Hyperornithinemia-hyperammonemia-homocitrullinuria: a rare neurometabolic disorder in two siblings.

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is an extremely rare disorder of urea cycle, with few patients reported worldwide. Despite hyperammonemia control, the long-term outcome remains poor with progressive neurological deterioration. We report the clinical, biochemical, and molecular features of two Lebanese siblings diagnosed with this disorder and followed for 8 and 15 years, respectively. Variable clinical manifestations and neurological outcome were observed. The patient with earlier onset of symptoms had a severe neurological deterioration while the other developed a milder form of the disease at an older age. Diagnosis was challenging in the absence of the complete biochemical triad and the non-specific clinical presentations. Whole exome sequencing revealed a homozygous variant, p.Phe188del, in the SLC25A15 gene, a French- Canadian founder mutation previously unreported in Arab patients. Hyperammonemia was controlled in both patients but hyperonithinemia persisted. Frequent hyperalaninemia spikes and lactic acidosis occured concomitantly with the onset of seizures in one of the siblings. Variable neurological deterioration and outcome were observed within the same family. This is the first report from the Arab population of the long-term outcome of this devastating neurometabolic disorder.

Stellar scintillation statistics and the impact of aperture averaging on space-to-ground optical communications.

Statistical probability distributions characterizing received optical power fluctuations, or scintillation, enable performance predictions of space-to-ground optical communication systems. In this paper, we present measurements of stellar scintillation over a wide range of elevation angles and turbulence conditions collected simultaneously with a 5 cm and 40 cm telescope aperture, which allows a comparison between minimal and significant aperture averaging conditions. The measured data is compared to a reasonable set of candidate probability distribution functions (PDFs), including lognormal, which is most often cited in the literature for weak to moderate scintillation. For scintillation indices (SIs) less than about 0.2, the Nakagami-m distribution provides the best representation of the collected data for both apertures and imposes a greater lasercom link penalty than a lognormal distribution, which has been inaccurately implemented as the default probability distribution in the literature. For larger values of the SI, the scintillation is best characterized by a Gamma-Gamma distribution. Additionally, the measured temporal covariance for weak to moderate scintillation conditions is found to be in reasonably good agreement with theoretical predictions.

Hospital-based Health Information Technology Infrastructure: Evidence of Reduced Medicare Payments and Racial Disparities Among Patients With ADRD.

BACKGROUND: Alzheimer disease and related dementia (ADRD) is one of the most expensive health conditions in the United States. Understanding the potential cost-savings or cost-enhancements of Health Information Technology (HIT) can help policymakers understand the capacity of HIT investment to promote population health and health equity for patients with ADRD. OBJECTIVES: This study examined access to hospital-based HIT infrastructure and its association with racial and ethnic disparities in Medicare payments for patients with ADRD. RESEARCH DESIGN: We used the 2017 Medicare Beneficiary Summary File, inpatient claims, and the American Hospital Association Annual Survey. Our study focused on community-dwelling Medicare fee-for-service beneficiaries who were diagnosed with ADRD. Our study focused on hospital-based telehealth-postdischarge (eg, remote patient monitoring) and telehealth-treatment (eg, psychiatric and addiction treatment) services. RESULTS: Results showed that hospital-based telehealth postdischarge services were associated with significantly higher total Medicare payment and acute inpatient Medicare payment per person per year among patients with ADRD on average. The associations between hospital-based telehealth-treatment services and payments were not significant. However, the association varied by patient's race and ethnicity. The reductions of the payments associated with telehealth postdischarge and treatment services were more pronounced among Black patients with ADRD. Telehealth-treatment services were associated with significant payment reductions among Hispanic patients with ADRD. CONCLUSION: Results showed that having hospital-based telehealth services might be cost-enhancing at the population level but cost-saving for Black and Hispanic patients with ADRD. Results suggested that personalized HIT services might be necessary to reduce the cost associated with ADRD treatment for racial and ethnic minority groups.

Physiological characterization of electrodermal activity enables scalable near real-time autonomic nervous system activation inference.

