Effect of the basilar invagination (type B) on cervical spine: a case-control study at MRI.

OBJECTIVE: To evaluate the effect of the basilar invagination (BI) type B on cervical spine. METHODS: The research protocol used head magnetic resonance imaging (MRI) exams from 41 participants with BI type B and 158 controls. The criterion for BI was the distance of the odontoid apex to Chamberlain's line (DOCL) equal to or greater than 7 mm. The clivus length (CLI), clivus canal angle (CCA), Welcker's basal angle (WBA), Boogaard's angle (BOA), upper cervical lordosis angle (UCL), and total cervical lordosis angle (CL) were evaluated. The descriptive analysis, group comparisons, and correlations between skull base and cervical spine parameters were performed at the 95% confidence interval. RESULTS: Participants with BI type B showed shorter clivus length (CLI: 25.7mm±7.3); greater angulation of the skull base (WBA: 126.5±10.4); greater inclination foramen magnum (BOA: 151.5±14.5); decrease in the value of the (CCA: 131.6±15); and greater angulations of UCL (17.9 ±13.8) and CL (29.7 ±19.9) in comparison to the control group (P < 0.05). Clivus length and CCA correlated inversely with UCL and CL, while BOA correlated directly with UCL and CL. The WBA did not correlate with CL (P < 0.05). CONCLUSION: The deformation of skull base in the BI of type B caused, on average, a hyperlordosis of almost 30 degrees in the C2-C6 segment. This change was approximately 17º in the C2-C4, with the clivus hypoplasia being a risk factor for cervical hyperlordosis.

Assessment of cognitive function in elderly patients with heart failure.

OBJECTIVE: To compare the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tests for the identification of cognitive deficit (CD) in elderly patients with heart failure (HF). METHODS: This was a cross-sectional study with an observational design involving 43 elderly patients with HF of both sexes, treated by the Unified Health System, who were able to understand and follow the study instructions. A sociodemographic and clinical questionnaire and the MMSE and MoCA neurocognitive tests were applied. RESULTS: The mean age of the patients was 67 years; 67.44% were male; 53.49% were white; 58.14% had 1-4 years of schooling; 58.14% had an income of half to one minimum wage; 55.81% were married; 53.49% had a family history of HF; 90.7% denied smoking; 83.72% denied alcohol intake; 65.12% did not practice physical activity; 83.72% were hypertensive; 30.23% were diabetic; 57.89% had LVEF ≥ 50%; 39.53% have NYHA II; and 88.37% did not have a pacemaker. In the identification of CD, the MMSE test detected it in 25.58% of the patients, while the MoCA test identified it in 23.26% (p=0.043). CONCLUSION: It was concluded that the MMSE test performed better than the MoCA test in the identification of CD in elderly patients with HF.

DNA lesions that block transcription induce the death of Trypanosoma cruzi via ATR activation, which is dependent on the presence of R-loops.

Trypanosoma cruzi is the etiological agent of Chagas disease and a peculiar eukaryote with unique biological characteristics. DNA damage can block RNA polymerase, activating transcription-coupled nucleotide excision repair (TC-NER), a DNA repair pathway specialized in lesions that compromise transcription. If transcriptional stress is unresolved, arrested RNA polymerase can activate programmed cell death. Nonetheless, how this parasite modulates these processes is unknown. Here, we demonstrate that T. cruzi cell death after UV irradiation, a genotoxic agent that generates lesions resolved by TC-NER, depends on active transcription and is signaled mainly by an apoptotic-like pathway. Pre-treated parasites with α-amanitin, a selective RNA polymerase II inhibitor, become resistant to such cell death. Similarly, the gamma pre-irradiated cells are more resistant to UV when the transcription processes are absent. The Cockayne Syndrome B protein (CSB) recognizes blocked RNA polymerase and can initiate TC-NER. Curiously, CSB overexpression increases parasites' cell death shortly after UV exposure. On the other hand, at the same time after irradiation, the single-knockout CSB cells show resistance to the same treatment. UV-induced fast death is signalized by the exposition of phosphatidylserine to the outer layer of the membrane, indicating a cell death mainly by an apoptotic-like pathway. Furthermore, such death is suppressed in WT parasites pre-treated with inhibitors of ataxia telangiectasia and Rad3-related (ATR), a key DDR kinase. Signaling for UV radiation death may be related to R-loops since the overexpression of genes associated with the resolution of these structures suppress it. Together, results suggest that transcription blockage triggered by UV radiation activates an ATR-dependent apoptosis-like mechanism in T. cruzi, with the participation of CSB protein in this process.

Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation in Cryptococcus neoformans.

There is an urgent need for new antifungal drugs to treat invasive fungal diseases. Unfortunately, the echinocandin drugs that are fungicidal against other important fungal pathogens are ineffective against Cryptococcus neoformans, the causative agent of life-threatening meningoencephalitis in immunocompromised people. Contributing mechanisms for echinocandin tolerance are emerging with connections to calcineurin signaling, the cell wall, and membrane composition. In this context, we discovered that a defect in phosphate uptake impairs the tolerance of C. neoformans to the echinocandin caspofungin. Our previous analysis of mutants lacking three high affinity phosphate transporters revealed reduced elaboration of the polysaccharide capsule and attenuated virulence in mice. We investigated the underlying mechanisms and found that loss of the transporters and altered phosphate availability influences the cell wall and membrane composition. These changes contribute to the shedding of capsule polysaccharide thus explaining the reduced size of capsules on mutants lacking the phosphate transporters. We also found an influence of the calcineurin pathway including calcium sensitivity and an involvement of the endoplasmic reticulum in the response to phosphate limitation. Furthermore, we identified membrane and lipid composition changes consistent with the role of phosphate in phospholipid biosynthesis and with previous studies implicating membrane integrity in caspofungin tolerance. Finally, we discovered a contribution of phosphate to titan cell formation, a cell type that displays modified cell wall and capsule composition. Overall, our analysis reinforces the importance of phosphate as a regulator of cell wall and membrane composition with implications for capsule attachment and antifungal drug susceptibility.

Varroa destructor mite population dynamics in africanized honeybee (Apis mellifera) colonies in a semi-arid region.

Most published data on mite infestation rates in semi-arid regions have been collected over only 3 or 4 months during a specific period of the year. Therefore, the aim of this study was to observe parasite-host dynamics of hygienic and non-hygienic Africanized bee colonies considering environmental factors that may influence Varroa destructor mite infestation rates in a semi-arid region. To this end, the brood puncture method was applied to 37 colonies, forming two groups, namely G1, encompassing 16 hygienic colonies, and G2, comprising 21 non-hygienic colonies. After forming the groups, 300 worker bees from each colony were examined monthly for mite infestations and the data were correlated with climatological records. The monthly infestation average was considered low, below 10%, except in November, when it reached 12.19% ± 6.45. No statistically significant difference was observed for inter-group infestation rates (P > 0.05). When mite infestation rates were associated with climatic variables, they were linked to colony losses (32%) due to swarming. No significant correlations between hygienic behaviour and parasite infestation rates were noted. Nonetheless, these results support the idea that there is no need to apply acaricides for V. destructor control in Brazil.

Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence.

The fungal pathogen Cryptococcus neoformans is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How C. neoformans manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.

Quality of life in children and adolescents with blood coagulation disorders and hemoglobinopathies.

