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Immune checkpoint inhibitor drugs can trigger autoimmune endocrine reactions as a known side effect. Several cases of immunotherapy-induced autoimmune endocrinopathies have been described, but multiple sequential endocrine toxicities are a rare occurrence. A 39-year-old patient with metastatic melanoma started adjuvant therapy with pembrolizumab. One month later he presented with asymptomatic thyrotoxicosis and, within several weeks, overt hypothyroidism, for which he started levothyroxine therapy. Subsequently the patient developed central adrenal insufficiency due to probable hypophysitis, and steroid replacement therapy was started. Pembrolizumab therapy was then discontinued. After a few months, a full recovery of pituitary function was observed, but primary adrenal insufficiency occurred, requiring additional fludrocortisone therapy. The described clinical case is a very uncommon case of triple endocrinological toxicity from immunotherapy. The clinical and biochemical manifestations of immunotherapy-induced endocrinopathies can be variable and atypical; therefore, it is necessary to pay special attention to any clue of hormonal dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3–36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [−0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [−0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [−0.14 to 0.24], p = 0.61), and whole body (sMD: −0.12, 95% CI [−0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: −0.58, 95% CI [−0.77 to −0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

This essay focuses on the disavowed histories of Italy's fascist past with a specific focus on how select historical disavowals reverberate in the present through the law of restricted citizenship, policies governing the lives of migrants, and recent pro-natal campaigns. I take as the occasion for my discussion, the 2017 exhibit at the "Museo della Shoah" in Rome, entitled "The Enemy Race: Nazi and Italian Fascist Propaganda." Through representations of the child during Mussolini's reign, the exhibit represents Mussolini's investment in the Italian child, conceived of as Catholic, Aryan, and born on Italian soil. His regime aimed to cultivate a future generation that would purify the nation through physical vitality, a belief in racial elitism, and loyalty to the nation state, while casting Jewish and "non-Italian" children as enemy subjects. I argue that the pedagogical impulse of the "Museo della Shoah" aims, not only to represent life histories that have been imperfectly erased from post-war memory, but also to recognize such a project as an interminable process of reflection that unfolds in a country that continues to suffer under the weight of its disavowed colonial and anti-Semitic history.

Abstract Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p

The Pitangui Synclinorium is located in the northwestern portion of the Quadrilátero Ferrífero mineral province, São Francisco Craton, in southeast Brazil. It corresponds to a NW-SE-trending synformal structure composed of an Archean greenstone belt sequence, which is covered by Paleoproterozoic metasedimentary rocks to Neoproterozoic sedimentary rocks, and surrounded by Archean granite-gneiss complexes. This study reports the first detailed 1:25.000 scale geological mapping in the Pitangui Synclinorium and provides cartographic, stratigraphic and petrographic improvements, allowing the formalization of its lithostratigraphic units and unraveling the sedimentary and volcanic depositional environments. The Archean Pitangui greenstone belt occurs in most parts of the homonymous synclinorium, and is subdivided into the Pitangui Group and the Antimes Formation. The metavolcano-sedimentary sequence of the Pitangui Group comprises basal mafic/ultramafic metavolcanic rocks with subordinate felsic/intermediate metavolcanic and metavolcaniclastic rocks of the Rio Pará Formation, suggesting a bimodal volcanism. It is followed by volcanogenic and chemical metasedimentary rocks of the Rio São João Formation, and pelitic to sandy metasedimentary rocks of the Onça do Pitangui Formation deposited in subaqueous environments mainly corresponding to submarine fan systems. The occurrence of clastic rocks increases towards the top of the sequence. The Antimes Formation comprises quartzites and metaconglomerates related to fluvial and fan delta depositional environments. The Pitangui greenstone belt is overlapped, in the central and northwest regions of the study area, by the Fazenda Tapera Formation, a Paleoproterozoic siliciclastic package containing arkosic metasandstones, metagreywackes and metarhythmites deposited in a shallow marine environment. Subordinated tuff layers occur as ash/fall deposits from distal volcanism. Neoproterozoic clastic-chemical sedimentary rocks of the Bambuí Group cover the northern portions of the synclinorium, and are mainly composed of diamictites, limestones, marls and rhythmites from the Carrancas (lacustrine or restricted marine), Sete Lagoas (shallow marine) and Serra de Santa Helena formations (deep water grading to prodelta and delta front).

Summary: Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.

Objective: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on coronavirus disease-19 (COVID-19)-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact. Study design and methods: 117 patients (81 males, 64 ± 13 years) hospitalized for COVID-19 between 1 March and 30 April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurement s, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death. Results: At admission, 26.5% patients had hyponatremia, and 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders ('mixed dysnatremia'). Lower sodium levels at admission were correlated with higher C reactive protein (CRP) (P = 0.039) and serum lactate levels (P = 0.019), but not interleukin-6 (IL-6). Hypernatremia and a wider sodium variability were associated with maximum required ventilation, need for ICU assistance and duration of the hospitalization. Mean estimated time to Intensive Care Unit (ICU) admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (log-ra nk test P = 0.032). Conclusions: Sodium alterations frequently affect hospitalized COVID-19 pati ents. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and the need for intens ive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients’ prognosis.

The flower market is characterized by being both eager for novelties and highly competitive. The exploration of native species with ornamental potential represents a remarkable area of research, since it entails the introduction and development of novel promising ornamental crops. The genus Glandularia, widely distributed in Argentina, holds an enormous ornamental potential, due to the variety of colors of its inflorescences (red, violet, white, rose and lily), and extended flowering period. There is little information on tissue culture of Glandularia, thus highlighting the relevance of this research. In this work, the conditions for in vitro multiplication of G. peruviana were optimized. It was concluded that WPM supplemented with TDZ, in concentrations ranging from 1.1 to 9.0 μM, was the most adequate treatment, rendering a multiplication rate of approximately 10 de novo shoots per explant. This paper presents a protocol for the in vitro propagation of this species and introduces interesting prospects in the application of biotechnological tools to breed Glandularia.

Achyrocline satureioides (Lam.) DC. es un arbusto originario de América del Sur. Es muy utilizada en la medicina popular, además, por su color y arquitectura, tiene potencial ornamental como planta para decorar parques o jardines. Como la mayoría de las plantas nativas aromáticas-medicinales, sus poblaciones sufren una fuerte erosión genética debido a acciones antrópicas, como la sobreexplotación y el avance de la frontera agrícola o la urbana. Una forma de ayudar a evitar la extinción de poblaciones es comenzar con el proceso de domesticación y mejora de estas especies, para cambiar el paradigma extractivista por el productivo. La obtención de nuevas variedades poliploides es una forma rápida de generar individuos con órganos más grandes y mayor resistencia al estrés, entre otras propiedades que caracterizan a la poliploidía, para utilizarlos directamente o como insumo para un programa de mejoramiento. El objetivo del presente trabajo es obtener y caracterizar individuos poliploides de A. satureioides aplicando colchicina, in vivo, sobre sus yemas laterales.