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.

The processes and outcomes related to 'family-centred care' in neuromotor and functional rehabilitation contexts for children with cerebral palsy: A scoping review.

OBJECTIVE: The aim of this study is to identify the main processes and outcomes related to family-centred care (FCC) in neuromotor and functional rehabilitation of preschool children with cerebral palsy (CP). BACKGROUND: FCC is considered a reference for best practices in child rehabilitation. CP is the most common cause of physical disability in childhood with repercussions on functionality. There is a gap in knowledge of the practical principles of FCC, and it is necessary to develop a reference model for the practice of child rehabilitation professionals. METHODS: In this scoping review, the main databases selected were as follows: LILACS; Pubmed; Embase; The Cochrane Library; CINAHL (EBSCO); Scopus; Web of Science; PEDro (Physiotherapy Evidence Database); Open Gray and other banks of thesis. The terms combined in the search strategy were as follows: 'Family-centered', 'Family-centred' and 'CP'. Inclusion criteria are as follows: studies on preschool-aged children with CP, undergoing family-centred functional therapeutic interventions (FCFTI) with outcomes on bodily structures and functions and/or activities and/or participation. RESULTS: The main participatory care methods identified were home intervention, environmental enrichment, collaborative realistic goal setting, planning of home-based activities and routine, child assessment feedback, family education/training, family coaching, encouraging discussion, observation of therapist and supervised practice. The main relational care qualities identified were as follows: respect, active listening, treat parents as equals, clear language, respect parents' ability to collaborate, demonstrate genuine care for the family, appreciate parents' knowledge and skills, demonstrate competence, experience and commitment. The main outcomes identified in children were improvement in motor and cognitive function and the child's functional ability. The main parentaloutcomes identified were empowerment, feeling of competence, self-confidence, motivation and engagement. CONCLUSION: The main differences in FCFTI programs refer to the parental education/guidance component and the amount of intervention carried out by parents. It is possible that the elements chosen by the therapist in a FCFTI depend on characteristics of the child and caregivers.

A systematic review of the perspectives of botulinum toxin use on the quality of life of neurological patients with drooling.

OBJECTIVE: To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life. MATERIALS AND METHODS: This systematic review was registered with the International Prospective Register of Systematic Reviews (CRD 42,023,435,242) and conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic search was performed in the PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and clinical trial databases until August 2023, no language restriction. Cohort studies and randomized clinical trials of patients diagnosed with drooling and neurological impairment who used botulinum toxin on the salivary gland were included, which evaluated subjective quality of life parameters. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and Risk of Bias 2 tools. The certainty of the evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Eight studies involving 317 patients were included. All studies, through subjective parameters, suggested the effectiveness of botulinum toxin in reducing drooling, resulting in an improvement in the quality of life. Three studies demonstrated improvements in swallowing and four in cases of respiratory diseases. Two clinical trials had a high risk of bias, whereas one had low risk. The five cohort studies that were evaluated had a high risk of bias. The certainty of the evidence was considered low. CONCLUSIONS: Based on the patient/caregivers' perception of improvement in drooling, dysphagia, and respiratory symptoms, it can be inferred that botulinum toxin application reduces subjective drooling in neurologically compromised patients. Its impact contributes to the general well-being and quality of life. CLINICAL RELEVANCE: Injection of botulinum toxin into the salivary glands can be considered an alternative technique to surgical or medicinal approaches in reducing drooling. It is effective, less invasive and without significant side effects. It promotes a positive impact on the well-being and quality of life of neurological patients.

