Public Health Response to Clusters of Rapid HIV Transmission Among Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex with Men - Metropolitan Atlanta, Georgia, 2021-2022.

During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data,† medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs.

Attitudes and Beliefs About HIV Treatment as Prevention Among People Who are Not Engaged in HIV Care, 2018-2019.

Treatment as prevention (TasP) is an effective HIV prevention strategy. Our objectives were to explore TasP attitudes and beliefs among people with HIV (PWH) who are not engaged in care and to examine attitudes and beliefs by selected characteristics. We sampled PWH who had participated in the Medical Monitoring Project (MMP), a structured interview survey, from June 2018-May 2019 to participate in 60-minute semi-structured telephone interviews. We obtained sociodemographic and behavioral quantitative data from the MMP structured interview. We used applied thematic analysis to analyze the qualitative data and integrated the qualitative and quantitative data during analysis. Negative attitudes and beliefs, especially skepticism and mistrust, about TasP were pervasive. Only one participant who identified as female, was not sexually active, and had not heard of TasP held positive attitudes and beliefs about TasP. TasP messages should use clear and unambiguous language, address mistrust, and reach people who are not engaged in medical care.

Barriers and Facilitators to HIV Service Access among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in Metropolitan Atlanta-a Qualitative Analysis.

Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.

Expression of acid-labile subunit (ALS) in developing and adult zebrafish and its role in dorso-ventral patterning during development.

Mammalian acid-labile subunit (ALS) is a serum protein that binds binary complexes between Insulin-like growth factors (IGFs) and Insulin-like growth factor-binding proteins (IGFBPs) extending their half-life and keeping them in the vasculature. Human ALS deficiency (ACLSD), due to homozygous or compound heterozygous mutations in IGFALS, leads to moderate short stature with reduced levels of IGF-I and IGFBP-3. There is only one corresponding zebrafish ortholog gene and it has not yet been studied. In this study we elucidate the role of igfals during zebrafish development. In zebrafish embryos igfals mRNA is expressed throughout development, mainly in the brain and subsequently also in the gut and swimbladder. To determine its role during development, we knocked down igfals gene product using morpholinos (MOs). Igfals morphant embryos displayed dorsalization in different degrees of severity, including a shortened trunk and loss of tail. Furthermore, co-injection of human IGFALS (hIGFALS) mRNA was able to rescue the MO-induced phenotype. Finally, overexpression of either hIGFALS or zebrafish igfals (zigfals) mRNA leads to ventralization of embryos including a reduced head and enlarged tail. These findings suggest that als plays an important role in dorso-ventral patterning during zebrafish development.

Characterization of four Latin American families confirms previous findings and reveals novel features of acid-labile subunit deficiency.

OBJECTIVE: Acid-labile subunit deficiency (ACLSD), caused by inactivating mutations in both IGFALS gene alleles, is characterized by marked reduction in IGF-I and IGFBP-3 levels associated with mild growth retardation. The aim of this study was to expand the known phenotype and genetic characteristics of ACLSD by reporting data from four index cases and their families. DESIGN: Auxological data, biochemical and genetic studies were performed in four children diagnosed with ACLSD and all available relatives. METHODS: Serum levels of IGF-I, IGFBP-3, acid-labile subunit (ALS), and in vitro ternary complex formation (ivTCF) were determined. After sequencing the IGFALS gene, pathogenicity of novel identified variants was evaluated by in vitro expression in transfected Chinese hamster ovarian (CHO) cells. ALS protein was detected in patients' sera and CHO cells conditioned media and lysates by Western immunoblot (WIB). RESULTS: Four index cases and four relatives were diagnosed with ACLSD. The following variants were found: p.Glu35Glyfs*17, p.Glu35Lysfs*87, p.Leu213Phe, p.Asn276Ser, p.Leu409Phe, p.Ala475Val and p.Ser490Trp. ACLSD patients presented low IGF-I and low or undetectable levels of IGFBP-3 and ALS. Seven out of 8 patients did not form ivTCF. CONCLUSIONS: This study confirms previous findings in ACLSD, such as the low IGF-I and a more severe reduction in IGFBP-3 levels, and a gene dosage effect observed in heterozygous carriers (HC). In addition, father-to-son transmission (father compound heterozygous and mother HC), preservation of male fertility, and marginal ALS expression with potential involvement in preserved responsiveness to rhGH treatment, are all novel aspects, not previously reported in this condition.

