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The goal of this study was to evaluate whether fine-needle aspirate cytology of a previous surgical site was predictive of recurrence for incompletely excised mast cell tumors (MCTs). Electronic medical records were searched for dogs diagnosed with MCTs; those with histologically confirmed, incompletely resected MCTs evaluated by scar aspiration cytology within 60 days after surgery were included for analysis. Variables were compared between groups using Fisher's exact test and logistic regression. Twenty-nine cutaneous and 7 subcutaneous tumors were evaluated. Local recurrence, confirmed by either histopathology or cytology, occurred in 13.8% of cases. No significant differences were identified for any variables other than surgical site cytology status. The negative predictive value of surgical site aspirate cytology without residual mast cell tumor was 93.5%, with an overall predictive accuracy of 88.9%. For the dogs evaluated in this report, surgical site aspiration cytology was predictive of local disease control for incompletely resected MCTs., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Future planning has emerged as a global issue for families of individuals with intellectual and developmental disabilities due to the longer lives and limited long-term services and supports in the adult disability system. While it has received greater attention, most future planning studies only included parents of individuals with intellectual and developmental disabilities within the context of European or American countries. The purpose of this study was to examine future planning among siblings of individuals with intellectual and developmental disabilities in South Korea., Method: In this study, 185 Korean siblings of individuals with intellectual and developmental disabilities responded to a survey., Results: Few siblings engaged in future planning activities and reported a range of barriers to conduct future planning. Further, greater future planning involvement was associated with older siblings, greater advocacy level and greater sibling caregiving., Conclusion: For future research, culturally relevant measures and intervention should be addressed., (© 2020 John Wiley & Sons Ltd.)

Dental panoramic X-ray imaging is a popular diagnostic method owing to its very small dose of radiation. For an automated computer-aided diagnosis system in dental clinics, automatic detection and identification of individual teeth from panoramic X-ray images are critical prerequisites. In this study, we propose a point-wise tooth localization neural network by introducing a spatial distance regularization loss. The proposed network initially performs center point regression for all the anatomical teeth (i.e., 32 points), which automatically identifies each tooth. A novel distance regularization penalty is employed on the 32 points by considering L 2 regularization loss of Laplacian on spatial distances. Subsequently, teeth boxes are individually localized using a multitask neural network on a patch basis. A multitask offset training is employed on the final output to improve the localization accuracy. Our method successfully localizes not only the existing teeth but also missing teeth; consequently, highly accurate detection and identification are achieved. The experimental results demonstrate that the proposed algorithm outperforms state-of-the-art approaches by increasing the average precision of teeth detection by 15.71 % compared to the best performing method. The accuracy of identification achieved a precision of 0.997 and recall value of 0.972. Moreover, the proposed network does not require any additional identification algorithm owing to the preceding regression of the fixed 32 points regardless of the existence of the teeth., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Saline migrants into freshwater habitats constitute among the most destructive invaders in aquatic ecosystems throughout the globe. However, the evolutionary and physiological mechanisms underlying such habitat transitions remain poorly understood. To explore the mechanisms of freshwater adaptation and distinguish between adaptive (evolutionary) and acclimatory (plastic) responses to salinity change, we examined genome-wide patterns of gene expression between ancestral saline and derived freshwater populations of the Eurytemora affinis species complex, reared under two different common-garden conditions (0 versus 15 PSU). We found that evolutionary shifts in gene expression (between saline and freshwater inbred lines) showed far greater changes and were more widespread than acclimatory responses to salinity (0 versus 15 PSU). Most notably, 30-40 genes showing evolutionary shifts in gene expression across the salinity boundary were associated with ion transport function, with inorganic cation transmembrane transport forming the largest Gene Ontology category. Of particular interest was the sodium transporter, the Na + /H + antiporter (NHA) gene family, which was discovered in animals relatively recently. Thirty key ion regulatory genes, such as NHA paralogue #7, demonstrated concordant evolutionary and plastic shifts in gene expression, suggesting the evolution of ion transporter function and plasticity during rapid invasions into novel salinities. Moreover, freshwater invasions were associated with the evolution of reduced plasticity in the freshwater population, again for the same key ion transporters, consistent with the predicted evolution of canalization following adaptation to stressful conditions. Our results have important implications for understanding evolutionary and physiological mechanisms of range expansions by some of the most widespread invaders in aquatic habitats., (© 2020 John Wiley & Sons Ltd.)

Suppressors of cytokine signaling (SOCS) exhibit diverse antiinflammatory effects. Since ROS acts as a critical mediator of inflammation, we have investigated the anti-inflammatory mechanisms of SOCS via ROS regulation in monocytic/macrophagic cells. Using PMA-differentiated monocytic cell lines and primary BMDMs transduced with SOCS1 or shSOCS1, the LPS/TLR4-induced inflammatory signaling was investigated by analyzing the levels of intracellular ROS, antioxidant factors, inflammasome activation, and pro-inflammatory cytokines. The levels of LPS-induced ROS and the production of pro-inflammatory cytokines were notably down-regulated by SOCS1 and up-regulated by shSOCS1 in an NAC-sensitive manner. SOCS1 up-regulated an ROS-scavenging protein, thioredoxin, via enhanced expression and binding of NRF-2 to the thioredoxin promoter. SOCS3 exhibited similar effects on NRF-2/thioredoxin induction, and ROS downregulation, resulting in the suppression of inflammatory cytokines. Notably thioredoxin ablation promoted NLRP3 inflammasome activation and restored the SOCS1-mediated inhibition of ROS and cytokine synthesis induced by LPS. The results demonstrate that the anti-inflammatory mechanisms of SOCS1 and SOCS3 in macrophages are mediated via NRF-2-mediated thioredoxin upregulation resulting in the downregulation of ROS signal. Thus, our study supports the anti-oxidant role of SOCS1 and SOCS3 in the exquisite regulation of macrophage activation under oxidative stress. [BMB Reports 2020; 53(12): 640-645].

