolide resistance-associated mutations were found at positions 2057, 2058, 2059, or T2611C. None of the isolates carried the tet(C) gene. We found no evidence for genomic resistance in this large, clinically relevant dataset.

Benefits of the Neurogenic Potential of Melatonin for Treating Neurological and Neuropsychiatric Disorders.

There are several neurological diseases under which processes related to adult brain neurogenesis, such cell proliferation, neural differentiation and neuronal maturation, are affected. Melatonin can exert a relevant benefit for treating neurological disorders, given its well-known antioxidant and anti-inflammatory properties as well as its pro-survival effects. In addition, melatonin is able to modulate cell proliferation and neural differentiation processes in neural stem/progenitor cells while improving neuronal maturation of neural precursor cells and newly created postmitotic neurons. Thus, melatonin shows relevant pro-neurogenic properties that may have benefits for neurological conditions associated with impairments in adult brain neurogenesis. For instance, the anti-aging properties of melatonin seem to be linked to its neurogenic properties. Modulation of neurogenesis by melatonin is beneficial under conditions of stress, anxiety and depression as well as for the ischemic brain or after a brain stroke. Pro-neurogenic actions of melatonin may also be beneficial for treating dementias, after a traumatic brain injury, and under conditions of epilepsy, schizophrenia and amyotrophic lateral sclerosis. Melatonin may represent a pro-neurogenic treatment effective for retarding the progression of neuropathology associated with Down syndrome. Finally, more studies are necessary to elucidate the benefits of melatonin treatments under brain disorders related to impairments in glucose and insulin homeostasis.

Evaluation and Clinical Impact of Biofire FilmArray Pneumonia Panel Plus in ICU-Hospitalized COVID-19 Patients.

Microbiological diagnosis by using commercial multiplex quantitative PCR systems provides great advantages over the conventional culture. In this work, the Biofire FilmArray Pneumonia Panel Plus (FAPP+) was used to test 144 low respiratory tract samples from 105 COVID-19 patients admitted to an Intensive Care Unit (ICU), detecting 78 pathogens in 59 (41%) samples. The molecular panel was evaluated by using the conventional culture (CC) as comparator, which isolated 42 pathogens in 40 (27.7%) samples. The overall percentage of agreement was 82.6%. Values of sensitivity (93%), specificity (62%), positive predictive value (50%), and negative predictive value (96%) were obtained. The mean time elapsed from sample extraction to modification of antibiotic treatment was 7.6 h. A change in antimicrobial treatment after the FAPP+ results was performed in 27% of patients. The FAPP+ is a highly sensitive diagnostic method that can be used to significantly reduce diagnostic time and that allows an early optimization of antimicrobial treatment.

Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration.

Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer's pathology. Neurodegenerative processes observed in the brains of aged SAMP8 mice at 10 months of age include the presence of damaged neurons, disorganization in the layers of the brain cortex, alterations in neural processes and the length of neuronal prolongations and ß-amyloid accumulation in the cortex and hippocampus. This neurodegeneration may be associated with neurogenic responses in the hippocampal dentate gyrus of these mice, since we observed a neurogenic niche of neural stem and progenitor/precursors cells in the hippocampus of SAMP8 mice. However, hippocampal neurogenesis seems to be compromised due to alterations in the cell survival, migration and/or neuronal maturation of neural precursor cells due to the neurodegeneration levels in these mice. Chronic treatment with melatonin for 9 months decreased these neurodegenerative processes and the neurodegeneration-induced neurogenic response. Noticeably, melatonin also induced recovery in the functionality of adult hippocampal neurogenesis in aged SAMP8 mice.

Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

Patients with severe COVID-19 often need mechanical ventilation to help them breathe and other types of intensive care. The outcome for many of these patients depends on how their immune system reacts to the infection. If the inflammatory response triggered by the immune system is too strong, this can cause further harm to the patient. One gene that plays an important role in inflammation is IFIH1 which encodes a protein that helps the body to recognize viruses. There are multiple versions of this gene which each produce a slightly different protein. It is possible that this variation impacts how the immune system responds to the virus that causes COVID-19. To investigate, Amado-Rodríguez, Salgado del Riego et al. analyzed the IFIH1 gene in 227 patients admitted to an intensive care unit in Spain for severe COVID-19 between March and December 2020. They found that patients with a specific version of the gene called TT experienced less inflammation and were more likely to survive the infection. Physicians typically treat patients with moderate to severe COVID-19 with corticosteroid drugs that reduce the inflammatory response. However, Amado-Rodríguez, Salgado del Riego et al. found that patients with the TT version of the IFIH1 gene were at greater risk of dying if they received corticosteroids. The team then applied the distribution of IFIH1 variants among different ethnic ancestries to data from a previous clinical trial, and simulated the effects of corticosteroid treatment. This 'mock' clinical trial supported their findings from the patient-derived data, which were also validated by laboratory experiments on immune cells from individuals with the TT gene. The work by Amado-Rodríguez, Salgado del Riego et al. suggests that while corticosteroids benefit some patients, they may cause harm to others. However, a real-world clinical trial is needed to determine whether patients with the TT version of the IFIH1 gene would do better without steroids.