The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.

Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits.

The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H2S/KATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H2S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H2S/KATP channel pathways, possibly through direct activation of NOS and CSE.

Racial Differences in Social Determinants of Health and Outcomes Among Hispanic/Latino Persons with HIV-United States, 2015-2020.

BACKGROUND: Hispanic/Latino people with HIV (PWH) experience disparities in health outcomes compared with other racial and ethnic groups. Disaggregated data based on race for Hispanic/Latino PWH in the United States are rarely reported, potentially masking inequities. METHODS: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV. We used weighted interview and medical record data collected from June 2015-May 2021 to examine differences in social determinants of health (SDH) and health outcomes by self-reported race among Hispanic/Latino adults with diagnosed HIV. RESULTS: Compared with White Hispanic/Latino PWH, Black Hispanic/Latino PWH were more likely to be unemployed (PR, 1.4; CI, 1.2-1.8), have a disability (PR, 1.3; CI, 1.2-1.5), have experienced homelessness (PR, 1.8; CI, 1.2-2.6), and have been incarcerated (PR, 2.6; CI, 1.5-4.5). American Indian/Alaska Native (AI/AN) (PR, 1.8; CI, 1.1-2.7) and multiracial (PR, 2.0; CI, 1.4-2.9) Hispanic/Latino PWH were more likely to have experienced homelessness than White Hispanic/Latino PWH. Black (PR, 1.3; CI, 1.2-1.5) and multiracial (PR, 1.2; CI, 1.1-1.5) Hispanic/Latino PWH were more likely to be virally unsuppressed than White Hispanic/Latino PWH. CONCLUSION: Black, multiracial, and AI/AN Hispanic/Latino PWH experience disparities in SDH and HIV outcomes. Lumping Hispanic/Latino people into one racial and ethnic category obscures health disparities, which might limit our progress towards reaching national HIV goals. Future studies should consider disaggregating by other factors such as Hispanic origin, place of birth, immigration status, and primary language. Doing so recognizes the diversity of the Hispanic/Latino population.

Characterization of Three Cases of Primary Hypogalactia in Jalisco, Mexico.

INTRODUCTION: Human lactation should be taken into account as an important issue for the international agenda. Despite advances in lactation information and knowledge, insufficient milk production is still a concern for mothers and health practitioners, including International Board Certified Lactation Consultants and others. Primary hypogalactia, or insufficient milk production is uncommon, but should be considered when there is poor weight gain and decreased urine output in infants despite good latch-on and suckling, or anatomic differences in the physical exam of the lactating breast. MAIN ISSUE: This case series presents three cases illustrating insufficient milk production resulting in infants who experienced significant dehydration and poor weight gain. MANAGEMENT: Primary hypoplasia was diagnosed by means of a thorough interview and physical examination that entailed a consultation with a physician who was also an International Board Certified Lactation Consultant. CONCLUSION: Awareness of an infant's feeding needs and proper evaluation of a child's health status is paramount if health care providers are to identify the important factors contributing to breastfeeding problems. In some instances, breastfeeding goals cannot be achieved, and then the provider's role becomes support in coming to terms with persistent insufficient milk production, and coordinating appropriate supplementation to meet each baby's nutritional needs.

Healthcare-Associated Infections: Pre- and Post-pandemic Microbiological Profile and Antibiotic Resistance.

