Unveiling ancestral threads: Exploring CCR5 ∆32 mutation frequencies in Colombian populations for HIV/AIDS therapeutics.

AIDS remains a significant global health challenge since its emergence in 1981, with millions of deaths and new cases every year. The CCR5 ∆32 genetic deletion confers immunity to HIV infection by altering a cell membrane protein crucial for viral entry. Stem cell transplants from homozygous carriers of this mutation to HIV-infected individuals have resulted in viral load reduction and disease remission, suggesting a potential therapeutic avenue. This study aims to investigate the relationship between genetic ancestry and the frequency of the CCR5 ∆32 mutation in Colombian populations, exploring the feasibility of targeted donor searches based on ancestry composition. Utilizing genomic data from the CÓDIGO-Colombia consortium, comprising 532 individuals, the study assessed the presence of the CCR5 ∆32 mutation and examined if the population was on Hardy-Weinberg equilibrium. Individuals were stratified into clusters based on African, American, and European ancestry percentages, with logistic regression analysis performed to evaluate the association between ancestry and mutation frequency. Additionally, global genomic databases were utilized to visualize the worldwide distribution of the mutation. The findings revealed a significant positive association between European ancestry and the CCR5 ∆32 mutation frequency, underscoring its relevance in donor selection. African and American ancestry showed negative but non-significant associations with CCR5 ∆32 frequency, which may be attributed to the study's limitations. These results emphasize the potential importance of considering ancestry in donor selection strategies, reveal the scarcity of potential donors in Colombia, and underscore the need to consider donors from other populations with mainly European ancestry if the CCR5 ∆32 stem cell transplant becomes a routine treatment for HIV/AIDS in Colombia.

Clinical characteristics and severity markers in hospitalized COVID-19 patients from western Mexico: a comparative analysis of Delta and Omicron variants.

Introduction: COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus notable for its rapid mutation rate, which has led to the emergence of various variants such as Delta and Omicron, each with potentially different levels of transmissibility and virulence. Therefore, this study aims to compare clinical charactheristics and markers associated with the severity of COVID-19 in hospitalized patients from western Mexico who were infected with the Delta and Omicron variants of SARS-CoV-2. Methods: This cross-sectional study involved 66 patients hospitalized for COVID-19, diagnosed by RT-qPCR. SARS-CoV-2 variants were identified through whole genome sequencing using the COVIDseq platform from Illumina. Upon admission, patients underwent a clinical history assessment, blood gas analysis, and blood biometry. Additionally, several tests and markers were measured, including the percentage of neutralizing antibodies, erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), and ferritin. Results and discussion: Patients hospitalized with the Omicron were found to be older, compared to those infected with the Delta (64 vs. 54 years, p = 0.006). Additionally, a higher proportion of male patients were observed in the Omicron compared to the Delta (p = 0.029). Both Omicron and Delta variants were associated with lymphopenia, although the lymphocyte count was lower in Omicron (0.9 vs. 0.56 10x3/L; p = 0.007). The COVID-GRAM scale indicated a high risk for severe disease in both groups, but the score was higher in Omicron compared to Delta (157 vs. 128 points; p = 0.0004). Patients infected with Omicron exhibited a lower percentage of neutralizing antibodies than those with Delta (35.99 vs. 81%; p < 0.05), regardless of their vaccination status. Among the markers assessed, globular ESR was found to be lower in Omicron compared to Delta (30.5 vs. 41.5 mm/h; p = 0.001), while ferritin levels were higher in patients infected with the Omicron (1,359 vs. 960.6 µg/L; p = 0.007). In patients with severe COVID-19, markers such as lymphopenia, neutralizing antibody levels, ferritin, and COVID-GRAM scores are elevated in the Omicron variant, while only the leukocyte count and ESR for the Delta variant.

Case report on activated PI3K-delta syndrome.

BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) [OMIM 615513] is an inborn error of immunity with autosomal dominant inheritance caused by a pathogenic variant in the PIK3CD gene. The prevalence ratio of APDS is < 1: 1,000,000 newborns. The main clinical features of APDS are sinopulmonary infections, benign lymphoproliferation, autoinflammatory disease, and a major risk of lymphoid neoplasms. CLINICAL CASE: A 17-year-old female with a history of pneumonia at 9 months of age subsequently developed recurrent respiratory tract infections, bronchiectasis, perforated otitis media, unilateral tonsillar lymphoid hyperplasia, pansinusitis, recurrent oral candidiasis, and chronic rhinitis. Laboratory studies reported persistent leukopenia and lymphopenia, low CD4 lymphocyte subpopulation, and persistently elevated immunoglobulin M immunoglobulin studies with values up to 692 mg/dL. An inborn error of immunity next-generation sequencing and multiplex ligation-dependent probe amplification analysis detected a heterozygous pathogenic variant in the PIK3CD gene, compatible with APDS. Treatment with monthly injectable gamma globulin and prophylactic antibiotics was started, allowing better control of the infectious processes. CONCLUSION: This is the second case of APDS reported in Mexico in the literature. It is important to be aware of this condition to make a timely diagnosis, which requires a high clinical suspicion and immunological and genetic studies to provide adequate treatment and prevent complications.

