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Introduction Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study.Research design and methods We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations.Results Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation.Conclusions HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Background & Aims: Mounting evidence suggests the gastrointestinal microbiome is a determinant of peripheral immunity and central neurodegeneration, but the local disease mechanisms remain unknown. Given its potential relevance for early diagnosis and therapeutic intervention, we set out to map the pathogenic changes induced by bacterial amyloids in the gastrointestinal tract and its enteric nervous system. Methods: To examine the early response, we challenged primary murine myenteric networks with curli, the prototypical bacterial amyloid, and performed shotgun RNA sequencing and multiplex enzyme-linked immunosorbent assay. Using enteric neurosphere-derived glial and neuronal cell cultures, as well as in vivo curli injections into the colon wall, we further scrutinized curli-induced pathogenic pathways. Results: Curli induced a proinflammatory response, with strong up-regulation of Saa3 and the secretion of several cytokines. This proinflammatory state was induced primarily in enteric glia, was accompanied by increased levels of DNA damage and replication, and triggered the influx of immune cells in vivo. The addition of recombinant Serum Amyloid A3 (SAA3) was sufficient to recapitulate this specific proinflammatory phenotype while Saa3 knock-out attenuated curli-induced DNA damage and replication. Similar to curli, recombinant SAA3 caused a strong up-regulation of Saa3 transcripts, illustrating its self-amplifying potential . Since colonization of curli-producing Salmonella and dextran sulfate sodium–induced colitis triggered a significant increase in Saa3 transcripts as well, we assume SAA3plays a central role in enteric dysfunction. Inhibition of dual leucine zipper kinase, an upstream regulator of the c-Jun N-terminal kinase pathway responsible for SAA3 production, attenuated curli- and recombinant SAA3-induced Saa3 up-regulation, DNA damage, and replication in enteric glia. Conclusions: Our results position SAA3 as an important mediator of gastrointestinal vulnerability to bacterial-derived amyloids and demonstrate the potential of dual leucine zipper kinase inhibition to dampen enteric pathology.

Abstract Background Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood. Case presentation After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells’ surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls. Conclusion Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation.

Background Valproic acid (VPA), a histone deacetylase inhibitor, has shown improved outcomes when used as a pharmaceutical intervention in animal studies of hemorrhage, septic shock, and combined injuries. This study was designed to investigate the ability of VPA to mitigate ischemia–reperfusion injury produced by prolonged tourniquet application to an extremity.Methods The ischemia–reperfusion model in anesthetized rats was established using hemorrhage and a 3-hour tourniquet application. VPA was administered intravenously prior to tourniquet wear and removal. Ischemia–reperfusion injury was evaluated by investigating pathway signaling, immune modulation of cytokine release, remote organ injury, and skeletal muscle function during convalescence.Results We found that VPA sustained Protein kinase B (Akt) phosphorylation and Insulin-like growth factor signaling and modulated the systemic release of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-6 after 2 hours of limb reperfusion. Additionally, VPA attenuated a loss in glomerular filtration rate at 3 days after injury. Histological and functional evaluation of extremity skeletal muscle at 3, 7, and 21 days after injury, however, demonstrated no significant differences in myocytic degeneration, necrotic formation, and maximal isometric tetanic torque.Conclusions Our results demonstrate that VPA sustains early prosurvival cell signaling, reduces the inflammatory response, and improves renal function in a hemorrhage with prolonged ischemia and reperfusion model. However, these do not translate into meaningful preservation in limb function when applied as a pharmaceutical augmentation to tourniquet wear.Level of evidence IV.

