A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda.

Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%-30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.

Chronic cold exposure causes left ventricular hypertrophy that appears to be physiological.

Exposure to winter cold causes an increase in energy demands to meet the challenge of thermoregulation. In small rodents, this increase in cardiac output leads to a profound cardiac hypertrophy, 2-3x that typically seen with exercise training. The nature of this hypertrophy and its relevance to winter mortality remains unclear. Our goal was to characterize cold-induced cardiac hypertrophy and to assess its similarity to either exercise-induced (physiological) hypertrophy or the pathological hypertrophy of hypertension. We hypothesized that cold-induced hypertrophy will most closely resemble exercise-induced hypertrophy, but be another unique pathway for physiological cardiac growth. We found that cold-induced hypertrophy was largely reversed after return to warm temperatures. Further, metabolic rates were elevated while gene expression and mitochondrial enzyme activities indicative of pathology were absent. A gene expression panel comparing hearts of exercised and cold exposed mice further suggests that these activities are similar, although not identical. In conclusion, we found that chronic cold led to a phenotype that most closely resembled physiological hypertrophy, with enhanced metabolic rate, without induction of fetal genes , but with decreased expression of genes associated with fatty acid oxidation, suggesting that heart failure is not a cause of winter mortality in small rodents and identifying a novel approach for the study of cardiac growth.

Lens epithelial cell response to polymer stiffness and polymer chemistry.

Posterior capsule opacification (PCO) is the most common complication of cataract surgery, and intraocular lens (IOL) implantation is the standard of care for cataract patients. Induction of post-operative epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LEC) is the main mechanism by which PCO forms. Previous studies have shown that IOLs made with different materials have varying incidence of PCO. The aim of this paper was to study the interactions between human (h)LEC and polymer substrates. Polymers and copolymers of 2-hydroxyethyl methacrylate (HEMA) and 3-methacryloxypropyl tris (trimethylsiloxy) silane (TRIS) were synthesized and evaluated due to the clinical use of these materials as ocular biomaterials and implants. The chemical properties of the polymer surfaces were evaluated by contact angle, and polymer stiffness and roughness were measured using atomic force microscopy. In vitro studies showed the effect of polymer mechanical properties on the behavior of hLECs. Stiffer polymers increased α-smooth muscle actin expression and induced cell elongation. Hydrophobic and rough polymer surfaces increased cell attachment. These results demonstrate that attachment of hLECs on different surfaces is affected by surface properties in vitro, and evaluating these properties may be useful for investigating prevention of PCO.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

The Effect of Intranasal Plus Transcranial Photobiomodulation on Neuromuscular Control in Individuals with Repetitive Head Acceleration Events.

Objective: This proof-of-concept study was to investigate the relationship between photobiomodulation (PBM) and neuromuscular control. Background: The effects of concussion and repetitive head acceleration events (RHAEs) are associated with decreased motor control and balance. Simultaneous intranasal and transcranial PBM (itPBM) is emerging as a possible treatment for cognitive and psychological sequelae of brain injury with evidence of remote effects on other body systems. Methods: In total, 43 (39 male) participants, age 18-69 years (mean, 49.5; SD, 14.45), with a self-reported history of concussive and/or RHAE and complaints of their related effects (e.g., mood dysregulation, impaired cognition, and poor sleep quality), completed baseline and posttreatment motor assessments including clinical reaction time, grip strength, grooved pegboard, and the Mini Balance Evaluation Systems Test (MiniBEST). In the 8-week interim, participants self-administered itPBM treatments by wearing a headset comprising four near-infrared light-emitting diodes (LED) and a near-infrared LED nasal clip. Results: Posttreatment group averages in reaction time, MiniBEST reactive control subscores, and bilateral grip strength significantly improved with effect sizes of g = 0.75, g = 0.63, g = 0.22 (dominant hand), and g = 0.34 (nondominant hand), respectively. Conclusion: This study provides a framework for more robust studies and suggests that itPBM may serve as a noninvasive solution for improved neuromuscular health.

A cytomics-on-a-chip platform and diagnostic model stratifies risk for oral lichenoid conditions.

OBJECTIVE: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs. STUDY DESIGN: All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) and nonlichenoid (OLC-) (N = 237) histologic features in a population with OPMDs. RESULTS: The OLC Index discriminated OLC+ and OLC- subjects with area under the curve (AUC) of 0.76. Diagnostic accuracy of the OLC Index was not significantly different from expert clinician impressions, with AUC of 0.81 (P = .0704). Percent agreement was comparable across all raters, with 83.4% between expert clinicians and histopathology, 78.3% between OLC Index and expert clinician, and 77.3% between OLC Index and histopathology. CONCLUSIONS: The cytomics-on-a-chip tool and integrated diagnostic model have the potential to facilitate both the triage and diagnosis of patients presenting with OPMDs and OLCs.

