Unraveling the RAGE-NF-κB pathway: implications for modulating inflammation in diabetic neuropathy through photobiomodulation therapy.

Diabetic peripheral neuropathy (DPN) is a primary complication observed in diabetes that severely affects quality of life. Recent evidence suggests that photobiomodulation (PBM) is a promising therapy against painful conditions and nerve damage. However, the effects of PBM on DPN remains mostly unknown. In the present study, we investigated the efficacy of PBM therapy in modulating proinflammatory cytokine expression in both central and peripheral nervous systems of rats with Streptozotocin (STZ)-induced type 1 diabetes. Male Wistar rats were allocated into control (naïve), diabetic (STZ), and treatment (STZ + PBM) groups. A single intraperitoneal (i.p.) injection of STZ (85 mg/kg) was administered for the induction of diabetes. Animals were subjected to 10 treatment sessions, every other day. The results herein presented indicate that PBM treatment diminishes Receptor for Advanced Glycation End-products (RAGE) and Nuclear Factor Kappa B (NF-Ï°B) expression in peripheral nervous system and suppresses TNF-α expression in central nervous system tissues. Furthermore, PBM-therapy in diabetic rats also induces increased levels of the anti-inflammatory protein IL-10 in both peripheral and central nervous system. Collectively, our findings demonstrate compelling evidence that PBM-therapy modulates cytokine dynamics and influences RAGE/NF-Ï°B axis in a STZ-induced model of type 1 diabetes.

Growth and physiological response of proactive and reactive juvenile "tambaqui" (Colossoma macropomum) in a recirculating aquaculture system.

This study evaluated the growth and physiological response of proactive and reactive Colossoma macropomum juveniles in a recirculating aquaculture system (RAS). In Phase 1 of the experiment (50 days of cultivation), juveniles, weighing 2.16 ± 0.52 g, were stocked in 12 28-L tanks to test the following treatments: proactive (PT), reactive (RT) and mixed (MT) composed of reactive (MRT) and proactive (MPT) animals. In Phase 2 of the experiment (40 days of cultivation), the animals were transferred to 175-L tanks with the same treatments as Phase 1. The animals were fed twice a day with commercial diet during both phases. After Phase 1, MPT animals showed higher growth than MRT animals (P < 0.05), and higher weight gain and daily weight than PT animals (P < 0.05). After Phase 2, PT animals showed higher weight gain and daily weight gain than RT and MT animals (P < 0.05), as did MPT animals compared to PT animals. Performance for RT animals was superior (P < 0.05) to that of MRT animals. Glucose (P < 0.04) and cholesterol (P < 0.01) were higher for RT animals compared to PT animals. Cholesterol was higher for MPT animals compared to MRT animals (P < 0.01), while plasma protein was lower (P < 0.001). Glucose (P < 0.001) and cholesterol (P < 0.01) were higher for MPT animals compared to PT animals and for MRT animals compared to RT animals (glucose P < 0.02, cholesterol P < 0.01). After 90 days of cultivation, proactive animals cultivated separately presented better performance. When cultivated together, reactive animals experienced a decrease in performance and both stress coping styles showed more signs of stress.

Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil.

Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21 days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

Consumption of carbonated soft drinks, fruits and vegetables and association with macroeconomic indicators: the analysis of students from seventy-four countries (2003-2015).

This study aimed to compare fruits and vegetables (FV), and carbonated soft drink (CSD) consumption among adolescents from seventy-four countries, according to macroeconomic indicators. This is an ecological study, developed with countries evaluated through the Global School-based Student Health Survey (2003-2014) and the National School Health Survey (PeNSE-Brazil, 2015). The percentages of students in each country who consumed CSD and FV daily and their association with the Human Development Index (HDI) and the Gross National Income per capita (GNIpc) were assessed. Scatter plots were constructed for each marker, and a multilevel model was tested to consider the effects of region in the associations. The overall prevalence of daily CSD consumption was 54·1 %. CSD consumption was positively associated with HDI and GNIpc through multilevel models, and Central and South America showed a considerable higher consumption compared with other regions. Overall, FV daily consumption was 67·9 % and 74·6 %, respectively, and no associations with macroeconomic indicators were found. The study shows concerning rates of CSD consumption among adolescents, and a trend of increased consumption with the improvement of the country's development and GNIpc. This points for the importance of public policies that regulate food and beverage industries to reduce CSD consumption and related co-morbidities among adolescents.

Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice.

Low-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associated with anti-inflammatory effects. Therefore, in high fat diet (HFD)-induced obese mice, we modulated CB2 signaling and investigated its effects on energy homeostasis and hypothalamic microgliosis/astrogliosis. We observed no effect on caloric intake and body weight gain in control diet-fed animals that received prolonged icv infusion of the CB2 receptor agonist HU308. Interestingly, we observed a decrease in glucose tolerance in HFD-fed animals treated with HU308. Prolonged icv infusion of HU308 increases astrogliosis in the ventromedial nucleus (VMH) of obese animals and reduced HFD-induced microgliosis in the hypothalamic arcuate (ARC) but not in the paraventricular (PVN) or VMH nuclei. These data indicate that central CB2 signaling modulates glucose homeostasis and glial reactivity in obesogenic conditions, irrespective of changes in body weight.

Flavanone Glycosides, Triterpenes, Volatile Compounds and Antimicrobial Activity of Miconia minutiflora (Bonpl.) DC. (Melastomataceae).

Chemical composition of the essential oils and extracts and the antimicrobial activity of Miconia minutiflora were investigated. The flavanone glycosides, pinocembroside and pinocembrin-7-O-[4″,6″-HHDP]-ß-D-glucose, were identified, along with other compounds that belong mainly to the triterpene class, besides the phenolics, gallic acid and methyl gallate. Sesquiterpenes and monoterpenes were the major compounds identified from the essential oils. Screening for antimicrobial activity from the methanolic extract of the leaves showed that the MIC and MMC values against the tested microorganisms ranged from 0.625 to 5 mg·mL−1 and that the extract was active against microorganisms, Staphyloccocus aureus, Escherichia coli, and Bacillus cereus.

Challenges for obesity management in a unified health system: the view of health professionals.

BACKGROUND: Obesity is an increasingly prevalent chronic condition. Its multiple causes and the complexity of its treatment pose challenges for health professionals. OBJECTIVE: To explore and describe the challenges for obesity management in the Brazilian Unified Health System according to health professionals. METHODS: An exploratory quantitative web-based study, carried out in 2018 with health professionals, developed from the first stage of a national project that aims to examine the management of obesity in Brazil. The questionnaire was self-applied. Invitations to participate in the research were sent by the Ministry of Health, Health Department of Minas Gerais and members of the research group. We collected data on sex, age, professional category, region and level of care. The challenges were investigated using a Likert scale and categorized into structure and work process. RESULTS: We evaluated 1323 professionals, of which about 45% were dietitians, 90.2% were women, and 83.1% self-reported working in primary health care. The main barriers cited included a high demand for curative and individual assistance, the presence of comorbidities, and the absence or insufficient access to instructional materials, professional qualification and lack of support. CONCLUSION: Obesity management is a critical challenge for all professionals. Barriers were related to the work process and structural aspects and reinforce the need to empower health teams. We propose that permanent education activities should be established, as well as the development of instructional materials that are applicable to routine work. Finally, the results may be used to develop policies and strategies to improve obesity management.

Essential oil of Ocimum gratissimum (Linnaeus, 1753): efficacy for anesthesia and transport of Oreochromis niloticus.

