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.

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.

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.

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.

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.

PPARα (Peroxisome Proliferator-activated Receptor α) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed at high levels in the hepatocyte, consistent with its role in promoting insulin clearance in liver. CEACAM1 also mediates a negative acute effect of insulin on fatty acid synthase activity. Western blot analysis reveals lower hepatic CEACAM1 expression during fasting. Treating of rat hepatoma FAO cells with Wy14,643, an agonist of peroxisome proliferator-activated receptor α (PPARα), rapidly reduces Ceacam1 mRNA and CEACAM1 protein levels within 1 and 2 h, respectively. Luciferase reporter assay shows a decrease in the promoter activity of both rat and mouse genes by Pparα activation, and 5'-deletion and block substitution analyses reveal that the Pparα response element between nucleotides -557 and -543 is required for regulation of the mouse promoter activity. Chromatin immunoprecipitation analysis demonstrates binding of liganded Pparα toCeacam1promoter in liver lysates ofPparα(+/+), but notPparα(-/-)mice fed a Wy14,643-supplemented chow diet. Consequently, Wy14,643 feeding reduces hepatic Ceacam1 mRNA and CEACAM1 protein levels, thus decreasing insulin clearance to compensate for compromised insulin secretion and maintain glucose homeostasis and insulin sensitivity in wild-type mice. Together, the data show that the low hepatic CEACAM1 expression at fasting is mediated by Pparα-dependent mechanisms. Changes in CEACAM1 expression contribute to the coordination of fatty acid oxidation and insulin action in the fasting-refeeding transition.

The glucocorticoid receptor: cause of or cure for obesity?

Glucocorticoid hormones (GCs) are important regulators of lipid metabolism, promoting lipolysis with acute treatment but lipogenesis with chronic exposure. Conventional wisdom posits that these disparate outcomes are mediated by the classical glucocorticoid receptor GRα. There is insufficient knowledge of the GC receptors (GRα and GRß) in metabolic conditions such as obesity and diabetes. We present acute models of GC exposure that induce lipolysis, such as exercise, as well as chronic-excess models that cause obesity and lipid accumulation in the liver, such as hepatic steatosis. Alternative mechanisms are then proposed for the lipogenic actions of GCs, including induction of GC resistance by the GRß isoform, and promotion of lipogenesis by GC activation of the mineralocorticoid receptor (MR). Finally, the potential involvement of chaperone proteins in the regulation of adipogenesis is considered. This reevaluation may prove useful to future studies on the steroidal basis of adipogenesis and obesity.

Hand-foot syndrome associated with use of sorafenib in a patient with papillary thyroid cancer: a case report.

BACKGROUND: Hand-foot syndrome (HFS), also known as palmar-plantar Erythrodysesthesia (PPE), acral erythema or Burgdorf reaction, is a dermatologic toxic reaction to certain chemotherapies, including sorafenib. A high incidence of adverse events is already described in dermatological clinical trials of this drug, but its use in medical practice, common in the patient with metastatic thyroid carcinoma has not yet been reported. Sorafenib (BAY 43-9006) is an orally administered multi-level kinase inhibitor, approved for treatment of solid tumors such as renal cell carcinoma, hepatocellular carcinoma and recently for metastatic thyroid carcinoma. CASE PRESENTATION: We report a case of a 29 year old Latin woman diagnosed with papillary thyroid carcinoma, who was initially given a total thyroidectomy, central and bilateral neck lymph node removal followed by a radioiodine therapy. Subsequent evaluation indicated locoregional progressive disease and metastatic involvement in both lungs. Following this, the patient was prescribed 200 mg of sorafenib administered every 12 hours, but after four days, she presented with a skin reaction compatible with hand-foot syndrome. After discontinuation of the therapy, this reaction ceased. CONCLUSION: Sorafenib as a new therapeutic option for patients with radioactive iodine (RAI)-resistant metastatic differentiated thyroid cancer, it is important that clinicians are fully aware of the potential adverse effects. All patients on Sorafenib therapy should be educated to recognize the first symptoms to obtaining the maximal benefit from this anti-neoplastic rescue therapy.

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.

