Diagnostic utility of exome sequencing followed by research reanalysis in human brain malformations.

This study aimed to determine the diagnostic yield of singleton exome sequencing and subsequent research-based trio exome analysis in children with a spectrum of brain malformations seen commonly in clinical practice. We recruited children ≤ 18 years old with a brain malformation diagnosed by magnetic resonance imaging and consistent with an established list of known genetic causes. Patients were ascertained nationally from eight tertiary paediatric centres as part of the Australian Genomics Brain Malformation Flagship. Chromosome microarray was required for all children, and those with pathogenic copy number changes were excluded. Cytomegalovirus polymerase chain reaction on neonatal blood spots was performed on all children with polymicrogyria with positive patients excluded. Singleton exome sequencing was performed through a diagnostic laboratory and analysed using a clinical exome sequencing pipeline. Undiagnosed patients were followed up in a research setting, including reanalysis of the singleton exome data and subsequent trio exome sequencing. A total of 102 children were recruited. Ten malformation subtypes were identified with the commonest being polymicrogyria (36%), pontocerebellar hypoplasia (14%), periventricular nodular heterotopia (11%), tubulinopathy (10%), lissencephaly (10%) and cortical dysplasia (9%). The overall diagnostic yield for the clinical singleton exome sequencing was 36%, which increased to 43% after research follow-up. The main source of increased diagnostic yield was the reanalysis of the singleton exome data to include newly discovered gene-disease associations. One additional diagnosis was made by trio exome sequencing. The highest phenotype-based diagnostic yields were for cobblestone malformation, tubulinopathy and lissencephaly and the lowest for cortical dysplasia and polymicrogyria. Pathogenic variants were identified in 32 genes, with variants in 6/32 genes occurring in more than one patient. The most frequent genetic diagnosis was pathogenic variants in TUBA1A. This study shows that over 40% of patients with common brain malformations have a genetic aetiology identified by exome sequencing. Periodic reanalysis of exome data to include newly identified genes was of greater value in increasing diagnostic yield than the expansion to trio exome. This study highlights the genetic and phenotypic heterogeneity of brain malformations, the importance of a multidisciplinary approach to diagnosis and the large number of patients that remain without a genetic diagnosis despite clinical exome sequencing and research reanalysis.

Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment. Inhibiting ß-adrenergic signalling could enhance ICI activity; however, blocking this pathway for this purpose has yielded conflicting results. The primary objective of this study was to evaluate the effect of beta-blocker use on overall survival and progression-free survival during ICI therapy. Methods A multicentric, retrospective, observational study was conducted in four Portuguese institutions. Patients with advanced non-small cell lung cancer treated with ICIs between January 2018 and December 2019 were included. Those using beta blockers for non-oncological reasons were compared with non-users. Results Among the 171 patients included, 36 concomitantly received beta blockers and ICIs. No significant increase was found in progression-free survival among patients who took ß-blockers (HR 0.74, 95% confidence interval (CI) 0.48-1.12, p = 0.151), and no statistically significant difference was found in overall survival. An apparent trend was observed towards better outcomes in the beta-blocker group, with a median overall survival of 9.93 months in the group not taking ß-blockers versus 14.90 months in the ß-blocker group (p = 0.291) and a median progression-free survival of 5.37 in the group not taking ß-blockers versus 10.87 months in the ß-blocker group (p = 0.151). Nine (25%) patients in the beta-blocker group and 16 (12%) in the non-beta-blocker group were progressive disease-free at the end of follow-up. This difference between the two groups is statistically significant (p = 0.047). Conclusion Our study found no statistically significant evidence that beta blockers enhance the effectiveness of immunotherapy. Using adrenergic blockade to modulate the immune system shows promise, warranting the need to develop prospective clinical studies.

A New Advancement in Germination Biotechnology of Purple Creole Corn: Bioactive Compounds and In Situ Enzyme Activity for Water-Soluble Extract and Pan Bread.

