Diagnosis and Treatment of Pituitary Apoplexy, A True Endocrine Emergency.

Pituitary apoplexy (PA) is a clinical syndrome resulting from a hemorrhagic infarction of the pituitary gland. It is characterized by the sudden onset of visual disturbances, nausea, vomiting, headache and occasionally, signs of meningeal irritation and an altered mental status. The exact pathogenesis of PA remains to be elucidated, although tumor overgrowth of its blood supply remains the most popular theory. Main risk factors for the development of PA include systemic, iatrogenic, and external factors as well as the presence of an underlying pituitary tumor. The diagnostic approach of PA includes both neuroimaging and evaluation of pituitary secretory function. PA is a potentially life-threatening condition which should be managed with hemodynamic stabilization, correction of electrolyte abnormalities and replacement of hormonal deficiencies. PA treatment should be individualized based on the severity of the clinical picture which may vary widely. Treatment options include conservative management with periodic follow-up or neurosurgical intervention, which should be decided by a multidisciplinary team. We conducted a systematic review of the literature to unveil the frequency of PA predisposing factors, clinical and biochemical presentations, management strategies and outcomes.

Uncovering physical activity trade-offs in transportation policy: A spatial agent-based model of Bogotá, Colombia.

BACKGROUND: Transportation policies can impact health outcomes while simultaneously promoting social equity and environmental sustainability. We developed an agent-based model (ABM) to simulate the impacts of fare subsidies and congestion taxes on commuter decision-making and travel patterns. We report effects on mode share, travel time and transport-related physical activity (PA), including the variability of effects by socioeconomic strata (SES), and the trade-offs that may need to be considered in the implementation of these policies in a context with high levels of necessity-based physical activity. METHODS: The ABM design was informed by local stakeholder engagement. The demographic and spatial characteristics of the in-silico city, and its residents, were informed by local surveys and empirical studies. We used ridership and travel time data from the 2019 Bogotá Household Travel Survey to calibrate and validate the model by SES. We then explored the impacts of fare subsidy and congestion tax policy scenarios. RESULTS: Our model reproduced commuting patterns observed in Bogotá, including substantial necessity-based walking for transportation. At the city-level, congestion taxes fractionally reduced car use, including among mid-to-high SES groups but not among low SES commuters. Neither travel times nor physical activity levels were impacted at the city level or by SES. Comparatively, fare subsidies promoted city-level public transportation (PT) ridership, particularly under a 'free-fare' scenario, largely through reductions in walking trips. 'Free fare' policies also led to a large reduction in very long walking times and an overall reduction in the commuting-based attainment of physical activity guidelines. Differential effects were observed by SES, with free fares promoting PT ridership primarily among low-and-middle SES groups. These shifts to PT reduced median walking times among all SES groups, particularly low-SES groups. Moreover, the proportion of low-to-mid SES commuters meeting weekly physical activity recommendations decreased under the 'freefare' policy, with no change observed among high-SES groups. CONCLUSIONS: Transport policies can differentially impact SES-level disparities in necessity-based walking and travel times. Understanding these impacts is critical in shaping transportation policies that balance the dual aims of reducing SES-level disparities in travel time (and time poverty) and the promotion of choice-based physical activity.

Mesenchymal stem cells induce an immunosuppressive microenvironment in pituitary tumors.

BACKGROUND: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSC) and immune cells among others. MSC have been isolated from different tumors and they favor tumor cell growth, however, their role in pituitary tumors (PT) remains unknown. Herein we report the presence of MSCs in 2 ACTH-secreting PT causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF) and 2 non tumoral pituitary glands (MS). METHODS: We have analyzed their transcriptomic profiles by RNAseq and compared MSC in terms of their immunosuppressive effects against lymphoid T cell and macrophage populations by means of co-cultures and flow cytometry. RESULTS: Our transcriptomic analysis revealed molecular differences between MSC derived from non-tumoral pituitaries and MSC derived from PT. Two distinct subpopulations of MSC, one displaying immunosuppressive properties and the other with increased pro-proliferative capabilities, regardless of their origin. MSC derived from ACTH- and nonfunctioning PT, but not those derived from non-tumoral glands significantly inhibited the proliferation of activated T cells, favored the generation of Tregs and promote M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony stimulating factor (M-CSF) and IL-10. Importantly, MSC derived from ACTH-PT showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors. CONCLUSION: This study demonstrates the presence of at least two MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSC may have important implications in PT growth.

Long-Term Monitoring of the Traditional Knowledge of Plant Species Used for Culinary Purposes in the Valencia Region, South-Eastern Spain.