Comparison of in-house SARS-CoV-2 genome extraction procedures. A need for COVID-19 pandemic.

Among the methods used to diagnose COVID-19, those based on genomic detection by q(RT)-PCR are the most sensitive. To perform these assays, a previous genome extraction of the sample is required. The dramatic increase in the number of SARS-CoV-2 detection assays has increased the demand for extraction reagents hindering the supply of commercial reagents. Homemade reagents and procedures could be an alternative. Nasopharyngeal samples were extracted by seven different methods as well as the automatic method MagNaPure96, to detect SARS-CoV-2. All protocols show sensitivity higher than 87 %, in comparison with reference method, for detecting SARS-CoV-2 as well as human ß- globin. Our results support that these procedures, using common and cheap reagents, are effective to extract RNA (from SARS-CoV-2) or DNA (from human ß-globin) genome from nasopharyngeal swabs. Furthermore, these procedures could be easily adopted by routine diagnostic laboratories to implement detection methods to help to fight against COVID-19 pandemic.

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model.

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

SARS-CoV-2 analysis on environmental surfaces collected in an intensive care unit: keeping Ernest Shackleton's spirit.

BACKGROUND: Intensive care unit workers are at high risk of acquiring COVID-19 infection, especially when performing invasive techniques and certain procedures that generate aerosols (< 5 µm). Therefore, one of the objectives of the health systems should implement safety practices to minimize the risk of contagion among these health professionals. Monitoring environmental contamination of SARS-CoV-2 may help to determine the potential of the environment as a transmission medium in an area highly exposed to SARS-CoV-2, such as an intensive care unit. The objective of the study was to analyze the environmental contamination by SARS-CoV-2 on surfaces collected in an intensive care unit, which is dedicated exclusively to the care of patients with COVID-19 and equipped with negative pressure of - 10 Pa and an air change rate of 20 cycles per hour. Furthermore, all ICU workers were tested for COVID-19 by quantitative RT-PCR and ELISA methods. RESULTS: A total of 102 samples (72 collected with pre-moistened swabs used for collection of nasopharyngeal exudates and 30 with moistened wipes used in the environmental microbiological control of the food industry) were obtained from ventilators, monitors, perfusion pumps, bed rails, lab benches, containers of personal protective equipment, computer keyboards and mice, telephones, workers' shoes, floor, and other areas of close contact with COVID-19 patients and healthcare professionals who cared for them. The analysis by quantitative RT-PCR showed no detection of SARS-CoV-2 genome in environmental samples collected by any of the two methods described. Furthermore, none of the 237 ICU workers was infected by the virus. CONCLUSIONS: Presence of SARS-CoV-2 on the ICU surfaces could not be determined supporting that a strict cleaning protocol with sodium hypochlorite, a high air change rate, and a negative pressure in the ICU are effective in preventing environmental contamination. These facts together with the protection measures used could also explain the absence of contagion among staff inside ICUs.

Micosis cutánea por Curvularia pallescens en un paciente trasplantado pulmonar: primer caso descrito en España / Subcutaneous infection by Curvularia pallescens in a lung transplant recipient: first report in Spain

