Concomitant Treatment with Doxycycline and Rifampicin in Balb/c Mice Infected with Brucella abortus 2308 Fails to Reduce Inflammation and Motor Disability.

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.

Convergence between helminths and breast cancer: intratumoral injection of the excretory/secretory antigens of the human parasite Toxocara canis (EST) increase lung macro and micro metastasis.

Introduction: Worldwide, breast cancer is the most important cancer in incidence and prevalence in women. Different risk factors interact to increase the probability of developing it. Biological agents such as helminth parasites, particularly their excretory/secretory antigens, may play a significant role in tumor development. Helminths and their antigens have been recognized as inducers or promoters of cancer due to their ability to regulate the host's immune response. Previously in our laboratory, we demonstrated that chronic infection by Toxocara canis increases the size of mammary tumors, affecting the systemic response to the parasite. However, the parasite does not invade the tumor, and we decided to study if the excretion/secretion of antigens from Toxocara canis (EST) can affect the progression of mammary tumors or the pathophysiology of cancer which is metastasis. Thus, this study aimed to determine whether excretion/secretion T. canis antigens, injected directly into the tumor, affect tumor growth and metastasis. Methods: We evaluated these parameters through the monitoring of the intra-tumoral immune response. Results: Mice injected intratumorally with EST did not show changes in the size and weight of the tumors; although the tumors showed an increased microvasculature, they did develop increased micro and macro-metastasis in the lung. The analysis of the immune tumor microenvironment revealed that EST antigens did not modulate the proportion of immune cells in the tumor, spleen, or peripheral lymph nodes. Macroscopic and microscopic analyses of the lungs showed increased metastasis in the EST-treated animals compared to controls, accompanied by an increase in VEGF systemic levels. Discussion: Thus, these findings showed that intra-tumoral injection of T. canis EST antigens promote lung metastasis through modulation of the tumor immune microenvironment.

Frontal Cortex Lipid Alterations During the Onset of Alzheimer's Disease.

Background: Although sporadic Alzheimer's disease (AD) is a neurodegenerative disorder of unknown etiology, familial AD is associated with specific gene mutations. A commonality between these forms of AD is that both display multiple pathogenic events including cholinergic and lipid dysregulation. Objective: We aimed to identify the relevant lipids and the activity of their related receptors in the frontal cortex and correlating them with cognition during the progression of AD. Methods: MALDI-mass spectrometry imaging (MSI) and functional autoradiography was used to evaluate the distribution of phospholipids/sphingolipids and the activity of cannabinoid 1 (CB1), sphingosine 1-phosphate 1 (S1P1), and muscarinic M2/M4 receptors in the frontal cortex (FC) of people that come to autopsy with premortem clinical diagnosis of AD, mild cognitive impairment (MCI), and no cognitive impairment (NCI). Results: MALDI-MSI revealed an increase in myelin-related lipids, such as diacylglycerol (DG) 36:1, DG 38:5, and phosphatidic acid (PA) 40:6 in the white matter (WM) in MCI compared to NCI, and a downregulation of WM phosphatidylinositol (PI) 38:4 and PI 38:5 levels in AD compared to NCI. Elevated levels of phosphatidylcholine (PC) 32:1, PC 34:0, and sphingomyelin 38:1 were observed in discrete lipid accumulations in the FC supragranular layers during disease progression. Muscarinic M2/M4 receptor activation in layers V-VI decreased in AD compared to MCI. CB1 receptor activity was upregulated in layers V-VI, while S1P1 was downregulated within WM in AD relative to NCI. Conclusions: FC WM lipidomic alterations are associated with myelin dyshomeostasis in prodromal AD, suggesting WM lipid maintenance as a potential therapeutic target for dementia.

In vitro effect of diazoxon on cell signaling and second messengers in Nile tilapia (Oreochromis niloticus) leukocytes.

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides (OPs). Some reports have shown that diazinon (DZN) causes immunotoxic effects; diazoxon (DZO), the oxon metabolite of DZN, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of DZO on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that DZO leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, DZO does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, DZO inhibits leukocyte responsiveness to PMA and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that DZO significantly affects key molecular parameters related to cell signaling.

Effect of Pediococcus acidilactici and mango seed polyphenols on the fermentative profile of the indigestible fraction of yam bean.

