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1.
Exp Appl Acarol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088133

ABSTRACT

There is limited knowledge about tick diversity in the Amazon region. Here, we survey small terrestrial mammals for tick infestation at the Rio Pardo settlement, Amazonas State, Brazil. Sampling included rainy and dry seasons and four ecotones (primary forest, forest in regeneration, field crops and households). Each animal was inspected for ticks, which, if present, were placed in 70% alcohol and identified. Parasitological indexes were calculated and the presence/absence of ticks on hosts was tested for possible associations with independent variables (ecotone, host sex, host order, host family, host age and season). A total of 208 small mammals were captured, 47 individuals (10 species) in the primary forest, 124 (15 species) in the forest in regeneration, 11 (7 species) in the field crops, and 26 (4 species) in the households. A total of 14 small mammals were infested by ticks (overall prevalence: 6.7%; 95% CI: 3.72 - 11.04%), which consisted of 51 specimens that were identified into four species, as follows: Amblyomma humerale (32 nymphs); Ixodes luciae (6 females); Amblyomma coelebs (1 nymph); and Ornithodoros mimon (1 larva). In addition, 11 larvae were retained as Amblyomma spp. Only host order showed association (P = 0.002) with tick infestation, with marsupials 5.5 times more infested than rodents. Our record of O. mimon on D. marsupialis is the first on this host species, and the first record of a Argasidae tick in the Brazilian state of Amazonas. To the best of our knowledge, this is the first study that actively screened free-living terrestrial small mammals and provided data on prevalence, mean intensity and mean abundance of tick infestations in the Brazilian Amazonas state.

2.
EFSA J ; 22(8): e8960, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39104808

ABSTRACT

The EFSA Panel on Food Contact Materials (FCM) assessed the safety of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt', used as additives up to 0.3% in polyethylene terephthalate (PET), polyamide (PA), thermoplastic polyurethane (TPU), polylactic acid (PLA) and poly(vinyl chloride) (PVC) in contact with all food types for long-term storage at room temperature and below, after hot-fill and/or heating. The substances consist of the chemical classes wax esters, carboxylic acids, alcohols and calcium salts of acids, along with an unidentified organic fraction up to ■■■■■ w/w. Migration into 10% ethanol and 4% acetic acid was below 0.012 mg/kg for each chemical class, and about 0.001 mg/kg for the unidentified fraction. In isooctane, migration was up to 0.297 mg/kg food for wax esters, below 0.01 mg/kg food for the other chemical classes and about 0.02 mg/kg food for the unidentified fraction. The contact with dry food and food simulated by 20% ethanol were considered covered by the migration tests with aqueous simulants. Based on genotoxicity assays and compositional analyses, the constituents of the chemical classes did not raise a concern for genotoxicity. The potential migration of individual constituents or groups of chemically-related compounds of the unidentified fraction would result in exposures below (for aqueous food) and above (for fatty food) the threshold of toxicological concern for genotoxic carcinogens. Therefore, the FCM Panel concluded that the substances are not of safety concern for the consumer, if used as additives up to 0.3% w/w in PET, PLA and rigid PVC materials and articles intended for contact with all food types except for fatty foods, for long-term storage at room temperature and below, including hot-fill and/or heating up to 100°C for up to 2 h.

3.
Article in English | MEDLINE | ID: mdl-39102174

ABSTRACT

Assessing measurement invariance and the interplay of discrimination, microaggressions, and resilience among Black women living with HIV (BWLWH) across time utilizing latent class and repeated measure analysis may provide novel insights. A total of 151 BWLWH in a southeastern U.S. city completed surveys focused on multiple forms of microaggressions and discrimination (race, gender, sexual orientation, or HIV-related) and resilience factors (social support, self-efficacy, post-traumatic growth) at baseline, 3 months, and 6 months. To capture the psychosocial domains of discrimination, microaggressions, and resilience, three latent factors were developed and measured across three time points. Latent class analysis was also conducted to identify and compare meaningful subgroups based on varying levels of discrimination, microaggressions, and resilience reported. Three latent classes were created. MI testing suggested that measurement invariance was partially met (established metric invariance and scalar invariance), and it is possible to compare factor means of discrimination, microaggressions, and resilience across time. Latent factor mean scores of microaggressions and discrimination decreased after 3 and 6 months and increased for resilience after 6 months and varied over time across the three latent classes identified. The subgroup with the lowest level of discrimination and microaggressions and the highest level of resilience reported at baseline, experienced increases in resilience after months 3 and 6. Clinical interventions, research, and policies aimed at promoting resilience and reducing structural and social barriers linked to racism, sexism, HIV stigma, and classism are needed to improve the health and well-being of BWLWH.

