Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.

BACKGROUND: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS: The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS: From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION: The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING: US National Institutes of Health.

An analysis of protein language model embeddings for fold prediction.

The identification of the protein fold class is a challenging problem in structural biology. Recent computational methods for fold prediction leverage deep learning techniques to extract protein fold-representative embeddings mainly using evolutionary information in the form of multiple sequence alignment (MSA) as input source. In contrast, protein language models (LM) have reshaped the field thanks to their ability to learn efficient protein representations (protein-LM embeddings) from purely sequential information in a self-supervised manner. In this paper, we analyze a framework for protein fold prediction using pre-trained protein-LM embeddings as input to several fine-tuning neural network models, which are supervisedly trained with fold labels. In particular, we compare the performance of six protein-LM embeddings: the long short-term memory-based UniRep and SeqVec, and the transformer-based ESM-1b, ESM-MSA, ProtBERT and ProtT5; as well as three neural networks: Multi-Layer Perceptron, ResCNN-BGRU (RBG) and Light-Attention (LAT). We separately evaluated the pairwise fold recognition (PFR) and direct fold classification (DFC) tasks on well-known benchmark datasets. The results indicate that the combination of transformer-based embeddings, particularly those obtained at amino acid level, with the RBG and LAT fine-tuning models performs remarkably well in both tasks. To further increase prediction accuracy, we propose several ensemble strategies for PFR and DFC, which provide a significant performance boost over the current state-of-the-art results. All this suggests that moving from traditional protein representations to protein-LM embeddings is a very promising approach to protein fold-related tasks.

Common data elements for arthrogryposis multiplex congenita: An international framework.

AIM: To facilitate multisite studies and international clinical research, this study aimed to identify consensus-based, standardized common data elements (CDEs) for arthrogryposis multiplex congenita (AMC). METHOD: A mixed-methods study comprising of several focus group discussions and three rounds of modified Delphi surveys to achieve consensus using two tiered-rating scales were conducted. RESULTS: Overall, 45 clinical experts and adults with lived experience (including 12 members of an AMC consortium) participated in this study from 11 countries in North America, Europe, and Australia. The CDEs include 321 data elements and 19 standardized measures across various domains from fetal development to adulthood. Data elements pertaining to AMC phenotypic traits were mapped according to the Human Phenotype Ontology. A universal governance structure, local operating protocols, and sustainability plans were identified as the main facilitators, whereas limited capacity for data sharing and the need for a federated informatics infrastructure were the main barriers. INTERPRETATION: Collection of systematic data on AMC using CDEs will allow investigations on etiological pathways, describe epidemiological profile, and establish genotype-phenotype correlations in a standardized manner. The proposed CDEs will facilitate international multidisciplinary collaborations by improving large-scale studies and opportunities for data sharing, knowledge translation, and dissemination.

Hearing loss and cognition: A protocol for ensuring speech understanding before neurocognitive assessment.

INTRODUCTION: Many neurocognitive evaluations involve auditory stimuli, yet there are no standard testing guidelines for individuals with hearing loss. The ensuring speech understanding (ESU) test was developed to confirm speech understanding and determine whether hearing accommodations are necessary for neurocognitive testing. METHODS: Hearing was assessed using audiometry. The probability of ESU test failure by hearing status was estimated in 2679 participants (mean age: 81.4 ± 4.6 years) using multivariate logistic regression. RESULTS: Only 2.2% (N = 58) of participants failed the ESU test. The probability of failure increased with hearing loss severity; similar results were observed for those with and without mild cognitive impairment or dementia. DISCUSSION: The ESU test is appropriate for individuals who have variable degrees of hearing loss and cognitive function. This test can be used prior to neurocognitive testing to help reduce the risk of hearing loss and compromised auditory access to speech stimuli causing poorer performance on neurocognitive evaluation.

Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Systems spatiotemporal dynamics of traumatic brain injury at single-cell resolution reveals humanin as a therapeutic target.

BACKGROUND: The etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains. METHODS: We profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24-h) and subacute (7-day) phases of mTBI at single-cell resolution. RESULTS: We demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling implied astrocytes as a key regulator of the cell-cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, and mt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes. CONCLUSIONS: Our results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Risk factors associated with occupational noise-induced hearing loss in the Hispanic community health study/study of Latinos: A cross-sectional epidemiologic investigation.