Yam bean is an important source of dietary fiber and other components that comprise the total indigestible fraction (TIF), which can be fermented by the colonic microbiota and produce metabolites with beneficial health effects. Therefore, the objective of this study was to evaluate the in vitro colonic fermentation of yam bean TIF and the changes caused by the addition of a polyphenolic extract of mango seed and the lactic acid bacteria Pediococcus acidilactici. The mango seed extract was obtained by ultrasound-assisted extraction, and the microbial growth rate and viability of P. acidilactici were determined using a Neubauer chamber. Yam bean TIF was isolated by triple enzymatic hydrolysis and subjected to in vitro colonic fermentation in combination with treatments with mango seed extract and P. acidilactici suspensions. Changes in pH, total soluble phenols (TSP), and antioxidant capacity (AOX) were evaluated. Furthermore, the production of metabolites was quantified by HPLC-DAD-MS and GC-MS. The Growth rate of P. acidilactici was 0.1097 h-1 with 97.5 % viability at 7 h of incubation. All TIF treatments showed a high capacity of fermentation, and the addition of mango seed extract increased the TSP content and AOX in DPPH and FRAP assays. A total of Forty-six volatile metabolites were detected, with highlighting the presence of esters, benzenes, aldehydes, and short-chain fatty acids. Five phenolic compounds associated with mango by-products were quantified during all fermentation process, despite the concentration of the extract. P. acidilactici did not substantially modify the fermentative profile of TIF. However, further studies such as the evaluation of the abundance of microbial communities may be necessary to observe whether it can generate changes during colonic fermentation.

Imipramine Administration in Brucella abortus 2308-Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count.

Brucellosis infection causes non-specific symptoms such as fever, chills, sweating, headaches, myalgia, arthralgia, anorexia, fatigue, and mood disorders. In mouse models, it has been associated with increased levels of IL-6, TNF-α, and IFN-γ, a decrease in serotonin and dopamine levels within the hippocampus, induced loss of muscle strength and equilibrium, and increased anxiety and hopelessness. Imipramine (ImiP), a tricyclic antidepressant, is used to alleviate neuropathic pain. This study evaluated the effects of ImiP on Balb/c mice infected with Brucella abortus 2308 (Ba) at 14- and 28-days post-infection. Serum levels of six cytokines (IFN-γ, IL-6, TNF-α, IL-12, MCP-1. and IL-10) were assessed by FACS, while the number of bacteria in the spleen was measured via CFU. Serotonin levels in the hippocampus were analyzed via HPLC, and behavioral tests were conducted to assess strength, equilibrium, and mood. Our results showed that mice infected with Brucella abortus 2308 and treated with ImiP for six days (Im6Ba14) had significantly different outcomes compared to infected mice (Ba14) at day 14 post-infection. The mood was enhanced in the forced swimming test (FST) (p < 0.01), tail suspension test (TST) (p < 0.0001), and open-field test (p < 0.0001). Additionally, there was an increase in serotonin levels in the hippocampus (p < 0.001). Furthermore, there was an improvement in equilibrium (p < 0.0001) and muscle strength (p < 0.01). Lastly, there was a decrease in IL-6 levels (p < 0.05) and CFU count in the spleen (p < 0.0001). At 28 days, infected mice that received ImiP for 20 days (Im20Ba28) showed preservation of positive effects compared to infected mice (Ba28). These effects include the following: (1) improved FST (p < 0.0001) and TST (p < 0.0001); (2) better equilibrium (p < 0.0001) and muscle strength (p < 0.0001); (3) decreased IL-6 levels (p < 0.05); and (4) reduced CFU count in the spleen (p < 0.0001). These findings suggest the potential for ImiP to be used as an adjuvant treatment for the symptoms of brucellosis, which requires future studies.

Quantitative evaluation of large corporate climate action initiatives shows mixed progress in their first half-decade.

