A real-world study of quality of life following treatment with xylometazoline hydrochloride in individuals with common cold.

BACKGROUND: The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. OBJECTIVE: To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. DESIGN: This was a decentralized, longitudinal, open-label study. METHODS: The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. RESULTS: Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. CONCLUSION: This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].

Impact of xylometazoline hydrochloride 0.1% on quality of life in people with blocked nose associated with the common coldThe common cold is a widespread, mild respiratory illness for which a hallmark symptom is a blocked or stuffy nose, which makes breathing and sleeping difficult. This study focused on how a nasal spray called Otrivin (containing xylometazoline hydrochloride 0.1%) impacts the quality of life (QoL) of people suffering from nasal congestion due to the common cold.Participants answered a questionnaire called the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), which helped understand how people experience respiratory symptoms and how different aspects of QoL were impacted. Participants also responded to eight additional QoL questions not covered in the WURSS-21.The results showed that from the first day of using the nasal spray, participants experienced significant relief from the blocked nose symptom and reported an overall improvement in their QoL and well-being, such as in sleep quality, energy levels, senses, and physical and social activities.In conclusion, this real-world study demonstrated that using xylometazoline hydrochloride 0.1% nasal spray during the common cold can significantly improve nasal congestion and various aspects of a person's daily life. These findings provide valuable evidence for using this nasal spray to relieve symptoms and enhance the overall well-being of individuals with the common cold.

Safety and Performance of Narhinel 0.9% Sodium Chloride Monodose and Otrisal 0.74% Sodium Chloride Monodose Nasal Saline Solutions and Nasal Aspirators in Real-World Settings: Postmarket Clinical Follow-up Study Results.

Background: Blocked or stuffy nose is a common and bothersome symptom of colds, particularly for young children who are unable to clear their noses on their own. Nasal saline solutions and nasal aspirators are designed to gently cleanse and remove blocking nasal secretions. Objective: To assess the safety and performance of 2 monodose isotonic saline solutions (Narhinel 0.9% and Otrisal 0.74% sodium chloride; GSK Consumer Healthcare SARL, a Haleon company, Nyon, Switzerland) and 2 nasal aspirators with disposable hard- and soft-nozzle refills used as a standalone or combination treatment. Methods: We conducted 2 observational, online questionnaire-based, postmarket clinical follow-up studies in Europeans who had used any of the devices ≥1 time in the past 6 months. Coprimary objectives were to confirm the safety and performance of the saline solutions (Narhinel and Otrisal, Study 1) and nasal aspirators (with hard- and soft-nozzle refills, Study 2). Safety was assessed via the proportion of patients reporting adverse events and/or device malfunctions while using the devices within the previous 6 months, and performance was assessed by satisfaction rated on a 5-point scale, with "satisfied" and "very satisfied" being the highest performance ratings. Results: A total of 1136 (Study 1) and 1237 (Study 2) questionnaires were initiated by volunteer participants. Less than 2% of participants reported adverse events for any evaluated product in the previous 6 months. Most participants were "satisfied" or "very satisfied" with the devices for their intended use, with 78% to 91% of participants in the Narhinel arm, 73%-94% in the Otrisal arm, 71% to 95% in the soft-nozzle arm, and 71% to 80% in the hard-nozzle arm giving these ratings. Conclusions: These data support the safety and performance of 2 monodose saline solutions (Narhinel and Otrisal) for nasal cleansing, nasal moisturization, and/or loosening nasal secretions, and of nasal aspirators (with hard- and soft-nozzle refills) for clearing a blocked nose and removing nasal secretions.

Cultivation of carbohydrate-rich microalgae with great settling properties using cooling tower wastewater.