The aim of this study was to evaluate the impact of oral conditions and health-related quality of life (HRQoL) on oral health-related quality of life (OHRQoL) in children and adolescents with blood coagulation disorders and hemoglobinopathies (BCDH). The study was cross-sectional and included 61 individuals aged 2 to 18 years with BCDH. Exams for dental caries (dmft/DMFT index), oral hygiene (simplified oral hygiene index - OHI-S), and gingival health (modified gingival index - MGI) were performed. The pediatric quality of life inventory™ (PedsQL™) generic core scale and oral health scale were used to measure HRQoL and OHRQoL. Spearman's correlation coefficient (ρ) and the Mann-Whitney test (α = 0.05) were conducted to assess the relationship between covariates and the PedsQL™ oral health scale. The mean PedsQL™ oral health scale score was 76.66 (SD = 21.36). Worse OHRQoL was correlated with poor oral hygiene (ρ = -0.383; p: 0.004), poor gingival health (ρ = -0.327; p = 0.014), and better HRQoL (ρ = 0.488; p < 0.001). Greater untreated dental caries experience was associated with worse OHRQoL (p = 0.009). Worse oral health status in children and adolescents with BCDH negatively impacts OHRQoL, and OHRQoL and quality of life analyzed from a generic perspective are positively correlated constructs in this population.

A consensus reverse docking approach for identification of a competitive inhibitor of acetyltransferase enhanced intracellular survival protein from Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which remains a significant global health challenge. The emergence of multidrug-resistant (MDR) Mtb strains imposes the development of new therapeutic strategies. This study focuses on the identification and evaluation of potential inhibitors against Mtb H37Ra through a comprehensive screening of an in-house chemolibrary. Subsequently, a promising pyrimidine derivative (LQM495) was identified as promising and then further investigated by experimental and in silico approaches. In this context, computational techniques were used to elucidate the potential molecular target underlying the inhibitory action of LQM495. Then, a consensus reverse docking (CRD) protocol was used to investigate the interactions between this compound and several Mtb targets. Out of 98 Mtb targets investigated, the enhanced intracellular survival (Eis) protein emerged as a target for LQM495. To gain insights into the stability of the LQM495-Eis complex, molecular dynamics (MD) simulations were conducted over a 400 ns trajectory. Further insights into its binding modes within the Eis binding site were obtained through a Quantum mechanics (QM) approach, using density functional theory (DFT), with B3LYP/D3 basis set. These calculations shed light on the electronic properties and reactivity of LQM495. Subsequently, inhibition assays and kinetic studies of the Eis activity were used to investigate the activity of LQM495. Then, an IC50 value of 11.0 ± 1.4 µM was found for LQM495 upon Eis protein. Additionally, its Vmax, Km, and Ki parameters indicated that it is a competitive inhibitor. Lastly, this study presents LQM495 as a promising inhibitor of Mtb Eis protein, which could be further explored for developing novel anti-TB drugs in the future.

Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice.

OBJECTIVES: This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. METHODS: The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. KEY FINDINGS: DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. CONCLUSIONS: Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.

Risk assessment due to natural radioactivity of stone dust and crushed stone Commercialized in construction stores in the state of Rio de Janeiro.

A systematic study of the distribution of the Naturally Occurring Radioactivity in stone dust and crushed stone, has been carried out with an objective of establishing reliable baseline data on the radiation level and hence to evaluate hazard indices approach and the production of radioactive heat (RHP) due to radiation exposure to the workers and to the inhabitants of the studied area. Twenty-six samples have been collected from different locations in the State of Rio de Janeiro (Brazil). To calculate the specific activity, gamma ray spectrometry and a detector of High Purity Germanium (HPGe; Canberra, 30% relative efficiency) was used. The activity concentration of 238U, 226Ra 232Th and 40K ranged from 29.3 ± 18.6 to 206.8 ± 21.5 Bq kg-1, 30.3 ± 1.0 to 134.3 ± 1.8, 27.9 ± 0.7 to 86.2 ± 0.9 Bq kg-1, and 734.9 ± 35.1 to 1204.8 ± 53.5 Bq kg-1, respectively. The mean values of the Iex, Iin, Iγ, Iα, AUI, IRP112Rn, IPA, IPI and IYu indices were 0.68 ± 0.09, 0.92 ± 0.12, 0.93 ± 0.12, 0.43 ± 0.07, 0.88 ± 0.20, 1.25 ± 0.21, 0.34 ± 0.05, 0.75 ± 0.10, 0.63 ± 0.08 and 34. ± 6.31, respectively. The average radioactive heat production (RHP) of 2.01 ± 0.28 µ Wm-3 was above the values found in the literature, which may contribute to the heat flow in the study area because the raw materials that make up the samples showed a high value of environmental radioactivity. The Brazilian Hazard Index to assess the radiological risk of crushed stone and stone dust was created and the average value was 0.74 ± 0.10, a value below 1, which means only moderate control over the use of these materials, with no indication of restriction to the its use.