Aryl Hydrocarbon Receptor as a Therapeutical Target of Environmentally Induced Skin Conditions.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, expressed in several tissues and involved in the response to environmental stressors. Studies have already associated exposure to environmental factors, such as organic air pollutants, products of the skin microbiota, and solar radiation, with the development/worsening of skin conditions, mediated by AhR. On the other hand, recent studies have shown that synthetic and natural compounds are able to modulate the activation of some AhR signaling pathways, minimizing the harmful response of these environmental stressors in the skin. Thus, AhR constitutes a new therapeutic target for the prevention or treatment of skin conditions induced by the skin exposome. Herein, an overview of potential AhR ligands and their biologic effects in environmentally induced skin conditions are presented. The literature survey pointed out divergences in the mechanism of action from a therapeutic perspective. Although most studies point to the benefits of ligand downregulation of AhR signaling, counteracting the toxic effects of environmental factors on the skin, some studies suggest the AhR ligand activation as a therapeutical mechanism for some skin conditions. Furthermore, both agonist and antagonist profiles were identified in the AhR modulation by the synthetic and natural compounds raised. Despite that, this target is still little explored, and further studies are needed to elucidate the molecular mechanisms involved and identify new AhR ligands with therapeutic potential. SIGNIFICANCE STATEMENT: The aryl hydrocarbon receptor (AhR) is involved in different skin physiological and pathological processes, including toxic mechanisms of environmental factors. Synthetic and natural AhR ligands have demonstrated therapeutic potential for skin conditions induced by these agents. Thus, a comprehensive understanding of the skin toxicity mechanisms involving the AhR, as well as the use of AhR modulators from a therapeutic perspective, provides an alternative approach to the development of new treatments for skin disorders induced by the exposome.

Exome sequencing for patients with developmental and epileptic encephalopathies in clinical practice.

AIM: To assess the clinical utility of exome sequencing for patients with developmental and epileptic encephalopathies (DEEs). METHOD: Over 2 years, patients with DEEs were recruited for singleton exome sequencing. Parental segregation was performed where indicated. RESULTS: Of the 103 patients recruited (54 males, 49 females; aged 2 weeks-17 years), the genetic aetiology was identified in 36 out of 103 (35%) with management implications in 13 out of 36. Exome sequencing revealed pathogenic or likely pathogenic variants in 30 out of 103 (29%) patients, variants of unknown significance in 39 out of 103 (38%), and 34 out of 103 (33%) were negative on exome analysis. After the description of new genetic diseases, a molecular diagnosis was subsequently made for six patients or through newly available high-density chromosomal microarray testing. INTERPRETATION: We demonstrate the utility of exome sequencing in routine clinical care of children with DEEs. We highlight that molecular diagnosis often leads to changes in management and informs accurate prognostic and reproductive counselling. Our findings reinforce the need for ongoing analysis of genomic data to identify the aetiology in patients in whom the cause is unknown. The implementation of genomic testing in the care of children with DEEs should become routine in clinical practice. WHAT THIS PAPER ADDS: The cause was identified in 35% of patients with developmental and epileptic encephalopathies. KCNQ2, CDKL5, SCN1A, and STXBP1 were the most frequently identified genes. Reanalysis of genomic data found the cause in an additional six patients. Genetic aetiology was identified in 41% of children with seizure onset under 2 years, compared to 18% with older onset. Finding the molecular cause led to management changes in 36% of patients with DEEs.

Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria's Undiagnosed Diseases Program.

BACKGROUND: Clinical exome sequencing typically achieves diagnostic yields of 30%-57.5% in individuals with monogenic rare diseases. Undiagnosed diseases programmes implement strategies to improve diagnostic outcomes for these individuals. AIM: We share the lessons learnt from the first 3 years of the Undiagnosed Diseases Program-Victoria, an Australian programme embedded within a clinical genetics service in the state of Victoria with a focus on paediatric rare diseases. METHODS: We enrolled families who remained without a diagnosis after clinical genomic (panel, exome or genome) sequencing between 2016 and 2018. We used family-based exome sequencing (family ES), family-based genome sequencing (family GS), RNA sequencing (RNA-seq) and high-resolution chromosomal microarray (CMA) with research-based analysis. RESULTS: In 150 families, we achieved a diagnosis or strong candidate in 64 (42.7%) (37 in known genes with a consistent phenotype, 3 in known genes with a novel phenotype and 24 in novel disease genes). Fifty-four diagnoses or strong candidates were made by family ES, six by family GS with RNA-seq, two by high-resolution CMA and two by data reanalysis. CONCLUSION: We share our lessons learnt from the programme. Flexible implementation of multiple strategies allowed for scalability and response to the availability of new technologies. Broad implementation of family ES with research-based analysis showed promising yields post a negative clinical singleton ES. RNA-seq offered multiple benefits in family ES-negative populations. International data sharing strategies were critical in facilitating collaborations to establish novel disease-gene associations. Finally, the integrated approach of a multiskilled, multidisciplinary team was fundamental to having diverse perspectives and strategic decision-making.

