Determining the relationship of p16INK4a and additional molecular markers of aging with clinical frailty in hematologic malignancy.

PURPOSE: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I2) in patients with HM. METHODS: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16INK4a expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I2) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I2. RESULTS: Age-adjusted p16INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09-0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11-0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16INK4a [AUC = 0.76, 95% CI (0.56-0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54-0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55-0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57-0.88); p = < 0.01] measures showed the greatest potential to identify clinical frailty using the I2. CONCLUSIONS: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM. IMPLICATIONS FOR CANCER SURVIVORS: We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.

Psychoneuroimmunology in multiple myeloma and autologous hematopoietic stem cell transplant: Opportunities for research among patients and caregivers.

Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients. An extensive psychoneuroimmunology (PNI) literature links distress with health via immune and neuroendocrine dysregulation as well as biological aging. However, data on PNI in the context of multiple myeloma - in patients or caregivers - are remarkably limited. Distress in MM patients has been associated with poorer outcomes including higher inflammation, greater one year post-HSCT hospital readmissions, and worse overall survival. Further, anxiety and depression are linked to biological aging and may contribute to the poor long-term health of both patients and caregivers. Because MM generally affects older adults, individual differences in biological aging may represent an important modifier of MM biology and HSCT treatment outcomes. There are a number of clinical scenarios in which biologically younger people could be prescribed more intensive therapies, with potential for greater benefit, by using a personalized cancer therapy approach based on the quantification of physiologic reserve. Further, despite considerable psychological demands, the effects of distress on health among MM caregivers is largely unexamined. Within this context, the current critical review highlights gaps in knowledge at the intersection of HSCT, inflammation, and biological aging in the context of MM. Research in this area hold promise for opportunities for novel and impactful psychoneuroimmunology (PNI) research to enhance health outcomes, quality of life, and longevity among both MM patients and their caregivers.

Comparing paediatric optometric vision care in Canada over a 14-year period.

PURPOSE: In Canada, teaching in paediatric eye care has increased in the past decade both within the optometry curriculum and as continuing education to optometrists. Paediatric vision care guidelines have also been established by North American optometric associations. This study examined whether this exposure was associated with changes in paediatric eye care in Canada over a 14-year period. METHODS: Canadian optometrists were invited to participate in an anonymous 35-item survey in 2007 and 2021. The surveys sought to investigate optometrist's recommendations for first eye examinations, the number of paediatric patients seen in a typical week and preparedness to provide eye examinations to children. Response frequencies were determined for each survey item. RESULTS: Across Canada, 133/1000 (13.3%) and 261/~6419 (~4.1%) optometrists responded to the survey in 2007 and 2021, respectively. No significant difference was found in the number of years practicing, days per week in practice and total number of patients seen per week. The modal age optometrists recommended children be seen for their first eye examination changed from 3-4 years in 2007 (53%) to 6-12 months in 2021 (61%). In 2007, 87% of respondents provided eye examinations to children <2 years, increasing to 94% in 2021 (p = 0.02). Despite a reduction in the recommended age between the two survey years, the most frequent age children were seen for their first eye examination was 3-4 years (30% in both surveys) and the most common age seen in a typical week remained unchanged (4-6 years-56% 2007; 66% 2021). CONCLUSION: Although optometrists' willingness to provide paediatric eye care increased over the past 14 years, the number of children seen in a typical week did not change. Barriers to determine why more children are not being seen at an earlier age need to be investigated.

Kinematic Assessment of Fine Motor Skills in Children: Comparison of a Kinematic Approach and a Standardized Test.

