Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction.

Macrophage immune checkpoint inhibitors, such as anti-CD47 antibodies, show promise in clinical trials for solid and hematologic malignancies. However, the best strategies to use these therapies remain unknown, and ongoing studies suggest they may be most effective when used in combination with other anticancer agents. Here, we developed an unbiased, high-throughput screening platform to identify drugs that render lung cancer cells more vulnerable to macrophage attack, and we found that therapeutic synergy exists between genotype-directed therapies and anti-CD47 antibodies. In validation studies, we found that the combination of genotype-directed therapies and CD47 blockade elicited robust phagocytosis and eliminated persister cells in vitro and maximized antitumor responses in vivo. Importantly, these findings broadly applied to lung cancers with various RTK/MAPK pathway alterations - including EGFR mutations, ALK fusions, or KRASG12C mutations. We observed downregulation of ß2-microglobulin and CD73 as molecular mechanisms contributing to enhanced sensitivity to macrophage attack. Our findings demonstrate that dual inhibition of the RTK/MAPK pathway and the CD47/SIRPa axis is a promising immunotherapeutic strategy. Our study provides strong rationale for testing this therapeutic combination in patients with lung cancers bearing driver mutations.

Risk factors for toxocariasis during incarceration: the One Health intervention approach.

Despite potential exposure to soil-transmitted helminths, especially when stray dogs and cats are present, toxocariasis in inmate populations remains to be established. Accordingly, the present study assessed the seroprevalence and associated risk factors of toxocariasis at the Women's State Penitentiary of Parana, Brazil. A total of 234/370 (63.2%; 95% CI 58.2-68.0) women inmates and 28/87 (32.2%; 95% CI 23.3-42.6) correctional officers were seropositive for anti-Toxocara spp. IgG by ELISA, with inmates 2.62-fold more likely positive (p = 0.00000026). The univariate model has identified that non-white (OR = 1.58, p = 0.047) and older than 39 years (OR = 1.28, p = 0.032) inmates were associated with mild but significant odds for seropositivity. Elementary or higher educational level was considered a protective factor for seropositivity. The presence of Toxocara spp. eggs was observed in 10/15 (66.7%) collected soil samples by centrifuge-flotation in Zinc Sulfate, and molecular analysis by PCR identified only Toxocara cati in these eggs. An intervention program was established with regular trap-neuter-release, with gradual removal for adoption (donation campaigns), treatment, and euthanasia when necessary (particularly due to advanced sporotrichosis). In addition, an educational awareness agenda was proposed, aiming to reduce soil contamination and accidental intake by the incarcerated population. A total of 40 feral cats were trapped, 20 males and 20 females, mostly adults. After trapping, 36 cats were neutered, treated, and microchipped in the Veterinary Teaching Hospital (VTH) at the Federal University of Paraná. Five trapped feral cats were euthanized, four diagnosed with advanced sporotrichosis, and one already neutered cat (not herein) with complications due to feline immunodeficiency virus (FIV). Female inmates presented higher seroprevalence for Toxocara spp. antibodies when compared to correctional officers, significantly associated with age, self-declared ethnicity (non-white), and lack of formal education. Despite the non-natural scenario of a state penitentiary, the One Health approach of Toxocara spp. has highlighted the interdisciplinary nature of the study and its relevance in understanding the complex interactions between human, animal, and environmental factors, particularly impacting female inmates. Further studies should establish the rate of inmate infection over time while deprived of liberty.

The effects of drying methods and harvest season on piperine, essential oil composition, and multi-elemental composition of black pepper.

This study aimed to evaluate the piperine content, essential oil composition, and multi-elemental composition of black pepper samples according to different drying methods and harvest season. Differences in essential oil composition and B, Ca, K, Mg, and S were noted according to sampling campaign, indicating secondary metabolism plant alterations. Mechanical drying resulted in essential oil composition changes due to high temperature exposure during processing. Increases in Fe and Cr contents when employing mechanical dryers with direct heating were also observed, due to direct contact with metallic structures and particulate material from the burning process. The As and Pb contents of several samples were higher than the maximum permissible limits, reaching 0.46 and 0.56 mg kg-1, respectively, thus surpassing legislation safety limitations for human consumption.

Spatial Distribution of Bat Shelters and Livestock Rabies in Southern Brazil.