"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.

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.

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.

Screening for Severe Acute Respiratory Syndrome Coronavirus 2 in Close Contacts of Individuals With Confirmed Infection: Performance and Operational Considerations.

BACKGROUND: Point-of-care and decentralized testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies. METHODS: A prospective diagnostic accuracy study was conducted among close contacts of coronavirus disease 2019 (COVID-19) cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and 1 molecular method were evaluated for usability and performance against reference reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens. RESULTS: Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during ≥1 visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta variants emerged increasingly during implementation. The overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and those with cycle threshold (Ct) values <34 and lower among oligosymptomatic or asymptomatic cases. Assuming a 24-hour time to results for RT-PCR, the cumulative sensitivity of an anterior nares swab rapid antigen test was >70% and almost 90% after 4 days. CONCLUSIONS: The near-immediate time to results for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

Computer-based training for cognitive behavioral therapy for Spanish-speaking substance users: adaptation and satisfaction.

There are few available culturally and linguistically adapted behavioral health interventions for substance use among Spanish-speaking adults. The authors describe the cultural adaptation of an innovative computer-based training for cognitive behavioral therapy program (CBT4CBT). Based in cognitive-behavioral skills training, CBT4CBT utilizes a telenovela to teach monolingual Spanish-speaking adults who have migrated to the United States to recognize triggers; avoid these situations; and cope more effectively with the consequences of substance use. Participants endorsed high levels of satisfaction with the program content and found the material to be easy to understand and relevant to their life experiences.

Religiosity and Spirituality in Latinx Individuals with Substance Use Disorders: Association with Treatment Outcomes in a Randomized Clinical Trial.

Although many studies have examined religiosity as a protective factor for substance use, few have considered its relationship to treatment outcomes among Latinx adults. Using data from 89 individuals participating in a randomized clinical trial evaluating a culturally adapted Spanish-language version of web-based cognitive behavioral therapy (CBT4CBT-Spanish) for substance use, we evaluated the relationship between religiosity, as measured by the Religious Background and Behavior questionnaire, and treatment outcomes. Overall, there were few significant correlations between religiosity scores and treatment outcomes. Past-year religiosity was positively correlated with one measure of abstinence for those randomized to CBT4CBT-Spanish, but this did not persist during a six-month follow-up period. Findings suggest that religiosity may be associated with short-term abstinence outcomes among Latinx adults receiving a culturally adapted cognitive behavioral therapy treatment. However, additional research is needed with larger and more heterogenous Latinx populations.

Diagnostic reference levels for fluoroscopically guided procedures in a South African tertiary hospital.

BACKGROUND: The burgeoning usage and complexity of fluoroscopically guided procedures (FGPs) contribute to extended examination times and increased risk of adverse radiation effects. Diagnostic reference levels (DRLs) play a pivotal role in dose optimization. There are limited DRL data for FGPs in low- and middle-income countries (LMICs). PURPOSE: To determine local DRLs (LDRLs) for common FGPs in the South African (SA) context and compare these with published international data. MATERIAL AND METHODS: A three-year, retrospective study of the 15 most frequently performed FGPs at a SA institution. For each procedure, the 50th and 75th percentiles of kerma area product (KAP), reference point air kerma (Ka,r), and fluoroscopy time data were derived. Published international FGP DRL data were collated and compared with the 75th percentiles of local institutional dosage parameters. RESULTS: The commonest FGPs were aorto-bifemoral diagnostic angiography (n = 590), aorto-bifemoral interventional angiography (n = 287), nephrostomy (n = 265), and bronchial arterial embolization (BAE) (n = 208). Selective abdominal vessel interventional angiography (KAP = 170 Gy . cm2; Ka,r = 877 mGy) recorded the highest LDRL dosages; BAE was the longest procedure (LDRL = 38 min). Nephrostomies achieved the lowest LDRLs across all parameters (KAP = 10 Gy . cm2; Ka,r = 63 mGy, fluoroscopy time = 4.3 min). All Tygerberg Hospital LDRLs with comprehensive comparable data were within or below published ranges. CONCLUSION: This study advances international radiation protection initiatives, addresses the paucity of LMIC DRL data, demonstrates broad alignment of Tygerberg Hospital FGP practice with international norms and highlights areas for optimization of institutional practice.