Clarifying the impact of dual optical feedback on semiconductor lasers through analysis of the effective feedback phase.

Time-delayed optical feedback is known to trigger a wide variety of complex dynamical behavior in semiconductor lasers. Adding a second optical feedback loop is naturally expected to further increase the complexity of the system and its dynamics, but due to interference between the two feedback arms, it was also quickly identified as a way to improve the laser stability. While these two aspects have already been investigated, the influence of the feedback phases, i.e., sub-wavelength changes in the mirror positions, on the laser behavior still remains to be thoroughly studied, despite indications that this parameter could have a significant impact. Here, we analyze the effect of the feedback phase on the laser stability in a dual-feedback configuration. We show an increased sensitivity of the laser system to feedback phase changes when two-feedback loops are present and clarify the interplay between the frequency shift induced by the feedback and the interferometric effect between the two feedback arms.

ENIGMA's simple seven: Recommendations to enhance the reproducibility of resting-state fMRI in traumatic brain injury.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

Mother's Croup Reveals That Parainfluenza Virus Is the Cause of Her Son's Viral Parotitis.

In modern practice viral parotitis is unlikely to be due to mumps. Case and surveillance studies have detected a host of other viruses in mumps-negative viral parotitis, but because of their weak association with viral parotitis, it has been difficult to establish causality. This case report is unique because a familial pair presented in tandem with different manifestations of an infection with the parainfluenza virus. These circumstances allowed the strong association of the parainfluenza virus with the mother's croup to be substituted for the normally weak association of the parainfluenza virus with the son's viral parotitis. This strongly inferred that the parainfluenza virus caused the patient's viral parotitis and provides the best evidence to date of a virus other than mumps causing viral parotitis.

The Obesity Epidemic Is Not the Victims' Fault.

The Centers for Disease Control and Prevention recently issued two statements that 1) maintain that obesity causes diabetes and other expressions of the metabolic syndrome and 2) that imply obesity is the victim's fault. Both statements are incorrect and potentially harmful.

Pediatric Cluster Headache Case Series: Symptomatic Cases and the Migraine Relationship.

BACKGROUND: Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions, which may delay diagnosis. Differentiating cluster headache from migraine is important regarding treatment as well as diagnostic workup of secondary headache etiologies. METHODS: Cases at a single pediatric children's hospital from 2015 to 2023 diagnosed with cluster headache before the age of 18 years were reviewed. RESULTS: Twenty-five cases were identified of which 22 cases met criteria for either chronic, episodic, or probable cluster headache. Three cases were diagnosed with cluster headache by their provider, but documentation was insufficient to meet criteria for cluster headache. There were 16 females and 9 males between ages 6 and 17 years. Five cases were identified as symptomatic, 2 cases as chronic, 7 cases as episodic, and 13 cases as probable cluster headache. Symptomatic etiologies include Graves disease, optic neuritis, prolactinoma, hypothalamic pilocytic astrocytoma with carotid stenosis, and congenital right eye blindness. Migrainous features were common, including 76% with nausea, 36% with vomiting, 68% with photophobia, and 56% with phonophobia. Patients with cluster headache also had an independent diagnosis of migraine in 64%. CONCLUSION: Children with cluster headache have a high frequency of migrainous symptoms and co-occurrent diagnosis of migraine. A careful history may differentiate cluster headache from migraine and treated accordingly. Children with cluster headache features should undergo screening for secondary causes with appropriate imaging and other studies. Except for prolactinoma, the symptomatic associations noted in this case series have not been reported before.

Control of vortex orientation of ultrashort optical pulses using a spatial chirp.

Introducing a spatial chirp into a pulse with a longitudinal vortex, such as a standard pulsed Laguerre-Gauss beam, results in a vortex pulse with an arbitrary orientation of the phase line singularity between longitudinal and transverse, depending on the amount of chirp. Analytical expressions are given for such pulses with arbitrary topological charge valid at any propagation distance.

Transit Time Theory for a Droplet Passing through a Slit in Pressure-Driven Low Reynolds Number Flows.

