An Examination of Positive and Negative Outcomes During the COVID-19 Pandemic Among Persons With Multiple Sclerosis.

IMPORTANCE: This study provides information to clinicians about how persons with MS coped in both positive and negative ways during a potentially traumatic experience (the coronavirus disease 2019 [COVID-19] pandemic), which will help clinicians to provide better services to this population in the face of stressful events. OBJECTIVE: To describe both positive and negative outcomes among persons with multiple sclerosis (MS) and to examine whether resilience and social support were related to positive and negative outcomes during the peak of the pandemic. DESIGN: An online survey administered during the COVID-19 pandemic. PARTICIPANTS: Participants were 74 individuals with MS and 104 healthy controls (HCs) recruited through social media and community support groups. OUTCOMES AND MEASURES: The survey included questionnaires that assessed both positive and negative responses to the pandemic, including benefit finding, loneliness, and distress. Resilience and social support were also assessed. RESULTS: Differences were noted between persons with MS and HCs on negative but not positive outcomes. Better social support and resilience were related to positive outcomes. CONCLUSIONS AND RELEVANCE: Both persons with MS and HCs were similar in benefit finding and stress management. However, negative outcomes were worse in the MS group. Our findings shed light on the importance of individuals with MS adopting a positive outlook to help during times of adversity. What This Article Adds: Among persons with disabilities such as multiple sclerosis, finding benefits during stressful times can be a potential coping mechanism. Furthermore, resilience and social support should be taken into account to moderate the effects of adverse events.

Toddlers at Elevated Likelihood for Autism: Exploring Sensory and Language Treatment Predictors.

Baseline child characteristics may predict treatment outcomes in children with or at elevated likelihood of developing autism (EL-ASD). Little is known about the role of child sensory and language features on treatment outcome. Participants were randomly assigned to a parent-mediated intervention or control condition. Analyses explored the relationship between baseline child sensory and language characteristics and changes in ASD symptoms over approximately 9 months. Higher baseline sensory hyporeactivity was significantly related to less improvement in social communication (SC) for the treatment group only. More baseline atypical vocalizations were significantly related to less improvement on SC across treatment and control groups. This work provides an initial framework to encourage the tailoring of interventions for EL-ASD children, suggesting sensory reactivity and atypical vocalizations may be useful behaviors to consider in treatment planning.

Management of children with glucose-6-phosphate dehydrogenase deficiency presenting with acute haemolytic crisis during the SARs-COV-2 pandemic.

BACKGROUND AND OBJECTIVES: Shortage of blood during the severe acute respiratory syndrome-COV-2 (SARs-COV-2) pandemic impacted transfusion practice. The primary aim of the study is to assess management of acute haemolytic crisis (AHC) in glucose-6-phosphate dehydrogenase(G6PD)- deficient children during SARs-COV-2 pandemic, and then to assess blood donation situation and the role of telemedicine in management. METHODS: Assessment of G6PD-deficient children attending the Emergency Department (ER) with AHC from 1 March 2020 for 5 months in comparison to same period in the previous 2 years, in three paediatric haematology centres. AHC cases presenting with infection were tested for SARs-COV-2 using RT-PCR. Children with Hb (50-65 g/L) and who were not transfused, were followed up using telemedicine with Hb re-checked in 24 h. RESULTS: A 45% drop in ER visits due to G6PD deficiency-related AHC during SARs-COV-2 pandemic in comparison to the previous 2 years was observed. 10% of patients presented with fever and all tested negative for COVID-19 by RT-PCR. 33% of patients had Hb < 50 g/L and were all transfused. 50% had Hb between 50 and 65 g/L, half of them (n = 49) did not receive transfusion and only two patients (4%) required transfusion upon follow up. A restrictive transfusion strategy was adopted and one of the reasons was a 39% drop in blood donation in participating centres. CONCLUSION: Fewer G6PD-deficient children with AHC visited the ER during SARs-COV-2 and most tolerated lower Hb levels. Telemedicine was an efficient tool to support their families. A restrictive transfusion strategy was clear in this study.

131 -Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal-epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo.

