Photoactivated Cyclic Polyphthalaldehyde Microcapsules for Payload Delivery.

Microcapsules with a cyclic polyphthalaldehyde (cPPA) shell and oil core were fabricated by an emulsification process. The low ceiling temperature cPPA shell was made phototriggerable by incorporating a photoacid generator (PAG). Photoactivation of the PAG created a strong acid which catalyzed cPPA depolymerization, resulting in the release of the core payload, as quantified by 1H NMR. The high molecular weight cPPA (197 kDa) yielded uniform spherical microcapsules. The core diameter was 24.8 times greater than the cPPA shell thickness (2.4 to 21.6 µm). Nonionic bis(cyclohexylsulfonyl)diazomethane (BCSD) and N-hydroxynaphthalimide triflate (HNT) PAGs were used as the PAG in the microcapsule shells. BCSD required dual stimuli of UV radiation and post-exposure baking at 60 °C to activate cPPA depolymerization while room temperature irradiation of HNT resulted in instantaneous core release. A 300 s UV exposure (365 nm, 10.8 J/cm2) of the cPPA/HNT microcapsules resulted in 66.5 ± 9.4% core release. Faster core release was achieved by replacing cPPA with a phthalaldehyde/propanal copolymer. A 30 s UV exposure (365 nm, 1.08 J/cm2) resulted in 82 ± 13% core release for the 75 mol % phthalaldehyde/25 mol % propanal copolymer microcapsules. The photoresponsive shell provides a versatile polymer microcapsule technology for on-demand, controlled release of hydrophobic core payloads.

The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter.

The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.6 years) and applied a watershed algorithm to define separate regional parcellations. We report biometrical twin modeling for five anatomically distinct regions: (1) Posterior, (2) Superior frontal and parietal, (3) Anterior and inferior frontal with deep areas, (4) Occipital, and (5) Anterior periventricular. We tested competing multivariate hypotheses to identify unique influences and to explain sources of covariance among the parcellations. Family aggregation could be entirely explained by additive genetic influences, with additive genetic variance (heritability) ranging from 0.69 to 0.79. Most genetic correlations between parcellations ranged from moderate to high (rg = 0.57-0.85), although two were small (rg = 0.35-0.39), consistent with varying degrees of unique genetic influences. This proof-of-principle investigation demonstrated the value of our novel, data-driven parcellations, with identifiable genetic and environmental differences, for future exploration.

Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial.

Background: DNA polymerase gamma (POLG)-related disorders are a group of rare neurodegenerative mitochondrial diseases caused by pathogenic variants in POLG, the gene encoding POLG. Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis. At present, there are no effective treatments for POLG-related disorders. Methods: In this study we report the interim 6-month data from a long term open-label, single arm phase 2 trial, in which we assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders. dC/dT was given enterally in powder form, dissolved in water. The primary outcome measures included Newcastle Mitochondrial Disease Scale (NMDS) score, serum growth differentiation factor 15 (GDF-15; a biomarker of mitochondrial dysfunction), electroencephalography (EEG), seizure diary, and blood and urine tests to assess end organ and mitochondrial function. Secondary outcome measures included recording of all adverse events to evaluate the safety of the intervention. The trial is registered with ClinicalTrials.gov, NCT04802707 (https://clinicaltrials.gov/ct2/show/NCT04802707). Data were collected from 14 October, 2021 to 13 December, 2023. Findings: We present 6-month interim data from the first ten people with POLG-related disorders enrolled in the trial, six with Alpers-Huttenlocher syndrome, two with ataxia-neuropathy spectrum, and two who do not fit into a classical POLG-related phenotype. During the 6 months of treatment, NMDS score improved from a mean of 27.3 at baseline to 20.7 at 6 months (estimated difference 6.0; 95% CI 2.5-∞). GDF-15 values remained stable or decreased in all patients; the mean decreased from 1031 pg/ml to 729 pg/ml (estimated difference 200; 95% CI 12-∞). 8/10 patients had abnormal baseline EEG; improvement in EEG was seen in 5 of these 8. There were no significant changes in other blood and urine testing. Regarding adverse events, two patients experienced diarrhea that spontaneously resolved. Interpretation: dC/dT is a promising treatment option for people with POLG-related disorders. Further research is needed to assess the long-term safety and efficacy in POLG-related disorders, as well as safety and efficacy in other mitochondrial DNA depletion disorders. Funding: This study was primarily funded by the Liam Foundation, with additional funding from the Savoy Foundation, Grand Défi Pierre Lavoie Foundation, and Fonds de Recherche du Québec - Santé.

