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Summary Objective This systematic review aimed to clarify whether there are any significant long-term sequelae to wearing mandibular advancement devices focusing on dental and skeletal effects in adults with OSA. Materials and methods Databases, including PubMed, Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and SAGE Journals. Hand searches and grey literature were also used. A piloted data collection form was used to extract the appropriate data. Results Twenty-three reports of 19 studies were included. Five had serious risk of bias while 18 had moderate risk of bias. Meta-analysis revealed a significant change in overbite and overjet. I-squared analysis showed a high level of statistical heterogeneity. A moderate correlation was found between wear time and amount of change. Conclusion Mandibular advancement devices will cause a small but statistically significant change in the dentition of long-term wearers. Skeletal changes are generally secondary to dental changes.

For adolescents new to the United States, the experience of war and acculturative stressors may play complex roles during early stages of adjustment to a new culture and country. The overall purpose of this study was to deepen understanding of the experiences of adolescents who are new to the United States, also called “newcomers”, through the examination of pre-migration war exposure and post-migration acculturative stressors as predictors of psychosocial adjustment and academic achievement. The study sample included newcomer immigrant and refugee youth (N = 184) with an average of 3.5 years in the United States. Triangulated data were collected from youth, teachers, and official school records. Results indicated that the participants who were exposed to war (N = 57) experienced more self-reported and teacher-reported anxiety, more self-reported conduct problems, and had lower academic achievement than participants who had not been exposed to war. Acculturative stressors also predicted more self-reported anxiety, conduct problems, and lower academic achievement, but only for those adolescents without war exposure, suggesting that exposure to traumatic events like war may change newcomer adolescents’ response to acculturative stressors. This may be related to the development of coping or growth that follows after trauma, which enable youth to navigate other life challenges. Understanding potential risk and resilience associated with war exposure among newly arrived students can assist clinicians, educators, and researchers in creating solutions to difficulties in psychosocial adjustment and academic performance.

Background: The study was conducted to explore challenges faced by trained informal health providers referring individuals with suspected mental disorders for treatment, and potential opportunities to counter these challenges. Methods: The study used a qualitative focus group approach. It involved community health workers, traditional and faith healers from Makueni County in Kenya. Ten Focus Group Discussions were conducted in the local language, recorded and transcribed verbatim and translated. Using a thematic analysis approach, data were entered into NVivo 7 for analysis and coding. Results: Results demonstrate that during the initial intake phase, challenges included patients' mistrust of informal health providers and cultural misunderstanding and stigma related to mental illness. Between initial intake and treatment, challenges related to resource barriers, resistance to treatment and limitations of the referral system. Treatment infrastructure issues were reported during the treatment phase. Various suggestions for solving these challenges were made at each phase. Conclusions: These findings illustrate the commitment of informal health providers who have limited training to a task-sharing model under difficult situations to increase patients' access to mental health services and quality care. With the identified opportunities, the expansion of this type of research has promising implications for rural communities.

Background To meet federal requirements under Title VI of the Civil Rights Act, the state of California instituted policies requiring that comprehensive mental health services in native languages be made available to limited English proficiency (LEP) populations when concentrations exceed “threshold” levels. Methods This paper builds on promising results from quantitative evaluations by reporting on qualitative interviews with Latino and Vietnamese LEP clients in mental health services (N = 20) to examine the awareness, impact, and implications of these threshold language policies. Results Results suggest that, while individuals are often not aware of the policies themselves, the language-related services they receive that are prompted by the policies are critical to treatment initiation and retention. Results also convey the complexities of using interpreters for sensitive psychological topics, and suggest that, for LEP individuals seeking mental health treatment, providers who speak their native languages are generally preferred. Conclusions Access to language-appropriate services seems to be an important part of why LEP populations seek mental health treatment. However, there are multiple variables that factor into the usage and usefulness of such services.

Immigrant youth are often exposed to numerous psychosocial stressors, placing them at risk for psychological distress. Little research assesses psychopathology in this population during early stages of acculturation. This study compared student and teacher reports of psychological symptoms in a diverse sample of recently immigrated youth. Students (N = 174) attended public high schools in a northeastern city. Students and teachers independently completed the Achenbach System of Empirically Based Assessment, and four DSM-derived subscales were explored. Psychological symptoms among immigrant students were higher than normative rates. Across all subscales, teacher ratings of student symptoms were significantly lower than student self-reported symptoms, and this difference was larger than that found in a normative sample. Results suggest that many immigrant youth experience psychological problems but may not be perceived as being in distress. Therefore, the most effective assessment approach may be active screening, rather than relying on self initiated help-seeking or teacher observation alone.

This study examined stigma (both the perception that mental illness is stigmatized and stigma concerns about entering treatment) and other treatment concerns along with subsequent treatment engagement within three months in a sample of 42 black adults referred to public-sector outpatient treatment. Contrary to expectation, perceived stigma of mental illness was unrelated to treatment engagement; however having stigma or other concerns about treatment was associated with increased odds of engagement. Findings indicate the importance of examining stigma as a multi-dimensional construct and raise questions about the utility of addressing stigma as a way of promoting service use in black adults. More work is clearly needed to understand the complex relationship between stigma and help-seeking in black populations and other underserved groups.

Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer’s disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection.