The failure of chemotherapy especially in triple negative breast cancer (TNBC) patients has been correlated with the overexpression of the mesenchymal-epithelial transition factor (c-Met) receptor. Thus, the hepatocyte growth factor (HGF)/c-Met signaling axis has gained considerable attention as a valid molecular target for breast cancer therapy. This study reports for the first time the discovery of the 131 -oxophorbines pheophorbide A and protopheophorbide A along with chlorophyllide A from Ziziphus lotus, an edible typical Tunisian plant, as the potent antiproliferative compounds against the human breast cancer cells MDA-MB-231 and MCF-7. Compared to other compounds, protopheophorbide A exerted the highest light-independent antiproliferative effect against the metastatic TNBC MDA-MB-231 cells (IC50 = 6.5 µM). In silico, this compound targeted the kinase domain of multiple c-Met crystal structures. It potently inhibited the kinase domain phosphorylation of wild and mutant c-Met in Z-LYTE kinase assay. Protopheophorbide A inhibited HGF-induced downstream c-Met-dependent cell proliferation, survival, adhesion and migration through RAF/MEK/ERK and PI3K/PTEN/AKT signaling pathways modulation, ROS generation and activation of JNK and p38 pathways. Interestingly, this compound impaired the ability of the MDA-MB-231 cells to adhere at different extracellular matrix proteins by reducing the HGF-induced expression of integrins αv, ß3, α2, and ß1. Moreover, protopheophorbide A exhibited anti-migratory properties (IC50 = 2.2 µM) through impacting the expression levels of E-cadherin, vimentin, ß-catenin, FAK, Brk, Rac, and Src proteins. Importantly, treatment with protopheophorbide A significantly inhibited the MDA-MB-231 tumor growth in vivo. Our results suggest that protopheophorbide A could be a novel c-Met inhibitory lead with promise to control c-Met/HGF-dependent breast malignancies.

Rutin as A Novel c-Met Inhibitory Lead for The Control of Triple Negative Breast Malignancies.

Triple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor. The cell free Z'-LYTE kinase assay, Western blot and in silico docking experiments uncovered, for the first time, c-Met kinase as a potential mechanistic target for rutin-mediated anticancer effects on TNBC cell lines. Likewise, the intraperitoneal injection of rutin at 30 mg/kg, 3X/week, significantly reduced the growth of the TNBC MDA-MB-231/GFP orthotopic xenograft in nude mouse model. These results clearly designate the functional dietary flavonoid rutin as a potential lead for the prevention and control of c-Met-dependent breast malignancies.

IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients.

BACKGROUND: Hepatocellular carcinoma has been recorded the commonest cancer in Egypt. This increasing incidence may be attributed to the high prevalence of hepatitis C virus with its complications, so this study aimed to investigate the association between the potentially functional polymorphisms of IL12A and IL12B genes as a risk factor of development of hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) infection in an Egyptian population. MATERIALS AND METHODS: We genotyped two loci of IL12 which were rs568408 (3'UTR G>A) for IL12A and rs3212227 (3'UTR A>C) for IL12B in 78 patients with HCC on top of chronic HCV infection. In addition, 64 cancer-free chronic HCV patients were studied, besides 92 healthy subjects who were included as control. RESULTS: Study of rs568408 (G>A) gene polymorphism showed that the A allele is higher while the G allele is lower in HCC cases than cancer-free chronic HCV patients (p = 0.006*). The A-containing genotypes AG and (AG+AA) were higher while the GG was lower (p = 0.009* and p = 0.005*), respectively. The study of the rs3212227 (A>C) polymorphism showed neither statistically significant differences between the C and A allele (p = 0.2) nor between CC, AC, or AC+CC in HCC cases and cancer-free chronic HCV patients (p = 0.7, p = 0.2, and p = 0.29), respectively. CONCLUSION: Our findings showed that IL12A rs568408 (G>A) polymorphism may contribute to the risk of HCC on top of chronic HCV infection, whereas that of IL12B rs3212227 (A>C) do not.

Rationally designed hecogenin thiosemicarbazone analogs as novel MEK inhibitors for the control of breast malignancies.

