Anisometropia and Amblyopia Outcomes in Early Versus Late Resolution of Congenital Nasolacrimal Duct Obstruction in Older Infants.

PURPOSE: Congenital nasolacrimal duct obstruction is a known risk factor for amblyopia and anisometropia. The purpose of this study was to investigate whether the rate of anisometropia and amblyopia development differed based on the age at CNLDO resolution in older infants. METHODS: This retrospective chart review at a single tertiary children's hospital from 2007 to 2017 compared early versus late spontaneous resolution (cutoff 12 months) and intervention (cutoff 15 months) groups presenting at ≥9 months of age, comparing visual outcomes, including anisometropia (≥1 D of sphere or cylinder) and amblyopia (≥2 levels difference in Teller acuity or optotype testing). Parents/guardians were contacted by phone for missing data on spontaneous resolution or intervention status. RESULTS: A total of 462 patients were included (152 early; 310 late group). The early group presented at a median age of 12.0 (interquartile range: 10.0, 13.0) months, while the late group presented at 21.0 (interquartile range: 15.0, 32.0) months. Unilateral disease occurred in 62% and 59%, respectively. Anisometropia was seen in (12/102) 12% of early versus (25/243) 10% of late patients (p = 0.686, 95% CI: -0.059, 0.088), and amblyopia in (4/131) 3% of early versus (14/286) 5% of late patients (p = 0.322, 95% CI: -0.061, 0.018). In patients presenting <24 months without undergoing surgery, spontaneous resolution occurred in 76% between 12 and 24 months (n = 41). CONCLUSIONS: Anisometropia and amblyopia rates did not significantly differ between early and delayed intervention for congenital nasolacrimal duct obstruction in this retrospective cohort presenting beyond 9 months of age to a children's hospital. This study found frequent late spontaneous resolution.

The occurrence of bone and joint cancers and their association with rural living and radon exposure in Iowa.

Primary bone and joint cancers are rare and understudied, yet these neoplasms are difficult to treat and impact all age groups. To explore the long-term changes in the occurrence of bone and joint cancers, patients diagnosed with these neoplasms between 1975 and 2016 were identified in the Surveillance Epidemiology and End Results of the National Cancer Institute of the USA. The age-adjusted incidence (AAIR) and mortality (AAMR) rates were calculated for three decades and compared to AAIR and AAMR in years 1975-1984. By using the population-based cancer registries of the USA, Iowa was identified as a state with increased cases of bone and joint malignancies. The bone and joint cancer cases in Iowa were correlated with the percentage of rural population, the average farmland size, or the residential radon levels. Results demonstrated that the mean AAIR of bone and joint cancers for US female and male patients (< 50 years of age) increased from 0.57 (95% C.I. 0.55-0.63) and 0.76 (95% C.I. 0.69-0.82) for years 1975-1984 to 0.71 (95% C.I. 0.66-0.76) and 0.94 (95% C.I. 0.87-1.07) for years 2005-2014, respectively. The increase in bone and joint cancer cases in Iowa positively correlated with the percentage rural population (R = 0.222, P < 0.02), and the average farmland size (R = 0.236, P < 0.02) but not the radon levels (R = - 0.038, P < 0.7). The findings revealed that patients younger than 50 years of age and those who resided in rural areas and engaged in farming were more likely to be diagnosed with primary bone and joint cancers.

Numeracy and Preventive Health Care Service Utilization among Middle-Aged and Older Adults in the U.S.

Objectives: Determine whether a specific numeracy skill cut-point(s) reflects an empirical threshold in the context of preventive health service utilization, and identify associations between numeracy and preventive health services utilization among middle-aged and older adults in the United States.Methods: A nationally representative sample (n = 2,989) of adults 45 years and older from the International Assessment of Adult Competencies (PIAAC) was analyzed. Binary logistic regression was used to examine the utilization of dental checkup, vision screening, influenza vaccination, and osteoporosis screening, using multiple numeracy level classifications.Results: A dichotomous classification of numeracy skill levels (low vs. moderate to high proficiency) was associated with dental checkup utilization, but vision screening, influenza vaccination, and osteoporosis screening.Conclusions: Middle-aged and older adults with sufficient numeracy skills are more likely to have had a dental check up in the past 12 months. Findings suggest that numeracy may be more relevant for long-term vs. short-term risk assessment in determining preventive health care service utilization.Clinical Implications: Two-level numeracy categories are recommended in preventive health contexts. Numeracy proficiency-sensitive risk communication by health care providers and education programs may enhance awareness of preventive health care and promote the utilization of specific preventive health service utilization among older adults.

