Hybrid framework of fatigue: connecting motivational control and computational moderators to gamma oscillations.

Introduction: There is a need to develop a comprehensive account of time-on-task fatigue effects on performance (i.e., the vigilance decrement) to increase predictive accuracy. We address this need by integrating three independent accounts into a novel hybrid framework. This framework unites (1) a motivational system balancing goal and comfort drives as described by an influential cognitive-energetic theory with (2) accumulating microlapses from a recent computational model of fatigue, and (3) frontal gamma oscillations indexing fluctuations in motivational control. Moreover, the hybrid framework formally links brief lapses (occurring over milliseconds) to the dynamics of the motivational system at a temporal scale not otherwise described in the fatigue literature. Methods: EEG and behavioral data was collected from a brief vigilance task. High frequency gamma oscillations were assayed, indexing effortful controlled processes with motivation as a latent factor. Binned and single-trial gamma power was evaluated for changes in real- and lagged-time and correlated with behavior. Functional connectivity analyses assessed the directionality of gamma power in frontal-parietal communication across time-on-task. As a high-resolution representation of latent motivation, gamma power was scaled by fatigue moderators in two computational models. Microlapses modulated transitions from an effortful controlled state to a minimal-effort default state. The hybrid models were compared to a computational microlapse-only model for goodness-of-fit with simulated data. Results: Findings suggested real-time high gamma power exhibited properties consistent with effortful motivational control. However, gamma power failed to correlate with increases in response times over time, indicating electrophysiology and behavior relations are insufficient in capturing the full range of fatigue effects. Directional connectivity affirmed the dominance of frontal gamma activity in controlled processes in the frontal-parietal network. Parameterizing high frontal gamma power, as an index of fluctuating relative motivational control, produced results that are as accurate or superior to a previous microlapse-only computational model. Discussion: The hybrid framework views fatigue as a function of a energetical motivational system, managing the trade-space between controlled processes and competing wellbeing needs. Two gamma computational models provided compelling and parsimonious support for this framework, which can potentially be applied to fatigue intervention technologies and related effectiveness measures.

Real-life effectiveness of dupilumab in chronic rhinosinusitis with nasal polyps. Results from eight Hungarian centres with 12-month follow-up.

BACKGROUND: Research on the immune mechanism behind chronic rhinosinusitis (CRS) has revealed various new endotypes, leading to targeted therapies, especially for severe uncontrolled CRS. Biologics are novel therapeutic strategies providing targeted treatment for the difficult-to-treat recalcitrant CRSwNP patients. Dupilumab is a fully human-derived monoclonal antibody that binds to IL4Rα, inhibiting the signalling of both IL-4 and IL-13. In Hungary, it is approved for the treatment of uncontrolled CRSwNP according to criteria based on the EPOS2020 and the Hungarian guidelines. METHODOLOGY: This study aimed to collect and evaluate real-world therapeutic data of CRSwNP patients treated with dupilumab. One hundred thirty-five patients from eight different referral centres have been enrolled in this study, who received dupilumab since 2020. All subjects were adult patients (over 18 years) with uncontrolled CRSwNP. Baseline data collection included demographics, medical history, previous surgeries, related comorbidities, total endoscopic nasal polyp score (NPS), SNOT22, nasal congestion parameters measured with visual analogue scale (VAS) and nasal obstruction evaluation scale (NOSE), loss of smell score (LSS) and eosinophil count. 300 mg dupilumab was administered subcutaneously every second week. Follow up visits were performed after 6 and 12 months. RESULTS: After 6 and 12 months of treatment significant improvement was detected in all clinical parameters. Safety was proved, no severe side effects occurred, and no rescue treatment was necessary. CONCLUSIONS: Our real-life findings show that continuous dupilumab treatment is effective and safe in daily clinical practice in CRSwNP and other type 2 comorbidities such as bronchial asthma and NERD.

Silver Lining Study: Missileer Fatigue Mitigation During 2020 Coronavirus Pandemic.