Wastewater treatment and simultaneous production of value-added products with microalgae represent a sustainable alternative. Industrial wastewater, characterized by high C/N molar ratios, can naturally improve the carbohydrate content in microalgae without the need for any external source of carbon while degrading the organic matter, macro-nutrients, and micro-nutrients. This study aimed to understand the treatment, reuse, and valorization mechanisms of real cooling tower wastewater (CWW) from a cement-processing industry mixed with domestic wastewater (DW) to produce microalgal biomass with potential for synthesis of biofuels or other value-added products. For this purpose, three photobioreactors with different hydraulic retention times (HRT) were inoculated simultaneously using the CWW-DW mixture. Macro- and micro-nutrient consumption and accumulation, organic matter removal, algae growth, and carbohydrate content were monitored for 55 days. High COD (> 80%) and macronutrient removals (> 80% of N and P) were achieved in all the photoreactors, with heavy metals below the limits established by local standards. The best results showed maximum algal growth of 1.02 g SSV L-1 and 54% carbohydrate accumulation with a C/N ratio of 31.24 mol mol-1. Additionally, the harvested biomass presented a high Ca and Si content, ranging from 11 to 26% and 2 to 4%, respectively. Remarkably, big flocs were produced during microalgae growth, which enhanced natural settling for easy biomass harvesting. Overall, this process represents a sustainable alternative for CWW treatment and valorization, as well as a green tool for generating carbohydrate-rich biomass with the potential to produce biofuels and fertilizers.

Surface, satellite ozone variations in Northern South America during low anthropogenic emission conditions: a machine learning approach.

2020 presented the ideal conditions for studying the air quality response to several emission reductions due to the COVID-19 lockdowns. Numerous studies found that the tropospheric ozone increased even in lockdown conditions, but its reasons are not entirely understood. This research aims to better understand the ozone variations in Northern South America. Satellite and reanalysis data were used to analyze regional ozone variations. An analysis of two of the most polluted Colombian cities was performed by quantifying the changes of ozone and its precursors and by doing a machine learning decomposition to disentangle the contributions that precursors and meteorology made to form O3. The results indicated that regional ozone increased in most areas, especially where wildfires are present. Meteorology is associated with favorable conditions to promote wildfires in Colombia and Venezuela. Regarding the local analysis, the machine learning ensemble shows that the decreased titration process associated with the NO plummeting owing to mobility reduction is the main contributor to the O3 increase (≈50%). These tools lead to conclude that (i) the increase in O3 produced by the reduction of the titration process that would be associated with an improvement in mobile sources technology has to be considered in the new air quality policies, (ii) a boost in international cooperation is essential to control wildfires since an event that occurs in one country can affect others and (iii) a machine learning decomposition approach coupled with sensitivity experiments can help us explain and understand the physicochemical mechanism that drives ozone formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s11869-023-01303-6.

Avoidable mortality due to long-term exposure to PM2.5 in Colombia 2014-2019.

OBJECTIVE: To compare estimates of spatiotemporal variations of surface PM2.5 concentrations in Colombia from 2014 to 2019 derived from two global air quality models, as well as to quantify the avoidable deaths attributable to the long-term exposure to concentrations above the current and projected Colombian standard for PM2.5 annual mean at municipality level. METHODS: We retrieved PM2.5 concentrations at the surface level from the ACAG and CAMSRA global air quality models for all 1,122 municipalities, and compare 28 of them with available concentrations from monitor stations. Annual mortality data 2014-2019 by municipality of residence and pooled effect measures for total, natural and specific causes of mortality were used to calculate the number of annual avoidable deaths and years of potential life lost (YPLL) related to the excess of PM2.5 concentration over the current mean annual national standard of 25 µg/m3 and projected standard of 15 µg/m3. RESULTS: Compared to surface data from 28 municipalities with monitoring stations in 2019, ACAG and CAMSRA models under or overestimated annual mean PM2.5 concentrations. Estimations from ACAG model had a mean bias 1,7 µg/m3 compared to a mean bias of 4,7 µg/m3 from CAMSRA model. Using ACAG model, estimations of total nationally attributable deaths to PM2.5 exposure over 25 and 15 µg/m3 were 142 and 34,341, respectively. Cardiopulmonary diseases accounted for most of the attributable deaths due to PM2.5 excess of exposure (38%). Estimates of YPLL due to all-cause mortality for exceeding the national standard of 25 µg/m3 were 2,381 years. CONCLUSION: Comparison of two global air quality models for estimating surface PM2.5 concentrations during 2014-2019 at municipality scale in Colombia showed important differences. Avoidable deaths estimations represent the total number of deaths that could be avoided if the current and projected national standard for PM2.5 annual mean have been met, and show the health-benefit of the implementation of more restrictive air quality standards.