Deficits in fine motor skills have been reported in some children with neurodevelopmental disorders such as amblyopia or strabismus. Therefore, monitoring the development of motor skills and any potential improvement due to therapy is an important clinical goal. The aim of this study was to test the feasibility of performing a kinematic assessment within an optometric setting using inexpensive, portable, off-the-shelf equipment. The study also assessed whether kinematic data could enhance the information provided by a routine motor function screening test (the Movement Assessment Battery for Children, MABC). Using the MABC-2, upper limb dexterity was measured in a cohort of 47 typically developing children (7-15 years old), and the Leap motion capture system was used to record hand kinematics while children performed a bead-threading task. Two children with a history of amblyopia were also tested to explore the utility of a kinematic assessment in a clinical population. For the typically developing children, visual acuity and stereoacuity were within the normal range; however, the average standardized MABC-2 scores were lower than published norms. Comparing MABC-2 and kinematic measures in the two children with amblyopia revealed that both assessments provide convergent results and revealed deficits in fine motor control. In conclusion, kinematic assessment can augment standardized tests of fine motor skills in an optometric setting and may be useful for measuring visuomotor function and monitoring treatment outcomes in children with binocular vision anomalies.

Status of Vision and Eye Care Among Patients in Rehabilitation Hospital Units: A Cross-Sectional Study.

OBJECTIVES: The prevalence of vision disorders is high among geriatric and hospital inpatient populations, yet they often go undetected, resulting in consequences such as falls or prolonged recovery time. A needs assessment study was conducted to investigate levels of vision and the potential prevalence of unmanaged/undiagnosed ocular disorders among adult inpatients in a hospital-based rehabilitation unit. DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Inpatient rehabilitation units of an acute care hospital system in Ontario, Canada. Adults (n = 112) in a hospital inpatient rehabilitation unit participated from October 2018 to February 2019. METHODS: Participants were surveyed regarding their demographic, ocular, and medical data and spectacle wear. Visual acuity, contrast sensitivity, visual fields, and stereoacuity plus the spectacle condition were directly assessed. RESULTS: The majority (75%) were found to have reduced habitual vision while in hospital. Nearly 60% of participants reported at least some difficulty reading a newspaper or distinguishing a face or were "not happy with their vision." This was despite 80% of participants reporting that they had an eye care practitioner and 70% that they had an eye examination within the last 2 years. More than half (51.8%) of the participants received the recommendation to follow up with their eye care practitioner on discharge from the hospital. CONCLUSIONS AND IMPLICATIONS: Reduced vision and vision disorders has a high prevalence among hospital patients in rehabilitation units and should be evaluated at or soon after hospital intake. By incorporating vision screening tools, necessary precautions may be taken to avoid possible falls and promote recovery.

Understanding the health effects of caregiving stress: New directions in molecular aging.

Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers' health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16INK4a, and epigenetic age could help to reconcile mixed literature on caregiving's sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes -together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.

Validation of the Waterloo Differential Visual Acuity Test (WatDAT) and Comparison With Existing Pediatric Tests of Visual Acuity.

Purpose: The new Waterloo Differential Acuity Test (WatDAT) is designed to allow recognition visual acuity (VA) measurement in children before they can typically undertake matching tests. The study purpose was to validate WatDAT in adults with normal and reduced VA. Methods: Eighty adults (18 to <40 years of age) participated (32 normal VA, 12 reduced VA, and 36 simulated reduced VA). Monocular VA was measured on two occasions in random order for WatDAT (versions with 3 and 5 distractors for Faces and Patti Pics house among circles), Lea Symbols, Kay Pictures and Patti Pics matching tests, Teller Acuity Cards, Cardiff Acuity Test, and Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart. Pediatric tests were validated against ETDRS using limits of agreement (LoA), sensitivity, and specificity. The LoA for repeatability were also determined. Results: WatDAT showed minimal bias compared with ETDRS, and LoAs, which were similar to pediatric matching tests (0.241-0.250). Both preferential looking tests showed higher bias and LoAs than ETDRS. Matching tests showed good agreement with ETDRS, except for Kay Pictures and Lea Uncrowded test, which overestimated VA. WatDAT showed high sensitivity (>0.96) and specificity (>0.79), which improved with criterion adjustment and were significantly higher than for the preferential looking tests. LoA for repeatability for WatDAT 3 Faces and WatDAT 5 Faces were comparable with the ETDRS. Conclusions: WatDAT demonstrates good agreement and repeatability compared with the gold-standard ETDRS letter chart, and performed better than preferential looking tests, the alternative until a child can undertake a matching VA test. Translational Relevance: Good validity of the Waterloo Differential Acuity Test was demonstrated in adults as a first step to showing its potential for detecting childhood visual disorders.

