The spermidine analogue GC7 (N1-guanyl-1,7-diamineoheptane) induces autophagy through a mechanism not involving the hypusination of eIF5A

The exogenous administration of spermidine promotes longevity in many model organisms. It has been proposed that this anti-age activity of spermidine is related to this polyamine's ability to promote autophagy. Since spermidine is the substrate for the eIF5A post-translational modification by hypusination, we asked ourselves whether mature eIF5A may represent the link between spermidine and autophagy induction. To test this hypothesis, we inhibited the conversion of native eIF5A by a pharmacological approach, using the N1-guanyl-1,7-diamineoheptane (GC7), a spermidine analogue which competitively and reversibly inhibits deoxyhypusine synthase (DHS). In addition, we also employed genetic approaches by ablating both the eIF5A protein itself and DHS, the rate limiting enzyme catalyzing the conversion of lysine to hypusine. Collectively the data presented in this study demonstrate that the mature eIF5A (hypusinated form) is not involved in the autophagic pathway and that the inhibitor of DHS, GC7, produces off-target effect(s) resulting in marked induction of basal autophagy. These data are relevant in light of the fact that GC7 is considered a potent and selective inhibitor of DHS and is a potential candidate drug for cancer, diabetes and HIV therapy

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

Cutaneous mucormycosis

Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic patients and individuals with immunosuppression. It is usually acquired by direct inoculation through trauma. The clinical presentation is nonspecific, but an indurated plaque that rapidly evolves to necrosis is a common finding. Diagnosis should be confirmed by demonstration of the etiological agent and new molecular diagnostic tools have recently been described. It is an invasive life-threatening disease and in order to improve survival, a prompt diagnosis and multidisciplinary management should be provided. The treatment of choice is amphotericin B, but new azoles, such as posaconazole and isavuconazole, must be considered. Keywords: Mucormycosis; Mucorales; Mucor; Zygomycosis; Rhizopu

A gene expression atlas for different kinds of stress in the mouse brain

Stressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”

The application of structural retinal biomarkers to evaluate the effect of intravitreal ranibizumab and dexamethasone intravitreal implant on treatment of diabetic macular edema

Background: The aim of this study was to compare the therapeutic effect of intravitreal treatment with ranibizumab and dexamethasone using specific swept-source optical coherence tomography retinal biomarkers in patients with diabetic macular edema (DME). Methods: 156 treatment-naïve patients with DME were divided in two groups: 75 patients received 3 monthly intravitreal injections of ranibizumab 0.5 mg (Lucentis®) (Group 1) and 81 patients received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®) (Group 2). Patients were evaluated at baseline (V1), at three months post-treatment in Group 1, and at two months post-treatment in Group 2 (V2). Best-corrected visual acuity (BCVA) and swept source-OCT were recorded at each interval. Changes between V1 and V2 were analyzed using the Wilcoxon test and differences between the two groups of treatment were assessed using the Mann-Whitney test. Multiple regression analysis was performed to evaluate the possible OCT biomarker (CRT, ICR, CT, SND, HRS) as predictive factors for final visual acuity improvement. Results: In both groups, BCVA improved (p-value < 0.0001), and a significant reduction in central retinal thickness, intra-retinal cysts, red dots, hyper-reflective spots (HRS), and serous detachment of neuro-epithelium (SDN) was observed. A superiority of dexamethasone over ranibizumab in reducing the SDN height (p-value = 0.03) and HRS (p-value = 0.01) was documented. Conclusions: Ranibizumab and dexamethasone are effective in the treatment of DME, as demonstrated by functional improvement and morphological biomarker change. DME associated with SDN and HRS represents a specific inflammatory pattern for which dexamethasone appears to be more effective

Detection and control of pregnancy hypertension using self-monitoring of blood pressure with automated telemonitoring: cost analyses of the BUMP Randomized Trials

BACKGROUND: Pregnancy hypertension continues to cause maternal and perinatal morbidity. Two linked UK randomized trials showed adding self-monitoring of blood pressure (SMBP) with automated telemonitoring to usual antenatal care did not result in earlier detection or better control of pregnancy hypertension. This article reports the trials’ integrated cost analyses. METHODS: Two cost analyses. SMBP with usual care was compared with usual care alone in pregnant individuals at risk of hypertension (BUMP 1 trial [Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension], n=2441) and with hypertension (BUMP 2 trial, n=850). Clinical notes review identified participant-level antenatal, intrapartum, and postnatal care and these were costed. Comparisons between trial arms used means and 95% CIs. Within BUMP 2, chronic and gestational hypertension cohorts were analyzed separately. Telemonitoring system costs were reported separately. RESULTS: In BUMP 1, mean (SE) total costs with SMBP and with usual care were £7200 (£323) and £7063 (£245), respectively, mean difference (95% CI), £151 (−£633 to £936). For the BUMP 2 chronic hypertension cohort, corresponding figures were £13 384 (£1230), £12 614 (£1081), mean difference £323 (−£2904 to £3549) and for the gestational hypertension cohort were £11 456 (£901), £11 145 (£959), mean difference £41 (−£2486 to £2567). The per-person cost of telemonitoring was £6 in BUMP 1 and £29 in BUMP 2. CONCLUSIONS: SMBP was not associated with changes in the cost of health care contacts for individuals at risk of, or with, pregnancy hypertension. This is reassuring as SMBP in pregnancy is widely prevalent, particularly because of the COVID-19 pandemic. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334149