Cultivating photosynthetic microorganisms in cooling water waste and urban effluents as a strategy of water regeneration and valorization.

Contaminants from cooling water waste (CWW) generated by industries represent an environmental hazard if discharged into aquatic bodies and soil without treatment. Most treatment strategies are energy-demanding and costly; hence, low-cost and sustainable treatment alternative technologies are needed. The present study proposed cyanobacteria culture as a low-cost biological method to treat cooling water waste (CWW) while simultaneously producing carbohydrates. For this purpose, CWW from a cooling tower was evaluated in different dilutions with domestic wastewater (DW) (DW25% -CWW75%, DW50% -CWW50%, DW25% -CWW75%, DW100%, and CWW100%) (v/v). The CWW provided a high content of inorganic carbon and low content of N and P, which resulted in a high C/N ratio promoting a fast carbohydrate accumulation but low biomass production. In contrast, cultures with higher DW concentrations achieved similar results in 14 days. The best results were obtained with DW25% -CWW75%, achieving up to 52 ± 18% carbohydrate content on day 8, with the highest biomass concentration of 1.7 ± 0.12 g L-1 on day 14. This culture removed >94% of TAN, N-NO3- and P-PO43-, and 84 ± 10.82% of COD. This strategy could be a promising approach to treating CWW and DW from the same industry and producing value-added products and bioenergy.

Silvopastoral systems and remnant forests enhance carbon storage in livestock-dominated landscapes in Mexico.

A large area of the terrestrial land surface is used for livestock grazing. Trees on grazing lands provide and can enhance multiple ecosystem services such as provisioning, cultural and regulating, that include carbon sequestration. In this study, we assessed the above- and belowground carbon stocks across six different land-uses in livestock-dominated landscapes of Mexico. We measured tree biomass and soil organic carbon (SOC) stocks in fodder banks, live fences, pasturelands with dispersed trees, secondary forests, and primary forests from three different geographical regions and compared them with conventional open pasturelands respectively. We also calculated tree diversity indices for each land-use and their similarity with native primary forests. The aboveground woody biomass stocks differed significantly between land-uses and followed the gradient from less diverse conventional open pasturelands to silvopastoral systems and ecologically complex primary forests. The SOC stocks showed a differential response to the land-use gradient dependent on the study region. Multivariate analyses showed that woody biomass, fine root biomass, and SOC concentrations were positively related, while land-use history and soil bulk density showed an inverse relationship to these variables. Silvopastoral systems and forest remnants stored 27-163% more carbon compared to open pasturelands. Our results demonstrate the importance of promoting appropriate silvopastoral systems and conserving forest remnants within livestock-dominated landscapes as a land-based carbon mitigation strategy. Furthermore, our findings also have important implications to help better manage livestock-dominated landscapes and minimize pressures on natural protected areas and biodiversity in the hotspots of deforestation for grassland expansion.

Spatio-temporal analysis of PM2.5 and policies in Northwestern South America.

This paper analyzes the spatio-temporal variations, and exceedances of the PM2.5 concentrations in Northwestern South America at different scales to assess the implemented policies and identify the involved phenomena. Through reanalysis and ground-based data, we found that high PM2.5 levels in most cities of the region are caused by wildfires and local emissions, including the capital cities of Venezuela, Ecuador, Colombia, and Panamá. In-situ measurements suggest that the majority of the cities comply with the local but not with the WHO guidelines, indicating that local annual limits should be more restrictive. Two peaks in the daily variations of PM2.5 (related to vehicle emissions) and also a steeper decrease around noon (associated with an increase in wind speed and in the boundary layer height) were identified. The trend-analysis shows that Bogotá and Medellín have a decreasing PM2.5 annual-trend (between -0.8µgm-3 and -1.7µgm-3) that corresponds to effective policies. In contrast, Cali has a positive annual-trend (0.8µgm-3) most likely because of Short-Range Transport produced by a northerly-flow from a highly polluted neighboring city, which also affects Cali's PM2.5 diurnal cycle, or by local-dynamics. The exceedances show that the policies are working on an annual but not at a daily time-scale. These results serve as a first input for additional studies, with the aim of gaining a better understanding of the contaminant before adapting current policies or implementing new policies and measures that need to include a joint international, regional, and inter-city efforts regarding pollution transport.

Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatiroidismo primario con imágenes negativas / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatireoidismo primário com imagens negativas

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient's case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia's main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

Introducción. La hipercalcemia hipocalciúrica familiar es un trastorno hereditario poco común del metabolismo del calcio en donde una alteración del punto de ajuste de la secreción de hormona paratiroidea ocasiona hipercalcemia con hipocalciuria relativa. Algunos datos sugieren que su prevalencia es de alrededor de 74.1 por 100,000 habitantes. Los pacientes muchas veces son asintomáticos. Sin embargo, pueden desarrollar síntomas leves y un adenoma paratiroideo hiperactivo, que representa su principal diagnóstico diferencial. El objetivo fue describir el caso de un paciente y resaltar la importancia de la sospecha y el diagnóstico clínico para evitar exploraciones quirúrgicas cervicales innecesarias en búsqueda de adenomas paratiroideos. Reporte de caso. Este es el caso de un hombre de 40 años con un perfil bioquímico compatible con hiperparatiroidismo primario, con imágenes anatómicas y funcionales negativas para adenoma, además de una relación de depuración de calcio/creatinina menor a 0.001, con consideración de hipercalcemia hipocalciúrica familiar. Los estudios genéticos evidencian una mutación en el gen del receptor sensor del calcio y confirman el diagnóstico. Discusión. El principal diagnóstico diferencial de la hipercalcemia hipocalciúrica familiar es un adenoma paratiroideo hiperactivo. En ambos casos, es posible que no haya síntomas o que estos sean leves; el calcio sérico excede al límite superior, y la paratohormona es mayor de 25pg/ml. Se debe usar la relación de depuración de calcio/creatinina para diferenciar entre estas patologías y evitar exploraciones quirúrgicas cervicales innecesarias. Aparte de la falta de información sobre este tema, la evidencia apoya el uso de calciomiméticos para tratar la hipercalcemia sintomática. Conclusiones. Los pacientes con hipercalcemia leve, con valores de hormona paratiroidea mayores de 25pg/ml y con una relación de depuración de calcio/creatinina menor de 0.001, o los pacientes con hiperparatiroidismo primario con imágenes negativas, no deben ser sometidos a exploraciones quirúrgicas cervicales. En estos casos, la hipercalcemia hipocalciúrica familiar representa un diagnóstico confiable; se puede administrar Cinacalcet en casos de hipercalcemia sintomática.

Introdução. A hipercalcemia hipocalciúrica familiar é um distúrbio hereditário raro do metabolismo do cálcio, no qual uma alteração no ponto de ajuste da secreção do hormônio da paratireóide causa hipercalcemia com hipocalciúria relativa. Alguns dados sugerem que sua prevalência gira em torno de 74.1 por 100,000 habitantes. Os pacientes geralmente são assintomáticos. No entanto, eles podem desenvolver sintomas leves e um adenoma de paratireoide hiperativo, que representa seu principal diagnóstico diferencial. O objetivo foi descrever o caso de um paciente e destacar a importância da suspeita clínica e do diagnóstico para evitar exploração cirúrgica cervical desnecessária em busca de adenomas de paratireoide. Relato de caso. É o caso de um homem de 40 anos com perfil bioquímico compatível com hiperparatireoidismo primário, com imagens anatômicas e funcionais negativas para adenoma, além de relação depuração de cálcio/creatinina menor que 0.001, considerando hipercalcemia hipocalciúrica familiar. Estudos genéticos revelam uma mutação no gene receptor da sensibilidade ao cálcio e confirmam o diagnóstico. Discussão. O principal diagnóstico diferencial da hipercalcemia hipocalciúrica familiar é um adenoma de paratireoide hiperativo. Em ambos os casos, os sintomas podem estar ausentes ou leves; o cálcio sérico excede o limite superior e o hormônio da paratireóide é superior a 25pg/ml. A relação depuração de cálcio/creatinina deve ser usada para diferenciar entre essas patologias e evitar exploração cirúrgica cervical desnecessária. Além da falta de informações sobre esta questão, as evidências apoiam o uso de calcimiméticos para tratar a hipercalcemia sintomática. Conclusões. Pacientes com hipercalcemia leve, com valores de hormônio da paratireóide maiores que 25pg/ml e uma relação de depuração de cálcio/creatinina menor que 0.001, ou pacientes com hiperparatireoidismo primário com imagens negativas, não devem ser submetidos a exploração cirúrgica cervical. Nesses casos, a hipercalcemia hipocalciúrica familiar representa um diagnóstico confiável; Cinacalcet pode ser administrado em casos de hipercalcemia sintomática.