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

BACKGROUND: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. MATERIALS AND METHODS: We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. RESULTS: Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. CONCLUSIONS: Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.

Impact of combined management strategies of monensin and virginiamycin in high energy diets on ruminal fermentation and nutrients utilization.

Feed additives such as monensin (MON) and virginiamycin (VM) are commonly utilized in feedlot diets to enhance rumen fermentation. Nevertheless, the precise effects of combining MON and VM during specific feedlot periods and the advantages of this combination remain unclear. This study was designed to investigate the effects of withdrawal of MON when associated with VM during the adaptation and finishing periods on ruminal metabolism, feeding behavior, and nutrient digestibility in Nellore cattle. The experimental design was a 5 × 5 Latin square, where each period lasted 28 days. Five rumen-cannulated Nellore yearling bulls were used (414,86 ± 21,71 kg of body weight), which were assigned to five treatments: (1) MON during the entire feeding period; (2) VM during the entire feeding period; (3) MON + VM during the adaptation period and only VM during the finishing period 1 and 2; (4) MON + VM during the entire feeding period; (5) MON + VM during the adaptation and finishing period 1 and only VM during the finishing period 2. For the finishing period 1, animals fed T3 had improved potential degradability of dry matter (p = 0.02). Cattle fed T3 and T5 had the highest crude protein degradability when compared to animals receiving T2 (p = 0.01). Animals fed T2 and T3 had reduced the time (p < 0.01) and area under pH 6.2 (p = 0.02). Moreover, animals fed T4 had greater population of protozoa from the genus Diplodinium (p = 0.04) when compared to those from animals fed T2, T3 and T5. For the finishing period 2, animals fed T3 had greater starch degradability when compared to animals receiving T4 and T5 (p = 0.04). Animals fed T3, T4 and T5 had increased the duration of time in which pH was below 5.6 (p = 0.03). The area under the curve for ruminal pH 5.2 and pH 5.6 was higher for the animals fed T3 (p = 0.01), and the area under pH 6.2 was higher for the animals fed T3 and T5 (p < 0.01) when compared to animals receiving T2. There is no substantial improvement on the rumen fermentation parameters by the concurrent utilization of MON and VM molecules, where the higher starch and protein degradability did not improve the rumen fermentation.

Nutrient retention after crop harvest in a typic hapludults amended with biochar types under no-tillage system.

The utilization of biochar's as soil amendments for enhancing nutrient retention in subsoils present potential limitations. To address this issue, we conducted a greenhouse experiment to assess the effects of various biochar's derived from animal manures (swine manure, poultry litter, cattle manure) and plant residues (rice straw, soybean straw, corn straw) when applied to surface of an acidic soil. Our study focused on wheat crops under a no-tillage system, with a subsequent evaluation of the residual impacts on soybeans. The experimental design involved the application of biochar's at different rates i.e. 10 and 20 Mg ha-1, followed by the assessment of their influence on NPK levels, pH, and exchangeable Al in stratified soil layers (0-5, 5-10, 10-15, and 15-25 cm). Furthermore, we investigated the interplay between biochar doses and the application of nitrogen (N) in the top 5 cm of soil, specifically examining NO 3 - , NH 4 + , P and K levels. Our findings revealed that in the top 5 cm of soil, biochar doses and N application significantly affected NO 3 - , NH 4 + , P and K concentrations. However, in deeper soil layers, no significant differences were observed among biochar doses with or without N application. Interestingly, K levels were impacted throughout all soil depths, regardless of the presence or absence of N application. Moreover, biochar application up to a 5 cm depth induced favorable changes in soil pH and reduced exchangeable Al. In contrast, deeper layers experienced a decrease in soil pH and an increase in exchangeable Al following biochar treatment. In conclusion, our study demonstrates that biochar's can effectively retain NPK nutrients, enhance soil pH, and decrease exchangeable Al, independent of the type and dosage of application under a no-tillage system. Nonetheless, the efficacy of biochar amendments may vary with soil depth and type of nutrient, warranting careful consideration for maximizing their benefits in sustainable agricultural practices.