Germination is a simple and cost-effective technology that enhances the technological, sensory, and nutritional potential of grains, making them more attractive for use in the food industry. Germinating indigenous seeds is an alternative to increase noticeability and add value to these grains, which hold social and economic significance in the regions where they are cultivated, such as creole purple pericarp corn (PPCC) from the Couto Magalhães de Minas region in Brazil. This study aimed to optimize the germination parameters of time (24-96 h) and temperature (18-32 °C) for PPCC to produce water-soluble extracts and bread. Endogenous enzymes resulting from the germination process significantly enhanced (p < 0.10) the technological (total reducing sugars, total soluble solids, and soluble proteins) and biological properties (γ-aminobutyric acid, total soluble phenolic compounds, and antioxidant capacity) of the water-soluble extracts. The optimum point for obtaining the extracts was found to be at 85.3 h at 30.46 °C (with desirability of 90.42%), and this was statistically validated. The incorporation of germinated PPCC flours into bread was also promising (p < 0.10) and had a positive impact on the dough property (dough volume increase) and the final product, especially in terms of instrumental texture (springiness, cohesiveness, gumminess, chewiness, and resilience), resulting in a softer texture (lower firmness and hardness). The addition of PPCC flours did not alter instrumental color parameters, which may lead to greater consumer acceptance due to imperceptible differences in color to untrained individuals, with the optimized point at 96 h at 29.34 °C, with a desirability of 92.60%. Therefore, germinated PPCC shows promise for use as a base for obtaining water-soluble extracts and in bread as a replacement for commercial flour improvers, while also adding value to a raw material that is part of the local culture and agrobiodiversity.

Impact of COVID-19 on Unaccompanied Immigrant Minors and Families: Perspectives from Clinical Experts and Providers.

The number of unaccompanied immigrant minors (UIMs) and families from Central America seeking asylum in the U.S. continues to rise. This growth, combined with restrictive government policies, led to crowded and suboptimal conditions in Customs and Border Patrol and non-governmental organization facilities. COVID-19 further taxed facilities and exacerbated uncertainty surrounding length of detention, basic human rights, and family reunification. The current project features testimonies from the authors who work as clinical experts and providers in Texas - a top destination for Central American immigrants. In collaboration with a deputy director of a not-for-profit human rights organization, volunteer psychologists, and the director of a humanitarian respite center, we describe challenges faced by administrators and clinical staff in addressing the mental health needs of immigrant children and families during the COVID-19 pandemic. The primary themes identified were anti-immigrant policies that occurred concurrently with COVID-19; difficulty implementing COVID-19 protocols alongside scarcity of supplies and volunteers; increased mental health needs among UIMs and immigrant families; and challenges in UIM placement upon release from custody. Strategies for addressing clinical challenges in the near- and long-term and opportunities for improvement in care systems to immigrant youth, including correcting anti-immigrant policies, addressing ongoing COVID-19 protocols and challenges, meeting mental and physical health needs, facilitating release and reunification for unaccompanied immigrant minors, and maximizing youth resilience through trauma-informed interventions, are presented.

Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?

Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying peritoneal carcinomatosis is not clearly defined, but a clear preference for omental spread has been described. Growing evidence suggests that adipose tissue plays a role in promoting cancer onset and progression. Moreover, obesity can lead to changes in the original functions of adipocytes, resulting in metabolic and inflammatory changes in the adipose tissue microenvironment, potentially increasing the risk of tumor growth. However, the specific roles of adipocytes in ovarian cancer have not yet been fully elucidated. Due to the undeniable link between obesity and cancer, the adipose tissue microenvironment could also present a promising therapeutic target that warrants further research. This review discusses the complex relationship between ovarian cancer and the adipose tissue microenvironment.

A decolonial and liberation lens to social justice research: Upholding promises for diverse, inclusive, and equitable psychological science.