To increase resistant starch (RS) content of rice flour, soft and normal rice flours were cross-linked with different flour concentrations (40, 50%). RS contents, morphology, and baking qualities of cross-linked Singil rice flour (CSRF) and Hopyeong rice flour (CHRF) were compared. Amylose and protein contents of Singil flour were higher than those of Hopyeong flour. The protein content of CSRF maintained but that of CHRF reduced. Although the RS content increased after cross-linking, the degree of RS was higher 50% flour than 40% flour. The shape of cross-linked rice flour particles changed into starch granules with debris. The overall quality and texture of CSRF40 cupcake showed the highest scores by preference test. These results suggest that CSRF can be used as a high RS rice flour substitute for wheat flour, because soft rice is easy to make flour., Competing Interests: Conflict of interestNo potential conflict of interest relevant to this article was reported., (© The Korean Society of Food Science and Technology 2020.)

This study evaluated changes in intraocular pressure (IOP) with face-down positioning (FDP) following surgical treatment of idiopathic macular hole. We retrospectively reviewed the records of 130 patients diagnosed with idiopathic macular hole who underwent pars plana vitrectomy (PPV) with intravitreal gas injection after fluid-gas exchange. We analyzed IOP changes in both eyes following FDP over the course of 7 days. The mean IOP of the operated eyes was 14.98±2.95 mmHg preoperatively and 16.82±3.12 and 15.57±6.10 mmHg on postoperative days 2 and 7, respectively. In contralateral eyes, the mean IOP changed from 14.78±3.15 mmHg preoperatively to 16.27±1.87 and 14.40±4.14 mmHg on postoperative days 2 and 7, respectively. On postoperative day 2, the IOP increased in both eyes compared to the preoperative values, but the increase was significant only in operated eyes (p = 0.039). In contralateral eyes, the IOP on postoperative day 7 was significantly decreased compared with that on postoperative day 2 (p = 0.021) and in eyes with an axial length ≥ 23.0 mm, compared with the preoperative values (p = 0.042). The IOP of the operated eyes on postoperative day 7 was higher than that of the contralateral eyes (p = 0.039). Based on a short-term follow-up, FDP after PPV with intravitreal gas tamponade for the treatment of idiopathic macular hole may cause IOP elevation not only in the operated, but also in the contralateral eyes; the IOP increase in contralateral eyes was not as significant as that in operated eyes and was not maintained over 7 days after surgery; the IOP change seems to be affected by axial length and lens status., Competing Interests: The authors have declared that no competing interests exist.

Background: As adults with intellectual and developmental disabilities (IDD) have longer lives, parents may remain caregivers into old age. In addition, it is unknown who will fulfil caregiving roles after parents are no longer able to be caregivers. In the current study, we explored the nature (e.g. number of hours of caregiving) and correlates of parental caregiving for their adult offspring with intellectual and developmental disabilities and their future caregiving plans., Method: In the United States, data were collected from 334 parents of adults with intellectual and developmental disabilities via a national survey., Results: Altogether, 55% of the sample spent more than 15 hr conducting caregiving per week. Individual characteristics (e.g. maladaptive behaviour and functional abilities) and parent characteristics (e.g. physical proximity of the adult with intellectual and developmental disabilities and caregiving ability) positively correlated with caregiving hours. Notably, 38.58% of participants were unsure who would fulfil caregiving roles., Conclusion: Implications for research about caregiving and practice are discussed., (© 2020 John Wiley & Sons Ltd.)

Ghrelin administration increases food intake, body weight (BW), adiposity, and blood glucose. In contrast, although mouse models lacking ghrelin or its receptor (Growth Hormone Secretagogue Receptor (GHSR)) exhibit life-threatening hypoglycemia in starvation-like states, they do not exhibit appreciable reductions in food intake, BW, adiposity, blood glucose, or survival when food availability is unrestricted. This suggests the existence of a parallel neuromodulatory system that can compensate for disruptions in the ghrelin system in certain settings. Here, we hypothesized that the cannabinoid CB1 receptor (CB1R) may encode this putative redundancy, and as such, that genetic deletion of both GHSR and CB1R would exaggerate the metabolic deficits associated with deletion of GHSR alone. To test this hypothesis, we assessed food intake, BW, blood glucose, survival, and plasma acyl-ghrelin in ad libitum-fed male wild-type mice and those that genetically lack GHSR (GHSR-nulls), CB1R (CB1R-nulls), or both GHSR and CB1R (double-nulls). BW, fat mass, and lean mass were similar in GHSR-nulls and wild-types, lower in CB1R-nulls, but not further reduced in double-nulls. Food intake, plasma acyl-ghrelin, and blood glucose were similar among genotypes. Deletion of either GHSR or CB1R alone did not have a statistically-significant effect on survival, but double-nulls demonstrated a statistical trend towards decreased survival (p = 0.07). We conclude that CB1R is not responsible for the normal BW, adiposity, food intake, and blood glucose observed in GHSR-null mice in the setting of unrestricted food availability. Nor is CB1R required for plasma acyl-ghrelin secretion in that setting. However, GHSR may be protective against exaggerated mortality associated with CB1R deletion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.