The purpose of this study was to estimate the prevalence of occupational noise exposure and risk factors of occupational noise-induced hearing loss (NIHL) in Hispanic/Latino adults included in the baseline wave of the Hispanic Community Health Study/Study of Latinos collected from 2008 to 2011. Sequential multiple linear regression modeled the relationship between occupational NIHL (defined as a 3-, 4-, 6-kHz pure-tone average [PTA]) and occupation type, self-reported noise exposure, cardiovascular disease (CVD) risk score, and hearing protective device (HPD) use. The final model controlled for sex, age, and recreational noise exposure. Among 12,851 included participants, approximately 40% (n = 5036) reported occupational noise exposure "Sometimes" (up to 50% of the time) or "Frequently" (75-100% of the time). In the final fitted model, longest-held occupation and CVD risk were associated with poorer hearing. Specifically, those in non-skilled, service, skilled, and military/police/other job categories had between 2.07- and 3.29-dB worse PTA than professional/office workers. Additionally, a shift in the CVD risk score category from low to medium was associated with a 2.25- and 8.20-dB worse PTA for medium and high CVD risk, respectively. Age and sex were also significantly associated with poorer hearing, such that men presented with 6.08 dB worse PTA than women, and for every one-year increase in age, PTA increased by 0.62 dB (ps < .001). No interactions were seen between noise*sometimes or frequent exposure to other ototoxic agents and PTA (ps = .33 & .92, respectively). The prevalence of occupational noise exposure was high in this cross-sectional investigation of adults from Hispanic/Latino backgrounds. Findings contribute to the extant literature by demonstrating that risk factors for occupational NIHL in adults from varying Hispanic/Latino backgrounds are consistent with those of other previously studied groups.

Asymptomatic endometrial thickening in postmenopausal women: predictor of malignant pathology?

It is not standardised what is the endometrial thickness that discriminates between normal and potentially malignant. The objective of this study was to determine the endometrial thickness cut-off point from which the risk of endometrial cancer (EC) increases in asymptomatic postmenopausal women; and to evaluate the risk factors linked to malignant endometrial pathology as well as other associated ultrasound findings.This was a retrospective observational study that included hysteroscopies performed at the Hospital Materno-Infantil on 267 asymptomatic menopausal women with an increase in endometrial thickness (AET) >5 mm, from 2015 to 2019. The results shows that the prevalence of malignant pathology in asymptomatic postmenopausal women with a casual finding of endometrial thickening was 3.7%. This percentage was 16.3% when the cut-off point of AET was established at 10 mm. There was a significant association for the diagnosis of malignant pathology with this cut-off point.There is a significant association between the 10 mm endometrial thickness cut-off point from which the risk of EC increases in asymptomatic postmenopausal women.Impact statementWhat is already known on this subject? Several studies have established the cut-off point for asymptomatic endometrial thickening (AET) for atypical endometrial hyperplasia and endometrial cancer at 10 mm. Although no cut-off point has optimal accuracy for the diagnosis of malignant endometrial pathology, it has been found that with a cut-off value of AET >10 mm no cases are missed. Likewise, a cut-off point of AET > 11 mm may provide a balance between cancer detection and histopathological workup extension.What do the results of this study add? A significant association was found at the cut-off point of AET > 10 mm, which suggests that screening postmenopausal women at this thickness is acceptable and unlikely to miss cases of endometrial hyperplasia and endometrial cancer.What are the implications of these findings for clinical practice and/or further research? After analysing our results we can conclude, like other published studies, that by establishing a cut-off point of 10 mm we obtain a good discrimination between benign and malignant pathology, which would allow us to diagnose 100% of malignant pathology. Above this cut-off point, the risk of endometrial cancer increases, and it would therefore be advisable to extend the study. A multicentre study is needed to confirm the cut-off point at which the risk of endometrial cancer increases in postmenopausal women with asymptomatic endometrial thickening.

Interferon-stimulated gene 15 and ISGylation are upregulated in glioblastoma.

Interferon stimulated gene 15 (ISG15) encodes a 15-kDa ubiquitin-like protein that acts as a posttranslational modifier of target proteins via ISGylation, a catalytic process similar to ubiquitination. Protein ISGylation is associated with the modulation of protein stability and protein-protein interactions. Furthermore, non-conjugated ISG15 (free ISG15) is secreted to act as a cytokine-like protein in some cellular contexts. The expression of ISG15 in some cancer types is dysregulated, but its expression status in glioblastoma, a malignant brain tumor highly aggressive and invasive, requires more studies. To explore the potential of ISG15 as a biomarker for glioblastoma, we first evaluated the ISG15 levels in glioblastoma cell lines and the effect of IFN-γ treatment on protein levels and localization of ISG15. In addition, we analyzed the ISG15 levels in glioblastoma samples compared to healthy brain tissue. Our results indicate that ISG15 levels are increased in glioblastoma and are upregulated in response to IFN-γ stimulus, suggesting that ISG15 and ISGylation may play a central role in glioblastoma progression. Thus, ISG15/ISGyaltion may be useful as biomarkers of this type of malignant brain tumors.