In the face of harmful disparities and inequities, it is crucial for researchers to critically reflect on methodologies and research practices that can dismantle systems of oppression, accommodate pluralistic realities, and facilitate opportunities for all communities to thrive. Historically, knowledge production for the sciences has followed a colonial and colonizing approach that continues to silence and decontextualize the lived experiences of people of color. This article acknowledges the harm to people of color communities in the name of research and draws from decolonial and liberation frameworks to advance research practices and psychological science toward equity and social justice. In this article, we propose a lens rooted in decolonial and liberatory principles that researchers can use to rethink and guide their scientific endeavors and collaborations toward more ethical, equitable, inclusive, respectful, and pluralistic research practices. The proposed lens draws on literature from community psychology and our lessons learned from field studies with historically marginalized Latinx communities to highlight six interrelated tensions that are important to address in psychological research from a decolonizing and liberatory lens. These interrelated tensions involve conflicting issues of (a) power, (b) competence, (c) practices and theories, (d) rationale, (e) approach, and (f) trust. In addition, seven practical recommendations and examples for decolonial and liberatory research practices are outlined. The recommendations can assist researchers in identifying ways to ameliorate and address the interrelated tensions to give way to decolonial and liberatory research practices. Community and social justice scientists have the responsibility to decommission oppressive research practices and engage in decolonization and liberation toward a valid, ethical, equitable, and inclusive psychological science. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Enrollment of Spanish-speaking Latinx adults in clinical trials: Five lessons learned from a randomized study in substance use treatment.

Latinx individuals are the largest ethnic minoritized group in the United States (US) at 19% of the population. However, they remain underrepresented in clinical research, accounting for less than 8% of clinical trial participants. Consideration of cultural values could help overcome barriers to inclusion in clinical trials and result in better recruitment and retention of Latinx individuals. In this commentary, we describe general guidance on culturally responsive modifications to facilitate the successful recruitment and retention of Spanish-speaking Latinx participants in Randomized Clinical Trials (RCTs) for substance use. We identify five culturally responsive strategies to help enroll participants in RCTs: 1. Create an ethnically diverse research team, 2. Assess available community partners, 3. Familiarize oneself with the target community, 4. Establish confianza (trust) with participants, and 5. Remain visible to participants and staff from recruitment sites. Representation of Latinx individuals in clinical trials is essential to ensure treatments are responsive to their needs and equitydriven. Some of these strategies can further research in helping to promote the participation of Latinx individuals experiencing substance use concerns, including outreach to those not seeking treatment.

Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer: A Clinical Case Involving Long-Term Survival.

Peritoneal metastasis is the most common pattern of synchronous and metachronous dissemination in gastric cancer (GC) and is associated with a poor prognosis. Even though systemic chemotherapy is the standard of care, the optimal therapeutic approach to peritoneal disease in this setting is yet to be defined. We present a case of a 26-year-old female diagnosed with locally advanced GC who developed peritoneal carcinomatosis (PC). The patient underwent cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC) with complete remission. She remained disease-free after six years, presenting with peritoneal recurrence 70 months after the procedure. This report describes a rare case of long-term survival following a controversial therapeutic approach.

Liderando juntos y revueltos: A collectivistic leadership approach to address Latinx immigrant health and psychological needs.

Psychologists are positioned to help address societal and public health crises in beneficial ways, including collectively working with public sectors to serve marginalized communities. This article highlights the relevance of helping to address societal and public health crises with collectivistic psychological leadership approaches and uses Latinx psychology leaders for addressing the current immigrant needs among Latinx communities. We draw attention to the domains needed for collectivistic psychological leadership that are culturally nuanced and equity, diversity, and inclusion-focused to advance the well-being of historically marginalized immigrant communities. Finally, the article highlights how our collectivistic approach operates in the public sector by describing the creation of the Latinx Immigrant Health Alliance (LIHA) and targeted outcomes. Briefly, the LIHA informally started in 2017 and was founded in 2020 to fill a gap in Latinx immigrant health at the heart of systemic inequalities during the global pandemic, explicit anti-immigrant rhetoric, and anti-Latinx policies. The LIHA aims to collectively work with community organizations to promote Latinx immigration health research, policy, education, training, and effective interventions. We include future directions and opportunities for collectivistic psychological leadership to address today's complex social issues. In particular, we call for the translation of psychological methods and other skills (e.g., research, clinical skills, policy, quantitative and qualitative methodology) into public action for better wellness of our communities, as well as the advancement of social justice, health equity, and inclusion for historically marginalized communities. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol.