Chaperoning steroidal physiology: lessons from mouse genetic models of Hsp90 and its cochaperones.

The molecular chaperone Hsp90 is abundant, ubiquitous, and catholic to biological processes in eukaryotes, controlling phosphorylation cascades, protein stability and turnover, client localization and trafficking, and ligand-receptor interactions. Not surprisingly, Hsp90 does not accomplish these activities alone. Instead, an ever-growing number of cochaperones have been identified, leading to an explosion of reports on their molecular and cellular effects on Hsp90 chaperoning of client substrates. Notable among these clients are many members of the steroid receptor family, such as glucocorticoid, androgen, estrogen and progesterone receptors. Cochaperones typically associated with the mature, hormone-competent states of these receptors include p23, the FK506-binding protein 52 (FKBP52), FKBP51, protein phosphatase 5 (PP5) and cyclophilin 40 (Cyp40). The ultimate relevance of these cochaperones to steroid receptor action depends on their physiological effects. In recent years, the first mouse genetic models of these cochaperones have been developed. This work will review the complex and intriguing phenotypes so far obtained in genetically-altered mice and compare them to the known molecular and cellular impacts of cochaperones on steroid receptors. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

Suppression of protein kinase C theta contributes to enhanced myogenesis in vitro via IRS1 and ERK1/2 phosphorylation.

BACKGROUND: Differentiation and fusion of skeletal muscle myoblasts into multi-nucleated myotubes is required for neonatal development and regeneration in adult skeletal muscle. Herein, we report novel findings that protein kinase C theta (PKCθ) regulates myoblast differentiation via phosphorylation of insulin receptor substrate-1 and ERK1/2. RESULTS: In this study, PKCθ knockdown (PKCθshRNA) myotubes had reduced inhibitory insulin receptor substrate-1 ser1095 phosphorylation, enhanced myoblast differentiation and cell fusion, and increased rates of protein synthesis as determined by [3H] phenylalanine incorporation. Phosphorylation of insulin receptor substrate-1 ser632/635 and extracellular signal-regulated kinase1/2 (ERK1/2) was increased in PKCθshRNA cells, with no change in ERK5 phosphorylation, highlighting a PKCθ-regulated myogenic pathway. Inhibition of PI3-kinase prevented cell differentiation and fusion in control cells, which was attenuated in PKCθshRNA cells. Thus, with reduced PKCθ, differentiation and fusion occur in the absence of PI3-kinase activity. Inhibition of the ERK kinase, MEK1/2, impaired differentiation and cell fusion in control cells. Differentiation was preserved in PKCθshRNA cells treated with a MEK1/2 inhibitor, although cell fusion was blunted, indicating PKCθ regulates differentiation via IRS1 and ERK1/2, and this occurs independently of MEK1/2 activation. CONCLUSION: Cellular signaling regulating the myogenic program and protein synthesis are complex and intertwined. These studies suggest that PKCθ regulates myogenic and protein synthetic signaling via the modulation of IRS1and ERK1/2 phosphorylation. Myotubes lacking PKCθ had increased rates of protein synthesis and enhanced myotube development despite reduced activation of the canonical anabolic-signaling pathway. Further investigation of PKCθ regulated signaling may reveal important interactions regulating skeletal muscle health in an insulin resistant state.

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.

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.

FKBP38 peptidylprolyl isomerase promotes the folding of cystic fibrosis transmembrane conductance regulator in the endoplasmic reticulum.

