Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing, and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the potential to move along one direction in another migration mode coined ratchetaxis. We report that focal contact distributions collectively dictate cell directionality, and bias is non-linearly increased by gap distance between adhesive regions. Focal contact dynamics on micro-patterns allow to integrate these phenomena in a model where each focal contact is translated into a force with known amplitude and direction, leading to quantitative predictions for cell motion in new conditions with their successful experimental tests. Altogether, our study shows how local and minute timescale dynamics of focal adhesions and their distribution lead to long-term cellular motion with simple geometric rules. A record of this paper's Transparent Peer Review process is included in the Supplemental Information.

Intussusception has been linked with rotavirus vaccine (RVV) as a rare adverse reaction. In view of limited background data on intussusception in India and in preparation for RVV introduction, a surveillance network was established to document the epidemiology of intussusception cases in Indian children.

Minocycline, an FDA-approved second-generation semisynthetic tetracycline, exerts antioxidant, anti-apoptotic and anti-inflammatory effects, independent of its antimicrobial properties. Interleukin (IL)-17A is an immune and inflammatory mediator, and its sustained induction is associated with various cardiovascular diseases. Here we investigated (i) whether IL-17A induces cardiomyocyte contractile depression and death, (ii) whether minocycline reverses IL-17A's negative inotropic effects and (iii) investigated the underlying molecular mechanisms. Indeed, treatment with recombinant mouse IL-17A impaired adult cardiomyocyte contractility as evidenced by a 34% inhibition in maximal velocity of shortening and relengthening after 4 h (P < .01). Contractile depression followed iNOS induction at 2 h (2.13-fold, P < .01) and NO generation at 3 h (3.71-fold, P <.01). Further mechanistic investigations revealed that IL-17A-dependent induction of iNOS occurred via TRAF3IP2, TRAF6, TAK1, NF-κB, and p38MAPK signaling. 1400 W, a highly specific iNOS inhibitor, suppressed IL-17A-induced NO generation and contractile depression, where as the NO donors SNAP and PAPA-NONOate both suppressed cardiomyocyte contractility. IL-17A also stimulated cardiomyocyte IL-1β and TNF-α secretion, however, their neutralization failed to modulate IL-17A-mediated contractile depression or viability. Further increases of IL-17A concentration and the duration of exposure enhanced IL-1β and TNF-α secreted levels, buthad no impact on adult cardiomyocyte viability. However, when combined with pathophysiological concentrations of IL-1β or TNF-α, IL-17A promoted adult cardiomyocyte death. Importantly, minocycline blunted IL-17A-mediated deleterious effects, indicating its therapeutic potential in inflammatory cardiac diseases.

To compare differences in self-reported musculoskeletal pain before and after receiving rapid acupuncture for pain at an outpatient emergency department.

The newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function.

Numerous currently incurable human diseases have been causally linked to mutations in connexin (Cx) genes. In several instances, pathological mutations generate abnormally active Cx hemichannels, referred to also as "leaky" hemichannels. The goal of this study was to assay the in vivo efficacy of a potent antagonist antibody targeting Cx hemichannels.

Brevundimonas mediterranea D151-2-6 is a marine bacterium that has been isolated from 6582-m hadal sediment of the Pacific Ocean. Here, we present the complete genome sequence of B. mediterranea D151-2-6. The genome of strain D151-2-6 is 3,383,373 base pairs in size. It contains one circular chromosome with an average G + C content of 67.41%, 53 tRNAs, and 3270 protein-coding genes. Genomic analysis of strain D151-2-6 revealed that its genome is more highly enriched in genes that encode proteins involved in signal transduction and transcription than any of the other available completely sequenced Brevundimonas genomes. Some of these genes might improve ecological fitness in the hadal extreme environment. Genomic information on B. mediterranea D151-2-6 provides insights into the adaptation strategies and physiological features of Brevundimonas spp. in the hadal environment.

Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA.

