We investigated experimentally the settling behaviour of vertically aligned spherical particles within various quiescent media at different release frequencies. The particles had a diameter of $d = ...4$ mm and density of $\rho _s = 2200$ kg m$^{-3}$, and were released near the free surface of water, ethanol, a G60 water–glycerine mixture (60 % glycerine by weight) and oil media at frequencies of $f_P = 4$, 6 and 8 Hz, thereby allowing study of Galileo numbers, $Ga \in 16, 976$. Particle tracking velocimetry quantified the motion of nearly 800 particles in a 600 mm high tank, and particle image velocimetry examined flow patterns around the particles. Results revealed that the centre of mass of the particle trajectories exhibited preferential in-plane motions, with significant lateral dispersion and large $Ga$ in water and ethanol, and nearly vertical paths with low $Ga$ in the G60 mixture and oil media. Varying degrees of particle separation resulted in higher terminal velocities than for a single particle. Hence, particle drag decreased in all cases, with the oil medium showing the highest drag reduction under the closest particle separation, reaching up to nearly 70 % of that for the single particle. The vertical and lateral pair dispersions, $R^2_z$ and $R^2_L$, exhibited ballistic scaling, with dependences on the initial separation, $r_0$, and the type of medium. With large $Ga$, $R^2_z$ displayed a ballistic regime followed by a slower rate, whereas with small $Ga$, $R^2_z$ maintained a consistent ballistic regime throughout settling. Finally, normalized $R^2_z$ demonstrated distinct scaling (exponent 2/3 and 1) dependent on the normalized initial separation and $Ga$.
Abstract Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a ...food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).
Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe ...single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond.
The Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this activation requires an ...interaction between their pleckstrin homology (PH) domains and the products of phosphoinositide 3-Kinase, which localizes Tec kinases to membrane RAFTs. Rlk/Txk is a Tec related kinase expressed in T cells that lacks a pleckstrin homology domain, having instead a palmitoylated cysteine-string motif. To evaluate Rlk's function in T cell receptor signaling cascades, we examined the requirements for Rlk localization and activation by Src family kinases.
We demonstrate that Rlk is also associated with RAFTs, despite its lack of a pleckstrin homology domain. Rlk RAFT association requires the cysteine-string motif and is independent of PI3 Kinase activity. We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. Mutation of this tyrosine also prevents increased tyrosine phosphorylation of Rlk after stimulation of the T cell receptor, suggesting that Rlk is phosphorylated by Src family kinases in response to T cell receptor engagement.
Like the other related Tec kinases, Rlk is associated with lipid RAFTs and can be phosphorylated and activated by Src family kinases, supporting a role for Rlk in signaling downstream of Src kinases in T cell activation.
•Reports an umbrella review on risk/protective factors for post-traumatic stress disorder (PTSD).•Several risk factors show convincing evidence of association with PTSD.•Findings may help optimize ...prediction and prevention.
Approximately one third of individuals who experience a severe traumatic event will develop posttraumatic stress disorder (PTSD). It is crucial to identify what factors may be associated with increased or decreased risk for PTSD. We conducted an umbrella review of systematic reviews and meta-analyses of risk/protective factors for PTSD and assessed and graded the evidence of the association between each factor and PTSD. Thirty-three systematic reviews and meta-analyses were included and 130 potential risk factors were identified. Of those, 57 showed a significant association with PTSD. Being female or being indigenous people of the Americas, among the sociodemographic factors; history of physical disease and family history of psychiatric disorder, among the pretrauma factors; and cumulative exposure to potentially traumatic experiences, trauma severity, and being trapped during an earthquake, among the peritrauma factors, showed convincing or highly suggestive evidence of an association with PTSD. Data from prospective studies were less conclusive. Our results have the potential of helping refine PTSD prediction models and contributing to the design of prevention strategies.
Purpose
To evaluate the outcomes of REPA and establish if any differences in complications and evolution are present between males and females.
Methods
A retrospective study including consecutive ...patients operated by REPA approach between November 2017 and April 2019 was conducted. Demographic data, operative times, postoperative complications, and hospital stay were analyzed. The EuraHS-QoL score was used to assess postoperative pain, daily activity constraints, and aesthetic discomfort. The results were compared between sexes. Statistical analysis was performed using SPSS 19.