The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Index cases will be randomized for their close contacts to participate in either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure. Registration: This trial is registered at ISCTRN (ISRCTN91602092).

An Exploratory Study of Healing Circles as a Strategy to Facilitate Resilience in an Undocumented Community.

Within the United States (U.S.), the COVID-19 pandemic highlighted critical inequalities affecting undocumented communities and resulting in particularly heightened stress for members of these communities. In addition to the stress associated to COVID-19, immigrants in the U.S. were more than ever subjected to a hostile anti-immigrant climate under Trump's administration. Given this compounded stress, the impact of the pandemic on mental health is likely to be disproportionately experienced by undocumented immigrants. In response, a group of psychologists partnered with a leading immigrant rights advocacy organization and formed a reciprocal collaboration to support undocumented communities. A major focus of the collaboration is to foster learning, supporting members of the immigrant community to contribute to their own well-being and others in the community. Accordingly, the collaborative developed and delivered a web-based mental health education session to the immigrant community and to practitioners serving this population. The session presented the use of healing circles as a strength-based approach to building resilience and also sought feedback regarding specific features of healing circles that can enhance their effectiveness in managing distress. Survey data and qualitative findings from this study show that those who participated in the web-based program perceived the session as validating and informative. Findings also underscored the need for creating safe spaces for community members to be vulnerable about their lived experiences while promoting ownership of their narratives. We discuss practical implications pertaining to the development and facilitation of social support groups for immigrants led by non-specialist community members trained for this role.

Dentro de los Estados Unidos (EE. UU.), la pandemia de COVID-19 acentuó desigualdades críticas que afectan a las comunidades indocumentadas, provocando un nivel de estrés particularmente alto entre los miembros de estas comunidades. Además del estrés asociado con el COVID-19, los inmigrantes en los EE. UU. estuvieron más que nunca sujetos a un clima antiinmigrante y hostil bajo la administración de Trump. Dado este estrés agravado, es probable que los inmigrantes indocumentados experimenten el impacto de la pandemia en su salud mental de manera desproporcionada. En respuesta, un grupo de psicólogos se unió a una organización líder en defensa de los derechos de los inmigrantes y formó una colaboración recíproca para apoyar a las comunidades indocumentadas. Un enfoque central de esta colaboración ha sido fomentar el aprendizaje, apoyando así a los miembros de la comunidad inmigrante para que contribuyan a su propio bienestar y al de los demás en la comunidad. Por consiguiente y a través de esta colaboración, se desarrolló y presentó una sesión de educación en línea sobre salud mental a la comunidad de inmigrantes, así como a los profesionales que sirven a esta comunidad. La sesión presentó el uso de círculos curativos como una estrategia basada en las capacidades para desarrollar la resiliencia y buscó también obtener retroalimentación sobre características específicas de estos círculos que puedan aumentar su efectividad en el manejo de la angustia. Los hallazgos de la encuesta y cualitativos de este estudio muestran que los participantes percibieron la sesión como validante e informativa. Los hallazgos también destacaron la necesidad de crear espacios seguros para que los miembros de la comunidad puedan ser vulnerables sobre sus experiencias vividas mientras se promueve la propiedad de sus narrativas. Discutimos las implicaciones prácticas relacionadas al desarrollo y la facilitación de grupos de apoyo social para inmigrantes dirigidos por miembros de la comunidad capacitados para asumir dicho rol.

The efficacy of neuromuscular training, with minimal or no equipment, on performance of youth athletes: A systematic review with meta-analysis.

