Frequent Disengagement and Subsequent Mortality Among People With HIV and Hepatitis C in Canada: A Prospective Cohort Study.

Background: The cascade of care, commonly used to assess HIV and hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals' engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people with HIV and HCV. Methods: We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers biannually. Markov multistate models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) reengaged (reentry into cohort after being LTFU); (3) withdrawn from the study (ie, moved); (4) death; otherwise remained (5) engaged-in-care. Results: A total of 1809 participants met the eligibility criteria and contributed 12 591 person-years from 2003 to 2022. LTFU was common, with 46% experiencing at least 1 episode, of whom only 57% reengaged. One in 5 (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (adjusted hazards ratio [aHR], 1.37; 95% confidence interval [CI], 1.13-1.67), evidence of HCV treatment but no sustained virologic response result (aHR, 1.99; 95% CI, 1.56-2.53), and recent incarceration (aHR, 1.94; 95% CI, 1.58-2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Interpretation: Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.

Geographical disparities in gastroenterologists and transient elastography across Canada.

Background: In the next decade, the incidence and prevalence of advanced liver disease are expected to increase across Canada. However, little is known about the country's resources for monitoring patients requiring specialized care. A resource assessment was conducted to evaluate regional disparities of specialists and transient elastography machines across Canada. Methods: Demographic data on licenced gastroenterologists were obtained from Scott's Medical Directory as of October 2022. The primary location of each specialist was linked to 2016 Statistics Canada to obtain the population size and density of provinces/territories and census division (CD). Results were summarized per 100,000 persons. CDs were classified as resource scare or approaching resource scarcity. A list of transient elastography (TE) was provided by KNS Canada Inc. and summarized per 1,000,000 persons by province. Results: Eight hundred fifty-three specialists were identified. Rates of gastroenterologists per 100,000 people ranged from 0 in the territories to 2.9 in Quebec. Half the provinces had fewer than 2.0 gastroenterologists per 100,000 persons. Gastroenterologists were concentrated in 24% (71/293) of the CDs across Canada. We identified resource-scarce CDs as areas with no gastroenterologists and in the highest tercile of population density, which accounted for 33% (1 of 3) in Prince Edward Island, 32% in Quebec, 25% in Ontario, 7% in British Columbia, and 4% in Manitoba. Only 94 TEs were identified nationwide. Conclusion: We found significant variation in liver-specific resources across Canada. Given the increasing number of people living with liver disease, policies must be implemented to address access to specialized care.

Reduction of double-strand DNA break repair exacerbates vascular aging.

Advanced age is the greatest risk factor for cardiovascular disease (CVD), the leading cause of death. Arterial function is impaired in advanced age which contributes to the development of CVD. One underexplored hypothesis is that DNA damage within arteries leads to this dysfunction, yet evidence demonstrating the incidence and physiological consequences of DNA damage in arteries, and in particular, in the microvasculature, in advanced age is limited. In the present study, we began by assessing the abundance of DNA damage in human and mouse lung microvascular endothelial cells and found that aging increases the percentage of cells with DNA damage. To explore the physiological consequences of increases in arterial DNA damage, we evaluated measures of endothelial function, microvascular and glycocalyx properties, and arterial stiffness in mice that were lacking or heterozygous for the double-strand DNA break repair protein ATM kinase. Surprisingly, in young mice, vascular function remained unchanged which led us to rationalize that perhaps aging is required to accumulate DNA damage. Indeed, in comparison to wild type littermate controls, mice heterozygous for ATM that were aged to ~18 mo (Old ATM +/-) displayed an accelerated vascular aging phenotype characterized by increases in arterial DNA damage, senescence signaling, and impairments in endothelium-dependent dilation due to elevated oxidative stress. Furthermore, old ATM +/- mice had reduced microvascular density and glycocalyx thickness as well as increased arterial stiffness. Collectively, these data demonstrate that DNA damage that accumulates in arteries in advanced age contributes to arterial dysfunction that is known to drive CVD.

Impact of Interprofessional Communication on Safety in the Neonatal Intensive Care Unit.

