Pregnancy as a window of opportunity for dementia prevention: a narrative review.

Dementia is a debilitating condition with a disproportionate impact on women. While sex differences in longevity contribute to the disparity, the role of the female sex as a biological variable in disease progression is not yet fully elucidated. Metabolic dysfunctions are drivers of dementia etiology, and cardiometabolic diseases are among the most influential modifiable risk factors. Pregnancy is a time of enhanced vulnerability for metabolic disorders. Many dementia risk factors, such as hypertension or blood glucose dysregulation, often emerge for the first time in pregnancy. While such cardiometabolic complications in pregnancy pose a risk to the health trajectory of a woman, increasing her odds of developing type 2 diabetes or chronic hypertension, it is not fully understood how this relates to her risk for dementia. Furthermore, structural and functional changes in the maternal brain have been reported during pregnancy suggesting it is a time of neuroplasticity for the mother. Therefore, pregnancy may be a window of opportunity to optimize metabolic health and support the maternal brain. Healthy dietary patterns are known to reduce the risk of cardiometabolic diseases and have been linked to dementia prevention, yet interventions targeting cognitive function in late life have largely been unsuccessful. Earlier interventions are needed to address the underlying metabolic dysfunctions and potentially reduce the risk of dementia, and pregnancy offers an ideal opportunity to intervene. This review discusses current evidence regarding maternal brain health and the potential window of opportunity in pregnancy to use diet to address neurological health disparities for women.

Identification of nutrition factors in the metabolic syndrome and its progression over time in older adults: analysis of the TUDA cohort.

BACKGROUND: Nutrition is recognized as playing an important role in the metabolic syndrome (MetS), but the dietary components involved are unclear. We aimed to investigate nutrition factors in relation to MetS and its progression in older adults over a follow-up period of 5.4 years. METHODS: Community-dwelling adults (≥ 60y) from the Trinity-Ulster-Department-of-Agriculture study, sampled at baseline (2008-12) and follow-up (2014-18; n 953), were classified as 'with MetS' by having three or more of: waist circumference (≥ 102 cm, males; ≥ 88 cm, females); HDL-cholesterol (< 1.0 mmol/L, males; < 1.3 mmol/L, females); triglycerides (≥ 1.7 mmol/L); blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mmHg); and hemoglobin A1c (≥ 39 mmol/mol). RESULTS: MetS was identified in 67% of participants, increasing to 74% at follow-up. Predictors at baseline for the development of metabolic syndrome (MetS) at follow-up were higher waist circumference (odds ratio [95%CI]; 1.06 [1.01-1.11]), but not BMI, and increased triglyceride concentrations (2.01 [1.29-3.16]). In dietary analysis (at follow-up), higher protein (g/kg bodyweight/day) and monounsaturated fatty acid (g/day) intakes were each associated with lower risk of MetS (0.06 [0.02-0.20] and 0.88 [0.78-1.00], respectively), whilst higher protein was also associated with lower abdominal obesity (0.10 [0.02-0.51]) and hypertension (0.22 [0.00-0.80]). Furthermore, participants with, compared to without, MetS consumed less high-quality protein foods (P = 0.006) and more low-quality protein foods (P < 0.001), as defined by the protein digestibility-corrected amino acid score. CONCLUSIONS: Dietary interventions targeting protein quantity and quality may have specific benefits in preventing or delaying the progression of MetS in at-risk older people, but this requires investigation in the form of randomized trials.

Oral cancer detection and progression prediction using noninvasive cytology-based DNA ploidy approach.

BACKGROUND: Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions. METHODS: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS). RESULTS: The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site. CONCLUSION: Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.

Sex differences in acute early life stress-enhanced fear learning in adult rats.

Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.

Ceftazidime Poloxamer Gel: Expanding the Therapeutic Armamentarium for Ciprofloxacin-Resistant Pseudomonas Mastoid Cavity Otorrhea.