OBJECTIVES: To investigate the effects of neuromuscular training, with minimal or no equipment, on physical performance of youth athletes. DESIGN: Systematic review with meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, PEDro and SportDiscuss from inception to March/2022. SELECTION CRITERIA: youth athletes (15-24years), from Olympic team sports; used neuromuscular training 2-3 times/week for, at least, 6 weeks; had a control group/usual training group; physical performance as outcomes; randomized controlled trial. DATA SYNTHESIS: Pooled estimate of standardized mean difference (SMD), and 95% confidence interval (95%CI). RESULTS: Thirty-four studies (1111 participants) were included. Results showed that neuromuscular training improved power (SMD: 0.84 [95%CI: 0.58, 1.10]; n = 805; I2 = 64%), speed (SMD: -1.12 [95%CI: -1.68, -0.57]; n = 688; I2 = 90%) and agility (SMD: -1.21 [95%CI: -1.60, -0.83]; n = 571; I2 = 76%) compared to control group, but showed no difference between groups for muscle strength (Quadriceps SMD: 0.34 [95%CI: -0.02, 0.69]; n = 132; I2 = 0%, Hamstrings: SMD: 0.64 [95%CI: -0.04, 1.33]; n = 132; I2 = 71%), balance and flexibility. CONCLUSION: Clinically, neuromuscular training with minimal equipment may be useful for teams with limited resources to improve mainly athletes' power and agility, including those interventions that were designed to injury prevention. Future high-quality studies are likely to change these estimates.

Australian healthcare professionals' perspectives on genetic counseling and genetic diagnosis in vascular anomalies.

Genomic technologies are now utilized for the genetic diagnosis of vascular anomalies. This provides the opportunity for genetic counselors to make a significant contribution to patient care for this complex disease. The aim of this study was to explore Australian healthcare professionals' perspectives on the relatively recent integration of molecular diagnostic testing for vascular anomalies, with or without genetic counseling support. Nine semi-structured interviews were conducted with Australian healthcare professionals involved in the provision of care for individuals with vascular anomalies. Thematic analysis identified six themes: (1) Molecular diagnosis is beneficial; (2) psychosocial needs can motivate families to pursue a molecular diagnosis; (3) molecular genetic testing for vascular anomalies is complex; (4) genetic service provision is not a one size fits all; (5) a client-centered approach for genetic service provision can go a long way; and (6) the value of genetic counselors. Based on our findings, implementation of a vascular anomalies genetic diagnostic program inclusive of genetic counseling may be challenging, yet such programs are likely to benefit both patients and their families, as well as healthcare professionals. As this paradigm shift unfolds, genetic counselors have an opportunity to contribute to the vascular anomaly field by educating healthcare professionals and patients, by participating in multidisciplinary clinics to support complex cases and by raising awareness regarding their practice and potential contributions.

Buscando la Calma Dentro de la Tormenta: A Brief Review of the Recent Literature on the Impact of Anti-Immigrant Rhetoric and Policies on Stress Among Latinx Immigrants.

The mental health burden associated with anti-immigrant rhetoric and ever-changing immigration policies is undeniable, though the psychological and emotional sequalae may remain invisible for years to come. Exclusionary immigration policies, as a form of structural racism, have also led to an epidemic of stress-related health within the Latinx community, particularly the Latinx immigrant community, across the United States. Recent examples of anti-Latinx and anti-immigrant rhetoric and policies include the 45th President's implementation of the Zero Tolerance policy, Migrant Protection Protocols, and Title 42. The recognition of previous and existing anti-immigrant policies, and the impact on Latinx immigrants, is critical in understanding the manifestation of psychological stress to prevent it from becoming chronic. For mental health providers, attention to existing policies that can be detrimental to the Latinx immigrant community is essential to understanding their mental health trajectory and applying frameworks that honor an individual's psychological stress to prevent pathologizing the immigrant experience and negative health outcomes. The objective of the present brief review is to shed light on recent research and offer recommendations for practice (eg, educating the Latinx community about the link between the immigrant experience and psychological stress) and policy (eg, drafting of legislation aimed at rescinding harmful immigration policies) regarding the relation between aggressive anti-immigration rhetoric and psychological stress among Latinx immigrants in the United States.