BACKGROUND: In recent years, healthcare-associated infections (HAIs) have been a priority topic for global institutions such as the World Health Organization because, during the COVID-19 pandemic, the role of HAIs as co-morbidity in infected patients was evident. HAIs can cause disability and mortality and lead to excessive healthcare costs. This work aims to calculate the prevalence of HAIs from 2019 to 2023 to determine their microbiological profile and antibiotic resistance. METHODS: A cross-sectional design was used for this study. To describe the population, univariate analysis, measures of central tendency, frequencies, and proportions were used. RESULTS: The present study included 3,936 HAI notifications, which showed a significant decrease in their number during the COVID-19 pandemic, especially in 2020. In 2021 and 2022, the numbers increased rapidly to around 30%. The most prevalent HAI type was ventilator-associated pneumonia, which had the highest prevalence in 2020. Regarding microorganism isolation, percentages increased after 2020 from 46% to 67%, with Acinetobacter baumannnii beingthe most frequent during and after pandemics. The microbiological profile showed multidrug resistance in several microorganisms. CONCLUSIONS: HAIs are a global health concern. The number of cases has been increasing since the COVID-19 pandemic with regard to the multidrug-resistant microorganism. HAIs have an important impact on the quality of life, morbidity, mortality, and financial concerns for health services. Global strategies should be adapted for different regions, since the panaroma in developed countries allows for programs to be established for the prevention and control of HAIs in a better way than in low-income countries that lack adequate infrastructure and resources.

Novel Insulin-Like Growth Factor 1 Gene Mutation: Broadening of the Phenotype and Implications for Insulin Resistance.

CONTEXT: Insulin-like growth factor (IGF)1 gene mutations are extremely rare causes of pre- and postnatal growth retardation. Phenotype can be heterogenous with varying degrees of neurosensory deafness, cognitive defects, glucose metabolism impairment and short stature. OBJECTIVE: This study describes a 12.6-year-old girl presenting with severe short stature and insulin resistance, but with normal hearing and neurological development at the lower limit of normal. METHODS: DNA was obtained from the proband and both parents for whole exome sequencing (WES). In silico analysis was performed to predict the impact of the IGF1 variant on IGF1 and insulin receptors (IGF1R and IR) signaling. Phosphorylation of the IGF1R at activating Tyr residues and cell proliferation analyses were used to assess the ability of each subject's IGF1 to bind and activate IGF1R. RESULTS: The proband had low immunoreactive IGF1 in serum and WES revealed a novel homozygous IGF1 missense variant (c.247A>T), causing a change of serine 83 for cysteine (p.Ser83Cys; p.Ser35Cys in mature peptide). The proband's parents were heterozygous for this mutation. In silico analyses indicated the pathogenic potential of the variant with electrostatic variations with the potential of hampering the interaction with the IGF1R but strengthening the binding to IR. The mutant IGF1 protein had a significantly reduced activity on in vitro bioassays. CONCLUSION: We describe a novel IGF1 mutation leading to severe loss of circulating IGF1 immunoreactivity and bioactivity. In silico modeling predicts that the mutant IGF1 could interfere with IR signaling, providing a possible explanation for the severe insulin resistance observed in the patient. The absence of significant hearing and neurodevelopmental involvement in the present case is unusual and broadens the clinical spectrum of IGF1 mutations.

Frequency of urinary pesticides in children: a scoping review.

Pesticides are any mix of ingredients and substances used to eliminate or control unwanted vegetable or animal species recognized as plagues. Its use has been discussed in research due to the scarcity of strong scientific evidence about its health effects. International literature is still insufficient to establish a global recommendation through public policy. This study aims to explore international evidence of the presence of pesticides in urine samples from children and their effects on health through a scoping review based on the methodology described by Arksey and O'Malley. The number of articles resulting from the keyword combination was 454, and a total of 93 manuscripts were included in the results and 22 were complementary. Keywords included in the search were: urinary, pesticide, children, and childhood. Children are exposed to pesticide residues through a fruit and vegetable intake environment and household insecticide use. Behavioral effects of neural damage, diabetes, obesity, and pulmonary function are health outcomes for children that are commonly studied. Gas and liquid chromatography-tandem mass spectrometry methods are used predominantly for metabolite-pesticide detection in urine samples. Dialkylphosphates (DAP) are common in organophosphate (OP) metabolite studies. First-morning spot samples are recommended to most accurately characterize OP dose in children. International evidence in PubMed supports that organic diets in children are successful interventions that decrease the urinary levels of pesticides. Several urinary pesticide studies were found throughout the world's population. However, there is a knowledge gap that is important to address (public policy), due to farming activities that are predominant in these territories.