FKBP51 and the molecular chaperoning of metabolism.

The molecular chaperone FK506-binding protein 51 (FKBP51) is gaining attention as a meaningful biomarker of metabolic dysfunction. This review examines the emerging contributions of FKBP51 in adipogenesis and lipid metabolism, myogenesis and protein catabolism, and glucocorticoid-induced skin hypoplasia and dermal adipocytes. The FKBP51 signaling mechanisms that may explain these metabolic consequences are discussed. These mechanisms are diverse, with FKBP51 independently and directly regulating phosphorylation cascades and nuclear receptors. We provide a discussion of the newly developed compounds that antagonize FKBP51, which may offer therapeutic advantages for adiposity. These observations suggest we are only beginning to uncover the complex nature of FKBP51 and its molecular chaperoning of metabolism.

A review on cyanobacteria cultivation for carbohydrate-based biofuels: Cultivation aspects, polysaccharides accumulation strategies, and biofuels production scenarios.

Cyanobacterial biomass has constituted a crucial third and fourth-generation biofuel material, with great potential to synthesize a wide range of metabolites, mainly carbohydrates. Lately, carbohydrate-based biofuels from cyanobacteria, such as bioethanol, biohydrogen, and biobutanol, have attracted attention as a sustainable alternative to petroleum-based products. Cyanobacteria can perform a simple process of saccharification, and extracted carbohydrates can be converted into biofuels with two alternatives; the first one consists of a fermentative process based on bacteria or yeasts, while the second alternative consists of an internal metabolic process of their own in intracellular carbohydrate content, either by the natural or genetic engineered process. This study reviewed carbohydrate-enriched cyanobacterial biomass as feedstock for biofuels. Detailed insights on technical strategies and limitations of cultivation, polysaccharide accumulation strategies for further fermentation process were provided. Advances and challenges in bioethanol, biohydrogen, and biobutanol production by cyanobacteria synthesis and an independent fermentative process are presented. Critical outlook on life-cycle assessment and techno-economical aspects for large-scale application of these technologies were discussed.

Asociación VACTERL con poliquistosis renal en un recién nacido: reporte de caso

Las malformaciones son causas importantes de mortalidad infantil, enfermedad crónica y discapacidad en muchos países, y ocasionan 3,2 millones de discapacidades al año. La asociación VACTERL involucra defectos vertebrales, atresia anal, fístula traqueoesofágica y displasia renal, así como anormalidades en las extremidades. Nuestro objetivo es describir las características generales de la asociación VACTERL y realizar un acercamiento a otros casos en la literatura. Nuestro caso trata de una recién nacida a las 35 semanas con grave dificultad respiratoria, que ingresa a la UCI neonatal por descompensación hemodinámica. Tiene un antecedente de poliquistosis renal bilateral a las 25 semanas dado por ecografía. En el examen físico se evidencia agenesia de órganos sexuales y ano imperforado, y en la radiografía se observa patrón atelectásico, cardiomegalia y posición dextrógira de la silueta cardiaca. La paciente fue diagnosticada con asociación VACTERL y ano imperforado. Sufrió un paro respiratorio y falleció luego de dos días.

Malformations are important causes of infant mortality, chronic disease and disability in many countries, causing 3.2 million disabilities per year. The VATERL association includes vertebral defects, anal atresia, tracheoesophageal fistula and renal dysplasia, as well as limb abnormalities. This case report aims to provide the general characteristics of the VACTERL association and discuss other cases found in the medical literature. This is the case of a female newborn delivered at 35 weeks of pregnancy with severe respiratory distress, who was admitted to the neonatal ICU due to hemodynamic decompensation. She had a history of bilateral polycystic kidney disease found by ultrasound at 25 weeks of pregnancy. A physical examination showed vaginal agenesis and imperforate anus. Atelectasis, cardiomegaly and dextroposition of the cardiac silhouette were observed in a radiography. The patient was diagnosed with VACTERL association and imperforate anus. She died 2 days after a respiratory arrest.