Results
Fifty-four patients were included and 53.7% were male. Patients had a mean age of 50.7 years and a mean BMI of 28.7. The average RAD (Rectus Abdominis Diastasis) size was 2.6 cm (range of 2–5 cm). Seroma was significantly more frequent in males, with an incidence of 55.2 and 24% for females (
p
= 0.02). Three cases required reintervention (5.5% of total cases), which corresponded to a cystic seroma, an abdominal wall hematoma, and a hernia recurrence. The three cases were males and a
p
value of 0.04 was obtained when comparing reintervention rates between males and females. No cases of surgical wound infection nor cutaneous necrosis were recorded. No conversions were needed. The mean postoperative pain was 2.25, the mean daily activity constraints score was 2.63, and the degree of aesthetic discomfort was 1.23 with no significant differences between groups.
Conclusion
The correction of small midline defect associated with minor RAD using REPA seems feasible and reproducible. REPA had achieved good results in females, but in males, the outcomes were poorer.
To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS).
The GEAS-SS ...multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain.
Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p<0.001), lymphopenia (p<0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p<0.001) and cryoglobulins (p<0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p<0.001), immunosuppressants (p<0.001), intravenous immunoglobulins (p=0.008) and rituximab (p<0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved.
13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.
Retention in prevention of mother-to-child transmission (PMTCT) care is critical to prevent vertical HIV transmission and reduce morbidity and mortality of mother-infant pairs. We investigated ...whether weekly, interactive text-messaging improved 18-month postpartum retention in PMTCT care. This randomised, two-armed, parallel trial was conducted at six PMTCT clinics in western Kenya. Pregnant women with HIV at least 18 years of age with access to a mobile phone, able to text-message, or had somebody who could text on their behalf, were eligible. Participants were randomly assigned at a 1:1 ratio in block sizes of four to the intervention or control group. The intervention group received weekly text messages asking "How are you?" ("Mambo?" in Swahili) and were requested to respond within 48 h. Healthcare workers called women who indicated a problem or did not respond. The intervention was administered up to 24 months after delivery. Both groups received standard care. The primary outcome was retention in care at 18 months postpartum (i.e., clinic attendance 16-24 months after delivery based on data from patient files, patient registers and Kenya's National AIDS and STI Control Programme database), which was analysed by intention-to-treat. Researchers and data collectors were masked to group assignment, while healthcare workers were not. Between June 25th, 2015, and July 5th, 2016, we randomly assigned 299 women to the intervention and 301 to standard care only. Follow-up concluded on July 26th, 2019. The proportion of women retained in PMTCT care at 18 months postpartum was not significantly different between the intervention (n = 210/299) and control groups (n = 207/301) (risk ratio 1.02, 95% confidence interval 0.92-1.14, p = 0.697). No adverse events related to the mobile phone intervention were reported. Weekly, interactive text-messaging was not associated with improved retention in PMTCT care at 18 months postpartum or linkage to care up to 30 months postpartum in this setting. (ISRCTN No. 98818734).
•We report the novel variant p.R1560P in MYH7 gene as a founder mutation in Southern Spain.•Most patients display the classic Laing distal myopathy phenotype.•Interestingly, neck flexor weakness is ...revealed as early sign in some cases.•MRI shows early involvement of the sartorius muscle, even in asymptomatic carriers.
MYH7 gene mutations are associated with wide clinical and genetic heterogeneity. We report a novel founder mutation in MYH7 in Southern Spain (Andalucía). We studied two index patients and 24 family members from two apparently independent families by physical examination, serum creatine-kinase, muscle MRI, sequencing studies and genetic linkage analysis. Sixteen individuals were heterozygous for a (p.R1560P) variant in the MYH7 gene. Haplotype was consistent with a common ancestor for the two families. The patients displayed the classic Laing distal myopathy phenotype, with hanging first toe as the initial presentation, even in mildly affected patients who declared themselves asymptomatic, although neck flexor weakness was revealed as an early sign in some cases. MRI showed that the sartorius was the first muscle involved, even in two out of three asymptomatic carriers. Our findings support the novel variant p.R1560P in MYH7 as a founder mutation in Andalucía. The early involvement of the sartorius muscle in MRI may be useful as an indicator of affection status.
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