INTRODUCTION: The U.S. Air Force's Intercontinental Ballistic Missile (ICBM) force stands ready to launch weapons 365 days per year. Since its inception, missileers vigilantly operate launch consoles on a 3-day cycle: minimum 24-hour alert-shift/24-hour travel-admin/24-hour off, leading to concerns that health, morale, and alertness are chronically impacted. In 2020, a Missileer Occupational Health Assessment (OHA) revealed 76% of respondents struggle with being rested for duty and 29% of respondents never feel adequately rested for duty. Later that year, 20th Air Force initiated long-duration operations to safeguard from the SARS CoV-2 (COVID-19) Pandemic, resulting in increased operations tempo, and exacerbating crew fatigue.341st Operations Group and 341st Medical Group at Malmstrom Air Force Base enacted interventions to mitigate crew fatigue and support continued readiness during pandemic operations. They recorded, analyzed, and compiled findings in this report, including recommendations for long-term ICBM operations at Missile Wings. MATERIALS AND METHODS: All participants were Nuclear and Missile Operations Officers, or missileers, were continuously evaluated with qualitative and quantitative measures to ensure safety of the force during a period of unprecedented change. Interventions implemented and evaluated during the 9-month period included: environmental modifications, scheduling changes, and crew education on fatigue management, nutrition, anticipatory sleep preparation, and fitness. Most notably, the 341st Operations Group examined various 3-person and 4-person shift-length and alert duration schedules. Psychomotor vigilance testing results validated safety of operators and delta between pre- and post-shift measurements. Crew force readiness trends were analyzed for force-health awareness. Pre- and post-OHA results were compared for subjective changes. Fatigue and health-related outcomes were collected from a safety monitoring effort during standard and COVID-19 operations at 341st Missile Wing. RESULTS: Findings from qualitative and quantitative data indicate the optimal schedule is a 3-week cycle:7-day alert/7-day recovery/7-day training-administrative utilizing 4-member or 3-member crews for low tempo operations. Crews experimented with shift-lengths of 24hrs-on/24hrs-off, 16hrs-on/8hrs-off, and 12hrs-on/12hrs-off. Maximum safe alert duration is 7 days due to task fatigue onset between 8 and 10 days. Short and long duration Duties Not to Include Flight (DNIF) (also known as Duties Not to Include Alert (DNIA) among missileers) rates decreased from the first to last month of the period by 74.6% and 79.2%, respectively. The number of alerts missed per month decreased 86% from baseline. The 2021 OHA found a 7% decline in members seeking separation, and absence of sleep, fatigue, and physical or mental health as missileer concerns. CONCLUSIONS: This analysis has identified a sustainable alert rotation of 7/7/7 with emphasis on protected recovery and training time and has been continued after concluding pandemic operations, creating consistent schedule stability where there once was none. If executed properly, this alert rotation, regardless of shift-length selected, has potential to improve trust between crews and leadership, provides adequate recovery time between alerts to maintain health, and improves wellness, family stability, morale, unit cohesion, and crew force retention. Notably, all Air Force Global Strike Missile Operations Groups adjusted scheduling practices to align with these findings.

Impact of parity and delivery mode on pelvic floor function in young women: a 3D ultrasound evaluation.

INTRODUCTION AND HYPOTHESIS: The objectives were to evaluate clinical and anatomical parameters assessed by three-dimensional pelvic floor ultrasound (3D ultrasound) in parous and nulliparous women of childbearing age and to assess underreported symptoms of sexual dysfunction (SD), urinary incontinence (UI) and flatus incontinence (FI). METHODS: Women without complaints of pelvic floor dysfunction, aged 20-50 years, were eligible for this prospective cross-sectional study. They completed the King's Health Questionnaire, Female Sexual Function Index and St Mark's Incontinence Score adapted for this study. Next, a physical examination and 3D ultrasound were performed. The scores obtained in the questionnaires were compared with the 3D ultrasound data. RESULTS: In total, 326 women were invited to participate. Of these, 203 women met the inclusion criteria, and their cases were classified as nulliparity (NU, 59), vaginal delivery (VD, 80), forceps delivery (FD, 18) and caesarean section (CS, 48). These groups were homogeneous regarding age (p=0.096), parity (p=0.051) and body mass index (p=0.06). The hiatal dimension (HD; p=0.003) and transverse diameter (TD) (p=0.001) were significantly different among the groups. Compared with the NU and CS groups, the VD and FD groups had an increased HD and TD. The frequencies of underreported symptoms identified by questionnaires were as follows: SD (46.3%), UI (35%) and FI (28%). After VD and FD, women were more likely to present UI (p<0.001), FI (p<0.001) and SD (p=0.002) than the women with NU and those who had undergone a CS. UI was related to a greater HD (p=0.002) and anteroposterior diameter (p=0.022), FI was associated with a thinner left pubovisceral muscle (p=0.013), and SD was related to a greater HD (p=0.026). CONCLUSIONS: Three-dimensional ultrasound can identify mild morphological changes in young women with apparently normal physical examinations, mainly after VD and FD. In such individuals, these findings are associated with higher incidences of underreported sexual, urinary and anal symptoms.

