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1.
Braz. j. biol ; 83: e247374, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1285623

RESUMO

Abstract The present study was conducted to evaluate the diversity, distribution (C) and relative abundance (RA) of the mosquito fauna (Diptera: Culicidae) of Malakand and Dir Lower, Pakistan. Collection of specimens (n = 1087) was made during September 2018 to July 2019 at six different habitats including freshwater bodies, rice fields, animal sheds, indoors, drains and sewage waters. Specimens were collected through light traps, pyrethrum spray, aspirators and nets and subsequently killed, preserved and then arranged in entomological boxes for identification. Three genera were identified namely Culex, Anopheles and Aedes. A total of fourteen species were identified namely: Cx. quinquefasciatus (Say, 1823), An. stephensi (Liston, 1901), Cx. tritaeniorhynchus (Giles, 1901), Ae. vittatus (Bigot, 1861), An. maculatus (Theobald, 1901), An. fluviatilis (James, 1902), Cx. vishnui (Theobald, 1901), Ae. aegypti (Linnaeus, 1762) An. subpictus (Grassi, 1899), An. dthali (Patton, 1905), An. culicifascies (Giles, 1901), An. pallidus (Theobald, 1901), Ae. albopictus (Skuse, 1894) and An. annularis (van der Wulp, 1884). Cx. quinquefasciatus was found constantly distributed in the study area with RA = 16.5% and C = 100%. An. annularis was found as a satellite species, sporadically distributed in the study area having RA = 0.9% and C = 17%. Diversity indices of mosquitoes in the studied habitats were found as, Shannon-Wiener Index (2.415), Simpson Index (9.919), Fisher's Index (2.269) and Margalef's Index (1.859). A statistically significant difference was recorded in mosquito diversity in the six habitats (Kruskal-Wallis, chi-squared, H = 17.5, df = 5, P = 0.003 at α = 0.05). The present study encompasses mosquito fauna of Malakand, Pakistan with respect to diversity, relative abundance and distribution in diverse habitats and all seasons of the year. This will assist scientists working in various fields related with epidemiology, medical and veterinary entomology, ecology and allied areas of biological sciences.


Resumo O presente estudo foi conduzido para avaliar a diversidade, distribuição (C) e abundância relativa (RA) da fauna de mosquitos (Diptera: Culicidae) de Malakand e Dir Lower, Paquistão. A coleta de espécimes (n = 1087) foi feita durante o período de setembro de 2018 a julho de 2019 em seis habitats diferentes, incluindo corpos d'água, campos de arroz, galpões de animais, ambientes internos, ralos e águas residuais. Os espécimes foram coletados por meio de armadilhas luminosas, spray de piretro, aspiradores e redes e posteriormente mortos, preservados e depois dispostos em caixas entomológicas para identificação. Três gêneros foram identificados, nomeadamente Culex, Anopheles e Aedes. Um total de 14 espécies foi identificado, a saber: Cx. quinquefasciatus (Say, 1823), An. stephensi (Liston, 1901), Cx. tritaeniorhynchus (Giles, 1901), Ae. vittatus (Bigot, 1861), An. maculatus (Theobald, 1901), An. fluviatilis (James, 1902), Cx. vishnui (Theobald, 1901), Ae. aegypti (Linnaeus, 1762), An. subpictus (Grassi, 1899), An. dthali (Patton, 1905), An. culicifascies (Giles, 1901), An. pallidus (Theobald, 1901), Ae. albopictus (Skuse, 1894) e An. annularis (Van der Wulp, 1884). Cx. quinquefasciatus foi encontrado constantemente distribuído na área de estudo com AR = 16,5% e C = 100%. A. annularis foi encontrada como espécie satélite, distribuída esporadicamente na área de estudo com RA = 0,9% e C = 17%. Os índices de diversidade de mosquitos nos habitats estudados foram encontrados como índice de Shannon-Wiener (2,415), índice de Simpson (9,919), índice de Fisher (2,269) e índice de Margalef (1,859). Uma diferença estatisticamente significativa foi registrada na diversidade de mosquitos nos seis habitats (Kruskal-Wallis, qui-quadrado, H = 17,5, df = 5, P = 0,003 em α = 0,05). O presente estudo abrange a fauna de mosquitos de Malakand, Paquistão, com respeito à diversidade, abundância relativa e distribuição em diversos habitats e em todas as estações do ano. Isso ajudará os cientistas que trabalham em vários campos relacionados com a epidemiologia, entomologia médica e veterinária, ecologia e áreas afins das ciências biológicas.