This study focused on the epidemiological characterization and spatial distribution of bat shelters concerning livestock animal rabies in Paraná State, southern Brazil. A spatiotemporal cluster analysis was performed based on rabies-positive cases and the Desmodus rotundus shelters. A total of 1742 suspect rabies cases submitted for diagnosis from 2011 to 2017 were analyzed; 481 (27.61%) were positive, and 1261 (72.39%) were negative by direct immunofluorescence and biological testing in mice. Out of the positive samples, 413/481 (85.8%) was bovine, 44/481 (9.1%) equine, 6/481 (1.2%) sheep, 5/481 (1.0%) bubaline, and 14/481 (2.9%) were bats. From 22 Regional Units of Agricultural Health, the northeast 129 (26.82%) and central 86 (17.88%) units had the highest recurrence rates of positive cases. Paraná State was continuously endemic for livestock rabies, with the highest caseload seen in the southern-central regions, which was associated with the highest number of vampire bat shelters and natural geographical characteristics favoring bat housing. There was a decrease in the number of rabies cases in livestock in 2013 and 2014. Spatiotemporal analyses of point process mapping and control of D. rotundus shelters and suspected livestock rabies cases in the study area were steady and statistically correlated. However, as bats may travel up to 35-40 km to prey on cattle clusters, bat shelter locations may not be the most sensitive measure of exposure. Furthermore, future studies should consider landscape features such as altitude as potential associated risk factors. Rabies vaccination of livestock and bat hematophagous shelters identification combined with bat control is recommended to increase the efficacy of preventive measures, particularly in natural geographic characteristics favoring local bat housing.

Hemotropic mycoplasmas (hemoplasmas) in free-ranging bats from Southern Brazil.

Hemotropic mycoplasmas (hemoplasmas) are bacteria distributed worldwide and affect domestic and wildlife animals and human beings. Hemoplasmas have been described infecting hematophagous and non-hematophagous bats; however, transmission risk and zoonotic potential in vampire bats remain to be fully established. This study aimed to evaluate the presence of hemotropic mycoplasma species in free-ranging bats from this area using a universal PCR protocol for hemoplasmas. Accordingly, ten blood samples were collected from six male common vampire bats (Desmodus rotundus), two male hairy-legged vampire bats (Diphylla ecaudata), and two female non-hematophagous Pallas's mastiff bats (Molossus sp.) from the Curitiba's region, Paraná State, Southern Brazil. A total of eight (8/10) blood samples were positive byconventional PCR; five (5/6) Desmodus rotundus, two (2/2) Diphylla ecaudata, and one (1/2) Molossus sp. bats. The analyses of the partial sequence of the 16S rDNA gene suggest that the hemoplasma detected in Desmodus rotundus in South Brazil has a high identity compared to the hemoplasma circulating in vampire bats from Central and South America.

Multi-element rice grains analysis by ICP OES and classification by processing types.

As major food staple, rice (Oryza sativa L.) is cultivated in irrigated fields absorbing widely trace elements wich may or may not migrate during processing types. Thus, we aimed to evaluate five national rice brands found in local market, in order to verify concentration of elements As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Sn, Sr, V, Tl and Zn, presenting the differences and migration patterns between brown, parboiled and polished rice for each brand. Data were evaluated using ANOVA, post-hoc Tukey and PCA. The two major components presented 94.33% variance, indicating strong differentiation in samples by their processing types from their mineral composition. K is widely distributed over the grain, Mg, Fe and Ba are more distributed in the outer layers being more susceptible to loss, and Ca, Sr and Zn are more sensitive to the parboiling hydrothermal process.

Bat rabies surveillance and risk factors for rabies spillover in an urban area of Southern Brazil.

BACKGROUND: Bat rabies surveillance data and risk factors for rabies spillover without human cases have been evaluated in Curitiba, the ninth biggest city in Brazil, during a 6-year period (2010-2015). A retrospective analysis of bat complaints, bat species identification and rabies testing of bats, dogs and cats has been performed using methodologies of seasonal decomposition, spatial distribution and kernel density analysis. RESULTS: Overall, a total of 1003 requests for bat removal have been attended to, and 806 bats were collected in 606 city locations. Bat species were identified among 13 genera of three families, with a higher frequency of Nyctinomops in the central-northern region and Molossidae scattered throughout city limits. Out of the bats captured alive, 419/806 (52.0%) healthy bats were released due to absence of human or animal contacts. The remaining 387/806 (48.0%) bats were sent for euthanasia and rabies testing, which resulted in 9/387 (2.32%) positives. Linear regression has shown an increase on sample numbers tested over time (regression: y = 2.02 + 0.17×; p < 0.001 and r2 = 0.29), as well as significant seasonal variation, which increases in January and decreases in May, June and July. The Kernel density analysis showed the center-northern city area to be statistically important, and the southern region had no tested samples within the period. In addition, a total of 4769 random and suspicious samples were sent for rabies diagnosis including those from dogs, cats, bats and others from 2007 to 2015. While all 2676 dog brains tested negative, only 1/1136 (0.088%) cat brains tested positive for rabies. CONCLUSION: Only non-hematophagous bats were collected during the study, and the highest frequency of collections occurred in the center-northern region of the city. Rabies spillover from bats to cats may be more likely due to the registered exposure associated with cats' innate hunting habits, predisposing them to even closer contact with potentially infected bats. Although associated with a very low frequency of rabies, cats should always be included in rabies surveillance and vaccination programs.

ICP-OES and Micronucleus Test to Evaluate Heavy Metal Contamination in Commercially Available Brazilian Herbal Teas.