Electrodermal activities (EDA) are any electrical phxenomena observed on the skin. Skin conductance (SC), a measure of EDA, shows fluctuations due to autonomic nervous system (ANS) activation induced sweat secretion. Since it can capture psychophysiological information, there is a significant rise in the research work for tracking mental and physiological health with EDA. However, the current state-of-the-art lacks a physiologically motivated approach for real-time inference of ANS activation from EDA. Therefore, firstly, we propose a comprehensive model for the SC dynamics. The proposed model is a 3D state-space representation of the direct secretion of sweat via pore opening and diffusion followed by corresponding evaporation and reabsorption. As the input to the model, we consider a sparse signal representing the ANS activation that causes the sweat glands to produce sweat. Secondly, we derive a scalable fixed-interval smoother-based sparse recovery approach utilizing the proposed comprehensive model to infer the ANS activation enabling edge computation. We incorporate a generalized-cross-validation to tune the sparsity level. Finally, we propose an Expectation-Maximization based deconvolution approach for learning the model parameters during the ANS activation inference. For evaluation, we utilize a dataset with 26 participants, and the results show that our comprehensive state-space model can successfully describe the SC variations with high scalability, showing the feasibility of real-time applications. Results validate that our physiology-motivated state-space model can comprehensively explain the EDA and outperforms all previous approaches. Our findings introduce a whole new perspective and have a broader impact on the standard practices of EDA analysis.

Patient-reported health outcomes of SARS-CoV-2-tested patients presenting to emergency departments: a propensity score-matched prospective cohort study.

OBJECTIVE: This study aimed to compare the long-term physical and mental health outcomes of matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients controlling for seasonal effects. STUDY DESIGN: This was a retrospective cohort study. METHODS: This study enrolled patients presenting to emergency departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive eligible consenting patients who presented between March 1, 2020, and July 14, 2021, and were tested for SARS-CoV-2. Research assistants randomly selected four site and date-matched SARS-CoV-2-negative controls for every SARS-CoV-2-positive patient and interviewed them at least 30 days after discharge. We used propensity scores to match patients by baseline characteristics and used linear regression to compare Veterans RAND 12-item physical health component score (PCS) and mental health component scores (MCS), with higher scores indicating better self-reported health. RESULTS: We included 1170 SARS-CoV-2-positive patients and 3716 test-negative controls. The adjusted mean difference for PCS was 0.50 (95% confidence interval [CI]: -0.36, 1.36) and -1.01 (95% CI: -1.91, -0.11) for MCS. Severe disease was strongly associated with worse PCS (ß = -7.4; 95% CI: -9.8, -5.1), whereas prior mental health illness was strongly associated with worse MCS (ß = -5.4; 95% CI: -6.3, -4.5). CONCLUSION: Physical health, assessed by PCS, was similar between matched SARS-CoV-2-positive and SARS-CoV-2-negative patients, whereas mental health, assessed by MCS, was worse during a time when the public experienced barriers to care. These results may inform the development and prioritization of support programs for patients.

Deploying Bots in Healthcare to Find Revenue Cycle Improvements.

SUMMARY: Doing more with less has been a business mantra for decades. Healthcare leaders have implemented flex scheduling and job sharing, streamlined workflows, committed to process improvement techniques such as Lean, hired retirees, gained efficiencies from remote work ... and the list goes on. Each tactic has yielded productivity improvements, yet the need to do more with less continues. Postpandemic challenges include staff recruitment and retention, labor inflation, and dwindling margins, all of which must be addressed while maintaining corporate cultures. The journey with bots described here started in this dynamic environment, and the work has not been single-threaded. The organization featured here-an integrated delivery network-has digital front-door and back-end robotic process automation (RPA) projects underway. The digital front-door initiative supports patient self-registration and automates authorizations and insurance verification processes. The back-end patient financial services RPA project replaces and enhances existing technology. Revenue cycle as a multidepartment function is leadership's poster child for RPA, and the revenue cycle team is tasked to demonstrate the value of the technology. This article covers the initial steps and lessons learned in the process.

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

Robust point-process Granger causality analysis in presence of exogenous temporal modulations and trial-by-trial variability in spike trains.