2.
Braz. j. biol ; 82: e241110, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1278500

RESUMO

Abstract Plasmodium vivax is the most common human malaria parasite in Asian countries including Pakistan. Present study was designed to explore the genetic diversity of plasmodium vivax genotypes based on Pvmsp-3α and Pvmsp-3βgenes using allelic specific nested PCR and RFLP assays markers from field isolates in district Mardan, Pakistan. Blood samples of 200 P. vivax malarial patients were collected after taking their written informed consent. Genetic diversity in nested PCR products was determined by Restriction Fragment Length Polymorphism (RFLP) utilizing Alu1 and PstI restriction enzymes for alpha and beta gene products digestion, respectively. For analysis the genetic diversity of the sub allelic variants of Pvmsp3α and Pvmsp3β genes, Chi-Square test was performed by utilizing Minitab programming software 18. The P value 0.05 was considered as statistically significant. For Pvmsp-3α genes after gel electrophoresis of digested products, four distinct genotypes were obtained from total of 50 samples; type A: 35 (70%) (1.5-2.0 kb), 12 of type B (24%) (1.5-1.7 kb), 2 of type C (4%) (0.5-1.5) and one for type D (2%) (0.5-0.65 kb) which could be characterized into 9 allelic pattern (A1-A4, B1-B3, C1, D), in which A3 remained the most predominant. For Pvmsp-3βgenes, three distinct genotypes were obtained from 50 samples; 40(80%) of type A (1.5-2.5 kb), 9 (18%) of type B (1.0-1.5kb) and 1(2%) of type C (0.65 kb) which could be characterized into 6 allelic patterns (A1-A3, B1-B2, and C1). Most dominant one in Type A was A1 alleles which were noted (46%), while in Type B, the most dominant were B1 (10%).This study is the first ever report of molecular epidemiology and genetic variation in Pvmsp-3α and Pvmsp-3β genes of P. vivax isolates by using PCR/RFLP from District Mardan and showed a remarkable level of genetic diversity in the studied genes of circulating parasites in the study area. The results of this study will contribute in future studies about the genetic structure of parasite and vaccine development against the malaria.


Resumo O Plasmodium vivax é o parasita da malária humana mais comum nos países asiáticos, incluindo o Paquistão. O presente estudo foi desenhado para explorar a diversidade genética de genótipos de Plasmodium vivax baseados nos genes Pvmsp-3α e Pvmsp-3β, usando marcadores de ensaios alélicos nested PCR e RFLP de isolados de campo no distrito de Mardan, Paquistão. Amostras de sangue de 200 pacientes com malária por P. vivax foram coletadas após assinatura do termo de consentimento livre e esclarecido. A diversidade genética em produtos de PCR nested foi determinada por polimorfismo de fragmento de restrição (RFLP) utilizando as enzimas de restrição Alu1 e PstI para a digestão dos produtos dos genes alfa e beta, respectivamente. Para análise da diversidade genética das variantes subalélicas dos genes Pvmsp3α e Pvmsp3β, o teste Qui-quadrado foi realizado utilizando o software de programação Minitab 18. O valor P = 0,05 foi considerado estatisticamente significativo. Para os genes Pvmsp-3α, após eletroforese em gel de produtos digeridos, quatro genótipos distintos foram obtidos de um total de 50 amostras; tipo A: 35 (70%) (1,5-2,0 kb), 12 do tipo B (24%) (1,5-1,7 kb), 2 do tipo C (4%) (0,5-1,5) e um para o tipo D (2%) (0,5-0,65 kb), que podem ser caracterizados em nove padrões alélicos (A1-A4, B1-B3, C1, D), em que A3 permaneceu como o mais predominante. Para Pvmsp-3βgenes, três genótipos distintos foram obtidos a partir de 50 amostras; 40 (80%) do tipo A (1,5-2,5 kb), 9 (18%) do tipo B (1,0-1,5 kb) e 1 (2%) do tipo C (0,65 kb), que podem ser caracterizados em seis padrões alélicos (A1-A3, B1-B2 e C1). Os mais dominantes no tipo A foram o alelo A1, observados em 46%, enquanto, no tipo B, os mais dominantes foram B1 (10%). Este estudo é o primeiro relato de epidemiologia molecular e variação genética em Pvmsp-3α. Os genes Pvmsp-3β de isolados de P. vivax utilizando PCR/RFLP do Distrito Mardan mostraram um nível notável de diversidade genética nos genes estudados de parasitas circulantes na área de estudo. Os resultados desse estudo contribuirão em estudos futuros sobre a estrutura genética do parasita e o desenvolvimento de vacinas contra a malária.