Natural products have documented oncology success history as valuable scaffolds for selective target modulation. Herein, the sapogenin hecogenin (1) was screened for its anti-breast cancer inhibitory capacity using in vitro assays, including proliferation, cytotoxicity, migration, invasion assays, and Western blotting. The results identified 1 as a propitious hit with modest activities attributed to the concurrent down-regulation of mitogen activated protein kinase kinase/extracellular signal-regulated kinase (MEK) distinctive downstream effectors. Guided by in silico 3D-structural insights of MAPK kinase domain, an extension strategy was adopted at 1's C-3 and C-12 aimed at the design of novel hecogenin-based analogs with improved target binding affinity. Thirty-three analogs were prepared and tested, among which hecogenin 12-(3'-methylphenyl thiosemicarbazone) (30) displayed the most potent selective anticancer effects. Analog 30 demonstrated antiproliferative, antimigratory and anti-invasive activities at low µM level, compared to the negligible effect on the non-tumorigenic MCF-10A mammary epithelial cells. Durable regression of breast tumor xenografts in athymic nude mice was observed after treatments with 30, compared to its parent hecogenin at the same dose regimen, confirmed the hit-to-lead promotion of this analog. Hecogenin-12-thiosemicarbazones, represented by 30, is a novel MEK inhibitory lead class to control breast neoplasms.

Usnic Acid Benzylidene Analogues as Potent Mechanistic Target of Rapamycin Inhibitors for the Control of Breast Malignancies.

(+)-Usnic acid (1) is a common bioactive lichen-derived secondary metabolite with a characteristic dibenzofuran scaffold. It displayed low micromolar antiproliferative activity levels and, notably, induced autophagy in a panel of diverse breast cancer cell lines, suggesting the mechanistic (formerly "mammalian") target of rapamycin (mTOR) as a potential macromolecular target. The cellular autophagic markers were significantly upregulated due to the inhibition of mTOR downstream effectors. Additionally, 1 showed an optimal binding pose at the mTOR kinase pocket aided by multiple interactions to critical amino acids. Rationally designed benzylidene analogues of 1 displayed excellent fitting into a targeted deep hydrophobic pocket at the core of the kinase cleft, through stacking with the phenolic side chain of the Tyr2225 residue. Several potent analogues were generated, including 52, that exhibited potent (nM concentrations) antiproliferative, antimigratory, and anti-invasive activities against cells from multiple breast cancer clonal lines, without affecting the nontumorigenic MCF-10A mammary epithelial cells. Analogue 52 also exhibited potent mTOR inhibition and autophagy induction. Furthermore, 52 showed potent in vivo antitumor activity in two athymic nude mice breast cancer xenograft models. Collectively, usnic acid and analogues are potential lead mTOR inhibitors appropriate for future use to control breast malignancies.

The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion.

Fungi of the genus Penicillium produce unique and chemically diverse biologically active secondary metabolites, including indole alkaloids. The role of dysregulated hepatocyte growth factor (HGF) and its receptor, c-Met, in the development and progression of breast carcinoma is documented. The goal of this work is to explore the chemistry and bioactivity of the secondary metabolites of the endophytic Penicillium chrysogenum cultured from the leaf of the olive tree Olea europea, collected in its natural habitat in Egypt. This fungal extract showed good inhibitory activities against the proliferation and migration of several human breast cancer lines. The CH2Cl2 extract of P. chrysogenum mycelia was subjected to bioguided chromatographic separation to afford three known indole alkaloids; meleagrin (1), roquefortine C (2) and DHTD (3). Meleagrin inhibited the growth of the human breast cancer cell lines MDA-MB-231, MDA-468, BT-474, SK BR-3, MCF7 and MCF7-dox, while similar treatment doses were found to have no effect on the growth and viability of the non-tumorigenic human mammary epithelial cells MCF10A. Meleagrin also showed excellent ATP competitive c-Met inhibitory activity in Z-Lyte assay, which was further confirmed via molecular docking studies and Western blot analysis. In addition, meleagrin treatment caused a dose-dependent inhibition of HGF-induced cell migration, and invasion of breast cancer cell lines. Meleagrin treatment potently suppressed the invasive triple negative breast tumor cell growth in an orthotopic athymic nude mice model, promoting this unique natural product from hit to a lead rank. The indole alkaloid meleagrin is a novel lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies.

Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C-Met.