Radical surgery for liver hydatidosis.

We have carefully read the article by Ramia et al. titled "Radical surgery in hepatic hydatidosis: an analysis of results in an endemic area", where the authors prioritize ultrasonographic assessment according to the World Health Organization (WHO) classification as a strategy for the surgical planning of hepatic hydatid cyst (HHC). However, they did not consider drug therapy or the use of contrast-enhanced computed tomography (CECT) during preoperative assessment, despite them being considered surgical success factors in the literature.

COUP-TFII revisited: Its role in metabolic gene regulation.

Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) is an orphan member of the nuclear receptor family of transcriptional regulators. Although hormonal activation of COUP-TFII has not yet been identified, rodent genetic models have uncovered vital and diverse roles for COUP-TFII in biological processes. These include control of cardiac function and angiogenesis, reproduction, neuronal development, cell fate and organogenesis. Recently, an emerging body of evidence has demonstrated COUP-TFII involvement in various metabolic systems such as adipogenesis, lipid metabolism, hepatic gluconeogenesis, insulin secretion, and regulation of blood pressure. The potential relevance of these observations to human pathology has been corroborated by the identification of single nucleotide polymorphism in the human COUP-TFII promoter controlling insulin sensitivity. Of particular interest to metabolism is the ability of COUP-TFII to interact with the Glucocorticoid Receptor (GR). This interaction is known to control gluconeogenesis, principally through direct binding of COUP-TFII/GR complexes to the promoters of gluconeogenic enzyme genes. However, it is likely that this interaction is critical to other metabolic processes, since GR, like COUP-TFII, is an essential regulator of adipogenesis, insulin sensitivity, and blood pressure. This review will highlight these unique roles of COUP-TFII in metabolic gene regulation.

Deletion of the glucocorticoid receptor chaperone FKBP51 prevents glucocorticoid-induced skin atrophy.

FKBP51 (FK506-binding protein 51) is a known co-chaperone and regulator of the glucocorticoid receptor (GR), which usually attenuates its activity. FKBP51 is one of the major GR target genes in skin, but its role in clinical effects of glucocorticoids is not known. Here, we used FKBP51 knockout (KO) mice to determine FKBP51's role in the major adverse effect of topical glucocorticoids, skin atrophy. Unexpectedly, we found that all skin compartments (epidermis, dermis, dermal adipose and CD34+ stem cells) in FKBP51 KO animals were much more resistant to glucocorticoid-induced hypoplasia. Furthermore, despite the absence of inhibitory FKBP51, the basal level of expression and glucocorticoid activation of GR target genes were not increased in FKBP51 KO skin or CRISPR/Cas9-edited FKBP51 KO HaCaT human keratinocytes. FKBP51 is known to negatively regulate Akt and mTOR. We found a significant increase in AktSer473 and mTORSer2448 phosphorylation and downstream pro-growth signaling in FKBP51-deficient keratinocytes in vivo and in vitro. As Akt/mTOR-GR crosstalk is usually negative in skin, our results suggest that Akt/mTOR activation could be responsible for the lack of increased GR function and resistance of FKBP51 KO mice to the steroid-induced skin atrophy.

Protein phosphatase 5 and the tumor suppressor p53 down-regulate each other's activities in mice.

Protein phosphatase 5 (PP5), a serine/threonine phosphatase, has a wide range of biological functions and exhibits elevated expression in tumor cells. We previously reported that pp5-deficient mice have altered ataxia-telangiectasia mutated (ATM)-mediated signaling and function. However, this regulation was likely indirect, as ATM is not a known PP5 substrate. In the current study, we found that pp5-deficient mice are hypersensitive to genotoxic stress. This hypersensitivity was associated with the marked up-regulation of the tumor suppressor tumor protein p53 and its downstream targets cyclin-dependent kinase inhibitor 1A (p21), MDM2 proto-oncogene (MDM2), and phosphatase and tensin homolog (PTEN) in pp5-deficient tissues and cells. These observations suggested that PP5 plays a role in regulating p53 stability and function. Experiments conducted with p53+/-pp5+/- or p53+/-pp5-/- mice revealed that complete loss of PP5 reduces tumorigenesis in the p53+/- mice. Biochemical analyses further revealed that PP5 directly interacts with and dephosphorylates p53 at multiple serine/threonine residues, resulting in inhibition of p53-mediated transcriptional activity. Interestingly, PP5 expression was significantly up-regulated in p53-deficient cells, and further analysis of pp5 promoter activity revealed that p53 strongly represses PP5 transcription. Our results suggest a reciprocal regulatory interplay between PP5 and p53, providing an important feedback mechanism for the cellular response to genotoxic stress.

