Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disorder. The disease is characterized by degeneration of upper and lower motor neurons, leading to death usually ...within five years after the onset of symptoms. While most cases are sporadic, 5%-10% of cases can be associated with familial inheritance, including ALS type 6, which is associated with mutations in the Fused in Sarcoma (FUS) gene. This work aimed to evaluate how the most frequent ALS-related mutations in FUS, R521C, R521H, and P525L affect the protein structure and function. We used prediction algorithms to analyze the effects of the non-synonymous single nucleotide polymorphisms and performed evolutionary conservation analysis, protein frustration analysis, and molecular dynamics simulations. Most of the prediction algorithms classified the three mutations as deleterious. All three mutations were predicted to reduce protein stability, especially the mutation R521C, which was also predicted to increase chaperone binding tendency. The protein frustration analysis showed an increase in frustration in the interactions involving the mutated residue 521C. Evolutionary conservation analysis showed that residues 521 and 525 of human FUS are highly conserved sites. The molecular dynamics results indicate that protein stability could be compromised in all three mutations. They also affected the exposed surface area and protein compactness. The analyzed mutations also displayed high flexibility in most residues in all variants, most notably in the interaction site with the nuclear import protein of FUS.
Neonicotinoid seed dressings have caused concern world-wide. We use large field experiments to assess the effects of neonicotinoid-treated crops on three bee species across three countries (Hungary, ...Germany, and the United Kingdom). Winter-sown oilseed rape was grown commercially with either seed coatings containing neonicotinoids (clothianidin or thiamethoxam) or no seed treatment (control). For honey bees, we found both negative (Hungary and United Kingdom) and positive (Germany) effects during crop flowering. In Hungary, negative effects on honey bees (associated with clothianidin) persisted over winter and resulted in smaller colonies in the following spring (24% declines). In wild bees (Bombus terrestris and Osmia bicornis), reproduction was negatively correlated with neonicotinoid residues. These findings point to neonicotinoids causing a reduced capacity of bee species to establish new populations in the year following exposure.
Purpose
The enhanced view totally extraperitoneal (eTEP) concept first applied to inguinal hernias has become an important tool in the armamentarium of ventral hernia repair. The purpose of this ...report is to date the first brazilian robotic-assisted eTEP ventral hernia repair case series.
Methods
A review of a prospectively maintained database was conducted in patients who underwent robotic-assisted enhanced view totally extraperitoneal (eTEP) for ventral hernia repair between June 2018 and January 2020. Patients demographics, preoperative hernia characteristics, intraoperative variables and postoperative outcomes were evaluated.
Results
Our review identified 74 patients submitted to the procedure. Thirty-one patients (41.8%) presented primary ventral hernias (PVHs) and 43 patients (58.2%) presented incisional hernias (IHs). Female patients were predominant in both groups PVHs and IHs with 17 (22.9%) and 22 (29.7%) respectively, with a total of 39 patients (52.7%). Mean BMI was 29.1 kg/m
2
(range 21.3–48.0 kg/m
2
) with higher mean BMI rates of 30.3 kg/m
2
in the IHs group (range 22–48 years). A lateral dock setup was utilized in 55 cases (74.4%), having the inferior and superior dock setup in 18 (24.3%) and 1 (1.3%) cases respectively. Mean console time was 148.3 (range 75–277 min) and 192.6 min (range 66–301 min) in the PVHs and IHs groups respectively. There were no intraoperative complications or conversions. Average length of stay was 1.5 days. Four patients were readmitted within 30 days of surgery. There were no reoperation or cases of intraparietal herniation in this cohort. No hernia recurrence was verified during the mean 230.7 days of follow up in both groups.
Conclusion
We present the first brazilian series to-date of the robotic assisted eTEP approach for ventral hernia repairs. Although long term outcomes require further analysis, its feasibility and reproducibility in experienced surgeons hands are evident, with safe and acceptable early postoperative outcomes.
This study aimed to evaluate the effects of resistance training (RT) combined with prebiotic β-glucan (BG) ingestion (Saccharomyces cerevisiae) in ovariectomized (OVX) mice.