3.
Braz. j. biol ; 82: e243670, 2022. tab
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1278509

RESUMO

Abstract For the proper growth of fish, it is necessary to feed the fish with a proper and balanced diet. A study was conducted to find out the effect of different protein-based diets on fingerlings of Tor putitora (mahseer). A feed with dietary protein levels of 35%, 40%, 45%, and 50% were prepared. The effect of different protein-based feed on weight gain, standard growth rate (SGR), food conversion ratio (FCR), percent weight gain, food conversion efficiency (FCE), and protein efficiency ratio (PER) was studied. An increase was observed in the growth rate with an increase in protein concentration up to 45%. The fingerlings fed a 45% protein diet shown the highest growth, followed by 50%, 40%, and 35%. The SGR value was greatest for 45% protein diet (8.56) followed by 50% and 40%, while the least values were observed for 35% protein feed (1.57). The same trend was observed for FCE. The highest PER values was observed in fishes fed 45% protein-based feed (0.65) followed by 50% (0.56), 40% (0.38) and35% (0.17). The food conversion ratio was lowest for 45% protein diet (3.41), while the greatest for 35% protein feed (16.85). It was concluded that a 45% protein-based diet was the best feed formulation for higher production of Tor putitora. However, research on the same percentage of protein diet is recommended for yearlings.


Resumo Para o bom crescimento dos peixes, é necessário alimentá-los com uma alimentação adequada e balanceada. Um estudo foi realizado para descobrir o efeito de diferentes dietas à base de proteínas em alevinos de Tor putitora (mahseer). Foi preparado um alimento com níveis de proteína dietética de 35%, 40%, 45% e 50%. O efeito de diferentes alimentos à base de proteína no ganho de peso, taxa de crescimento padrão (SGR), taxa de conversão alimentar (FCR), ganho de peso percentual, eficiência de conversão alimentar (FCE) e taxa de eficiência proteica (PER) foi estudado. Foi observado um aumento na taxa de crescimento com um aumento na concentração de proteína de até 45%. Os alevinos alimentados com dieta de 45% de proteína apresentaram o maior crescimento, seguidos de 50%, 40% e 35%. O valor de SGR foi maior para dieta com 45% de proteína (8,56), seguido de 50% e 40%, enquanto os menores valores foram observados para ração com 35% de proteína (1,57). A mesma tendência foi observada para FCE. Os maiores valores de PER foram observados em peixes alimentados com 45% de ração à base de proteína (0,65), seguido por 50% (0,56), 40% (0,38) e 35% (0,17). A taxa de conversão alimentar foi menor para a dieta com 45% de proteína (3,41), enquanto a maior para a dieta com 35% de proteína (16,85). Concluiu-se que a dieta à base de proteína de 45% foi a melhor formulação alimentar para maior produção de Tor putitora. No entanto, a pesquisa sobre a mesma porcentagem de dieta proteica é recomendada para animais de um ano.

4.
Braz. j. biol ; 82: e231509, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249242

RESUMO

Abstract The present study was aimed at comparing the brain size of mahseer (Tor putitora) in relation to their body weight and standard length, to investigate the potential impact of rearing environment on brain development in fish. The weight of the brain and three of its subdivisions cerebellum (CB), optic tectum (OT), and telencephalon (TC) were measured for both wild and hatchery-reared fish. The data was analysed using multiple analysis of covariance (MANCOVA), analysis of covariance (ANCOVA), and discriminate function analysis (DFA). We found the fish reared under hatchery conditions exhibit smaller brain size related to body weight, when compared to the wild ones. A significant (p<0.5) difference was observed in the length of CB and OT concerning the standard body length while no significant difference was found in TC of the fish from both the origins. The results of the current study highlight a logical assumption that neural deficiency affects the behaviour of fish, that's why the captive-reared fish show maladaptive response and face fitness decline when released to the natural environment for wild stock enhancement. The current study concluded that hatchery-reared fish exhibit variations in gross brain morphology as compared to their wild counterpart.