IntroductionDepressive Disorders are on the rise worldwide. This is also the case in Latin America (LatAm). Treatment-Resistant Depressive Disorder (TRD) poses additional burden to patients with depression. Impacts quality of life (QoL) and other dimensions, and standard of care (SOC) is insufficient to achieve the desired clinical outcomes. Evidence from LatAm is, however, lacking. The present study was devised as a 1-year follow-up of the SOC in TRD patients in LatAm to explore the burden of TRD.MethodsThis was an observational, multinational, longitudinal study. Patients with clinical diagnosis of TRD in LatAm were included in a 1-year follow-up with SOC. Beyond the Sociodemographic characterization, outcome measures were QoL (EQ-5D-5L), disability (Sheehan Disability Scale - SDS), work productivity (Work Productivity and Activity Incapacity Questionnaire: depression - WPAI:D) and depression severity (Patient Health Questionnaire-PHQ9). Patients were assessed every 3-months and comparison was performed based on change from baseline to each visit and end of study (EOS - 12 months).ResultsPatients averaged 48 (± 13.12) years, mostly female (80.9%) and married/consensual union (42.5%) or single patients (34.4%). Despite the SOC treatment, three-quarters of the patients remained symptomatic at EOS, regardless of the significant longitudinal decrease (p ≤ 0.001). Similar trends were found for disability (p ≤ 0.001) -82.2% of the patients reporting work/school disruption at EOS-, percentage of work (34%) and activity impairment (40%) at EOS (p ≤ 0.001) and only 29.2% of patients with depressive severity “none” at EOS (p ≤ 0.001). The results portray the need to improve clinical outcomes in this complex and burdensome disease in LatAm.DiscussionHere we show that the burden of TRD remains significant in essential dimensions of everyday life at EOS underlining the need for better therapeutic solutions. The improvements in most patients do not provide the desired outcome of return to the state before the condition. Further research should focus on identifying which treatments provide better outcomes in a real-world context.

Monitoring of cryptic or threatened species poses challenges for population assessment and conservation, as imperfect detection gives rise to misleading inferences about population status. We used a dynamic occupancy model that explicitly accounted for occupancy, colonization, local extinction and detectability to assess the status of the endemic Critically Endangered Bermuda skink Plestiodon longirostris. During 2015–2017, skinks were detected at 13 of 40 surveyed sites in Bermuda, two of which were new records. Ten observation-level and site-specific covariates were used to explore drivers of occupancy, colonization, extinction and detectability. Sites occupied by skinks tended to be islands with rocky coastal habitat and prickly pear cacti; the same variables were also associated with reduced risk of local extinction. The presence of seabirds appeared to encourage colonization, whereas the presence of cats had the opposite effect. The probability of detection was p = 0.45, and on average, five surveys were needed to reliably detect the presence of skinks with 95% certainty. However, skinks were unlikely to be detected on sites with cat and rat predators. Dynamic occupancy models can be used to elucidate drivers of occupancy dynamics, which in turn can inform species conservation management. The survey effort needed to determine population changes over time can be derived from estimates of detectability.

Environmental enrichment has been shown to enhance the behavioural repertoire and reduce the occurrence of abnormal behaviours, particularly in zoo-housed mammals. However, evidence of its effectiveness in reptiles is lacking. Previously, it was believed that reptiles lacked the cognitive sophistication to benefit from enrichment provision, but studies have demonstrated instances of improved longevity, physical condition and problem-solving behaviour as a result of enhancing husbandry routines. In this study, we evaluate the effectiveness of food- and scent-based enrichment for three varanid species (Komodo dragon, emerald tree monitor lizard and crocodile monitor). Scent piles, scent trails and hanging feeders resulted in a significant increase in exploratory behaviour, with engagement diminishing ≤330 min post provision. The provision of food- versus scent-based enrichment did not result in differences in enrichment engagement across the three species, suggesting that scent is just as effective in increasing natural behaviours. Enhancing the environment in which zoo animals reside is important for their health and wellbeing and also provides visitors with the opportunity to observe naturalistic behaviours. For little known and understudied species such as varanids, evidence of successful (and even unsuccessful) husbandry and management practice is vital for advancing best practice in the zoo industry.