Unsupervised protein embeddings outperform hand-crafted sequence and structure features at predicting molecular function.

MOTIVATION: Protein function prediction is a difficult bioinformatics problem. Many recent methods use deep neural networks to learn complex sequence representations and predict function from these. Deep supervised models require a lot of labeled training data which are not available for this task. However, a very large amount of protein sequences without functional labels is available. RESULTS: We applied an existing deep sequence model that had been pretrained in an unsupervised setting on the supervised task of protein molecular function prediction. We found that this complex feature representation is effective for this task, outperforming hand-crafted features such as one-hot encoding of amino acids, k-mer counts, secondary structure and backbone angles. Also, it partly negates the need for complex prediction models, as a two-layer perceptron was enough to achieve competitive performance in the third Critical Assessment of Functional Annotation benchmark. We also show that combining this sequence representation with protein 3D structure information does not lead to performance improvement, hinting that 3D structure is also potentially learned during the unsupervised pretraining. AVAILABILITY AND IMPLEMENTATION: Implementations of all used models can be found at https://github.com/stamakro/GCN-for-Structure-and-Function. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

EEG abnormalities and clinical phenotypes in pre-school children with autism spectrum disorder.

BACKGROUND: Abnormalities on electroencephalography (EEG) results have been reported in a high percentage of children with Autism Spectrum Disorder (ASD). The purpose of this study was to explore the prevalence of EEG abnormalities in a clinical population of pre-school children with Autism Spectrum Disorder and the differences in terms of the following phenotypic characteristics: adaptive behavior, executive functioning, severity of Autism Spectrum Disorder core symptoms, and comorbidity symptoms. METHODS: A cross-sectional analysis of 69 children who attended the Autism Spectrum Disorder early diagnosis program with electroencephalography and clinical diagnosis was performed. A battery of questionnaires was also made to parents to evaluate emotions, behavior, and functional skills for daily living. RESULTS: Out of 69 pre-school children with Autism Spectrum Disorder, twenty nine (42%) had abnormalities in electroencephalography results. The group with abnormal epileptiform electroencephalography exhibited more impairment in executive functioning and social-relationship coexisting symptoms. CONCLUSIONS: The presence of an abnormal epileptiform electroencephalography in pre-school children with ASD already suggests a worse development in clinical features.

Hispanic/Latino Perspectives on Hearing Loss and Hearing Healthcare: Focus Group Results.

OBJECTIVES: To better understand the hearing health learning needs of Hispanic/Latino adults by assessing hearing healthcare (HHC) knowledge, attitudes, and behaviors to inform the development of a culturally and linguistically appropriate self-management program. Through a series of focus groups with members of the target audience, this study explored knowledge about hearing loss and interventions, cultural facilitators and barriers to HHC utilization, and preferences for hearing health education and information delivery. Opinions were also received on patient education materials designed to increase self-efficacy for managing hearing loss in daily life. DESIGN: This work was guided by a practical framework of culturally competent interventions for addressing disparities in health and healthcare, centered on structural, clinical, and organizational barriers to care. A hybrid individualistic social psychology and social constructionist approach was used to build programmatic theory related to the primary research objective. Focus group goals were to generate a combination of personal opinions and collective experiences from participants with an a priori plan to analyze data using combined content analysis/grounded theory methods. Purposive sampling was used to select 31 participants who were Spanish-speaking, identified as Hispanic/Latino, and who had normal hearing or self-reported hearing difficulties. Thirteen focus groups were conducted using Microsoft Teams, and each group was audio and video recorded for later off-line transcription, translation, and analysis. A constant comparison approach was used to systematically organize focus group data into a structured format for interpretation. Transcripts were coded independently by two investigators, and emergent themes were derived and interpreted from the coded data. RESULTS: Major and minor themes tied to the framework for culturally competent interventions included those related to sociocultural barriers to care. Structural barriers, including inconsistent access to quality care, lack of culturally and linguistically appropriate patient education materials, appointment wait times and intake processes, and referrals to specialty care, were most frequently experienced by participants. Clinical barriers most frequently cited were a lack of culturally and linguistically congruent healthcare providers and lack of language access during healthcare visits. Other major themes included hearing loss lived experiences, family and familism, and hearing-related patient education needs and preferences. CONCLUSIONS: Focus group results were integrated into a Spanish-language hearing loss self-management program that is currently being evaluated in a randomized controlled trial. The themes uncovered provided insight regarding the knowledge, attitudes, and beliefs about hearing loss and HHC, including hearing-related learning needs, of Hispanic/Latino adults in this sample.