The aim of this study is to inventory and study ethnobotanical knowledge of edible plants in the Valencian Community (Spain). In respect to culinary uses, 92 species of plant were reported to be edible, finding the following uses: 58 raw, 52 cooked, 16 fried, 7 dried, 21 in liquors and beverages, 25 in dessert and sweets, 11 as seasoning, 17 in pickles, and 10 to curdle milk. We prepared a database that includes genus, family, scientific, and vernacular names in Spanish and Catalan for each plant. We also created a classification of nine edible uses and plant parts used, being Asteraceae (n = 18), Brassicaceae (n = 7), Chenopodiaceae (n = 6), and Rosaceae (n = 6) the families most characterized for gastronomic purposes. The species with the most elevated cultural importance (CI) values were Foeniculum vulgare (CI = 1.389), Cynara scolymus (CI = 1.374), Papaver rhoeas (CI = 1.211), Beta vulgaris (CI = 1.167), and Juglans regia (CI = 1.155). The most used parts were the leaves (71), flowers (25), and branches (19), while the least used were roots (9) and seeds (8). Traditional knowledge of these plants helps to preserve traditional cuisine, promote the local economy and, in several species, encourage their cultivation.

Dynamic Model Validation and Simulation of Acetone-Toluene and Benzene-Toluene Systems for Industrial Volatile Organic Compound (VOC) Abatement.

Environmental impact mitigation is one of the grand challenges for industries globally. Volatile organic compounds (VOCs) are solvents whose emissions are potentially toxic to human health and ecosystems yet indispensable for the manufacturing of life-saving medicine. Adsorption with activated carbon columns is an established countermeasure for end-of-pipe emission control, whose efficiency, however, is impeded by irregular bed saturation due to the complex nature of its inputs. This work presents the application of a validated nonisothermal adsorption model to examine multicomponent trace mixtures of acetone-toluene and benzene-toluene on activated carbon. Our results indicate preferential adsorption of toluene over both acetone and benzene for all concentrations examined, which is in agreement with experimental data. Moreover, moderate temperature variations and pressure drops are revealed. Finally, Glueckauf's hodograph theory is employed for maximum outlet concentration prediction and compared with simulation results and experimental data, thus providing valuable insights into nonisothermal VOC abatement, which paves the way for industrial operation optimization.

Increases in regional brain volume across two native South American male populations.

Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46-83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity.

The molecular biology of sporadic acromegaly.

GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.

Efficacy of Omalizumab for the treatment of Bullous Pemphigoid. Spanish multicenter real-world experience.

BACKGROUND: Bullous Pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are elderly and associate multiple comorbidities. Topical and systemic corticosteroids are considered as the first-line treatment for BP and immunosuppressors are used as steroid-sparing treatments but both have side effects and contraindications which are even more common in this elderly population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease this side effects while achieving equal or better effectiveness response rates.Omalizumab is a monoclonal antibody that targets IgE that has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES AND METHODOLOGY: To assess the efficacy and security of Omalizumab for the treatment of BP, we carried out a multicenter, retrospective, observational study including patients diagnosed of BP who received omalizumab for at least 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment was measured and we evaluate the possible correlation with clinical response. We excluded patients treated with Omalizumab for less than 3 months as we consider this duration is insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment we used the percentage of BSA improvement. RESULTS: We included 36 patients. The vast majority associate multiple comorbidities and all patients had used other systemic therapies apart from corticoids before Omalizumab.83% experienced some kind of treatment response and 42% of all patient treated achieved complete response.We did not find any correlation between higher levels and a better response (p=0,1791).All patients tolerated Omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it obtained clinical response in most patients and nearly half of the cases achieving complete response. It showed no side effects which is crucial in elderly patients suffering from BP.

Short-term associations between fine particulate air pollution and cardiovascular and respiratory mortality in 337 cities in Latin America.

Ambient air pollution is a health concern in Latin America given its large urban population exposed to levels above recommended guidelines. Yet no studies have examined the mortality impact of air pollutants in the region across a wide range of cities. We assessed whether short-term levels of fine particulate matter (PM2.5) from modeled estimates, are associated with cardiovascular and respiratory mortality among adults in 337 cities from 9 Latin American countries. We compiled mortality, PM2.5 and temperature data for the period 2009-2015. For each city, we evaluated the association between monthly changes in PM2.5 and cardiovascular and respiratory mortality for sex and age subgroups using Poisson models, adjusted for seasonality, long-term trend, and temperature. To accommodate possibly different associations of mortality with PM2.5 by age, we included interaction terms between changes in PM2.5 and age in the models. We combined the city-specific estimates using a random effects meta-regression to obtain mortality relative risks for each sex and age group. We analyzed 3,026,861 and 1,222,623 cardiovascular and respiratory deaths, respectively, from a study population that represents 41 % of the total population of Latin America. We observed that a 10 µg/m3 increase in monthly PM2.5 is associated with an increase of 1.3 % (95 % confidence interval [CI], 0.4 to 2.2) in cardiovascular mortality and a 0.9 % increase (95 % CI -0.6 to 2.4) in respiratory mortality. Increases in mortality risk ranged between -0.5 % to 3.0 % across 6 sex-age groups, were larger in men, and demonstrated stronger associations with cardiovascular mortality as age increased. Socioeconomic, environmental and health contexts in Latin America are different than those present in higher income cities from which most evidence on air pollution impacts is drawn. Locally generated evidence constitutes a powerful instrument to engage civil society and help drive actions to mitigate and control ambient air pollution.