BACKGROUND: In light of the complex advances in neonatal intensive care units (NICU), it is essential that healthcare providers (HCPs) are equipped with the appropriate skills to effectively communicate between disciplines to provide safe, quality care. However, many HCPs acknowledge that they are not confident in their ability to communicate effectively with peers. PURPOSE AND DESIGN: This study aimed to identify perceived barriers and facilitators of communication among HCPs in a NICU setting. This study took place in a 60-bed NICU that utilized multiple disciplines of HCPs. Using a qualitative, cross-sectional design, 2 surveys were administered, namely, a demographic survey with open-ended questions and the Safety Attitudes Questionnaire (SAQ). RESULTS: Findings indicated inverse relationships in age/experience and perceptions of management. Total SAQ scores ranged from 45 to 77 (N = 28, M = 62.47, SD = 9.40). The SAQ highlight that total scores above 75 correspond with positive perceptions of safety in the NICU. CONCLUSION: The statistical evidence derived from this study contributes to the evaluation of HCP-perceived communication barriers and facilitators. The identification of perceived barriers and facilitators of communication in an ICU setting may serve as a distinct, evidence-based foundation to develop interventions that emphasize the value of communication.

Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments.

In advanced age, increases in oxidative stress and inflammation impair endothelial function, which contributes to the development of cardiovascular disease (CVD). One plausible source of this oxidative stress and inflammation is an increase in the abundance of senescent endothelial cells. Cellular senescence is a cell cycle arrest that occurs in response to various damaging stimuli. In the present study, we tested the hypothesis that advanced age results in endothelial cell telomere dysfunction that induces senescence. In both human and mouse endothelial cells, advanced age resulted in an increased abundance of dysfunctional telomeres, characterized by activation of DNA damage signaling at telomeric DNA. To test whether this results in senescence, we selectively reduced the telomere shelterin protein telomere repeat binding factor 2 (Trf2) from endothelial cells of young mice. Trf2 reduction increased endothelial cell telomere dysfunction and resulted in cellular senescence. Furthermore, induction of endothelial cell telomere dysfunction increased inflammatory signaling and oxidative stress, resulting in impairments in endothelial function. Finally, we demonstrate that endothelial cell telomere dysfunction-induced senescence impairs glucose tolerance. This likely occurs through increases in inflammatory signaling in the liver and adipose tissue, as well as reductions in microvascular density and vasodilation to metabolic stimuli. Cumulatively, the findings of the present study identify age-related telomere dysfunction as a mechanism that leads to endothelial cell senescence. Furthermore, these data provide compelling evidence that senescent endothelial cells contribute to age-related increases in oxidative stress and inflammation that impair arterial and metabolic function.

Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions.

Aging increases the risk of atherosclerotic cardiovascular disease which is associated with arterial senescence; however, the mechanisms responsible for the development of cellular senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) remain elusive. Here, we study the effect of aging on arterial DNA damage and telomere dysfunction. Aging resulted in greater DNA damage in ECs than VSMCs. Further, telomere dysfunction-associated DNA damage foci (TAF: DNA damage signaling at telomeres) were elevated with aging in ECs but not VMSCs. Telomere length was modestly reduced in ECs with aging and not sufficient to induce telomere dysfunction. DNA damage and telomere dysfunction were greatest in atheroprone regions (aortic minor arch) versus non-atheroprone regions (thoracic aorta). Collectively, these data demonstrate that aging results in DNA damage and telomere dysfunction that is greater in ECs than VSMCs and elevated in atheroprone aortic regions.

Internal consistencies of the delayed trunk muscle reaction times following a treadmill-induced slip perturbation while holding and not holding a tray.

BACKGROUND: Reaction time task performance using electromyography (EMG) has been widely studied in the evaluation of motor responses. However, specific testing conditions with tray usage and the reliability of the bilateral trunk muscle reactions have not been proven. RESEARCH QUESTIONS: Are there internal consistencies of the reaction times for a particular condition, such as a handheld task, among the examiners? Is there a delayed reaction time on the dominant abdominal muscle in response to a treadmill-induced slip perturbation while holding or not holding a tray? METHODS: One hundred and nineteen right upper and lower limb dominant individuals (71 female and 48 male subjects) were exposed to a treadmill-induced slip perturbation (0.24 m/s velocity for 1.2 cm) for 0.10 s in standing. The EMG electrodes were placed on both sides of the rectus abdominis (RA) and erector spinae (ES) muscles. The reliability of the test was established by using Cronbach's alpha, intra-class correlation coefficients (ICC2, k), and the standard error of measurements. RESULTS: The results for holding a tray indicated a high degree of consistency based on Cronbach's alpha for the left RA (0.79), right RA (0.86), left ES (0.82), and right ES (0.73) muscles. However, there was a significant reaction time difference among trunk muscles (F = 10.58, p = 0.002) while not holding a tray. The post-hoc results indicated that the right RA muscle was delayed more than the bilateral ES muscles, although there was no significant difference with the left RA muscle. SIGNIFICANCE: Overall, the EMG analyses for the reaction times were highly consistent with and without tray usage. The reaction times of the dominant abdominal muscles were delayed while not holding a tray. Given the high reliability, compensatory strategies by trunk dominance might be considered with a tray usage task.