Niveles de vitamina D en dermatólogos y residentes de dermatología de diferentes regiones de Colombia: un estudio piloto / Vitamin D Levels in Dermatologists and Residents of Dermatology in Different Areas of Colombia: a Pilot Study

Introducción: La deficiencia de vitamina D es considerada una pandemia. En la actualidad existen numerosas publicaciones que documentan esta deficiencia en pacientes con osteopenia y/o osteoporosis; sin embargo, no hay estudios en Colombia ni en Latinoamérica que evalúen la deficiencia e insuficiencia de vitamina D en población sana, ni en dermatólogos, quienes pueden ser susceptibles de adquirir esta deficiencia por las largas jornadas laborales y la falta de exposición solar. Objetivo: Determinar la prevalencia de deficiencia de vitamina D en dermatólogos y residentes de dermatología en Colombia, y establecer sí la región de origen estaba asociada a niveles de vitamina D. Metodología: estudio tipo piloto, observacional, analítico de corte transversal, en el cual se incluyeron dermatólogos y residentes de dermatología asistentes al congreso Colombiano de dermatología 2016. A todos los participantes se les aplicó un cuestionario, se practicó examen físico y se midió niveles de 25 hidroxi vitamina D3. Resultados: 100 participantes fueron incluidos en el estudio: la edad media fue 39 años, el 67 % eran mujeres, con prevalencia de insuficiencia o deficiencia de vitamina D del 96% y concentración media de vitamina D de 18.20 ng/ml. Conclusiones: La deficiencia de vitamina D es altamente prevalente en dermatólogos y residentes de dermatología en Colombia, se sugieren intervenciones preventivas en esta población, debido a la alta morbimortalidad relacionada con tal deficiencia...(AU)

Introduction: Vitamin D deficiency is considered as a pandemic. Now, there are lots of publications documenting this deficiency in patients with osteopenia and / or osteoporosis; however, there are no studies either in Colombia or Latin America that evaluate vitamin D deficiency and insufficiency in a healthy population, or in dermatologists, who can be susceptible to acquire this deficiency by the long working hours and the lack of sun exposure. Objective: To determine the prevalence of vitamin D deficiency in dermatologists and residents of dermatology in Colombia and to establish if the area of origin was associated with vitamin D levels. Methodology: This is a pilot, observational, cross-sectional and analytical study in which dermatologists and dermatology residents attending to the 2016 Colombian Congress of Dermatology were included. All participants were given a questionnaire; a physical exam was performed to them and their levels of 25-hydroxyvitamin D3 were measured as well. Results: 100 participants were included in this study: their average age was 39 years; 67% of them were women, with a prevalence of vitamin D deficiency or insufficiency of 96% and with a mean of vitamin D concentration of 18.20 ng/ml. Conclusions: Vitamin D deficiency is highly prevalent in dermatologists and residents of dermatology in Colombia. With this population, some preventive interventions are suggested due to the high morbimortality related to such deficiency...(AU)

