Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North ...American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several X-linked genes are involved in neuronal differentiation and may contribute to the generation of sex dimorphisms in the brain. Previous results showed that XX hypothalamic neurons grow faster, ...have longer axons, and exhibit higher expression of the neuritogenic gene
neurogenin 3
(
Ngn3
) than XY before perinatal masculinization. Here we evaluated the participation of candidate X-linked genes in the development of these sex differences, focusing mainly on
Kdm6a
, a gene encoding for an H3K27 demethylase with functions controlling gene expression genome-wide. We established hypothalamic neuronal cultures from wild-type or transgenic Four Core Genotypes mice, a model that allows evaluating the effect of sex chromosomes independently of gonadal type. X-linked genes
Kdm6a
,
Eif2s3x
and
Ddx3x
showed higher expression in XX compared to XY neurons, regardless of gonadal sex. Moreover,
Kdm6a
expression pattern with higher mRNA levels in XX than XY did not change with age at E14, P0, and P60 in hypothalamus or under 17β-estradiol treatment in culture. Kdm6a pharmacological blockade by GSK-J4 reduced axonal length only in female neurons and decreased the expression of neuritogenic genes
Neurod1
,
Neurod2
and
Cdk5r1
in both sexes equally, while a sex-specific effect was observed in
Ngn3
. Finally,
Kdm6a
downregulation using siRNA reduced axonal length and
Ngn3
expression only in female neurons, abolishing the sex differences observed in control conditions. Altogether, these results point to
Kdm6a
as a key mediator of the higher axogenesis and
Ngn3
expression observed in XX neurons before the critical period of brain masculinization.
The B.1.1.529 (Omicron) variant, first detected in November 2021, was responsible for a surge in U.S. infections with SARS-CoV-2, the virus that causes COVID-19, during December 2021-January 2022 ...(1). To investigate the effectiveness of prevention strategies in household settings, CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021-February 2022. Persons with sequence-confirmed Omicron infection and their household contacts were interviewed. Omicron transmission occurred in 124 (67.8%) of 183 households. Among 431 household contacts, 227 were classified as having a case of COVID-19 (attack rate AR = 52.7%).
The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively. The AR was lower among household contacts of index patients who isolated (41.2%, 99 of 240) compared with those of index patients who did not isolate (67.5%, 112 of 166) (p-value <0.01). Similarly, the AR was lower among household contacts of index patients who ever wore a mask at home during their potentially infectious period (39.5%, 88 of 223) compared with those of index patients who never wore a mask at home (68.9%, 124 of 180) (p-value <0.01). Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in household settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Pacemakers and defibrillators were explanted post mortem in Canada, tested and resterilized, and implanted in patients in underserved countries. The incidence of infection at 2 years among patients ...with reused devices was not significantly different from that among matched control patients who received new devices.
Objective
Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The ...objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.
Methods
We performed a comprehensive characterisation of longitudinal antiviral B‐cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.
Results
We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.
Conclusion
Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus‐infected individuals have significantly elevated levels of extracellular ATP in circulation.
We show a comprehensive study to correlate two pathologies associated with haemorrhagic fever with renal syndrome (HFRS), thrombocytopenia and kidney dysfunction, with changes in the circulating B‐cell compartment (cells and antibodies). We show that thrombocytopenia is associated with mobilization of both activated and resting plasmablasts and plasma cells in circulation. However, the level of kidney dysfunction associated with longitudinal development of neutralizing antibodies in patients and associated with the reduction of surface CD27 expression on both plasmablasts and B cells in circulation. The low CD27 expression might be explained by elevated levels of ATP that could contribute to shedding of CD27 from B cells by a MMP‐8‐dependent mechanism.
Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements ...(ALKr) in Latin America.
A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed.
Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%).
Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.
Here we present an occurrence dataset that contributes to the knowledge of tropical fish distribution in coastal habitats from the Terminos Lagoon Flora and Fauna Protection Area, one of the largest ...lagoon ecosystems in the Gulf of Mexico. Fish are high biomass keystone species in the Terminos Lagoon which provide socio-economic and ecosystem services. An initiative in 1980 was carried out to systematically sample the fish community of Terminos Lagoon for an annual cycle; the effectiveness of its results led to replicate in the lagoon the same sampling design for three more campaigns in 1998, 2010 and 2016. Constituted as a Flora and Fauna Protection Area in 1994, the Terminos Lagoon has received many efforts to inventory its biodiversity, particularly on the fish community since the 70s; however, these studies did not have consistent survey protocols, nor the longevity of the present study, which was over four decades.
A total of 141 fish species, belonging to 90 genera, 49 families, 20 orders and two classes are presented in this study. Information on fish species occurrence data is provided corresponding to the Terminos Lagoon coastal ecosystem, southern Gulf of Mexico, assembled from four time periods at 1980, 1998, 2010 and 2016. The records form part of a consistently homogeneous database compilation, mostly derived from the research programme's sampled material on tropical fishery resources of the "Instituto de Ecologia, Pesquerias y Oceanografia del Golfo de Mexico (EPOMEX)". The current dataset represents the first and most comprehensive online open-access source of information concerning the fish community occurring along and wide of the Terminos Lagoon ecosystem, with 1,249 data records and a total count of 48,717 organisms. Data are available through the Ocean Biodiversity Information System (OBIS).
The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control ...of disease activity.
Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared.
A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant NS). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 0.62-8.75 vs 2.5 0-5 at baseline).
Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.
We describe trends in high-grade cervical lesions (CIN2+), identified through population-based surveillance in 2008–2015. In addition to changed screening recommendations, observed CIN2+ declines ...among screened women aged 18–24 years indicate a population-level impact of human papillomavirus vaccination.
Abstract
Background
We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations.
Methods
We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008–2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time.
Results
A total of 16572 CIN2+ cases were reported. Among women aged 18–20 and 21–24 years, CIN2+ rates declined in all sites, whereas in women aged 25–29, 30–34, and 35–39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008–2009, rates among screened women were significantly lower for all 3 periods in women aged 18–20 years (2010–2011: IRR 0.82, 95% confidence interval CI 0.67–0.99; 2012–2013: IRR 0.63, 95% CI 0.47–0.85; 2014–2015: IRR 0.44, 95% CI 0.28–0.68) and lower for the latter 2 time periods in women aged 21–24 years (2012–2013: IRR 0.86, 95% CI 0.79–0.94; 2014–2015: IRR 0.61, 95% CI 0.55–0.67).
Conclusions
From 2008–2015, both CIN2+ rates and cervical cancer screening declined in women aged 18–24 years. The significant decreases in CIN2+ rates among screened women aged 18–24 years are consistent with a population-level impact of HPV vaccination.
Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination ...strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.
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First dose of Sputnik V results in 94% seroconversion rate in naive individualsA second dose greatly increases antibody titers and neutralizing capacityOne dose in seropositive individuals elicits higher titers than two doses in naiveThere is no evident benefit of using a second dose in previously infected individuals
Rossi et al. provide data on antibody responses to Sputnik V vaccine in naive and previously infected volunteers. This study shows a high seroconversion rate following the first dose in naive individuals. In seropositive participants, a single dose of Sputnik V elicits a fast and robust antibody response without apparent benefit from a second dose.
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