Resumo O presente estudo teve como objetivo comparar o tamanho do cérebro de mahseer (Tor putitora) em relação ao seu peso corporal e comprimento padrão, para investigar o impacto potencial do ambiente de criação no desenvolvimento do cérebro em peixes. O peso do cérebro e três de suas subdivisões — cerebelo (CB), tectum óptico (OT) e telencéfalo (TC) — foram medidos para peixes selvagens e criados em incubadoras. Os dados foram analisados usando análise múltipla de covariância (MANCOVA), análise de covariância (ANCOVA) e análise de função discriminante (DFA). Descobrimos que os peixes criados em condições de incubação apresentam menor tamanho do cérebro em relação ao peso corporal quando comparados aos selvagens. Uma diferença significativa (p <0,5) foi observada no comprimento do CB e OT em relação ao comprimento corporal padrão, enquanto nenhuma diferença significativa foi encontrada no CT dos peixes de ambas as origens. Os resultados do estudo atual destacam uma suposição lógica de que a deficiência neural afeta o comportamento dos peixes. É por isso que os peixes criados em cativeiro mostram uma resposta mal adaptativa e enfrentam declínio de aptidão quando liberados no ambiente natural para o aprimoramento do estoque selvagem. O estudo atual concluiu que os peixes criados em incubadoras exibem variações na morfologia cerebral bruta em comparação com suas contrapartes selvagens.

5.
Transl Oncol ; 14(10): 101184, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333275

RESUMO

BACKGROUND: The translocation t(15:19) produces the oncogenic BRD4-NUT fusion which is pathognomonic for NUT carcinoma (NC), which is a rare, but extremely aggressive solid tumor. Comprehensive genomic profiling (CGP) by hybrid-capture based next generation sequencing of 186+ genes of a cohort of advanced cancer cases with a variety of initial diagnoses harboring BRD4-NUT may shed further insight into the biology of these tumors and possible options for targeted treatment. CASE PRESENTATION: Thirty-one solid tumor cases harboring a BRD4-NUT translocation are described, with only 16% initially diagnosed as NC and the remainder carrying other diagnoses, most commonly NSCLCNOS (22%) and lung squamous cell carcinoma (NSCLC-SCC) (16%). The cohort was all microsatellite stable and harbored a low Tumor Mutational Burden (TMB, mean 1.7 mut/mb, range 0-4). In two index cases, patients treated with immune checkpoint inhibitors (ICPI) had unexpected partial or better responses of varying duration. Notably, four cases - including the two index cases - were negative for PD-L1 expression. Neo-antigen prediction for BRD4-NUT and then affinity modeling of the peptide-MHC (pMHC) complex for an assessable index case predicted very high affinity binding, both on a ranked (99.9%) and absolute (33 nM) basis. CONCLUSIONS: CGP identifies BRD4-NUT fusions in advanced solid tumors which carry a broad range of initial diagnoses and which should be re-diagnosed as NC per guidelines. A hypothesized mechanism underlying responses to ICPI in the low TMB, PD-L1 negative index cases is the predicted high affinity of the BRD4-NUT fusion peptide to MHC complexes. Further study of pMHC affinity and response to immune checkpoint inhibitors in patients with NC harboring BRD4-NUT is needed to validate this therapeutic hypothesis.

6.
Braz J Biol ; 83: e247374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431916

RESUMO

The present study was conducted to evaluate the diversity, distribution (C) and relative abundance (RA) of the mosquito fauna (Diptera: Culicidae) of Malakand and Dir Lower, Pakistan. Collection of specimens (n = 1087) was made during September 2018 to July 2019 at six different habitats including freshwater bodies, rice fields, animal sheds, indoors, drains and sewage waters. Specimens were collected through light traps, pyrethrum spray, aspirators and nets and subsequently killed, preserved and then arranged in entomological boxes for identification. Three genera were identified namely Culex, Anopheles and Aedes. A total of fourteen species were identified namely: Cx. quinquefasciatus (Say, 1823), An. stephensi (Liston, 1901), Cx. tritaeniorhynchus (Giles, 1901), Ae. vittatus (Bigot, 1861), An. maculatus (Theobald, 1901), An. fluviatilis (James, 1902), Cx. vishnui (Theobald, 1901), Ae. aegypti (Linnaeus, 1762) An. subpictus (Grassi, 1899), An. dthali (Patton, 1905), An. culicifascies (Giles, 1901), An. pallidus (Theobald, 1901), Ae. albopictus (Skuse, 1894) and An. annularis (van der Wulp, 1884). Cx. quinquefasciatus was found constantly distributed in the study area with RA = 16.5% and C = 100%. An. annularis was found as a satellite species, sporadically distributed in the study area having RA = 0.9% and C = 17%. Diversity indices of mosquitoes in the studied habitats were found as, Shannon-Wiener Index (2.415), Simpson Index (9.919), Fisher's Index (2.269) and Margalef's Index (1.859). A statistically significant difference was recorded in mosquito diversity in the six habitats (Kruskal-Wallis, chi-squared, H = 17.5, df = 5, P = 0.003 at α = 0.05). The present study encompasses mosquito fauna of Malakand, Pakistan with respect to diversity, relative abundance and distribution in diverse habitats and all seasons of the year. This will assist scientists working in various fields related with epidemiology, medical and veterinary entomology, ecology and allied areas of biological sciences.