INTRODUCCIÓN: El síndrome de la Fosfoinositida 3-cinasa delta activado (Activated Phosphoinositide 3-kinase δ síndrome, APDS) [OMIM 615513] es un error innato de la inmunidad con patrón de herencia autosómica dominante causada por una variante patogénica heterocigota del gen PIK3CD. Su prevalencia es < 1: 1,000,000 nacidos vivos. Las principales manifestaciones clínicas son infecciones sinopulmonares, linfoproliferación benigna, autoinmunidad y aumento del riesgo de malignización linfoide. CASO CLÍNICO: Femenino de 17 años de vida con antecedentes de neumonía a los 9 meses de edad, posteriormente infecciones de vías respiratorias recurrentes, bronquiectasias, otitis media perforada, hiperplasia linfoide de amigdala unilateral, pansinusitis, candidiasis oral recurrente y rinitis crónica. Los estudios de laboratorio reportaron leuco linfopenia persistente, subpoblación linfocitaria con CD4 baja y estudios de inmunoglobulinas con IgM persistentemente elevada con valor de hasta 692 mg/dl. Se realizó estudio molecular de secuenciación de siguiente generación (NGS por sus siglas en inglés Next-Generation Sequencing) y amplificación de sondas dependientes de ligandos múltiples (MLPA por sus siglas en inglés Multiplex Ligation-dependent Probe Amplification) dirigido a errores innatos de la inmunidad que detectó una variante patogénica en estado heterocigoto en el gen PIK3CD, compatible con APDS. Se inició tratamiento con gammaglobulina intravenosa mensual y antibiótico profiláctico, permitiendo mejor control de los procesos infecciosos. CONCLUSIONES: Este es el segundo caso reportado en la literatura de APDS en México, por lo que es importante su conocimiento para poder realizar un diagnóstico oportuno, para el cual se requiere una alta sospecha clínica, además de estudios inmunológicos y genéticos, con la finalidad de otorgar el tratamiento adecuado y prevenir complicaciones.

Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

BACKGROUND: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRß in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. RESULTS: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. CONCLUSIONS: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

Clinical profile and parameters of patients monoinfected with HBV and infected with HDV in Western Amazon.

Background: Hepatitis Delta represents a greater risk in the progression of advanced liver disease and HCC compared with HBV. The exact mechanism that determines the spontaneous clearance of delta virus or its progression to cirrhosis remains unknown. Therefore, this study aimed to analyze the clinical profile of HBV and HBV/HDV individuals in the Western Amazon. Methods: The study was carried out at the Specialized Outpatient Clinic for Viral Hepatitis belonging to the Centro de Pesquisa em Medicina Tropical de Rondônia/CEPEM. 100 individuals were included, stratified into two groups: 50 with hepatitis B virus and 50 with hepatitis Delta virus. Results: The overall mean age was 48 years. For the HBV and HDV groups, 66 % (33/50) and 54 % (27/50) were men and 56 % (28/50) and 58 % (29/50) were on antiviral treatment, respectively. Patients with detectable HDV-RNA demonstrated high levels of ALT and AST compared to individuals with undetectable HDV-RNA. Comparative analysis between HBV carriers and infected with HDV shows significant differences in terms of age, HBV-DNA levels, albumin, hepatomegaly and splenomegaly. Conclusion: Several markers were important for differentiating HBV and HDV infections. HDV-RNA detectable showed significant changes in biomarkers compared to undetectable patients, suggesting a possible worse prognostic effect in this group.

Multisensor Magnetic Scanning Microscope for Remanent Magnetic Field Measurements.