High perceptual load is thought to impair the early processing of task-irrelevant distractors. In contrast, for emotional faces, previous studies have shown that early event-related potentials (ERPs), the P1, the N170, and, albeit to a lesser degree, the EPN, are relatively resistant to perceptual load manipulations. However, the temporal dynamics of the interaction between load and processing of emotional distractor faces have been neglected so far. In this preregistered EEG study (N = 40), we investigated effects of perceptual load and different interstimulus intervals (ISIs) on ERPs to fearful and neutral task-irrelevant faces. We used a task with identical visual input regardless of perceptual load (high vs. low), and four ISIs between task and face onset (100 ms, 300 ms, 600 ms, 900 ms). Results show that emotional ERP modulations depend on load manipulations as well as on specific ISIs between the perceptual task and face onset. Emotional P1 effects were modulated by load, irrespective of the ISI, while emotional N170 and EPN effects were independent of load, but modulated by the ISI. In particular, emotion effects for the EPN were only observed after a prolonged period between load task and face onset (ISI900), suggesting a strong vulnerability of this component to any competing task. Taken together, our findings show that early ERP components for fearful expressions show dissociable responses to load and timing manipulations.

Diabetic nephropathy (DN), one of the main causes of end-stage renal disease, still remains as a challenge of clinical management. This study aimed to determine whether deficiency of the thromboxane (TX) prostanoid receptor (TP), which mediates the contractile activities of all prostanoids, alleviates the development of DN and if so, to examine the underlying mechanism(s). Diabetes was induced by high fat diet and streptozotocin injection in wild-type (WT) mice and those with TP deficiency (TP-/-). Here we show that WT and TP-/- mice developed diabetes with a similar blood glucose level; however, signs of renal functional impairments and pathologies occurred to a lesser extent in TP-/- than in WT mice. Also, the extent of an increase in the expression level of transforming growth factor-β1 (TGF-β1), a common pathological mediator of DN, in diabetic renal cortexes of TP-/- mice was lower than that of WT counterparts. Moreover, we noted that expression levels of cyclooxygenase (COX)-2 and calcium-dependent phospholipase A2 (cPLA2) as well as levels of prostaglandin E2 and TXA2 in diabetic renal cortexes were increased as compared to those of non-diabetic conditions. These results thus demonstrate that possibly due to up-regulated cPLA2 and COX-2 that lead to increased prostanoid syntheses in diabetic renal cortexes, TP-/- alleviates DN development. In addition, our results suggest that such an effect of TP-/- might be related to the suppression of TGF-β1 up-regulation that is commonly associated with the disease condition.

The purpose of this study was to investigate the sensitivity and specificity of a standardized placebo protocol using a moist swab pad application in children and adolescents with psychogenic seizures vs epileptic seizures.

Anatomically accurate 3D models of 10 healthy nasal cavities are developed from computerized tomography (CT) scan images. Considering anatomical and physiological importance of different parts of the nasal cavity, the surface of each nasal passage is divided to eleven anatomical surfaces. Also the coronal cross sections in the nasal passage are divided to six sub-sections that share the total nasal passage airflow. The details of the flow field, heat transfer and water-vapor transport are numerically investigated for resting and low activity conditions. The mean and standard deviation of the different anatomical and air conditioning parameters such as: surface area, wall shear stress, heat and moisture transfer on different parts of the nasal passage surfaces and volume flow rates through different sections are presented. Results show that the percentages of airflow for inferior, middle and superior meatuses are 11.3 ± 6.4, 36.5 ± 9.5, 1.9 ± 0.81 % respectively and 4.1 ± 2.1 % of air passes through olfactory area. The inhaled air passing from the remaining surface (main passage) is 46.2 ± 10 %. Heat and moisture fluxes are highest in the anterior part of the nasal cavity, turbinates and lower part of the septum respectively. The percentage of the heat transfer from turbinates is 25.7 ± 3.9 % of total nasal heat transfer.

Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets.

The genetic basis of suicide attempts (SA) remains unclear. Especially the role of copy number variations (CNVs) remains to be elucidated. The present study aimed to identify susceptibility variants associated with SA among Chinese with major depressive disorder (MDD), covering both CNVs and single-nucleotide polymorphisms (SNPs).