Assessment of radiological hazards from radioactivity natural of cement used in Dwellings in Rio de Janeiro, Brazil.

Brazil is the fourth largest cement consumer in the world and the largest producer in Latin America, around 1.3% of global production. The main inputs in the manufacture of cement are limestone and clay. Few studies have been carried out in the country on the risk of these materials used in civil construction. Therefore, the objective of this present work is to evaluate the radiological danger that they can present to society. Gamma spectrometry analysis on 16 samples of different brands of cement used as construction material in Rio de Janeiro (Brazil) was performed in this study, using an HPGe detector and the Genie 2000 data acquisition software. Samples were set to count for an accumulation time of 14,400 s (4 h) and all measurements were corrected to eliminate background and backscattering. Activity concentrations are determined for 226Ra was from (41.2 ± 1.6 to 174.9 ± 3.9) Bq kg-1, 232Th was from (15.7 ± 0.5 to 43.1 ± 0.7) Bq kg-1 and 40K was from (82.6 ± 7.2 to 254 ± 17) Bq kg-1. To assess radiological health risks: mean values of Radium Activity Equivalent 150.0 ± 3.4 Bq kg-1, Annual Gonadal Dose Equivalent 468 ± 11 µSv year-1 and Lifetime Excess Cancer Risk (ELCR) 2.42 ± 0.06 were calculated. Total Absorbed Dose Rates ranged from 72.2 ± 1.7 to 225.1 ± 5.2 nGy h-1. The damage to collective health was also estimated from the annual effective dose rates with an estimated total cost of damage to health of US$ 130 million. Values are generally within global limits reported by UNSCEAR.

Synthetic angiotensin II peptide derivatives confer protection against cerebral and severe non-cerebral malaria in murine models.

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.

Complexed amino acid minerals vs. bis-glycinate chelated minerals: Impact on the performance of old laying hens.

The present study was to evaluate the effect of trace minerals (Zn, Mn, and Cu) from complexed amino acid minerals (ZMCAA) and bis-glycinate chelated minerals (ZMCGly) in laying hen diets on performance, internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 × 2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low (20, 20, and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high (40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey's test (P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production (P = 0.01), egg weight (P = 0.02), egg mass (P = 0.01), and lower feed conversion ratio (P = 0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height (P = 0.01), albumen weight (P = 0.01), and eggshell thickness (P < 0.01). The deposition of Zn (P < 0.01), Mn (P < 0.01), and Cu (P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight (P = 0.04) and bone densitometry (P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi (P = 0.02) and shorter crypt depth (P = 0.01) in the duodenum. Jejunum and ileum measurements were influenced by the level and source of trace minerals (P < 0.05). Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

Association of Bacillus subtilis and Bacillus amyloliquefaciens: minimizes the adverse effects of necrotic enteritis in the gastrointestinal tract and improves zootechnical performance in broiler chickens.