This study presents BioElectrochemical Treatment Technology (BETT) as a new wastewater management solution toward the Net-Zero future. The results reported herein were collected from a BETT pilot system installed at a large brewery in Los Angeles, CA, United States processing 0.6 m3. day-1 of raw brewery wastewater with a high content of fruit pulp. Removal of Chemical Oxygen Demand (COD), Total Suspended Solids (TSS) and protein in mg.L-1 per day or percentage were evaluated over 2 months of continuous operation of the Demo Unit. The GHG emissions associated with the power consumed, biomass produced, and carbon dioxide emitted were estimated and compared to aerobic and anaerobic solutions. It was demonstrated that BETT can process wastewater with higher organic load than most conventional anaerobic systems. The inflow COD loading varied between 48,550 mg/L to 116,200 mg/L, and BETT achieved up to 33% COD removal in 4-h HRT. The TSS removal reached values as high as 79% with incoming TSS concentrations up to 34,000 mg/L TSS. BETT did not directly generate methane and demonstrated 89 and 49% lower landfill methane emissions than aerobic and anaerobic technologies, respectively. The overall reduction in CO2 emissions, both direct and indirect, was estimated to be 85–90% compared to existing practices.

Abstract To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman’s correlation against age. Additionally, patients were divided by age into group 1 ( 40 WCGA). Differences between groups were tested with the Mann–Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman’s correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann–Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at

The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs’ WT1-treated cells when compared with controls, resulting in a loss of the cell’s viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.

Purpose: To describe the appearance of vitreous opacities using dynamic ultra-widefield infrared confocal scanning laser ophthalmoscopy (IRcSLO). Design: Retrospective case series. Methods: Eyes of patients complaining of myodesopsia were analyzed using dynamic ultra-widefield IRcSLO imaging (Nidek Mirante, Nidek Co., Ltd., Gamagori, Japan), and classified according to a vitreous opacity severity scale. Results: Thirty eyes of 21 patients were included in this study. The average age was 56 years. Symptom duration ranged from 1 to more than 365 days. The most common cause of vitreous floaters was posterior vitreous detachment (63.3%), followed by vitreous syneresis (23.3%), asteroid hyalosis (10%) and vitreous hemorrhage (3.3%). Opacities were classified as Grade 1 in three eyes (10%), Grade 2 in 10 eyes (33.3%), Grade 3 in 11 eyes (36.6%), Grade 4 in two eyes (6.6%) and Grade 5 in four eyes (13.3%). Patients with Grade 1 opacities were younger than patients with opacities Grade 2 or greater. A visible Weiss ring could be identified in 0% of eyes with Grade 1 opacities, 40% of eyes with Grade 2 opacities, 100% of eyes with Grade 3 opacities, and 100% of eyes with Grade 4 opacities. In patients with Grade 5 opacities, a Weiss ring could not be identified. Conclusion: Dynamic ultra-widefield IRcSLO imaging is a useful tool to evaluate patients with vitreous floaters. It allows for accurate visualization of the number, density, and behavior of the shadows that vitreous opacities project over a very wide area of the retina, which has a positive correlation with patient perception of floaters.

Abstract Background Adipokines and the myokine irisin, involved in mechanisms associated with obesity and metabolic syndrome (MS), are understudied in the pediatric population. Objective To investigate the relationship between irisin, and leptin, resistin, adiponectin, adipsin, anthropometric and cardiovascular risk factors in Mexican children. Methods A cross-sample of 126 Mexican children aged 6–12 years old were classified as normal weight (n = 46), obese (n = 40), and MS (n = 40) according to CDC’s and Cook’s age-modified criteria for obesity and MS. Anthropometric parameters and blood pressure were determined and percentiles calculated for age and gender. Irisin, leptin, adiponectin, adipsin, resistin, triglycerides, glucose, high-density lipoprotein cholesterol (HDL-c) levels, and physical activity were determined. Statistical tests for differences between groups, correlation, and multiple regression analyses were performed. Results Irisin plasma levels were significantly lower in the obese (6.08 [4.68–6.65]) and MS groups (6.46 [5.74–7.02]) compared with the normal-weight group (8.05 [7.24–8.94]) (p