Disordered collagen production by fibroblasts in response to tissue injury contributes to pulmonary fibrosis (PF). Therefore, elimination of collagen deposition has becoming a potential target in PF treatment which despite standard anti-fibrosis regiment still remains challenge. Curcumin and curcumol are regarded as the main active components extraction from the rhizomes of Curcuma zedoaria, which is widely used for inhibition the proliferation of multiple cells. However, the molecular basis for the function of curcumin and curcumol in limiting fibrogenesis still unknown. In this study, we have investigated the effects of curcumin and curcumol in the fibroblast overproliferation model human lung fibroblast (HLF) inducing by TGF-β1. The growth-inhibitory effects of the components wasn't observed from 8 to 64 μg/ml. Administration of curcumin or curcumol significantly diminished the level of hydroxyproline hydroxyproline and α-smooth muscle actin (α-SMA), also the collagen Ⅰ (Col-Ⅰ) and collagen Ⅲ (Col-Ⅲ) deposition were reduced in the HLF. Furthermore, related to the collagen synthesis proteins including N-terminal pro-peptide for Type Ⅰ collagen (PⅠNP), N-terminal pro-peptide for Type Ⅲ collagen (PⅢNP) and prolyl-hydroxylase (PHD) were degraded gracefully at dose-dependent manner. Autophagy as the scavenger was crippled in TGF-β1-fibroblast overproliferation HLF, conversely the increased autophagosomes have been spotted in cytoplasm under transmission electron microscope which is consistent with up-regulation of Beclin1 and ATG7 after treatment with curcumin or curcumol in this study. Additionally, blocking autophagy by inhibitor chloroquine (CQ) caused collagen deposition, providing further evidence regard to autophagy activation capacity of curcumin and curcumol. Our findings provide a detailed understanding that the function of curcumin and curcumol on decreasing collagen deposition mediating by autophagy mechanism, which may also inspire the further research on PF at different perspectives.

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary "patterns" of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: -2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF.

Transforming growth factor beta-1 (TGF-β1) signaling is increased and mitochondrial function is decreased in multiple models of pulmonary hypertension (PH) including lambs with increased pulmonary blood flow (PBF) and pressure (Shunt). However, the potential link between TGF-β1 and the loss of mitochondrial function has not been investigated and was the focus of our investigations. Our data indicate that exposure of pulmonary arterial endothelial cells (PAEC) to TGF-β1 disrupted mitochondrial function as determined by enhanced mitochondrial ROS generation, decreased mitochondrial membrane potential, and disrupted mitochondrial bioenergetics. These events resulted in a decrease in cellular ATP levels, decreased hsp90/eNOS interactions and attenuated shear-mediated NO release. TGF-β1 induced mitochondrial dysfunction was linked to a nitration-mediated activation of Akt1 and the subsequent mitochondrial translocation of endothelial NO synthase (eNOS) resulting in the nitration of carnitine acetyl transferase (CrAT) and the disruption of carnitine homeostasis. The increase in Akt1 nitration correlated with increased NADPH oxidase activity associated with increased levels of p47phox, p67phox, and Rac1. The increase in NADPH oxidase was associated with a decrease in peroxisome proliferator-activated receptor type gamma (PPARγ) and the PPARγ antagonist, GW9662, was able to mimic the disruptive effect of TGF-β1 on mitochondrial bioenergetics. Together, our studies reveal for the first time, that TGF-β1 can disrupt mitochondrial function through the disruption of cellular carnitine homeostasis and suggest that stimulating carinitine homeostasis may be an avenue to treat pulmonary vascular disease.

The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes.

One in 5 young people grow up in a family where one parent has experienced a mental health problem or substance use concern. Compared with their same-aged peers, these youth are at a higher risk of academic failure and acquiring a substance abuse and/or mental health issue. There is a paucity of accessible, age-appropriate interventions that address their needs.