Soft objects squeezing through small apertures are crucial for many in vivo and in vitro processes. Red blood cell transit time through splenic inter-endothelial slits (IESs) plays a crucial role in blood filtration and disease progression, while droplet velocity through constrictions in microfluidic devices is important for effective manipulation and separation processes. As these transit phenomena are not well understood, we sought to establish analytical and numerical solutions of viscous droplet transit through a rectangular slit. This study extends from our former theory of a circular pore because a rectangular slit is more realistic in many physiological and engineering applications. Here, we derived the ordinary differential equations (ODEs) of a droplet passing through a slit by combining planar Poiseuille flow, the Young-Laplace equations, and modifying them to consider the lubrication layer between the droplet and the slit wall. Compared to the pore case, we used the Roscoe solution instead of the Sampson one to account for the flow entering and exiting a rectangular slit. When the surface tension and lubrication layer were negligible, we derived the closed-form solutions of transit time. When the surface tension and lubrication layer were finite, the ODEs were solved numerically to study the impact of various parameters on the transit time. With our solutions, we identified the impact of prescribed pressure drop, slit dimensions, and droplet parameters such as surface tension, viscosity, and volume on transit time. In addition, we also considered the effect of pressure drop and surface tension near critical values. For this study, critical surface tension for a given pressure drop describes the threshold droplet surface tension that prevents transit, and critical pressure for a given surface tension describes the threshold pressure drop that prevents transit. Our solutions demonstrate that there is a linear relationship between pressure and the reciprocal of the transit time (referred to as inverse transit time), as well as a linear relationship between viscosity and transit time. Additionally, when the droplet size increases with respect to the slit dimensions, there is a corresponding increase in transit time. Most notably, we emphasize the initial antagonistic effect of surface tension which resists droplet passage but at the same time decreases the lubrication layer, thus facilitating passage. Our results provide quantitative calculations for understanding cells passing through slit-like constrictions and designing droplet microfluidic experiments.

Sport-Specific Recovery Trajectories for NCAA Collegiate Athletes Following Concussion.

The recovery trajectories of collegiate athletes with sport-related concussion (SRC) are well characterized in contact/collision sports but are less well understood in limited contact sports with lower risk, reducing the ability of clinicians to effectively manage the return-to-play (RTP) process. The current study investigated the time to asymptomatic and RTP across a broad range of male and female collegiate sports and sought to group sports by recovery intervals. Data from the Concussion Assessment, Research and Education (CARE) Consortium included 1049 collegiate athletes who sustained a SRC while participating in game or practice/training of their primary sport. Injury setting and subsequent clinical presentation data were obtained. Survival analysis using the Cox Proportional Hazard model estimated the median recovery times for each sport. Optimal univariate K-means clustering grouped sports into recovery categories. Across all sports, median time to asymptomatic following SRC ranged from 5.9 (female basketball) to 8.6 days (male wrestling). Median RTP protocol duration ranged from 4.9 days (female volleyball) to 6.3 days (male wrestling). Median total RTP days ranged from 11.2 days (female lacrosse) to 16.9 days (male wrestling). Sport clusters based on recovery differences in time to asymptomatic (3) and RTP protocol duration (2) were identified. The findings from this study of a large sample of more than 1000 NCAA collegiate athletes with SRC show there exists ranges in recovery trajectories. Clinicians can thus manage athletes with similar guidelines, with individualized treatment and recovery plans.

Elevated temperature alters microbial communities, but not decomposition rates, during 3 years of in situ peat decomposition.

IMPORTANCE: Microbial community changes in response to climate change drivers have the potential to alter the trajectory of important ecosystem functions. In this paper, we show that while microbial communities in peatland systems responded to manipulations of temperature and CO2 concentrations, these changes were not associated with similar responses in peat decomposition rates over 3 years. It is unclear however from our current studies whether this functional resiliency over 3 years will continue over the longer time scales relevant to peatland ecosystem functions.

Modulated super-Gaussian laser pulse to populate a dark rovibrational state of acetylene.

A pulse-shaping technique in the mid-infrared spectral range based on pulses with a super-Gaussian temporal profile is considered for laser control. We show a realistic and efficient path to the population of a dark rovibrational state in acetylene (C2H2). The laser-induced dynamics in C2H2 are simulated using fully experimental structural parameters. Indeed, the rotation-vibration energy structure, including anharmonicities, is defined by the global spectroscopic Hamiltonian for the ground electronic state of C2H2 built from the extensive high-resolution spectroscopy studies on the molecule, transition dipole moments from intensities, and the effects of the (inelastic) collisions that are parameterized from line broadenings using the relaxation matrix [A. Aerts, J. Vander Auwera, and N. Vaeck, J. Chem. Phys. 154, 144308 (2021)]. The approach, based on an effective Hamiltonian, outperforms today's ab initio computations both in terms of accuracy and computational cost for this class of molecules. With such accuracy, the Hamiltonian permits studying the inner mechanism of theoretical pulse shaping [A. Aerts et al., J. Chem. Phys. 156, 084302 (2022)] for laser quantum control. Here, the generated control pulse presents a number of interferences that take advantage of the control mechanism to populate the dark state. An experimental setup is proposed for in-laboratory investigation.