Background/aims: Fractionated ionizing radiation (FIR) is an anti-cancer protocol widely applied for the treatment of diverse types of cancers to reduce damage to normal cells. However, cancer cells receiving multiple irradiations at low doses during FIR, often develop resistance to the therapy exhibiting malignant features including epithelial to mesenchymal transition (EMT). The present study has been performed to elucidate the mechanism of FIR-induced EMT signaling pathways and to identify a molecular target for radioresistance modulated by suppressors of cytokine signaling (SOCS)1., Methods: Colorectal cancer cell lines received FIR with a daily dose of 2 Gy for 3 days. Generation of intracellular reactive oxygen species (ROS) and its role in EMT signaling induced by FIR were analyzed in SOCS1 over-expressing and knock-down cells. ROS were measured by DCF fluorescence using flow cytometry. Expression levels of EMT markers and signaling molecules were analyzed by Western blotting and confocal microscopy., Results: FIR induced ROS and changes in EMT markers including down-regulation of E-cadherin with up-regulation of Twist and Snail. Pretreatment of anti-oxidant N-acetyl cysteine (NAC) abrogated the FIR-induced ROS generation and EMT response. Mechanistic studies indicated that the FIR-induced ROS-mediated EMT signaling proceeded through Akt→Src→Erk pathways. In accordance with the anti-ROS function, SOCS1 blocked the FIR-induced EMT and the associated signaling pathways through thioredoxin (Trx1) up-regulation. This is evidenced by the observation that Trx1 ablation in SOCS1 over-expressing cells negated the inhibitory action of SOCS1 by restoring the FIR-induced ROS and EMT markers. In addition, we have obtained data supporting that the FIR-induced ROS is derived from functional mitochondria and NADPH oxidases (Nox), which are both down-regulated by SOCS1., Conclusion: The results demonstrate that ROS signal acts as a mediator of the FIR-induced EMT. The data also suggest a potential anti-tumor function of SOCS1 by blocking the FIR therapy-induced resistance through the counter-regulation of ROS generating and scavenging systems., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Background: Secondary spontaneous pneumothorax is generally managed by surgery, if pneumothorax was not improved following chest tube insertion or in the event of persistent air leakage lasting more than 5 days. However, if surgery is not an option, chemical pleurodesis with sclerosants can be performed. Several sclerosants have been used in the chemical pleurodesis of secondary spontaneous pneumothorax, However, there is still controversy for what is the ideal sclerosant for Secondary spontaneous pneumothorax. The use of Viscum album L. for chemical pleurodesis in patients with secondary spontaneous pneumothorax aged >65 years has not been described to date, despite its extensive use. The authors tried to find out the effect of Viscum album L. for sclerosant for Secondary spontaneous pneumothorax in elder., Methods: This retrospective analysis examined 25 patients (aged >65 years) with secondary spontaneous pneumothorax with persistent air leakage who underwent chemical pleurodesis with Abnova Viscum-F ® ( V. album L.)., Results: The duration of chest tube drainage was 5.08 days after chemical pleurodesis. Adverse effects related to chemical pleurodesis with Abnova Viscum-F ® were fever (7/25), pain (4/25), leukocytosis (10/25), and dyspnea with desaturation (7/25); however all the patients recovered without sequela and were subsequently discharged., Conclusions: The present study demonstrated the successful use of chemical pleurodesis with V. album L. in the management of elderly patients with secondary spontaneous pneumothorax. Because of the high probability of dyspnea with desaturation in the elderly, caution must be exercised., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-708). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

We have investigated the effects of hydrogen adsorption on the [Formula: see text] topological insulator by using the density functional theory calculations. We found that hydrogen adsorption on the surface leads to surface reconstruction to reduce the band bending effect. Contrasting to a previous report that hydrogen adsorption transforms the single Dirac cone at the Brillouin zone center into three Dirac cones at the zone boundary, the Dirac cones at the zone center corresponding to the topological surface states were confirmed to be robust against the hydrogen adsorption and surface reconstruction. Hydrogen adsorption induces a Rashba-like spin-splitting of the topological surface state, and can introduce Rashba-like quantum well states within the bulk gap, which can be attributed to a semiconductor-like band bending at an interface.

Background: Given the increasing lifespans of individuals with intellectual and developmental disabilities (IDD), siblings may fulfil multiple caregiving roles simultaneously for their ageing parents, their offspring, and their brother or sister with IDD. Yet, little is known about compound sibling caregivers. The purpose of this study was to compare the perspectives of compound, single and non-caregiving siblings of adults with IDD., Method: This study investigated 332 adult siblings of individuals with IDD in the United States via a national web-based survey. Participants included: 152 non-caregivers, 94 single caregivers (i.e., caregivers only for their brothers and sisters with IDD), and 86 compound caregivers (i.e., caregivers for their brothers and sisters with IDD and at least one other vulnerable individual)., Results: Single and compound sibling caregivers (versus non-caregivers) had more positive relationships and conducted greater advocacy and future planning activities., Conclusions: Given the potential for compound sibling caregiving, further investigation is warranted., (© 2020 John Wiley & Sons Ltd.)

The ability of populations to expand their geographical ranges, whether as invaders, agricultural strains or climate migrants, is currently one of the most serious global problems. However, fundamental mechanisms remain poorly understood regarding factors that enable certain populations, such as biological invaders, to rapidly transition to novel habitats. According to one hypothesis, environmental fluctuations in the native range could promote successful invasions by imposing balancing selection on key traits and maintaining the genetic variation that enables rapid adaptation in novel habitats. Here we test the genomic predictions of this hypothesis by performing whole-genome sequencing of multiple independent invasive freshwater and native saline populations of the copepod Eurytemora affinis complex. We found that invasive populations have repeatedly responded to selection through the parallel use of the same single-nucleotide polymorphisms and genomic loci, to a much greater degree than expected. These same loci were enriched for signatures of long-term balancing selection in the native ranges, with 15-47% of loci exhibiting significant signatures of balancing selection. The strong association between parallel evolution in the invaded range and balancing selection in the native range supports the hypothesis that fluctuating habitats can promote invasive success and that balancing selection might serve as a widespread and important mechanism that enables rapid adaptation in nature.

Background: Circulating cell-free tumor DNA (ctDNA)-based mutation profiling, if sufficiently sensitive and comprehensive, can efficiently identify genomic targets in advanced lung adenocarcinoma. Therefore, the authors investigated the accuracy and clinical utility of a commercially available digital next-generation sequencing platform in a large series of patients with non-small cell lung cancer (NSCLC)., Methods: Plasma-based comprehensive genomic profiling results from 8388 consecutively tested patients with advanced NSCLC were analyzed. Driver and resistance mutations were examined with regard to their distribution, frequency, co-occurrence, and mutual exclusivity., Results: Somatic alterations were detected in 86% of samples. The median variant allele fraction was 0.43% (range, 0.03%-97.62%). Activating alterations in actionable oncogenes were identified in 48% of patients, including EGFR (26.4%), MET (6.1%), and BRAF (2.8%) alterations and fusions (ALK, RET, and ROS1) in 2.3%. Treatment-induced resistance mutations were common in this cohort, including driver-dependent and driver-independent alterations. In the subset of patients who had progressive disease during EGFR therapy, 64% had known or putative resistance alterations detected in plasma. Subset analysis revealed that ctDNA increased the identification of driver mutations by 65% over standard-of-care, tissue-based testing at diagnosis. A pooled data analysis on this plasma-based assay demonstrated that targeted therapy response rates were equivalent to those reported from tissue analysis., Conclusions: Comprehensive ctDNA analysis detected the presence of therapeutically targetable driver and resistance mutations at the frequencies and distributions predicted for the study population. These findings add support for comprehensive ctDNA testing in patients who are incompletely tested at the time of diagnosis and as a primary option at the time of progression on targeted therapies., (© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Our density functional theory calculations show that tiny-gap semiconductor SiGe monolayer is a quantum valley Hall insulator with a spontaneous electric polarization and, under a small biaxial strain, undergoes a topological phase transition between the states with opposite valley Chern numbers. The topological phase transition entails abrupt inversion of the in-plane electric polarization corresponding to inversion of the sublattice pseudospin polarization, while the out-of-plane electric polarization shows a linear response to the biaxial strain as well as to the perpendicular electric field regardless of the phase transition. Thus, the quantum valley Hall state entails in-plane ferroelectricity corresponding to a sublattice pseudospin ferromagnetism.