Non-traditional risk factors of progression of chronic kidney disease in adult population: a scoping review.

Chronic kidney disease (CKD) has become a public health concern over the last several years. Nowadays developed countries spend around 3% of their annual health-care budget on patients with CKD. According to the scientific community the most remarkable risk factors for CKD are diabetes and hypertension. Unknown CKD etiology has been reported as a global phenomenon including uncommon risk factors such as: dehydration, leptospirosis, heat stress, water quality, and others. This study aims to report non-traditional risk factors for ESRD based on a scoping review methodology. The scoping review methodology described by Arksey and O'Malley was used by performing an extensive review of the information. A total of 46 manuscripts were reviewed. The non-traditional ESRD risk factors are depicted based on six categories. Gender and ethnicity have been considered as risk factors for ESRD. Erythematous systemic lupus (ESL) is reported as an important risk factor for ESRD. Pesticide use has been an significant risk factor due to its effects on human and environmental health. Some compounds commonly used in homes against insects and plants are related to ESRD. Congenital and hereditary diseases in the urinary tract have been studied as a cause of ESRD in children and young adults. End-stage renal disease is a major concern for public health on a global level. As it can be seen, non-traditional risk factors are several and have different etiologies. It is necessary to put the issue on the table and add it to the public agenda in order to find multidisciplinary solutions.

Securing access to a comprehensive diagnostic panel for children with suspected acute lymphoblastic leukemia: Results from the Mexico in Alliance with St. Jude "Bridge Project".

Background: The "Bridge Project" is a Mexico in Alliance with St. Jude (MAS) initiative developed in 2019 to improve access, accuracy, and timeliness of specialized diagnostic studies for patients with suspected acute lymphoblastic leukemia (ALL). The project strategy relies on service centralization to improve service delivery, biological characterization, risk-group classification, and support proper treatment allocation. Methods: This is an ongoing prospective multisite intersectoral quality improvement (QI) project available to all patients 0-18 years of age presenting with suspected ALL to the 14 actively participating institutions in 12 Mexican states. Institutions send specimens to one centralized laboratory. From a clinical standpoint, the project secures access to a consensus-derived comprehensive diagnostic panel. From a service delivery standpoint, we assess equity, timeliness, effectiveness, and patient-centeredness. From an implementation science standpoint, we document feasibility, utility, and appropriateness of the diagnostic panel and centralized approach. This analysis spans from July 2019 to June 2023. Results: 612 patients have accessed the project. The median age was 6 years (IQR 3-11), and 53% were males. 94% of the specimens arrived within 48 hours, which documents the feasibility of the centralized model, and 100% of the patients received precise and timely diagnostic results, which documents the effectiveness of the approach. Of 505 (82.5%) patients with confirmed ALL, 463/505 (91.6%) had B-cell ALL, and 42/505 (8.3%) had T-cell ALL. High-hyperdiploidy was detected by DNA index in 36.6% and hypodiploidy in 1.6%. 76.6% of the patients had conclusive karyotype results. FISH studies showed t(12;21) in 15%, iAMP21 in 8.5%, t(1;19) in 7.5%, t(4;11) in 4.2%, t(9;22) in 3.2%, del(9)(p21) in 1.8%, and TRA/D (14)(q11.2) rearrangement in 2.4%. Among B-cell ALL patients, 344/403 (85.1%) had Day 15 MRD<1% and 261/305 (85.6%) Day 84 MRD<0.01. For T-cell ALL patients 20/28 (71.4%) had Day 29 MRD<0.01% and 19/22 (86.4%) Day 84 MRD<0.01%. Conclusions: By securing access to a standardized consensus-derived diagnostic panel, the Bridge Project has allowed better characterization of childhood ALL in Mexico while producing unprecedented service improvements and documenting key implementation outcomes. We are using these results to inform iterative changes to the diagnostic panel and an associated treatment guideline (MAS-ALL18).