Assessing directional influences between neurons is instrumental to understand how brain circuits process information. To this end, Granger causality, a technique originally developed for time-continuous signals, has been extended to discrete spike trains. A fundamental assumption of this technique is that the temporal evolution of neuronal responses must be due only to endogenous interactions between recorded units, including self-interactions. This assumption is however rarely met in neurophysiological studies, where the response of each neuron is modulated by other exogenous causes such as, for example, other unobserved units or slow adaptation processes. Here, we propose a novel point-process Granger causality technique that is robust with respect to the two most common exogenous modulations observed in real neuronal responses: within-trial temporal variations in spiking rate and between-trial variability in their magnitudes. This novel method works by explicitly including both types of modulations into the generalized linear model of the neuronal conditional intensity function (CIF). We then assess the causal influence of neuron i onto neuron j by measuring the relative reduction of neuron j's point process likelihood obtained considering or removing neuron i. CIF's hyper-parameters are set on a per-neuron basis by minimizing Akaike's information criterion. In synthetic data sets, generated by means of random processes or networks of integrate-and-fire units, the proposed method recovered with high accuracy, sensitivity and robustness the underlying ground-truth connectivity pattern. Application of presently available point-process Granger causality techniques produced instead a significant number of false positive connections. In real spiking responses recorded from neurons in the monkey pre-motor cortex (area F5), our method revealed many causal relationships between neurons as well as the temporal structure of their interactions. Given its robustness our method can be effectively applied to real neuronal data. Furthermore, its explicit estimate of the effects of unobserved causes on the recorded neuronal firing patterns can help decomposing their temporal variations into endogenous and exogenous components.

An HIT-Supported Care Coordination Framework for Reducing Structural Racism and Discrimination for Patients With ADRD.

Black and Latinx Americans are disproportionately at greater risk for having Alzheimer's disease and related dementias (ADRD) than White Americans. Such differences in risk for ADRD are arguably explained through health disparities, social inequities, and historical policies. Structural racism and discrimination (SRD), defined as "macro-level conditions that limit opportunities, resources, and well-being of less privileged groups," have been linked with common comorbidities of ADRD, including hypertension, obesity, diabetes, depression. Given the historical impact of SRD-including discriminatory housing policies resulting in racial residential segregation that has been shown to limit access to education, employment, and healthcare-Black and Latinx populations with ADRD are directly or indirectly negatively affected by SRD in terms of access, quality and cost for healthcare. Emerging studies have brought to light the value of structural-level hospital and public health collaboration on care coordination for improving healthcare quality and access, and thus could serve as a macro-level mechanism for addressing disparities for minoritized racial and ethnic populations with ADRD. This paper presents a conceptual framework delineating how care coordination can successfully be achieved through health information technology (HIT) systems and ultimately address SRD. To address health inequities, it is therefore critical that policy initiatives invest in HIT capacities and infrastructures to promote care coordination, identify patient needs and preferences, and promote engagement of patients with ADRD and their caregivers.

Negative Emotionality Interacts with Trauma Exposure to Prospectively Predict Posttraumatic Stress Disorder Symptoms During Firefighters' First 3 Years of Service.

Firefighters (FFs) protect the public despite significant risks to their health and well-being stemming from frequent trauma exposure and other occupational stressors. A minority of FFs develop posttraumatic stress disorder (PTSD) or related mental health problems, whereas most remain remarkably resilient despite enormous stress. This points toward substantial variability in responses to traumatic stress among FFs. Personality, particularly negative emotionality (NEM), has been shown to predict the development of PTSD in other trauma-exposed populations, yet has not been prospectively studied in relation to PTSD in FFs. The aim of this secondary analysis from a broader study of mental health in FFs was to test whether preemployment NEM predicted PTSD symptom severity over time by influencing how FFs respond to traumatic experiences. In this first prospective study of the development of PTSD symptoms in professional FFs, 322 FFs were recruited from seven urban fire academies across the United States and followed over their first 3 years of fire service. We assessed NEM during the fire academy as well as trauma exposure and both self-reported and clinician-rated PTSD symptoms at 1-, 2-, and 3-year follow-ups. Level of trauma exposure and NEM predicted PTSD symptoms over time, and NEM moderated the effect of trauma exposure on clinician-rated PTSD symptoms across both trauma exposure measures at 1- and 3-year follow-ups, f2 = .03-.10, but not at 2-year follow-up nor for self-reported PTSD symptoms. These findings indicate that NEM, assessed upon entry into a high-risk occupation, is useful in predicting PTSD symptom development.

Energy balance of torrefied microalgal biomass with production upscale approached by life cycle assessment.