Aircrew Actual vs. Prescriptive Sleep Schedules and Resulting Fatigue Estimates.

BACKGROUND: Fatigue is an insidious and costly occurrence in the aviation community, commonly a consequence of insufficient sleep. Some organizations use scheduling tools to generate prescriptive sleep schedules to help aircrew manage their fatigue. It is important to examine whether aircrew follow these prescriptive schedules, especially in very dynamic environments. The current study compares aircrew sleep during missions to prescriptive sleep schedules generated by a mission scheduling tool. METHODS: Participating in the study were 44 volunteers (Mage= 28.23, SDage= 4.23; Proportionmale= 77.27%) from a C-17 mobility squadron providing 25 instances of sleep and mission data (80 flights total). Aircrew wore actigraph watches to measure sleep during missions and prescriptive sleep schedules were collected. Actual and prescriptive sleep was compared with calculated performance effectiveness values per minute across mission flights. RESULTS: Prescriptive schedules generally overestimated effectiveness during missions relative to estimated actual sleep, potentially causing shifts in effectiveness to ranges of increased risk requiring elevated fatigue mitigation efforts. Actual and prescriptive effectiveness estimates tended to increasingly diverge over the course of missions, which magnifies differences on longer missions. DISCUSSION: The current study suggests that aircrew sleep during missions often does not align with prescriptive sleep schedules generated by mission planning software, resulting in effectiveness estimates that are generally lower than predicted. This might discourage aircrew from using mission effectiveness graphs as a fatigue mitigation tool. Additionally, because fatigue estimates factor into overall operational risk management processes, these schedules might underestimate risks to safety, performance, and health. Morris MB, Veksler BZ, Krusmark MA, Gaines AR, Jantscher HL, Gunzelmann G. Aircrew actual vs. prescriptive sleep schedules and resulting fatigue estimates. Aerosp Med Hum Perform. 2021; 92(10):806814.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Functional Equivalence of Sleep Loss and Time on Task Effects in Sustained Attention.

Research on sleep loss and vigilance both focus on declines in cognitive performance, but theoretical accounts have developed largely in parallel in these two areas. In addition, computational instantiations of theoretical accounts are rare. The current work uses computational modeling to explore whether the same mechanisms can account for the effects of both sleep loss and time on task on performance. A classic task used in the sleep deprivation literature, the Psychomotor Vigilance Test (PVT), was extended from the typical 10-min duration to 35 min, to make the task similar in duration to traditional vigilance tasks. A computational cognitive model demonstrated that the effects of time on task in the PVT were equivalent to those observed with sleep loss. Subsequently, the same mechanisms were applied to a more traditional vigilance task-the Mackworth Clock Task-providing a good fit to existing data. This supports the hypothesis that these different types of fatigue may produce functionally equivalent declines in performance.

The effect of nasal provocation with a single-dose allergen on the physical and cognitive performance of patients with ragweed allergy.

