Gene-Environment Interaction Between CYP1B1 and Oral Contraception on Frontal Fibrosing Alopecia.

Importance: Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies. Objective: To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk. Design, Setting, and Participants: This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023. Main Outcome and Measure: The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model. Results: Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02). Conclusions and Relevance: This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.

Motor Output Variability in Movement Disorders: Insights From Essential Tremor.

Findings on individuals with essential tremor suggest that tremor (within-trial movement unsteadiness) and inconsistency (trial-to-trial movement variance) stem from distinct pathologies and affect function uniquely. Nonetheless, the intricacies of inconsistency in movement disorders remain largely unexplored, as exemplified in ataxia where inconsistency below healthy levels is associated with greater pathology. We advocate for clinical assessments that quantify both tremor and inconsistency.

Distribution of gamma-ray elements in Cerro do Jarau impact structure and a proposal of geothermal modeling.

Large meteorite impacts release kinetic energy that induces rock deformation, high temperatures and fluid circulation during the cratering process. To understand the correlation between rock deformation and fluid circulation, it is relevant to investigate post-impact hydrothermal flux and its relation to the local geology. The Cerro do Jarau impact structure is a ~13.5 km diameter impact structure located in southern Brazil and formed on Cretaceous continental flood basalts of the Serra Geral Formation and underlying sedimentary strata. This study collected ground gamma-ray data over the structure and produced K, eTh and eU concentrations, eTh/K ratio and F-factor maps to characterize it in terms of its radiometric signatures and their respective spatial distribution. A general decrease in the concentration of the three elements was observed from the outer-rim towards the center of the crater. The central area is defined by very low radiometric values, with relatively high K values, thus indicating the occurrence of K-bearing rocks. Numerical simulations using the HYDROTHERM 3 code showed the fluid circulation pattern over the impact structure. Data interpretation resulted in a scenery consistent with potential fluid remobilization within the impact structure related to hydrothermal processes in the late stages of the crater formation process.

Evaluation of the satisfaction and experiences of oncology patients and doctors using teleconsultation during the COVID-19 pandemic.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the Gustave Roussy Cancer Center introduced teleconsultation via telephone, as an alternative to face-to-face consultation to reduce patient hospital visits. This study was designed to assess patient and doctor satisfaction with this modality of care in oncology patient care during the period of the pandemic and beyond. METHODS: We designed two questionnaires based on validated scores to assess satisfaction from teleconsultation in patients (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) and doctors (Telehealth Usability Questionnaire [TUQ]), and anxiety levels in both groups (anxiety section of the Hospital Anxiety and Depression Scale [HADS], HADS-A). These were electronically sent to patients and doctors with experience of at least one remote consultation during the first wave of the COVID-19 pandemic. RESULTS: 239 patients and 32 doctors were eligible for the analyses. In the patient group, the mean satisfaction scores were 79.5 (SD 18.1) and 74.92 (SD 15.3) for EORTC OUT-PATSAT 35 and TSQ, respectively. In the doctor group, the mean satisfaction scores were 67.1 (SD 12.7) and 64.9 (SD 13.9) for TUQ and TUQ for Skype for Business, respectively. 65.7% of patients and 81.2% of doctors had no/low anxiety. Univariable analyses in patients showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores with anxiety and gender, with lower mean scores in women compared to men. Multivariable analysis showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores to anxiety in both patients and doctors. CONCLUSIONS: Teleconsultation via telephone is an acceptable modality of care for oncology patients, with high satisfaction from its implementation during the pandemic reported by patients and doctors. This was consistent across responder groups with different characteristics. An individualized approach to patients should be implemented for the safe and effective use of teleconsultation in oncology beyond the pandemic.

Unique Neural Mechanisms Underlying Speed Control of Low-Force Ballistic Contractions.

According to the speed-control hypothesis, the rate of force development (RFD) during ballistic contractions is dictated by force amplitude because time to peak force (TPF) remains constant regardless of changes in force amplitude. However, this hypothesis has not been tested at force levels below 20% of an individual's maximum voluntary contraction (MVC). Here, we examined the relationship between the RFD and force amplitude from 2 to 85% MVC and the underlying structure of muscle activity in 18 young adults. Participants exerted ballistic index finger abductions for 50 trials in each of seven randomly assigned force levels (2, 5, 15, 30, 50, 70, and 85% MVC). We quantified TPF, RFD, and various EMG burst characteristics. Contrary to the speed-control hypothesis, we found that TPF was not constant, but significantly varied from 2 to 85% MVC. Specifically, the RFD slope from 2 to 15% MVC was greater than the RFD slope from 30 to 85% MVC. Longer TPF at low force levels was associated with the variability of EMG burst duration, whereas longer TPF with higher force levels was associated with the EMG burst integral. Contrary to the speed-control hypothesis, we found that the regulation of TPF for low and high force levels was different, suggesting that neuronal variability is critical for force levels below 30% MVC and neuronal amplitude for force levels above 30% MVC. These findings present compelling new evidence highlighting the limitations of the speed-control hypothesis underscoring the need for a new theoretical framework.

A Rare Case of COVID-19 Related Acute Necrotizing Encephalopathy With the RANBP2 Mutation in a Pediatric Patient.

Acute necrotizing encephalopathy (ANE) is a rare childhood neurological disorder. The familiar type of ANE (ANE1) is associated with a mutation in the RANBP2 gene. Both SARS-CoV-2 and RANBP2 mutations are responsible for the manifestation of a hyper-inflammatory response that invades the central nervous system and plays a key role in the rapid progression of encephalopathy.

Visual Information Processing in Older Adults: Force Control and Motor Unit Pool Modulation.

Increased visual information about a task impairs force control in older adults. To date, however, it remains unclear how increased visual information changes the activation of the motor unit pool differently for young and older adults. Therefore, this study aimed to determine how increased visual information alters the activation of the motor neuron pool and influences force control in older adults. Fifteen older adults (66-86 years, seven women) and fifteen young adults (18-30 years, eight women) conducted a submaximal constant force task (15% of maximum) with ankle dorsiflexion for 20 s. The visual information processing was manipulated by changing the amount of force visual feedback into a low-gain (0.05°) or high-gain (1.2°) condition. Older adults exhibited greater force variability, especially at high-gain visual feedback. This exacerbated force variability from low- to high-gain visual feedback was associated with modulations of multiple motor units, not single motor units. Specifically, increased modulation of multiple motor units from 10 to 35 Hz may contribute to the amplification in force variability. Therefore, our findings suggest evidence that high-gain visual feedback amplifies force variability of older adults which is related to increases in the activation of motor neuron pool from 10 to 35 Hz.

Urinary NT-proBNP: A Useful Biomarker for the Diagnosis of Respiratory Distress in the Neonatal Population.

OBJECTIVE: To determine the diagnostic accuracy of urinary NT-proBNP levels in the detection and classification of the severity of respiratory distress in neonates after birth. METHODS: We compared the urinary NT- proBNP levels between the respiratory distress (RD) group and the control group on the 1st, 3rd, and 5th day of life (DOL). RESULTS: The RD group (55 neonates) showed higher levels of NT-proBNP compared to the control group (63 neonates) on DOL1 (585.4 pg/ml vs 396.1 pg/ml (p=0.014)), DOL3 (805.1 pg/ml vs 271.9 pg/ml (p<0.001)) and DOL5 (409.7 pg/ml vs 94.4 pg/ml (p<0.001)). Especially, on DOL5, the area under the ROC curve was 0.884 and the NT-proBNP cut-off value (221.8 pg/ml) showed a sensitivity of 71% and specificity of 79%. The RD group was subclassified into neonates with mild (21 neonates), moderate (19 neonates), and severe (15 neonates) disease. NT-proBNP cut-off point of 668 pg/ml for DOL5 can safely differentiate neonates with severe disease from those with mild and moderate disease (combined subgroups) since the sensitivity was 80% and specificity was 77.5% for DOL5. CONCLUSION: Urinary NT-proBNP levels are a useful biomarker in detecting clinical signs of respiratory distress in neonates that are born within the first week of life; they can also detect neonates that are vulnerable to severe forms of the disease.

Physical urticaria: Clinical features, pathogenesis, diagnostic work-up, and management.

Physical urticaria is a type of urticaria in which recurrent wheals and/or angioedema occur following exposure of the skin to a physical stimulus. It is classified according to its triggers, which may be mechanical (friction, pressure, and vibration), thermal (cold and heat), or solar electromagnetic radiation. Symptoms of different physical urticarias can develop following specific activities that expose patients to an eliciting stimulus and may be variably accompanied by mucosal involvement and systemic symptoms, including nausea, headache, or even anaphylaxis. Differentiation of physical urticaria from other chronic urticarias requires careful clinical assessment and confirmatory provocation testing, which in turn can inform appropriate management. This clinical review provides an evidence-based summary of the epidemiology, clinical features, pathogenesis, diagnostic work-up, and management of physical urticaria.

Adolescent boys who participate in sports exhibit similar ramp torque control with young men despite differences in strength and tendon characteristics.

PURPOSE: The goal of this paper was to determine if sports participation influences torque control differently for adolescent boys and young men during a slow ramp task. METHODS: Twenty-one adolescent boys (11 athletes) and 31 young men (16 athletes) performed a slow ramp increase in plantar flexion torque from 0 to maximum. We quantified torque control as the coefficient of variation (CV) of torque during the ramp and quantified the Achilles tendon mechanical properties using ultrasonography. RESULTS: Relative to adolescent boys, young men were taller, heavier, stronger, and had a longer and stiffer Achilles tendon. However, these characteristics were not different between athletes and non-athletes in adolescent boys. For the CV of torque, there was a significant interaction with sports participation, indicating that only adolescent boys who were non-athletes had greater variability than young men. The CV of torque of all participants was predicted from the maximum torque and torque oscillations from 1 to 2 Hz, whereas the CV of torque for adolescent boys was predicted only from torque oscillations from 1 to 2 Hz. CONCLUSION: These findings suggested that adolescent boys who participate in sports exhibited lower torque variability during a slow ramp task, which was not explained by differences in Achilles tendon properties or strength.

The Differences Between RSV and no RSV Acute Bronchiolitis in Hospitalized Infants: A Cross-Sectional Study.

To identify the differences between the RSV and non-RSV bronchiolitis in hospitalized infants in a Greek tertiary pediatric unit and the possible risk factors related to severe forms of the illness. We performed a retrospective cross-sectional data analysis by reviewing medical records of patients that were hospitalized for acute bronchiolitis from 2012 to 2019. The patients with RSV bronchiolitis were found to require antibiotic treatment, IV fluids, adrenaline, and hypertonic saline inhalations more frequently than the non-RSV patients. They also required prolonged hospitalization, especially those that were admitted to PICU, and received oxygen therapy for longer periods. We searched risk factors for severe forms of the disease according to the need for admission to PICU, the supplemental oxygen and the extended length of hospital stay, concurrently. The patients with RSV bronchiolitis developed more severe illness in comparison with patients with bronchiolitis due to other respiratory viruses.

The Rates of Breastfeeding in Baby-Friendly Hospitals in Greece: A Nationwide Survey.

BACKGROUND: Exclusive breastfeeding (EBF) remains the cornerstone of infant nutrition for the first six months of life, presenting multiple short and long term benefits. The purpose of this study is the demonstration of EBF rates of infants born in baby-friendly hospitals (BFH) and the factors that positively influence EBF. METHODS: The study was conducted in all four of the BFH that exist in Greece, between 2020 and 2022. The study sample consisted of 1200 mothers, taken from the 7101 that delivered at those hospitals during the time of the study. A questionnaire was used that included questions to evaluate the infant's nutrition after birth, after exiting the maternity hospital and during the 2nd, 4th and 6th month of age. The WHO guidelines on EBF and breastfeeding (BF), as well as the "Infant and Young Child Feeding" indicators, were used. RESULTS: The EBF rate within 1 h after birth was 71.3%, which gradually declined to 21.2% in the 6th month. The respective rate of BF was 94.5% and declined to 66.1%. The logistic regression revealed that attending antenatal breastfeeding courses, vaginal delivery, full-term pregnancies and the mothers' advanced education level constitute independent positive prognostic factors for increased EBF rates. CONCLUSION: The results of the first national study on BFH are presented. Despite the improvement of EBF rates in Greece, compared to the latest available data from 2018, reinforcement of EBF promotion measures is required in order to approach the WHO's targets by 2025.

Human Breast Milk: The Key Role in the Maturation of Immune, Gastrointestinal and Central Nervous Systems: A Narrative Review.

Premature birth is a major cause of mortality and morbidity in the pediatric population. Because their immune, gastrointestinal and nervous systems are not fully developed, preterm infants (<37 weeks of gestation) and especially very preterm infants (VPIs, <32 weeks of gestation) are more prone to infectious diseases, tissue damage and future neurodevelopmental impairment. The aim of this narrative review is to report the immaturity of VPI systems and examine the role of Human Breast Milk (HBM) in their development and protection against infectious diseases, inflammation and tissue damage. For this purpose, we searched and synthesized the data from the existing literature published in the English language. Studies revealed the significance of HBM and indicate HBM as the best dietary choice for VPIs.

Increased temporal stride variability contributes to impaired gait coordination after stroke.

Heightened motor variability is a prominent impairment after stroke. During walking, stroke survivors show increased spatial and temporal variability; however, the functional implications of increased gait variability are not well understood. Here, we determine the effect of gait variability on the coordination between lower limbs during overground walking in stroke survivors. Ambulatory stroke survivors and controls walked at a preferred pace. We measured stride length and stride time variability, and accuracy and consistency of anti-phase gait coordination with phase coordination index (PCI). Stroke survivors showed increased stride length variability, stride time variability, and PCI compared with controls. Stride time variability but not stride length variability predicted 43% of the variance in PCI in the stroke group. Stride time variability emerged as a significant predictor of error and consistency of phase. Despite impaired spatial and temporal gait variability following stroke, increased temporal variability contributes to disrupted accuracy and consistency of gait coordination. We provide novel evidence that decline in gait coordination after stroke is associated with exacerbated stride time variability, but not stride length variability. Temporal gait variability may be a robust indicator of the decline in locomotor function and an ideal target for motor interventions that promote stable walking after stroke.

Suppression of Axial Tremor by Deep Brain Stimulation in Patients with Essential Tremor: Effects on Gait and Balance Measures.

Background: Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET). Methods: Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sex-matched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks. Results: With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor. Discussion: The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks. Highlights: ET patients exhibit tremor in various body locations during gait and balance.DBS reduced stride length variability and sway path length.DBS-induced improvements in gait and balance were associated with reduction in axial tremor.

NT-proBNP Concentrations in the Umbilical Cord and Serum of Term Neonates: A Systematic Review and Meta-Analysis.

The detection of NT-proBNP levels both in umbilical cord blood (UCB) samples and in serum samples collected from healthy term neonates during the neonatal period. A systematic review of relevant literature in accordance with PRISMA guidelines was conducted. For quality appraisal, the potential risk of bias was assessed using the BIOCROSS evaluation tool. The random-effects and fixed-effects models were used to calculate weighted mean differences with a corresponding 95% confidence interval. A total of forty (40) studies met the inclusion criteria for the systematic review. After further examination, eighteen (18) studies (1738 participants) from the UCB sample group and fourteen (14) studies (393 participants) from the serum sample group were selected to perform a meta-analysis. Using the fixed-effects model, the mean intervals of NT-proBNP in UCB and serum samples were 492 pg/mL (95% CI: 480−503 pg/mL) and 1341 pg/mL (95% CI: 1286−1397 pg/mL), respectively. A higher concentration of ΝΤ-proBNP was observed in the serum sample group compared to the UCB samples (p < 0.001). We present the intervals of NT-proBNP in UCB and in the serum of healthy term neonates. The determination of the potential effect of perinatal factors on the biomarker's reference range was also aimed.

Motor Training After Stroke: A Novel Approach for Driving Rehabilitation.

Background: A key component of safe driving is a well-timed braking performance. Stroke-related decline in motor and cognitive processes slows braking response and puts individuals with stroke at a higher risk for car crashes. Although the impact of cognitive training on driving has been extensively investigated, the influence of motor interventions and their effectiveness in enhancing specific driving-related skills after stroke remains less understood. We compare the effectiveness of two motor interventions (force-control vs. strength training) to facilitate braking, an essential skill for safe driving. Methods: Twenty-two stroke survivors were randomized to force-control training or strength training. Before and after training, participants performed a braking task during car-following in a driving simulator. We quantified the cognitive and motor components of the braking task with cognitive processing time and movement execution time. Results: The cognitive processing time did not change for either training group. In contrast, the movement execution became significantly faster (14%) following force-control training but not strength training. In addition, task-specific effects of training were found in each group. The force-control group showed improved accuracy and steadiness of ankle movements, whereas the strength training group showed increased dorsiflexion strength following training. Conclusion: Motor intervention that trains ankle force control in stroke survivors improves the speed of movement execution during braking. Driving rehabilitation after stroke might benefit from incorporating force-control training to enhance the movement speed for a well-timed braking response.