Traumatic thoracic aortic injuries (TTAI) are associated with high rates of morbidity and mortality. They are classified according to the extent of damage and computed tomography angiography has the ...highest sensitivity and specificity for identifying the degree of injury and potential associated lesions. Treatment strategies for TTAI are based on the type and extent of injury and associated lesions. The patient's degree of stability can also help to define the choice of treatment, which can be conventional or endovascular surgery (EVAR) or even conservative management in selected cases. Among patients with adequate vascular anatomy, endovascular surgery is associated with better survival and fewer risks. The objective of this article is to describe a series of four cases followed up at a tertiary service in a Brazilian state that has few centers that provide high complexity care. Endovascular therapy was employed as the preferred method. All four patients had favorable outcomes, with no complications up to discharge, and are currently in outpatient follow-up.
Germline CDH1 point or small frameshift mutations can be identified in 30–50% of hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1 genomic rearrangements would be found in ...HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or small frameshift mutations. We screened germline DNA from the 93 mutation negative probands for large genomic rearrangements by Multiplex Ligation-Dependent Probe Amplification. Potential deletions were validated by RT–PCR and breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In-silico analysis of the CDH1 locus was used to determine a potential mechanism for these rearrangements. Six of 93 (6.5%) previously described mutation negative HDGC probands, from low GC incidence populations (UK and North America), carried genomic deletions (UK and North America). Two families carried an identical deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons 1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The statistically significant over-representation of Alus around breakpoints indicates it as a likely mechanism for these deletions. When all mutations and deletions are considered, the overall frequency of CDH1 alterations in HDGC is ∼46% (73/160). CDH1 large deletions occur in 4% of HDGC families by mechanisms involving mainly non-allelic homologous recombination in Alu repeat sequences. As the finding of pathogenic CDH1 mutations is useful for management of HDGC families, screening for deletions should be offered to at-risk families.
Systemic sclerosis (SSc) is a clinically complex and challenging disease, that leads to skin fibrosis. Its most frequent complication is interstitial lung disease (ILD), which leads to a worse ...prognosis. In this situation, cyclophosphamide is considered the gold standard for its treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option.
This paper objective was to analyze the scientific evidence on the RTX effects on SSc.
A systematic review (SR) was performed including clinical trials (CTs) on the use of RTX in SSc, published up to May 2020. The studies were identified through systematic searches in bibliographic databases using a predefined search strategy. The following databases were used: PUBMED, SCOPUS, SCIELO, LILACS, SCIENCE DIRECT, WEB OF SCIENCE, COCHRANE, WHOLIS, PAHO and EMBASE. Also, a manual search was performed. The methodological quality of the studies was determined using Jadad scale, Risk of Bias Tool (RoB 2.0) and Risk of Bias in Non-Randomized Studies - of Interventions tool (ROBINS-I). A meta-analysis of the randomized CTs was performed, using Review Manager.
Ten CTs were included in this SR. Of these, three were randomized and seven were non-randomized. Five showed a statistically significant improvement in forced vital capacity (FVC) at some time during follow-up. Regarding the skin, eight studies showed statistically significant improvements according toa the modified Rodnan skin score. The meta-analysis found positive effects of RTX in SSc, with a statistical significance for lung disease.
Rituximab is a promising strategy for the SSc-associated ILD and cutaneous fibrosis treatment. PROSPERO registration number: CRD42019132018.
Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive ...series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0–2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.
E-cadherin (CDH1) is a cancer predisposition gene mutated in families meeting clinically defined hereditary diffuse gastric cancer (HDGC). Reliable estimates of cancer risk and spectrum in germline ...mutation carriers are essential for management. For families without CDH1 mutations, genetic-based risk stratification has not been possible, resulting in limited clinical options.
To derive accurate estimates of gastric and breast cancer risks in CDH1 mutation carriers and determine if germline mutations in other genes are associated with HDGC.