Purpose This study aims to compare the impact of active allergic rhinitis on physical and cognitive abilities of trained allergic athletes to untrained allergic patients. Methods Cognitive, respiratory, and fitness functions were assessed before and after allergen exposure. Participants in both groups were provoked intranasally with ragweed allergen. Results The group of athletes revealed significantly higher average values in peak inspiratory flow and fitness index before and after provocation. In neuropsychological assessments, athletes performed significantly better after allergen provocation in complex working memory capacity. Due to single acute allergen exposure, the size of the nasal cavity and nasal inspiratory peak flow significantly decreased in both groups. The physical performance of both groups did not change after provocation. Executive functions and complex working memory capacity of athletes significantly improved resulting from provocation. Conclusions A single-shot allergen in high dose might cause an increase in mental concentration, which was more pronounced in the group of athletes. This study indicates that acute exposure to allergen cannot affect the physical performance and may result in increased mental focus in patients with allergy notwithstanding the declining respiratory functions.

Visual Working Memory Resources Are Best Characterized as Dynamic, Quantifiable Mnemonic Traces.

Visual working memory (VWM) is a construct hypothesized to store a small amount of accurate perceptual information that can be brought to bear on a task. Much research concerns the construct's capacity and the precision of the information stored. Two prominent theories of VWM representation have emerged: slot-based and continuous-resource mechanisms. Prior modeling work suggests that a continuous resource that varies over trials with variable capacity and a potential to make localization errors best accounts for the empirical data. Questions remain regarding the variability in VWM capacity and precision. Using a novel eye-tracking paradigm, we demonstrate that VWM facilitates search and exhibits effects of fixation frequency and recency, particularly for prior targets. Whereas slot-based memory models cannot account for the human data, a novel continuous-resource model does capture the behavioral and eye tracking data, and identifies the relevant resource as item activation.

Ramadan and diabetes - knowledge, attitude and practices of general practitioners; a cross-sectional study.

BACKGROUND AND AIMS: Fasting during Ramadan is obligatory for all Muslims across the world. Through literature review, it has been found out that there are various articles published for the awareness of patients and general population regarding safe fasting during Ramadan. But very few studies highlight the Ramadan specific knowledge of general practitioners engaged in providing care to people with diabetes. This study aims to describe the practice, knowledge and attitude of general practitioners regarding treatment and dietary modifications for people with diabetes during Ramadan across Pakistan. METHODS: A cross-sectional descriptive study was undertaken among a sample of 274 general practitioners. Data was collected by means of a questionnaire that consisted of 25 questions that were structured according to three categories i-e. Ramadan specific knowledge, diet and physical activity and treatment modification related knowledge and practices of GPs. RESULTS: Out of the total population of GPs surveyed, 70% responded correctly to the questions while 30% responded incorrectly. 1/4(th) of GPs incorrectly responded to questions regarding basic concepts of diabetes and Ramadan. 1/3(rd) of GPs responded incorrectly regarding questions on diet. Almost 40% of the GPs responded incorrectly to the questions regarding drug dosage adjustment in people with diabetes during Ramadan. However, more than 80% responded in agreement regarding alteration in medication timings. CONCLUSION: Almost one third of the studied populations of general practitioners across Pakistan lack the knowledge of basic principles that are important to be employed in the management of diabetes during Ramadan. Hence there is need to promote educational programmes and CMEs to improve the knowledge of our GPs that should be reflected by their sound clinical practices in the field of diabetes.

Sexual steroids in urogynecology.

The decline in sex hormone levels that accompanies the menopause has substantial effects on the tissues of the urogenital system, leading to atrophic changes. These changes can have negative effects on sexual and urinary function. The authors evaluate the repercussion of hypoestrogenism and sexual steroids on some elements of the pelvic floor and lower urinary tract. They summarize their research work and review significant published papers. They emphasize the changes in urinary mucosae, periurethral vessels, muscular layer, connective tissue, gene expression, autonomic nervous system receptors, as well as the main clinical aspects involved.

Estrogen therapy influence on periurethral vessels in postmenopausal incontinent women using Dopplervelocimetry analysis.