Purpose: The primary objective of the study described here was to compare rates of patient adherence to anticancer medications filled at an internal health system specialty pharmacy (HSSP) vs external specialty pharmacies. The primary outcome was the medication possession ratio (MPR), and the secondary outcomes included proportion of days covered (PDC), and time to treatment (TTT)., Methods: A retrospective chart review was conducted to compare the MPR, PDC, and TTT for patients who received oral anticancer therapy using prescriptions claim data. A t test or Wilcoxon test was used to explore the effect of demographic and other factors on adherence and TTT. A multiple regression model with backward elimination was used to analyze significant factors to identify covariates significantly associated with the outcomes., Results: Of the 300 patients screened for study inclusion, 204 patients whose records had complete MPR and PDC data and 164 whose records had TTT data were included in the analysis. There were significant between-group differences in mean MPR and mean PDC with patient use of the HSSP vs external pharmacies (1.00 vs 0.75 [P < 0.001] and 0.95 vs 0.7 [P < 0.001], respectively). Pharmacy type (P = 0.024) and tumor type (P = 0.048) were significantly associated with TTT., Conclusion: The multiple regression analysis indicated that oncology patients who filled their anticancer medication precriptions at an internal HSSP at an academic medical center had significantly higher adherence, as measured by MPR and PDC, and quicker TTT than those who filled their prescriptions at an external specialty pharmacy., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Chemokines are involved in the pathogenesis of various autoimmune diseases, including Graves' orbitopathy (GO), but comprehensive analyses of the dynamics of these cytokines and their receptors in such diseases remain lacking. In this study, we investigated the expressions of chemokines and their receptors during adipogenesis and inflammation in primary cultured orbital fibroblasts from patients with GO., Methods: The messenger RNA (mRNA) expression levels of chemokines were compared between GO (n = 6) and non-GO (n = 5) orbital tissues by real-time polymerase chain reaction. After adipogenesis was induced in primary cultured orbital fibroblasts from patients with GO (n =5) and following stimulation with interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the mRNA expression levels of chemokines and their receptors were analyzed., Results: Chemokines were significantly downregulated in GO orbital tissues compared to non-GO orbital tissues ( p < 0.05). Adipogenesis resulted in a strong increase in mRNA expression levels of chemokines and their receptors at an early stage (day 1); however, expression levels started to decrease thereafter and, eventually, decreased to below basal levels at the end of adipogenesis (day 10). Following stimulation with IL-1β and TNF-α, the mRNA expression levels of chemokines and their receptors increased, showing different responses to various proinflammatory cytokines., Conclusions: Chemokines were strongly upregulated in the early phase of adipogenesis before decreasing continuously until the end of adipogenesis. Also, overt mature GO tissues showed reduced mRNA expression of chemokines compared to controls, which might indicate the existence of a shorter window for effective medical inflammatory treatment. The heightened levels of chemokines and their receptors observed after stimulation with IL-1β and TNF-α suggest a crucial role of proinflammatory cytokines in the pathogenesis of GO and, further, support the idea that chemokines could be used as biomarkers of GO activity., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Ophthalmological Society.)

Despite recent innovations and advances in early diagnosis, the prognosis of advanced gastric cancer remains poor due to a limited number of available therapeutics. Here, we employed pharmacogenomic analysis of 37 gastric cancer cell lines and 1345 small-molecule pharmacological compounds to investigate biomarkers predictive of cytotoxicity among gastric cancer cells to the tested drugs. We discovered that expression of CCNA2 , encoding cyclin A2, was commonly associated with responses to polo-like kinase 1 (PLK1) inhibitors (BI-2536 and volasertib). We also found that elevated CCNA2 expression is required to confer sensitivity to PLK1 inhibitors through increased mitotic catastrophe and apoptosis. Further, we demonstrated that CCNA2 expression is elevated in KRAS mutant gastric cancer cell lines and primary tumors, resulting in an increased sensitivity to PLK1 inhibitors. Our study suggests that CCNA2 is a novel biomarker predictive of sensitivity to PLK1 inhibitors for the treatment of advanced gastric cancer, particularly cases carrying KRAS mutation.

Rare genetic diseases are the result of a continuous forward genetic screen that nature is conducting on humans. Here, we present epistemological and systems biology arguments highlighting the importance of studying these rare genetic diseases. We contend that the expanding catalog of mutations in ∼4,000 genes, which cause ∼6,500 diseases and their annotated phenotypes, offer a wide landscape for discovering fundamental mechanisms required for human development and involved in common diseases. Rare afflictions disproportionately affect the nervous system in children, but paradoxically, the majority of these disease-causing genes are evolutionarily ancient and ubiquitously expressed in human tissues. We propose that the biased prevalence of childhood rare diseases affecting nervous tissue results from the topological complexity of the protein interaction networks formed by ubiquitous and ancient proteins encoded by childhood disease genes. Finally, we illustrate these principles discussing Menkes disease, an example of the discovery power afforded by rare diseases., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Histaminergic neurons of the tuberomammillary nucleus (TMN) are wake-promoting and contribute to the regulation of energy homeostasis. Evidence indicates that melanocortin 4 receptors (MC4R) are expressed within the TMN. However, whether the melanocortin system influences the activity and function of TMN neurons expressing histidine decarboxylase (HDC), the enzyme required for histamine synthesis, remains undefined., Methods: We utilized Hdc-Cre mice in combination with whole-cell patch-clamp electrophysiology and in vivo chemogenetic techniques to determine whether HDC neurons receive metabolically relevant information via the melanocortin system., Results: We found that subsets of HDC-expressing neurons were excited by melanotan II (MTII), a non-selective melanocortin receptor agonist. Use of melanocortin receptor selective agonists (THIQ, [D-Trp 8 ]-γ-MSH) and inhibitors of synaptic transmission (TTX, CNQX, AP5) indicated that the effect was mediated specifically by MC4Rs and involved a glutamatergic dependent presynaptic mechanism. MTII enhanced evoked excitatory post-synaptic currents (EPSCs) originating from electrical stimulation of the perifornical lateral hypothalamic area (PeFLH), supportive of melanocortin effects on the glutamatergic PeFLH projection to the TMN. Finally, in vivo chemogenetic inhibition of HDC neurons strikingly enhanced the anorexigenic effects of intracerebroventricular administration of MTII, suggesting that MC4R activation of histaminergic neurons may restrain the anorexigenic effects of melanocortin system activation., Conclusions: These experiments identify a functional interaction between the melanocortin and histaminergic systems and suggest that HDC neurons act naturally to restrain the anorexigenic effect of melanocortin system activation. These findings may have implications for the control of arousal and metabolic homeostasis, especially in the context of obesity, in which both processes are subjected to alterations., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objectives: Evaluate different non-continuous temperature monitoring practices for detection of out-of-range temperatures (above or below the recommended temperature range of 2-8°C for refrigeration units), which are called excursions, within vaccine storage units., Methods: Simulations based on temperature data collected by 243 digital data loggers operated in vaccine storage units at health care providers who participated in a CDC-sponsored continuous temperature monitoring pilot project, from 2012 to 2015. In the primary analysis, we evaluate: (1) twice-daily current temperature readings without minimum and maximum readings (min/max), (2) twice-daily current temperature readings with once-daily min/max, and (3) twice-daily current temperature readings with twice-daily min/max., Results: Recording current temperature twice-daily without min/max resulted in the detection of 4.8-6.4% of the total number of temperature excursions. When min/max readings were introduced, the percentage of detected temperature excursions increased to 27.8-96.6% with once-daily min/max and to 34.8-96.7% with twice-daily min/max., Conclusions: Including min/max readings improves the ability of a temperature monitoring practice to detect temperature excursions. No combination of the non-continuous temperature monitoring practices were able to consistently detect all simulated temperature excursions., Competing Interests: Conflict of interest: The authors declare they have no conflict of interest.

We have investigated the valley Chern number and gapless edge states in wide-gap semiconductor SiC and BN monolayers by using the density functional theory calculations. We found that while SiC monolayer has a non-quantized valley Chern number due to a partial mixing of the Berry curvature peaks pertaining to the opposite valleys, there exist topologically protected gapless edge states within the bulk gap, leading to a quantum valley Hall effect. Doping of the opposite charge carriers causes a backscattering-free valley current flowing on the opposite edge, which can be used for experimental confirmation and application at room temperature. BN monolayer, on the other hand, was found to have gapped edge states due to the too large staggered AB-sublattice potentials.

Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods., Results: Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception., Conclusions: These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.

Most siblings of individuals with intellectual and developmental disabilities (IDD) report positive sibling relationships. However, extant research often only examines the perspective of the nondisabled sibling; it is unclear whether siblings with IDD report close sibling relationships. Thus, the aim of this study was to understand adult sibling relationships from the perspectives of both siblings with and without IDD. Using dyadic interviews, we examined the perspectives of eight adult sibling dyads. The study was conducted in the United States. Data were analyzed using constant comparative analysis and cross-case analysis to identify themes within and across dyads. Overall, siblings with and without IDD reported enjoying spending time with one another. However, siblings with and without Down syndrome (versus autism spectrum disorder) reported more reciprocal sibling relationships, more frequent contact, and a greater range of shared activities. Implications for future research and practice are discussed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Our density functional theory calculations show that while AB-stacked bilayer silicene has a non-quantized spin-valley Chern number, there exist backscattering-free gapless edge states within the bulk gap, leading to a quantum spin-valley Hall effect. Using a tight-binding model for a honeycomb bilayer, we found that the interlayer potential difference and the staggered AB-sublattice potential lead to abrupt and gradual change of the valley Chern number from a quantized value to zero, respectively, while maintaining backscattering-free gapless edge states if the valley Chern number is not too close to zero. Under an inversion symmetry-breaking potential in the form of the staggered AB-sublattice potential, such as an antiferromagnetic order and a hexagonal diatomic sheet, a finite but non-quantized (spin-)valley Chern number can correspond to a quantum (spin-)valley Hall insulator.

Background: For decades, trauma has been recognized globally as a major cause of death. Reducing the mortality of patients with trauma is an extremely pressing issue, particularly for those with severe trauma. An early and accurate assessment of the risk of mortality among patients with severe trauma is important for improving patient outcomes., Methods: We performed a retrospective medical record review of 582 patients with severe trauma admitted to the emergency department between July 2011 and June 2016. We analyzed the associations of in-hospital mortality with the baseline characteristics and initial biochemical markers of patients with severe trauma on admission., Results: The overall in-hospital mortality rate was 14.9%. Multivariate logistic regression analysis showed that the patient's Rapid Emergency Medicine Score (REMS; odds ratio [OR], 1.186; 95% confidence interval [CI], 1.018-1.383; p=0.029), Emergency Trauma Score (EMTRAS; OR, 2.168; 95% CI, 1.570-2.994; p<0.001), serum lactate levels (SLL; OR, 1.298; 95% CI, 1.118-1.507; p<0.001), and Injury Severity Score (ISS; OR, 1.038; 95% CI, 1.010-1.130; p=0.021) were significantly associated with in-hospital mortality., Conclusion: The REMS, EMTRAS, and SLL can easily and rapidly be used as alternatives to the injury severity score to predict in-hospital mortality for patients who present to the emergency department with severe trauma., Competing Interests: Conflict of interest No potential conflict of interest relevant to this article was reported., (Copyright © 2019 by The Korean Society for Thoracic and Cardiovascular Surgery. All rights Reserved.)