Testing for CDH1 germline mutations was performed on 183 index cases meeting clinical criteria for HDGC. Penetrance was derived from 75 mutation-positive families from within this and other cohorts, comprising 3858 probands (353 with gastric cancer and 89 with breast cancer). Germline DNA from 144 HDGC probands lacking CDH1 mutations was screened using multiplexed targeted sequencing for 55 cancer-associated genes.
Accurate estimates of gastric and breast cancer risks in CDH1 mutation carriers and the relative contribution of other cancer predisposition genes in familial gastric cancers.
Thirty-one distinct pathogenic CDH1 mutations (14 novel) were identified in 34 of 183 index cases (19%). By the age of 80 years, the cumulative incidence of gastric cancer was 70% (95% CI, 59%-80%) for males and 56% (95% CI, 44%-69%) for females, and the risk of breast cancer for females was 42% (95% CI, 23%-68%). In CDH1 mutation-negative index cases, candidate mutations were identified in 16 of 144 probands (11%), including mutations within genes of high and moderate penetrance: CTNNA1, BRCA2, STK11, SDHB, PRSS1, ATM, MSR1, and PALB2.
This is the largest reported series of CDH1 mutation carriers, providing more precise estimates of age-associated risks of gastric and breast cancer that will improve counseling of unaffected carriers. In HDGC families lacking CDH1 mutations, testing of CTNNA1 and other tumor suppressor genes should be considered. Clinically defined HDGC families can harbor mutations in genes (ie, BRCA2) with different clinical ramifications from CDH1. Therefore, we propose that HDGC syndrome may be best defined by mutations in CDH1 and closely related genes, rather than through clinical criteria that capture families with heterogeneous susceptibility profiles.
The BoneMedLeg research project was developed to address current research concerns related to the use of skeletal reference collections for forensic purposes. These concerns were partly addressed by ...amassing a new reference collection which incorporates unclaimed human remains sourced from two municipal cemeteries in the city of Porto, Portugal. Amassed between 2012 and 2014 the collection was developed with permission from and in partnership with the Municipality of Porto, in a manner that is similar to that of other skeletal reference collections in Portugal. Traditionally, municipalities have bequeathed human remains that are cleared from temporary primary and secondary burial plots at local cemeteries and deemed unclaimed, to museums and universities for research purposes. The BoneMedLeg collection currently includes a total of 95 individuals, of which only 81 are fully identified (38 males and 43 females), with ages ranging from 21 days to 94 years, and a mean age of about 62 years. Years of death range from 1969 to 2003, and years of birth from 1891 to 1969. Only about half of the individuals are documented as to cause of death, which includes a considerable diversity of etiologies, from oncological to cardiovascular system disorders, and also traumatic injuries. The collection is more representative of an unskilled working class and aged population, due to one of the main sourced cemeteries disproportionately serving more socioeconomic disadvantaged communities and reflecting the demographics of the city over the past 40 years. In addition to describing the history and curatorial process of the collection in detail, this paper also discusses its broad legal framework and potential biases in its profile and composition which can inform and help plan future research projects.
The measurement of the spatial distribution of volumetric soil water content in the Pantanal is highly difficult, but it can be performed indirectly from vegetation and water indices estimated by ...remote sensors. Thus, we assessed the relationship between volumetric soil water content (VSWC) and indices of the vegetation and water by TM Landsat 5 images in pasture and forest in the Pantanal of State of Mato Grosso. The VSWC was measured daily by a TDR on a non-flooded pasture in the Fazenda Miranda (FMI) and on a floodplain monodominant area of Vochysia divergens Pohl in the RPPN SESC Pantanal, locally known as Cambarazal (Cam). The VSWC in FMI was significantly correlated with the local rainfall, but it was 5 months delayed with rainfall in Cam. The temporal dynamics of vegetation and water indices were significantly correlated with VSWC. However, some spectral indices were negatively correlated with VSWC in Cam. It suggested different responses to VSWC in each study site. As the vegetation in FMI is water limited, the biomass increased directly with the VSWC during the wet season. The combined effect of the presence of dense woody vegetation and the occurrence of flooding in Cam influenced on the non-positive correlation between VSWC and vegetation and water indices. This article demonstrates the need for further research on the relationship of VSWC and spectra indices in the Pantanal.