Summary: Most neurological disorders display impaired synaptic connectivity. Hence, modulation of synapse formation may have therapeutic relevance. However, the high density and small size of synapses complicate their quantification. To improve synapse-oriented screens, we analyzed the labeling performance of synapse-targeting antibodies on neuronal cell cultures using segmentation-independent image analysis based on sliding window correlation. When assessing pairwise colocalization, a common readout for mature synapses, overlap was incomplete and confounded by spurious signals. To circumvent this, we implemented a proximity ligation-based approach that only leads to a signal when two markers are sufficiently close. We applied this approach to different marker combinations and demonstrate its utility for detecting synapse density changes in healthy and compromised cultures. Thus, segmentation-independent analysis and exploitation of resident protein proximity increases the sensitivity of synapse quantifications in neuronal cultures and represents a valuable extension to the analytical toolset for in vitro synapse screens.

Reseña crítica del libro Etnobiología del pueblo kakataibo, escrito por Roberto Zariquiey y publicado el año 2018 como resultado de un estudio etnobiológico colaborativo de más tres años por parte de la Pontificia Universidad Católica del Perú (PUCP) e investigadores del pueblo Kakataibo de la comunidad nativa de Yamino, de la provincia de Padre Abad, en el departamento de Ucayali, Perú. La presente reseña busca dar una mirada a cada uno de los capítulos resaltando los aspectos que, a nuestro entender, resultan importantes de destacar pues constituyen hallazgos importantes en cuanto a las estrategias de nominación animal y vegetal kakataibo, así como para la preservación y transmisión de los conocimiento etnobiológicos del pueblo del mismo nombre.

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, MetS, and healthy controls. Serum irisin levels were significantly lower in the MetS (6.6 [2.8-18.0] ng/mL) and T2DM (6.8 [2.2-23.2] ng/mL) groups compared with controls (30.3 [24.6-57.1] ng/mL). Negative correlations between irisin and the BMI percentile (R=−0.358), WC percentile (R=−0.308), and triglycerides (R=−0.284) were identified, while positive associations with TC (R=0.287), HDL-c (R=0.488), and LDL-c (R=0.414) were observed. Significant negative correlations were found between irisin and sNCAM (R=−0.382), sICAM-2 (R=−0.300), sVCAM-1 (R=−0.292), MCP-1 (R=−0.308), and IFN-α2 (R=−0.406). Of note, lower concentrations of most sCAMs (sICAM-1, sPSGL-1, sP-selectin, sEpCAM, sICAM-2, sALCAM, sPECAM-1, sCD44, sVCAM-1, sICAM-3, sL-selectin, and sNCAM) were shown in T2DM subjects compared with MetS patients. Lower irisin levels induce a lack of inhibition of oxidative stress and inflammation. In T2DM, higher ROS, AGEs, glucotoxicity, and inflammation trigger endothelial cell apoptosis, which downregulates the sCAM expression as a compensatory mechanism to prevent further vascular damage. In opposition, in subjects with MetS that have not yet developed T2DM and its accompanying stressors, the upregulation of the sCAM expression is ensued.

Abstract Background Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9. Methods To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests. Results Our results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH. Conclusion Our systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.

Emerging infectious diseases are an increasingly important threat to wildlife conservation, with amphibian chytridiomycosis, caused by Batrachochytrium dendrobatidis, the disease most commonly associated with species declines and extinctions. However, some amphibians can be infected with B. dendrobatidis in the absence of disease and can act as reservoirs of the pathogen. We surveyed robber frogs (Eleutherodactylus spp.), potential B. dendrobatidis reservoir species, at three sites on Montserrat, 2011–2013, and on Dominica in 2014, to identify seasonal patterns in B. dendrobatidis infection prevalence and load (B. dendrobatidis genomic equivalents). On Montserrat there was significant seasonality in B. dendrobatidis prevalence and B. dendrobatidis load, both of which were correlated with temperature but not rainfall. B. dendrobatidis prevalence reached 35% in the cooler, drier months but was repeatedly undetectable during the warmer, wetter months. Also, B. dendrobatidis prevalence significantly decreased from 53.2% when the pathogen emerged on Montserrat in 2009 to a maximum 34.8% by 2011, after which it remained stable. On Dominica, where B. dendrobatidis emerged seven years prior to Montserrat, the same seasonal pattern was recorded but at lower prevalence, possibly indicating long-term decline. Understanding the dynamics of disease threats such as chytridiomycosis is key to planning conservation measures. For example, reintroductions of chytridiomycosis-threatened species could be timed to coincide with periods of low B. dendrobatidis infection risk, increasing potential for reintroduction success.

The design and implementation of a solar tracker based on panoramic images captured by a fisheye camera are proposed. Such images receive a digital treatment to estimate the sun azimuth and the elevation angles. These angles are fed to a microcontroller, handling an accelerometer with a gyroscope, that positions the solar tracker to the angle of solar elevation and a compass to set the azimuth angle concerning the north, either magnetic or geographic. The proposed system works satisfactorily to guide the solar tracker regardless of whether it is a sunny or cloudy day.

Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establishing the association of circulating irisin in children and adolescents with T2DM has not been described in the literature. The objective of this study was to determine irisin plasma concentration and its association with metabolic and adiposity markers and with hs-CRP, a surrogate marker of inflammation used in clinical practice, in a pediatric population with T2DM. A cross-sample of 40 Mexican children and adolescents aged 7-17 were recruited, 20 diagnosed with T2DM and 20 healthy controls. Plasma irisin levels were found to be lower in the T2DM group compared with controls, which could be attributed to a reduced PGC-1α activity in muscle tissue with a consequent decrease in FNDC5 and irisin expression. Irisin concentration was found to be positively correlated with HDL-c, LDL-c, and total cholesterol, while negatively correlated with BMI, waist circumference, and triglycerides. However, after multiple regression analysis, only HDL-c correlation remained significant. hs-CRP was higher in the T2DM group and positively associated with adiposity markers, unfavorable lipid profile, insulin levels, and HOMA-IR, but no association with irisin was found. Given the favorable metabolic effects attributed to irisin, the low plasma levels found in children and adolescents with T2DM could exacerbate the inflammatory and metabolic imbalances and the intrinsic cardiovascular risk of this disease. We propose an “irisin-proinflammatory/anti-inflammatory axis” to explain the role of irisin as a metabolic regulator in obesity and T2DM.

Vitamin D deficiency is highly prevalent worldwide. It has been associated with heart failure (HF) given its immunoregulatory functions. In-vitro and animal models have shown protective roles through mechanisms involving procollagen-1, JNK2, calcineurin/NFAT, NF-κB, MAPK, Th1, Th2, Th17, cytokines, cholesterol-efflux, oxLDL, and GLUT4, among others. A 12-month follow-up in HF patients showed a high prevalence of vitamin D deficiency, with no seasonal variation (64.7−82.4%). A positive correlation between serum 25(OH)D concentration and dietary intake of vitamin D-rich foods was found. A significant inverse correlation with IL-1β (R = −0.78), TNF-α (R = −0.53), IL-6 (R = −0.42), IL-8 (R = −0.41), IL-17A (R = −0.31), LDL-cholesterol (R = −0.51), Apo-B (R = −0.57), total-cholesterol (R = −0.48), and triglycerides (R = −0.32) was shown. Cluster analysis demonstrated that patients from cluster three, with the lowest 25(OH)D levels, presented the lowermost vitamin D intake, IL-10 (1.0 ± 0.9 pg/mL), and IL-12p70 (0.5 ± 0.4 pg/mL), but the highest TNF-α (9.1 ± 3.5 pg/mL), IL-8 (55.6 ± 117.1 pg/mL), IL-17A (3.5 ± 2.0 pg/mL), total-cholesterol (193.9 ± 61.4 mg/dL), LDL-cholesterol (127.7 ± 58.2 mg/dL), and Apo-B (101.4 ± 33.4 mg/dL) levels, compared with patients from cluster one. Although the role of vitamin D in the pathogenesis of HF in humans is still uncertain, we applied the molecular mechanisms of in-vitro and animal models to explain our findings. Vitamin D deficiency might contribute to inflammation, remodeling, fibrosis, and atherosclerosis in patients with HF.