Using Organoids to Model Sex Differences in the Human Brain.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell-derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome-linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

Sex differences are a contributing factor in neuropsychiatric conditions such as autism, which is more prevalent in males. Sex differences occur through interactions between sex steroid hormones such as estrogen and testosterone and sex chromosomes (chrX and chrY). Human stem cell­derived brain organoids are laboratory models that mimic brain development. For example, in individuals with neurodevelopmental conditions, brain organoids have revealed an imbalance of neuron populations compared with neurotypical individuals. In this review, we discuss sex steroid and sex chromosome influences on brain development and challenges of this model that need to be taken into account when studying sex differences.

Participatory design in telehealth research: Practical case examples.

Participatory design (PD) is a methodology that emphasizes user participation in the design of new technologies to leverage change within organizations and services. PD originated in the computer science field in the 1970s and 1980s when new programs and technologies were developed to empower workers, by involving them in decisions that affected them. PD in health research has been proven to change clinical practice. Genuine user involvement that includes all stakeholders, and robust collaborations across sciences, sectors, and disciplines are basic elements of successful research to change clinical practice and to implement novel technical and organizational approaches. This paper summarizes seven case studies involving the use of PD in telehealth research. All cases presented promoted organizational changes supported by health information and communications technology, and have been implemented at either international, national, regional, or local levels. We describe how PD can be applied in health sciences and used to facilitate organizational changes, new perspectives, and new communications methods. The relevance and suitability of PD as a research design in health science is explained, and recommendations for conducting PD studies in telehealth research are presented. In PD, mutual learning and co-creation is facilitated. Consequently, learning from users, rather than studying them, corroborates our understanding and the emergence of new knowledge.

Eye tracking insights into physician behaviour with safe and unsafe explainable AI recommendations.

We studied clinical AI-supported decision-making as an example of a high-stakes setting in which explainable AI (XAI) has been proposed as useful (by theoretically providing physicians with context for the AI suggestion and thereby helping them to reject unsafe AI recommendations). Here, we used objective neurobehavioural measures (eye-tracking) to see how physicians respond to XAI with N = 19 ICU physicians in a hospital's clinical simulation suite. Prescription decisions were made both pre- and post-reveal of either a safe or unsafe AI recommendation and four different types of simultaneously presented XAI. We used overt visual attention as a marker for where physician mental attention was directed during the simulations. Unsafe AI recommendations attracted significantly greater attention than safe AI recommendations. However, there was no appreciably higher level of attention placed onto any of the four types of explanation during unsafe AI scenarios (i.e. XAI did not appear to 'rescue' decision-makers). Furthermore, self-reported usefulness of explanations by physicians did not correlate with the level of attention they devoted to the explanations reinforcing the notion that using self-reports alone to evaluate XAI tools misses key aspects of the interaction behaviour between human and machine.

The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy.

Introduction: Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Methods: Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. Results: There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. Discussion: The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

Transcriptional and cellular response of hiPSC-derived microglia-neural progenitor co-cultures exposed to IL-6.

Elevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but the mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool to study the effects of IL-6 on features relevant for human neurodevelopment in vitro. We previously reported that hiPSC-derived microglia-like cells (MGLs) respond to IL-6, but neural progenitor cells (NPCs) in monoculture do not. Therefore, we investigated whether co-culturing hiPSC-derived MGLs with NPCs would trigger a cellular response to IL-6 stimulation via secreted factors from the MGLs. Using N=4 donor lines without psychiatric diagnosis, we first confirmed that NPCs can respond to IL-6 through trans-signalling when recombinant IL-6Ra is present, and that this response is dose-dependent. MGLs secreted soluble IL-6R, but at lower levels than found in vivo and below that needed to activate trans-signalling in NPCs. Whilst transcriptomic and secretome analysis confirmed that MGLs undergo substantial transcriptomic changes after IL-6 exposure and subsequently secrete a cytokine milieu, NPCs in co-culture with MGLs exhibited a minimal transcriptional response. Furthermore, there were no significant cell fate-acquisition changes when differentiated into post-mitotic cultures, nor alterations in synaptic densities in mature neurons. These findings highlight the need to investigate if trans-IL-6 signalling to NPCs is a relevant disease mechanism linking prenatal IL-6 exposure to increased risk for psychiatric disorders. Moreover, our findings underscore the importance of establishing more complex in vitro human models with diverse cell types, which may show cell-specific responses to microglia-released cytokines to fully understand how IL-6 exposure may influence human neurodevelopment.

Opportunities for Enhanced Public Health Surveillance via Molecular Detection and Sequencing of Diverse Respiratory Viruses From Self-collected SARS-CoV-2 Antigen Test Swabs.

We sequenced and genotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, adenovirus, and respiratory syncytial virus, among other pathogens, from residual anterior nasal swabs self-collected for rapid SARS-CoV-2 antigen testing at the US Naval Academy. This is a key proof-of-concept for an acute respiratory infection surveillance approach, which could leverage prevalent SARS-CoV-2 antigen self-testing.

Water-Enhancing Gels Exhibiting Heat-Activated Formation of Silica Aerogels for Protection of Critical Infrastructure During Catastrophic Wildfire.

A promising strategy to address the pressing challenges with wildfire, particularly in the wildland-urban interface (WUI), involves developing new approaches for preventing and controlling wildfire within wildlands. Among sprayable fire-retardant materials, water-enhancing gels have emerged as exceptionally effective for protecting civil infrastructure. They possess favorable wetting and viscoelastic properties that reduce the likelihood of ignition, maintaining strong adherence to a wide array of surfaces after application. Although current water-enhancing hydrogels effectively maintain surface wetness by creating a barricade, they rapidly desiccate and lose efficacy under high heat and wind typical of wildfire conditions. To address this limitation, unique biomimetic hydrogel materials from sustainable cellulosic polymers crosslinked by colloidal silica particles are developed that exhibit ideal viscoelastic properties and facile manufacturing. Under heat activation, the hydrogel transitions into a highly porous and thermally insulative silica aerogel coating in situ, providing a robust protective layer against ignition of substrates, even when the hydrogel fire suppressant becomes completely desiccated. By confirming the mechanical properties, substrate adherence, and enhanced substrate protection against fire, these heat-activatable biomimetic hydrogels emerge as promising candidates for next-generation water-enhancing fire suppressants. These advancements have the potential to dramatically improve the ability to protect homes and critical infrastructure during wildfire.

Haptoglobin phenotype and levels in type 2 diabetes and effects of fenofibrate.

AIMS/HYPOTHESIS: In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects. MATERIALS AND METHODS: In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in n = 200) at 2 years post-randomization to fenofibrate or placebo. RESULTS: The Hp phenotypes 1-1, 2-1, and 2-2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (P < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): -0.27 (-0.32, -0.23) mg/mL in Hp 1-1, -0.29 (-0.31, -0.27) mg/mL in Hp 2-1 and -0.05 (-0.07, -0.02) mg/mL in Hp 2-2 (P = 0.005 and P = 0.055 vs Hp 1-1 and Hp 2-1, respectively)). At 2 years post-randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate-group levels remained similar to the 6 week levels. CONCLUSIONS: In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2-2.

Telemedicine at a University Ophthalmology Practice During the Beginning of the COVID-19 Pandemic.