Corporate climate initiatives such as the Science-Based Targets initiative and RE100 have gained significant prominence in recent years, with considerable increases in membership and several ex-ante studies stating how they could bring substantive emissions reductions beyond national goals. However, studies evaluating their progress are scarce, raising questions on how members achieve targets and whether their contributions are genuinely additional. Here we assess these initiatives by disaggregating membership by sector and geographic region and then thoroughly evaluating their progress between 2015-2019 using public environmental data disclosed by 102 of their largest members by revenue. Our results show that the collective Scope 1 and 2 emissions of these companies have fallen by 35.6%, with companies generally on track or exceeding scenarios keeping global warming below 2 °C. However, most of these reductions are concentrated in a small number of intensive companies. Most members show little evidence of emission reductions within their operations, only achieving progress via renewable electricity purchases. We highlight how intermediate steps regarding data robustness and implementation of sustainability measures are lacking: 75% of public company data is independently verified at low levels of assurance, and 71% of renewable electricity is obtained through low-impact or undisclosed sourcing models.

Characterization and In Vivo Assay of Allantoin-Enriched Pectin Hydrogel for the Treatment of Skin Wounds.

This work describes a liquid allantoin-enriched pectin hydrogel with hydrophilic behavior that is supported by the presence of functional groups related to healing efficacy. A topical study shows the effect of the hydrogel application on surgically induced skin wound healing in a rat model. Contact angle measurements confirm hydrophilic behavior (11.37°), while Fourier-transform infrared spectroscopy indicates the presence of functional groups related to the healing effectiveness (carboxylic acid and amine groups). Allantoin is distributed on the surface and inside the amorphous pectin hydrogel surrounded by a heterogeneous distribution of pores. This promotes wound drying with better interaction between the hydrogel and cells involved in the wound healing process. An experimental study with female Wistar rats indicates that the hydrogel improves wound contraction, reducing around 71.43% of the total healing time and reaching total wound closure in 15 days.

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates.

Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. This review focuses on the scientific evidence of exposure to OPs and their toxic effects on the immune system of non-target organisms (invertebrates and vertebrates) from a descriptive perspective of the immuno-toxic mechanisms associated with susceptibility to the development of bacterial, viral, and fungal infectious diseases. During the exhaustive review, we found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.

Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson's Disease.

Multiple evidences suggest that mitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease via the selective cell death of dopaminergic neurons, such as that which occurs after prolonged exposure to the mitochondrial electron transport chain (ETC) complex I inhibitor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP). However, the effects of chronic MPTP on the ETC complexes and on enzymes of lipid metabolism have not yet been thoroughly determined. To face these questions, the enzymatic activities of ETC complexes and the lipidomic profile of MPTP-treated non-human primate samples were determined using cell membrane microarrays from different brain areas and tissues. MPTP treatment induced an increase in complex II activity in the olfactory bulb, putamen, caudate, and substantia nigra, where a decrease in complex IV activity was observed. The lipidomic profile was also altered in these areas, with a reduction in the phosphatidylserine (38:1) content being especially relevant. Thus, MPTP treatment not only modulates ETC enzymes, but also seems to alter other mitochondrial enzymes that regulate the lipid metabolism. Moreover, these results show that a combination of cell membrane microarrays, enzymatic assays, and MALDI-MS provides a powerful tool for identifying and validating new therapeutic targets that might accelerate the drug discovery process.

Hematologic analysis of hospitalized patients and outpatients infected with SARS-CoV-2 and possible use as a prognostic biomarker.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem; this has caused thousands of deaths around the world. This infection induces hematologic alterations, and it is necessary to recognize predictive biomarkers to address the need for hospitalization or the severity of the disease. This study aimed to analyze different parameters in outpatients and hospitalized patients infected with SARS-CoV-2 and determine whether hematic biometry can be used for prognosis rapidly. We analyzed 689 patients, of whom 355 were outpatients (162 women and 193 men) and 334 required hospitalization (197 men and 137 women). The average age of the hospitalized patients was 46 years (men, 49 years; women, 52 years), whereas the average age of the outpatients was 49 years (men, 51 years; women, 44 years). Hematologic parameters were analyzed and compared between the outpatients and hospitalized patients. The patients were divided into groups by age and sex. We found that in the hospitalized patients, the erythrocyte, hematocrit, and hemoglobin levels decreased, whereas the outpatients did not experience changes in the erythroid series. In leukocytes, these increased significantly, as they did in neutrophils; however, lymphocytopenia was observed. In the outpatients, we observed normal levels of neutrophils and lymphopenia. We can conclude that hematic biometry can be used as a biomarker, and the relation between neutrophils and lymphocytes is indicated for understanding the development and prognosis of the disease.