ABSTRACT The effects of machinery traffic and cover crops on soil physical properties have been underexplored under no-till agricultural production in subtropical environments. The objective of this ...study was to quantify the soil water infiltration rate and related soil physical properties in response to tractor traffic levels (0, 2, 5, and 20 passes) and the presence or absence of cover crops in a Xanthic Hapludox soil over two growing seasons under no-till conditions. The experiment was carried out in a randomized block design arranged in a factorial scheme with four replications. The traffic factor was constituted by the number of passes with a 6 Mg weight tractor. The winter crop management practices factor consisted of the cover crops (i) black oat (Avena strigosa) in 2017 and turnip (Raphanus sativus var. oleiferus) in 2018 compared with (ii) fallow with spontaneous vegetation. The soil water infiltration rate increased with cover crops when compared to fallow. Regarding tractor traffic levels, shortly after soil compaction, there was a lower water infiltration rate at 20 passes, 45 mm h-1 lower than the absence of tractor traffic. The soil water infiltration rate was positively correlated with macroporosity and negatively correlated with soil bulk density. After 14 months of soil compaction caused by tractor traffic, an improvement in the soil physical properties and the water infiltration rate was found, which were enhanced by the inclusion of cover crops.
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•Liposomes and lipid nanoparticles conferred a 40% photoprotection increase to AVO.•All lipid formulations demonstrated high AVO loading (7–12%)•Anionic lipid nanoparticles can be ...used in UV-blocking gels or wearable textiles.•ω3 included in lipid formulations demonstrated antioxidant properties.•Cationic formulations should be limited to non-wearable textiles.
Given the growing harmful effects of ultraviolet (UV) radiation there is an urgent need to develop effective strategies to prevent skin damages. Therefore, hydrogel or cotton and wool fabrics were impregnated with avobenzone (AVO)-loaded and omega-3 (ω3)-enriched lipid formulations (liposomes – LIP, nanostructured lipid carriers – NLC and solid lipid nanoparticles – SLN) to obtain UV blocking sunscreen gel or functional textiles. To evaluate the physicochemical characteristics of AVO and the sun blocking performance of the formulations incorporated in hydrogels or textiles, in silico and in vitro studies were conducted. In silico studies indicated that AVO can permeate the epithelium, and lipid formulations could be a promising strategy for incorporating and retaining AVO. Furthermore, all lipid formulations showed an entrapment efficiency of AVO of ca. 100 % and a loading capacity between 7 and 12 %. The presence of AVO was confirmed by ATR-FTIR and SEM analysis. In vitro release profiles showed that the UV filter was almost totally retained within the lipid formulations (release of only 4.2 ± 2.5 % at 6 h) with similar results obtained for textiles. After assessing the cytotoxicity, cationic formulations loaded with AVO showed to be cytotoxic in a human keratinocyte cell line (NCTC 2544 cells) as opposed to AVO-loaded anionic formulations after 24 h. Photodegradation studies demonstrated that lipid formulations have photoprotective properties by stabilizing AVO but the photoprotective role could not be attributed to ω3 despite its antioxidant effect evaluated by ATR-FTIR. Overall, it is possible to conclude that SLN and NLC were more effective as UV protectors than LIP, and that each formulation can have different applications. Negatively charged NLC and SLN can be used for UV protection in contact with the skin either in sunscreen gel or clothing, while positively charged NLC and SLN should be reserved as UV protectors of tissues not in contact with skin (e.g., umbrellas, curtains, etc.).
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