Magnetic Scanning Microscopy (MSM) emerged with the aim of allowing the visualization of magnetic fields of a sample or material through scanning and proved particularly useful for geology, biomedicine, characterization of magnetic materials, and in the steel industry. In this regard, the reading system of an MSM was modified using a µ-metal magnetic shielding structure to analyze remanent fields. The MSM was adapted to perform readings using two different types of sensors. The sensitive area of the sensors was evaluated, and the HQ-0811 (AKM-Asahi KaseiTM Microdevices) and STJ-010 (Micro MagneticsTM) sensors were chosen, with the HQ-0811 standardized on Printed Circuit Boards (PCBs) to facilitate handling and increase the system's robustness. In the shielded chamber, two piezoelectric ANC-150 stepper motors (Attocube Systems) were used, arranged planarly, to allow the movement of the analyzed samples under the mounted sensors. To acquire data from the sensors, the Precision Current Source Model 6220 and the Nanovoltmeter Model 2182A (both from Keithley) were used, along with Keithley's Delta-Mode integrated system. To analyze the system's effectiveness, three distinct samples were analyzed for calibration, and a MATLAB program was written to analyze the images and extract the material's magnetization. Additionally, a rock sample from the Parnaíba Basin was mapped to demonstrate the system's capabilities.

Comparative analysis of asymptomatic infection prevalence in Beta, Delta, and Omicron surges of COVID-19.

BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a devastating impact on the global population, with an estimated 650 million people infected and more than 6.6 million lives lost. Asymptomatic individuals have been shown to play a significant role in the transmission of the virus. Therefore, this study aims to investigate and compare the prevalence of asymptomatic individuals across three waves associated with the Beta, Delta, and Omicron variants of the virus. METHODS: This retrospective study was conducted between December 2020 and March 2022. The study population consisted of passengers on international flights who were referred to the Gerash Clinical and Molecular Diagnosis Laboratory. Real-time PCR was employed for the diagnosis of SARS-CoV-2. RESULTS: Out of a total of 8592 foreign travelers referred to our laboratory, 139 (1.16 %) tested positive for SARS-CoV-2 infection and were asymptomatic. During the Beta surge, 35 (1.49 %) out of 2335 passengers tested positive for SARS-CoV-2. In the Delta surge, 31 (0.6 %) out of 5127 passengers tested positive. However, during the Omicron surge, a significantly higher number of passengers, specifically 73 (6.46 %) out of 1130, had a positive result for the SARS-CoV-2 test. CONCLUSION: Considering the significant role of asymptomatic transmission in the spread of COVID-19, it is imperative to reconsider health policies when dealing with future surges of the Omicron subvariants. Additionally, we strongly recommend that the World Health Organization prioritize the development and distribution of second-generation vaccines that target not only disease but also infection prevention.

Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review.

Concomitant use of cannabinoids with other drugs may result in pharmacokinetic drug-drug interactions, mainly due to the mechanism involving Phase I and Phase II enzymes and/or efflux transporters. Cannabinoids are not only substrates but also inhibitors or inducers of some of these enzymes and/or transporters. This narrative review aims to provide the available information reported in the literature regarding human data on the pharmacokinetic interactions of cannabinoids with other medications. A search on Pubmed/Medline, Google Scholar, and Cochrane Library was performed. Some studies were identified with Google search. Additional articles of interest were obtained through cross-referencing of published literature. All original research papers discussing interactions between cannabinoids, used for medical or recreational/adult-use purposes, and other medications in humans were included. Thirty-two studies with medicinal or recreational/adult-use cannabis were identified (seventeen case reports/series, thirteen clinical trials, and two retrospective analyses). In three of these studies, a bidirectional pharmacokinetic drug-drug interaction was reported. In the rest of the studies, cannabinoids were the perpetrators, as in most of them, concentrations of cannabinoids were not measured. In light of the widespread use of prescribed and non-prescribed cannabinoids with other medications, pharmacokinetic interactions are likely to occur. Physicians should be aware of these potential interactions and closely monitor drug levels and/or responses. The existing literature regarding pharmacokinetic interactions is limited, and for some drugs, studies have relatively small cohorts or are only case reports. Therefore, there is a need for high-quality pharmacological studies on cannabinoid-drug interactions.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease.

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Follitropin delta combined with menotropin in patients at risk for poor ovarian response during in vitro fertilization cycles: a prospective controlled clinical study.

BACKGROUND: The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 µg (180 IU), according to the algorithm developed by the manufacturer, and based on patient's ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL. METHODS: This study involved a prospective intervention group of 44 women who received 12 µg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 µg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome. RESULTS: Women who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001). CONCLUSIONS: In women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 µg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely. TRIAL REGISTRATION: U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm ).

Concentrations, sources and risks of polycyclic aromatic hydrocarbons in sediments from the Parnaiba Delta basin, Northeast Brazil.