OBJECTIVE: To present and evaluate the treatment of ciprofloxacin-resistant Pseudomonas mastoid cavity otorrhea with a ceftazidime thermosensitive poloxamer gel. STUDY DESIGN: A retrospective clinical capsule report. PATIENTS: Three patients diagnosed with ciprofloxacin-resistant Pseudomonas otorrhea in the setting of a previous canal-wall-down mastoidectomy between March 2019 and June 2023 visiting our tertiary care institution were retrospectively reviewed. INTERVENTION: Application of a 2% ceftazidime thermosensitive poloxamer gel to mastoid cavity. MAIN OUTCOME MEASURES: No evidence of disease during microscopic inspection of the ear within a month of initial treatment or bacterial eradication on subsequent culture. RESULTS: Two patients had complete resolution of symptoms and achieved a safe and dry ear after topical application of the hydrogel. The second patient had pseudomonal eradication on culture, but persistent otorrhea due to other multidrug-resistant bacteria and an anatomically unfavorable mastoid cavity, which ultimately resolved after revision surgery. CONCLUSIONS: This small case series suggests that topical treatment of mastoid cavity otorrhea with a 2% ceftazidime poloxomer gel is a potential therapeutic avenue in patients with ciprofloxacin-resistant Pseudomonas .

Endoscopic repair of tracheoesophageal fistulas: A contemporary multi-institutional case series and literature review.

OBJECTIVES: Recurrent and primary tracheoesophageal fistulas (TEFs) are a challenging surgical pathology to treat, as standard open surgical approaches are associated with high morbidity and mortality. As such, endoscopic modalities have gained interest as an alluring alternative, yet variable success rates have been reported in the literature. The aim of this study was to provide a contemporary update of the literature and describe our institutional experience with the bronchoscopic obliteration of recurrent and primary TEFs. METHODS: Retrospective chart review of all pediatric patients having undergone endoscopic TEF repair at two pediatric academic centers in Montreal, Canada and Lille, France between January 1, 2008 to December 31, 2020. RESULTS: 28 patients with TEFs (20 recurrent, 8 primary) underwent a total of 48 endoscopic procedures. TEF repair was performed under endoscopic guidance using various combinations of techniques, including fistula de-epithelialization (endoscopic brush, thulium laser, trichloroacetic acid-soaked pledgets or electrocautery), tissue adhesives, submucosal augmentation, esophageal clip and stenting. Successful closure was achieved in 16 patients (57 %), while 12 (43 %) required eventual open or thoracoscopic repair. The mean number of endoscopic procedures was 1.7. There were no major treatment-related complications such as pneumothorax, mediastinitis or death (mean follow-up 50.8 months). CONCLUSIONS: Endoscopic repair of recurrent or primary TEFs is a valuable component of our therapeutic armamentarium and may contribute to decreased surgical morbidity in this complex patient population. Families should be counselled that endoscopic results may be more modest than with open or thoracoscopic approaches, and multiple procedures may be required.

Neuroprotective amyloid ß N-terminal peptides differentially alter human α7- and α7ß2-nicotinic acetylcholine (nACh) receptor single-channel properties.

BACKGROUND AND PURPOSE: Oligomeric amyloid ß 1-42 (oAß1-42) exhibits agonist-like action at human α7- and α7ß2-containing nicotinic receptors. The N-terminal amyloid ß1-15 fragment (N-Aß fragment) modulates presynaptic calcium and enhances hippocampal-based synaptic plasticity via α7-containing nicotinic receptors. Further, the N-Aß fragment and its core sequence, the N-amyloid-beta core hexapeptide (N-Aßcore), protect against oAß1-42-associated synapto- and neurotoxicity. Here, we investigated how oAß1-42, the N-Aß fragment, and the N-Aßcore regulate the single-channel properties of α7- and α7ß2-nicotinic receptors. EXPERIMENTAL APPROACH: Single-channel recordings measured the impact of acetylcholine, oAß1-42, the N-Aß fragment, and the N-Aßcore on the unitary properties of human α7- and α7ß2-containing nicotinic receptors expressed in nicotinic-null SH-EP1 cells. Molecular dynamics simulations identified potential sites of interaction between the N-Aß fragment and orthosteric α7+/α7- and α7+/ß2- nicotinic receptor binding interfaces. KEY RESULTS: The N-Aß fragment and N-Aßcore induced α7- and α7ß2-nicotinic receptor single-channel openings. Relative to acetylcholine, oAß1-42 preferentially enhanced α7ß2-nicotinic receptor single-channel open probability and open-dwell times. Co-application with the N-Aßcore neutralized these effects. Further, administration of the N-Aß fragment alone, or in combination with acetylcholine or oAß1-42, selectively enhanced α7-nicotinic receptor open probability and open-dwell times (compared to acetylcholine or oAß1-42). CONCLUSIONS AND IMPLICATIONS: Amyloid-beta peptides demonstrate functional diversity in regulating α7- and α7ß2-nicotinic receptor function, with implications for a wide range of nicotinic receptor-mediated functions in Alzheimer's disease. The effects of these peptides on α7- and/or α7ß2-nicotinic receptors revealed complex interactions with these subtypes, providing novel insights into the neuroprotective actions of amyloid ß-derived fragments against the toxic effects of oAß1-42.