The Boundary of HIV Care: Barriers and Facilitators to Care Engagement Among People with HIV in the United States.

Treating people with HIV (PWH) quickly and effectively to achieve viral suppression is a key strategy for Ending the HIV Epidemic. Understanding barriers and facilitators to HIV care engagement could improve outcomes among PWH and reduce HIV infections. We sampled PWH who participated in the Medical Monitoring Project from June 2018 to May 2019 and were not engaged in HIV care to participate in 60-min semistructured telephone interviews on barriers and facilitators to HIV care engagement. We used applied thematic analysis and placed codes into themes based on their frequency and salience. Participants reported various intrapersonal, health system, and structural barriers to care. We conceptualize the boundary of care as the space between the stages of the HIV care continuum, where PWH may find themselves when they lack intrapersonal, health system, and structural support. Research and interventions tackling these barriers are needed to improve outcomes among PWH and reduce HIV infections.

Using Semistructured Telephone Interviews to Collect Qualitative Data From People With HIV Who Are Not in Medical Care: Implementation Study.

BACKGROUND: The Medical Monitoring Qualitative (MMP-Qual) Project was designed to collect qualitative data from people with HIV not engaged in medical care that would complement quantitative data collected by the Medical Monitoring Project (MMP)-a national surveillance system-and inform the MMP's recruitment and data collection methods. OBJECTIVE: Our objectives were to describe the methodology of this project, reflect on the challenges and lessons learned from conducting qualitative telephone interviews at a national level, and describe how we used and plan to use the qualitative data to evaluate our recruitment procedures and quantitative data collection instrument as well as knowledge of HIV care engagement. METHODS: We used stratified purposive sampling to identify and recruit participants who had participated in the structured MMP interview into the MMP-Qual Project. To be eligible, participants must have had an HIV diagnosis, be aged ≥18 years, have lived in an MMP jurisdiction, and have not been engaged in HIV medical care. From August 1, 2018, to May 31, 2019, we conducted semistructured telephone interviews with 36 people with HIV across the United States about several topics (eg, facilitators and barriers to care and experience with surveys). Four trained interviewers conducted semistructured 60-minute telephone interviews with 36 participants. Data collection lasted from August 1, 2018, to May 31, 2019. RESULTS: From 2018 to 2019, 113 people were eligible to participate in the MMP-Qual Project. Of the people recruited, 28% (22/79) refused to participate. Of those who agreed to participate, 63% (36/57) were interviewed, and 37% (21/57) were no-shows. Of the 34 participants for whom we had complete data, 15 (44%) were aged ≥50 years, 26 (76%) identified as male, 22 (65%) were Black or African American, and 12 (35%) lived in the Southern United States. CONCLUSIONS: We learned that it is possible to obtain rich qualitative data from people with HIV who are not in care via telephone interviews and that this mode might be conducive to talking about sensitive topics. We also learned the importance of flexibility, communication, and coordination because we relied on health department staff to perform recruitment and had difficulty implementing our original sampling strategy. We hope that other projects will learn from our experience conducting qualitative telephone interviews with people with HIV on a national level. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/40041.

Type 1 Insulin-Like Growth Factor Receptor Nuclear Localization in High-Grade Glioma Cells Enhances Motility, Metabolism, and In Vivo Tumorigenesis.

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility and metabolism without affecting their proliferation. In vivo, IGF1R has the capacity to translocate to the nucleus and allows not only a higher proliferation rate and the earlier development of tumors but also renders the cells sensitive to OSI906 therapy. With this work, we provide evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization.

Patient Experiences with Telemedicine for HIV Care During the First COVID-19 Wave in Atlanta, Georgia.