Assuntos
Culicidae , Animais , Ecologia , Ecossistema , Paquistão , Estações do Ano
7.
Future Oncol ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463133

RESUMO

Aim: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods: Retrospective analysis of HER2/ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2+ advanced esophagogastric cancer who received first-line trastuzumab. Results: Overall HER2/ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR]: 0.63; 95% CI: 0.43-0.90) and overall survival (aHR: 0.51; 95% CI: 0.33-0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR: 0.56; 95% CI: 0.35-0.88) and overall survival (aHR: 0.52; 95% CI: 0.30-0.91). Conclusion: HER2/ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab.

8.
Br J Dermatol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254667

RESUMO

We appreciate the interest shown by Pathania regarding our manuscript,1 and enjoyed reading his additional comments on multisystem inflammatory syndrome in adults (MIS-A)/children (MIS-C) and kawasaki disease (KD). Our patient had a 3-days history of fever, and the rash appeared within a day of fever. Fever and rash subsided promptly with intravenous steroids (hydrocortisone 100mg Q8H) which was given from emergency suspecting drug rash (azithromycin and mefenamic acid taken for the fever).

9.
Braz J Biol ; 82: e231509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076158

RESUMO

The present study was aimed at comparing the brain size of mahseer (Tor putitora) in relation to their body weight and standard length, to investigate the potential impact of rearing environment on brain development in fish. The weight of the brain and three of its subdivisions cerebellum (CB), optic tectum (OT), and telencephalon (TC) were measured for both wild and hatchery-reared fish. The data was analysed using multiple analysis of covariance (MANCOVA), analysis of covariance (ANCOVA), and discriminate function analysis (DFA). We found the fish reared under hatchery conditions exhibit smaller brain size related to body weight, when compared to the wild ones. A significant (p<0.5) difference was observed in the length of CB and OT concerning the standard body length while no significant difference was found in TC of the fish from both the origins. The results of the current study highlight a logical assumption that neural deficiency affects the behaviour of fish, that's why the captive-reared fish show maladaptive response and face fitness decline when released to the natural environment for wild stock enhancement. The current study concluded that hatchery-reared fish exhibit variations in gross brain morphology as compared to their wild counterpart.


Assuntos
Cyprinidae , Animais , Peso Corporal , Encéfalo , Meio Ambiente
10.
J Oncol Pharm Pract ; : 10781552211026375, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34152210

RESUMO

INTRODUCTION: The use of TKIs in CML has dramatically altered the natural course of the disease and improved outcomes for patients. TKIs overall have a very favorable safety profile. Dasatinib, a second generation TKI, is commonly used as a first-line treatment option in CML. CASE REPORT: We describe the first two reported cases of first-line dasatinib induced aplastic anemia in CML. In both patients, pancytopenia occurred within one year of diagnosis/starting dasatinib. Both bone marrow biopsies showed hypocellularity with mild fibrosis and persistent BCR-Abl1 positivity. MANAGEMENT & OUTCOME: Dose reduction was attempted without success in both patients. In one patient, multiple TKIs were trialed, while in the other, growth factor support was attempted; neither regimen was effective. Ultimately, the cytopenias associated with dasatinib were only resolved after immunosuppression in one patient and allogeneic stem cell transplant in the other patient. DISCUSSION: Prior reports have shown that aplasia/aplastic anemia can rarely be associated with imatinib and nilotinib. Here we show that dasatinib can lead to this phenomenon as well. This diagnosis should be considered in patients with CML who unexpectedly develop cytopenias.

