Tuberculosis is an infectious disease with a major global impact, ranked in the top 10 mortality causes worldwide. In an immunocompetent individual, the host defence mechanisms control Mycobacterium ...tuberculosis infection and induce the latent form of the disease. However, in the presence of diseases or therapies, which exert an immunosuppressive effect, latent tuberculosis can be re‐activated. Psoriasis is an immune‐mediated, inflammatory disease, and its treatment has rapidly evolved over the last few years. It has long been recognized that the tumour necrosis factor (TNF)‐α inhibitors are associated with increased risk of reactivation of latent tuberculosis infection. Thus, international guidelines have been suggesting tuberculosis screening before starting the treatment with all biological agents since then. In addition, the institution of chemoprophylaxis in the presence of latent tuberculosis and the annual screening for tuberculosis thereafter have also been indicated. However, anti‐tuberculosis treatments can have significant side‐effects and there are currently several contraindications to their use. The risk benefit of starting anti‐tuberculous treatment should be carefully weighed up. The emergence of new biological drugs for the treatment of psoriasis, such as interleukin (IL)‐17 and IL‐23 inhibitors, has reignited the subject of tuberculosis reactivation as it is possible that IL‐17 and 23 blockade do not carry the same risk of TB reactivation as TNF‐α inhibitors. Although preclinical studies have shown that cytokines IL‐17 and IL‐23 have a possible role against infection with M. tuberculosis, data from clinical trials and post‐marketing surveillance with drugs that inhibit these cytokines appear to suggest that they are not crucial to this response. In this article, we review the available data on tuberculosis reactivation after the treatment of psoriasis with IL‐17 and IL‐23 inhibitors, and its possible impact on the way we currently manage latent tuberculosis infection before or after starting treatment with these new drugs.
Summary Background The incidence of microcephaly in Brazil in 2015 was 20 times higher than in previous years. Congenital microcephaly is associated with genetic factors and several causative agents. ...Epidemiological data suggest that microcephaly cases in Brazil might be associated with the introduction of Zika virus. We aimed to detect and sequence the Zika virus genome in amniotic fluid samples of two pregnant women in Brazil whose fetuses were diagnosed with microcephaly. Methods In this case study, amniotic fluid samples from two pregnant women from the state of Paraíba in Brazil whose fetuses had been diagnosed with microcephaly were obtained, on the recommendation of the Brazilian health authorities, by ultrasound-guided transabdominal amniocentesis at 28 weeks' gestation. The women had presented at 18 weeks' and 10 weeks' gestation, respectively, with clinical manifestations that could have been symptoms of Zika virus infection, including fever, myalgia, and rash. After the amniotic fluid samples were centrifuged, DNA and RNA were extracted from the purified virus particles before the viral genome was identified by quantitative reverse transcription PCR and viral metagenomic next-generation sequencing. Phylogenetic reconstruction and investigation of recombination events were done by comparing the Brazilian Zika virus genome with sequences from other Zika strains and from flaviviruses that occur in similar regions in Brazil. Findings We detected the Zika virus genome in the amniotic fluid of both pregnant women. The virus was not detected in their urine or serum. Tests for dengue virus, chikungunya virus, Toxoplasma gondii , rubella virus, cytomegalovirus, herpes simplex virus, HIV, Treponema pallidum , and parvovirus B19 were all negative. After sequencing of the complete genome of the Brazilian Zika virus isolated from patient 1, phylogenetic analyses showed that the virus shares 97–100% of its genomic identity with lineages isolated during an outbreak in French Polynesia in 2013, and that in both envelope and NS5 genomic regions, it clustered with sequences from North and South America, southeast Asia, and the Pacific. After assessing the possibility of recombination events between the Zika virus and other flaviviruses, we ruled out the hypothesis that the Brazilian Zika virus genome is a recombinant strain with other mosquito-borne flaviviruses. Interpretation These findings strengthen the putative association between Zika virus and cases of microcephaly in neonates in Brazil. Moreover, our results suggest that the virus can cross the placental barrier. As a result, Zika virus should be considered as a potential infectious agent for human fetuses. Pathogenesis studies that confirm the tropism of Zika virus for neuronal cells are warranted. Funding Consellho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ).