Water and mosquitoes as key components of the infective cycle of Francisella tularensis in Europe: a review.

Francisella tularensis is the pathogen of tularemia, a zoonotic disease that have a broad range of hosts. Its epidemiology is related to aquatic environments, particularly in the subspecies holarctica. In this review, we explore the role of water and mosquitoes in the epidemiology of Francisella in Europe. F. tularensis epidemiology has been linked to natural waters, where its persistence has been associated with biofilm and amebas. In Sweden and Finland, the European countries where most human cases have been reported, mosquito bites are a main route of transmission. F. tularensis is present in other European countries, but to date positive mosquitoes have not been found. Biofilm and amebas are potential sources of Francisella for mosquito larvae, however, mosquito vector capacity has not been demonstrated experimentally, with the need to be studied using local species to uncover a potential transmission adaptation. Transstadial, for persistence through life stages, and mechanical transmission, suggesting contaminated media as a source for infection, have been studied experimentally for mosquitoes, but their natural occurrence needs to be evaluated. It is important to clear up the role of different local mosquito species in the epidemiology of F. tularensis and their importance in all areas where tularemia is present.

Susceptibility of Tetranychus urticae to the Alkaloidal Extract of Zanthoxylum schreberi Bark: Phenotypic and Biochemical Insights for Biotechnological Exploitation.

Tetranychus urticae Koch, a phytophagous mite, is one of the most significant crop pests globally. The primary method employed for controlling T. urticae involves chemical means, utilizing synthesized products, posing the risk of developing resistance. The urgency for novel strategies integrated into pest management programs to combat this mite is becoming increasingly imperative. Botanical pesticides emerge as a promising tool to forestall arthropod resistance. Among these, extracts from Rutaceae plants, abundant in bioactive specialized metabolites, have demonstrated potential as insecticides and miticides. In this study, various concentrations of alkaloidal extracts sourced from the bark of Zanthoxylum schreberi J.F.Gmel. (Rutaceae) were evaluated against T. urticae adult females. Furthermore, the extract's combination with three distinct commercial acaricides (i.e., chlorfenapyr, cyflumetofen, and abamectin) was also assessed for this mite. Chemical characterization of the extract via LC-MS allowed for the annotation of various compounds related to ten benzylisoquinoline-derived alkaloids. The extract, both alone and in combination with commercial insecticides, yielded varying responses, inducing over 40% mortality at 2% w/w, demonstrating a 90% repellency rate at the same concentration, and exerting a moderate impact on fecundity. These treatments extended beyond phenotypic responses, delving into the biochemical effects on treated T. urticae females through an exploration of the impact on four enzymes, i.e., acetylcholinesterase (AChE), glutathione S-transferase (GST), esterases (GE), and P450-like monooxygenases (PMO). Employing consensus docking studies and in vitro enzymatic evaluations, it was discovered that the Z. schreberi-derived extract and its constituents significantly affected two key enzymes, AChE and GST (IC50 < 6 µM), which were associated with the phenotypic observations of T. urticae females. The evaluation of alkaloid-rich botanicals showcases promising potential as a relevant biotechnological strategy in addressing mite-related concerns, offering a pathway toward innovative and sustainable pest management solutions.

Semi-automated approaches for interrogating spatial heterogeneity of tissue samples.

Tissues are spatially orchestrated ecosystems composed of heterogeneous cell populations and non-cellular elements. Tissue components' interactions shape the biological processes that govern homeostasis and disease, thus comprehensive insights into tissues' composition are crucial for understanding their biology. Recently, advancements in the spatial biology field enabled the in-depth analyses of tissue architecture at single-cell resolution, while preserving the structural context. The increasing number of biomarkers analyzed, together with whole tissue imaging, generate datasets approaching several hundreds of gigabytes in size, which are rich sources of valuable knowledge but require investments in infrastructure and resources for extracting quantitative information. The analysis of multiplex whole-tissue images requires extensive training and experience in data analysis. Here, we showcase how a set of open-source tools can allow semi-automated image data extraction to study the spatial composition of tissues with a focus on tumor microenvironment (TME). With the use of Lunaphore COMET platform, we interrogated lung cancer specimens where we examined the expression of 20 biomarkers. Subsequently, the tissue composition was interrogated using an in-house optimized nuclei detection algorithm followed by a newly developed image artifact exclusion approach. Thereafter, the data was processed using several publicly available tools, highlighting the compatibility of COMET-derived data with currently available image analysis frameworks. In summary, we showcased an innovative semi-automated workflow that highlights the ease of adoption of multiplex imaging to explore TME composition at single-cell resolution using a simple slide in, data out approach. Our workflow is easily transferrable to various cohorts of specimens to provide a toolset for spatial cellular dissection of the tissue composition.