"It's fundamental to the work that we do": Genetic counselors' perceptions of their role in clients' mental well-being.

The role of a genetic counselor is to assist individuals and their families to comprehend and adapt to genetic information. However, a genetic counselor's role in clients' mental well-being is unclear. Mental well-being is an important component of overall health and it can be affected during the adaptation to genetic information. It is, therefore, essential to consider how mental well-being is viewed in genetic counseling practice. Our research aimed to investigate genetic counselors' perceptions of their role in clients' mental well-being. Our objectives were to (1) understand what genetic counselors perceived their role to be in clients' mental well-being and (2) investigate what factors influence genetic counselors' perceptions of practice. We recruited participants via advertisements in the Human Genetics Society of Australasia and the Australasian Society of Genetic Counselors newsletters, and through the Genetic Support Network of Victoria social media. We completed semi-structured in-depth interviews with 12 Australian genetic counselors and analyzed the interviews using inductive thematic analysis. We found that genetic counselors viewed clients' mental well-being as an important and crucial part of their practice. Three key themes were identified, first, all the participants' views of clients' mental well-being were shaped by personal and professional beliefs. Second, all participants noted that there were factors external to them, such as workplace and professional guidelines, which shaped their role in clients' mental well-being. Third, all those interviewed noted the boundaries of their professional role in clients' mental well-being. From these three themes, we determined that genetic counselors see clients' mental well-being as an integral part of their practice. Our findings add to the extant literature and can shape future practice in this field. Furthermore, we identified how future research priorities could further our knowledge in this area.

Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.

Synthesis and antimicrobial activity of molecular hybrids based on eugenol and chloramphenicol pharmacophores.

In the constant search for new pharmacological compounds, molecular hybridisation is a well-known technique whereby two or more known pharmacophoric subunits are combined to create a new "hybrid" compound. This hybrid is expected to maintain the characteristics of the original compounds whilst demonstrating improvements to their pharmacological action. Accordingly, we report here a series of molecular hybrid compounds based upon eugenol and chloramphenicol pharmacophores. The hybrid compounds were screened for their in vitro antimicrobial potential against Gram-negative and Gram-positive bacteria and also rapidly growing mycobacteria (RGM). The results highlight that the antimicrobial profiles of the hybrid compounds improve in a very clear fashion when moving through the series. The most prominent results were found when comparing the activity of the hybrid compounds against some of the multidrug-resistant clinical isolates of Pseudomonas aeruginosa, methicillin-resistant clinical isolates of Staphylococcus aureus (MRSA) and clinical isolates of rapidly growing mycobacteria.

Percepção de residentes de curso multiprofissional em saúde em relação à importância de cuidados odontológicos no hospital / Percepción de residentes de un curso multidisciplinario de salud sobre la importancia de la atención odontológica en el hospitalResumen / Perception of residents of a multiprofessionalresidency program in hospital care regarding the importance of oral careAbstract

O estudo objetivou conhecer a percepção de residentes multiprofissionais de um hospital público sobre a importância dos cuidados odontológicos no cenário hospitalar. Foi realizado um estudo do tipo transversal, observacional, descritivo com amostra por conveniência, composta por 63 residentes do Programa de Residência Multiprofissional Integral de Saúde Hospitalar (RIMUSH) do Hospital Universitário Lauro Wanderley. O instrumento de coleta de dados foi um questionário adaptado contendo sete perguntas. Para análise, os residentes foram divididos em dois grupos, o grupo 1 (G1) possui cirurgião-dentista (CD) na equipe multiprofissional e o grupo 2 (G2) não possui CD na equipe. A maioria dos residentes respondeu que avaliação odontológica nos pacientes hospitalizados é muito importante, que condições sistêmicas, medicações e condição de saúde bucal impactam na recuperação. Porém, os residentes do G1 compreenderam melhor as atribuições do CD na equipe, assim como quando indicar um pedido de consulta odontológica comparados aos do G2. Conclui-se que os residentes das demais áreas da saúde percebem a importância da Odontologia Hospitalar e que a presença do CD nas equipes de residência contribui para a capacitação desses profissionais, para a troca de saberes interprofissionais e para a promoção de assistência integral (AU).