This study aimed to evaluate the essential oil of Ocimum gratissimum L. (EOOG) for anesthesia and in the transport of Oreochromis niloticus. Experiment I determined the time of anesthesia induction and recovery during anesthesia of O. niloticus exposed to different concentrations of EOOG (0, 30, 90, 150, and 300 mg L-1). Based on data from Experiment I, Experiment II evaluated the effect of 0, 30, and 90 mg L-1 EOOG on blood parameters and oxidative stress immediately after anesthesia induction and 1 h after recovery. Experiment III evaluated the effect of 0, 5, and 10 mg L-1 EOOG on blood variables immediately after 4.5 h of transport of juveniles. Concentrations between 90 and 150 mg L-1 EOOG were efficient for anesthesia and recovery. The use of 90 mg L-1 of EOOG prevented an increase in plasma glucose. Other changes in blood parameters and oxidative stress are discussed. The use of 10 mg L-1 EOOG in transport increased plasma glucose and decreased hematocrit values immediately after transport. It is concluded that the use of 90 and 150 mg L-1 EOOG causes anesthesia and recovery in O. niloticus within the time intervals considered ideal. The use of 90 mg L-1 EOOG favored stable plasma glucose soon after anesthesia induction and 1 h after recovery, but caused changes in the antioxidant defense system by increasing hepatic and kidney ROS. The transport of 12 g O. niloticus for 4.5 h can be performed with concentration of 5 mg L-1 of EOOG.

Physiological and metabolic responses in juvenile Colossoma macropomum exposed to hypoxia.

This study aimed to evaluate hematological, biochemical, and gasometric parameters of tambaqui juveniles (Colossoma macropomum) exposed to hypoxia and subsequent recovery. Six animals were subjected to normoxia (basal) treatment with dissolved oxygen (DO) 6.27 ± 0.42 mg L-1. Water flow and aeration were reduced for 3 days (hypoxia), during which DO was 0.92 ± 0.37 mg L-1. Water flow and aeration were then reestablished with DO remaining similar to basal. The treatments were as follows: normoxia (basal); 24 h after initiating hypoxia (24H); 72 h after initiating hypoxia (72H); 24 h after reestablishing normoxia (24R); 48 h after reestablishing normoxia (48R); and 96 after reestablishing normoxia (96R). The highest glucose level was recorded at 24H (P < 0.05); the highest lactate level was at 72R; and the highest blood pH was at 24H and 72H (P < 0.05). The highest concentration of PvCO2 was at 24H (P < 0.05), while at 96R it was equivalent to basal (P > 0.05). The variable PvO2 was only higher than basal at 24R (P < 0.05). Juvenile C. macropomum managed to reestablish the main stress indicators (glucose and lactate) at 96R, while the other indicators varied during the study, with homeostatic physiology being reestablished during the recovery period.

The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats.

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (†P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, †P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (†P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (†P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats.

Coexistence of risk behaviors for being overweight among Brazilian adolescents.

This study aimed to evaluate the magnitude of and the factors associated with the coexistence of risk behaviors for being overweight among Brazilian adolescents. This is a cross-sectional study with a representative sample of adolescents (mostly aged 13-15years) enrolled from public and private schools of Brazil in 2012. The co-occurring sedentary behavior and inadequate food consumption (regular intake of sugary and fried foods, and irregular consumption of fruits and vegetables-FV) was estimated using a Venn diagram. Sociodemographic, familial, and behavioral factors associated with the number of risk behaviors for being overweight were identified using an ordinal logistic regression analysis. Sedentary behavior was observed in 62.0% of adolescents. Regular intake of sugary or fried food was observed in 55.3% and 23.5% of adolescents, respectively, with 51.9% having an inadequate intake of FV. At least one risk behavior was reported in >90.0% of adolescents; 6.1% reported all 4. Being female, having a higher maternal education level, attending private school, not having breakfast or meals with parents regularly, eat watching television, and not practicing weekly leisure time physical activity were associated with an increased chance of having multiple risk behaviors. This study observed a high prevalence of coexisting of risk behaviors, which was associated with sociodemographic, familial, and behavioral factors. These findings may contribute to a clearer understanding of the associations between different behaviors among adolescents, and may be used to improve public health surveillance and to develop strategies that address multiple behaviors, in order to prevent overweight among adolescents.

A Curated Cell Life Imaging Dataset of Immune-enriched Pancreatic Cancer Organoids with Pre-trained AI Models.