11.
Braz J Biol ; 82: e241110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133560

RESUMO

Plasmodium vivax is the most common human malaria parasite in Asian countries including Pakistan. Present study was designed to explore the genetic diversity of plasmodium vivax genotypes based on Pvmsp-3α and Pvmsp-3ßgenes using allelic specific nested PCR and RFLP assays markers from field isolates in district Mardan, Pakistan. Blood samples of 200 P. vivax malarial patients were collected after taking their written informed consent. Genetic diversity in nested PCR products was determined by Restriction Fragment Length Polymorphism (RFLP) utilizing Alu1 and PstI restriction enzymes for alpha and beta gene products digestion, respectively. For analysis the genetic diversity of the sub allelic variants of Pvmsp3α and Pvmsp3ß genes, Chi-Square test was performed by utilizing Minitab programming software 18. The P value 0.05 was considered as statistically significant. For Pvmsp-3α genes after gel electrophoresis of digested products, four distinct genotypes were obtained from total of 50 samples; type A: 35 (70%) (1.5-2.0 kb), 12 of type B (24%) (1.5-1.7 kb), 2 of type C (4%) (0.5-1.5) and one for type D (2%) (0.5-0.65 kb) which could be characterized into 9 allelic pattern (A1-A4, B1-B3, C1, D), in which A3 remained the most predominant. For Pvmsp-3ßgenes, three distinct genotypes were obtained from 50 samples; 40(80%) of type A (1.5-2.5 kb), 9 (18%) of type B (1.0-1.5kb) and 1(2%) of type C (0.65 kb) which could be characterized into 6 allelic patterns (A1-A3, B1-B2, and C1). Most dominant one in Type A was A1 alleles which were noted (46%), while in Type B, the most dominant were B1 (10%).This study is the first ever report of molecular epidemiology and genetic variation in Pvmsp-3α and Pvmsp-3ß genes of P. vivax isolates by using PCR/RFLP from District Mardan and showed a remarkable level of genetic diversity in the studied genes of circulating parasites in the study area. The results of this study will contribute in future studies about the genetic structure of parasite and vaccine development against the malaria.


Assuntos
Plasmodium vivax , Proteínas de Protozoários , Variação Genética , Genótipo , Humanos , Paquistão , Plasmodium vivax/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Proteínas de Protozoários/genética
12.
Braz J Biol ; 82: e243670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161428

RESUMO

For the proper growth of fish, it is necessary to feed the fish with a proper and balanced diet. A study was conducted to find out the effect of different protein-based diets on fingerlings of Tor putitora (mahseer). A feed with dietary protein levels of 35%, 40%, 45%, and 50% were prepared. The effect of different protein-based feed on weight gain, standard growth rate (SGR), food conversion ratio (FCR), percent weight gain, food conversion efficiency (FCE), and protein efficiency ratio (PER) was studied. An increase was observed in the growth rate with an increase in protein concentration up to 45%. The fingerlings fed a 45% protein diet shown the highest growth, followed by 50%, 40%, and 35%. The SGR value was greatest for 45% protein diet (8.56) followed by 50% and 40%, while the least values were observed for 35% protein feed (1.57). The same trend was observed for FCE. The highest PER values was observed in fishes fed 45% protein-based feed (0.65) followed by 50% (0.56), 40% (0.38) and35% (0.17). The food conversion ratio was lowest for 45% protein diet (3.41), while the greatest for 35% protein feed (16.85). It was concluded that a 45% protein-based diet was the best feed formulation for higher production of Tor putitora. However, research on the same percentage of protein diet is recommended for yearlings.


Assuntos
Ração Animal , Cyprinidae , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas na Dieta
13.
Hum Pathol ; 114: 110-119, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33961839

RESUMO

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although viral infection is known to trigger inflammatory processes contributing to tissue injury and organ failure, it is unclear whether direct viral damage is needed to sustain cellular injury. An understanding of pathogenic mechanisms has been handicapped by the absence of optimized methods to visualize the presence and distribution of SARS-CoV-2 in damaged tissues. We first developed a positive control cell line (Vero E6) to validate SARS-CoV-2 detection assays. We then evaluated multiple organs (lungs, kidneys, heart, liver, brain, intestines, lymph nodes, and spleen) from fourteen COVID-19 autopsy cases using immunohistochemistry (IHC) for the spike and the nucleoprotein proteins, and RNA in situ hybridization (RNA ISH) for the spike protein mRNA. Tissue detection assays were compared with quantitative polymerase chain reaction (qPCR)-based detection. SARS-CoV-2 was histologically detected in the Vero E6 positive cell line control, 1 of 14 (7%) lungs, and none (0%) of the other 59 organs. There was perfect concordance between the IHC and RNA ISH results. qPCR confirmed high viral load in the SARS-CoV-2 ISH-positive lung tissue, and absent or low viral load in all ISH-negative tissues. In patients who die of COVID-19-related organ failure, SARS-CoV-2 is largely not detectable using tissue-based assays. Even in lungs showing widespread injury, SARS-CoV-2 viral RNA or proteins were detected in only a small minority of cases. This observation supports the concept that viral infection is primarily a trigger for multiple-organ pathogenic proinflammatory responses. Direct viral tissue damage is a transient phenomenon that is generally not sustained throughout disease progression.