4.
Elife ; 122024 Aug 20.
Article in English | MEDLINE | ID: mdl-39163103

ABSTRACT

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.


Subject(s)
Blood Platelets , Cell Differentiation , Oligodendrocyte Precursor Cells , Remyelination , Animals , Oligodendrocyte Precursor Cells/physiology , Remyelination/physiology , Mice , Blood Platelets/physiology , Encephalomyelitis, Autoimmune, Experimental/pathology , Mice, Inbred C57BL , Multiple Sclerosis/pathology , Disease Models, Animal , Oligodendroglia/physiology , Female
5.
Viral Immunol ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39149804

ABSTRACT

Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

7.
Food Sci Nutr ; 12(7): 5131-5146, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39055210

ABSTRACT

Diabetes mellitus is a metabolic disorder commonly associated with atherosclerosis. Plants with therapeutic potential, such as Lippia origanoides Kunth, emerge as effective alternatives for treating these diseases. Therefore, this work aims to analyze the antihyperglycemic and antidyslipidemic potential of the hydroalcoholic extract of Lippia origanoides Kunth (ELo) in alloxan-diabetic rats. Animals were treated orally: normal control, hyperglycemic control, positive control glibenclamide (5 mg/kg), and groups treated with ELo (75, 150, and 250 mg/kg). Preclinical evaluation of ELo showed hypoglycemic, hypolipidemic, hepatic, and renal protective effects. At all doses, ELo significantly reduced hyperglycemia, triglycerides, total cholesterol, low-density lipoprotein, atherogenic index, atherogenic coefficient, and cardiovascular risk index (p < .05). Elo at different doses promoted an increase in insulin release compared to untreated animals (p < .05) and showed α-glucosidase inhibitory activity (p < .05). Also, ELo (250 mg/kg group) showed maximum reduction of hyperglycemia, alanine transaminase, aspartate aminotransferase, malonaldehyde, and urea compared to the hyperglycemic and glibenclamide groups, and creatinine only compared to the hyperglycemic groups (p < .05). The promising action of ELo in the context of diabetes may be related to the synergistic action of flavonoid compounds identified in liquid chromatography, whose pharmacological capabilities have already been documented in previous studies. The mechanisms may be the stimulation of insulin release; the inhibitory activity of α-glucosidase; improving general clinical conditions; and the antioxidant effects of the extract. These findings pave the way for the future development of an herbal presentation of L. origanoides Kunth as a hypoglycemic and cardiovascular protector with a lipid-lowering effect.

8.
Rev Assoc Med Bras (1992) ; 70(6): e20240045, 2024.
Article in English | MEDLINE | ID: mdl-39045962

ABSTRACT

OBJECTIVE: The objective of this study was to assess the clinical and uterine cervix characteristics of patients displaying vaginal discharge with positive results for Mycoplasma sp. and/or Ureaplasma spp. METHODS: An analytical cross-sectional study involving women aged 18-45 years was conducted. Microbiological assessments included Ureaplasma and Mycoplasma cultures, as well as human papillomavirus hybrid capture using ecto and endocervix swabs. All tests were two-tailed, and significance was set at p<0.05. RESULTS: Among 324 women, Ureaplasma prevalence was 17.9%, and Mycoplasma prevalence was 3.1%. The Ureaplasma-positive group exhibited a higher frequency of urinary tract infections (39.1 vs. 19%, p=0.002) and human papillomavirus (39.7 vs. 12.8%, p≤0.001) compared with controls. The Mycoplasma-positive group showed a higher frequency of non-contraceptive use compared with controls (66.2 vs. 30.0%, p=0.036). Abnormal colposcopic findings were more prevalent in the Mycoplasma/Ureaplasma-positive group than in controls (positive: 65% vs. control: 35%, p=0.001). Pap smear findings did not differ between the groups. CONCLUSION: Ureaplasma spp. was associated with urinary tract infections and human papillomavirus, while the presence of Mycoplasma sp. was linked to reduced contraceptive use. When analyzing both pathogens together, a higher frequency of abnormal colposcopic findings was observed, with no difference in cytological findings in the positive group.