Speech-in-noise testing: Innovative applications for pediatric patients, underrepresented populations, fitness for duty, clinical trials, and remote services.

Speech perception testing, defined as providing standardized speech stimuli and requiring a listener to provide a behavioral and scored response, has been an integral part of the audiologic test battery since the beginning of the audiology profession. Over the past several decades, limitations in the diagnostic and prognostic validity of standard speech perception testing as routinely administered in the clinic have been noted, and the promotion of speech-in-noise testing has been highlighted. This review will summarize emerging and innovative approaches to speech-in-noise testing with a focus on five applications: (1) pediatric considerations promoting the measurement of sensory and cognitive components separately; (2) appropriately serving underrepresented populations with special attention to racial, ethnic, and linguistic minorities, as well as considering biological sex and/or gender differences as variables of interest; (3) binaural fitness for duty assessments of functional hearing for occupational settings that demand the ability to detect, recognize, and localize sounds; (4) utilization of speech-in-noise tests in pharmacotherapeutic clinical trials with considerations to the drug mechanistic action, the patient populations, and the study design; and (5) online and mobile applications of hearing assessment that increase accessibility and the direct-to-consumer market.

A neurotrophic approach to treating hearing loss: Translation from animal models to clinical proof-of-concept.

Currently, there are no approved medicines available for the treatment of hearing loss. However, research over the past two decades has contributed to a growing understanding of the pathological mechanisms in the cochlea that result in hearing difficulties. The concept that a loss of the synapses connecting inner hair cells with the auditory nerve (cochlear synaptopathy) contributes to hearing loss has gained considerable attention. Both animal and human post-mortem studies support the idea that these synapses (ribbon synapses) are highly vulnerable to noise, ototoxicity, and the aging process. Their degeneration has been suggested as an important factor in the speech-in-noise difficulties commonly experienced by those suffering with hearing loss. Neurotrophins such as brain derived neurotrophic factor (BDNF) have the potential to restore these synapses and provide improved hearing function. OTO-413 is a sustained exposure formulation of BDNF suitable for intratympanic administration that in preclinical models has shown the ability to restore ribbon synapses and provide functional hearing benefit. A phase 1/2 clinical trial with OTO-413 has provided initial proof-of-concept for improved speech-in-noise hearing performance in subjects with hearing loss. Key considerations for the design of this clinical study, including aspects of the speech-in-noise assessments, are discussed.

Development, assessment, and monitoring of audiologic treatment fidelity in the aging and cognitive health evaluation in elders (ACHIEVE) randomised controlled trial.

OBJECTIVE: Studies investigating hearing interventions under-utilise and under-report treatment fidelity planning, implementation, and assessment. This represents a critical gap in the field that has the potential to impede advancements in the successful dissemination and implementation of interventions. Thus, our objective was to describe treatment fidelity planning and implementation for hearing intervention in the multi-site Ageing and Cognitive Health Evaluation in Elders (ACHIEVE) randomised controlled trial. DESIGN: Our treatment fidelity plan was based on a framework defined by the National Institutes of Health Behaviour Change Consortium (NIH BCC), and included strategies to enhance study design, provider training, and treatment delivery, receipt, and enactment. STUDY SAMPLE: To assess the fidelity of the ACHIEVE hearing intervention, we distributed a checklist containing criteria from each NIH BCC core treatment fidelity category to nine raters. RESULTS: The ACHIEVE hearing intervention fidelity plan satisfied 96% of NIH BCC criteria. Our assessment suggested a need for including clear, objective definitions of provider characteristics and non-treatment aspects of intervention delivery in future fidelity plans. CONCLUSIONS: The ACHIEVE hearing intervention fidelity plan can serve as a framework for the application of NIH BCC fidelity strategies for future studies and enhance the ability of researchers to reliably implement evidence-based interventions.

Social Ecology of Hypertension Management Among Latinos Living in the U.S.-Mexico Border Region.