Trust and Access: Eye Information-seeking Practices and Preferences among Canadians.

SIGNIFICANCE: This study highlights the value that the public places on obtaining trusted and accessible health-related information and their preference for obtaining it from their health care practitioners. Previous research has not been specific to Canadians or vision. Findings can be used to increase eye health literacy and eye care utilization. PURPOSE: Canadians underuse eye care and underestimate the occurrence of asymptomatic eye disease. This study explored eye information-seeking practices and preferences among a group of Canadians. METHODS: Using snowball sampling, a 28-item online survey collected respondent perceptions about their eye and health information-seeking practices and preferences. Questions examined electronic device access, information source use, and demographics. Two open-ended questions examined information-seeking practices and preferences. Respondents were at least 18 years old and living in Canada. Individuals working in eye care were excluded. Response frequencies and z scores were computed. Written comments were assessed using content analysis. RESULTS: Respondents searched for less eye than health information ( z scores ≥ 2.25, P < .05). For eye and health information, primary care providers were the used and preferred source, and reliance on Internet searches was greater than desired. Trust and access drove information-seeking practices. Respondent comments suggested that a hierarchy of trust operates across My Health Team, My Network, and My External Sources, with a persistent threat posed by Discredited Sources. Access to information sources seemed mediated by enablers (Convenience and Accessible Features) and barriers (Unreachable Health Team and Absent Systems). Eye information was seen as more specialized and harder to find. There was a high regard for health care practitioners who provide their patients with curated trusted information. CONCLUSIONS: These Canadians value trusted and accessible health-related information. They prefer eye and health information from their health care practitioners and value when their health team provides online curated information, particularly regarding eyes.

Teaching cultural safety principles: optometry student perceptions.

CLINICAL RELEVANCE: Providing optometry learners with cultural safety training can improve patient safety and health outcomes among Indigenous Peoples. BACKGROUND: Healthcare practitioners require cultural safety training to provide safe eye care to Indigenous Peoples in Canada. Culturally safe care requires optometrists to critically reflect upon their unconscious biases and power differences that impact patient care. Informed by the cultural safety literature and working directly with learners, revisions were made to first and second-year optometry clinic experience courses in a Canadian Doctor of Optometry program. This descriptive study examined student feedback on curricular changes, focused on enhancing cultural safety. METHODS: An 8-item, anonymous, online survey was offered to all learners (n = 178) enrolled in clinic experience courses at in fall 2021 and winter 2022. The survey addressed student understanding of cultural safety, comfort with self-reflective activities, and course effectiveness in teaching patient-centred care. Six items used a 5-point Likert response scale. Descriptive statistics were analyzed (Wilcoxon and Wilcoxon-Pratt). Two open-ended items were analysed using content analysis for themes. RESULTS: Thirty-three surveys were completed. Overall respondents found the clinic experience courses provided effective training in cultural safety and were of professional value. Comfort engaging in self-reflective activities increased (before: mean response 4.0; after: 4.4), and students made connections with societal problems (overall mean 3.5) and with bias/power differential (overall mean 4.0). Suggested changes to support the learning objectives included increased clinic observation, scaffolding these topics in additional courses, and adding relevant literature (e.g. anti-racism) and guest speakers with Indigenous knowledge and experience. CONCLUSION: Optometry learners were favourable about the inclusion of cultural safety concepts in their clinic experience courses. Their feedback points to areas for improvement including deepening course content, and collaborating with Indigenous Peoples in content, course design, and cross-curricular scaffolding.

What the Canadian public (mis)understands about eyes and eye care.