Resilience as a measure of preparedness for pandemic influenza outbreaks.

The global crisis generated by COVID-19 has heightened awareness of pandemic outbreaks. From a public health preparedness standpoint, it is essential to assess the impact of a pandemic and also the resilience of the affected communities, which is the ability to withstand and recover quickly after a pandemic outbreak. The infection attack rate has been the common metric to assess community response to a pandemic outbreak, while it focuses on the number of infected it does not capture other dimensions such as the recovery time. The aim of this research is to develop community resilience measures and demonstrate their estimation using a simulated pandemic outbreak in a region in the USA. Three scenarios are analysed with different combinations of virus transmissibility rates and non-pharmaceutical interventions. I The inclusion of the resilience framework in the pandemics outbreak analysis will enable decision makers to capture the multi dimensional nature of community response.

Emotional Coping Strategies for Informal Caregivers of Hospitalized Patients: A Study of Distress and Overload.

Purpose: Informal caregivers constitute a vulnerable population group that has forsaken their activities and life projects with the sole purpose of caring for a dependent individual without receiving any form of compensation in return. Emotionally, this population has been neglected by both the state and family members, exacerbating distress levels among them. The objective is to analyze the impact of emotional coping strategies on the experiences of distress and emotional burden among adult informal caregivers tending to hospitalized individuals. Sample and Methods: The role of emotional coping strategies in caregiver burden and psychological distress was examined in 460 informal adult caregivers from Guayaquil, Ecuador, who participated in an online survey. The instruments used included the Depression, Anxiety, and Stress Scale (DASS 21), the Zarit Burden Inventory (ZBI), and the Emotional Coping Questionnaire (Cuestionario de Afrontamiento Emocional). The analysis involved a multiple regression to iteratively select variables, aiming to build a simpler and more explanatory model. Results: Employing multiple regression analysis with a stepwise model selection procedure, it was found that 16.5% of the variance in depression, 19.5% of the variance in anxiety, 19.8% of the variance in stress, and 32% of the variance in burden were predicted by specific coping strategies. Additionally, the impact of burden was estimated by the participants' gender, with greater burden observed among males due to societal role expectations. Conclusion: This study underscores the importance of emotional coping in the experience of informal caregivers and suggests that psychological interventions should focus on developing adaptive strategies to manage the stress and emotional burden associated with caregiving.

Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria.

Background: Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. Methods: We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Results: Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. Conclusion: This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.

Additive manufacturing of Ni-free Ti-based shape memory alloys: A review.

Ni-free Ti-based Shape Memory Alloys composed of non-toxic elements have been studied as promising candidates for biomedical applications. However, high tool wear makes them complex to manufacture with conventional techniques. In this way, Additive Manufacturing technologies allow to fabricate complex three-dimensional structures overcoming their poor workability. Control of composition, porosity, microstructure, texture and processing are the key challenges for developing Ni-free Ti-based Shape Memory Alloys. This article reviews various studies conducted on the Additive Manufacturing of Ni-free Ti-based shape memory alloys, including their processing, microstructures and properties.

Unveiling the Inner Structure of Micrometric Hollow Polymeric Fibers Using Synchrotron X-Ray Nanotomography.

In this study, a novel application of synchrotron X-ray nanotomography based on high-resolution full-field transmission X-ray microscopy for characterizing the structure and morphology of micrometric hollow polymeric fibers is presented. By employing postimage analysis using an open-source software such as Tomviz and ImageJ, various key parameters in fiber morphology, including diameter, wall thickness, wall thickness distribution, pore size, porosity, and surface roughness, were assessed. Electrospun polycaprolactone fibers with micrometric diameters and submicrometric features with induced porosity via gas dissolution foaming were used to this aim. The acquired synchrotron X-ray nanotomography data were analyzed using two approaches: 3D tomographic reconstruction and 2D radiographic projection-based analysis. The results of the combination of both approaches demonstrate unique capabilities of this technique, not achievable by other available techniques, allowing for a full characterization of the internal and external morphology and structure of the fibers as well as to obtain valuable qualitative insights into the overall fiber structure.