Background: Acute type A aortic dissection complicated by malperfusion is a life - threatening emergency. The optimal management strategy for malperfusion remains controversial., Case Presentation: A 46-year-old man presented to another institution with acute type A aortic dissection with abdominal aorta occlusion. Motor and sensory grade of both lower extremities were zero. Immediate antegrade distal perfusion of both lower extremities was achieved, and total arch replacement with left axillo-bifemoral bypass was performed. At the time of discharge, motor and sensory grades of both lower extremities were 2 and 3, respectively., Conclusion: This case demonstrates many of the techniques in the management of acute type A aortic dissection with abdominal aorta occlusion. In this case, direct antegrade perfusion of both lower extremities and axillo-bifemoral bypass may be helpful for patients presenting with severe malperfusion of both lower extremities with acute type A aortic dissection.

Objectives: To evaluate the effectiveness and safety of combined treatment (image guided thrombectomy and endovascular therapy with open femoral access) for acute lower limb ischemia., Methods: From 2009 to 2017, 52 patients (44 men, eight women, mean 67.2 years) underwent combined treatment for acute thrombotic occlusion of lower extremity arteries. The patients presented with acute limb ischemia and we selectively perform combined treatment in the cases with challenging clinical considerations (e.g. various spectrum of thrombus, underlying atherosclerotic lesions). Combined treatment included cutdown of common femoral artery, thrombectomy using a Fogarty balloon catheter, balloon angioplasty, stenting, and catheter-introduced thrombus fragmentation and aspiration. Patients' medical records were retrospectively reviewed and follow-up data were collected. The technical and clinical success rates and limb salvage were assessed. The Kaplan-Meier method was used to analyze primary patency rates and overall survival rates. Univariate analyses were performed to determine the factors related to clinical outcomes., Results: Technical and clinical success rate was 90.4% and 80.8%, respectively. The mean follow-up duration was 26.5 ± 25.8 months. Primary patency was 91.4%, 86.1%, and 74.6% at six months, 1-, and 2-year, respectively. Limb salvage without amputation was 88.5% (46/52). The overall survival rates at six months, 1-, and 3-year were 82.6%, 80.2, and 56.9%, respectively. The 30-day mortality was 5.8% (3/52). Univariate analysis showed that percutaneous transluminal angioplasty (PTA) type (balloon versus stent) was related to clinical failure., Conclusions: Combined treatment can be effective and safe for ALI patients even under challenging clinical conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: As individuals with intellectual and developmental disabilities (IDD) grow older, siblings are likely to become caregivers for their brothers and sisters with IDD. Thus, it is important to identify the correlates of sibling caregiving to facilitate transitions to caregiving roles., Method: This study involved the secondary analysis of a national data set of 429 adult siblings of individuals with IDD., Results: Current sibling caregiving was positively correlated with sibling relationship quality, sibling advocacy and future planning, maladaptive behaviours of individuals with IDD, and family size. Current sibling caregiving was negatively correlated with parent caregiving abilities and functional abilities of individuals with IDD. Further, among siblings who provided care, the level and nature of sibling caregiving were negatively correlated with parent caregiving abilities., Conclusions: The results identify the correlates of current caregiving among siblings of individuals with IDD. More research is needed to understand current sibling caregiving., (© 2019 John Wiley & Sons Ltd.)

Introduction: An Inferior vena cava (IVC) filter is an intravascular filter that is implanted into the IVC to prevent pulmonary embolism in medical, surgical, and trauma patients. The insertion of an IVC filter is a relatively safe procedure, but rarely may be associated with symptomatic perforation of the IVC wall, particularly in the long term., Patient Concerns and Diagnosis: A 74-year-old-woman with a medical history of IVC filter insertion visited the emergency department complaining of abdominal pain. A computed tomography scan showed perforation of the IVC wall and penetration into the duodenum by one of the filter's struts., Interventions: We performed a laparotomy to remove the IVC filter., Outcomes: Postoperatively, the patient was admitted to the general ward. On hospital day 12, she was discharged without any complications. We followed her up and computed tomography did not show any abnormal findings six months after discharge., Lessons: There is currently no evidence testifying to the benefits of IVC filter removal. Detailed, evidence-based guidelines on the indications, timing and procedure for IVC filter removal are needed. Documenting cases of long-term complications of IVC filter s such as in this patient serve to accelerate the publication of updated guidelines and are aimed at improving outcomes of similar cases in the future.

The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain largely unclear. With various mouse models and a leptin neutralizing antibody, we demonstrated that hyperleptinemia is a driving force for metabolic disorders. A partial reduction of plasma leptin levels in the context of obesity restores hypothalamic leptin sensitivity and effectively reduces weight gain and enhances insulin sensitivity. These results highlight that a partial reduction in plasma leptin levels leads to improved leptin sensitivity, while pointing to a new avenue for therapeutic interventions in the treatment of obesity and its associated comorbidities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ionotropic glutamate receptors (iGluRs) are ligand-gated cation channels that mediate fast excitatory neurotransmission in the mammalian central nervous system. In the model plant Arabidopsis thaliana , a family of 20 glutamate receptor-like proteins (GLRs) shares similarities to animal iGluRs in sequence and predicted secondary structure. However, the function of GLRs in plants is little known. In the present study, a serine site (Ser-860) of AtGLR3.7 phosphorylated by a calcium-dependent protein kinase (CDPK) was identified and confirmed by an in vitro kinase assay. Using a bimolecular fluorescence complementation and quartz crystal microbalance analyses, the physical interaction between AtGLR3.7 and the 14-3-3ω protein was confirmed. The mutation of Ser-860 to alanine abolished this interaction, indicating that Ser-860 is the 14-3-3ω binding site of AtGLR3.7. Compared with wild type, seed germination of the glr3.7-2 mutant was more sensitive to salt stress. However, the primary root growth of GLR3.7-S860A overexpression lines was less sensitive to salt stress than that of the wild-type line. In addition, the increase of cytosolic calcium ion concentration by salt stress was significantly lower in the glr3.7-2 mutant line than in the wild-type line. Moreover, association of 14-3-3 proteins to microsomal fractions was less in GLR3.7-S860A overexpression lines than in GLR3.7 overexpression line under 150 mM NaCl salt stress condition. Overall, our results indicated that GLR3.7 is involved in salt stress response in A. thaliana by affecting calcium signaling., (Copyright © 2019 Wang, Lee, Lin, Lee, Chen, Chang and Chang.)