El estudio tuvo como objetivo conocer la percepción de los residentes multidisciplinarios de un hospital público sobre la importancia de la atención odontológica en el ámbito hospitalario. Se realizó un estudio transversal, observacional, descriptivo, con una muestra de conveniencia, conformada por 63 residentes del Programa de Residencia Multiprofesional Integral en Salud Hospitalaria (RIMUSH) del Hospital Universitario Lauro Wanderley. El instrumento de recolección de datos fue un cuestionario adaptado que contenía siete preguntas. Para el análisis, los residentes fueron divididos en dos grupos, el grupo 1 (G1) tiene un cirujano dentista (CD) en el equipo multidisciplinario y el grupo 2 (G2) no tiene un dentista en el equipo. La mayoría de los residentes respondieron que la evaluación dental en pacientes hospitalizados es muy importante, que las condiciones sistémicas, los medicamentos y la condición de salud oral impactan en la recuperación. Sin embargo, los residentes de G1 entendieron mejor las funciones del CD en el equipo, así como cuándo indicar una solicitud de cita dental en comparación con G2. Los residentes de otras áreas de salud se dan cuenta de la importancia de la Odontología Hospitalaria y la presencia de CD en los equipos de residencia contribuye a la formación de estos profesionales, al intercambio de conocimientos interprofesionales y a la promoción de la atención integral (AU).

This study aimed to investigate the perception of multiprofessional residents of a public hospital about the importance of oral care in the hospital setting. A cross-sectional, observational study of descriptive design was conducted with a convenience sample, including 63 residents of the Multiprofessional Integrated Residency Program in Hospital Care (RIMUSH) at the University Hospital Lauro Wanderley. The instrument used for data collection was an adapted questionnaire containing seven questions. For the analysis, residents were divided into two groups: group 1 (G1) included a dental surgeon (DS) in the multiprofessional team, and group 2 (G2) did not include a DS in the team. Most residents answered that dental evaluation of hospitalized patients was very important, and that systemic conditions, medications and oral health had a significant impact on recovery. However, G1 residents had better understanding of the duties of the DS in the team and of timely referral of hospitalized patients for a dental consultation, compared to G2. Residents of other Health Care courses realize the importance of Hospital Dentistry and understand that the presence of DSs in residency teams is acontributing factor to the qualification of these professionals, exchange of interprofessional knowledge and promotion of comprehensive care (AU).

Applying an Antiracist Approach to Promoting Health Equity and Psychological Well-Being in Unaccompanied Immigrant Minors.

Unaccompanied immigrant minors (UIMs) are a fast-growing demographic in the United States, doubling in population since 2014.1 According to the Office of Refugee Resettlement, a UIM is someone under the age of 18 years who enters the United States without lawful status and an accompanying guardian.2 Most UIMs in the United States originate from the Central American northern triangle (ie, El Salvador, Guatemala, Honduras), with violence, extreme poverty, and family re-unification as the top 3 reasons for migration.1,3 Repeated exposure to stressful and/or traumatic events at home, during migration, and upon arrival increases UIMs' risk for psychological distress and mental disorders.3 UIMs' repeated encounters with race-based trauma (eg, racism, discrimination) further heightens this risk.3 The repercussions of these events are compounded by the fact that UIMs lack the adversity buffering effect that is traditionally associated with the presence of a caregiver.3 Furthermore, UIMs' mental health risk is augmented by their interaction with US systems (eg, legal, immigration, child welfare, educational, healthcare) with policies and practices that are discriminatory, are exclusionary, propagate the view of UIMs as racialized threats to society, and fail to consider their developmental context.3,4 Considering these risks, it is imperative to the well-being and positive development of UIMs that they have access to quality mental health services (MHS).