Subject(s)
Cervix Uteri , Mycoplasma Infections , Mycoplasma , Ureaplasma Infections , Ureaplasma , Humans , Female , Adult , Ureaplasma Infections/microbiology , Ureaplasma Infections/epidemiology , Cross-Sectional Studies , Mycoplasma Infections/epidemiology , Mycoplasma Infections/microbiology , Ureaplasma/isolation & purification , Young Adult , Middle Aged , Adolescent , Cervix Uteri/microbiology , Cervix Uteri/pathology , Mycoplasma/isolation & purification , Vaginal Discharge/microbiology , Prevalence , Papillomavirus Infections/microbiology , Urinary Tract Infections/microbiology , Urinary Tract Infections/epidemiology , Brazil/epidemiology , Vaginal Smears
9.
An Acad Bras Cienc ; 96(3): e20231355, 2024.
Article in English | MEDLINE | ID: mdl-39046024

ABSTRACT

The aim of this study is to identify the factors associated with mortality in patients with COVID-19 undergoing invasive mechanical ventilation at a university hospital in Northeastern Brazil. This is a retrospective cohort from April to August 2020 through an analysis of medical records, considering the demographic profile, comorbidities, complications, supports, respiratory and laboratory parameters. A total of 65 patients required invasive mechanical ventilation, of which 64.6% died in the ICU. They were older, had more comorbidities, shorter length of stay in the intensive care unit, received more support such as palliative care and two vasopressors simultaneously, showed lower levels of pH, hemoglobin and calcium, and higher levels of bicarbonate, lactate, prothrombin time, international normalized ratio, troponin and ferritin at the start of invasive mechanical ventilation. Furthermore, the time course of pH, arterial oxygen partial pressure to fractional inspired oxygen ratio, arterial carbon dioxide partial pressure, lactate, hemoglobin, platelets, lymphocytes, neutrophil-to-lymphocyte ratio, coagulation parameters, calcium, urea, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, ferritin, static compliance, airway resistance, tidal volume, and noradrenaline doses showed association with mortality. There was a high mortality rate in invasively mechanically ventilated COVID-19 patients, with some associated factors identified at the start of invasive mechanical ventilation and others identified over time.


Subject(s)
COVID-19 , Hospitals, University , Respiration, Artificial , Humans , COVID-19/mortality , Retrospective Studies , Male , Female , Middle Aged , Brazil/epidemiology , Respiration, Artificial/statistics & numerical data , Aged , SARS-CoV-2 , Intensive Care Units/statistics & numerical data , Hospital Mortality , Risk Factors , Adult , Comorbidity , Length of Stay/statistics & numerical data
10.
Article in English | MEDLINE | ID: mdl-39041283

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011. METHODS: This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020. RESULTS: The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti-phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%. CONCLUSION: The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution.

11.
Toxicon ; 248: 107847, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025449

ABSTRACT

Contributing to the assessment of potential physiological changes in microalgae subjected to different concentrations and types of cyanotoxins, this study investigated the inhibitory effects of cyanotoxins on the growth, density, biomass, and ecotoxicity of Chlorella vulgaris. Chlorella vulgaris was exposed to crude extracts of cyanobacteria producing microcystin-LR (MC-LR), saxitoxin (SXT), anatoxin-a (ATX-A), and cylindrospermopsin (CYN) with initial concentrations of 5.0, 2.05, 0.61, and 1.42 µg.L-1, respectively. The experiments were conducted under controlled conditions, and monitoring of growth and cell inhibition occurred at 24h, 48h, 72h, and 96h. Chlorophyll-a content and ecotoxicity assessment were conducted with samples collected after 96h of exposure to cyanotoxins. The growth assays of Chlorella vulgaris, with results expressed in terms of average growth rates (doublings/day), indicated the following order for cyanotoxins: SXT (2.03) > CYN (1.66) > MC-LR (1.56) > ATX-A (0.18). This assay revealed the prominent inhibitory potential of ATX-A on Chlorella vulgaris growth compared to the other toxins evaluated. Regarding the inhibition of the photosynthetic process, expressed in terms of the percentage inhibition of Chlorophyll-a, the following order for cyanotoxins was obtained: ATX-A (82%) > MC-LR (76%) > STX (46%) > CYN (16%). These results also indicated that among the cyanotoxins, ATX-A was the most detrimental to the photosynthetic process. However, contrary to the observations in the growth study, SXT proved to be more harmful than CYN in terms of Chlorophyll-a inhibition. Finally, the results of the toxicity assay revealed that only ATX-A and MC-LR exerted a chronic influence on Chlorella vulgaris under the investigated conditions.