In this study, in situ, real-time and high-resolution vertical measurements of dissolved greenhouse gases (GHGs) such as nitrous oxide (N2O) and methane (CH4) and nutrients are reported for the eastern South Pacific (ESP); a region with marked zonal gradients, ranging from highly productive and suboxic conditions in coastal upwelling systems to oligotrophic and oxygenated conditions in the subtropical gyre. Four high-resolution vertical profiles for gases (N2O and CH4) and nutrients (NO3- and PO43-) were measured using a Pumped Profiling System (PPS), connected with a liquid degassing membrane coupled with Cavity Ring-Down Spectroscopy (CRDS) and a nutrient auto-analyzer, respectively. The membrane-CRDS system maintains a linear response over a wide range of gas concentrations, detecting N2O and CH4 levels as low as 0.0774 ± 0.0004 and 0.1011 ± 0.001 ppm, respectively. Continuous profiles for gases and nutrients were similar to those reported throughout the ESP, with pronounced N2O and CH4 peaks at the upper oxycline and at the base of the euphotic zone and pycnocline, respectively, in the coastal zone; but almost constant depth profiles in the subtropical gyre. Additionally, other vertical gas and nutrient structures were observed using continuous sampling, which would not have been detected by discrete sampling. Our results demonstrate that continuous measurements can be a potentially useful methodology for future GHGs cycle studies.

Bacterial communities are frequently found in symbiotic associations with most animal species. The characteristically moist amphibian skin provides a good environment for the growth of some species of bacteria; among these a few can act as a first line defense mechanism against infections. Amphibians in the wild have relatively high exposure to bacteria through environmental transmission and through interactions with different conspecifics, whilst in captivity animals interact with fewer individuals, as well as experiencing a less complex environment through which to obtain their bacterial community. Here we compared the skin microbiota of captive and wild Mantella aurantiaca to investigate whether the captive environment was affecting individuals' skin associated bacteria. This could have survivorship implications if captive animals had a different skin microbial community in comparison to wild counterparts and they were to be used in a reintroduction program. The microbial community were characterized through 16S rRNA amplicon sequencing methodology. Analyses showed that captive individuals had significantly lower diversity of bacterial species and lower relative abundant microbiota when compared to wild populations; this could result in captive frogs released back to the wild probably has greater susceptibility to infections due to inadequate skin microbiota.

Adaptations to captivity that reduce fitness are one of many reasons, which explain the low success rate of reintroductions. One way of testing this hypothesis is to compare an important behavioural response in captive and wild members of the same species. Thanatosis, is an anti-predator strategy that reduces the risk of death from predation, which is a common behavioral response in frogs. The study subjects for this investigation were captive and wild populations of Mantella aurantiaca. Thanatosis reaction was measured using the Tonic Immobility (TI) test, a method that consists of placing a frog on its back, restraining it in this position for a short period of time and then releasing it and measuring how much time was spent feigning death. To understand the pattern of reaction time, morphometric data were also collected as body condition can affect the duration of thanatosis. The significantly different TI times found in this study, one captive population with shorter responses, were principally an effect of body condition rather than being a result of rearing environment. However, this does not mean that we can always dismiss the importance of rearing environment in terms of behavioural skills expressed.

Acoustic communication is highly influential in the expression of social behavior by anuran amphibians, transmitting information about the individual's physical condition and motivation. We studied the phonotactic (approach movements) responses of wild and captive male golden mantella frogs to conspecific wild and captive playback calls to determine the impact of captivity on social behaviour mediated by vocalisations. Calls were recorded from one wild and two captive populations. Phonotaxis experiments were then conducted by attracting M. aurantiaca males across a PVC grid on the forest floor or enclosure floor to a speaker. For each playback, the following parameters were recorded to define the accuracy of phonotaxis: (1) number of jumps; (2) jump angles; (3) jump distances; (4) path straightness. During this experiment we observed that wild frogs had a similar behavioural (phonotaxis) response to calls independent of their source while frogs from Chester Zoo had a significantly stronger response to calls of other conspecifics held separately at Chester Zoo. The lack of appropriate phonotaxis response by captive bred frogs to the calls of wild conspecifics could have serious negative conservation implications, if the captive bred individuals were released back to the wild.