Después de la tormenta: Collective trauma following Hurricane Maria in a northeastern Puerto Rican community in the United States.

Hurricane Maria was the largest disaster in Puerto Rico's history, affecting Puerto Rican communities throughout the United States. We conducted focus groups using a grounded theory approach with adults displaced from Puerto Rico to a northeastern community 12 (n = 5) and 17 months (n = 7) postdisaster. Key informant interviews were also conducted with nine community advocates working with displaced hurricane survivors. Emerging themes reflect narrative and social identity processes following collective trauma. Findings emphasize the need for timely and long-term disaster responses that build on community strengths without leaving communities to cope on their own. We discuss how incorporating group storytelling in postdisaster research is a culturally sensitive practice that can promote resiliency among survivors.

Parental experiences of ultrarapid genomic testing for their critically unwell infants and children.

PURPOSE: To explore parental experiences of ultrarapid genomic testing for their critically unwell infants and children. METHODS: Parents of critically unwell children who participated in a national ultrarapid genomic diagnosis program were surveyed >12 weeks after genomic results return. Surveys consisted of custom questions and validated scales, including the Decision Regret Scale and Genomics Outcome Scale. RESULTS: With 96 survey invitations sent, the response rate was 57% (n = 55). Most parents reported receiving enough information during pretest (n = 50, 94%) and post-test (n = 44, 83%) counseling. Perceptions varied regarding benefits of testing, however most parents reported no or mild decision regret (n = 45, 82%). The majority of parents (31/52, 60%) were extremely concerned about the condition recurring in future children, regardless of actual or perceived recurrence risk. Parents whose child received a diagnostic result reported higher empowerment. CONCLUSION: This study provides valuable insight into parental experiences of ultrarapid genomic testing in critically unwell children, including decision regret, empowerment, and post-test reproductive planning, to inform design and delivery of rapid diagnosis programs. The findings suggest considerations for pre- and post-test counseling that may influence parental experiences during the testing process and beyond, such as the importance of realistically conveying the likelihood for clinical and/or personal utility.

Intake of selected foods and beverages and serum uric acid levels in adults: ELSA-Brasil (2008-2010).

OBJECTIVE: To investigate the association between the intake of selected food groups and beverages and serum uric acid (UA). DESIGN: Cross-sectional study using the baseline data (2008-2010) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Food intake was assessed by food frequency questionnaire with 114 items. Linear and logistic regressions investigated the associations between the daily intake of each food group (servings/d) and UA (mg/dl) and hyperuricemia (UA ≥ 6·8 mg/dl), respectively. All the analyses were adjusted for potential confounders, energy intake and all food groups. SETTING: Teaching and research institutions from six Brazilians states. SUBJECTS: The participants were 14 320 active and retired civil servants, aged 35-74 years. RESULTS: Higher intake of dairy products was associated with lower serum UA levels in both sexes, with a statistical dose-response gradient. High meat intake was associated with high UA only in women, and high intake of organ meats, in men. Intake of fish and fruits, vegetables and legumes were not associated with serum UA. In men, moderate and high intake of alcoholic beverages, specifically beer and spirits, but not wine, increased UA. In women, only high intake of alcoholic beverages, specifically beer, was associated with increased serum UA. Similar associations were seen for hyperuricemia. CONCLUSIONS: Results suggest a potential beneficial role of dairy products consumption on UA levels. The association between alcohol intake and UA differed according to type of beverage and between sexes. Results reinforce the need to consider the whole diet in the analysis and to conduct sex stratified analysis.

Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System.

Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems. Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. Exposures: Ultra-rapid exome sequencing. Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%). Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

The Ex Vivo Skin Model as an Alternative Tool for the Efficacy and Safety Evaluation of Topical Products.

The development of alternative approaches for safety and efficacy testing that avoid the use of animals is a worldwide trend, which relies on the improvement of current models and tools so that they better reproduce human biology. Human skin from elective plastic surgery is a promising experimental model to test the effects of topically applied products. As the structure of native skin is maintained, including cell population (keratinocytes, melanocytes, Langerhans cells and fibroblasts) and dermal matrix (containing collagen, elastin, glycosaminoglycans, etc.), it most closely matches the effects of substances on in vivo human skin. In this review, we present a collection of results that our group has generated over the last years, involving the use of human skin and scalp explants, demonstrating the feasibility of this model. The development of a test system with ex vivo skin explants, of standard size and thickness, and cultured at the air-liquid interface, can provide an important tool for understanding the mechanisms involved in several cutaneous disorders.

Impact of the Petrochemical Complex on the Air Quality of an Urban Area in the City of Rio de Janeiro, Brazil.

In the city of Rio de Janeiro (Brazil), the districts located in the northern area are considered the most critical regarding ozone levels year-round. In this study, the potential factors that contribute to high levels of ozone in the district of Irajá were investigated. The obtained results clearly showed that, in spite of the high correlation of ozone concentrations with wind speed and temperature, ozone episodes depend on the ratios of volatile organic compounds (VOCs) to nitrogen oxides (NOx) rather than on the individual VOC and NOx levels, as expected for the VOC-controlled condition typical of the urban area of Rio de Janeiro. Moreover, high VOCs/NOx ratios are highly dependent on the transport of air masses. When pollutants are transported from urban areas with heavy vehicular flux and high NOx concentrations, ozone levels are reduced. When air masses are transported from the industrial petrochemical area, NOx levels are relatively low, and ozone episodes are frequent.

Two sporulated Bacillus enhance immunity in Galleria mellonella protecting against Candida albicans.

The aim of this study was to evaluate the effects of Bacillus subtilis and Bacillus atrophaeus on Galleria mellonella immunity challenged by Candida albicans. Firstly, we analyzed the susceptibility of G. mellonella to bacilli (vegetative and sporulating forms). It was found that both vegetative and sporulating forms were not pathogenic to G. mellonella at a concentration of 1 × 104 cells/larva. Next, larvae were pretreated with two species of Bacillus, in the vegetative and sporulating forms, and then challenged with C. albicans. In addition, the gene expression of antimicrobial peptides (AMPs) such as Gallerimycin, Gloverin, Cecropin-D and Galiomicin was investigated. Survival rates increased in the Bacillus treated larvae compared with control larvae inoculated with C. albicans only. Cells and spores of Bacillus spp. upregulated Gloverin, Galiomicin and Gallerimycin genes in relation to the control group (PBS + PBS). When these larvae were infected with C. albicans, the group pretreated with spores of B. atrophaeus and B. subtilis showed a greater increase in expression of Galiomycin (49.08-fold and 13.50-fold) and Gallerimycin (27.88-fold and 68.15-fold), respectively, compared to the group infected with C. albicans only (p = 0.0001). After that, we investigated the effects of B. subtilis and B. atrophaeus on immune system of G. mellonella evaluating the number of hemocytes, quantification of melanization, cocoon formation and colony forming units (CFU) count. Hemocyte count increased in response to stimulation by Bacillus, and a higher increase was achieved when larvae were inoculated with B. subtilis spores (p = 0.0011). In the melanization assay, all groups tested demonstrated lower production of melanin compared to that in the phosphate-buffered saline (PBS) group. In addition, full cocoon formation was observed in all groups analyzed, which corresponded to a healthier wax worm. Hemolymph culture revealed higher growth of B. atrophaeus and B. subtilis in the groups inoculated with spores. We concluded that spores and cells of B. atrophaeus and B. subtilis stimulated the immune system of G. mellonella larvae and protected them of C. albicans infection.