We explored experiences with telemedicine among persons with HIV (PWH) during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. A convenience sample of adults (>18 years) receiving care in an urban clinic in Atlanta were invited to participate. Patients completed a structured survey that assessed the usefulness, quality, satisfaction, and concerns with telemedicine services (telephone calls) received during the first wave of the COVID-19 pandemic (March-May 2020). Demographic, plasma HIV-1 RNA, and CD4+ T cell count data were obtained through medical chart abstraction. Bootstrapped t-tests and chi-square tests were used to examine differences in patient experiences by age, sex, and race. Of 406 PWH contacted, 101 completed the survey (median age 55 years, 84% men, 77% Black, 98% virally suppressed, median CD4 count 572 cells/µL). The main HIV care disruptions experienced were delays in follow-up visits (40%), difficulty getting viral load measured (35%), and difficulty accessing antiretroviral therapy (21%). Participant ratings for quality (median score 6.5/7), usefulness (median score 6.0/7), and satisfaction (median score 6.3/7) with telemedicine were high. However, 28% of patients expressed concerns about providers' ability to examine them and about the lack of laboratory tests. More women had concerns about providers' ability to examine them (92% vs. 50%, p = .005) and about the safety of their personal information (69% vs. 23%, p = .002) compared with men. No age or race differences were observed. Although PWH are generally satisfied with telephone-based telemedicine, concerns with its use were notable, particularly among women. Future HIV telemedicine models should address these.

"I don't regret it at all. It's just I wish the process had a bit more humanity to it a bit more holistic": a qualitative, community-led medication abortion study with Black and Latinx Women in Georgia, USA.

Traditional family planning research has excluded Black and Latinx leaders, and little is known about medication abortion (MA) among racial/ethnic minorities, although it is an increasingly vital reproductive health service, particularly after the fall of Roe v. Wade. Reproductive justice (RJ) community-based organisation (CBO) SisterLove led a study on Black and Latinx women's MA perceptions and experiences in Georgia. From April 2019 to December 2020, we conducted key informant interviews with 20 abortion providers and CBO leaders and 32 in-depth interviews and 6 focus groups (n = 30) with Black and Latinx women. We analysed data thematically using a team-based, iterative approach of coding, memo-ing, and discussion. Participants described multilevel barriers to and strategies for MA access, wishing that "the process had a bit more humanity … [it] should be more holistic." Barriers included (1) sociocultural factors (intersectional oppression, intersectional stigma, and medical experimentation); (2) national and state policies; (3) clinic- and provider-related factors (lack of diverse clinic staff, long waiting times); and (4) individual-level factors (lack of knowledge and social support). Suggested solutions included (1) social media campaigns and story-sharing; (2) RJ-based policy advocacy; (3) diversifying clinic staff, offering flexible scheduling and fees, community integration of abortion, and RJ abortion funds; and (4) social support (including abortion doulas) and comprehensive sex education. Findings suggest that equitable MA access for Black and Latinx communities in the post-Roe era will require multi-level intervention, informed by community-led evidence production; holistic, de-medicalised, and human rights-based care models; and intersectional RJ policy advocacy.

Applying Bioinformatic Platforms, In Vitro, and In Vivo Functional Assays in the Characterization of Genetic Variants in the GH/IGF Pathway Affecting Growth and Development.

Heritability accounts for over 80% of adult human height, indicating that genetic variability is the main determinant of stature. The rapid technological development of Next-Generation Sequencing (NGS), particularly Whole Exome Sequencing (WES), has resulted in the characterization of several genetic conditions affecting growth and development. The greatest challenge of NGS remains the high number of candidate variants identified. In silico bioinformatic tools represent the first approach for classifying these variants. However, solving the complicated problem of variant interpretation requires the use of experimental approaches such as in vitro and, when needed, in vivo functional assays. In this review, we will discuss a rational approach to apply to the gene variants identified in children with growth and developmental defects including: (i) bioinformatic tools; (ii) in silico modeling tools; (iii) in vitro functional assays; and (iv) the development of in vivo models. While bioinformatic tools are useful for a preliminary selection of potentially pathogenic variants, in vitro-and sometimes also in vivo-functional assays are further required to unequivocally determine the pathogenicity of a novel genetic variant. This long, time-consuming, and expensive process is the only scientifically proven method to determine causality between a genetic variant and a human genetic disease.