Purpose: The aim of the research was to evaluate the use of teleophthalmology at a university practice during the COVID-19 pandemic, specifically examining precision, effectiveness, and patient satisfaction. Patients and Methods: Telemedicine visits were offered to new and established patients requesting appointments with the Stony Brook University Department of Ophthalmology between March 30 and June 2, 2020. Records from these visits were reviewed for chief complaint, past medical and ocular history, diagnoses, treatment/management, and providers' sub-specialty. Precision was determined by comparing agreement between diagnoses of the telemedicine visit with those of the subsequent in-person visit. The decision to follow up in person was made by the physician and patient. Diagnostic precision as well as progression, improvement, or stability of patients' symptoms were determined by the physician's assessment at follow-up visits. Post-telemedicine visit satisfaction surveys were sent to all patients. Results: Telemedicine visits were offered to 783 patients, 520 (66.4%) of whom accepted. Of these 520 patients, 409 (78.7%) were established and 105 (20.2%) had in-person, follow-up visits. Overall, the diagnostic precision of the follow-up visits was 89.5%. Precision differed significantly across ophthalmologic subspecialties. Of the patients who had in-person follow-up visits, 56.8% remained stable, 32.4% improved, and 10.8% worsened. Established patients presented with more extensive ocular histories/procedures and experienced a higher percentage of worsening symptoms/disease stage compared to new patients. Oculoplastics/orbit was the most prevalent diagnostic subspecialty that worsened. Surveys were sent to all patients completing telemedicine visits, 15.0% of whom responded. Overall satisfaction was 91.9%, although only 23.0% of respondents preferred telemedicine to an in-office visit. Conclusion: Telehealth provides high levels of precision and patient satisfaction for a wide range of ophthalmologic visits, although most patients still prefer in-office examinations. Employing teleophthalmology for follow-up and emergency care may provide patients with an effective alternative during pandemic situations and beyond.

Telemedicine involves integration of modern telecommunications technology into medical practice. Over the years, it has demonstrated greater and more widespread utility for different medical specialties, including ophthalmology. As a response to the recent COVID-19 pandemic, the Stony Brook University Department of Ophthalmology provided an option of telemedicine for patients in lieu of in-person eye examinations. In this paper, Stony Brook ophthalmologists report on their experience with teleophthalmology, particularly regarding its utilization, accuracy, effectiveness, precision, and acceptability. The authors examined the records of 520 patients who had telemedicine encounters between March 30 and June 2, 2020. Precision was determined by comparing the initial and final diagnoses of all patients who had an in-person follow-up appointment following a telemedicine visit. Of 105 patients that followed up, precision was determined to be 89.5%. Precision was compared across ophthalmologic subspecialties and found to be statistically similar (p>0.05). Approximately a third of patients improved, while nearly 11% worsened. Established and oculoplastics patients were more significantly likely to worsen. Surverys were sent out to study patients to gauge their satisfaction with their telemedicine experience. Although satisfaction was nearly 92%, only 23% of patients preferred telemedicine to an in-person physician encounter. The authors conclude that teleophthalmology provides a high level of diagnostic precision and patient satisfaction; nevertheless, most patients prefer in-person physician encounters. Telemedicine may provide an effective alternative to in-person ophthalmology assessments, especially during a pandemic. There appears to be a lesser but potentially useful role for teleophthalmology in a non-pandemic setting.

The Mayo Leadership Impact Index Adapted for Matrix Leadership Structures: Initial Validity Evidence.