Introdução: a deficiência de vitamina D é considerada uma pandemia. Existem agora inúmeras publicações documentando essa deficiência em pacientes com osteopenia e / ou osteoporose; no entanto, não há estudos na Colômbia ou na América Latina que avaliem a deficiência e insuficiência de vitamina D na população saudável, nem em dermatologistas, que podem ser suscetíveis de adquirir essa deficiência devido aos longos dias de trabalho e falta de exposição solar. Objetivo: Determinar a prevalência de deficiência de vitamina D em dermatologistas e residentes de dermatologia na Colômbia e determinar se a região de origem estava associada a níveis de vitamina D. Metodologia: estudo piloto, observacional, transversal, analítico em que dermatologistas e residentes de dermatologia presentes no Congresso Colombiano de Dermatologia 2016 foram incluídos. Todos os participantes receberam um questionário, exame físico e níveis de 25 hidroxi vitamina D3. Metodologia: estudo piloto, observacional, transversal, analítico em que dermatologistas e residentes de dermatologia presentes no Congresso Colombiano de Dermatologia 2016 foram incluídos. Todos os participantes receberam um questionário, exame físico e níveis de 25 hidroxi vitamina D3. Resultados: 100 participantes foram incluídos no estudo: idade média foi de 39 anos, 67% eram mulheres, com prevalência de deficiência de vitamina D ou insuficiência de 96% e concentração média de vitamina D de 18.20 ng/ml. Conclusões: A deficiência de vitamina D é altamente prevalente em dermatologistas e residentes de dermatologia na Colômbia. As intervenções preventivas nesta população, são sugeridas por causa da alta morbidade e mortalidade associada a esta deficiência...(AU)

Protein Phosphatase PP5 Controls Bone Mass and the Negative Effects of Rosiglitazone on Bone through Reciprocal Regulation of PPARγ (Peroxisome Proliferator-activated Receptor γ) and RUNX2 (Runt-related Transcription Factor 2).

Peroxisome proliferator-activated receptor γ (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Ser-112 is required for its adipocytic activity, whereas phosphorylation of RUNX2 at serine 319 (Ser-319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine. Mice deficient in PP5 phosphatase have increased osteoblast numbers and high bone formation, which results in high bone mass in the appendicular and axial skeleton. This is associated with a substantial decrease in lipid-containing marrow adipocytes. Indeed, in the absence of PP5 the MSC lineage allocation is skewed toward osteoblasts and away from lipid accumulating adipocytes, although an increase in beige adipocyte gene expression is observed. In the presence of rosiglitazone, PP5 translocates to the nucleus, binds to PPARγ and RUNX2, and dephosphorylates both factors, resulting in activation of PPARγ adipocytic and suppression of RUNX2 osteoblastic activities. Moreover, shRNA knockdown of PP5 results in cells refractory to rosiglitazone treatment. Lastly, mice deficient in PP5 are resistant to the negative effects of rosiglitazone on bone, which in wild type animals causes a 50% decrease in trabecular bone mass. In conclusion, PP5 is a unique phosphatase reciprocally regulating PPARγ and RUNX2 activities in marrow MSC.

FKBP51 Null Mice Are Resistant to Diet-Induced Obesity and the PPARγ Agonist Rosiglitazone.

FK506-binding protein-51 (FKBP51) is a molecular cochaperone recently shown to be a positive regulator of peroxisome proliferator-activated receptor (PPAR)γ, the master regulator of adipocyte differentiation and function. In cellular models of adipogenesis, loss of FKBP51 not only reduced PPARγ activity but also reduced lipid accumulation, suggesting that FKBP51 knock-out (KO) mice might have insufficient development of adipose tissue and lipid storage ability. This model was tested by examining wild-type (WT) and FKBP51-KO mice under regular and high-fat diet conditions. Under both diets, FKBP51-KO mice were resistant to weight gain, hepatic steatosis, and had greatly reduced white adipose tissue (WAT) but higher amounts of brown adipose tissue. Under high-fat diet, KO mice were highly resistant to adiposity and exhibited reduced plasma lipids and elevated glucose and insulin tolerance. Profiling of perigonadal and sc WAT revealed elevated expression of brown adipose tissue lineage genes in KO mice that correlated increased energy expenditure and a shift of substrate oxidation to carbohydrates, as measured by indirect calorimetry. To directly test PPARγ involvement, WT and KO mice were fed rosiglitazone agonist. In WT mice, rosiglitazone induced whole-body weight gain, increased WAT mass, a shift of substrate oxidation to lipids, and elevated expression of PPARγ-regulated lipogenic genes in WAT. In contrast, KO mice had reduced rosiglitazone responses for these parameters. Our results identify FKBP51 as an important regulator of PPARγ in WAT and as a potential new target in the treatment of obesity and diabetes.