12.
Carbohydr Polym ; 342: 122356, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39048219

ABSTRACT

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.


Subject(s)
Doxorubicin , Galactose , Mannans , Nanoconjugates , Doxorubicin/pharmacology , Doxorubicin/chemistry , Mannans/chemistry , Mannans/pharmacology , Galactose/chemistry , Galactose/analogs & derivatives , Humans , Nanoconjugates/chemistry , Hydrogen-Ion Concentration , Drug Liberation , Cell Line, Tumor , Drug Carriers/chemistry , Cell Survival/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
13.
Nutrients ; 16(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39064620

ABSTRACT

Health literacy (HL) is a crucial factor influencing health-related decisions, including dietary patterns. The Mediterranean diet is widely recognized as one of the healthiest eating patterns. This study aims to explore the association between HL levels among adults in socially vulnerable contexts and their adoption of the Mediterranean diet. Conducted as part of a cluster-randomized trial in primary schools, the research involved 557 parents of children aged 6 to 10 who consented to participate. HL was assessed using the HLS questionnaire, while adoption of the Mediterranean diet was evaluated using the MEDAS questionnaire. Participants also provided anthropometric and sociodemographic data via a questionnaire, from which BMI was calculated (weight/height2). Education level was categorized as higher education or lower and professional status was classified based on occupational categories. Generalized linear models and logistic regression were employed for analysis. The findings indicate a direct association between HL level and adoption of the Mediterranean diet (B = 0.022, 95% CI 0.010-0.035, p < 0.001), underscoring the influence of HL on dietary choices. Specifically, the healthcare dimension of HL emerges as pivotal in shaping dietary behaviors, particularly towards the Mediterranean diet. These results underscore the importance of policies and programs aimed at enhancing HL, especially among socially vulnerable populations. Prioritizing public health interventions to improve HL is critical for promoting better dietary decision-making.


Subject(s)
Diet, Mediterranean , Health Literacy , Humans , Diet, Mediterranean/statistics & numerical data , Male , Female , Cross-Sectional Studies , Adult , Child , Surveys and Questionnaires , Feeding Behavior , Parents , Middle Aged
14.
Microorganisms ; 12(7)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39065160

ABSTRACT

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

15.
Plants (Basel) ; 13(14)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39065488

ABSTRACT

Zinc enrichment of edible food products, through the soil and/or foliar application of fertilizers, is a strategy that can increase the contents of some nutrients, namely Zn. In this context, a workflow for agronomic enrichment with zinc was carried out on irrigated Vitis vinifera cv. Syrah, aiming to evaluate the mobilization of photoassimilates to the winegrapes and the consequences of this for winemaking. During three productive cycles, foliar applications were performed with ZnSO4 or ZnO, at concentrations ranging between 150 and 1350 g.ha-1. The normal vegetation index as well as some photosynthetic parameters indicated that the threshold of Zn toxicity was not reached; it is even worth noting that with ZnSO4, a significant increase in several cases was observed in net photosynthesis (Pn). At harvest, Zn biofortification reached a 1.2 to 2.3-fold increase with ZnSO4 and ZnO, respectively (being significant relative to the control, in two consecutive years, with ZnO at a concentration of 1350 g.ha-1). Total soluble sugars revealed higher values with grapes submitted to ZnSO4 and ZnO foliar applications, which can be advantageous for winemaking. It was concluded that foliar spraying was efficient with ZnO and ZnSO4, showing potential benefits for wine quality without evidencing negative impacts.

16.
Invest Educ Enferm ; 42(2)2024 Jun.
Article in English | MEDLINE | ID: mdl-39083841

ABSTRACT

Objective: To build and validate an educational technology consisting of a flipchart to promote self-efficacy in newborn care. Methods: A methodological study was carried out in two stages: (i) creation of the flipchart and (ii) validation by 25 experts and 50 people who could be the target audience (pregnant women, mothers or family members of newborns). Clarity, language, practical relevance and theoretical relevance were reviewed using the Suitability Assessment of Materials (SAM) instrument. The Content Validity Index and the Flesch Readability Index were calculated. Results: The serial album "Can you take care of your baby" consists of 30 pages. The overall Content Validity Index was 0.93 among experts and 1.0 among the target audience. The flipchart was considered superior quality material, reaching an agreement percentage of 94.9, indicating that it is suitable as an educational technology. Participants suggested adjustments, incorporated into the material for printed production. Conclusion: The flipchart developed and with content validated by experts is suitable for use in health education activities that aim to promote self-efficacy in caring for newborns.


