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1.
Cell ; 186(18): 3862-3881.e28, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37572660

RESUMO

Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.


Assuntos
Vias Neurais , Comportamento Sexual Animal , Animais , Masculino , Neurônios/fisiologia , Recompensa , Comportamento Sexual Animal/fisiologia , Camundongos
2.
Cell ; 183(3): 605-619.e22, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33031743

RESUMO

Exploration of novel environments ensures survival and evolutionary fitness. It is expressed through exploratory bouts and arrests that change dynamically based on experience. Neural circuits mediating exploratory behavior should therefore integrate experience and use it to select the proper behavioral output. Using a spatial exploration assay, we uncovered an experience-dependent increase in momentary arrests in locations where animals arrested previously. Calcium imaging in freely exploring mice revealed a genetically and projection-defined neuronal ensemble in the basolateral amygdala that is active during self-paced behavioral arrests. This ensemble was recruited in an experience-dependent manner, and closed-loop optogenetic manipulation of these neurons revealed that they are sufficient and necessary to drive experience-dependent arrests during exploration. Projection-specific imaging and optogenetic experiments revealed that these arrests are effected by basolateral amygdala neurons projecting to the central amygdala, uncovering an amygdala circuit that mediates momentary arrests in familiar places but not avoidance or anxiety/fear-like behaviors.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Núcleo Central da Amígdala/fisiologia , Comportamento Exploratório/fisiologia , Rede Nervosa/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/diagnóstico por imagem , Comportamento Animal/fisiologia , Núcleo Central da Amígdala/diagnóstico por imagem , Feminino , Locomoção , Aprendizado de Máquina , Masculino , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Imagem Óptica
4.
EMBO J ; 40(16): e107913, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34191328

RESUMO

The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how mitochondrial processes regulate the behavior of aggregation-prone polyQ protein derived from human huntingtin. Expression of Q97-GFP rapidly led to insoluble cytosolic aggregates and cell death. Although aggregation impaired mitochondrial respiration only slightly, it considerably interfered with the import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97-GFP, whereas Mia40 overexpression strongly suppressed the formation of toxic Q97-GFP aggregates both in yeast and in human cells. Based on these observations, we propose that the post-translational import of mitochondrial precursor proteins into mitochondria competes with aggregation-prone cytosolic proteins for chaperones and proteasome capacity. Mia40 regulates this competition as it has a rate-limiting role in mitochondrial protein import. Therefore, Mia40 is a dynamic regulator in mitochondrial biogenesis that can be exploited to stabilize cytosolic proteostasis.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Peptídeos/metabolismo , Agregação Patológica de Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Linhagem Celular , Citosol/metabolismo , Humanos , Mitocôndrias/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Saccharomyces cerevisiae
5.
Emerg Infect Dis ; 30(11): 2441-2444, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39447207

RESUMO

Analysis of clinical and environmental Vibrio cholerae O1 strains obtained during 2008-2015 in Nigeria showed that lineages Afr9 and Afr12 carrying cholera toxin and Vibrio pathogenicity island 1 can be isolated from water. Our findings raise concerns about the role of the environment in maintenance and emergence of cholera outbreaks in Nigeria.


Assuntos
Toxina da Cólera , Cólera , Ilhas Genômicas , Nigéria/epidemiologia , Toxina da Cólera/genética , Cólera/epidemiologia , Cólera/microbiologia , Humanos , Vibrio cholerae/genética , Vibrio cholerae/patogenicidade , Vibrio cholerae/classificação , Surtos de Doenças , Vibrio cholerae O1/genética , Vibrio cholerae O1/classificação , Vibrio cholerae O1/isolamento & purificação , Vibrio cholerae O1/patogenicidade , História do Século XXI , Microbiologia Ambiental
6.
Emerg Infect Dis ; 30(8): 1729-1732, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043427

RESUMO

Vibrio mimicus bacteria have caused sporadic cases and outbreaks of cholera-like diarrhea throughout the world, but the association of lineages with such events is unexplored. Genomic analyses revealed V. mimicus lineages carrying the virulence factors cholera toxin and toxin coregulated pilus, one of which has persisted for decades in China and the United States.