Objective: The sympathetic nervous system (SNS) is a key regulator of the metabolic and endocrine functions of adipose tissue. Increased SNS outflow promotes fat mobilization, stimulates non-shivering thermogenesis, promotes browning, and inhibits leptin production. Most of these effects are attributed to norepinephrine activation of the Gs-coupled beta adrenergic receptors located on the surface of the adipocytes. Evidence suggests that other adrenergic receptor subtypes, including the Gi-coupled alpha 2 adrenergic receptors might also mediate the SNS effects on adipose tissue. However, the impact of acute stimulation of adipocyte Gs and Gi has never been reported., Methods: We harness the power of chemogenetics to develop unique mouse models allowing the specific and spatiotemporal stimulation of adipose tissue Gi and Gs signaling. We evaluated the impact of chemogenetic stimulation of these pathways on glucose homeostasis, lipolysis, leptin production, and gene expression., Results: Stimulation of Gs signaling in adipocytes induced rapid and sustained hypoglycemia. These hypoglycemic effects were secondary to increased insulin release, likely consequent to increased lipolysis. Notably, we also observed differences in gene regulation and ex vivo lipolysis in different adipose depots. In contrast, acute stimulation of Gi signaling in adipose tissue did not affect glucose metabolism or lipolysis, but regulated leptin production., Conclusion: Our data highlight the significance of adipose Gs signaling in regulating systemic glucose homeostasis. We also found previously unappreciated heterogeneity across adipose depots following acute stimulation. Together, these results highlight the complex interactions of GPCR signaling in adipose tissue and demonstrate the usefulness of chemogenetic technology to better understand adipocyte function., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Internationally, it has been recognised that parents need to advocate for their children with disabilities to receive services. However, many parents find advocacy difficult because of systemic and logistical barriers. As such, parents of children with disabilities may seek a special education advocate to help them understand their child's rights and secure services. Yet little research has been conducted about programmes to develop special education advocates., Methods: In this study, we conducted a comparison study to determine the association of an advocacy programme (i.e. the Volunteer Advocacy Project) on a primary outcome (i.e. special education knowledge) and other outcomes (i.e. family-school partnership, empowerment and parent well-being). Specifically, in 2017, 34 participants, all mothers of children with disabilities, were recruited from disability organisations in the USA. Seventeen mothers participated in the intervention group (i.e. the advocacy training), while 17 mothers participated in the wait list control group. The Volunteer Advocacy Project is a 36 hr advocacy training for individuals to gain instrumental and affective knowledge to advocate for their own children with disabilities and for other families. All participants completed a pre-survey and post-survey; only intervention group participants completed a 6-month follow-up survey., Results: Compared with 17 wait list control group participants, the 17 intervention group participants demonstrated improvements in special education knowledge, P = 0.002, η 2  = 0.32, and self-mastery, P = 0.04, η 2  = 0.15, and decreases in the quality of family-school partnerships, P = 0.002, η 2  = 0.32. At the follow-up survey, intervention group participants demonstrated increases in empowerment, P = 0.04, η 2  = 0.29, and special education knowledge, P = 0.02, η 2  = 0.38., Conclusions: Implications for research including the need for a randomised controlled trial are discussed; also, practitioners need to evaluate advocacy training programmes regarding their effectiveness., (© 2019 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Parents often provide the bulk of caregiving supports for their adult offspring with intellectual and developmental disabilities (IDD). Given the longer lives of people with IDD, however, such caregiving roles may transition to siblings. Thus, it is critical to conduct future planning among family members (e.g., parents, siblings) to prepare for the transition of caregiving roles. To this end, we interviewed 10 parent-sibling dyads ( N = 20) of people with IDD about long-term planning. Both parents and siblings reported family-related and systemic barriers to developing future plans. Siblings (unlike parents) reported wanting more communication among family members about planning. Implications for future research and practice are discussed.

Objective: This study describes the process of choosing a clinical outcome measure for a statewide performance outcome system for children receiving publicly funded mental health services in California., Methods: The recommendation is based on a five-phase approach, including an environmental scan of measures used by state mental health agencies; a statewide provider survey; a scientific literature review; a modified Delphi panel; and final rating of candidate measures by using nine minimum criteria informed by stakeholder priorities, scientific evidence, and state statute., Results: Only 10 states reported use of at least one standardized measure for outcome measurement. In California, the most frequently reported measures were the Child and Adolescent Needs and Strengths (CANS) (N=33), the Child Behavior Checklist (N=14), and the Eyberg Child Behavior Inventory (N=12). Based on modified Delphi panel ratings, only the Achenbach System of Empirically Based Assessment, the Strengths and Difficulties Questionnaire, and the Pediatric Symptom Checklist (PSC) were rated on average in the high-equivocal to high range on effective care, scientific acceptability, usability, feasibility, and overall utility. The PSC met all nine minimum criteria for recommendation for statewide use. In its final decision, the California Department of Health Care Services mandated use of the PSC and CANS., Conclusions: There is a lack of capacity to compare child clinical outcomes across states and California counties. Frequently used outcome measures were often not supported by scientific evidence or Delphi panel ratings. Policy action is needed to promote the selection of a common clinical outcome measure and measurement methodology for children receiving publicly funded mental health care.

Objectives: To identify a broad range of research priorities to inform the studies seeking to improve population health outcomes based on the engagement of diverse stakeholders., Methods: A multi-step, participatory and mixed-methods approach was adopted to solicit and structure the investigative themes from diverse stakeholders. The priority setting exercise involved four key phases: (1) feedback from community leadership; (2) interim ranking survey and focus group discussions during the population health symposium; (3) individual in-depth interviews with stakeholders in the community; and (4) synthesis of the research priorities from the multistep process., Results: Diverse stakeholders in Singapore, comprising community partnership leaders, health care and social service providers, users of population health services, patients and caregivers, participated in the research priority setting exercise. Initial 14 priorities were identified from six community leadership feedback, 42 survey responses, two focus groups (n = 16) and 95 in-depth interviews. The final integrated research agenda identified six priorities: empower residents and patients to take charge of their health; improve care transition and management through relationship building and communication; enhance health-social care interface; improve respite care services for long-term caregivers; develop primary care as a driving force for care integration; and capacity building for service providers. Selected research questions in each priority area were also generated to develop novel models of care, foster collaboration, implement optimal services and enhance understanding of the end users' care needs., Conclusions: This study illuminates that greater community engagement in research priority setting for population health can facilitate the formulation of evidence-based research agendas that matter to the care providers and service users in the community. The outcomes derived from this exercise will help focus researchers' efforts through which meaningful gains can be made for population health., Competing Interests: The authors have declared that no competing interests exist.