ANTECEDENTES: El género Curvularia incluye hongos filamentosos dematiáceos cada vez más reconocidos como patógenos en pacientes inmunocomprometidos. Las entidades clínicas más comunes con las que se asocia este hongo son la sinusitis alérgica, la infección cutánea y la queratitis. En este trabajo se describe el primer caso descrito en España de infección cutánea por Curvularia pallescens y su tratamiento. CASO CLÍNICO: Un varón de 68 años con antecedente de trasplante pulmonar acudió al servicio de dermatología por presentar una lesión cutánea en la rodilla de 6 meses de evolución. Se realizó una biopsia cutánea para estudio. La histopatología mostró una intensa reacción inflamatoria inespecífica en la dermis y mediante la tinción de Grocott y ácido peryódico de Schiff se observaron abundantes hifas septadas y esporas en la dermis. El cultivo de la muestra reveló un hongo filamentoso cuyo examen microscópico permitió identificar el género como Curvularia. Mediante espectrometría de masas MALDI-TOF e identificación molecular, el hongo finalmente se identificó como Curvularia pallescens. Se realizó resección quirúrgica de la lesión y el paciente recibió tratamiento con posaconazol, con resolución clínica de la lesión. CONCLUSIONES: El género Curvularia debe ser considerado un agente causal de micosis subcutáneas en pacientes inmunodeprimidos. Este caso clínico constituye el primero descrito en España producido por esta especie, el cual presentó buena respuesta clínica tras resección quirúrgica y tratamiento con posaconazol

BACKGROUND: Curvularia is a filamentous dematiaceous fungus increasingly recognized as a pathogen in immunocompromised patients. The most common clinical entities associated with this fungus are allergic sinusitis, cutaneous infection and keratitis. In this article, a report on the first clinical case of Curvularia pallescens cutaneous infection in Spain and its treatment is described. CASE REPORT: A 68 year-old man with a history of lung transplantation presented to Dermatology Unit due to a skin lesion in the knee that had been evolving for 6 months. A skin biopsy was performed for its study. In the histopathological study, an intense and non-specific inflammatory reaction in the dermis was observed, and with Grocott stain and periodic acid Schiff abundant septate hyphae and spores were found in the dermis. The culture of the sample revealed a filamentous fungus whose microscopic examination allowed to identify the genus as Curvularia. Using MALDI-TOF mass spectrometry and molecular identification, the fungus was finally identified as Curvularia pallescens. The patient underwent surgical resection of the lesion and was treated with posaconazole, evolving favorably. CONCLUSIONS: The species of Curvularia should be considered causal agents of fungal skin infections in immunosuppressed patients. This clinical case, which showed good clinical response after surgical resection and treatment with posaconazole, is the first described in Spain due to this species

[Subcutaneous infection by Curvularia pallescens in a lung transplant recipient: First report in Spain]. / Micosis cutánea por Curvularia pallescens en un paciente trasplantado pulmonar: primer caso descrito en España.

BACKGROUND: Curvularia is a filamentous dematiaceous fungus increasingly recognized as a pathogen in immunocompromised patients. The most common clinical entities associated with this fungus are allergic sinusitis, cutaneous infection and keratitis. In this article, a report on the first clinical case of Curvularia pallescens cutaneous infection in Spain and its treatment is described. CASE REPORT: A 68 year-old man with a history of lung transplantation presented to Dermatology Unit due to a skin lesion in the knee that had been evolving for 6 months. A skin biopsy was performed for its study. In the histopathological study, an intense and non-specific inflammatory reaction in the dermis was observed, and with Grocott stain and periodic acid Schiff abundant septate hyphae and spores were found in the dermis. The culture of the sample revealed a filamentous fungus whose microscopic examination allowed to identify the genus as Curvularia. Using MALDI-TOF mass spectrometry and molecular identification, the fungus was finally identified as Curvularia pallescens. The patient underwent surgical resection of the lesion and was treated with posaconazole, evolving favorably. CONCLUSIONS: The species of Curvularia should be considered causal agents of fungal skin infections in immunosuppressed patients. This clinical case, which showed good clinical response after surgical resection and treatment with posaconazole, is the first described in Spain due to this species.

Selective autophagy, lipophagy and mitophagy, in the Harderian gland along the oestrous cycle: a potential retrieval effect of melatonin.

Sexual dimorphism has been reported in many processes. However, sexual bias in favour of the use of males is very present in science. One of the main reasons is that the impact of hormones in diverse pathways and processes such as autophagy have not been properly addressed in vivo. The Harderian gland is a perfect model to study autophagic modulation as it exhibits important changes during the oestrous cycle. The aim of this study is to identify the main processes behind Harderian gland differences under oestrous cycle and their modulator. In the present study we show that redox-sensitive transcription factors have an essential role: NF-κB may activate SQSTM1/p62 in oestrus, promoting selective types of autophagy: mitophagy and lipophagy. Nrf2 activation in dioestrus, leads the retrieval phase and restoration of mitochondrial homeostasis. Melatonin's receptors show higher expression in dioestrus, leading to decreases in pro-inflammatory mediators and enhanced Nrf2 expression. Consequently, autophagy is blocked, and porphyrin release is reduced. All these results point to melatonin as one of the main modulators of the changes in autophagy during the oestrous cycle.