CLINICAL RELEVANCE: Inadequate public knowledge about eyes and eye care poses avoidable risks to vision-related quality of life. BACKGROUND: This study of eye care knowledge among Canadians extends earlier findings from focus groups. METHODS: Perceptions about eyes and eye care were sought using a 21-item online survey and snowball sampling. Inclusion criteria were living in Canada and being at least 18-years old; eye care professionals and staff were excluded. Response frequencies were converted to percentages, with eye condition items analysed according to 'expected' or 'unexpected' eye impacts. Proportions selecting these impacts or 'unsure' were determined. RESULTS: There were 424 respondents: 83.0% aged 20-65 years and 69.6% female. Mismatches existed between perceived recommendations and behaviours for booking eye exams: within two years (86.7% vs. 68.4%) and symptom-driven (3.3% vs. 13.0%). First eye exams after age one year were deemed appropriate by 43.6%. Few respondents associated glaucoma with no symptoms (6.0%) or amblyopia with blurred vision (13.5%). A notable proportion incorrectly related tunnel vision with age-related macular degeneration (AMD, 36.8%) and cataract (21.9%). Identifying all 'expected' responses was unlikely for glaucoma (1.9%), amblyopia (6.7%), and cataract (12.0%). Most respondents identified no 'expected' effects for glaucoma (63.8%) and AMD (46.2%) and some 'expected' effects for cataract (59.5%) and amblyopia (72.6%). Selecting 'unsure' was 9-10 times more common among respondents choosing no 'expected' impacts than those choosing some. Awareness of thyroid-associated eye disease was lowest (32.4%) of seven conditions. Respondents were most likely to consult optometrists for routine eye exams, eye disease, diabetes eye checks and blurred vision but family physicians for red eyes and sore eyes. Respondents typically paid for their eye exams and eyewear but wanted government to pay. CONCLUSION: Vision-threatening knowledge gaps and misinformation about eyes and eye care among Canadian respondents highlight the need for accessible, targeted public education.

Measuring recognition visual acuity in young children - testability with the Waterloo Differential Acuity Test (WatDAT).

CLINICAL RELEVANCE: Visual acuity measurement is important for the detection and monitoring of eye disorders. Developing accurate and sensitive visual acuity tests suitable for young children is therefore desirable. BACKGROUND: Recognition or form visual acuity (VA), which is measured with matching in children aged 3 years and up, is more sensitive for detecting visual deficits compared to resolution VA. The Waterloo Differential Acuity Test (WatDAT) is a proposed recognition VA test using the concept of identifying the "odd one out" among distractors. The WatDAT is expected to be cognitively easier than matching tests and therefore may be used in younger children. The purpose of this study is to investigate the testability of the WatDAT paradigm in children aged 12-36 months, and to determine the optimum format and number of distractors. METHODS: Fifty-one typically-developing children aged 12-36 months participated in the study. Data for Patti Pics (PP) and Face targets (FT) were collected for formats with 3, 4 and 5 distractors. The targets were presented binocularly on a computer touch screen at 30 cm. The task was to touch the face among identical non-faces or a house among circles. Following initial training, there were 5 presentations for each distractor format. Testability was defined as correctly identifying at least 4/5 presentations and was also determined for uncrowded PP symbols using matching. RESULTS: Of participants aged 18-36 months, 87% could perform the WatDAT PP targets with 3 distractors compared to 68% for the FT, while 48% could perform matching with PP. The testability for FT increased to 85% for children ≥22 months. Younger children showed lower testability. For the 3 distractor format, PP targets gave 9% testability in children 12 to <18 months, and FT gave a testability of 16% in children 12 to <22 months. CONCLUSION: WatDAT testability is higher than matching VA tests. This indicates that the newly developed WatDAT has potential for measuring recognition VA in children 18 months and older.

Repetitive negative thinking during pregnancy and postpartum: Associations with mental health, inflammation, and breastfeeding.