Mass Spectrometry for the Advancement of Lipid Analysis in Alzheimer's Research.

Recent technical advances in mass spectrometry, as applied to the analytical chemistry of lipid molecules, enable the simultaneous detection of the multiplicity of lipid complex species present in the human brain. This, in combination with quantitative studies carried out in plasma samples, helps to identify disease biomarkers including for Alzheimer's disease (AD). Mass spectrometry imaging (MSI) is particularly powerful for the anatomical localization of lipids in brain slices, identifying lipid modifications in postmortem frozen samples from AD patients.Human brain tissues are sectioned in a cryostat and then covered with a chemical matrix, such as mercaptobenzothiazole (MBT) or α-cyano-4-hydroxycinnamic acid (CHCA), to ionize the lipid molecules either by sublimation or by spraying. We describe the use of matrix-assisted laser desorption ionization (MALDI) in an LTQ-Orbitrap-XL mass spectrometer to scan brain tissue slices with high spatial resolution, analyzing 50 µm cell layers. The lipid spectra obtained for each pixel are transformed to color-coded intensity maps of hundreds of lipid species included those within a single tissue slice.

Post-COVID-19 Syndrome in Outpatients and Its Association with Viral Load.

INTRODUCTION: The COVID-19 pandemic is the result of the SARS-CoV-2 virus, which has caused more than 100 million infections and more than 2.5 million deaths worldwide, representing a serious public health problem. The gold method for detecting this virus is qRT-PCR, which is a semiquantitative technique where the viral load can be established through its cycle threshold (Ct). It has also been reported that COVID-19 generates long-term symptoms (post-COVID-19). METHODS: After three months, a survey was performed on 70 COVID-19 confirmed patients; subsequently, we divided them into four groups (persistent symptoms, chemo-sensitive, cognitive issues, and changes in habit) in order to determine the correlation between viral load and post-COVID-19 symptoms. RESULTS: Data show that fatigue, nervousness, anosmia, and diet changes are common long-term symptoms; in addition, a negative correlation was found between viral load and the number of post-COVID-19 symptoms. CONCLUSION: COVID-19 generates long-term symptoms which can cause problems with psychological and social repercussions.

Intratumoral Treatment with 5-Androstene-3ß, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3ß, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 µM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.

Cannabinoid Receptors and Glial Response Following a Basal Forebrain Cholinergic Lesion.

The endocannabinoid system modulates learning, memory, and neuroinflammatory processes, playing a key role in neurodegeneration, including Alzheimer's disease (AD). Previous results in a rat lesion model of AD showed modulation of endocannabinoid receptor activity in the basalo-cortical pathway following a specific lesion of basal forebrain cholinergic neurons (BFCNs), indicating that the glial neuroinflammatory response accompanying the lesion is related to endocannabinoid signaling. In this study, 7 days after the lesion, decreased astrocyte and increased microglia immunoreactivities (GFAP and Iba-1) were observed, indicating microglia-mediated neuroinflammation. Using autoradiographic studies, the density and functional coupling to G-proteins of endocannabinoid receptor subtypes were studied in tissue sections from different brain areas where microglia density increased, using CB1 and CB2 selective agonists and antagonists. In the presence of the specific CB1 receptor antagonist, SR141716A, [3H]CP55,940 binding (receptor density) was completely blocked in a dose-dependent manner, while the selective CB2 receptor antagonist, SR144528, inhibited binding to 25%, at best. [35S]GTPγS autoradiography (receptor coupling to Gi/0-proteins) evoked by CP55,940 (CB1/CB2 agonist) and HU308 (more selective for CB2) was abolished by SR141716A in all areas, while SR144528 blocked up to 51.8% of the coupling to Gi/0-proteins evoked by CP55,940 restricted to the nucleus basalis magnocellularis. Together, these results demonstrate that there are increased microglia and decreased astrocyte immunoreactivities 1 week after a specific deletion of BFCNs, which projects to cortical areas, where the CB1 receptor coupling to Gi/0-proteins is upregulated. However, at the lesion site, the area with the highest neuroinflammatory response, there is also a limited contribution of CB2.

Risk and Benefit Analysis of Fish Consumption in NW Mexico: Mercury, Selenium, and Fatty Acids.