Phosphoinositide 3-kinase (PI3K) signaling in hypothalamic neurons integrates peripheral metabolic cues, including leptin and insulin, to coordinate systemic glucose and energy homeostasis. PI3K is composed of different subunits, each of which has several unique isoforms. However, the role of the PI3K subunits and isoforms in the ventromedial hypothalamus (VMH), a prominent site for the regulation of glucose and energy homeostasis, is unclear. Here we investigated the role of subunit p110β in steroidogenic factor-1 (SF-1) neurons of the VMH in the regulation of metabolism. Our data demonstrate that the deletion of p110β in SF-1 neurons disrupts glucose metabolism, rendering the mice insulin resistant. In addition, the deletion of p110β in SF-1 neurons leads to the whitening of brown adipose tissues and increased susceptibility to diet-induced obesity due to blunted energy expenditure. These results highlight a critical role for p110β in the regulation of glucose and energy homeostasis via VMH neurons.

Adopting a proper topology is crucial for transmembrane proteins to perform their functions. We previously reported that ceramide regulates a transmembrane protein called TM4SF20 (transmembrane 4 L six family member 20) through topological inversion by altering the direction through which the protein is translocated across membranes during translation. This regulatory mechanism, denoted regulated alternative translocation (RAT), depends on a G XXX N motif present in the first transmembrane helix of TM4SF20. Here, using site-directed mutagenesis, we show that Asn-26 in the motif is crucial for RAT of TM4SF20, as it cannot be replaced even by Gln. In contrast, Gly-22 in the motif could be substituted by other small residues such as Ala and Ser without affecting RAT of TM4SF20. We further demonstrate that the G XXX N motif alone is insufficient to induce RAT of a transmembrane protein because TM4SF4, a relative of TM4SF20 that also contains the motif in the first transmembrane helix, did not undergo RAT. Using TM4SF40-TM4SF20 chimeras, we identified Pro-29 of TM4SF20 as another important element required for RAT of the protein. Substituting Pro-29 alone did not affect RAT of TM4SF20, whereas replacing Pro-29 together with either Leu-25 or Val-17 of TM4SF20 with the corresponding residues of TM4SF4 abolished RAT of TM4SF20. Because Val-17, Gly-22, Leu-25, Asn-26, and Pro-29 are predicted to reside along the same surface of the transmembrane helix, our results suggest that interactions with other proteins mediated by this surface during translocation may be critical for RAT of TM4SF20., (© 2019 Wang et al.)

Many siblings anticipate fulfilling caregiving roles for their brothers and sisters with intellectual and developmental disabilities (IDD). Given these roles and the importance of supported decision making, it is crucial to understand how individuals with IDD and their siblings make decisions. Using dyadic interviews, we examined the perspectives of nine sibling dyads ( N = 18) about decision making in relation to self-determination, independent living, and employment. The ages of participants ranged from 19 to 57. Data were analyzed using constant comparative analysis to identify themes. Decision making was characterized by: parents and siblings primarily identifying courses of action; the probability of respective consequences based on the person-environment fit; and the role of the sibling in making the final decision. Characteristics related to the individual with IDD, the family, the sibling, and the environment impacted decision making. Individuals with IDD were more likely to make their own decisions about leisure activities; however, siblings were more likely to make formal decisions for their brothers and sisters.

Background: Parents often face many barriers when taking care of their offspring with disabilities. In childhood, support needs vary with families of children with Down syndrome often reporting less caregiving challenges. However, it is unclear whether support needs vary in adulthood. This study compared parents of adults with Down syndrome (DS), autism spectrum disorder (ASD) and cerebral palsy (CP) regarding support needs of their offspring with intellectual and developmental disabilities (IDD) and their families., Method: Data were collected via a national survey in the United States with 189 parents of adults with IDD., Results: Across the quantitative and qualitative analyses, parents of adults with DS (versus CP and ASD) reported significantly greater recreational, natural supports, more formal services and less future planning barriers., Conclusion: The results indicate that the DS advantage may persist in adulthood regarding support needs. More research is needed to understand different types of support needs., (© 2018 John Wiley & Sons Ltd.)

In this study, we investigated the steroidogenic effect of Taraxacum officinale extract on mouse TM3 Leydig cells, which produce male hormones by increasing the levels of steroidogenic enzymes. Steroidogenic enzymes are involved in the production of testosterone in the testis. To date, the steroidogenic effect of T. officinale has not been reported. Therefore, we examined the steroidogenic effects of T. officinale extract (TOE) on mouse Leydig cells in vitro. Traditionally, plants have been used for the treatment of various kinds of ailments. For many years, some medicinal plants have been used to regulate steroidogenesis or late-onset hypogonadism (LOH). In particular, plants belonging to the genus Taraxacum have anti-inflammatory, anti-nociceptive, anti-oxidant, and anti-cancer properties. In this study, we determined whether the TOE exerts steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, such as the steroidogenic acute regulatory protein (STAR), CYP11A1, and translocator protein (TSPO) in the mitochondria and CYP17A1 in the smooth endoplasmic reticulum, in mouse Leydig cells. Our results showed that the TOE significantly increased the mRNA and protein levels of steroidogenic enzymes, thereby increasing the testosterone levels in mouse Leydig cells. Thus, our results indicate that the TOE increases the levels of steroidogenic enzymes, and further studies are required to establish the potential of this plant in regulating steroidogenesis and improving LOH.

Although adult siblings often fulfill caregiving roles for their brothers and sisters with intellectual and developmental disabilities (IDD) and report needing support, little intervention research has been conducted with adult siblings of individuals with IDD. The purpose of this pilot study was to examine the preliminary outcomes of a leadership and support program for adult siblings of individuals with IDD. Pre, post and follow-up survey data indicated that the program correlated with increased sibling connectedness and empowerment. Additionally, the program met sibling expectations with respect to: connectedness, empowerment, and resources. Siblings were highly satisfied with the program. Also, siblings wanted to impact systemic change, especially with respect to the adult service delivery system. Implications for research and practice are discussed., (© The British Society of Developmental Disabilities 2018.)