Assuntos
COVID-19/patologia , Fígado/virologia , Pulmão/virologia , SARS-CoV-2/patogenicidade , Animais , Autopsia/métodos , COVID-19/virologia , Chlorocebus aethiops , Progressão da Doença , Humanos , Imuno-Histoquímica/métodos , Fígado/química , Fígado/patologia , Pulmão/patologia , RNA Viral/metabolismo , Células Vero/virologia , Carga Viral/métodos
14.
Oncologist ; 26(5): 406-421, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33792103

RESUMO

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by absolute monocytosis, one or more lineage dysplasia, and proliferative features including myeloid hyperplasia, splenomegaly, and constitutional symptoms. Because of vast clinical heterogeneity in presentation and course, risk stratification is used for a risk-adapted treatment strategy. Numerous prognostic scoring systems exist, some of which incorporate mutational information. Treatment ranges from observation to allogeneic hematopoietic stem cell transplantation. Therapies include hydroxyurea for cytoreduction, hypomethylating agents, and the JAK1/2 inhibitor ruxolitinib to address splenomegaly and constitutional symptoms. Recently, oral decitabine with cedazuridine was approved and represents a convenient treatment option for CMML patients. Although novel therapeutics are in development for CMML, further work is needed to elucidate possible targets unique to the CMML clone. In this review, we will detail the pathophysiology, risk stratification, available treatment modalities, and novel therapies for CMML, and propose a modern treatment algorithm. IMPLICATIONS FOR PRACTICE: Chronic myelomonocytic leukemia (CMML) is a clinically heterogenous disease, which poses significant management challenges. The diagnosis of CMML requires bone marrow biopsy and aspirate with thorough evaluation. Risk stratification and symptom assessment are essential to designing an effective treatment plan, which may include hypomethylating agents (HMAs) in intermediate or high-risk patients. The recently approved oral decitabine/cedazuridine provides a convenient alternative to parenteral HMAs. Ruxolitinib may be effective in ameliorating proliferative symptoms and splenomegaly. Allogeneic stem cell transplantation remains the only treatment with curative potential; however, novel therapies are in clinical development which may significantly alter the therapeutic landscape of CMML.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Humanos , Hidroxiureia , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Mutação , Medição de Risco
15.
Mod Pathol ; 34(8): 1456-1467, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33795830

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.


Assuntos
COVID-19/fisiopatologia , Pulmão/fisiopatologia , Embolia Pulmonar/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Coagulação Sanguínea , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Causas de Morte , Citocinas/sangue , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Embolia Pulmonar/sangue , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , SARS-CoV-2/patogenicidade
16.
Nat Commun ; 12(1): 1382, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654076

RESUMO

Mechanistic understanding of oncogenic variants facilitates the development and optimization of treatment strategies. We recently identified in-frame, tandem duplication of EGFR exons 18 - 25, which causes EGFR Kinase Domain Duplication (EGFR-KDD). Here, we characterize the prevalence of ERBB family KDDs across multiple human cancers and evaluate the functional biochemistry of EGFR-KDD as it relates to pathogenesis and potential therapeutic intervention. We provide computational and experimental evidence that EGFR-KDD functions by forming asymmetric EGF-independent intra-molecular and EGF-dependent inter-molecular dimers. Time-resolved fluorescence microscopy and co-immunoprecipitation reveals EGFR-KDD can form ligand-dependent inter-molecular homo- and hetero-dimers/multimers. Furthermore, we show that inhibition of EGFR-KDD activity is maximally achieved by blocking both intra- and inter-molecular dimerization. Collectively, our findings define a previously unrecognized model of EGFR dimerization, providing important insights for the understanding of EGFR activation mechanisms and informing personalized treatment of patients with tumors harboring EGFR-KDD. Finally, we establish ERBB KDDs as recurrent oncogenic events in multiple cancers.