The Parnaíba River is the main river in the Parnaíba Delta basin, the largest delta in the Americas. About 18 polycyclic aromatic hydrocarbons (PAHs) were identified and the environmental risk associated with the sediments was evaluated. The study found that PAHs levels ranged from 5.92 to 1521.17 ng g-1, which was classified as low to high pollution, and that there were multiple sources of pollution along the river, with pyrolytic sources predominating, mainly from urban activity such as trucking, although the influence of rural activity cannot be ruled out. PAHs correlated with black carbon and organic matter and showed high correlation with acenaphthylene, phenanthrene, pyrene, benzo(a)anthracene, chrysene, benzo(ghi)perylene, and ∑PAHs. The benzo(a)pyrene levels were classified as a risk to aquatic life because the threshold effect level and the probable effect level were exceeded. In addition, the sediments were classified as slightly contaminated with a benzo(a)pyrene toxicity equivalent value of 108.43 ng g-1. Thus, the priority level PAH exhibited carcinogenic and mutagenic activity that posed a potential risk to human health.

Potency trends of cannabis in Jamaica during the period of 2014 to 2020.

Reports suggest that cannabis potency has dramatically increased over the last decade in the USA and Europe. Cannabinoids are the terpeno-phenolic compounds found in the cannabis plant and are responsible for its pharmacological activity. The two most prominent cannabinoids are delta-9-tetrahydrocannabinol (Δ9 THC) and cannabidiol (CBD). Cannabis potency is measured not only by the Δ9 THC levels but also by the ratio of Δ9 THC to other non-psychoactive cannabinoids, namely, CBD. Cannabis use was decriminalized in Jamaica in 2015, which opened the gates for the creation of a regulated medical cannabis industry in the country. To date, there is no information available on the potency of cannabis in Jamaica. In this study, the cannabinoid content of Jamaican-grown cannabis was examined over the period 2014-2020. Two hundred ninety-nine herbal cannabis samples were received from 12 parishes across the island, and the levels of the major cannabinoids were determined using gas chromatography-mass spectrometry. There was a significant increase (p < 0.05) in the median total THC levels of cannabis samples tested between 2014 (1.1%) and 2020 (10.2%). The highest median THC was detected in the central parish of Manchester (21.1%). During the period, THC/CBD ratios increased from 2.1 (2014) to 194.1 (2020), and there was a corresponding increase in the percent freshness of samples (CBN/THC ratios <0.013). The data show that a significant increase in the potency of locally grown cannabis has occurred in Jamaica during the last decade.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Omicron and Delta variant prevalence detection and identification during the fourth COVID-19 wave in Mexico using wastewater-based epidemiology.

Objectives: To identify the SARS-CoV-2 variants Delta and Omicron during the fourth wave of the COVID-19 pandemic in Mexico using samples taken from 19 locations in 18 out of the 32 states. Methods: The genetic material concentration was done with PEG/NaCl precipitation, SARS-CoV-2 presence was confirmed by reverse transcriptase-quantitative polymerase chain reaction assay, the variant detection was carried out using a commercial mutation detection panel kit, and variant/mutation confirmation was done by amplicon sequencing of receptor-binding domain target region. The study used 41 samples. Results: The Delta variant was confirmed in two samples during August 2021 (Querétaro and CDMX) and in three samples during November 2021 (Aguascalientes, Ciudad Juárez campuses, and Nuevo Leon). In December 2021, another sample with the Delta variant was confirmed in Nuevo Leon. Between January to March 2022 only the presence of Omicron was confirmed, (variant BA.1). Additionally, in this period six samples were identified with the status "Variant Not Determined". Conclusion: To our knowledge, this study is one of the first to identify Omicron and Delta variants with polymerase chain reaction in Mexico and Latin America and its distribution across the country with 56% Mexican states making it a viable alternative for variant detection without conducting a large quantity of sequencing of clinical tests.

Comparative analysis of asymptomatic infection prevalence in Beta, Delta, and Omicron surges of COVID-19

Abstract Background The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a devastating impact on the global population, with an estimated 650 million people infected and more than 6.6 million lives lost. Asymptomatic individuals have been shown to play a significant role in the transmission of the virus. Therefore, this study aims to investigate and compare the prevalence of asymptomatic individuals across three waves associated with the Beta, Delta, and Omicron variants of the virus. Methods This retrospective study was conducted between December 2020 and March 2022. The study population consisted of passengers on international flights who were referred to the Gerash Clinical and Molecular Diagnosis Laboratory. Real-time PCR was employed for the diagnosis of SARS-CoV-2. Results Out of a total of 8592 foreign travelers referred to our laboratory, 139 (1.16 %) tested positive for SARS-CoV-2 infection and were asymptomatic. During the Beta surge, 35 (1.49 %) out of 2335 passengers tested positive for SARS-CoV-2. In the Delta surge, 31 (0.6 %) out of 5127 passengers tested positive. However, during the Omicron surge, a significantly higher number of passengers, specifically 73 (6.46 %) out of 1130, had a positive result for the SARS-CoV-2 test. Conclusion Considering the significant role of asymptomatic transmission in the spread of COVID-19, it is imperative to reconsider health policies when dealing with future surges of the Omicron subvariants. Additionally, we strongly recommend that the World Health Organization prioritize the development and distribution of second-generation vaccines that target not only disease but also infection prevention.

Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection.

Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Assessment of clinical characteristics and viral load in individuals infected by Delta and Omicron variants of SARS-CoV-2.

In late 2021, a new variant of SARS-CoV-2 called Omicron emerged, replacing Delta worldwide. Although it has been associated with a lower risk of hospitalization and severe forms of COVID-19, there is little evidence of its relationship with specific symptoms and viral load. The aim of this study was to verify the relationship between Delta and Omicron variants of concern, viral load, and the occurrence of symptoms in individuals with COVID-19. Nasopharyngeal swab samples were collected and sequenced from patients with COVID-19 from the Northeast Region of Brazil between August 2021 and March 2022. The results showed a gradual replacement of the Delta variant by the Omicron variant during the study period. A total of 316 samples (157 Delta and 159 Omicron) were included. There was a higher prevalence of symptoms in Delta-infected individuals, such as coryza, olfactory and taste disturbances, headache, and myalgia. There was no association between viral load and the variants analyzed. The results reported here contribute to the understanding of the symptoms associated with the Delta and Omicron variants in individuals affected by COVID-19.

Essential and toxic elements in juvenile migratory commercial fish species in the Paraná River alluvial valley (South America): an approach for aquatic environmental monitoring.

The Paraná River is the sixth largest in the world, and the lower section of the river is one of the largest and most productive floodplain wetlands in South America. The alluvial plain is an important habitat for nursery and feeding areas for commercial fish; however, it has been heavily anthropized due to industries, agricultural activities, and the growth and expansion of metropolitan areas. The aim of this study was to determine element accumulation (As, Cd, Cr, Cu, Fe, Mn, Pb, and Zn) in young-of-the-year fish muscle from a floodplain lagoon of the lower Paraná River (Argentina) during summer and winter seasons, in relation with abiotic matrices (water and sediment). Four commercial fish species were assessed: sábalo (Prochilodus lineatus), boga (Megaleporinus obtusidens), dorado (Salminus brasiliensis), and pirapitá (Brycon orbignyanus). The concentrations of eight elements were detected by quadrupole inductively coupled plasma mass spectrometry. In water samples, Cd, Cr, Mn, Fe, and Zn levels were under the permissible limits for aquatic biota protection in both seasons, except for Pb (> 1 µg L-1) and Cu (> 2 µg L-1). In sediment, the average concentrations of all elements were under the limits set by national and international regulatory authorities. Differences in elemental concentrations between species and seasons were found. In general, the levels of elements in water were higher in summer than in winter, while in sediment, the lowest concentrations of elements were detected during the summer. The order of element concentration in fish muscle was Cd (0.01-0.04 µg g-1) < As (0.02-0.16 µg g-1) < Pb (0.03-0.23 µg g-1) < Mn (0.77-4.32 µg g-1) < Cu (1.01-4.07 µg g-1) < Cr (1.09-4.30 µg g-1) < Zn (15.8-31.7 µg g -1) < Fe (12.6-49.7 µg g-1). The accumulation assessment showed that the four fish species significantly accumulate Cr, Cu and Zn, and As and Zn from water and sediment, respectively. The correlation analysis showed a relationship between fish size and As, Cr, Cu, Fe, Mn, and Zn concentrations. Similarly, the highest values of element concentrations in muscle were detected during the summer when the fishes are early juveniles. The level of As, Cd, and Pb detected in B. orbignyanus, M. obtusidens, and P. lineatus juveniles suggested that these species had the potential to be used as biomarkers for assessing accumulation of toxic elements in the environment. Also, this study reveals that the accumulation patterns differ between size and fish species, which should be a considered insight at the moment of selecting a bioindicator to monitor pollution in the ecosystem.

Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad Anti-SARS-CoV-2 Neutralizing Antibody.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. The PK parameters at these high doses were proportional to the doses, with serum half-life of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with the tissues of these species, supporting the PK/Tox results and suggesting that, while IgG-A7 has a broad efficacy profile, it is not toxic in humans. Thus, the information generated in the CD-1 mice as a PK/Tox model complemented with the mouse and human TCR, could be of relevance as an alternative to Non-Human Primates (NHPs) in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.