Diagnóstico de meningitis/encefalitis en UCI con sistema de PCR múltiple. ¿Es tiempo de cambio? / Meningitis/Encephalitis diagnosis in ICU using Multiplex PCR system: is it time of change?

OBJETIVO: Evaluar el impacto clínico de la PCR-múltiple FilmArray(R) panel Meningitis/Encefalitis en el diagnóstico de infecciones del sistema nervioso central y comparar los resultados obtenidos y el tiempo necesario hasta el diagnóstico con las técnicas microbiológicas convencionales. PACIENTES Y MÉTODOS: Estudio prospectivo observacional en una Unidad de Cuidados Intensivos (UCI) de adultos de un hospital de tercer nivel. Se realizó punción lumbar a todos los pacientes y en el LCR extraído se realizó FilmArray(R) panel de meningitis /encefalitis, estudio citoquímico, Gram y cultivos microbiológicos convencionales. RESULTADOS: 21 pacientes ingresados con sospecha de Meningitis/Encefalitis. Edad: mediana 58,4 años (RIQ 38,1-67,3), APACHE II: mediana 18 (RIQ 12-24). La mediana de estancia en UCI fue de 4 días (RIQ 2-6) y la hospitalaria de 17 días (RIQ 14-28). Mortalidad 14,3%. Se estableció un diagnóstico clínico final de Meningitis/Encefalitis en 16 pacientes, con diagnóstico etiológico en 12 casos (75%). La etiología más frecuente fue Streptococcus pneumoniae (8 casos). FilmArray(R) permitió diagnóstico etiológico en 3 casos con cultivo negativo y el resultado implicó cambios en el tratamiento antibiótico de 7 de los 16 pacientes (43,8%). Para la totalidad de pacientes, FilmArray(R) presentó una sensibilidad y especificidad del 100% y 90% respectivamente. La mediana de tiempo hasta la obtención del resultado de FilmArray(R) fue de 2,9 horas (RIQ 2,1-3,8) y del cultivo incluyendo antibiograma 45,1 horas (RIQ 38,9-58,7). CONCLUSIONES: FilmArray(R) panel Meningitis/Encefalitis realiza un diagnóstico etiológico más precoz que los cultivos convencionales, muestra una mayor sensibilidad y permite realizar un tratamiento antimicrobiano dirigido

OBJECTIVE: To evaluate the clinical impact of Meningitis/Encephalitis FilmArray(R) panel for the diagnosis of cerebral nervous system infection and to compare the results (including time for diagnosis) with those obtained by conventional microbiological techniques. PATIENTS AND METHODS: A prospective observational study in an Intensive Care Unit of adults from a tertiary hospital was carried out. Cerebrospinal fluid from all patients was taken by lumbar puncture and assessed by the meningitis/encephalitis FilmArray(R) panel ME, cytochemical study, Gram, and conventional microbiological cultures. RESULTS: A total of 21 patients admitted with suspicion of Meningitis/Encephalitis. Median age of patients was 58.4 years (RIQ 38.1-67.3), median APACHE II 18 (RIQ 12-24). Median stay in ICU and median hospital stay was 4 (RIQ 2-6) and 17 days (RIQ 14-28), respectively. The overall mortality was 14.3%. A final clinical diagnosis of meningitis or encephalitis was established in 16 patients, obtaining the etiological diagnosis in 12 of them (75%). The most frequent etiology was Streptococcus pneumoniae (8 cases). FilmArray(R) allowed etiological diagnosis in 3 cases in which the culture had been negative, and the results led to changes in the empirical antimicrobial therapy in 7 of 16 cases (43.8%). FilmArray(R) yielded a global sensitivity and specificity of 100% and 90%, respectively. The median time to obtain results from the latter and conventional culture (including antibiogram) was 2.9 hours (RIQ 2.1-3.8) and 45.1 hours (RIQ 38.9-58.7), respectively. CONCLUSIONS: The Meningitis/Encephalitis FilmArray(R) panel was able to establish the etiologic diagnosis faster than conventional methods. Also, it achieved a better sensitivity and led to prompt targeted antimicrobial therapy

Utilidad de la PCR-múltiple (FilmArray Blood Culture Identification) en otros líquidos biológicos. Detección de Streptococcus pyogenes en absceso cerebral y líquido sinovial / Utility of multiplex PCR (FilmArray Blood Culture Identification) in other biological liquids. Detection of Streptococcus pyogenes in brain abscess and synovial fluid

No disponible