Exercise-induced irisin, a recently discovered myokine, has been linked to insulin resistance, obesity, and other diseases in adults; however, information in children is scarce and contradictory. We analyzed the limited evidence of irisin’s effects in children and adolescents, and its association with body composition, exercise training, cardiovascular risk factors, and metabolic diseases, as well as the results of dietetic interventions. Both positive and negative correlations between irisin concentrations and body mass index, fat mass, fat-free mass, and other anthropometric parameters were found. Likewise, contradictory evidence was shown associating irisin plasma levels with cardiovascular and metabolic parameters such as glucose, insulin resistance, and cholesterol and other lipid and fatty acid plasma levels in healthy children, as well as in those with obesity and the metabolic syndrome. Gender, puberty, and hormonal differences were also examined. Furthermore, important contradictory findings according to the type and duration of exercise and of dietetic interventions in healthy and unhealthy subjects were demonstrated. In addition, correlations between mother⁻infant relations and circulating irisin were also identified. This review discusses the potential role of irisin in health and disease in the pediatric population.

Irisin is considered to be a myokine and adipokine that may also participate in reproductive functions, as it increases significantly throughout pregnancy. However, the regulation of circulating irisin and its relationship with other cytokines has not been assessed thus far in pregnant women and their offspring.The aim of this study was to evaluate differences in irisin and cytokine concentrations between women at the end of pregnancy and their offspring, as well as the relationship between maternal and newborn irisin and maternal and newborn biomarkers.Twenty-eight mother/newborn pairs were included in this study. The following biomarkers were evaluated in maternal venous and arterial umbilical cord blood samples: irisin, 27 cytokine panel, total antioxidant capacity (TAC), total plasma protein, and free fatty acid concentration.The newborns had significantly lower irisin concentrations compared to their mothers (p = 0.03), but this difference was present only in babies born from mothers without labor prior to cesarean section delivery (p = 0.01). No significant differences in maternal and newborn irisin concentrations were found between diabetic and non-diabetic mothers or between overweight/obese and normal weight mothers. A significant positive correlation was found between TAC level and irisin concentration in newborns. Maternal and newborn interleukin (IL)-1β, IL-1RA, IL-5, IL-7, and interferon gamma-induced protein (IP)-10 levels were significantly positively correlated with irisin concentrations in both study groups. In addition, maternal IL1β, IL-5, IL-7, and IP-10 levels positively predicted maternal irisin concentrations. Furthermore, arterial cord blood TAC and IL-1β and IL1-RA levels positively predicted newborn irisin concentrations. Multiple regression analyses showed that maternal IL-13 negatively predicted offspring irisin levels (p = 0.03) and that maternal IL-1β positively predicted newborn irisin concentrations (p = 0.046).No evidence was found that serum irisin concentrations in mothers at pregnancy termination or those of their newborns correlated with maternal body mass index, the presence of diabetes mellitus, or free fatty acid levels. However, the results of this study indicated that cytokines might predict irisin concentration in mothers and their offspring, although interactions between irisin levels during pregnancy and the newborn have not yet been fully elucidated.

A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE) and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening.

After drawing a dose from an closed bevacizumab (Avastin) bottle, a fungus-like foreign body was observed inside. Samples from the vial were cultured in Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment was observed after 10 days. The species was identified as Scytalidium sp.Vial, analysis reported that the seal was lacking proper identification measures and that the label, batch number and expiry date did not correspond to a genuine product. Chemical analysis showed no protein, but 3% of polyethylene glycol, citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a significant risk for ophthalmology and oncology patients. The medical community should be aware of this situation in order to enforce adequate preventive measures.

Multiple posterior segment complications can occur after LASIK. Posterior vitreous detachment, macular holes, retinal hemorrhages, retinal detachment, and several other complications have been described. A case of posterior vitreous detachment with epiretinal membrane in a young adult after LASIK is reported. LASIK surgeons must be aware of the possibility of posterior segment complications after surgery.

Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time.