APP educativa : financiamiento y dise?o de un colegio municipal de alta calidad

La realidad educativa peruana atraviesa por una crisis estructural. La falta de inversi?n p?blica en infraestructura educativa y la baja calidad de la ense?anza que se brinda en los colegios estatales son algunos de los factores causantes de esta situaci?n. El examen PISA 2013, que compara el nivel educativo de los estudiantes de diversos pa?ses, mostr? que el Per? estaba en el ?ltimo lugar de Am?rica Latina en los tres rubros de la prueba: matem?tica, ciencia y comprensi?n lectora. Asimismo, la inversi?n peruana en educaci?n es una de las m?s bajas en la regi?n. Seg?n datos del Banco Mundial, en el 2006 M?xico y Cuba invirtieron el 9.11% y el 5.05% de su PBI, respectivamente, mientras que el Per? destin? solo el 2.52% del PBI para este fin. Ante esta realidad, en el 2014 el Gobierno anunci? un incremento de 0.4% del PBI, m?s de mil millones de soles, para mejorar la remuneraci?n de los docentes y la creaci?n del Programa Nacional de Infraestructura Educativa, con S/. 2,500 millones de soles durante el 2015. Al respecto, la investigaci?n contenida en este libro plantea un procedimiento para viabilizar la creaci?n de una instituci?n educativa b?sica regular que brinde servicios educativos de alto nivel, a trav?s de una APP, a un precio accesible para la poblaci?n. Al lograr que el proyecto educativo sea atractivo para los inversionistas privados, se contribuir? a cubrir la demanda de colegios y a superar el desbalance que existe en los colegios privados entre, por un lado, los precios de la matr?cula y las pensiones y, por otro, la prestaci?n de servicios educativos. La investigaci?n, centrada en el desarrollo de un proyecto de estas caracter?sticas en un distrito lime?o, permitir? evaluar la factibilidad t?cnica, econ?mica y legal de la creaci?n de un colegio v?a una APP municipal, para demostrar la viabilidad y las potencialidades de esta iniciativa

Angiografía cerebral por tomografía en el diagnóstico de aneurismas cerebrales en pacientes con hemorragia subaracnoidea

ResumenAntecedentes: El 85% de los casos de hemorragia subaracnoidea no traumática (HSA) es secundaria a ruptura de un aneurisma áníracraneanoK pu ádeníáfácacáón ó localázacáón íemprana permáíen intervenir al paciente con miras a disminuir el vasoespasmo yresangrado, causales de la alta morbilidad y mortalidad que tiene esta entidad. Objetivo: Evaluar la exactitud diagnóstica de la angiografía íopográfáca EangáoTCF freníe a la angáografía por susíraccáón dágáíal (angioDSA). Metodología: En nueve pacientescon HSA atendidos en un servicio de radiología, se comparó la exactitud diagnóstica de la angáoTC freníe a angáoapAK ResultadosW ia capacádad de la angáoTC para dáagnosíácar epAíáene sensábáládad de 8MIMB EfCVRB SVITJVMIO BFI especáfácádad de SSISB EfCVRB4VISJ8PISBFI valor predictivo positivo de 80% (IC95% 69,7-90,2) y valor predictivo negaíávo de SSISB EfCVRB 4VISJ8PISBFK ConclusiónW ia angáoTC es un método de imágenes diagnósticas útil en nuestro medio para la detección de aneurismas cerebrales luego de HSA.[Pinilla CA, Mantilla JC, Vargas O, Higuera E, Rey JJ. Angiografía cerebral por tomografía en el diagnóstico de aneurismas cerebrales en pacientes con hemorragia subaracnoidea. MedUNAB 2006; 9:93-97].Palabras clave: Hemorragia subaracnoidea, Aneurisma cerebral, Angiografía cerebral por tomografía computarizada helicoidal, Angiografía cerebral por substracción digital

The new Checklist of the Italian Fauna: marine Mollusca.

The mollusc fauna of the Mediterranean Sea is still considered as the best-known marine mollusc fauna in the world. The previous modern checklists of marine Mollusca were produced by joint teams of amateurs and professionals. During the last years the Italian Society of Malacology (Società Italiana di Malacologia – S.I.M.) maintained an updated version of the Mediterranean checklist, that served as the backbone for the development of the new Italian checklist. According to the current version (updated on April 1st, 2021), 1,777 recognised species of marine molluscs are present in the Italian Economic Exclusive Zone, including also the Tyrrhenian coasts of Corsica and the continental shelf of the Maltese archipelago. The new checklist shows an increase of 17% of the species reported in the 1995 Checklist. This is largely (yet not solely) due to the new wave of studies based on Integrative Taxonomy approaches. A total of 135 species (7.6%) are strictly endemic to the Italian waters; 44 species (2.5%) are alien and correspond to the 28% of the Mediterranean alien marine molluscs. All eight extant molluscan classes are represented. The families represented in the Italian fauna are 307, an increase of 14.6% from the first checklist, partly due to new records and partly to new phylogenetic systematics. Compared with the whole Mediterranean malacofauna, the Italian component represents 71% in species and 61% in families, which makes it a very remarkable part of the Mediterranean fauna