Evaluation of a Pilot Wellness Elective for Master of Public Health Students during the COVID-19 Pandemic.

BACKGROUND: Graduate student wellbeing is a public health issue in the United States. The COVID-19 outbreak exacerbated the mental health burden on graduate students worldwide. Culture of Wellness (PH 104) is a 2-week wellbeing elective course that teaches evidence-based wellbeing strategies for graduate students at a university in the United States. Our study aimed to evaluate the impact of this pilot wellbeing elective on Master of Public Health students' mental health and wellness during the COVID-19 pandemic. METHODS: Participants included 22 Master of Public Health students from the class of 2021 at a university in the United States. We provided a pre-course survey to students that assessed their perception of their own personal wellbeing, their knowledge about various wellbeing strategies, and their confidence in applying 13 wellbeing strategies before taking the course. Post-course students completed the same survey following course completion, as well as a matching evaluation and a five-month follow up survey. RESULTS: Of the 13 strategies taught, students reported significant improvements in their ability to apply 10 strategies. There was a significant increase in self-reported emotional and physical wellbeing, as well as a significant decrease in burnout. Five months post-course, more than three quarters of respondents used strategies taught in the course on a weekly basis or more. LIMITATIONS: This pilot study is limited by its small sample size, which may restrict the generalizability of the findings. CONCLUSIONS: The PH 104 Culture of Wellness course was effective in improving graduate students' wellbeing and confidence in applying wellbeing strategies.

Predicting trajectories of vocational indecision from motivational profiles in early adolescence.

BACKGROUND, OBJECTIVE AND HYPOTHESES: During emerging adulthood, vocational indecision (i.e., the inability to make coherent career choices) develops in a heterogeneous fashion, with three distinct patterns: low; decreasing (i.e., developmental or adaptative); high and stable or increasing (i.e., chronic or maladaptive). Among the determinants of vocational indecision that have been identified in past research, academic motivation is a crucial an excellent choice, since it is at school that students' vocational choices are validated or not. According to SDT, this motivation can vary both in quantity and quality, and students tend to experience more positive academic outcomes when their motivational profile is optimal (high quantity, high quality) as opposed to suboptimal (e.g., low quantity, low quality). Thus, the purpose of this longitudinal study was to verify if the patterns found with emerging adulthood students characterized vocational indecision in adolescent students, and if supported, to predict the belonging to the most problematic trajectory by using students' academic motivational profiles. We expected several distinct trajectories of vocational indecision that would differ in shape and magnitude, and several motivational profiles that vary in quality as well as in quantity. We also expected students in high-quality or quantity motivational profiles to be less likely to follow a chronic indecision trajectory. METHOD AND RESULTS: Using data from 384 students (56% female; Mage = 13.52 years; SD = .52 at Secondary 2) surveyed annually from Secondary 2 to 5, person-centered analyses enabled estimation of motivational profile in Secondary 2 and vocational indecision trajectories during the 4-year period. Results revealed four distinct patterns of vocational indecision during adolescence labelled Low and Stable, Moderate and Stable, Developmental and Chronic Intermittent. Four motivational profiles were also identified in Secondary 2, ranging from poor (Highly Amotivated) to moderate (Autonomous-Introjected) quality of self-determination level. Also, in reference to the most self-determined profile, students in the Mixed profile were at greatest risk of following Chronically-Intermittently Undecided trajectory. Finally, the most self-determined students were at greatest probability of following the Developmentally Undecided trajectory. CONCLUSION: Overall, the findings suggest that the student motivational functioning in early secondary school years could be used to identify students at risk of experiencing the negative indecision patterns across secondary school. Several theoretical and practical implications are suggested.