Estimating the Relationship Between the Symptom-Free Waiting Period and Injury Rates After Return-to-Play from Concussion: A Simulation Analysis Using CARE Consortium Data.

BACKGROUND: A key component of return-to-play (RTP) from sport-related concussion is the symptom-free waiting period (SFWP), i.e., the period during which athletes must remain symptom-free before permitting RTP. Yet, the exact relationship between SFWP and post-RTP injury rates is unclear. OBJECTIVE: We design computational simulations to estimate the relationship between the SFWP and rates of repeat concussion and non-concussion time-loss injury up to 30 days post-RTP for male and female collegiate athletes across 13 sports. METHODS: We leverage N = 735 female and N = 1,094 male post-injury trajectories from the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium. RESULTS: With a 6-day SFWP, the mean [95% CI] rate of repeat concussion per 1,000 simulations was greatest in ice hockey for females (20.31, [20.16, 20.46]) and American football for males (24.16, [24.05, 24.28]). Non-concussion time-loss injury rates were greatest in field hockey for females (153.66, [152.59, 154.74]) and wrestling for males (247.34, [246.20, 248.48]). Increasing to a 13-day SFWP, ice hockey for females (18.88, [18.79, 18.98]) and American football for males (23.16, [23.09, 24.22]) exhibit the greatest decrease in repeat concussion rates across all sports within their respective sexes. Field hockey for females (143.24, [142.53, 143.94]) and wrestling for males (237.73, [236.67, 237.90]) exhibit the greatest decrease in non-concussion time-loss injury rates. Males receive marginally smaller reductions in injury rates for increased SFWP compared to females (OR = 1.003, p ≤ 0.002). CONCLUSION: Longer SFWPs lead to greater reductions in post-RTP injury rates for athletes in higher risk sports. Moreover, SFWPs should be tailored to sport-specific post-RTP injury risks.

Barriers to Healthy Family Dinners and Preventing Child Obesity: Focus Group Discussions with Parents of 5-to-8-Year-Old Children.

BACKGROUND: Although numerous physical and mental health benefits for children have been linked to family dinners, many families still do not have regular family meals together. This study sought to identify the barriers that keep families from having dinners together. METHODS: We interviewed 42 parents of 5-to-8-year-old children in small focus groups to identify barriers and challenges that keep families from having healthy and consistent dinners together. RESULTS: Parents reported the main barriers were time (e.g., time strain and overscheduling, mismatched schedules, long work hours, etc.), lack of meal planning or failure to follow plans, lack of skills (e.g., cooking skills or nutritional awareness), external factors (e.g., daycare, schools, or extended family, and competing with advertising), and food-related challenges (e.g., picky eating, food allergies). Parents also suggested potential solutions to overcome these barriers. CONCLUSIONS: Overall, parents had a desire to have family dinners with their children, but they felt that there are many barriers keeping them from establishing or maintaining consistent family mealtimes. Future research, as well as child obesity prevention and intervention efforts, should consider these barriers and suggested solutions in efforts to promote healthy and consistent family meals as a means of lowering the prevalence of childhood obesity.

Redo fundoplication vs. Roux-en-Y gastric bypass conversion for failed anti-reflux surgery: which is better?

INTRODUCTION: Different techniques have been proposed for reoperation after failed anti-reflux surgery. However, there is no consensus on which should be preferred. We aim to report and compare the outcomes of different revisional techniques for failed anti-reflux surgery. METHODS: We performed a retrospective analysis of patients who underwent redo fundoplication (RF) or Roux-en-Y gastric bypass (RYGB) conversion after a failed fundoplication at our institution between 2016 and 2021. The primary outcome was long-term presence of reflux or dysphagia following revisional surgery. Secondary outcomes included 30-day perioperative complications as well as long-term use of anti-reflux medication and radiographic recurrence of hiatal hernia (HH). RESULTS: A total of 165 (median age 63 years, 73.9% female) patients were included. RF was performed in 120 (73 Toupet and 47 Nissen), RYGB in 38, and 7 patients had fundoplication takedown alone. The RYGB group had a significantly higher BMI, and more prior revisional surgeries compared to the other groups. Median operative time and length of stay were longer for RYGB. Twenty (12.1%) patients experienced postoperative complications, with the highest incidence in the RYGB group. Reflux and dysphagia improved significantly for the whole cohort, with the greatest improvement noted with reflux in the RYGB group (89.5% with preoperative reflux vs. 10.5% with postoperative reflux, p = < .001). On multivariable regression we found that prior re-operative surgery was associated with persistent reflux and dysphagia, whereas RYGB conversion was protective against reflux. CONCLUSION: Conversion to RYGB may offer superior resolution of reflux than RF, especially for obese patients.