Forty-eight mice were ...divided into six treatments: SHAM group and five OVX groups treated with saline (SAL), alendronate (ALE) (0.1 mg/kg), BG (62.5 mg/kg), RT (climbing a ladder with load) and the combination of BG + RT. All treatments were performed three times per week for 8 weeks starting 38 days after ovariectomy.
OVX effectiveness was confirmed by a reduction in uterus mass (p < 0.05). Femur weight was higher in the SHAM group, followed by the ALE and RT groups with intermediate values and the BG + RT, BG and SAL groups with the lowest values (p < 0.05). The bone mineral density (BMD
DEXA
) results were higher for the SHAM and RT groups compared to the other groups (p < 0.05). RT provided similar bone mass and resistance to fracture to ALE and SHAM. We found a similar number of osteocytes in the RT and SHAM groups, which was significantly higher than that found in animals receiving BG (p < 0.05). The BG + RT combination increased calcium bone concentration.
RT promoted benefits on bone health in the OVX model, which were not complemented by the consumption of BG.
The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, ...the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients.
We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA–IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group.
The risks of recurrence (hazard ratio HR 1.154, 95% confidence intervals CI 0.799–1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458–1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690–1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort.
We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation.
NCT04037124.
•Radical hysterectomy does not improve outcome of N1 cervical cancer patients.•Surgery completion brings no survival benefit irrespective of tumour size or type.•If N1 is diagnosed intraoperatively, further radical procedure should be abandoned.
Gradients of vascular endothelial growth factor (VEGF) induce single endothelial cells to become leading tip cells of emerging angiogenic sprouts. Tip cells then suppress tip-cell features in ...adjacent stalk cells via Dll4/Notch-mediated lateral inhibition. We report here that Smad1/Smad5-mediated BMP signaling synergizes with Notch signaling during selection of tip and stalk cells. Endothelium-specific inactivation of Smad1/Smad5 in mouse embryos results in impaired Dll4/Notch signaling and increased numbers of tip-cell-like cells at the expense of stalk cells. Smad1/5 downregulation in cultured endothelial cells reduced the expression of several target genes of Notch and of other stalk-cell-enriched transcripts (Hes1, Hey1, Jagged1, VEGFR1, and Id1-3). Moreover, Id proteins act as competence factors for stalk cells and form complexes with Hes1, which augment Hes1 levels in the endothelium. Our findings provide in vivo evidence for a regulatory loop between BMP/TGFβ-Smad1/5 and Notch signaling that orchestrates tip- versus stalk-cell selection and vessel plasticity.
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► BMP signaling is integral to priming blood vessel plasticity ► SMAD1/5 signaling in endothelium affects endothelial cell polarity and migration ► Reciprocal SMAD1/5 and Notch signaling is crucial for stalk cell selection ► HES1 and Id protein interactions strengthen Notch signaling in endothelium
Moya et al. define a role for BMP/Smad signaling in priming blood vessel plasticity. Interdependent endothelial crosstalk between Notch and Smad1/5 suppresses the activation of tip cell behavior; in addition, Smad1/5 regulates cell polarity and migration. These processes represent essential control mechanisms in sprouting angiogenesis and vascular development.
The aim of this study was to systematically review the literature to assess if low-temperature degradation (LTD) simulation in autoclave promotes deleterious impact on the mechanical properties and ...superficial characteristics of Y-TZP ceramics compared to the non-aged protocol. The MEDLINE via PubMed electronic database was searched with included peer-reviewed publications in English language and with no publication year limit. From 413 potentially eligible studies, 49 were selected for full-text analysis, 19 were included in the systematic review with 12 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Statistical analysis was performed using RevMan 5.1, with random effects model, at a significance level of p<0.05. Descriptive analysis of monoclinic phase content data showed that aging in autoclave promotes an increase in m-phase content (ranging from 0% up to 13.4% before and 2.13% up to 81.4% after aging) with intensity associated to the material susceptibility and to the aging parameters (time, pressure and temperature). Risk of bias analysis showed that only 1 study presented high risk, while the majority showed medium risk. Five meta-analyzes (factor: aging×control) were performed considering global and subgroups analyzes (pressure, time, temperature and m-phase % content) for flexural strength data. In the global analysis a significant difference (p<0.05) was observed between conditions, favoring non-aging group. Subgroup analysis revealed statistical difference (p<0.05) favoring non-aging, for aging time >20h. However, for shorter aging times (≤20h), there was no difference between groups. Pressure subgroup analysis presented a statistical difference (p<0.05) only when a pressure ≥2bar was employed, favoring non-aging group. Temperature subgroup analysis showed a statistical difference (p<0.05) only when temperature=134°C was used, favoring the non-aging group. M-phase % content analysis presented statistical difference (p<0.05) when more than 50% of m-phase content was observed, favoring non-aging group. High heterogeneity was found in some comparisons. Aging in autoclave promoted low-temperature degradation, impacting deleteriously on mechanical properties of Y-TZP ceramics. However, the effect of LTD depends on some methodological parameters indicating that aging time higher than 20h; pressure ≥2bar and temperature of 134°C are ideal parameters to promote LTD effects, and that those effect are only observed when more than 50% m-phase content is observed.
