The first signs of face aging appear in the midface, so procedures such as botulinum toxin and filler injections are performed there. However, no guidelines based on clinical anatomy describing the ...muscular and vascular components in vivo have been published. The aim of this research was to describe the depths of the midface muscles and the locations of vessels using ultrasonographic (US) imaging. US was applied at 12 landmarks on the midface in 88 volunteers (49 males and 39 females; 19–36 years) to detect sex differences in the depths of muscles and the locations of the vessels. The depths of the orbicularis oculi (OOc), levator labii superioris alaeque nasi (LLSAN), and zygomaticus minor (Zmi) differed significantly with sex at P7 (p = 0.001) and P8 (p = 0.017), P1 (p = 0.028), and P4 (p = 0.035), respectively. The facial artery, facial vein, angular artery, angular vein, and perforator vessels were found at P9, P2 and P10, P1, P1 and P5, and P8, P11 and P12, respectively. The findings indicate that the depths of the OOc, LLSAN, and Zmi muscles differ between the sexes and that the vessels appear at specific landmarks. This information could help in developing anatomical guidelines for several procedures.
Monogononta is the most speciose class of rotifers, with more than 2,000 species. The monogonont genus Brachionus is widely distributed at a global scale, and a few of its species are commonly used ...as ecological and evolutionary models to address questions related to aquatic ecology, cryptic speciation, evolutionary ecology, the evolution of sex and ecotoxicology. With the importance of Brachionus species in many areas of research, it is remarkable that the genome has not been characterized. This study aims to address this lacuna by presenting, for the first time, the whole‐genome assembly of the freshwater species Brachionus calyciflorus. The total length of the assembled genome was 129.6 Mb, with 1,041 scaffolds. The N50 value was 786.6 kb, and the GC content was 24%. A total of 16,114 genes were annotated with repeat sequences, accounting for 21% of the assembled genome. This assembled genome may form a basis for future studies addressing key questions on the evolution of monogonont rotifers. It will also provide the necessary molecular resources to mechanistically investigate ecophysiological and ecotoxicological responses.
Background Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic ...dermatitis (AD) risk remains poorly understood. Objective We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. Methods Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases COCOA) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children PSKC) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. Results In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 95% CI, 1.02-1.69; hazard ratio for anxiety, 1.41 95% CI, 1.06-1.89) and PSKC (odds ratio for distress, 1.85 95% CI, 1.06-3.25). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD ( P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios ( P = .037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels ( P = .010) and increased IgE levels at 1 year of age ( P = .005). Conclusion Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.
Obesity, characterized by excess lipid accumulation, has emerged as a leading public health problem. Excessive, adipocyte-induced lipid accumulation raises the risk of metabolic disorders. ...Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that can be obtained from abundant adipose tissue. High fat mass could be caused by an increase in the size (hypertrophy) and number (hyperplasia) of adipocytes. Reactive oxygen species (ROS) are involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). Lowering the level of ROS is important to blocking or retarding the adipogenic differentiation of hASCs. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that mediates various antioxidant enzymes and regulates cellular ROS levels. Neohesperidin dihydrochalcone (NHDC), widely used as artificial sweetener, has been shown to have significant free radical scavenging activity. In the present study, (
)-3-(4-chlorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (CTP), a novel NHDC analogue, was synthesized and examined to determine whether it could inhibit adipogenic differentiation. The inhibition of adipogenic differentiation in hASCs was tested using NHDC and CTP. In the CTP group, reduced Oil Red O staining was observed compared with the differentiation group. CTP treatment also downregulated the expression of PPAR-γ and C/EBP-α, adipogenic differentiation markers in hASCs, compared to the adipogenic differentiation group. The expression of FAS and SREBP-1 decreased in the CTP group, along with the fluorescent intensity (amount) of ROS. Expression of the Nrf2 protein was slightly decreased in the differentiation group. Meanwhile, in both the NHDC and CTP groups, Nrf2 expression was restored to the level of the control group. Moreover, the expression of HO-1 and NQO-1 increased significantly in the CTP group. Taken together, these results suggest that CTP treatment suppresses the adipogenic differentiation of hASCs by decreasing intracellular ROS, possibly through activation of the Nrf2 cytoprotective pathway. Thus, the use of bioactive substances such as CTP, which activates Nrf2 to reduce the cellular level of ROS and inhibit the adipogenic differentiation of hASCs, could be a new strategy for overcoming obesity.
The transition of human epidermal growth factor receptor 2 (HER2) status after neoadjuvant chemotherapy (NAC) in HER2-low breast cancer has not been thoroughly evaluated. Here, we evaluated the HER2 ...transition among HER2-zero and HER2-low breast cancer cases post-NAC and its impact on clinical outcomes.