Importance: Physician burnout has reached crisis levels. Supportive leadership is one of the strongest drivers of physician well-being, and monitoring supervisor support is key to developing well-being focused leadership skills. Existing measures of leader support were designed within "direct report" supervision structures limiting their applicability to matrixed leadership reporting structures where direct reports are not the predominant norm. Antecedently, no measure of leadership support is validated specifically for implementation in matrixed leadership structures. Objective: Adapt and validate the Mayo Leadership Impact Index (MLII) for settings with matrixed leadership structures. Design: A psychometric validation study utilizing classical test theory and item response theory. Setting: A tripartite hospital system in the southwestern US. Participants: Physician-respondents to a 2023 cross-sectional survey. Main Outcomes and Measures: After pilot testing, the adapted MLII was examined using a unidimensional graded response model and confirmatory factor analyses. Convergent validity was investigated via correlations with professional fulfillment, perceived autonomy support, self-valuation, and peer connectedness/respect. Divergent validity was tested via correlations with burnout. Results: Of the three candidate revisions of the MLII, the 9-item adaptation was selected for its superior validity/reliability indices. Standardized Cronbach's and Ordinal alpha coefficients were 0.958 and 0.973, respectively. CFA loadings exceeded 0.70 (p < 0.001), and coefficients of variation (R2) exceeded 0.60 for all items. GRM slope parameters indicated "high" to "very high" item discrimination. Items 2, 5, and 8 were the most informative. Positive correlations of the adapted MLII with professional fulfillment, perceived autonomy support, and peer connectedness/respect were observed, supporting convergent validity. Negative correlation with overall burnout supports divergent validity. Conclusions and Relevance: The findings provide evidence of the adapted MLII's validity, reliability, and appropriateness for implementation within matrixed leadership settings. Prior to this study, no leadership support measure had been validated for use among the growing number of healthcare systems with matrixed leadership reporting structures.

Question: : What is the validity and reliability of a well-being centered leadership measure adapted for use in healthcare systems with matrixed, multiform reporting structures? Findings: : Classical test theory and item response theory analyses of cross-sectional survey data from 158 physician-respondents supported the adapted measure's construct validity. All reliability coefficients were strong. Leadership ratings positively correlated with professional fulfillment, autonomy support, self-valuation, and peer connectedness/respect, and negatively correlated with burnout. Meaning: : Findings support the adapted measure's validity and reliability. This study is the first to demonstrate a valid empirical measure of well-being centered leadership behaviors in settings with multiform, matrixed leadership structures.

Effects of Hormonal Contraception and the Menstrual Cycle on Maximal Strength and Power Performance.

INTRODUCTION: To evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared to an eumenorrheic (EUM) cycle, on maximal strength and power between hormone phases. METHODS: One repetition max (1RM) leg press and bench press, peak force (PF) from knee extension and upright row isometric dynamometry, and power from vertical jump height (VJH) and reactive strength index (RSI; cm/s) were measured in 60 healthy, active women (mean ± standard deviation [SD]; Age: 26.5 ± 7.0 yrs, BMI: 22.5 ± 3.7 kg/m2) who were monophasic OC users for ≥6 months (n = 21), had a H-IUD for ≥6 months (n = 20), or had regularly naturally occurring menstrual cycle for ≥3 months or were using a non-hormonal IUD (EUM; n = 19). Participants were randomly assigned to begin in the follicular phase/placebo pill (low hormone phase; LHP) or in the luteal phase/active pill (high hormone phase; HHP) and were tested once in each phase. Estimates of total lean mass (LM), leg LM, and arm LM were measured via dual energy x-ray absorptiometry. Separate univariate ANCOVAs were used to assess the change from HHP to LHP between groups, with LM and progesterone as covariates. RESULTS: Leg press 1RM was significantly different across phases between groups (p = 0.027), with higher leg press 1RM in the HHP for the OC group (mean difference[∆HHP-LHP] ± standard error: ∆7.4 ± 15.9 kg; p = 0.043) compared to the H-IUD group (∆-8.9 ± 23.8 kg; p = 0.043). All groups demonstrated similar bench press 1RM, PF, VJH, and RSI between phases (p > 0.05). CONCLUSIONS: Lower body strength was greater in the HHP for OC users (5.6% increase) suggesting lower body maximal strength outcomes may be influenced by hormonal contraception type.

Resting Energy Expenditure, Metabolic and Sex Hormones in Two Phases of the Menstrual and Hormonal Contraceptive Cycles.

INTRODUCTION: Resting energy expenditure (REE) may fluctuate during the menstrual cycle (MC), due to the physiological effects of estradiol (E2) and progesterone (P4). This study examined changes in REE and metabolic hormones (leptin, ghrelin, thyroid hormones), and dietary intake in two hormonally distinct groups, naturally menstruating women (NoOC) and women using monophasic combined oral contraceptives (COC). METHODS: Measurements included REE by indirect calorimetry, body composition by bioimpedance, and blood samples for hormone analysis in the early follicular and mid-luteal phases of the MC in NoOC-group (n = 38) or the active and inactive phases of the COC cycle (COC, n = 19). Participants recorded their food intake for 3 days after measurements. A secondary analysis was completed for the NoOC-group without REE outliers (difference between measurements >1.5 × interquartile range, n = 4). RESULTS: In the NoOC-group, luteal phase REE was 40 kcal higher than follicular phase REE [95% confidence interval (CI): -2 kcal/d-82 kcal/d, d = 0.20, p = 0.061]. Leptin (d = 0.35, p < 0.001), T3 (d = 0.26, p = 0.05) and fat intake (d = 0.48, p = 0.027) were lower, and T4 (d = 0.21, p = 0.041) was higher in the luteal phase. After excluding outliers, REE was 44 kcal higher in the luteal phase than in the follicular phase (95% CI: 12 kcal/d-76 kcal/d, d = 0.22, p = 0.007). In the COC-group, the mean difference in REE was -2 kcal (95% CI-82 kcal/d-79 kcal/d) between active and inactive phases, while T3 was higher in the inactive phase (d = 0.01, p = 0.037). CONCLUSIONS: REE increases only slightly from the follicular to the luteal phase but remains unchanged between COC phases. Increases in T3, leptin, and fat intake during the luteal phase might echo metabolic fluctuations that parallel female sex hormones during the MC.

Beyond Menstrual Dysfunction: Does Altered Endocrine Function Caused by Problematic Low Energy Availability Impair Health and Sports Performance in Female Athletes?

Low energy availability, particularly when problematic (i.e., prolonged and/or severe), has numerous negative consequences for health and sports performance as characterized in relative energy deficiency in sport. These consequences may be driven by disturbances in endocrine function, although scientific evidence clearly linking endocrine dysfunction to decreased sports performance and blunted or diminished training adaptations is limited. We describe how low energy availability-induced changes in sex hormones manifest as menstrual dysfunction and accompanying hormonal dysfunction in other endocrine axes that lead to adverse health outcomes, including negative bone health, impaired metabolic activity, undesired outcomes for body composition, altered immune response, problematic cardiovascular outcomes, iron deficiency, as well as impaired endurance performance and force production, all of which ultimately may influence athlete health and performance. Where identifiable menstrual dysfunction indicates hypothalamic-pituitary-ovarian axis dysfunction, concomitant disturbances in other hormonal axes and their impact on the athlete's health and sports performance must be recognized as well. Given that the margin between podium positions and "losing" in competitive sports can be very small, several important questions regarding low energy availability, endocrinology, and the mechanisms behind impaired training adaptations and sports performance have yet to be explored.

The human craniospinal venous system and its influence on postural intracranial pressure: a review.

OBJECTIVE: The cerebral and spinal venous systems have similar functions but unique anatomical and physiological properties. CSF occupies space in the cranial and spinal vaults, is continuously produced, and has many roles, including maintaining a favorable environment for CNS structures. The influence of the cerebrospinal venous system on CSF dynamics has been theorized since the 1940s. Newer studies suggest venous outflow pattern alterations in response to changes in body position. However, the relationship of postural cerebrospinal venous outflow shifts with and their influence on CSF homeostasis is not well understood. METHODS: The authors searched the published literature related to the anatomy and function of vertebral venous plexus (VVP), CSF, and positional cerebral venous flow characteristics. A comprehensive collection of literature was compiled and reviewed, and the relationship between cerebrospinal and venous system changes and alterations in body positions, with an emphasis on the craniocervical system, is discussed. RESULTS: The VVP is a network of valveless veins extending from the sacrum to the cranium that are interconnected with the cranial dural sinuses. The internal VVP occupies space within the extradural spinal canal and functions to return spinal venous blood to the heart, but it has additional properties, including the capability of bidirectional venous flow, an intraspinal dilatory capacity, and a role in cerebral venous outflow. When one rises to the upright position, CSF shifts toward the spinal canal and force vectors change, leading to reduced intracranial CSF pressure; simultaneously, cerebral venous outflow shifts from the jugular vein to the VVP outflow pathway. The venous outflow shift mechanism and its purpose are poorly understood. The authors review the known physiology of the system, identify gaps in knowledge to direct future research, and propose an interpretation of these data, concluding that position-dependent CSF and cerebrospinal venous shifts are part of a complementary positional craniospinal pressure regulation system that must be kept in balance for optimal CNS function. CONCLUSIONS: Current knowledge of the cerebrospinal venous anatomy, dynamic flow characteristics in response to gravity, and the venous system's influence on CSF suggests that the VVP plays a role in influencing CSF pressure, and the authors hypothesize that it plays a role in supporting intracranial pressure in the upright body posture. Further research is needed to better characterize the functional relationship of the VVP to CSF dynamics as well as identify potentially related disease states.