Torrefaction is a thermochemical process used to convert the biomass into solid fuel. In this study, torrefaction increased the raw microalgal biomass' energy content from 20.22 MJ⋅kg-1 to 27.93 MJ⋅kg-1. To determine if more energy is produced than energy consumption from torrefaction, this study identified the energy balance of torrefied microalgal biomass production based on a life cycle approach. The energy analysis showed that, among all processes, torrefaction had the least amount of energy demand. The experimental setup, defined as scenario A, revealed that the principal source of energy demand, about 85%, was consumed on the microalgal growth using a photobioreactor system. A sensitivity analysis was also performed to determine the varying energy demand for torrefied microalgal biomass production. The different types of cultivation methods and various production scales were considered in scenarios B to D. Scenario D, which represented the commercial production-scale, the energy demand drastically decreased by 59.46% as compared to the experimental setup (scenario A). The open-pond cultivation system resulted in the least energy requirement, regardless of the production scale (scenarios B and C) among all the given scenarios. Unlike scenarios A and D, scenarios B and C identified the drying process to consume a high amount of energy. All the scenarios have shown an energy demand deficit. Therefore, efforts to decrease the energy demand on the upstream processes are needed to make the torrefied microalgal biomass a viable alternative energy source.

[Antinuclear antibodies in the diagnostics of rheumatic diseases]. / Antinukleäre Antikörper in der Diagnostik rheumatischer Erkrankungen.

Testing for antinuclear antibodies (ANA) on human epithelial cell lines (HEp-2) using indirect immunofluorescence (IIF) is central for ruling out or for diagnosing connective tissue diseases and other diseases, such as primary biliary cholangitis and autoimmune hepatitis as well as drug-induced ANA. The comprehensive description of 29 different ANA-IIF patterns by the international consensus of ANA patterns (ICAP) facilitates the harmonization of ANA-IIF diagnostics. Positive ANA tests are frequently observed in healthy individuals and a reason for referral to rheumatologists. In these cases, the detection of anti-DFS70 antibodies can be helpful to exclude systemic autoimmune rheumatic diseases.

Optical communications downlink from a low-earth orbiting 1.5U CubeSat.

In this article, we present the first demonstration of an optical communications downlink from a low-earth orbiting free-flying CubeSat. Two 1.5U vehicles, AC7-B&C, built under NASA's Optical Communications and Sensors Demonstration (OCSD) program were launched in November 2017 and subsequently placed into a 450-km, 51.6° inc. circular orbit. Pseudorandom data streams using on-off key (OOK) modulation were transmitted from AC-7B to a 40 cm aperture telescope located at sea level in El Segundo, CA. At 200 Mbps, without forward error correction (FEC), we achieved a 115-second link that was ~78% error free, with the remaining portion exhibiting an error rate below 1E-5. At the time of the engagement, the 1064-nm laser transmitter was operating at 2 W (half capacity) with a full width half maximum (FWHM) beam divergence of ~1 mrad, which was approximately double the anticipated pointing accuracy of the vehicle.

Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Outcome of Nonketotic Hyperglycinemia in Lebanon: 14-Year Retrospective Review.

Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed. The remainders were excluded for incomplete data. The majority of cases presented with seizures and hypsarrhythmia or burst suppression patterns. Half of the patients died. Survival varied between 7 days and 18 years. Seizures remained unresponsive with poor outcome, despite standard supportive care and antiepileptic therapy; however, two patients were responsive to ketogenic diet and one of them became seizure-free.Scarce data on the outcome of nonketotic hyperglycinemia patients from the Middle East and North Africa region are available. The ketogenic diet, in combination with standard therapies, appears to be effective in controlling the seizures in this devastating disorder. Larger multicenter studies are still needed to establish the role of the ketogenic diet in nonketotic hyperglycinemia.

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats.