We included 1288 patients with HER2-low or zero breast cancer who underwent NAC and surgery between 2014 and 2018 and had paired pre- and post-therapeutic HER2 status results.
Among patients who were HER2-zero pre-NAC (n = 650), 68% and 29% were HER2-zero and HER2-low, respectively, post-NAC. Among patients who were HER2-low pre-NAC (n = 638), 32% of patients showed HER2 changes (low to zero), and 59% of patients had a constant HER2-low status post-NAC. Patients with constant HER2-low or transitions from HER2-low to zero had a higher proportion of hormone receptor positivity (84% and 79%) than those with changes from HER2-zero to low (77%) or with constant HER2-zero (56%), respectively. Multivariable logistic regression analysis revealed that patients with oestrogen receptor positivity had a higher probability of gaining HER2-low expression than those with oestrogen receptor negativity (odds ratio 2.48). No significant differences were observed in terms of overall survival or disease-free survival between patients with and without HER2-changes according to their hormone receptor status, except in the post-therapeutic HER2-low, hormone receptor-negativity subset.
Temporal heterogeneity of HER2-low expression is observed in substantial numbers of post-NAC breast cancer patients. Clinical outcomes show no significant associations, except in the post-therapeutic HER2-low, hormone receptor negativity subset. The prognostic implications of HER2 transition in HER2-low breast cancer require further investigation.
•HER2-low expression is discordant between the primary tumour and residual disease.•HER2-low expression is unstable both in residual disease and advanced breast cancer.•HER2-low expression has a strong relationship with hormone-receptor positivity.•Changes in HER2 expression do not reflect a significant prognostic role.
The spread of American Bullfrog has a significant impact on the surrounding ecosystem. It is important to study the mechanisms of their spreading so that proper mitigation can be applied when needed. ...This study analyzes data from national surveys on bullfrog distribution. We divided the data into 25 regional clusters. To assess the spread within each cluster, we constructed temporal sequences of spatial distribution using the agglomerative clustering method. We employed Elementary Cellular Automata (ECA) to identify rules governing the changes in spatial patterns. Each cell in the ECA grid represents either the presence or absence of bullfrogs based on observations. For each cluster, we counted the number of presence location in the sequence to quantify spreading intensity. We used a Convolutional Neural Network (CNN) to learn the ECA rules and predict future spreading intensity by estimating the expected number of presence locations over 400 simulated generations. We incorporated environmental factors by obtaining habitat suitability maps using Maxent. We multiplied spreading intensity by habitat suitability to create an overall assessment of bullfrog invasion risk. We estimated the relative spreading assessment and classified it into four categories: rapidly spreading, slowly spreading, stable populations, and declining populations.
Although the introduction of human epidermal growth factor receptor (HER)2‐directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T‐DM1) in the treatment of ...HER2‐positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2‐positive mBC will eventually progress. Poziotinib is an oral pan‐HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open‐label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2‐positive mBC who had progressed from more than two HER2‐directed therapies. Patients received 12 mg poziotinib once daily on a 14‐day on/7‐day off schedule. Progression‐free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30–76) and had received a median of four prior therapies including two HER2‐directed therapies for advanced or metastatic cancers. The median follow‐up duration was 12 months. The median PFS was 4.04 months (95% confidence interval CI, 2.94–4.40 months), and median overall survival has not been reached. The most common treatment‐related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2‐positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases.
What's new?
Targeting human epidermal growth factor receptor 2 (HER2) has revolutionized treatment of HER2‐positive cancers but rapid resistance development causes significant clinical problems. In this phase II study, the authors tested poziotinib, a new oral pan‐HER inhibitor, in patients with metastatic breast cancer after two prior HER2‐directed therapies. Treatment with poziotinib achieved on average a progression‐free survival of ~4 months with relatively mild side effects (skin rash and diarrhoea), an encouraging result for patients with repeated treatment failure.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Formation of temporal association memory and context-specific fear memory is thought to require medial entorhinal cortex (MEC) inputs to the hippocampus during learning events. However, whether the ...MEC inputs are also involved in memory formation during a post-learning period has not been directly tested yet. To examine this possibility, we optogenetically inhibited axons and terminals originating from bilateral dorsal MEC excitatory neurons in the dorsal hippocampus for 5 min right after contextual fear conditioning (CFC). Mice expressing eNpHR3.0 exhibited significantly less freezing compared to control mice expressing EGFP alone during retrieval test in the conditioned context 1 day after learning. In contrast, the same optogenetic inhibition of MEC inputs performed 30 min before retrieval test did not affect freezing during retrieval test, excluding the possibility of non-specific deleterious effect of optical inhibition on retrieval process. These results support that contextual fear memory formation requires MEC inputs to the hippocampus during a post-learning period.
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