Assuntos
Toxina da Cólera , Ilhas Genômicas , Vibrio mimicus , China/epidemiologia , Humanos , Vibrio mimicus/genética , Vibrio mimicus/patogenicidade , Estados Unidos/epidemiologia , Toxina da Cólera/genética , Cólera/microbiologia , Cólera/epidemiologia , Filogenia , Vibrioses/microbiologia , Vibrioses/epidemiologia , Fatores de Virulência/genética
7.
Eur J Nucl Med Mol Imaging ; 51(8): 2467-2483, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38520513

RESUMO

PURPOSE: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). MATERIAL AND METHODS: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. RESULTS: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. CONCLUSION: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.


Assuntos
Lisina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico , Neoplasias da Próstata , Carga Tumoral , Ureia , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Antígeno Prostático Específico/sangue , Lisina/análogos & derivados , Ureia/análogos & derivados , Ureia/sangue , Pessoa de Meia-Idade , Recidiva , Cinética , Idoso de 80 Anos ou mais , Estudos Retrospectivos
8.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33536339

RESUMO

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Modelos Teóricos , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Feminino , Fluordesoxiglucose F18/farmacologia , Heterogeneidade Genética/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico
9.
Am J Perinatol ; 41(12): 1645-1651, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38190977

RESUMO

OBJECTIVE: It is important to determine whether the use of different quality improvement tools in neonatal resuscitation is well-received by health care teams and improves coordination and perceived quality of the stabilization of the newborn at birth. This study aimed to explore the satisfaction of personnel involved in resuscitation for infants under 32 weeks of gestational age (<32 wGA) at birth with the use of an assistance toolkit: Random Real-time Safety Audits (RRSA) of neonatal stabilization stations, the use of pre-resuscitation checklists, and the implementation of briefings and debriefings. STUDY DESIGN: A quasi-experimental, prospective, multicenter intervention study was conducted in five level III-A neonatal intensive care units in Madrid (Spain). The intervention involved conducting weekly RRSA of neonatal resuscitation stations and the systematic use of checklists, briefings, and debriefings during stabilization at birth for infants <32 wGA. The satisfaction with their use was analyzed through surveys conducted with the personnel responsible for resuscitating these newborns. These surveys were conducted both before and after the intervention phase (each lasting 1 year) and used a Likert scale response model to assess various aspects of the utility of the introduced assistance tools, team coordination, and perceived quality of the resuscitation. RESULTS: Comparison of data from 200 preintervention surveys and 155 postintervention surveys revealed statistically significant differences (p < 0.001) between the two phases. The postintervention phase scored higher in all aspects related to the effective utilization of these tools. Improvements were observed in team coordination and the perceived quality of neonatal resuscitation. These improved scores were consistent across personnel roles and years of experience. CONCLUSION: Personnel attending to infants <32 wGA in the delivery room are satisfied with the application of RRSA, checklists, briefings, and debriefings in the neonatal resuscitation and perceive a higher level of quality in the stabilization of these newborns following the introduction of these tools. KEY POINTS: · RRSA, checklists, briefings, and debriefings improve the quality of neonatal resuscitation at birth.. · These tools, when used together, are well-received and enhance perceived resuscitation quality.. · Perception of utility and quality improvement is consistent across roles and experience..


Assuntos
Atitude do Pessoal de Saúde , Lista de Checagem , Unidades de Terapia Intensiva Neonatal , Melhoria de Qualidade , Ressuscitação , Humanos , Recém-Nascido , Ressuscitação/normas , Estudos Prospectivos , Unidades de Terapia Intensiva Neonatal/normas , Espanha , Equipe de Assistência ao Paciente , Pessoal de Saúde , Feminino , Masculino
10.
Acta Chir Belg ; 124(2): 99-106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36948883