This study aimed to evaluate the efficiency and capacity of the probiotic composed of Bacillus subtilis and Bacillus amyloliquefaciens, in improving the zootechnical performance of broiler chickens challenged with Eimeria spp. and Clostridium perfringens. The broilers were distributed in a completely randomized design in poultry isolators (12 birds each), resulting in 3 treatments: T1 (control, no challenge and no Bacillus in diet), T2 (challenged with Eimeria spp., followed by Clostridium perfringens infection and no Bacillus in the diet), and T3 (challenged with Eimeria spp., Clostridium perfringens and treated with Bacillus subtilis and Bacillus amyloliquefaciens). They were evaluated for a period of 29 d, divided into preinitial (1-7 d of age), initial (8-21 d), and growth (22-29 d) phases. Assessments of body weight, weight gain, feed consumption, and feed conversion were conducted, along with the classification of the scores and optical microscopy of the tract gastrointestinal. The animals challenged and treated with the probiotic containing Bacillus spp. showed improved indicators of zootechnical performance. Additionally, the animals challenged and treated (T3) had a better score for intestinal lesions compared to the other treatment groups. Therefore, the probiotic consisting of Bacillus subtilis and Bacillus amyloliquefaciens could be considered an effective option for disease prevention and improving the zootechnical performance of broiler chickens.

Assessment and estimation of the effective dose due to external exposure from natural radioactivity of sands used in civil construction in the state of Rio de Janeiro,Brazil.

The presence of naturally occurring radioactivity in sand and other building materials results in indoor and outdoor exposure to the public. Sand is one of the main components in civil construction alongside cement, crushed stone and bricks. Thus, this research was carried out in twenty sand samples with the objective of investigating the hazard indices of natural radiation, due to the presence of 238U, 226Ra, 232Th and 40K in sand samples collected in some locations in the state of Rio de Janeiro (Brazil), analyzing by gamma spectrometry and using an HPGe detector. The technique used for gamma analysis was gamma spectrometry, and the software used to analyze peaks and obtain counts was LabSOCS. In this context, the average activity concentration values of 226Ra (66.7 ± 1.2) and 40K (647 ± 31) Bq kg-1 are higher than the world mean activity concentration of 50, 50 and 500 Bq kg-1 for these three radionuclides. However, the value of 232Th (40.6 ± 0.7) Bq kg-1 and Raeq (175 ± 5) Bq kg-1 are less than the world average of 50 Bq kg-1 and 370 Bq kg-1, respectively. The estimation of the average values for Annual Effective Dose (0.51 ± 0.01) and Dutch Radiation Performance Index (0.52 ± 0.01) was carried out, with values below the maximum recommended limit for the public. Only one sample had a higher value and the other samples are within the levels required for environmental control. However, the mean values found in this present study, when compared to those of other authors mentioned here, showed higher values. Therefore, most samples have safe values to be used by people in building their homes.

PI3K Signaling Pathways as a Molecular Target for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that effectively eliminate cancer cells, circumventing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed via the PI3K pathway, against human glioblastoma.

Bradykinin produced during Plasmodium falciparum erythrocytic cycle drives monocyte adhesion to human brain microvascular endothelial cells.

Cerebral malaria (CM) pathogenesis is described as a multistep mechanism. In this context, monocytes have been implicated in CM pathogenesis by increasing the sequestration of infected red blood cells to the brain microvasculature. In disease, endothelial activation is followed by reduced monocyte rolling and increased adhesion. Nowadays, an important challenge is to identify potential pro-inflammatory stimuli that can modulate monocytes behavior. Our group have demonstrated that bradykinin (BK), a pro-inflammatory peptide involved in CM, is generated during the erythrocytic cycle of P. falciparum and is detected in culture supernatant (conditioned medium). Herein we investigated the role of BK in the adhesion of monocytes to endothelial cells of blood brain barrier (BBB). To address this issue human monocytic cell line (THP-1) and human brain microvascular endothelial cells (hBMECs) were used. It was observed that 20% conditioned medium from P. falciparum infected erythrocytes (Pf-iRBC sup) increased the adhesion of THP-1 cells to hBMECs. This effect was mediated by BK through the activation of B2 and B1 receptors and involves the increase in ICAM-1 expression in THP-1 cells. Additionally, it was observed that angiotensin-converting enzyme (ACE) inhibitor, captopril, enhanced the effect of both BK and Pf-iRBC sup on THP-1 adhesion. Together these data show that BK, generated during the erythrocytic cycle of P. falciparum, could play an important role in adhesion of monocytes in endothelial cells lining the BBB.