Assuntos
Receptores ErbB/química , Receptores ErbB/metabolismo , Duplicação Gênica , Terapia de Alvo Molecular , Oncogenes , Sequência de Aminoácidos , Animais , Linhagem Celular , Proliferação de Células , Epitopos/metabolismo , Receptores ErbB/genética , Ligantes , Camundongos , Neoplasias/metabolismo , Fosforilação , Ligação Proteica , Domínios Proteicos , Multimerização Proteica , Relação Estrutura-Atividade
17.
Oncologist ; 26(4): e715-e718, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522043

RESUMO

The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. Herein, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500× coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), androgen receptor (AR) gene, and coalterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). Overall, cyclin sensitizing pathway genomic abnormalities were found in 9.7% of the 5,356 tumors. Frequent alterations included CCND1 amplification (4.2%) and CDKN2A and B loss (2.4% each). Alterations in possible resistance genes, RB1 and CCNE1, were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, whereas AR alterations were seen in 20.9% of tumors (~27.3% in anaplastic). Cyclin sensitizing alterations were also more frequently associated with concomitant AR alterations.


Assuntos
Genômica , Neoplasias da Próstata , Pontos de Checagem do Ciclo Celular , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
18.
Clin Cancer Res ; 27(11): 3126-3140, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33542076

RESUMO

PURPOSE: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents. EXPERIMENTAL DESIGN: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX). RESULTS: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition. CONCLUSIONS: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors.See related commentary by Openshaw et al., p. 2964.

19.
Am J Surg Pathol ; 45(5): 587-603, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481385

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.


Assuntos
COVID-19/patologia , Pulmão/patologia , Síndrome Respiratória Aguda Grave/patologia , Autopsia , Encéfalo/patologia , COVID-19/mortalidade , Estudos de Casos e Controles , Saúde Global , Humanos , Rim/patologia , Miocárdio/patologia , Síndrome Respiratória Aguda Grave/mortalidade , Baço/patologia
20.
Oncologist ; 26(1): e78-e89, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32885893

RESUMO

BACKGROUND: We describe the landscape of cyclin and interactive gene pathway alterations in 190,247 solid tumors. METHODS: Using comprehensive genomic profiling (315 genes, >500× coverage), samples were analyzed for alterations in activating/sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), hormone genes (estrogen receptor 1 [ESR1], androgen receptor [AR]), and co-alterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). RESULTS: Alterations in at least one cyclin activating/sensitizing gene occurred in 24% of malignancies. Tumors that frequently harbored at least one cyclin alteration were brain gliomas (47.1%), esophageal (40.3%) and bladder cancer (37.9%), and mesotheliomas (37.9%). The most frequent alterations included CDKN2A (13.9%) and CDKN2B loss (12.5%). Examples of unique patterns of alterations included CCND1 amplification in breast cancer (17.3%); CDK4 alterations in sarcomas (12%); CCND2 in testicular cancer (23.4%), and SMARCB1 mutations in kidney cancer (3% overall, 90% in malignant rhabdoid tumors). Alterations in resistance genes RB1 and CCNE1 affected 7.2% and 3.6% of samples. Co-occurrence analysis demonstrated a lower likelihood of concomitant versus isolated alterations in cyclin activating/sensitizing and resistance genes (odds ratio [OR], 0.35; p < .001), except in colorectal, cervical, and small intestine cancers. AR and cyclin activating/sensitizing alterations in prostate cancer co-occurred more frequently (vs. AR alterations and wild-type cyclin activating/sensitizing alterations) (OR, 1.79; p < .001) as did ESR1 and cyclin activating/sensitizing alterations in breast (OR, 1.62; p < .001) and cervical cancer (OR, 4.08; p = .04) (vs. ESR1 and cyclin wild-type activating/sensitizing alterations). CONCLUSION: Cyclin pathway alterations vary according to tumor type/histology, informing opportunities for targeted therapy, including for rare cancers. IMPLICATIONS FOR PRACTICE: Cyclin pathway genomic abnormalities are frequent in human solid tumors, with substantial variation according to tumor site and histology. Opportunities for targeted therapy emerge with comprehensive profiling of this pathway.


Assuntos
Glioma , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Genômica , Humanos , Masculino , Mutação
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