Subject(s)
Educational Technology , Infant Care , Self Efficacy , Humans , Infant, Newborn , Female , Infant Care/methods , Educational Technology/methods , Pregnancy , Adult , Male , Mothers/psychology , Health Education/methods , Family/psychology
17.
J Biomed Sci ; 31(1): 74, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014450

ABSTRACT

BACKGROUND: Prostate cancer (PrCa) is the most frequently diagnosed cancer in men. Variants in known moderate- to high-penetrance genes explain less than 5% of the cases arising at early-onset (< 56 years) and/or with familial aggregation of the disease. Considering that BubR1 is an essential component of the mitotic spindle assembly checkpoint, we hypothesized that monoallelic BUB1B variants could be sufficient to fuel chromosomal instability (CIN), potentially triggering (prostate) carcinogenesis. METHODS: To unveil BUB1B as a new PrCa predisposing gene, we performed targeted next-generation sequencing in germline DNA from 462 early-onset/familial PrCa patients and 1,416 cancer patients fulfilling criteria for genetic testing for other hereditary cancer syndromes. To explore the pan-cancer role of BUB1B, we used in silico BubR1 molecular modeling, in vitro gene-editing, and ex vivo patients' tumors and peripheral blood lymphocytes. RESULTS: Rare BUB1B variants were found in ~ 1.9% of the early-onset/familial PrCa cases and in ~ 0.6% of other cancer patients fulfilling criteria for hereditary disease. We further show that BUB1B variants lead to decreased BubR1 expression and/or stability, which promotes increased premature chromatid separation and, consequently, triggers CIN, driving resistance to Taxol-based therapies. CONCLUSIONS: Our study shows that different BUB1B variants may uncover a trigger for CIN-driven carcinogenesis, supporting the role of BUB1B as a (pan)-cancer predisposing gene with potential impact on genetic counseling and treatment decision-making.


Subject(s)
Chromosomal Instability , Genetic Predisposition to Disease , Prostatic Neoplasms , Protein Serine-Threonine Kinases , Humans , Male , Prostatic Neoplasms/genetics , Protein Serine-Threonine Kinases/genetics , Middle Aged , Germ-Line Mutation , Adult , Cell Cycle Proteins
19.
Vet Parasitol Reg Stud Reports ; 53: 101066, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39025540

ABSTRACT

Cuniculus paca, commonly known as the paca, is a rodent of the Cuniculidae family that is widely distributed throughout the Americas, including all Brazilian territories, and is abundant in the Amazon region. It is one of the most hunted species and faces significant predation in the extreme western Amazon region of Brazil because it constitutes a staple in the diet of local communities, for subsistence and commercial purposes. Understanding the helminthic fauna of these animals is of paramount importance, given that some nematodes have zoonotic potential and may pose risks to consumer health. This study aimed to contribute to the records of the nemtodes of this highly consumed species in the Amazon region, highlighting the occurrence of gastrointestinal parasites in free-living pacas intended for human subsistence consumption. The study was conducted in the Paranã da Floresta community, located in the municipality of Guajará, Amazonas from 2022 to 2023. The community members hunted this rodent for consumption and voluntarily provided the viscera for analysis. Nematodes were extracted from each organ. The organs were opened, and the contents were processed using a sieve (0.15 mm) and subsequently evaluated separately. In total, 10,157 nematodes were found in the 14 pacas. Based on morphological analyses, the nematodes were identified as Heligmostrongylus sedecimradiatus (n = 10,068), Trichuris sp. (n = 85), and Physaloptera sp. (n = 4). This study provides insights into the nematodes diversity of free-living pacas in the extreme Western Amazon region, emphasizing the importance of sanitary surveillance and public awareness of the risks associated with bushmeat consumption.


Subject(s)
Nematoda , Nematode Infections , Animals , Brazil/epidemiology , Nematoda/isolation & purification , Nematoda/classification , Nematode Infections/veterinary , Nematode Infections/parasitology , Nematode Infections/epidemiology , Cuniculidae/parasitology , Male , Female , Rodent Diseases/parasitology , Rodent Diseases/epidemiology , Humans
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