In a fibre-reinforced polymer (FRP) structure designed using the emerging damage tolerance and structural health monitoring philosophy, sensors and models that describe crack propagation will enable ...a structure to operate despite the presence of damage by fully exploiting the material's mechanical properties. When applying this concept to different structures, sensor systems and damage types, a combination of damage mechanics, monitoring technology, and modelling is required. The primary objective of this article is to demonstrate such a combination. This article is divided in three main topics: the damage mechanism (delamination of FRP), the structural health monitoring technology (fibre Bragg gratings to detect delamination), and the finite element method model of the structure that incorporates these concepts into a final and integrated damage-monitoring concept. A novel method for assessing a crack growth/damage event in fibre-reinforced polymer or structural adhesive-bonded structures using embedded fibre Bragg grating (FBG) sensors is presented by combining conventional measured parameters, such as wavelength shift, with parameters associated with measurement errors, typically ignored by the end-user. Conjointly, a novel model for sensor output prediction (virtual sensor) was developed using this FBG sensor crack monitoring concept and implemented in a finite element method code. The monitoring method was demonstrated and validated using glass fibre double cantilever beam specimens instrumented with an array of FBG sensors embedded in the material and tested using an experimental fracture procedure. The digital image correlation technique was used to validate the model prediction by correlating the specific sensor response caused by the crack with the developed model.
There is limited evidence about the use of medications among pregnant women with COVID‐19, as well as risk factors for hospitalization due to COVID‐19 in pregnancy. We aimed to describe the use of ...medications among SARS‐CoV‐2‐positive pregnant women at the time around infection and identify predictors for hospitalization due to COVID‐19 in two hospitals in Brazil. This is a hospital record‐based study among pregnant women with positive SARS‐CoV‐2 tests between March 2020 and August 2022 from two Brazilian hospitals. Characteristics of sociodemographic, obstetrical, and COVID‐19 symptoms were extracted retrospectively. The prevalence use of medications was based on self‐reported use, and this was administered at the hospital. Logistic regression was used to estimate predictors of hospitalization due to COVID‐19. There were 278 pregnant women included in the study, of which 41 (14.7%) required hospitalization due to COVID‐19. The remaining 237 (85.3%) had mild symptoms or were asymptomatic. Most of the women had the infection in the third trimester ( n = 149; 53.6%). The most prevalent medications used across all trimesters were analgesics (2.4% to 20.0%), antibacterials (15.0% to 23.1%), and corticosteroids (7.2% to 10.4%). Pre‐ or gestational hypertensive disorder (odds ratio (OR) 4.94, 95% confidence interval (CI) 1.65, 14.87) and having at least one dose of vaccine against SARS‐CoV‐2 (OR 0.13, 95% CI 0.04, 0.39) were associated with hospitalization due to COVID‐19. Analgesics, antibacterials, and corticosteroids were the most frequently used medications among pregnant women with COVID‐19. Women with hypertensive disorders have almost a five‐fold increased risk of hospitalization due to COVID‐19. Vaccination was the strongest protective factor for severe COVID‐19. The COVID‐19 vaccination among pregnant women should be promoted, and pregnant women diagnosed with COVID‐19 who have hypertensive disorders should be closely monitored.
Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 ...short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.
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