FK506-binding protein 38 (FKBP38), a membrane-anchored, tetratricopeptide repeat (TPR)-containing immunophilin, associates with nascent plasma membrane ion channels in the endoplasmic reticulum (ER). It promotes the maturation of the human ether-à-go-go-related gene (HERG) potassium channel and maintains the steady state level of the cystic fibrosis transmembrane conductance regulator (CFTR), but the underlying mechanisms remain unclear. Using a combination of steady state and pulse-chase analyses, we show that FKBP38 knockdown increases protein synthesis but inhibits the post-translational folding of CFTR, leading to reduced steady state levels of CFTR in the ER, decreased processing, and impaired cell surface functional expression in Calu-3 human airway epithelial cells. The membrane anchorage of FKBP38 is necessary for the inhibition of protein synthesis but not for CFTR post-translational folding. In contrast, the peptidylprolyl cis/trans isomerase active site is utilized to promote CFTR post-translational folding but is not important for regulation of protein synthesis. Uncoupling FKBP38 from Hsp90 by substituting a conserved lysine in the TPR domain modestly enhances CFTR maturation and further reduces its synthesis. Removing the N-terminal glutamate-rich domain (ERD) slightly enhances CFTR synthesis but reduces its maturation, suggesting that the ERD contributes to FKBP38 biological activities. Our data support a dual role for FKBP38 in regulating CFTR synthesis and post-translational folding. In contrast to earlier prediction but consistent with in vitro enzymological studies, FKBP38 peptidylprolyl cis/trans isomerase plays an important role in membrane protein biogenesis on the cytoplasmic side of the ER membrane, whose activity is negatively regulated by Hsp90 through the TPR domain.

Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ).

Glucocorticoid receptor-α (GRα) and peroxisome proliferator-activated receptor-γ (PPARγ) regulate adipogenesis by controlling the balance between lipolysis and lipogenesis. Here, we show that protein phosphatase 5 (PP5), a nuclear receptor co-chaperone, reciprocally modulates the lipometabolic activities of GRα and PPARγ. Wild-type and PP5-deficient (KO) mouse embryonic fibroblast cells were used to show binding of PP5 to both GRα and PPARγ. In response to adipogenic stimuli, PP5-KO mouse embryonic fibroblast cells showed almost no lipid accumulation with reduced expression of adipogenic markers (aP2, CD36, and perilipin) and low fatty-acid synthase enzymatic activity. This was completely reversed following reintroduction of PP5. Loss of PP5 increased phosphorylation of GRα at serines 212 and 234 and elevated dexamethasone-induced activity at prolipolytic genes. In contrast, PPARγ in PP5-KO cells was hyperphosphorylated at serine 112 but had reduced rosiglitazone-induced activity at lipogenic genes. Expression of the S112A mutant rescued PPARγ transcriptional activity and lipid accumulation in PP5-KO cells pointing to Ser-112 as an important residue of PP5 action. This work identifies PP5 as a fulcrum point in nuclear receptor control of the lipolysis/lipogenesis equilibrium and as a potential target in the treatment of obesity.

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.

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.

Fkbp52 regulates androgen receptor transactivation activity and male urethra morphogenesis.

Hypospadias is a common birth defect in humans, yet its etiology and pattern of onset are largely unknown. Recent studies have shown that male mice with targeted ablation of FK506-binding protein-52 (Fkbp52) develop hypospadias, most likely due to actions of Fkbp52 as a molecular co-chaperone of the androgen receptor (AR). Here, we further dissect the developmental and molecular mechanisms that underlie hypospadias in Fkbp52-deficient mice. Scanning electron microscopy revealed a defect in the elevation of prepucial swelling that led to the onset of the ventral penile cleft. Interestingly, expression of Fkbp52 was highest in the ventral aspect of the developing penis that undergoes fusion of the urethral epithelium. Although in situ hybridization and immunohistochemical analyses suggested that Fkbp52 mutants had a normal urethral epithelium signaling center and epithelial differentiation, a reduced apoptotic cell index at ventral epithelial cells at the site of fusion and a defect of genital mesenchymal cell migration were observed. Supplementation of gestating females with excess testosterone partially rescued the hypospadic phenotype in Fkbp52 mutant males, showing that loss of Fkbp52 desensitizes AR to hormonal activation. Direct measurement of AR activity was performed in mouse embryonic fibroblast cells treated with dihydrotestosterone or synthetic agonist R1881. Reduced AR activity at genes controlling sexual dimorphism and cell growth was found in Fkbp52-deficient mouse embryonic fibroblast cells. However, chromatin immunoprecipitation analysis revealed normal occupancy of AR at gene promoters, suggesting that Fkbp52 exerts downstream effects on the transactivation function of AR. Taken together, our data show Fkbp52 to be an important molecular regulator in the androgen-mediated pathway of urethra morphogenesis.