Interspecies Chemical Signaling in a Methane-Oxidizing Bacterial Community.

Multiple species of bacteria oxidize methane in the environment after it is produced by anaerobic ecosystems. These organisms provide reduced carbon substrates for species that cannot oxidize methane themselves, thereby serving a key role in these niches while also sequestering this potent greenhouse gas before it enters the atmosphere. Deciphering the molecular details of how methane-oxidizing bacteria interact in the environment enables us to understand an important aspect that shapes the structures and functions of these communities. Here we show that many members of the Methylomonas genus possess a LuxR-type acyl-homoserine lactone (acyl-HSL) receptor/transcription factor that is highly homologous to MbaR from the quorum-sensing (QS) system of Methylobacter tundripaludum, another methane oxidizer that has been isolated from the same environment. We reconstitute this detection system in Escherichia coli and use mutant and transcriptomic analysis to show that the receptor/transcription factor from Methylomonas sp. strain LW13 is active and alters LW13 gene expression in response to the acyl-HSL produced by M. tundripaludum These findings provide a molecular mechanism for how two species of bacteria that may compete for resources in the environment can interact in a specific manner through a chemical signal.IMPORTANCE Methanotrophs are bacteria that sequester methane, a significant greenhouse gas, and thereby perform an important ecosystem function. Understanding the mechanisms by which these organisms interact in the environment may ultimately allow us to manipulate and to optimize this activity. Here we show that members of a genus of methane-oxidizing bacteria can be influenced by a chemical signal produced by a possibly competing species. This provides insight into how gene expression can be controlled in these bacterial communities via an exogenous chemical signal.

The Roles of Education, Literacy, and Numeracy in Need for Health Information during the Second Half of Adulthood: A Moderated Mediation Analysis.

We examine complex pathways that link health information seeking behavior with education and health literacy (decomposed into general literacy and numeracy), and how these pathways differ by perceived health status (need) among a nationally representative sample of Americans age 50 and older (n = 2,750). Data come from the Program for International Assessment of Adult Competencies (PIAAC). Multi-group structural equation models were used to examine the use of eight health information sources (newspapers, magazines, internet, radio, TV, books, friends/family, and health professionals). Findings partially support the long-standing notion that health seeking behaviors are directly linked to educational attainment, and provide some of the first nationally representative evidence for how education functions through distinct health literacy components to shape health information seeking behaviors by health status. Findings from this moderated mediation analysis point to the importance of examining, and addressing, health literacy disparities in access to and use of health information.

Tundrenone: An Atypical Secondary Metabolite from Bacteria with Highly Restricted Primary Metabolism.

Methane-oxidizing bacteria, aerobes that utilize methane as their sole carbon and energy source, are being increasingly studied for their environmentally significant ability to remove methane from the atmosphere. Their genomes indicate that they also have a robust and unusual secondary metabolism. Bioinformatic analysis of the Methylobacter tundripaludum genome identified biosynthetic gene clusters for several intriguing metabolites, and this report discloses the structural and genetic characterization of tundrenone, one of these metabolites. Tundrenone is a highly oxidized metabolite that incorporates both a modified bicyclic chorismate-derived fragment and a modified lipid tail bearing a ß,γ-unsaturated α-hydroxy ketone. Tundrenone has been genetically linked to its biosynthetic gene cluster, and quorum sensing activates its production. M. tundripaludum's genome and tundrenone's discovery support the idea that additional studies of methane-oxidizing bacteria will reveal new naturally occurring molecular scaffolds and the biosynthetic pathways that produce them.

Clinical Neurologic Features and Evaluation of PTEN Hamartoma Tumor Syndrome: A Systematic Review.

BACKGROUND AND OBJECTIVES: PTEN hamartoma tumor syndrome (PHTS) is a well-recognized hereditary tumor syndrome and is now also recognized as a common cause of monogenic autism spectrum disorder. There is a vast spectrum of phenotypic variability across individuals with PHTS, and in addition to neurodevelopmental challenges, patients with PHTS may experience a wide variety of neurologic challenges, many of which have only recently been described. Thus, this systematic review aimed to summarize the breadth of the current knowledge of neurologic conditions in individuals with PHTS. METHODS: We conducted a systematic review using the MEDLINE and EMBASE databases until January 2023. We included studies that reported neurologic signs, symptoms, and diagnoses in patients with a diagnosis of PHTS. Two independent reviewers extracted data (neurologic diagnoses and patient details) from each study. Case reports, case series, prospective studies, and therapeutic trials were included. We assessed the quality of evidence using the appropriate tool from the JBI, depending on study design. RESULTS: One thousand nine hundred ninety-six articles were screened, and 90 articles met the inclusion criteria. The majority of the included studies were case reports (49/90, 54%) or small case series (31/90, 34%). Epilepsy secondary to cerebral malformations, neurologic deficits from spinal or cranial arteriovenous malformations, and rare tumors such as dysplastic cerebellar gangliocytoma are among the more severe neurologic features reported across patients with PHTS. One interventional randomized control trial examining neurocognitive endpoints was identified and did not meet its efficacy endpoint. DISCUSSION: Our systematic review defines a broad scope of neurologic comorbidities occurring in individuals with PHTS. Neurologic findings can be categorized by age at onset in individuals with PTHS. Our study highlights the need for additional clinical trial endpoints, informed by the neurologic challenges faced by individuals with PHTS.