INTRODUCTION: Repetitive negative thinking (RNT) is a transdiagnostic feature that predicts increased mental health risks, inflammation, and reduced engagement in health promoting behaviors. Depression, anxiety, stress, inflammation, higher body mass index (BMI), and low engagement in health behaviors are associated with adverse outcomes during pregnancy as well as postpartum. However, there is limited literature on the associations between RNT and these contributing factors in the perinatal period, an at-risk time during which women may benefit from clinical interventions directed at RNT. METHODS: This study examined the contribution of RNT to inflammation [interleukin (IL)-6] and breastfeeding duration through mediating indicators of mental health and BMI. Behavioral and biological assessments occurred during late pregnancy as well as at 4-6 weeks, 4 months, 8 months, and 12 months postpartum. RESULTS: RNT was positively associated with depressive symptoms, anxiety, and perceived stress (ps ≤ .001) at each assessment timepoint, with the strongest associations observed at the pregnancy assessment and significant, but attenuated, associations during postpartum (ps < .01). In modeling of the association between RNT and IL-6, the indirect effect of BMI was significant at each timepoint (95%CIs 0.0013, 0.0052). Women with lower RNT exhibited longer breastfeeding duration (p = .02). These effects were not significantly mediated by mental health indicators. CONCLUSIONS: Clinically meaningful relationships, in which RNT predicts mental health, inflammation, and health behavior engagement during pregnancy and postpartum were observed. Clinical interventions to reduce RNT may have unique benefits this time. LIMITATIONS: Further research is warranted to determine if therapies to reduce RNT confer unique benefits for maternal and child health.

Associations Between Gut Microbes and Social Behavior in Healthy 2-Year-Old Children.

OBJECTIVE: Emerging research has connected abundances of specific bacteria to differences in psychosocial behaviors in animals and adult humans. However, research assessing mind-microbiome associations in children is sparse with extant work primarily focused on populations with autism, making it unclear whether links are also present in typically developing children. The current study fills this gap by examining associations between prosocial-self-regulating temperaments (effortful control; EC) and the gut microbiome in typically developing children. METHODS: Maternal ratings of temperament were assessed in 77 toddlers 18 to 27 months of age (46.7% female, mean age = 23.14 months). Next-generation pyrosequencing of the V1-V3 region of the 16S rRNA gene was used to classify children's gut microbial composition from fecal samples. EC included the following subcategories: cuddliness, attentional focusing, attentional shifting, inhibitory control, and low-intensity pleasure. RESULTS: After adjusting for covariates, EC was positively associated with relative abundances of Akkermansia (Δ R2 = 0.117, b = 0.022, SE = 0.007, p = .002), with cuddliness (i.e., joy and ease of being held) driving the relation. Furthermore, attentional focusing was negatively associated with Alistipes (Δ R2 = 0.062, b = -0.011, SE = 0.005, p = .028). Permutational analysis of variance revealed no significant differences in community structure between high and low EC groups on the phylum level ( R2 = 0.00372, p = .745) or the genus level ( R2 = 0.01559, p = .276). CONCLUSIONS: Findings suggest that certain microbes may be linked to prosocial behaviors used to regulate emotion in typically developing children. Further research is needed to test whether these observations replicate in larger samples.

Evaluating visuomotor coordination in children with amblyopia.

Past research has reported deficits on reaching and grasping tasks in adults with amblyopia and degraded stereoacuity, but less is known about visuomotor deficits in children-specifically, for complex tasks that require movement sequencing. This study therefore compared the visuomotor performance in 21 children with abnormal binocular vision (patient group) due to amblyopia and/or strabismus to that of 236 children with normal binocular vision development (control group) ages 5-14 years. Visual acuity, stereoacuity, and hand-movement kinematics on a bead-threading task were assessed. The patient group showed significantly longer durations than the control group on grasp, thread, and total movement durations. Both groups of participants were then split into immature (ages 5-9 years) and mature (ages 10-14 years) groups based on the maturation age for these parameters in control children. Grasp duration was longer in both mature and immature patient groups; thread and total movement durations were longer in the mature patient group only. Grasp duration was the most disrupted kinematic parameter in children with disrupted binocular vision due to amblyopia and/or strabismus, regardless of age. The level of stereoacuity loss rather than the depth of visual acuity loss was associated with the severity of visuomotor deficits.

Perceived social support predicts self-reported and objective health and health behaviors among pregnant women.

Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p = 0.001), greater sleep quality (p = 0.001), fewer health-impairing behaviors (p = 0.02), and higher RBC omega-3 fatty acids (p = 0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.

Application of bifocal and progressive addition lenses in the management of accommodative esotropia: A comprehensive review of current practices.