Structure-Function Relationship of Iron Oxide Nanoflowers: Optimal Sizes for Magnetic Hyperthermia Depending on Alternating Magnetic Field Conditions.

Iron oxide nanoflowers (IONFs) that display singular magnetic properties can be synthesized through a polyol route first introduced almost 2 decades ago by Caruntu et al, presenting a multi-core morphology in which several grains (around 10 nm) are attached together and sintered. These outstanding properties are of great interest for magnetic field hyperthermia, which is considered as a promising therapy against cancer. Although of significantly smaller diameter, the specific adsorption rate (SAR) of IONFs reach values as large as for "magnetosomes" that are natural magnetic nanoparticles typically ~40 nm found in certain bacteria, which can be grown artificially but with much lower yield compared to chemical synthesis such as the polyol route. This work aims at better understanding the structure-property relationships, linking the internal IONF nanostructure as observed by HR-TEM to their magnetic properties. A library of mono- and multicore IONFs is presented, with diameters ranging from 11 to 30 nm in a narrow size distribution. More particularly, by relating their structural features to their magnetic properties investigated by utilizing AC magnetometry over a wide range of alternating magnetic field conditions, we showed that the SAR values of all synthesized batches vary with overall diameter and number of constituting cores.

Successful completion of orthodontic therapy in a patient with osteopetrosis: Case Report.

INTRODUCTION: Orthodontic therapy in patients with osteopetrosis (OP) of the jaws has typically been contraindicated owing to the presence of poorly perfused and extremely compact bone, and the potential risk for infection and osteomyelitis. As such, completed orthodontic cases in association with OP have rarely been published. PATIENT CONCERNS: A patient aged 14 years 6 months, with no known diagnosis of OP, sought orthodontic assessment for anterior crowding. CLINICAL FINDINGS: The patient exhibited a straight facial profile and increased mandibular facial height, competent lips, shallow mentolabial sulcus with mild mentalis strain, flat/reverse smile arc and wide buccal corridors on smiling. PRIMARY DIAGNOSIS: The patient had a Class I incisor relationship on Class I skeletal bases with bilateral Class I molars and Class II canine relationships. This was complicated by a crossbite involving the lateral incisors and a Bolton discrepancy due to small maxillary lateral incisors. A radiologic assessment revealed polyostotic OP of the oromaxillofacial complex. INTERVENTIONS: Treatment consisted of maxillary and mandibular fixed orthodontic therapy, bite turbos and elastics to level and align the dentition. Extractions of permanent teeth were not needed. OUTCOMES: At the conclusion of treatment, there was a slight left Class II malocclusion, with incomplete intercuspation on the left side due to tooth size discrepancy, possibly attributed to inadequate elastics compliance and the presence of osteopetrotic bone. The treatment was completed in 3 years, 1 year longer than anticipated. CONCLUSION: This report represents the second published account of a patient with OP successfully managed with comprehensive orthodontic care and without osseous complications. Obtaining cephalometric measurements on OP-affected patients may be imprecise owing to the presence of extremely dense bone and difficulty to identify bony landmarks. To reduce osteopetrotic sequelae, attending clinicians should consider reduced exertional orthodontic forces and closely monitor patients for adverse alveolar events.