Oxidative stress (OS) appears to be an important determinant during the different stages of progression of Alzheimer&rsquo, s Disease (AD). In particular, impaired antioxidant defense mechanisms, such as the decrease of glutathione (GSH) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), a master regulator of antioxidant genes, including those for GSH, are associated with OS in the human AD brain. Among the neuropathological hallmarks of AD, the soluble oligomers of amyloid beta (A) peptides seem to promote neuronal death through mitochondrial dysfunction and OS. In this regard, bifunctional antioxidants can exert a dual neuroprotective role by scavenging reactive oxygen species (ROS) directly and concomitant induction of antioxidant genes. In this study, among natural coumarins (esculetin, scopoletin, fraxetin and daphnetin), we demonstrated the ability of esculetin (ESC) to prevent and counteract ROS formation in neuronal SH-SY5Y cells, suggesting its profile as a bifunctional antioxidant. In particular, ESC increased the resistance of the SH-SY5Y cells against OS through the activation of Nrf2 and increase of GSH. In similar experimental conditions, ESC could also protect the SH-SY5Y cells from the OS and neuronal death evoked by oligomers of A1&ndash, 42 peptides. Further, the use of the inhibitors PD98059 and LY294002 also showed that Erk1/2 and Akt signaling pathways were involved in the neuroprotection mediated by ESC. These results encourage further research in AD models to explore the efficacy and safety profile of ESC as a novel neuroprotective agent.

Alzheimer’s disease (AD) is the most frequent type of dementia in older people. The complex nature of AD calls for the development of multitarget agents addressing key pathogenic processes. Donepezil, an acetylcholinesterase inhibitor, is a first-line acetylcholinesterase inhibitor used for the treatment of AD. Although several studies have demonstrated the symptomatic efficacy of donepezil treatment in AD patients, the possible effects of donepezil on the AD process are not yet known. In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ1-42 oligomer (AβO) injection in mice. Interestingly, PQM130 had already shown anti-inflammatory activity in different in vivo models and neuroprotective activity in human neuronal cells. The intracerebroventricular (i.c.v.) injection of AβO in mice caused the increase of memory impairment, oxidative stress, neurodegeneration, and neuroinflammation. Instead, PQM130 (0.5–1 mg/kg) treatment after the i.c.v. AβO injection reduced oxidative damage and neuroinflammation and induced cell survival and protein synthesis through the modulation of glycogen synthase kinase 3β (GSK3β) and extracellular signal–regulated kinases (ERK1/2). Moreover, PQM130 increased brain plasticity and protected mice against the decline in spatial cognition. Even more interesting is that PQM130 modulated different pathways compared to donepezil, and it is much more effective in counteracting AβO damage. Therefore, our findings highlighted that PQM130 is a potent multi-functional agent against AD and could act as a promising neuroprotective compound for anti-AD drug development.

Chalcones have shown a broad spectrum of biological activities with clinical potential against various diseases. The biological activities are mainly attributed to the presence in the chalcones of the α,β-unsaturated carbonyl system, perceived as a potential Michael acceptor. Chalcones could activate the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through a Michael addition reaction with the cysteines of Keap1, which acts as a redox sensor and negative regulator of Nrf2. This modification allows the dissociation of Nrf2 from the cytoplasmic complex with Keap1 and its nuclear translocation. At this level, Nrf2 binds to the antioxidant response element (ARE) and activates the expression of several detoxification, antioxidant and anti-inflammatory genes as well as genes involved in the clearance of damaged proteins. In this regard, the Keap1/Nrf2–ARE pathway is a new potential pharmacological target for the treatment of many chronic diseases. In this review we summarize the current progress in the study of Keap1/Nrf2–ARE pathway activation by natural and synthetic chalcones and their potential pharmacological applications. Among the pharmacological activities highlighted, anti-inflammatory activity was more evident than others, suggesting a multi-target Michael acceptor mechanism for the chalcones involving key regulators of the Nrf2 and nuclear factor- κB (NF-κB) pathways.

ATP-binding cassette (ABC) transporters, in particular P-glycoprotein (encoded by ABCB1), are important and selective elements of the blood-brain barrier (BBB), and they actively contribute to brain homeostasis. Changes in ABCB1 expression and/or function at the BBB may not only alter the expression and function of other molecules at the BBB but also affect brain environment. Over the last decade, a number of reports have shown that ABCB1 actively mediates the transport of beta amyloid (Aβ) peptide. This finding has opened up an entirely new line of research in the field of Alzheimer’s disease (AD). Indeed, despite intense research efforts, AD remains an unsolved pathology and effective therapies are still unavailable. Here, we review the crucial role of ABCB1 in the Aβtransport and how oxidative stress may interfere with this process. A detailed understanding of ABCB1 regulation can provide the basis for improved neuroprotection in AD and also enhanced therapeutic drug delivery to the brain.

A number of pathogenic factors have been implicated in the progression of Parkinson׳s disease (PD), including oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and signals mediating apoptosis cascade. 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major component in wasabi, a very popular spice in Japan and a member of the Brassica family of vegetables. This study was designed to investigate the neuroprotective effects of 6-MSITC in a PD mouse model. Mice were treated with 6-MSITC (5mg/kg twice a week) for four weeks after the unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). On the 28th day, 6-OHDA-injected mice showed behavioral impairments, a significant decrease in tyrosine hydroxylase (TH) and an increase in apoptosis. In addition, lesioned mice showed reduced glutathione levels and glutathione-S-transferase and glutathione reductase activities. Notably, 6-MSITC demonstrated neuroprotective effects in our experimental model strongly related to the preservation of functional nigral dopaminergic neurons, which contributed to the reduction of motor dysfunction induced by 6-OHDA. Furthermore, this study provides evidence that the beneficial effects of 6-MSITC could be attributed to the decrease of apoptotic cell death and to the activation of glutathione-dependent antioxidant systems. These findings may render 6-MSITC as a promising molecule for further pharmacological studies on the investigation for disease-modifying treatment in PD.