The Impact of Sleep on the Lives of Women Who Have Breast Cancer-Related Lymphedema: A Qualitative Exploration.

Background: Breast cancer survivors (BCSs) have many lifelong symptoms of anxiety, depression, lymphedema, and fatigue that can be exacerbated by sleep disturbance. However, little is known about unique factors contributing to sleep disturbance among BCSs with lymphedema; this requires further investigation to offer appropriate support and treatment to these individuals. Therefore, the objective of this study was to capture perceptions and experiences of lymphedema and sleep among BCSs with lymphedema. Methods and Results: Qualitative description guided data collection and analysis as part of a mixed-methods investigation to characterize sleep disturbance among BCSs with and without lymphedema. The participants were interviewed one-on-one using a semistructured interview guide. Inductive content analysis was completed using an iterative coding approach, condensing, and categorizing to develop four themes. Seven BCSs with lymphedema participated. From their narratives, four themes were developed: (1) mind and body fatigue are exacerbated by sleep disturbance; (2) fatigue impacted fragile coping and support systems; (3) fatigue influenced self-identity and roles in society; and (4) self-management strategies were used for sleep health. Conclusion: The participants' perceptions of sleep disturbances' impact on their lives endorse further investigation into optimal interventions to improve sleep quality and modify these impactful findings to create a higher quality of life for survivorship.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Use of dynamic tissue system adhesive skin closure device and multi-tissue platform porcine xenograft to achieve primary closure after wide local excision of a melanoma.

BACKGROUND: Wide local excision with sentinel lymph node biopsy has been the standard of care for melanoma with a Breslow depth greater than 1 mm. Wide local excision with 1- to 2-cm margins can result in large wounds that cannot be primarily closed. Traditionally, management has included reconstruction with autologous flaps and skin grafting. CASE REPORT: The authors of this case report achieved successful closure of a large posterior calf wound after 2-cm-wide local excision of the melanoma biopsy site in a 61-year-old male. The dermal lesion was a Clark level IV superficial spreading malignant melanoma with Breslow depth of 1.1 mm. Wound closure was achieved with a DTS adhesive skin closure device coupled with MTP xenograft powder as a healing adjunct. CONCLUSION: The results of this patient's case indicate that DTS adhesive skin closure device should be considered as an additional option for the closure of large defects following wide local excision in the management of melanoma.

Developing Porous Fibrin Scaffolds with Tunable Anisotropic Features to Direct Myoblast Orientation.

Functional regeneration of anisotropically aligned tissues such as ligaments, microvascular networks, myocardium, or skeletal muscle requires a temporal and spatial series of biochemical and biophysical cues to direct cell functions that promote native tissue regeneration. When these cues are lost during traumatic injuries such as volumetric muscle loss (VML), scar formation occurs, limiting the regenerative capacity of the tissue. Currently, autologous tissue transfer is the gold standard for treating injuries such as VML but can result in adverse outcomes including graft failure, donor site morbidity, and excessive scarring. Tissue-engineered scaffolds composed of biomaterials, cells, or both have been investigated to promote functional tissue regeneration but are still limited by inadequate tissue ingrowth. These scaffolds should provide precisely tuned topographies and stiffnesses using proregenerative materials to encourage tissue-specific functions such as myoblast orientation, followed by aligned myotube formation and recovery of functional contraction. In this study, we describe the design and characterization of novel porous fibrin scaffolds with anisotropic microarchitectural features that recapitulate the native tissue microenvironment and offer a promising approach for regeneration of aligned tissues. We used directional freeze-casting with varied fibrin concentrations and freezing temperatures to produce scaffolds with tunable degrees of anisotropy and strut widths. Nanoindentation analyses showed that the moduli of our fibrin scaffolds varied as a function of fibrin concentration and were consistent with native skeletal muscle tissue. Quantitative morphometric analyses of myoblast cytoskeletons on scaffold microarchitectures demonstrated enhanced cell alignment as a function of microarchitectural morphology. The ability to precisely control the anisotropic features of fibrin scaffolds promises to provide a powerful tool for directing aligned tissue ingrowth and enhance functional regeneration of tissues such as skeletal muscle.