Protocol for analyzing plasma cell-free DNA fragment end motifs from ultra-low-pass whole-genome sequencing.

Circulating cell-free DNA (cfDNA) fragment end motif profiles are a promising biomarker in precision oncology. Here, we present a protocol for analyzing plasma cfDNA fragment end motifs from ultra-low-pass whole-genome sequencing (WGS) data. We detail a pipeline composed of sequential bash scripts for processing post-alignment BAM files. Subsequently, we outline the procedure for downstream analysis and visualization of 4-mer as well as other n-mer cfDNA end motifs in R. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Cell-free DNA fragmentomics and second malignant neoplasm risk in patients with PTEN hamartoma tumor syndrome.

Individuals with PTEN hamartoma tumor syndrome (PHTS) harbor pathogenic germline PTEN variants that confer a significantly increased lifetime risk of various organ-specific cancers including second primary malignant neoplasms (SMNs). Currently, there are no reliable biomarkers that can predict individual-level cancer risk. Despite the highly promising value of cell-free DNA (cfDNA) as a biomarker for underlying sporadic cancers, the utility of cfDNA in individuals with known cancer-associated germline variants and subclinical cancers remains poorly understood. We perform ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA from plasma samples from patients with PHTS and cancer as well as those without cancer. Analysis of cfDNA reveals that patients with PHTS and SMNs have distinct cfDNA size distribution, aberrant genome-wide fragmentation, and differential fragment end motif frequencies. Our work provides evidence that cfDNA profiles may be used as a marker for SMN risk in patients with PHTS.

Development of a Technology-Based Dyadic Intervention for Underserved Colorectal Cancer Patients and Caregivers.

This study develops a technology-based dyadic intervention to enhance symptom management and health equity in underserved patients with colorectal cancer and their caregivers. Leveraging generative artificial intelligence, the intervention provides tailored educational contents to meet individual unmet needs.

A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children With PTEN Hamartoma Tumor Syndrome.

Background and Aims: PTEN hamartoma tumor syndrome (PHTS) confers a high risk of specific cancers and is the most common genetic cause of autism spectrum disorder (ASD). Gastrointestinal (GI) phenotypes in PHTS are poorly characterized in children. Thus, we aimed to characterize the GI and hepatic manifestations in children with PHTS and to investigate genotype-phenotype associations. Methods: We performed a retrospective chart review of prospectively accrued children with PHTS at 2 tertiary-care centers. Wilcoxon rank-sum, Chi-squared, and Fisher's exact tests and Firth's logistic regression were utilized to explore associations between variables. Results: This series included 80 children with disease-causing PTEN variants. Common GI manifestations included constipation in 41 (51%), feeding issues in 31 (39%), and polyps in 22 (28%) children. The polyps were of mixed histologic types. Eosinophilic gastrointestinal disorders were observed in 5 (6%) children. Crohn's disease, celiac disease, and protein-losing enteropathy were observed once each. Eosinophilic gastrointestinal disorders were observed exclusively in patients without ASD (P = .052). Nonsense PTEN variants were enriched in those with polyps (P = .029). Missense PTEN variants (OR 2.9, P = .034) and upper GI polyps (OR 4.4, P = .018) were associated with increased odds of constipation. Conclusion: Constipation and feeding issues are common in children with PHTS. Polyps are more prevalent in children with PHTS than previously described and associated with nonsense PTEN variants. Children without ASD represent a distinct patient subset with a predisposition to eosinophilic gastrointestinal disorders and possibly upper GI polyps. Endoscopic evaluation should continue to be performed in symptomatic children with PHTS, with consideration of closer follow-up in those without ASD.

Exploring the neurological features of individuals with germline PTEN variants: A multicenter study.