ACA Medicaid Expansion and Insurance Coverage Among New Mothers Living in Poverty.

BACKGROUND: Medicaid plays a critical role during the perinatal period, but pregnancy-related Medicaid eligibility only extends for 60 days post partum. In 2014, the Affordable Care Act's (ACA's) Medicaid expansions increased adult Medicaid eligibility to 138% of the federal poverty level in participating states, allowing eligible new mothers to remain covered after pregnancy-related coverage expires. We investigate the impact of ACA Medicaid expansions on insurance coverage among new mothers living in poverty. METHODS: We define new mothers living in poverty as women ages 19 to 44 with incomes below the federal poverty level who report giving birth in the past 12 months. We use 2010-2017 American Community Survey data and a difference-in-differences approach using parental Medicaid-eligibility thresholds to estimate the effect of ACA Medicaid expansions on insurance coverage among poor new mothers. RESULTS: A 100-percentage-point increase in parental Medicaid-eligibility is associated with an 8.8-percentage-point decrease (P < .001) in uninsurance, a 13.2-percentage-point increase (P < .001) in Medicaid coverage, and a 4.4-percentage-point decrease in private or other coverage (P = .001) among poor new mothers. The average increase in Medicaid eligibility is associated with a 28% decrease in uninsurance, a 13% increase in Medicaid coverage, and an 18% decline in private or other insurance among poor new mothers in expansion states. However, in 2017, there were ∼142 000 remaining uninsured, poor new mothers. CONCLUSIONS: ACA Medicaid expansions are associated with increased Medicaid coverage and reduced uninsurance among poor new mothers. Opportunities remain for expansion and nonexpansion states to increase insurance coverage among new mothers living in poverty.

A Review of Traumatic Brain Injury and the Gut Microbiome: Insights into Novel Mechanisms of Secondary Brain Injury and Promising Targets for Neuroprotection.

The gut microbiome and its role in health and disease have recently been major focus areas of research. In this review, we summarize the different ways in which the gut microbiome interacts with the rest of the body, with focus areas on its relationships with immunity, the brain, and injury. The gut⁻brain axis, a communication network linking together the central and enteric nervous systems, represents a key bidirectional pathway with feed-forward and feedback mechanisms. The gut microbiota has a central role in this pathway and is significantly altered following injury, leading to a pro-inflammatory state within the central nervous system (CNS). Herein, we examine traumatic brain injury (TBI) in relation to this axis and explore potential interventions, which may serve as targets for improving clinical outcomes and preventing secondary brain injury.

Internal Sinus Membrane Elevation in Patients With Less Than 5 mm Residual Bone Height.

Sinus membrane elevation can be accomplished through use of either a direct or indirect technique. The indirect or internal elevation technique lifts the sinus membrane by elevating it superiorly using osteotomes, with or without the use of grafting material. The authors reference a revolutionary randomized clinical trial in which tissue-level implants with a coronally flared design were placed in residual bone height of ≤4 mm using an internal sinus membrane elevation technique and describe an adaptation of the procedure discussed in that study and its successful use in a prosthodontics residency program.

Child-directed and nutrition-focused marketing cues on food packaging: links to nutritional content.

OBJECTIVE: We tested whether the presence of both child-targeted and nutrition-focused (i.e. parent-targeted) marketing cues on food packaging was associated with the nutritional content of these products. DESIGN: We conducted a quantitative content analysis of 403 food packages chosen randomly from the supermarket's online portal along with all products (n 312) from the cereal aisle in a supermarket from the Southeastern USA. We examined main and interaction effects for cues on nutritional content (e.g. energy density, sugar, sodium, fibre). SETTING: A regional supermarket chain in the Southeastern USA. RESULTS: Tests of main effects indicated that increased presence of nutritional cues was linked to more nutritious content (e.g. less sugar, less saturated fat, more fibre) while the increased presence of child-targeted cues was uniformly associated with less nutritious content (e.g. more sugar, less protein, less fibre). Among the interaction effects, results revealed that products with increased nutrition-focused and child-targeted cues were likely to contain significantly more sugar and less protein than other products. CONCLUSIONS: Products that seek to engage children with their packaging in the supermarket are significantly less nutritious than foods that do not, while product packages that suggest nutritional benefits have more nutritious content. More importantly, the study provides evidence that those products which try to engage both child and parent consumers are significantly less healthy in crucial ways (e.g. more sugar, less fibre) than products that do not.

Mesocarp cell turgor in Vitis vinifera L. berries throughout development and its relation to firmness, growth, and the onset of ripening.