Terrestrial carbon stock mapping is important for the successful implementation of climate change mitigation policies. Its accuracy depends on the availability of reliable allometric models to infer ...oven‐dry aboveground biomass of trees from census data. The degree of uncertainty associated with previously published pantropical aboveground biomass allometries is large. We analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types (4004 trees ≥ 5 cm trunk diameter). When trunk diameter, total tree height, and wood specific gravity were included in the aboveground biomass model as covariates, a single model was found to hold across tropical vegetation types, with no detectable effect of region or environmental factors. The mean percent bias and variance of this model was only slightly higher than that of locally fitted models. Wood specific gravity was an important predictor of aboveground biomass, especially when including a much broader range of vegetation types than previous studies. The generic tree diameter–height relationship depended linearly on a bioclimatic stress variable E, which compounds indices of temperature variability, precipitation variability, and drought intensity. For cases in which total tree height is unavailable for aboveground biomass estimation, a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height. However, to minimize bias, the development of locally derived diameter–height relationships is advised whenever possible. Both new allometric models should contribute to improve the accuracy of biomass assessment protocols in tropical vegetation types, and to advancing our understanding of architectural and evolutionary constraints on woody plant development.
Purpose
This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might ...determine their efficiency of intracellular drug delivery.
Methods
Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy.
Results
The fucoidan-coated PIBCA nanoparticles A
25
were internalized 3-fold more efficiently than R
25
due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A
100
nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A
0
, and 3-fold compared with R
0
and R
25
through non-endocytic energy-independent pathways and reached the cell cytoplasm.
Conclusion
Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.
Graphical abstract
The removal of a widespread used drug (i.e., ibuprofen) from water was investigated using high valuable carbon adsorbents obtained from chemical and physical activation of a bioresource (cork) and a ...municipal waste (plastic). The waste-derived carbons outperformed the adsorption capacity of commercial carbonaceous adsorbents due to their adequate features for the removal of the targeted compound. Regarding the adsorption mechanism, the results obtained point out that ibuprofen retention is favored in activated carbons with basic surface properties. On the other hand, the textural features also play an important role; the presence of a transport pores network (i.e., mesopores) is crucial to ensure the accessibility to the inner porosity, and the microporosity must be large enough to accommodate the ibuprofen molecule. Specifically, adsorbents with a large fraction of ultramicropores (pore widths <0.7
nm) are not adequate to effectively remove ibuprofen.
Objective
Tea tree oil (TTO) is an essential oil with anti-inflammatory properties, steam distilled from the plant
Melaleuca alternifolia
. We investigated the immunomodulatory properties of TTO and ...its components (terpinen-4-ol and alpha-terpineol) using lipopolysaccharide (LPS)-stimulated macrophages.
Methods
The ability of TTO, terpinen-4-ol and alpha-terpineol to modulate the macrophage response to bacterial LPS stimulation was assessed by ELISA for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 cytokine production and by western blotting for the activation of nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling, which are associated with the expression of pro-inflammatory cytokines. We used a human monocytic cell line (U937) differentiated into macrophages.
Results
LPS induced the production of all cytokines, and TTO and its components significantly reduced the production of IL-1β, IL-6 and IL-10. The production of TNF-α was not affected by either TTO or its major components. The modulation of cytokine production was not mediated by changes in NF-κB or p38 MAPK activation.
Conclusion
TTO, terpinen-4-ol and alpha-terpineol can suppress the production of inflammatory mediators in LPS-stimulated human macrophages; this inhibition was mediated by interfering with the NF-kB, p38 or ERK MAPK pathways.
IMPORTANCE: Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, ...most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. OBJECTIVE: To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. DESIGN, SETTING, AND PARTICIPANTS: We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. MAIN OUTCOMES AND MEASURES: Description of the major lesions caused by ZIKV congenital infection. RESULTS: Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. CONCLUSIONS AND RELEVANCE: Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.