OBJECTIVE: PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described. METHODS: Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6-12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported. RESULTS: One hundred and seven patients with PHTS (median age 8.7 years; range 3-21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS-ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service. INTERPRETATION: This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS.

Post-Acute and Long-Term Care Leaders' Perspectives on Leading During COVID-19.

Post-acute and long-term care (PALTC) delivery is complex, and the COVID-19 pandemic created additional complexities. This qualitative study investigates how PALTC administrators responded to the pandemic, factors that impacted their leadership role and decision-making. Participants from North Carolina (N = 15) and Pennsylvania (N = 6) were interviewed using an interview guide containing open-ended questions. The results revealed three themes: (1) critical knowledge and competencies; (2) resources, supports and essential actions taken; and (3) psychosocial impact. The findings suggest communication and relationship building were the most useful competencies. Lack of staff was a primary stress point during and after the pandemic.

Cost-related nonadherence in the Medicare program: the impact of Part D.

BACKGROUND: Cost-related nonadherence (CRN) among Medicare beneficiaries declined after the implementation of the Part D program, but it is unknown whether CRN changes varied on the basis of beneficiaries' change in drug coverage. OBJECTIVE: To determine how CRN changed with the introduction of Part D, and whether CRN changes from 2005 to 2006 varied between newly insured beneficiaries, continuously insured beneficiaries, and continuously uninsured beneficiaries. METHODS: CRN, drug coverage, and beneficiary characteristics in 2005 and 2006 were constructed from merged Medicare Current Beneficiary Survey Access to Care files (sample, n=8935). Change in CRN was modeled using multinomial logistic regression to identify predictors of resolved CRN (reported in 2005 but not in 2006), unresolved CRN (reported in 2005 and 2006), and new CRN (reported in 2006 but not in 2005), relative to no CRN (not reported in 2005 or 2006). RESULTS: Rates of CRN declined from 2005 to 2006 for all beneficiaries, with the greatest reductions (from 22.1% in 2005 to 14.3% in 2006) for newly insured beneficiaries who gained drug coverage through Part D. In adjusted analyses, newly insured beneficiaries were more likely to have resolved CRN (adjusted odds ratio [AOR] =1.7; 95% confidence interval, 1.3-2.2). Younger beneficiaries (under the age of 65 years) and beneficiaries with multiple chronic conditions, poor health, and depression were significantly more likely to report CRN. CONCLUSIONS: Part D coverage reduced but did not eliminate CRN for newly insured beneficiaries. Unresolved CRN persisted for newly insured and continuously uninsured beneficiaries, particularly among disabled beneficiaries.

Nursing home safety: does financial performance matter?

OBJECTIVES: This study examines the relationship between financial performance and selected safety measures of nursing homes in the State of Florida. METHODS: We used descriptive analysis on a total sample of 1,197. Safety information was from the Online Survey, Certification and Reporting (OSCAR) data of 2003 to 2005, while the financial performance measures were from the Medicare cost reports of 2002 to 2004. Finally, we examined the most frequently cited deficiencies as well as the relationship between financial performance and quality indicators. RESULTS: Nursing homes in the bottom quartile of financial performance perform poorly on most resident-safety measures of care; however, nursing homes in the top two financial categories also experienced a higher number of deficiencies. Nursing homes in the next to lowest quartile of financial performance category best perform on most of these safety measures. CONCLUSIONS: The results reinforce the need to monitor nursing home quality and resident safety in US nursing homes, especially among facilities with poor overall financial performance.

The use of governance tools in promotion of health care information technology adoption by physicians.

Electronic health records are important technology for health care with promises of streamlining and improving care. However, physicians have been slow to adopt the technology usually because of financial constraints. Third-party payers, including Medicare and Medicaid, are coming forward with solutions and funding. While payers have the most to gain in terms of cost savings, they have been slow to provide a solution to the financial dilemmas posed by the new technology. This article details some governance tools that are frequently used to alleviate the financial concerns. Grants, loans, and tax expenditures are some of the options available to physicians to purchase electronic health records and other types of health care information technology.

Associations Between Perceived Environmental Pollution and Mental Health in Middle-Aged and Older Adults in East Asia.

Given the widely used objective measures of environmental pollution in previous research, this study investigated subjective measures in relation to mental health among middle-aged and older adults in three East Asian countries-China, Japan, and South Korea. The samples from the 2010 East Asian Social Survey included 2502 Chinese, 1794 Japanese, and 871 South Korean adults aged 40 and older. Linear regression models were used to examine the associations between mental health measure (SF-12) and 4 perceived environmental pollution indicators (ie, air, water, noise, and pollution index). Greater perceived pollution indicators, as well as the perceived pollution index, were associated with poorer mental health, even after adjusting for covariates in all three countries. Although results need to be further verified in future research, national-level efforts to improve perceptions of environmental pollution may be useful to enhance the mental health of East Asian middle-aged and older adults.