BACKGROUND: The deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson's disease (PD). The majority of its actions are mediated by the transcription factor, VD3 receptor (VD3R). METHODS: The neuroprotective effects of VD3 were investigated on a PD model. Male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned (non-treated), and 6-OHDA-lesioned and treated with VD3 (7 days before the lesion, pre-treatment or for 14 days after the 6-OHDA striatal lesion, post-treatment). Afterwards, the animals were subjected to behavioral tests and euthanized for striatal neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and the Tukey test and considered significant for p < 0.05. RESULTS: We showed that pre- or post-treatments with VD3 reversed behavioral changes and improved the decreased DA contents of the 6-OHDA group. In addition, VD3 reduced the oxidative stress, increased (TH and DAT), and reduced (TNF-alpha) immunostainings in the lesioned striata. While significant decreases in VD3R immunoreactivity were observed after the 6-OHDA lesion, these changes were blocked after VD3 pre- or post-treatments. We showed that VD3 offers neuroprotection, decreasing behavioral changes, DA depletion, and oxidative stress. In addition, it reverses partially or completely TH, DAT, TNF-alpha, and VD3R decreases of immunoreactivities in the non-treated 6-OHDA group. CONCLUSIONS: Taken together, VD3 effects could result from its anti-inflammatory and antioxidant actions and from its actions on VD3R. These findings should stimulate translational research towards the VD3 potential for prevention or treatment of neurodegenerative diseases, as PD.

High-Risk Human Papillomavirus Detection in Urine Samples From a Referral Population With Cervical Biopsy-Proven High-Grade Lesions.

The aim of the study was to evaluate the performance of the HPV-HR test to detect high-risk human papillomavirus (HPV) in urine samples in comparison with a commercial molecular HPV test. MATERIALS AND METHODS: This is a prospective study, in which 350 patients diagnosed previously with cervical intraepithelial neoplasia (CIN) grade 2 or higher were enrolled. Urine and cervical specimens were collected. Urine was tested with the HPV-HR test and cervical specimens were tested with the Cobas. RESULTS: Of the 336 evaluable patients, there were 271 cases of CIN 2+, of which 202 were CIN 3+ and the remaining 65 patients were less than CIN 2. Positivity was 77.1% (95% confidence interval [CI] = 72.5-81.5) for the urine samples and 83.6% (95% CI = 79.6-87.6) for the cervical samples. Agreement between cervical and urine samples for HPV detection was 79.8% (κ = 0.363; 95% CI = 0.243-0.484). Sensitivity for CIN 2+ was 83.4% (95% CI = 78.4-87.6) for urine and 90.8% (95% CI = 86.7-92.9) for cervical samples. The sensitivity for CIN 3+ was 85.6% (95% CI = 80.0-90.2) for urine and 92.6% (95% CI = 88.0-95.8) for cervical samples. Specificity for worse than CIN 2 was 50.8% (95% CI = 33.7-59.0) and 46.2% (95% CI = 33.7-59.0) for urine and cervical samples, respectively. CONCLUSIONS: Although these results demonstrated slightly higher detection rates for HR-HPV and clinical sensitivity in cervical samples than in urine, when compared with histological diagnoses, urine sampling is a viable alternative to access women who do not participate in routine screening programs.

Escherichia coli RadD Protein Functionally Interacts with the Single-stranded DNA-binding Protein.

The bacterial single-stranded DNA binding protein (SSB) acts as an organizer of DNA repair complexes. The radD gene was recently identified as having an unspecified role in repair of radiation damage and, more specifically, DNA double-strand breaks. Purified RadD protein displays a DNA-independent ATPase activity. However, ATP hydrolytic rates are stimulated by SSB through its C terminus. The RadD and SSB proteins also directly interact in vivo in a yeast two-hybrid assay and in vitro through ammonium sulfate co-precipitation. Therefore, it is likely that the repair function of RadD is mediated through interaction with SSB at the site of damage.

Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.

Thousands of putative enhancers are characterized in the human genome, yet few have been shown to have a functional role in cancer progression. Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by up-regulation of the HGF receptor, MET. The mechanisms mediating such genomic responses to targeted therapy are unknown. Here, we identify lineage-specific enhancers at the MET locus for multiple common tumor types, including a melanoma lineage-specific enhancer 63 kb downstream from the MET TSS. This enhancer displays inducible chromatin looping with the MET promoter to up-regulate MET expression upon BRAF inhibition. Epigenomic analysis demonstrated that the melanocyte-specific transcription factor, MITF, mediates this enhancer function. Targeted genomic deletion (<7 bp) of the MITF motif within the MET enhancer suppressed inducible chromatin looping and innate drug resistance, while maintaining MITF-dependent, inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus guide functional disruption of regulatory DNA to decouple pro- and anti-oncogenic functions of a dominant transcription factor and block innate resistance to oncokinase therapy.