RESUMO

BACKGROUND: Post-operative hypoparathyroidism is the most frequent complication after total thyroidectomy. The identification of preoperative predictors could be helpful to identify patients at risk. This study aimed to evaluate the potential influence of preoperative PTH levels and their perioperative dynamics as a predictor of transient, protracted, and permanent post-operative hypoparathyroidism. METHODS: A prospective, observational study that includes 100 patients who underwent total thyroidectomy between September 2018 and September 2020. RESULTS: Transient hypoparathyroidism was present in 42% (42/100) of patients, 11% (11/100) developed protracted hypoparathyroidism, and 5% (5/100) permanent hypoparathyroidism. Patients who presented protracted hypoparathyroidism had higher preoperative PTH levels. The protracted and permanent hypoparathyroidism rate was higher in groups with greater preoperative PTH [0% group 1 (<40 pg/mL) vs. 5.7% group 2 (40-70 pg/mL) vs. 21.6% group 3 (>70 pg/mL); p = 0.03] and (0 vs. 8.3 vs. 20%; p = 0.442), respectively. The rate of protracted and permanent hypoparathyroidism was higher in patients with PTH at 24 h lower than 6.6 pg/mL and whose percentage of PTH decline was higher than 90%. The rate of transient hypoparathyroidism was higher in patients who showed a PTH decline rate of more than 60%. The percentage of PTH increase one week after surgery in patients with permanent hypoparathyroidism was significantly lower. CONCLUSION: The prevalence of protracted hypoparathyroidism was higher in groups with higher preoperative PTH levels. PTH levels 24 h after surgery lower than 6.6 pg/mL and a decline of more than 90% predict protracted and permanent hypoparathyroidism. The percentage of PTH increase a week after surgery could predict permanent hypoparathyroidism.


Patients who presented protracted and permanent hypoparathyroidism had higher preoperative PTH levels.Patients in groups with higher preoperative PTH levels showed higher rates of protracted and permanent hypoparathyroidism.The percentage of PTH variance one week after surgery in patients with permanent hypoparathyroidism was significantly lower and could predict permanent hypoparathyroidism.


Assuntos
Hipocalcemia , Hipoparatireoidismo , Humanos , Estudos Prospectivos , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Tireoidectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hormônio Paratireóideo , Hipocalcemia/complicações
11.
EMBO J ; 38(9)2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30886048

RESUMO

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence domain-containing transcription factor Sp1, and proteasomal degradation of misfolded Huntingtin is facilitated. Notably, all three core LUBAC components are transcriptionally regulated by Sp1, linking defective LUBAC expression to Huntington's disease. In support of a protective activity of linear ubiquitination, silencing of OTULIN, a deubiquitinase with unique specificity for linear polyubiquitin, decreases proteotoxicity, whereas silencing of HOIP has the opposite effect. These findings identify linear ubiquitination as a protein quality control mechanism and hence a novel target for disease-modifying strategies in proteinopathies.


Assuntos
Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Poliubiquitina/metabolismo , Processamento de Proteína Pós-Traducional , Fator de Transcrição Sp1/metabolismo , Proteína com Valosina/metabolismo , Adulto , Idoso , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Células Cultivadas , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/patologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Fator de Transcrição Sp1/genética , Ubiquitinação , Proteína com Valosina/genética
12.
Eur J Nucl Med Mol Imaging ; 50(11): 3439-3451, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37341747

RESUMO

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.


Assuntos
Boidae , Neoplasias da Próstata , Masculino , Animais , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Recidiva Local de Neoplasia
13.
Mem Inst Oswaldo Cruz ; 118: e230086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37971084

RESUMO

BACKGROUND: The Amazon Region hosts invaluable and unique biodiversity as well as mineral resources. Consequently, large illegal and artisanal gold mining areas exist in indigenous territories. Mercury has been used in gold mining, and some has been released into the environment and atmosphere, primarily affecting indigenous people such as the Yanomami. In addition, other heavy metals have been associated with gold mining and other metal-dispersing activities in the region. OBJECTIVE: Investigate the gut microbiome of two semi-isolated groups from the Amazon, focusing on metal resistance. METHODS: Metagenomic data from the Yanomami and Tunapuco gut microbiome were assembled into contigs, and their putative proteins were searched against a database of metal resistance proteins. FINDINGS: Proteins associated with mercury resistance were exclusive in the Yanomami, while proteins associated with silver resistance were exclusive in the Tunapuco. Both groups share 77 non-redundant metal resistance (MR) proteins, mostly associated with multi-MR and operons with potential resistance to arsenic, nickel, zinc, copper, copper/silver, and cobalt/nickel. Although both groups harbour operons related to copper resistance, only the Tunapuco group had the pco operon. CONCLUSION: The Yanomami and Tunapuco gut microbiome shows that these people have been exposed directly or indirectly to distinct scenarios concerning heavy metals.


Assuntos
Mercúrio , Metais Pesados , Microbiota , Humanos , Cobre , Níquel , Prata , Ouro , Microbiota/genética
14.
Mem Inst Oswaldo Cruz ; 118: e230081, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37909500

RESUMO

BACKGROUND: Pandrug-resistant (PDR) Klebsiella pneumoniae has been reported sporadically in many countries and remains rare in Brazil. OBJECTIVES: This study unravelled the genetic determinants involved with the PDR background of a clinical ST11 K. pneumoniae recovered in the Brazilian Amazon Region, where K. pneumoniae genomic and epidemiological information is scarce. METHODS: Kp196 was submitted to the antimicrobial susceptibility test by the disk-diffusion method and minimum inhibitory concentration (MIC) determination. The whole genome sequencing was obtained and the sequence type was determined by core genome multilocus sequence typing (cgMLST). Its intrinsic and acquired resistome was assessed by Comprehensive Antibiotic Resistance Database (CARD) and comparison with wild-type genes. FINDINGS: The analyses revealed that Kp196 belonged to the pandemic ST11 and presented the PDR phenotype. Its acquired resistome was composed of a huge set of clinically relevant resistance determinants, including bla CTX-M-15 and bla NDM-1, all found in the vicinity of mobile platforms. Considering its intrinsic resistome, the multidrug resistance, especially to colistin, tigecycline and fluoroquinolones, was multifactorial and attributed to modifications (indels, missense mutations, and gene disruption) in several housekeeping genes (arnT/phoQ/mgrB/ramR/acrB/gyrA/parC/ompK35-36-37). The Kp196 intrinsic resistome was also observed in a ST11 environmental strain, although harbouring distinct acquired resistomes. CONCLUSIONS: An accumulation of different resistance mechanisms regarding the intrinsic resistome accounts for a more stable resistome, strongly contributing to the Kp196 PDR phenotype.


Assuntos
Antibacterianos , Infecções por Klebsiella , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Klebsiella pneumoniae/genética , Brasil , beta-Lactamases/genética , Tipagem de Sequências Multilocus , Testes de Sensibilidade Microbiana
15.
Mem Inst Oswaldo Cruz ; 118: e230088, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37971095

RESUMO

BACKGROUND: The parasite Giardia duodenalis infects a wide range of vertebrate hosts, including domestic and wild animals as well as humans. Giardia is genotyped into eight assemblages (A-H). Zoonotic assemblages A and B have already been identified in humans and wild and domestic animals (non-human primates and cats) from Brazilian Amazon and in the world. Due to its zoonotic/zooanthroponotic nature, surveillance initiatives and the definition of Giardia assemblages are important in order to characterise the epidemiological scenario and to implement further control measures. OBJECTIVES: Determine assemblages of G. duodenalis in sloths from the Brazilian Amazon Region. METHODS: Faecal parasitological examination of sloths from Amazonas State. Polymerase chain reaction (PCR) targeting the beta giardin (BG), and genes from multilocus sequence typing (MLST) scheme, amplicon sequencing and phylogenetic analysis. FINDINGS: Here, we identified, by microscopy, Giardia in two northern sloths (Bradypus tridactylus). These two samples were submitted to molecular assays and it was revealed that both were infected by G. duodenalis assemblage A. Phylogenetic analysis showed that they belong to assemblage A within sequences from humans and wild and domestic animals. CONCLUSION: Therefore, besides showing, by the first time, the current presence of this parasite in sloths, our findings reveals that this wild animal species would be part of the zoonotic/zooanthroponotic scenario of this parasite in the Brazilian Amazon.


Assuntos
Giardia lamblia , Giardíase , Bichos-Preguiça , Animais , Humanos , Gatos , Giardia lamblia/genética , Bichos-Preguiça/genética , Tipagem de Sequências Multilocus , Filogenia , Brasil/epidemiologia , Fezes/parasitologia , Giardíase/epidemiologia , Giardíase/veterinária , Giardíase/diagnóstico , Zoonoses , Giardia/genética , Genótipo , Animais Domésticos , Animais Selvagens , Prevalência
16.
Arch Gynecol Obstet ; 308(6): 1817-1822, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37737882

RESUMO

PURPOSE: To evaluate the agreement rate between hysteroscopy and pathological examination in case of chronic endometritis. METHODS: A retrospective observational study carried out at Gynecology and Obstetrics Department, Puerta de Hierro Hospital, Autónoma University of Madrid, Spain, from January 2021 to June 2022 was performed by obtaining data from 115 medical records of women who underwent office hysteroscopies that was compared with the findings of final histological examination of endometrial biopsy. Cohen's kappa index was used to evaluate this agreement rate. In addition, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were obtained. RESULTS: The agreement between hysteroscopic findings and histological examination showed a modest result with a Cohen's kappa index of 34%. In addition, we obtained a specificity of 70% and a sensitivity of 64%. The positive and negative predictive value were 60.8% and 73.4%, respectively. An excellent agreement rate (100%) between histological and hysteroscopic results was observed in presence of hyperemia and micropolyps. CONCLUSION: Although the sample size is not as large as that of other studies published so far, the first glance of our experience is that hysteroscopic signs are not yet sufficient to make an accurate diagnosis of chronic endometritis, thus requiring a histopathological confirmation to make it.


Assuntos
Endometrite , Gravidez , Feminino , Humanos , Endometrite/diagnóstico , Endometrite/patologia , Sensibilidade e Especificidade , Endométrio/patologia , Histeroscopia/métodos , Estudos Retrospectivos , Doença Crônica
17.
Int J Mol Sci ; 24(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36901871

RESUMO

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.


Assuntos
Variações do Número de Cópias de DNA , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Mutação INDEL , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Polimorfismo de Nucleotídeo Único
18.
Trop Anim Health Prod ; 55(4): 257, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37395953

RESUMO

The objectives of this experiment were to evaluate the effects of increasing levels of orange molasses in replacement of flint corn grain in high-concentrate diets on dry matter intake (DMI), average daily gain (ADG), and feed efficiency (FE) of feedlot lambs. Thirty male lambs without defined racial pattern (30.3 ± 5.3 kg of initial BW; mean ± SD) were used in a randomized complete block design with 10 blocks and 3 treatments. The treatments were defined by partial replacement of flint corn by orange molasses in the diet with 90% of concentrate and 10% of Cynodon spp. hay, as follows: 0OM-control diet without orange molasses; 20OM-20% of orange molasses replacing flint corn; and 40OM-40% of orange molasses replacing flint corn (DM basis). The experiment lasted 72 days divided into 3 subperiods, with 1 subperiod of 16 days and 2 subperiods of 28 days. Animals were weighed after a 16-h fast on days 1, 16, 44, and 72 of the experimental periods to determine the ADG and FE. The DMI, ADG, and FE showed an interaction between treatments and experimental periods. The DMI in the first period decreased linearly (P < 0.01); in the third period, there was no effect of treatments (P > 0.05) on DMI. The ADG decreased linearly (P < 0.01) in the first period as the orange molasses increased. Otherwise, in the third period, ADG increased linearly (P = 0.05) as flint corn was replacement by orange molasses. The FE showed an interaction between treatment and period (P = 0.09). The first period had a decreased linear effect; in the third period, there was a trend (P = 0.07) of increased linear effect. There was no difference between the diets regarding the final BW of the lambs. In conclusion, the orange molasses can replace up to 40% of flint corn in diets for feedlot lambs without affecting final BW. However, it is important to consider the adaptation time proved to be very important for better use of orange molasses as a source of energy in diets for lambs.