Breast cancer is a major health problem affecting the female population worldwide. The triple-negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto-oncogenic receptor tyrosine kinase c-Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c-Met is proposed as a promising candidate target for the control of TNBCs. Lichens-derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen-derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer-guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone-derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA-MB-231 cell proliferation, migration, and invasion, with minimal toxicity to non-tumorigenic MCF-10A mammary epithelial cells. Molecular modeling, Z'-LYTE biochemical kinase assay and Western blot analysis identified c-Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA-MB-231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen-derived natural products are promising resources to discover novel c-Met inhibitors useful to control TNBCs.

Chemical and biological characterization of Melaleuca subulata (Cheel) Craven leaves' volatile constituents supported by chemometric analysis and molecular docking.

BACKGROUND: The genus Melaleuca (Myrtaceae) comprises dozens of essential oil (EO)-rich species that are appreciated worldwide for their various medicinal values. Additionally, they are renowned in traditional medicine for their antimicrobial, antifungal, and other skin-related activities. The current study investigated the chemical profile and skin-related activities of volatile constituents derived from M. subulata (Cheel) Craven (Synonym Callistemon subulatus) leaves cultivated in Egypt for the first time. METHODS: The volatile components were extracted using hydrodistillation (HD), headspace (HS), and supercritical fluid (SF). GC/MS and Kovat's retention indices were implemented to identify the volatile compounds, while the variations among the components were assessed using Principal Component Analysis and Hierarchical Cluster Analysis. The radical scavenging activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene assays. Moreover, the anti-aging effect was evaluated using anti-elastase, and anti-collagenase, while the antimicrobial potential was deduced from the agar diffusion and broth microdilution assays. Lastly, the molecular docking study was executed using C-docker protocol in Discovery Studio 4.5 to rationalize the binding affinity with targeted enzymes. RESULTS: The SF extraction approach offered the highest EO yield, being 0.75%. According to the GC/MS analysis, monoterpene hydrocarbons were the most abundant volatile class in the HD oil sample (54.95%), with α-pinene being the most copious component (35.17%). On the contrary, the HS and SF volatile constituents were pioneered with oxygenated monoterpenes (72.01 and 36.41%) with eucalyptol and isopulegone being the most recognized components, representing 67.75 and 23.46%, respectively. The chemometric analysis showed segregate clustering of the three extraction methods with α-pinene, eucalyptol, and isopulegone serving as the main discriminating phytomarkers. Concerning the bioactivity context, both SF and HD-EOs exhibited antioxidant effects in terms of ORAC and ß-carotene bleaching. The HD-EO displayed potent anti-tyrosinase activity, whereas the SF-EO exhibited significant anti-elastase properties. Moreover, SF-EO shows selective activity against gram-positive skin pathogens, especially S. aureus. Ultimately, molecular docking revealed binding scores for the volatile constituents; analogous to those of the docked reference drugs. CONCLUSIONS: M. subulata leaves constitute bioactive volatile components that may be indorsed as bioactive hits for managing skin aging and infection, though further in vivo studies are recommended.

A Combined Interventional Approach to Train Interview Skills in Autistic Transition-Age Youth.

BACKGROUND: The job interview can be challenging for autistic adolescents considering the required social communication skills. Further, having decreased awareness of personal strengths may make it difficult to advocate for oneself to a future employer. The purpose of the current pilot randomized controlled trial (RCT) is to examine the preliminary efficacy and feasibility of a combined interventional approach using: the Virtual Interview Tool for Autistic Transition-Age Youth (VIT-TAY) and Kessler Foundation Strength Identification and Expression (KF-STRIDE). METHOD: Twenty autistic transition-age youth (TAY) were randomly assigned to two groups: an intervention group (n = 10) that received 9 h of VIT-TAY (interviewing practice with a virtual human), and three lessons of KF-STRIDE (positive psychology intervention to learn and discuss one's personal character strengths) and a services-as-usual (SAU) group (n = 10). The primary outcome was measured using a video-recorded mock job interview performed at pre- and post-test, which was rated by blinded assessors. Secondary outcomes included self-reports of job interview skill, interview anxiety, work readiness and recent job search behavior. RESULTS: Paired samples t-tests revealed significant differences between pre- and post-test in the intervention group (but not the control group) on the mock interview total score (p = 0.02, d = 0.76) and self-reported job interview skills total score (p = 0.02, d = 0.75). The intervention group (but not the control group) had improvements in work-readiness (p = 0.06, d = 0.53) and job search behavior (p = 0.07, d = 0.52) that were characterized by medium effect sizes. CONCLUSIONS: This pilot study suggests that combining VIT-TAY with KF-STRIDE leads to improvements in performance-based and self-reported job interview skills.