Tumor organoids are three-dimensional in vitro models which can recapitulate the complex mutational landscape and tissue architecture observed in cancer patients, providing a realistic model for testing novel therapies, including immunotherapies. A significant challenge in organoid research in oncology lies in developing efficient and reliable methods for segmenting organoid images, quantifying organoid growth, regression and response to treatments, as well as predicting the behavior of organoid systems. Up to now, a curated dataset of organoids co-cultured with immune cells is not available. To address this gap, we present a new public dataset, comprising both phase-contrast images of murine and patient-derived tumor organoids of one of the deadliest cancer types, the Pancreatic Ductal Adenocarcinoma, co-cultured with immune cells, and state-of-the-art algorithms for object detection and segmentation. Our dataset, OrganoIDNetData, encompassing 180 images with 33906 organoids, can be a potential common benchmark for different organoids segmentation protocols, moving beyond the current practice of training and testing these algorithms on isolated datasets.

OrganoIDNet: a deep learning tool for identification of therapeutic effects in PDAC organoid-PBMC co-cultures from time-resolved imaging data.

PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) remains a challenging disease due to its complex biology and aggressive behavior with an urgent need for efficient therapeutic strategies. To assess therapy response, pre-clinical PDAC organoid-based models in combination with accurate real-time monitoring are required. METHODS: We established stable live-imaging organoid/peripheral blood mononuclear cells (PBMCs) co-cultures and introduced OrganoIDNet, a deep-learning-based algorithm, capable of analyzing bright-field images of murine and human patient-derived PDAC organoids acquired with live-cell imaging. We investigated the response to the chemotherapy gemcitabine in PDAC organoids and the PD-L1 inhibitor Atezolizumab, cultured with or without HLA-matched PBMCs over time. Results obtained with OrganoIDNet were validated with the endpoint proliferation assay CellTiter-Glo. RESULTS: Live cell imaging in combination with OrganoIDNet accurately detected size-specific drug responses of organoids to gemcitabine over time, showing that large organoids were more prone to cytotoxic effects. This approach also allowed distinguishing between healthy and unhealthy status and measuring eccentricity as organoids' reaction to therapy. Furthermore, imaging of a new organoids/PBMCs sandwich-based co-culture enabled longitudinal analysis of organoid responses to Atezolizumab, showing an increased potency of PBMCs tumor-killing in an organoid-individual manner when Atezolizumab was added. CONCLUSION: Optimized PDAC organoid imaging analyzed by OrganoIDNet represents a platform capable of accurately detecting organoid responses to standard PDAC chemotherapy over time. Moreover, organoid/immune cell co-cultures allow monitoring of organoid responses to immunotherapy, offering dynamic insights into treatment behavior within a co-culture setting with PBMCs. This setup holds promise for real-time assessment of immunotherapeutic effects in individual patient-derived PDAC organoids.

Arsenic bioaccumulation and biotransformation in different tissues of Nile tilapia (Oreochromis niloticus): A comparative study between As(III) and As(V) exposure and evaluation of antagonistic effects of selenium.

The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.

The Mini Nutritional Assessment-Short Form is more effective in predicting clinical outcomes among hospitalised patients with overweight than the Nutritional Risk Screening-2002.

Understanding of the association between nutritional risk and clinical outcomes in hospitalised patients with overweight is still at an early stage. Given the lack of specific tools for the patient with overweight, the objective of this study was to compare two of the main general screening instruments for assessing nutritional risk in predicting clinical outcomes in a population of hospitalised patients with overweight. A retrospective study was carried out in a medium-sized hospital in Brazil, with patients ≥20 years old admitted between July 2017 and December 2019. Patients who were overweight and had records of Nutritional Risk Screening-2002 (NRS-2002) and Mini-Nutritional Assessment-Short Form (MNA-SF) in their medical files were included in the study. Clinical outcomes data (longer length of stay, readmission during the study period and mortality before the end of study or during hospitalisation) were obtained. The Kappa coefficient assessed agreement between both tools, and their performance for predicting outcomes was analysed using characteristic receiver operating curves (ROC). Data were collected from 643 patients. The prevalence of nutritional risk was 17.7% and 36.1% according to the NRS-2002 and MNA-SF (k = 0.390; p < 0.001), respectively. According to both tools, all clinical outcomes were significantly more common among individuals at nutritional risk (p < 0.05). Only the MNA-SF showed a significant percentage of predictions for readmission (57.2%) and death during hospitalisation (65.7%). For mortality until the end of the study, the area under the ROC curve was similar for MNA-SF (60.5%) and NRS-2002 (60.7%; p = 0.057). The MNA-SF detected a greater proportion of nutritional risk among hospitalised patients with overweight and better predicted all clinical outcomes compared to the NRS-2002 and should be used to screen patients with overweight for nutritional risk.

