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Laura I Stirrat,1,2 Rebecca M Reynolds2,3 1Medical Research Council Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 2Tommy's Centre for Maternal and Fetal Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 3Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK Abstract: The prevalence of maternal obesity has increased significantly in recent years, and obesity is currently the most common comorbidity of pregnancy. Pregnancies of obese women are often defined as "high-risk" for the purposes of clinical care, with many well documented risks to the mother and developing baby. Maternal physiology and metabolism is dysregulated in the context of obesity, which may contribute to some of the adverse outcomes during pregnancy. Furthermore, maternal obesity has been hypothesized to cause harmful effects for the developing baby through "early life programming." This review will examine evidence from human studies for outcomes of offspring from obese women during pregnancy, during labor, during the neonatal period, and later in life. Keywords: pregnancy, short-term, physiology, metabolism, early life programming, neonatal complications, adverse intrauterine environment

The article discusses the guidelines on the care of pregnant women with obesity. Topics include the information on the risks of obesity during pregnancy and childbirth, the nutritional supplements to be recommended, the measurement of weight, height and body mass index and the factors to be considered in screening, diagnosing and managing maternal disease in obese pregnant women.

Objective: Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.Research Design and Methods: In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.Results: After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.Conclusions: DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation. [ABSTRACT FROM AUTHOR]

Objective: People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.Research Design and Methods: This was a cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.Results: In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).Conclusions: High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.Research Design and Methods: A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.Results: Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.Conclusions: In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline. [ABSTRACT FROM AUTHOR]

Case Summary: A 6-month-old male entire domestic shorthair cat presented for presumptive Toxoplasma myopathy that was non-responsive to antiprotozoal therapy. Clinical features included marked macroglossia, dysphagia, regurgitation, truncal muscle hypertrophy, pelvic limb gait abnormalities and megaoesophagus. Relevant diagnostics included serial creatine kinase activity, cardiac troponin I, fluoroscopic swallow study and routine muscle histopathology. Ultimately, post-mortem histopathology with immunostaining demonstrated markedly decreased or absent staining for the rod and carboxy terminus of dystrophin, confirming a dystrophin-deficient muscular dystrophy (MD). The misdiagnosis of toxoplasmosis was based on an increased IgG titre and muscle histopathology submitted to a local laboratory. Treatment for megaoesophagus included vertical feeding of wet food only, sildenafil and omeprazole. Dysphagia and regurgitation improved moderately. Presumptive hyperaesthesia and muscle pain were managed with anti-inflammatory doses of prednisolone. The patient was ultimately euthanased as a result of progressive MD signs and uraemia at 2 years of age., Relevance and Novel Information: This case report highlights the collective clinical features of MD, as they could be considered pathognomonic for this rare condition and must be differentiated from other myopathies via specific immunostaining of muscle biopsies. This is crucial to obtain a correct and early diagnosis, allowing instigation of potentially valuable treatments. Megaoesophagus is an inconsistent feature in feline MD in addition to the more commonly observed oropharyngeal dysphagia. Management with a canned diet, sildenafil, omeprazole and upright feeding was beneficial with moderate improvement in the frequency of regurgitation. Prednisolone was thought to minimise the presumptive myalgia., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: The objective of this study was to investigate the diagnostic potential of bacterial biomarkers by comparing the performance of molecular detection assays with clinical assessments of dog's oral health performed by veterinarians., Methods: Supragingival and subgingival plaque samples were collected from 127 client-owned dogs, pre-booked for procedures under general anesthesia, visiting veterinary practices in the United States. DNA was extracted and bacterial biomarkers quantified using quantitative polymerase chain reaction. Gingivitis and periodontitis were recorded by a trained clinician using the Weighted Gingivitis Periodontitis Score which involved assessing the buccal surfaces of 18 teeth while under general anesthesia. Intraoral dental radiographs of the left and right mandibular first molar teeth were also obtained. These data were then used to establish the diagnostic performance of the molecular assay to detect periodontitis., Results: An initial conscious, visual oral examination performed by the veterinarian identified 67.7% of dogs as having periodontitis, but examination under general anesthesia indicated a higher proportion (86.6%). Analysis of supragingival plaque samples collected by veterinarians from conscious and unconscious dogs demonstrated the assay had an accuracy of 77.7 to 80.9%, a sensitivity of 77.6 to 81.0%, and a specificity of 80.0%., Discussion: Use of this molecular screening tool in conscious dogs has the potential to improve early periodontal disease detection and support veterinary decision making, ultimately improving the oral health of dogs and consequently their quality of life., Competing Interests: CW, LC-M, RR, PB, TSM, TM, LH, PW, and AC are employees of Mars Petcare, a manufacturer of commercial petfood and provider of veterinary services. Mars Petcare has filed a number of patents relating to the compositional analysis of the canine oral microbiome as a diagnostic for canine periodontal disease. CH and MS-R received payment from Mars Petcare for consultation relating to this research. CH is employed by the company Colin Harvey LLC., (Copyright This work is authored by Wallis, Soltero-Rivera, Harvey, Reynolds, Carvell-Miller, Colyer, McKee, Millis, Bergman, Watson and Holcombe. © 2024 Mars Petcare UK and its affiliates for Wallis, Reynolds, Carvell-Miller, Colyer, Watson and Holcombe and © 2024 VCA Clinical Studies for McKee, Mills and Bergman.)

Craniofacial fibrous dysplasia (CFFD) is a benign, bony disease that may affect the skull base.1,2 Most cases are asymptomatic and observed; however, advanced disease can present with cranial neuropathy or craniofacial deformity requiring intervention.3-5 A 16-year-old adolescent girl with known CFFD involving the sphenoid and frontal bones with severe bilateral optic canal narrowing developed progressive right eye visual decline and frontal cosmetic deformity. Visual acuity worsened oculus dextrus (OD) to 20/30 with a new superior nasal scotoma and 20% loss in the retinal nerve fiber layer and remained oculus sinister (OS) 20/20. The patient was recommended a staged subfrontal craniotomy for right optic decompression and simultaneous correction cosmetic deformity followed by endonasal right optic decompression. On postoperative day one, visual acuity OD improved to 20/20; however, she developed OS visual decline to 20/800. Curiously, there were no episodes of intraoperative hypotension or additional iatrogenic compression. Use of methylprednisolone led to improvement OS 20/400. Given persistent visual decline, urgent second stage endonasal bilateral optic nerve decompression, rather than unilateral, was performed. Postoperatively, vision improved to OS 20/200. At one month, her vision improved to OD 20/15 and OS returned to 20/20 with a paracentral scotoma and 29% decline in left retinal nerve fiber layer with further improvement anticipated. This video describes a multidisciplinary, multistaged approach in treatment of optic nerve compression due to CFFD in addition to the management of unanticipated contralateral visual decline. The patient consented to the procedure and publication of her image. No Institutional Review Board/ethics committee approval was necessary for this case report., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Endovascular treatment of complex vascular pathologies in the pediatric population is often performed by nonpediatric subspecialists with adaptation of equipment and techniques developed for adult patients. We aimed to report our center's experience with safety and outcomes of endovascular treatments for pediatric vascular pathologies., Methods: We performed a retrospective review of our endovascular database. All patients ≤18 years who underwent endovascular treatment between January 1, 2004 and December 1, 2022 were included., Results: During the study time frame, 118 cerebral angiograms were performed for interventional purposes in 55 patients. Of these patients, 8(14.5%) had intracranial aneurysms, 21(38.2%) had intracranial arteriovenous malformations, 6(10.9%) had tumors, 5(9.1%) had arterial occlusions (n = 3) or dissections (n = 2), 8(14.5%) had vein of Galen malformations, and 7(12.7%) had other cerebrovascular conditions. Of the total 118 procedures, access-site complications occurred in 2(1.7%), intraprocedural complications occurred in 3(2.5%), and transient neurological deficits were observed after 2(1.7%). Treatment-related mortality occurred in 1(1.8%) patient., Conclusions: Neurointervention in pediatric patients was safe and effective in our experience., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The U.S. Food and Drug Administration is considering a policy to reduce nicotine in cigarettes to non-addictive levels. Although current evidence supports the public-health benefits of a reduced-nicotine policy, almost half of people who smoke (∼ 40%) do not support the policy. This study estimates the factors most strongly associated with support or opposition toward the policy, including tobacco use status, perceived effects of a reduced nicotine policy, trust in the FDA, and psychological distress. The study aims to inform messaging campaigns and policy makers., Methods: Data were collected in 2021 with nationally representative samples of U.S. adults (n = 1763). After receiving information about the reduced nicotine policy, participants indicated their beliefs and support for or opposition to the policy, along with other individual difference characteristics. Univariate population parameters and multinomial logistic regression coefficients were estimated., Results: In adjusted models, people who formerly or never smoked were less likely to oppose the policy compared to those who currently smoke; people with higher psychological distress and those who believe the policy will promote switching to e-cigarettes were more likely to oppose the policy. In addition, people were more likely to support the policy if they believed it would make quitting easier or that the FDA is trustworthy., Conclusions: Educational campaigns about reduced nicotine policy should expect higher impact by targeting prevalent perceptions and those more strongly associated with policy sentiment. In anticipation of the policy rollout, there may be a critical window to shape public opinion., Competing Interests: Declaration of competing interest D.L.A. has received funds for work done for the World Health Organization Tobacco Free Initiative, as a consultant for Pfizer and McKing Consulting, Inc. (Atlanta, GA, USA), as an employee of Cherokee National Operational Systems, and as a Special Government Employee of the U.S. Food and Drug Administration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Promoting minorities within medical specialties has been postulated to be crucial to patient care and recruitment of diverse candidates. This concept has been suspected but not formally studied in the minority of women faculty and trainees in neurosurgery. We aimed to quantitatively investigate the postulated correlation relative to female representation in neurosurgery., Methods: Data obtained from accredited neurosurgery residency programs were reviewed. Data describing the percentage of female residents and 6 demographic and 14 program-specific variables were collected. All program websites were reviewed to assess percentages of female faculty and visible commitment to diversity in applicants, evident through communicated policies, statements, or initiatives. Included programs were defined as "low" or "high" percentage of female residents or faculty relative to the grouped median value for both categories; groups were assessed for significant differences. Percentages of female faculty and residents and program-communicated diversity initiatives were investigated for significant correlation., Results: Female faculty and diversity data were available at 117 program sites; 81 programs reported female resident percentages. Analysis revealed a significant positive correlation between female faculty and female resident percentages. Programs with higher female resident percentages had higher levels of diversity in terms of race and ethnicity. No significant correlation was found between the percentage of female faculty or residents and a communicated diversity initiative., Conclusion: This study of current female representation in neurosurgery revealed a previously undocumented positive correlation between percentages of female faculty and female trainees. These data suggest a modifiable barrier to female entry into neurosurgical residency programs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Craniosynostosis is a developmental anomaly resulting from the premature fusion of cranial sutures, with an estimated incidence of 1 per 2000 to 1 per 2500 births.1 Surgical options for correction include open calvarial vault reconstruction, and more recently, endoscopic-assisted repairs that have been introduced to mitigate blood loss and hospital stay,2 although these remain understudied. In this operative video (Video), the authors present the case of an 11-month-old girl with right-sided coronal craniosynostosis that was treated with coronal cranial vault reconstruction with fronto-orbital advancement using computer-aided surgical simulation (KLS Martin Group), which has been studied previously with acceptable results when comparing the preoperative plan to the postoperative outcome.3 The patient was seen in follow-up at 1 month and 6 months and remained neurologically intact, continuing to meet all her developmental milestones appropriately. The patient's guardians consented to performance of the procedure and publication of the images. Institutional review board approval was deemed unnecessary. The participants and any identifiable individuals consented to publication of his/her images., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Craniofacial fibrous dysplasia (CFD) is a rare developmental disease of bone, which typically presents as a painless, expansile mass causing deformity of the craniofacial skeleton. In rare circumstances, compression of neurovascular structures may arise, causing symptoms such as pain, visual impairment, and hearing loss. Traditionally, CFD debulking has been performed with "freehand" techniques using preoperative imaging and anthropometric norms to determine the ideal amount of tissue removal. The advent of computer-assisted surgery, computer-aided design, and computer-aided manufacturing (CAD/CAM) has revolutionized the management of CFD. Surgeons can now fabricate patient-specific osteotomy/ostectomy guides, allowing for increased accuracy in bone removal and improved cosmetic outcomes. This series of 3 cases describe our institution's technique using patient-specific ostectomy "depth guides", which allow for maximum removal of fibro-osseous tissue while sparing deep and adjacent critical structures. These techniques can be widely applied to the craniofacial skeleton to assist in the surgical management of CFD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19., Design: Retrospective multicentre cohort., Setting: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland., Population: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021)., Methods: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia., Main Outcome Measures: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission., Results: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic., Conclusions: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: USA is considering reducing nicotine in cigarettes to non-addictive levels, coupled with promoting alternative nicotine delivery products (eg, e-cigarettes). However, effective communication is needed to reduce misperceptions about very low nicotine cigarettes (VLNCs) being less harmful than regular cigarettes., Methods: In 2022-2023, we conducted a four-group randomised clinical trial with a national probability sample from an online panel (971 adults who smoked cigarettes exclusively, 472 adults who dual used cigarettes and e-cigarettes and 458 adults aged 18-29 who had never smoked). Participants were randomised (parallel assignment) to one message condition: (1) VLNCs as harmful but easier to quit than regular cigarettes (n=468), (2) those who are not ready to quit should consider switching to e-cigarettes as less harmful alternatives (n=484), (3) combined (VLNC and e-cigarette messages; n=476) or (4) control condition (ie, water ads), n=473. The primary outcome was perceived absolute harm of VLNCs., Results: Perceived harm of VLNCs was higher in the VLNC condition compared with the e-cigarette and control conditions, and higher in the combined condition compared with the e-cigarette condition (adjusted p<0.05). Among adults who dual used, intention to switch to e-cigarettes was higher in the VLNC condition than the e-cigarette, combined or control conditions (adjusted p<0.05)., Conclusions: VLNC messages reduced the misperception that VLNCs are less harmful than cigarettes, but adding messages about e-cigarettes did not enhance desired outcomes. These VLNC messages can be considered during the rollout of a reduced nicotine policy., Trial Registration: NCT05506046., Competing Interests: Competing interests: DLA has received funds for work done for the World Health Organization Tobacco Free Initiative, as a Special Government Employee of the U.S. Food and Drug Administration, as a consultant for Pfizer, as an employee of Cherokee National Operational Systems and as an independent contractor for MK Consulting., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To reduce smoking and the harms it causes, countries, including the USA, are considering policies to reduce nicotine in combustible tobacco to minimally addictive levels. Effective messages about very low nicotine cigarettes (VLNCs) and this policy are crucial in combating misperceptions threatening the policy's effectiveness., Data and Methods: A discrete choice experiment assessed messages about VLNCs. Participants were 590 adults who smoked exclusively, 379 adults who both smoked and used e-cigarettes, 443 adults who formerly smoked and 351 young adults who never smoked (total n=1763). Seven message attributes were varied systematically (source, harm, chemicals, nicotine, satisfaction, addictiveness and quitting efficacy). Outcomes were selection of messages that generated the most positive attitude towards reduced nicotine policy, the greatest perceived harmfulness of VLNCs, and most strongly motivated quitting and initiating behaviour for VLNCs., Results: Information about specific harms and chemicals of VLNCs had the largest effects on selection of messages as eliciting more negative attitudes towards VLNCs policy, increasing perceived VLNC harmfulness, increasing motivation to quit VLNCs and decreasing motivation to try VLNCs. Messages with information about quitting efficacy were selected as more motivating to quit among those who smoke, but also more motivating to try VLNCs among those who do not smoke., Conclusion: Harm and chemical information can be prioritised to ensure VLNCs are not misperceived as less harmful than regular cigarettes. Messages about increased quitting efficacy and reduced addictiveness associated with VLNCs may backfire if presented to those who do not smoke., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment., Method: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry., Results: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ 2 =0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively., Conclusions: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This study investigated sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged military training. Twenty-three trainees (14 women) completed 44-wk military training (three terms of 14 wk with 2-wk adventurous training). Dietary intake and total energy expenditure were measured over 10 days during each term by weighed food and doubly labeled water. Body composition was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at the end of each term. Circulating metabolic and endocrine markers were measured at baseline and at the end of terms 2 and 3 . Absolute energy intake and total energy expenditure were higher, and energy balance was lower, for men than women ( P ≤ 0.008). Absolute energy intake and balance were lower, and total energy expenditure was higher, during term 2 than terms 1 and 3 ( P < 0.001). Lean mass did not change with training ( P = 0.081). Fat mass and body fat increased from term 1 to terms 2 and 3 ( P ≤ 0.045). Leptin increased from baseline to terms 2 and 3 in women ( P ≤ 0.002) but not in men ( P ≥ 0.251). Testosterone and free androgen index increased from baseline to term 3 ( P ≤ 0.018). Free thyroxine (T4) decreased and thyroid-stimulating hormone (TSH) increased from baseline to term 2 and term 3 ( P ≤ 0.031). Cortisol decreased from baseline to term 3 ( P = 0.030). IGF-I and total triiodothyronine (T3) did not change with training ( P ≥ 0.148). Men experienced greater energy deficits than women during military training due to higher total energy expenditure. NEW & NOTEWORTHY Energy deficits are common in military training and can result in endocrine and metabolic disturbances. This study provides first investigation of sex differences in energy balance, body composition, and endocrine and metabolic markers in response to prolonged and arduous military training. Men experienced greater energy deficits than women due to higher energy expenditure, which was not compensated for by increased energy intake. These energy deficits were not associated with decreases in fat or lean mass or metabolic or endocrine function.

Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies., Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study)., Measurements: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD)., Results: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores., Conclusions: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine., Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model., Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature ( p  > 0.063). There was no significant effect of treatment on heart rate ( p  = 0.364). There was a significant effect of time ( p  = 0.003) on heart rate with overall heart rates being less than baseline at 64 h., Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Reed, Berghaus, Reynolds, Holmes, Krikorian, Sakai, Ishikawa and Knych.)

Background and Objective: Computer-aided surgical simulation (CASS) can be used to virtually plan ideal outcomes of craniosynostosis surgery. Our purpose was to create a workflow analyzing the accuracy of surgical outcomes relative to virtually planned fronto-orbital advancement (FOA)., Methods: Patients who underwent FOA using CASS between October 1, 2017, and February 28, 2022, at our center and had postoperative computed tomography within 6 months of surgery were included. Virtual 3-dimensional (3D) models were created and coregistered using each patient's preoperative and postoperative computed tomography data. Three points on each bony segment were used to define the object in 3D space. Each planned bony segment was manipulated to match the actual postoperative outcome. The change in position of the 3D object was measured in translational (X, Y, Z) and rotational (roll, pitch, yaw) aspects to represent differences between planned and actual postoperative positions. The difference in the translational position of several bony landmarks was also recorded. Wilcoxon signed-rank tests were performed to measure significance of these differences from the ideal value of 0, which would indicate no difference between preoperative plan and postoperative outcome., Results: Data for 63 bony segments were analyzed from 8 patients who met the inclusion criteria. Median differences between planned and actual outcomes of the segment groups ranged from -0.3 to -1.3 mm in the X plane; 1.4 to 5.6 mm in the Y plane; 0.9 to 2.7 mm in the Z plane; -1.2° to -4.5° in pitch; -0.1° to 1.0° in roll; and -2.8° to 1.0° in yaw. No significant difference from 0 was found in 21 of 24 segment region/side combinations. Translational differences of bony landmarks ranged from -2.7 to 3.6 mm., Conclusion: A high degree of accuracy was observed relative to the CASS plan. Virtual analysis of surgical accuracy in FOA using CASS was feasible., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Objectives: Social determinants of health (SDOH) are nonmedical factors that affect health outcomes. Limited investigation has been completed on the potential association of these factors to adverse outcomes in pediatric populations. In this study, the authors aimed to analyze the effects of SDOH disparities and their relationship with outcomes after brain tumor resection or biopsy in children., Methods: The authors retrospectively reviewed the records of their center's pediatric patients with brain tumor. Black race, public insurance, median household income, and distance to hospital were the investigated SDOH factors. Univariate analysis was completed between number of SDOH factors and patient demographics. Multivariate linear regression models were created to identify coassociated determinants and outcomes., Results: A total of 272 patients were identified and included in the final analysis. Among these patients, 81 (29.8%) had no SDOH disparities, 103 (37.9%) had 1, 71 (26.1%) had 2, and 17 (6.2%) had 3. An increased number of SDOH disparities was associated with increased percentage of missed appointments ( P = .002) and emergency room visits ( P = .004). Univariate analysis demonstrated increased missed appointments ( P = .01), number of postoperative imaging ( P = .005), and number of emergency room visits ( P = .003). In multivariate analysis, decreased median household income was independently associated with increased length of hospital stay ( P = .02)., Conclusion: The SDOH disparities are prevalent and impactful in this vulnerable population. This study demonstrates the need for a shift in research focus toward identifying the full extent of the impact of these factors on postoperative outcomes in pediatric patients with brain tumor., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)