Phenolic profiling and bioactivity assessment of in vitro propagated Psidium cattleianum Sabine: A promising study.

Psidium cattleianum Sabine (strawberry guava) is an evergreen shrub that is grown as a fruiting hedge and has received significant consideration in the food and pharmaceutical disciplines. This study aims to set a promising protocol for in vitro propagation of P. cattleianum, along with profiling the phenolic content of the original plant (OP), induced callus (IC), and regenerated plantlets (RP) extracts, ultimately, evaluating their anti-inflammatory, antioxidant, and anticancer potential. Seeds were treated with commercial bleaching, HCl, and H2O2 to enhance the germination percentage and minimize the contamination percentage. Culturing sterilized leaf explants onto Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA), 2,4-dichloro phenoxy acetic acid, and kinetin showed the best callus induction, while supplementation of MS media with BA, adenine sulfate, naphthalene acetic acid, and gibberellic acid activated regeneration. Augmentation of MS media with indol-3-butyric acid recorded the maximum rooting percentage. Finally, the obtained rooted shoots were successfully acclimatized in sand and peat moss soil. HPLC-MS/MS profiles of OP, RP, and IC showed a variety of phenolic metabolites. IC extract decreased the viability of MCF-7, HepG2, and K-562 cancer cell lines. Also, OP exhibits strong antioxidant activity. P. cattleianum and its RP are profound sources of phenolic compounds promoted for promising applications in the food and pharmaceutical industries.

Phytochemical profile and antimicrobial activity of essential oils from two Syzygium species against selected oral pathogens.

BACKGROUND: The genus Syzygium (Myrtaceae) comprises several essential oil-rich species that are utilized traditionally for treating tooth infections and toothache. The current study aimed to extract essential oils (EOs) from the leaves of Syzygium samarangense and Syzygium malaccense cultivated in Egypt for the first time and screen their antimicrobial potential against oral-related pathogens. METHODS: The intended EOs were extracted using hydrodistillation (HD) by boiling fresh leaves with distilled water; supercritical fluid (SF) by extracting the dried leaves using supercritical CO2 at 40 °C and 150 bar; and the headspace (HS) in which the fresh leaves were heated in a glass vial and the vaporized aroma were analyzed. The volatile constituents were analyzed using GC/MS and identified by comparing the experimental Kovats' retention indices with the literature. The antimicrobial activity was assessed against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Candida albicans using agar diffusion, microwell dilution, and biofilm formation assays. Statistical significance (p < 0.05) was determined by applying one-way ANOVA and Duncan's post hoc test. RESULTS: The yield of the extracted EOs differs between the applied methods, and the SF approach harvested the maximum (0.52-0.46%). The GC-MS analysis of SF EOs revealed a discrepancy between the two species. Since S. malaccense showed an abundance of hydrocarbons represented mainly by squalene (60.60%), S. samarangense was deemed to have oxygenated sesquiterpenes exemplified in globulol (52.09%). On the other side, the HD and HS EOs were sequentially comparable, while differed in the percentage of their majors. γ-terpinene (33.06%) pioneered the HS-derived aroma of S. malaccense, while S. samarangense was abundant with α-pinene (30.18%). Concurrently, the HD EOs of S. malaccense and S. samarangense were commonly denoted by caryophyllene oxide (8.19%-18.48%), p-cymene (16.02%- 19.50%), and γ-terpinene (12.20%-17.84). Ultimately, both species EOs exhibited broad-spectrum antimicrobial potential, although the HD EO was more potent than the SF EO. The HD EOs of both species potently inhibited the growth of E. coli (MIC 3.75 µL/mL) and suppressed C. albicans biofilm formation by 83.43 and 87.27%, respectively. The SF-EOs efficiently suppressed the biofilm formation of Gram-positive bacteria by 76.45%-82.95%. CONCLUSION: EOs extracted from both species by different methods possessed a unique blend of volatile components with broad-spectrum antimicrobial activity. They were promoted as bioactive hits for controlling oral infections, however further investigations concerning their safety in clinical settings are needed.

Essential oils of Psidium cattleianum Sabine leaves and flowers: Anti-inflammatory and cytotoxic activities.

Introduction: Psidium cattleianum Sabine is a Brazilian native shrub cultivated for its edible fruit araçá (strawberry guava). P. cattleianum is recognized for health and food applications, although the essential oils (EOs) from the Egyptian inhabitant are not fully explored. The current study investigated the anti-inflammatory and cytotoxic activities of EOs from P. cattleianum leaves and flowers. Materials and methods: The EOs were obtained by three different methods viz; the conventional hydro-distillation, microwave assisted hydro-distillation, and supercritical fluid extraction, while their analysis was accomplished using GC/MS. The derived EOs were screened for their anti-inflammatory activity in the 5-lipoxygenase, COX-1, and COX-2 enzyme based assays, while the anticancer potential was deduced from MTT cytotoxic assay, cell cycle, and western blotting analysis. Results and discussion: Among other methods, supercritical fluid extraction offered the highest EO yield, 0.62% (leaves) and 1.4% (flowers). GC/MS identified ß-caryophyllene and α-humulene in both organs with high but variable percentages. The leaves demonstrated strong activity in inhibiting the 5-lipoxygenase enzyme (IC50 2.38), while the flowers, in inhibiting COX-2 (IC50 2.575). Moreover, the leaves showed potent, selective cytotoxicity to MCF-7 cells (IC50 5.32) via apoptosis by modulating the p53/Bax/Bcl2 axis. The deduced activities are possible due to the synergism between the volatile components that endorses P. cattleianum leaves' EOs in the management of breast cancer and inflammatory disorders.

Corrigendum: Essential oils of Psidium cattleianum Sabine leaves and flowers: anti-inflammatory and cytotoxic activities.

[This corrects the article DOI: 10.3389/fchem.2023.1120432.].

Development and adaptation of a strength-based job interview training tool for transition age youth on the autism spectrum using community engaged methods.

Introduction: Kessler Foundation Strength Identification and Expression (KF-STRIDE) is a strength-based job interview training tool developed for young adults on the autism spectrum. The intervention is based on a positive psychology framework to increase knowledge of character strengths, and how to relate them to a future employer. The current study sought to evaluate the acceptability, usability and feasibility of KF-STRIDE, as well as to guide adaptations to improve the tool's ability to meet the needs of those on the spectrum. Methods: Mixed methods (post-intervention surveys, and semi-structured interviews with key stakeholders) were used to inform the evaluation and consequent adaptations of KF-STRIDE. Results: The major findings of the study were that KF-STRIDE was found to be largely acceptable and usable. Importantly, however, our qualitative analysis revealed modifications that could help to better suit the needs of young adults on the spectrum, which included the incorporation of additional skills (i.e. etiquette, practicing hygiene) and more opportunities to practice job interviewing. Thus, we altered the implementation of the intervention to be web-based to improve accessibility. We incorporated the presence of an animated character to deliver the content, to eliminate the need for a highly trained interventionist. Discussion: KF-STRIDE was modified to increase access by incorporating feedback from the autism community. Future directions include assessing the efficacy of KF-STRIDE in young adults on the spectrum to identify whether employment outcomes are improved after using the tool.

The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway.