Increased tea consumption in combination with intensive pesticide use is generating heavy metal contaminations amongst Brazilian tea consumers, causing health concerns. Inductively coupled plasma optical emission spectrometry (ICP-OES) was applied to quantify minerals and heavy metals such as aluminum, barium, cadmium, lead, cobalt, copper, chromium, tin, manganese, molybdenum, nickel, selenium, silver, thallium, vanadium and zinc in Brazilian chamomile, lemongrass, fennel and yerba mate teas. Teas, purchased in local supermarkets, were prepared using infusion and acid digestion. Higher concentrations of Al were present in all samples. In the digested samples, the Al mean concentration was 2.41 µg g(-1) (sd = 0.72) for fennel and 33.42 µg g(-1) (sd = 17.18) for chamomile, whilst the sample C for chamomile tea presented the highest concentration with 51.62 µg g(-1) (sd = 9.17). The safety relation in decreasing order is fennel, lemongrass, chamomile and yerba mate. Chemometric analyses demonstrated a strong correlation between the elements Cd and Pb in the samples. Yerba mate had the highest amount of metal (100 mg kg(-1)), being the subject of a micronucleus test assay for cytotoxicity. The metals found in Yerba mate did not present cytotoxicity/mutagenicity using the micronucleus test. The inorganic contaminants in teas should have their impact carefully monitored.

Cat infected by a variant of bat rabies virus in a 29-year disease-free urban area of southern Brazil.

INTRODUCTION: After 29 years, rabies was detected in a cat in Curitiba, southern Brazil. METHODS: The fluorescent antibody test (FAT) and mouse inoculation test (MIT) were performed on central nervous system (CNS) samples. RESULTS: Direct immunofluorescence was negative, but the biological test was positive and rabies virus was characterized as variant 4 (from Tadarida brasiliensis). CONCLUSIONS: Reappearance of rabies in domestic animals warns of sylvatic-aerial risk of infection and the necessity of monitoring bats in historically rabies-free areas.

A feasibility study of cell phone and landline phone interviews for monitoring of risk and protection factors for chronic diseases in Brazil.

The study objective was to evaluate the feasibility of interviews by cell phone as a complement to interviews by landline to estimate risk and protection factors for chronic non-communicable diseases. Adult cell phone users were evaluated by random digit dialing. Questions asked were: age, sex, education, race, marital status, ownership of landline and cell phones, health condition, weight and height, medical diagnosis of hypertension and diabetes, physical activity, diet, binge drinking and smoking. The estimates were calculated using post-stratification weights. The cell phone interview system showed a reduced capacity to reach elderly and low educated populations. The estimates of the risk and protection factors for chronic non-communicable diseases in cell phone interviews were equal to the estimates obtained by landline phone. Eligibility, success and refusal rates using the cell phone system were lower than those of the landline system, but loss and cost were much higher, suggesting it is unsatisfactory as a complementary method in such a context.

A feasibility study of cell phone and landline phone interviews for monitoring of risk and protection factors for chronic diseases in Brazil / Exequibilidade do uso de entrevistas por telefone celular e por telefone fixo no monitoramento de fatores de risco e proteção para doenças crônicas

The study objective was to evaluate the feasibility of interviews by cell phone as a complement to interviews by landline to estimate risk and protection factors for chronic non-communicable diseases. Adult cell phone users were evaluated by random digit dialing. Questions asked were: age, sex, education, race, marital status, ownership of landline and cell phones, health condition, weight and height, medical diagnosis of hypertension and diabetes, physical activity, diet, binge drinking and smoking. The estimates were calculated using post-stratification weights. The cell phone interview system showed a reduced capacity to reach elderly and low educated populations. The estimates of the risk and protection factors for chronic non-communicable diseases in cell phone interviews were equal to the estimates obtained by landline phone. Eligibility, success and refusal rates using the cell phone system were lower than those of the landline system, but loss and cost were much higher, suggesting it is unsatisfactory as a complementary method in such a context.

Avaliar a exequibilidade do uso de entrevistas por telefone celular de forma complementar ao fixo para estimativas de fatores de risco e proteção para doenças crônicas não transmissíveis. Questionou-se: idade, sexo, escolaridade, cor, situação conjugal, posse de telefones fixos e celulares, estado de saúde, peso e altura, diagnóstico hipertensão arterial e diabetes, atividade física, alimentação, consumo de bebidas alcoólicas e tabagismo. As estimativas foram calculadas com peso pós-estratificação. Observou-se, na população entrevistada pelo celular, superestimação na idade entre 25 e 34 anos e subestimação na idade > 45 anos e na faixa de baixa escolaridade. No que se refere aos fatores de risco e proteção para doenças crônicas, as estimativas obtidas nas entrevistas por telefone celular foram iguais às obtidas pelo telefone fixo. As taxas de elegibilidade, de sucesso e de recusas do sistema por telefone celular foram menores do que as do sistema por telefonia fixa; ademais, a perda e o custo foram muito maiores no primeiro sistema, sugerindo que este é insatisfatório como complemento no atual contexto.