INTRODUCTION: While a growing body of research examines individual factors affecting the prevalence and management of hypertension among Latinos, less is known about how socioecological factors operate to determine health and affect implementation of interventions in rural communities. METHOD: We conducted eight focus groups to assess perceived risks and protective factors associated with managing hypertension among Latino adults and their family members living in two rural/frontier counties in the U.S.-Mexico border region. This analysis is part of a larger study, Corazon por la Vida (Heart for Life), which involved multiple data collection strategies to evaluate the effectiveness of a primary care and a promotora de salud intervention to manage hypertension. RESULTS: Of the 49 focus group participants, 70% were female and 30% were male, 39% were Spanish-only speakers, and 84% had hypertension. Participants' ages ranged between 18 and 75 years, and 63% reported annual incomes below $30,000. Drawing from a social-ecological framework to analyze focus group data, four major themes and subthemes emerged as factors facilitating or inhibiting disease management: (1) individual (emotional burdens, coping mechanisms), (2) social relationships (family as a source of support, family as a source of stress), (3) health system (trust/mistrust, patient-provider communication), and (4) environment (lack of access to safe exercise environment, lack of affordable food). CONCLUSION: Our findings are relevant to public health practitioners, researchers, and policymakers seeking to shift from individual level or single interventions aimed at improving treatment-modality adherence to multilevel or multiple interventions for rural Latino communities.

Role of hysteroscopy during conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer in patients who desire pregnancy.

Twenty-five percent of cases of endometrial cancer appear in women with unfulfilled reproductive desires. An adequate selection of patients and a close hysteroscopic follow-up to monitor the endometrial response to the levonorgestrel-releasing intrauterine system (LNG-IUS) may be a valid and safe option for these patients. This is a case series and review of the literature study. We included eight patients diagnosed of complex endometrial hyperplasia with atypia (CEHA) or stage 1AG1 well-differentiated endometrial cancer without myometrial invasion who desired to get pregnant and opted for a conservative treatment. Follow-up was performed with hysteroscopy and directed biopsy at 3, 6 and 12 months. Of the 854 cases of complex endometrial hyperplasia with atypia (CEHA)/endometrial cancer were diagnosed, 2.3% were candidates for conservative management. We obtained a favourable regression of 71.2% at 6 months and 57% at one year with hormonal treatment. Conservative treatment in complex endometrial hyperplasia with atypia (CEHA)/low-grade endometrial cancer in reproductive age patients with a strong desire for pregnancy is feasible.

FoldHSphere: deep hyperspherical embeddings for protein fold recognition.

BACKGROUND: Current state-of-the-art deep learning approaches for protein fold recognition learn protein embeddings that improve prediction performance at the fold level. However, there still exists aperformance gap at the fold level and the (relatively easier) family level, suggesting that it might be possible to learn an embedding space that better represents the protein folds. RESULTS: In this paper, we propose the FoldHSphere method to learn a better fold embedding space through a two-stage training procedure. We first obtain prototype vectors for each fold class that are maximally separated in hyperspherical space. We then train a neural network by minimizing the angular large margin cosine loss to learn protein embeddings clustered around the corresponding hyperspherical fold prototypes. Our network architectures, ResCNN-GRU and ResCNN-BGRU, process the input protein sequences by applying several residual-convolutional blocks followed by a gated recurrent unit-based recurrent layer. Evaluation results on the LINDAHL dataset indicate that the use of our hyperspherical embeddings effectively bridges the performance gap at the family and fold levels. Furthermore, our FoldHSpherePro ensemble method yields an accuracy of 81.3% at the fold level, outperforming all the state-of-the-art methods. CONCLUSIONS: Our methodology is efficient in learning discriminative and fold-representative embeddings for the protein domains. The proposed hyperspherical embeddings are effective at identifying the protein fold class by pairwise comparison, even when amino acid sequence similarities are low.

HPTE-Induced Embryonic Thymocyte Death and Alteration of Differentiation Is Not Rescued by ERα or GPER Inhibition but Is Exacerbated by Concurrent TCR Signaling.

Organochlorine pesticides, such as DDT, methoxychlor, and their metabolites, have been characterized as endocrine disrupting chemicals (EDCs); suggesting that their modes of action involve interaction with or abrogation of endogenous endocrine function. This study examined whether embryonic thymocyte death and alteration of differentiation induced by the primary metabolite of methoxychlor, HPTE, rely upon estrogen receptor binding and concurrent T cell receptor signaling. Estrogen receptor inhibition of ERα or GPER did not rescue embryonic thymocyte death induced by HPTE or the model estrogen diethylstilbestrol (DES). Moreover, adverse effects induced by HPTE or DES were worsened by concurrent TCR and CD2 differentiation signaling, compared with EDC exposure post-signaling. Together, these data suggest that HPTE- and DES-induced adverse effects on embryonic thymocytes do not rely solely on ER alpha or GPER but may require both. These results also provide evidence of a potential collaborative signaling mechanism between TCR and estrogen receptors to mediate adverse effects on embryonic thymocytes, as well as highlight a window of sensitivity that modulates EDC exposure severity.