Ulcerative colitis (UC), a chronic autoimmune disease of the gut with a relapsing and remitting nature, considers a major health-care problem. DSS is a well-studied pharmacologically-induced model for UC. Toll-Like Receptor 4 (TLR4) and its close association with p-38-Mitogen-Activated Protein Kinase (p-38 MAPK) and nuclear factor kappa B (NF-κB) has important regulatory roles in inflammation and developing UC. Probiotics are gaining popularity for their potential in UC therapy. The immunomodulatory and anti-inflammatory role of azithromycin in UC remains a knowledge need. In the present rats-established UC, the therapeutic roles of oral probiotics (60 billion probiotic bacteria per kg per day) and azithromycin (40 mg per kg per day) regimens were evaluated by measuring changes in disease activity index, macroscopic damage index, oxidative stress markers, TLR4, p-38 MAPK, NF-κB signaling pathway in addition to their molecular downstream; tumor necrosis factor alpha (TNFα), interleukin (IL)1ß, IL6, IL10 and inducible nitric oxide synthase (iNOS). After individual and combination therapy with probiotics and azithromycin regimens, the histological architecture of the UC improved with restoration of intestinal tissue normal architecture. These findings were consistent with the histopathological score of colon tissues. Each separate regimen lowered the remarkable TLR4, p-38 MAPK, iNOS, NF-κB as well as TNFα, IL1ß, IL6 and MDA expressions and elevated the low IL10, glutathione and superoxide dismutase expressions in UC tissues. The combination regimen possesses the most synergistic beneficial effects in UC that, following thorough research, should be incorporated into the therapeutic approach in UC to boost the patients' quality of life.

Systematic Review of the Relation Between Feeding Problems and Sensory Processing in Children With Autism Spectrum Disorder.

PURPOSE: Many studies have linked sensory sensitivities to feeding problems in children with autism spectrum disorder (ASD). Despite the importance of sensory processing for a variety of mealtime and eating skills, the specific sensory processes that may impact feeding problems in children with ASD have not been comprehensively reviewed. Thus, the goal of this systematic review was to understand the associations between sensory processing and feeding difficulties in children with ASD. METHOD: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, CINAHL Plus with Full Text (EBSCOhost), Scopus (Elsevier), and Embase (Elsevier) databases were searched from their dates of inception through the final search date of April 19, 2022, for English language studies that examined both sensory processing and feeding among children with ASD. Studies were assessed for quality using the Joanna Briggs Institute critical appraisal tools. RESULTS: A total of 27 studies were included. Findings supported the existence of a relationship between sensory processing and feeding problems in children with ASD. Specifically, studies reported that overall scores on sensory processing measures as well as measures of oral sensory processing were frequently associated with feeding problems. CONCLUSIONS: This review supports the development of future feeding interventions focusing on sensory processing given the relationship between sensory processing and feeding problems among children with ASD. Future research should focus on utilizing consistent feeding assessments specific to children with ASD and collect information on medical diagnoses that can impact feeding in order to report on feeding more holistically in this population. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21453909.

Caregiver responsiveness as a mechanism to improve social communication in toddlers: Secondary analysis of a randomized controlled trial.

Early intensive behavioral interventions (EIBI) for children at elevated likelihood for a later diagnosis of autism spectrum disorder (EL-ASD), are often delivered through parent-mediated models. An area of current exploration is whether changes in caregiver behaviors are a mechanism through which to improve and track child behaviors in these interventions. Toddlers and their caregivers participated in an intervention trial (randomized controlled trial) and were randomized to either a parent-mediated intervention (adapted responsive teaching; ART) or a control condition (referral to early intervention and monitoring; REIM). Changes in toddler social communication (SC) behaviors and characteristics of caregiver responsiveness (CR) were quantified over 8 months. Analyses were conducted to assess whether changes in CR mediated the relation between group (ART vs. REIM) and changes in child SC. Results of the current study indicated that caregivers who participated in a parent-mediated intervention improved in three domains of CR (contingent verbal sensitivity, responsivity, affect). CR was also found to be a mechanism through which children's SC skills improved. This work provides evidence that qualities of CR serve as mechanisms through which to improve and monitor child behaviors over the course of EIBIs. These results may lead to novel intervention targets, methods for tracking change, and tailored treatment planning for toddlers with EL-ASD. The data used in this study comes from a clinical trial that was prospectively registered with the Registry of Efficacy and Effectiveness Studies (Registry ID: 316.1v1). LAY SUMMARY: Interventions for toddlers with high likelihood for a later diagnosis of autism often include the caregiver as an active participant in the intervention. In this study, we aimed to understand qualities of caregiver responsiveness (CR) that facilitate improvements in child behaviors during intervention. Results show that increasing verbal CR and affect are ways to improve child social skills over the course of intervention.