Interventions to Reduce Healthcare Disparities in Cancer Screening Among Minority Adults: a Systematic Review.

BACKGROUND: Racial minority populations face an increased burden relative to cancer interventions. Compared with Caucasians, the cancer screening rate is substantially lower among African American, Asian American, Latinx American, and American Indian/Alaska Native populations. Barriers such as low health literacy, lack of health insurance, and miscommunication between patients and providers have been identified as important factors that result in low screening rates among minority adults. This study was designed to identify interventions targeting racial minority adults 40 years of age or older that were effective in increasing cancer screening uptake rates. METHODS: A systematic review of articles published in and after January 2009 was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Twenty-six published studies of cancer screening intervention tested with minority adults were identified through the searches of CINAHL, Global Health, PsycINFO, PubMed, and Scopus databases. RESULTS: Thirteen (50%) of the studies utilized lay community health workers to increase cancer awareness and knowledge and to encourage screening. These methods took place over the telephone, at community education sessions, or within the context of personalized patient navigation support. The intervention programs utilized culturally relevant materials as well as spoken and written information in the targeted population's native language. Various intervention designs resulted in statistically significant increases in cancer screening adherence. However, we found no intervention that consistently elevated cancer screening rates across all racial/ethnic minority adults. CONCLUSIONS: The finding suggests that highly segmented interventions are needed in order to improve cancer screening among various racial/ethnic minority adults.

Non-canonical role of wild-type SEC23B in the cellular stress response pathway.

While germline recessive loss-of-function mutations in SEC23B in humans cause a rare form of anaemia, heterozygous change-of-function mutations result in increased predisposition to cancer. SEC23B encodes SEC23 homologue B, a component of coat protein complex II (COPII), which canonically transports proteins from the endoplasmic reticulum (ER) to the Golgi. Despite the association of SEC23B with anaemia and cancer, the precise pathophysiology of these phenotypic outcomes remains unknown. Recently, we reported that mutant SEC23B has non-canonical COPII-independent function, particularly within the ER stress and ribosome biogenesis pathways, and that may contribute to the pathobiology of cancer predisposition. In this study, we hypothesized that wild-type SEC23B has a baseline function within such cellular stress response pathways, with the mutant protein reflecting exaggerated effects. Here, we show that the wild-type SEC23B protein localizes to the nucleus in addition to classical distribution at the ER/Golgi interface and identify multiple putative nuclear localization and export signals regulating nuclear-cytoplasmic transport. Unexpectedly, we show that, independently of COPII, wild-type SEC23B can also localize to cell nucleoli under proteasome inhibition conditions, with distinct distribution patterns compared to mutant cells. Unbiased proteomic analyses through mass spectrometry further revealed that wild-type SEC23B interacts with a subset of nuclear proteins, in addition to central proteins in the ER stress, protein ubiquitination, and EIF2 signalling pathways. We validate the genotype-specific differential SEC23B-UBA52 (ribosomal protein RPL40) interaction. Finally, utilizing patient-derived lymphoblastoid cell lines harbouring either wild-type or mutant SEC23B, we show that SEC23B levels increase in response to ER stress, further corroborating its role as a cellular stress response sensor and/or effector. Overall, these observations suggest that SEC23B, irrespective of mutation status, has unexplored roles in the cellular stress response pathway, with implications relevant to cancer and beyond that, CDAII and normal cell biology.

Literacy, Numeracy, and Health Information Seeking Among Middle-Aged and Older Adults in the United States.

Objectives: Health literacy is often viewed as an essential skill set for successfully seeking health information to make health-related decisions. However, this general understanding has yet to be established with the use of nationally representative data. The objective of this study was to provide the first nationally representative empirical evidence that links health information seeking behaviors with health literacy among middle-age to older adults in the United States. Methods: Data were obtained from the 2012/2014 Program for the International Assessment of Adult Literacy (PIAAC). Our analytic sample is representative of adults age 45 to 74 years (N = 2,989). Results: Distinct components of health literacy (i.e., literacy and numeracy) were uniquely associated with the use of different health information sources (e.g., health professionals, the Internet, television). Discussion: Findings should be useful for government agencies and health care providers interested in targeting health communications, as well as researchers who focus on health disparities.