Nonrefractive accommodative esotropia (NRAET) is a form of pediatric acquired strabismus in which the accommodative convergence to accommodation (AC/A) ratio is high. Accordingly, the near angle of esotropia is notably greater than the distance angle, and after full-cycloplegic correction, the near angle is not fully resolved. Nonsurgical plans to deal with convergence-excess esotropia include observation only and single vision lenses with or without a ground-in plus addition power. Bifocals and progressive addition lenses (PALs) are two available designs when the preferred management approach is near plus addition. There are inconsistent data regarding the practical effectiveness of these two optical modalities in providing ocular alignment. Several studies advocated using bifocals and PALs as the primary management strategy in patients with NRAET; however, because of developmental concerns, others affirm that early surgical intervention can be a more conservative strategy than optical treatment. They noted that this method might be ineffective or even pernicious due to the need to defer the surgical intervention. In practice, the prescription of near plus addition lenses in the two forms of bifocals and PALs could be a double-edged sword in the treatment course of patients with NRAET. Therefore, an individualized approach according to the age, degree of refractive error, AC/A ratio, esotropia angle at distance and near, coexisting amblyopia, and parents' economic and cosmetic concerns would be important before choosing any treatment option.

Lifetime stressor exposure, systemic inflammation during pregnancy, and preterm birth among Black American women.

Although Black American mothers and infants are at higher risk for morbidity and mortality than their White counterparts, the biological mechanisms underlying these phenomena remain largely unknown. To investigate the role that lifetime stressor exposure, perceived stressor severity, and systemic inflammatory markers might play, we studied how these factors were interrelated in 92 pregnant Black American women. We also compared inflammatory marker levels for women who did versus did not go on to give birth preterm. During the early third trimester, women completed the Stress and Adversity Inventory for Adults to assess the stressors they experienced over their lifetime. Women also provided blood samples for plasma interleukin (IL)-6, IL-8, IL-1ß, and tumor necrosis factor (TNF)-α quantification. Preterm births were identified by medical record review. Controlling for relevant covariates, there were significant positive associations between average levels of both overall and acute perceived stressor severity and plasma IL-1ß levels. Controlling for perceived stress at assessment and exposure to racial discrimination did not affect these results. Mediation models revealed that exposure to more chronic stressors was related to higher plasma IL-1ß levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1ß levels, as mediated by higher average levels of acute perceived stressor severity. Finally, women who went on to give birth preterm had higher levels of plasma IL-6. These data thus highlight the potential importance of assessing and addressing lifetime stressor exposure among mothers before and during maternal-infant care.

Early Changes in Interferon Gene Expression and Antibody Responses Following Influenza Vaccination in Pregnant Women.

BACKGROUND: Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine have identified changes in immune gene expression that were correlated with antibody responses. The current study was performed to define baseline blood transcriptional profiles and changes induced by inactivated influenza vaccine in pregnant women and to identify correlates with antibody responses. METHODS: Pregnant women were immunized with inactivated influenza vaccine during the 2013-2014 and 2014-2015 seasons. Blood samples were collected on day 0 (before vaccination) and on days 1 and 7 after vaccination for transcriptional profile analyses, and on days 0 and 30, along with delivery and cord blood samples, to measure antibody titers. RESULTS: Transcriptional analysis demonstrated overexpression of interferon-stimulated genes (ISGs) on day 1 and of plasma cell genes on day 7. Prevaccination ISG expression and ISGs overexpressed on day 1 were significantly correlated with increased H3N2, B Yamagata, and B Victoria antibody titers. Plasma cell gene expression on day 7 was correlated with increased B Yamagata and B Victoria antibody titers. Compared with women who were vaccinated during the previous influenza season, those who were not showed more frequent significant correlations between ISGs and antibody titers. CONCLUSIONS: Influenza vaccination in pregnant women resulted in enhanced expression of ISGs and plasma cell genes correlated with antibody responses. Brief summary: This study identified gene expression profiles of interferon-stimulated genes and plasma cells before vaccination and early after vaccination that were correlated with antibody responses in pregnant women vaccinated for influenza.

Immune and Epigenetic Pathways Linking Childhood Adversity and Health Across the Lifespan.

Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.