Vitis vinifera L. berries are non-climacteric fruit that exhibit a double sigmoid growth pattern and dynamic changes in gene expression, cell metabolism, and water relations at the onset of ripening. The cell-pressure probe was utilized to examine the relationships of turgor pressure (P) in mesocarp cells to growth, sugar accumulation, and fruit softening during development. In replications utilizing three different varieties, mesocarp cell P demonstrated a consistent pattern of a relative mid-range P early in development, followed by an increase to a maximum of about 0.35 MPa, and a subsequent rapid decline before ripening to less than 0.1 MPa. Fruit "apparent elastic modulus" (E, units of MPa), was introduced as a standard measure to describe ripening-related softening. E changed dynamically and synchronously with P during development and in response to water deficits for fruit grown in greenhouse and field conditions. Thus, E and P were positively and linearly related. Sugar accumulation did not increase significantly until P had declined to less than 0.1 MPa. The results suggest that P is an important determinant of fruit softening and that P decreases in conjunction with many of the physiological and gene expression changes that are known to occur at the onset of ripening.

Direct in situ measurement of cell turgor in grape (Vitis vinifera L.) berries during development and in response to plant water deficits.

Vitis vinifera L. berries are non-climacteric fruits that exhibit a double-sigmoid growth pattern, and at the point known as 'veraison', which is just before the beginning of the second period of rapid fruit growth, these berries undergo several abrupt physiological changes. Cell pressure probe was used to examine the in situ turgor (P) of cells in the mesocarp during berry development and in response to plant water deficits. Initial tests comparing attached and detached berries demonstrated that cell P was stable for up to 48 h after detachment from the vine, provided that water loss from the berry was prevented. Cell P at pre-dawn was on the order of 0.25 MPa pre-veraison (PreV) and was reduced by an order of magnitude to 0.02 MPa post veraison (PostV). Cell P declined slightly but significantly with depth from the berry surface PreV, but not PostV. When water was withheld from potted vines, cell P declined about 0.2 Mpa, as pre-dawn vine water potential declined about 0.6 MPa over 12 d, whereas cell P was completely insensitive to a 1.10 MPa decrease in pre-dawn vine water potential after veraison. Rewatering of stressed plants also resulted in a 24 h recovery of cell P before, but not after veraison. The substantial decline in cell P around veraison is consistent with the decline in berry firmness that is known to occur at this time, and the PostV insensitivity of P to changes in vine water status is consistent with current hypotheses that the PostV berry is hydraulically isolated from the vine. The fact that a measurable P of about 0.02 MPa and typical cell hydraulic/osmotic behaviour were exhibited in PostV berries, however, indicates that cell membranes remain intact after veraison, contrary to many current hypotheses that veraison is associated with a general loss of membrane function and cellular compartmentation in the grape berry. We hypothesize that cell P is low in the PostV berry, and possibly other fleshy fruits, because of the presence of regulated quantities of apoplastic solutes.

KIC, a novel Ca2+ binding protein with one EF-hand motif, interacts with a microtubule motor protein and regulates trichome morphogenesis.

Kinesin-like calmodulin binding protein (KCBP) is a microtubule motor protein involved in the regulation of cell division and trichome morphogenesis. Genetic studies have shown that KCBP is likely to interact with several other proteins. To identify KCBP-interacting proteins, we used the C-terminal region of KCBP in a yeast two-hybrid screen. This screening resulted in the isolation of a novel KCBP-interacting Ca2+ binding protein (KIC). KIC, with its single EF-hand motif, bound Ca2+ at a physiological concentration. Coprecipitation with bacterially expressed protein and native KCBP, gel-mobility shift studies, and ATPase assays with the KCBP motor confirmed that KIC interacts with KCBP in a Ca2+-dependent manner. Interestingly, although both Ca2+-KIC and Ca2+-calmodulin were able to interact with KCBP and inhibit its microtubule binding activity, the concentration of Ca2+ required to inhibit the microtubule-stimulated ATPase activity of KCBP by KIC was threefold less than that required for calmodulin. Two KIC-related Ca2+ binding proteins and a centrin from Arabidopsis, which contain one and four EF-hand motifs, respectively, bound Ca2+ but did not affect microtubule binding and microtubule-stimulated ATPase activities of KCBP, indicating the specificity of Ca2+ sensors in regulating their targets. Overexpression of KIC in Arabidopsis resulted in trichomes with reduced branch number resembling the zwichel/kcbp phenotype. These results suggest that KIC modulates the activity of KCBP in response to changes in cytosolic Ca2+ and regulates trichome morphogenesis.