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial.

INTRODUCTION: Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interindividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron. METHODS: A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A. RESULTS: Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the AA genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034). CONCLUSION: A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy. REGISTER: ClinicalTrials.gov.

Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders.

Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. Significance statement: A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.

An Alternative Technique for Monitoring the Live Interaction of Monocytes and Tumor Cells with Nanoparticles in the Mouse Lung.

Nanomaterials are increasingly used for the diagnosis and treatment of cancer, including lung cancer. For the clinical translation of nano-based theranostics, it is vital to detect and monitor their accumulation in the tumor, as well as their interaction with tumor, immune cells, and the tumor microenvironment (TME). While high resolution microscopy of fixed tumor specimens can provide some of this information from individual thin slices, it cannot capture cellular events over time and lacks 3D information of the tumor tissue. On the other hand, in vivo optical procedures either fall short of providing the necessary cellular resolution, as in the case of epifluorescence optical imaging, or are very demanding, as for instance intravital lung microscopy. We describe an alternative approach to investigate nanoparticle-cell interactions in entire mouse lung lobes, by longitudinal live cell confocal microscopy at nanometer resolution. By filling the lung ex vivo with 1% agarose, we were able to stabilize the lung lobes and visualize the interaction of fluorescent cells and nanoparticles for at least 4 hours post mortem. This high resolution ex vivo live cell imaging approach is an easy 4D tool for assessing several dynamic processes in tumor tissue, such as the traffic of cells, shedding of extracellular vesicles (EVs), and the accumulation of nanoparticles in tumor tissue. Graphic abstract: Schematic of the workflow for live cell imaging in the mouse lung.

Customized Photobiomodulation Modulates Pain and Alters Thermography Pattern in Patients with Knee Osteoarthritis: A Randomized Double-Blind Pilot Study.

Background: Photobiomodulation therapy (PBMT) modulates a wide variety of biological processes, leading to anti-inflammatory and analgesic effects. Understanding the mechanisms underlying therapeutic effects of PBMT remains challenging due to varying outcomes observed between wavelengths, dosage, and site of application. Our research group has dedicated close attention to customization and individualization of dosimetry for PBMT protocols. Preliminary data showed that using an individualized treatment could solve contradictory results reported by previous studies. Based on literature and our preliminary data on light absorption, the goal of the present pilot is to determine whether our individualized dosimetry is a feasible method to assist osteoarthritis (OA) pain control. Methods: This parallel two-arm controlled-pilot study aimed to assess whether personalized PBMT can be effective in the treatment of painful chronic knee OA. Thirty-one patients were randomly allocated into treatment and placebo group (sham irradiation), and the treatment procedure was performed twice a week, for 5 weeks. The PBMT was applied using 850 nm with continuous wave and a total of 526-1402 J each session. Individualized dosimetry was chosen based on each patient's body mass index and skin color. Quality-of-life (QOL) questionnaires and serum/urine analyses were performed before and after treatment was over. Both examiners and participants were blinded to group allocation. Results: Pain scores were reduced significantly in the 4th, 5th, and 10th sessions and remained lower 6 weeks posttherapy in the treatment group when compared to the placebo group. Moreover, the treatment group's results were improved in QOL questionnaires score, dopamine level, and in microcirculation. Conclusions: The present results provide initial evidence that customized photobiomodulation (PBM) reduce pain levels in short- and medium-term in patients with symptomatic knee OA when compared to placebo group. Furthermore, we have provided evidence that customized PBM is able to improve the QOL of those patients.

Serum biomarkers associated with SARS-CoV-2 severity.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.