UNLABELLED: Lack of estrogen affects the urinary tract mainly by diminishing vascular, muscular and epithelial trophism, resulting in negative effects on continence in postmenopausal women. Therefore, the use of estrogens in these patients may revert these alterations and lead to an expressive improvement of the urinary symptoms. OBJECTIVE: Study the effect of topical estrogen therapy (conjugated equine estrogens, estriol or promestriene) in periurethral vessels detected by Dopplervelocimetric analysis using, as parameters: the number of vessels, resistance and pulsatility indexes, as well as the minimum diastolic value. METHODS: Forty-one postmenopausal women with stress urinary incontinence were randomized into three groups according to different types of topical estrogen received during 3 months. Group 1 received conjugated equine estrogens, group 2 received estriol and group 3 received promestriene. Periurethral Dopplervelocimetry analysis was done before estrogen administration and during treatment in all groups. RESULTS: We observed an increase in the number of the periurethral vessels in group 1 and group 2, being higher in group 1 than in group 2. The pulsatility index remained unchanged in all three groups. The resistance index at the periurethral vessels reduced only at the conjugated estrogen group (group 1). In this same group we noticed an increase in the mean minimal diastolic value, meaning a better periurethral vascularization. CONCLUSION: Topical conjugated equine estrogens and estriol were effective in increasing the number of periurethral vessels in postmenopausal women with urinary stress incontinence, with the conjugated equine estrogens being the most effective intervention studied.

Hormonal influence on periurethral vessels in postmenopausal incontinent women using Doppler velocimetry analysis.

UNLABELLED: The lack of estrogen affects the urinary tract mainly by diminishing vascular, muscular and epithelial trophism, resulting in negative effects on continence in postmenopausal women. OBJECTIVE: Study the effect of hormone therapy (estrogen and progesterone) in periurethral vessels detected by Doppler velocimetric analysis using, as parameters, the number of vessels, resistance and pulsatility indexes, as well as the minimum diastolic value. METHODS: Thirty-eight postmenopausal women with stress urinary incontinence were randomized into two groups. The first consisted of women receiving 3 months of estrogen therapy previous to 3 months of continuous estrogen and progesterone combined therapy. The second comprised of women receiving 3 months of continuous estrogen and progesterone therapy. Periurethral Doppler velocimetric analysis was done before hormone administration and during treatment in both groups. RESULTS: We observed a statistically significant increased number of periurethral vessels during treatment in both groups. There was an increase in value of the mean minimum diastolic value during estrogen and progesterone therapy in Group 2. The resistance indexes diminished in both groups. However, they were not statistically significant. CONCLUSION: Hormonal therapy of short duration (3-6 months) had a positive effect on the urethral continence mechanism increasing the number of periurethral vessels either with estrogen alone or combined therapy (estrogen and progesterone).

Doppler velocimetry parameters of periurethral vessels in postmenopausal incontinent women receiving estrogen replacement.

Estrogen deficit causes significant alterations in the lower urinary tract of women, largely affecting urinary continence mechanisms. The urethral vascular bed accounts for about one-third of urethral pressure, and as it undergoes marked hormonal influence we became interested in investigating its behaviour both prior to and during estrogen replacement. We selected 25 postmenopausal patients with urinary stress incontinence and studied the periurethral vessels by means of Doppler velocimetry, analyzing the number of vessels, systolic peak, minimum diastole, resistance and pulsatility indexes and the A/B ratio, prior to estrogen replacement and after 1 and 3 months of hormone use. We concluded that estrogen replacement alone in postmenopausal women with urinary stress incontinence increased the number of periurethral vessels, systolic peak and minimum diastole; however, a trend of no statistical significance towards the reduction of resistance and pulsatility rates of periurethral vessels was found; nor was a significant difference in the A/B ratio shown.

Power Doppler of the urethra in continent or incontinent, pre- and postmenopausal women.

Urethral pressure should exceed bladder pressure, both at rest and on stress, for urinary continence to occur. A decrease in urethral pressure is a major factor explaining the pathogenesis of urinary incontinence. A number of elements, such as smooth and striated periurethral muscles, and connective, vascular and elastic tissues, contribute to urethral pressure. The periurethral vessels are influenced by hormonal changes during the menstrual cycle, during pregnancy and postmenopause. We studied the periurethral vessels in 97 women, 57 of whom were incontinent and 40 continent, using power color Doppler velocimetry. The number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes, as well as systolic-diastolic ratio, were assessed. Statistically significant differences were found between incontinent women in the premenopausal period and those in the postmenopausal period, regarding the number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes.