ABSTRACT
Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.
Subject(s)
Disease Outbreaks , Humans , Brazil/epidemiology , Male , Female , Adult , Young Adult , Adolescent , Middle Aged , Animals , Zoonoses/epidemiology , Zoonoses/virology , Herpesvirus 3, Human/genetics , Herpesvirus 3, Human/isolation & purification , Child , HIV Infections/epidemiology , HIV Infections/virology , Antibodies, Viral/blood , Aged , Immunoglobulin G/bloodABSTRACT
The Lambda variants of interest (VOI) (C37/GR/452Q.V1/21G) was initially reported in Lima, Peru but has gained rapid dissemination through other Latin American countries. Nevertheless, the dissemination and molecular epidemiology of the Lambda VOI in Brazil is unknown apart from a single case report. In this respect, we characterized the circulation of the SARS-CoV-2 Lambda VOI (C37/GR/452Q.V1/21G) in Sao Paulo State, Brazil. From March to June 2021, we identified seven Lambda isolates in a set of approximately 8000 newly sequenced genomes of the Network for Pandemic Alert of Emerging SARS-CoV-2 variants from Sao Paulo State. Interestingly, in three of the positive patients, the Lambda VOI infection was probably related to a contact transmission. These individuals were fully vaccinated to COVID-19 and presented mild symptoms. The remaining positive for Lambda VOI individuals showed different levels of COVID-19 symptoms and one of them needed hospitalization (score 5, WHO). In our study, we present a low level of Lambda VOI circulation in the Sao Paulo State. This reinforces the essential role of molecular surveillance for the effective SARS-CoV-2 pandemic response, especially in regard to circulating variants.
Subject(s)
COVID-19 , SARS-CoV-2 , Brazil/epidemiology , COVID-19/epidemiology , Humans , SARS-CoV-2/genetics , World Health OrganizationABSTRACT
Sao Paulo State, currently experiences a second COVID-19 wave overwhelming the healthcare system. Due to the paucity of SARS-CoV-2 complete genome sequencing, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand and monitor the spread of SARS-CoV-2 variants into the state. Through analysis of 210 SARS-CoV-2 complete genomes obtained from the largest regional health departments we identified cocirculation of multiple SARS-CoV-2 lineages such as B.1.1 (0.5%), B.1.1.28 (23.2%), B.1.1.7 (alpha variant, 6.2%), B.1.566 (1.4%), B.1.544 (0.5%), C.37 (0.5%) P.1 (gamma variant, 66.2%), and P.2 (zeta variant, 1.0%). Our analysis allowed also the detection, for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5%), characterized by the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. The most recent common ancestor of the identified strain was inferred to be mid-October to late December 2020. Our analysis demonstrated the P.1 lineage predominance and allowed the early detection of the South African strain for the first time in Brazil. We highlight the importance of SARS-CoV-2 active monitoring to ensure the rapid detection of potential variants for pandemic control and vaccination strategies. Highlights Identification of B.1.351 (beta) variant of concern in the Sao Paulo State. Dissemination of SARS-CoV-2 variants of concern and interest in the Sao Paulo State. Mutational Profile of the circulating variants of concern and interest.
Subject(s)
SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Brazil , COVID-19/immunology , COVID-19/virology , Genomics/methods , Humans , Mutation/genetics , Mutation/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
BACKGROUND: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. METHODS: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction (<7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. RESULTS: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. CONCLUSIONS: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.
ABSTRACT
Background: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Methods: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction (<7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. Results: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. Conclusions: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.(AU)
Subject(s)
Animals , Oligopeptides , Peptides/isolation & purification , Biochemistry/classification , Bradykinin , Viperidae , BothropsABSTRACT
Abstract Background: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Methods: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction ( 7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. Results: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. Conclusions: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.
ABSTRACT
Background: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Methods: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction (<7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. Results: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. Conclusions: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.(AU)
Subject(s)
Animals , Oligopeptides , Peptides/isolation & purification , Biochemistry/classification , Bradykinin , Viperidae , BothropsABSTRACT
The Ciidae of New Brunswick, Canada are reviewed. Seventeen species are recorded for New Brunswick, including the following 10 species that are newly recorded for the province: Ceracis singularis (Dury), Ceracis thoracicornis (Ziegler), Cis angustus Hatch, Cis fuscipes Mellié, Cis horridulus Casey, Cis striatulus Mellié, Dolichocis laricinus (Mellié), Malacocis brevicollis (Casey), Orthocis punctatus (Mellié), and Plesiocis cribrum Casey. Additional locality data are provided for the following species previously known from the province: Cis americanus Mannerheim, Cis creberrimus Mellié, Cis levettei (Casey), Cis submicans Abeille de Perrin, Dolichocis manitoba Dury, Hadreule elongatula (Gyllenhal), and Octotemnus glabriculus (Gyllenhal). Seven synonyms are proposed here; Cis pistoria Casey with Cis submicans Abeille de Perrin; Cis fraternus Casey, Cis macilentus Casey and Cis striolatus Casey with Cis striatulus Mellié; Dolichocis indistinctus Hatch with Dolichocis laricinus (Mellié); and Octotemnus denudatus Casey and Octotemnus laevis Casey with Octotemnus glabriculus (Gyllenhal). Lindgren funnel traps provided the majority of specimens for 15 of the 17 species reported from New Brunswick and were the sole source of specimens for seven of the 10 species newly reported here, suggesting they are a very useful tool for sampling Ciidae in the forests of New Brunswick.
ABSTRACT
Considerable effort has been expended in order to understand the mechanism of manganese catalases and to develop functional mimics for these enzymes. For many years, the most efficient reactivity mimic was [MnIVsalpn(mu-O)]2 [H2salpn = 1,3-bis(salicylideneiminato)propane], a compound that cycles between the MnIV2 and MnIII2 oxidation levels instead of the MnII2 and MnIII2 oxidation states used by the enzyme, with kcat = 250 s(-1) and kcat/KM = 1000 M(-1) s(-1). Recently, a truly exceptional high value of kcat was reported for the complex [Mn(bpia)(mu-OAc)]22+ [bpia = bis(picolyl)(N-methylimidazol-2-yl)amine]. On the basis of a calculated kcat value of 1100 s(-1) and an efficiency kcat/KM of 34 000 M(-1) s(-1), this complex has been suggested to represent a significant breakthrough in catalytic efficiencies of manganese catalase mimics. However, a plot of ri/[cat]T vs [H2O2]0, where the saturation value approaches 1.5 s(-1), is inconsistent with the 1100 s(-1) value tabulated for kcat. Similar discrepancies are observed for two other families of manganese complexes containing either a Mn2(mu-OPh)22+ core and different substituted tripodal ligands or complexes of methyl and ethyl salicylimidate, with an Mn2(mu-OPh)24+ core. Reevaluation of the kinetic parameters for these three systems reveals that the originally reported values were overestimated by a factor of approximately 1000 for both kcat and kcat/KM. We discuss the origin of the discrepancy between the previously published kinetic parameters and the newly derived values. Furthermore, we provide a short analysis of the existing manganese catalase mimics in an effort to provide sound directions for future investigations in this field.
Subject(s)
Biomimetic Materials/chemistry , Biomimetic Materials/metabolism , Catalase/metabolism , KineticsABSTRACT
Despite repeated campaigns promoting transplantation, the high donation refusal rate remains unchanged. We targeted a well-educated population to assess the impact of our current transplantation promoting programs and personal feelings toward new approaches to organ donation. A questionnaire was proposed in five universities to students and university staffs that would have been likely to benefit from previous information campaigns in two South American and three European countries. All of the 2321 people interviewed replied to at least one question. Organ shortage was considered as a serious public health issue. However, there was a widespread ignorance of religious precepts concerning transplantation that contributed to the low acceptance rate of organ sharing after death. Financial rewards for donors or their families remain controversial. There was a general agreement for early educational programs in schools. Most people still consider organ donation as a gift, but many would now agree to readily share body parts after death. This biased population of well-educated people has still little knowledge of organ donation. The negative impact of ignorance surrounding religious precepts and the high acceptance rate of educational programs in schools, justify supporting an intensive international effort in education that should also include Church leaders.
Subject(s)
Public Opinion , Tissue and Organ Procurement/ethics , Transplantation/psychology , Awareness , Education , Educational Status , Emotions , Europe , Female , Humans , Male , Religion , South America , Surveys and Questionnaires , Transplantation/educationABSTRACT
Our aim was to study the level of interobserver concordance in the Gleason scores of prostate needle biopsy specimens reported at 1 institution. A retrospective review of all prostate needle biopsy specimens in which a diagnosis of adenocarcinoma was made during the year 2000 was conducted. Parameters evaluated included the Gleason score, Gleason grades identified, the percentage of Gleason grades 4 and 5, and the percentage of tumor in the biopsy specimen. Our results demonstrated a 60% overall concordance in consensus Gleason scores, which increased to 80% when considered in groups of a Gleason score of less than 7 vs 7 or more. The greatest discordance seemed to be in distinguishing Gleason score 6 from 7 and was more frequent among biopsy specimens with lower tumor volumes, particularly among those with less than 30% involvement. A small percentage of Gleason grade 4 pattern might predict disagreement as well. Strategies for improving accuracy of Gleason score 7 should be devised, and consensus diagnosis for biopsy specimens that demonstrate a low percentage of tumor volume is recommended.
Subject(s)
Adenocarcinoma/pathology , Prostatic Neoplasms/pathology , Biopsy, Needle , Humans , Male , Observer Variation , Pathology, Clinical/standards , Prospective Studies , Reproducibility of Results , West IndiesABSTRACT
OBJECTIVE: To study absolute and interpeak latencies of the auditory brain response in infants exposed to cocaine and/or opiates in utero.Study design The sample included 477 exposed and 554 comparison infants matched for race, sex, and gestational age. Mothers were recruited at 4 urban university-based centers; most were black, receiving public assistance, and had received adequate prenatal care. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At 1 month, infants were tested by masked examiners with the auditory brain response. RESULTS: Analyses were conducted for exposed and comparison groups and for level of prenatal cocaine exposure with adjustment for covariates (alcohol, marijuana, tobacco, gestational age at birth, social class, and site). Heavy prenatal cocaine exposure (>/=3 days per week, first trimester) led to an increase in the I-III, I-V, and III-V interpeak latencies and to a shorter latency to peak I. Infants with prenatal opiate exposure showed a longer latency to peak V and a longer III-V interpeak latency. CONCLUSIONS: Prenatal cocaine and/or opiate exposure affects neural transmission. Detection of these effects requires a large sample with control for gestational age, other drugs, and level of cocaine use.