Green coffee bean isotopes have been used to trace the effects of different climatic and geological characteristics associated with the Hawaii islands. Isotope ratio mass spectrometry (IRMS) and ...inductively coupled plasma mass spectrometry ((MC)-ICP-SFMS and ICP-QMS) were applied to determine the isotopic composition of carbon (δ13C), nitrogen (δ15N), sulfur (δ34S), and oxygen (δ18O), the isotope abundance of strontium (87Sr/86Sr), and the concentrations of 30 different elements in 47 green coffees. The coffees were produced in five Hawaii regions: Hawaii, Kauai, Maui, Molokai, and Oahu. Results indicate that coffee plant seed isotopes reflect interactions between the coffee plant and the local environment. Accordingly, the obtained analytical fingerprinting could be used to discriminate between the different Hawaii regions studied.
Purpose
This study evaluated the reliability of cancer cases reported to the National Cancer Database (NCDB) during 2020, the first year of the COVID-19 pandemic.
Methods
Total number of cancer cases ...reported to the NCDB between January 2018 and December 2020 were calculated for all cancers and 21 selected cancer sites. The additive outlier method was used to identify structural breaks in trends compared with previous years. The difference between expected (estimated using the vector autoregressive method) and observed number of cases diagnosed in 2020 was estimated using generalized estimating equation under assumptions of the Poisson distribution for count data. Interrupted time series analysis was used to compare changes in the number of records processed by registrars each month of 2020. All models accounted for seasonality, regional variation, and random error.
Results
There was a statistically significant decrease (structural break) in the number of cases diagnosed in April 2020, with no recovery in number of cases during subsequent months, leading to a 12.4% deficit in the number of cases diagnosed during the first year of the pandemic. While the number of cancer records initiated by cancer registrars also decreased, the number of records marked completed increased during the first months of the pandemic.
Conclusion
There was a significant deficit in the number of cancer diagnoses in 2020 that was not due to cancer registrars’ inability to extract data during the pandemic. Future studies can use NCDB data to evaluate the impact of the pandemic on cancer care and outcomes.
Worldwide, about 11% of Tuberculosis (TB) cases occur in people living with HIV (PLHIV) and it is the leading cause of death in this population. An important step towards reducing the incidence and ...mortality of TB in PLHIV is to reduce the time from onset of symptoms to treatment. Factors related to TB treatment delay therefore need to be understood.
Using data from a prospective cohort study of patients diagnosed with TB at the National Institute of Infectious Disease, at the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil we conducted a survival analysis to identify factors associated with patient and health care treatment delay. In our analysis we included patients who were co-infected with TB and HIV (n = 201). Patients were followed during the course of their TB treatment and information regarding duration of symptoms, sociodemographics and clinical characteristics were collected at the baseline visit.
The median time from onset of initial symptoms to prescription of TB treatment (total delay) was 82 days. From initiation of symptoms to first visit at INI clinic (patient delay), the median was 51 days. From first visit to initiation of treatment (health care delay) the median was 16 days. Illiteracy was associated with greater patient delay Hazard Ratio (HR) = 2.25, CI 95% 1.29-3.94. Having had a previous episode of TB (HR = 0.53, CI 95% 0.37-0.74) and being married (HR = 0.71, CI 95% 0.54-0.94) were inversely related to patient delay. Illiteracy was also associated with greater health care delay (HR = 2.83, CI 95% 1.25-5.47) in contrast to high viral load (HR = 0.37, CI 95% 0.24-0.54) and weight loss greater than 10% (HR = 0.54, CI 95% 0.37-0.8), both of which were inversely related to health care delay.
This study highlights the existence of factors that lead to greater risk of delayed treatment of TB among patients co-infected with HIV and TB. These include factors that can be assessed through targeted interventions which have implications for improving treatment outcomes and, through reduced duration of infectiousness, reduce the incidence of TB in Brazil.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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