To balance the risks and benefits of fish consumption, selenium, fatty acids (DHA + EPA), and mercury in fishery products were determined. Analyzed products were canned tuna, frozen tuna (Thunnus albacares), smoked striped marlin (Tetrapturus audax), fresh Pacific sierra (Scomberomorus sierra), fresh dolphinfish (Coryphaena hippurus), fresh tilapia (Gerres cinereus), and fresh bullseye puffer (Sphoeroides annulatus). Mercury (µg g-1 wet weight) ranged from 0.01 (dolphinfish) to 0.23 (bullseye puffer); Se ranged from 0.12 to 0.25. EPA + DHA ranged from 1.16 to 10.72 mg g-1. Intake of EPA + DHA was comparable or above the recommended daily intake; Hg intake was below the reference dose but Se intake was below than recommended values for the different population groups. Considering the HBVSe, fishery products had positive values; i.e., they are healthy food items. According to the interaction of Hg and Se and the rate of fishery product consumption, the risk for consumers is below one percent.

Comparative Analysis of Age, Sex, and Viral Load in Outpatients during the Four Waves of SARS-CoV-2 in A Mexican Medium-Sized City.

Governments have implemented measures to minimize SARS-CoV-2 spread. However, these measures were relaxed, and the appearance of new variants has prompted periods of high contagion known as waves. In Mexico, four waves distributed between July and August 2020, January and February 2021, August and September 2021, and January and February 2022 have appeared. Current health policies discourage mass sampling, preferring to focus on the corrective treatment of severe cases. Outpatients are only advised to undergo brief voluntary confinement and symptomatic treatment, with no follow-up. Therefore, the present study aimed to analyze sex, age, and viral load in outpatients during the four waves in a medium-sized city in Mexico. For each wave, the date of peak contagion was identified, and data were collected within ±15 days. In this regard, data from 916 patients (434 men and 482 women) were analyzed. The age range of positive patients (37-45 years) presented a higher frequency during the first and third waves, while 28-36 years was the most frequent age range during the second and fourth waves, while the viral load values were significantly higher, for both sexes, during the fourth wave. Obtained data of COVID-19 prevalence in population segments can be used for decision-making in the design of effective public health policies.

Organophosphorus Pesticides as Modulating Substances of Inflammation through the Cholinergic Pathway.

Organophosphorus pesticides (OPs) are widespread insecticides used for pest control in agricultural activities and the control of the vectors of human and animal diseases. However, OPs' neurotoxic mechanism involves cholinergic components, which, beyond being involved in the transmission of neuronal signals, also influence the activity of cytokines and other pro-inflammatory molecules; thus, acute and chronic exposure to OPs may be related to the development of chronic degenerative pathologies and other inflammatory diseases. The present article reviews and discusses the experimental evidence linking inflammatory process with OP-induced cholinergic dysregulation, emphasizing the molecular mechanisms related to the role of cytokines and cellular alterations in humans and other animal models, and possible therapeutic targets to inhibit inflammation.

SARS-CoV-2 Transmission Risk Model in an Urban Area of Mexico, Based on GIS Analysis and Viral Load.

The COVID-19 pandemic highlighted health systems vulnerabilities, as well as thoughtlessness by governments and society. Due to the nature of this contingency, the use of geographic information systems (GIS) is essential to understand the SARS-CoV-2 distribution dynamics within a defined geographic area. This work was performed in Tepic, a medium-sized city in Mexico. The residence of 834 COVID-19 infected individuals was georeferenced and categorized by viral load (Ct). The analysis took place during the maximum contagion of the first four waves of COVID-19 in Mexico, analyzing 158, 254, 143, and 279 cases in each wave respectively. Then heatmaps were built and categorized into five areas ranging from very low to very high risk of contagion, finding that the second wave exhibited a greater number of cases with a high viral load. Additionally, a spatial analysis was performed to measure urban areas with a higher risk of contagion, during this wave this area had 19,203.08 km2 (36.11% of the city). Therefore, a kernel density spatial model integrated by meaningful variables such as the number of infected subjects, viral load, and place of residence in cities, to establish geographic zones with different degrees of infection risk, could be useful for decision-making in future epidemic events.

Handling and novel object recognition modulate fear response and endocannabinoid signaling in nucleus basalis magnocellularis.

Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naïve rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.