Assuntos
Citrus sinensis , Ovinos , Animais , Masculino , Brasil , Melaço , Dieta/veterinária , Zea mays , Minerais , Carneiro Doméstico , Ração Animal/análise
19.
Trop Anim Health Prod ; 55(2): 105, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36859568

RESUMO

Diets without forage increase the productivity in less time and favor greater practicality and better quality carcass. The corn grain is mostly used associated with pellets but processing these ingredients can bring benefits. The present study evaluated the effect of diets without forage based on whole or coarse ground corn associated with pelleted or ground protein supplement on performance, eating behavior, carcass characteristics, and ruminal morphology of feedlot lambs. Thirty-five Dorper × Santa Inês lambs were used, with 23.85 ± 3.88 kg of initial body weight and 88 ± 9 days old. The experimental design was in a randomized complete block, defined by body weight and age. The experimental diets were control (CONT), containing 90% of concentrate and 10% of forage (coastcross hay), and 4 diets without forage: WC+P, 70% whole flint corn and 30% pelleted protein supplement; WC+G, 70% whole flint corn and 30% ground protein supplement; GC+P, 70% ground flint corn and 30% pelleted protein supplement; and GC+G, 70% ground flint corn and 30% ground protein supplement. There was an interaction between treatments and experimental periods for DMI in kg/day (P = 0.01) and g/kg of BW0.75 (P < 0.01; Table 3). For the DMI in kg/day, no significant differences were observed between the treatments in any of the experimental periods. However, for DMI expressed in g/kg of BW0.75, the animals fed WC+P had lower DMI than the animals on the CONT (P < 0.01) only in the first period. The ADG, FBW, and FE were not affected by the treatments. Compared to CONT, forage-free diets decreased ingestion time (min/day) and rumination and chewing (min/day and min/g of dry matter). There was no effect of treatments for any of the carcass traits evaluated. The diets did not cause lesions suggestive of ruminitis. Forage-free diets containing whole or ground corn associated with pelleted or ground protein supplement can be used successfully for feedlot lambs; they provide proper performance and carcass characteristics, without harming the animal's health.


Assuntos
Dieta , Zea mays , Animais , Ovinos , Peso Corporal , Minerais , Fenótipo
20.
J Environ Sci (China) ; 124: 860-874, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182189

RESUMO

Particulate matter (PM2.5) samples were collected in the vicinity of an industrial chemical pole and analysed for organic and elemental carbon (OC and EC), 47 trace elements and around 150 organic constituents. On average, OC and EC accounted for 25.2% and 11.4% of the PM2.5 mass, respectively. Organic compounds comprised polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, anhydrosugars, phenolics, aromatic ketones, glycerol derivatives, aliphatic alcohols, sterols, and carboxyl groups, including aromatic, carboxylic and dicarboxylic acids. Enrichment factors > 100 were obtained for Pb, Cd, Zn, Cu, Sn, B, Se, Bi, Sb and Mo, showing the contribution of industrial emissions and nearby major roads. Principal component analysis revealed that vehicle, industrial and biomass burning emissions accounted for 66%, 11% and 9%, respectively, of the total PM2.5-bound PAHs. Some of the detected organic constituents are likely associated with plasticiser ingredients and thermal stabilisers used in the manufacture of PVC and other plastics in the industrial complex. Photooxidation products of both anthropogenic (e.g., toluene) and biogenic (e.g., isoprene and pinenes) precursors were also observed. It was estimated that biomass burning accounted for 13.8% of the PM2.5 concentrations and that secondary OC represented 37.6% of the total OC. The lifetime cancer risk from inhalation exposure to PM2.5-bound PAHs was found to be negligible, but it exceeded the threshold of 10-6 for metal(loi)s, mainly due to Cr and As.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Oligoelementos , Poluentes Atmosféricos/análise , Álcoois , Cádmio/análise , Carbono/análise , Ácidos Dicarboxílicos/análise , Monitoramento Ambiental , Cetonas , Chumbo/análise , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Cloreto de Polivinila/análise , Estações do Ano , Esteróis/análise , Tolueno/análise , Oligoelementos/análise , Emissões de Veículos/análise
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