Reading skills in males with 47,XXY: Risk factors and the influence of hormonal replacement therapy (HRT).

PURPOSE: 47,XXY is often associated with reduced expressive language and literacy skills. This retrospective cross-sectional study investigated risk factors (hormone replacement deficiency, pre-or postnatal diagnosis, and history of family learning disabilities [FLDs]) associated with reading skills in 152 males. METHODS: We analyzed Woodcock Reading Mastery Test scores among 7 prenatally diagnosed male hormone replacement therapy (HRT) groups using analysis of variance along with analysis of variance and 2 postnatally diagnosed male HRT groups (No-T and T) using t tests. Treated prenatally diagnosed males with FLDs were compared with an identically treated prenatal HRT group with no history of FLDs using a t test. RESULTS: In prenatally diagnosed males, significant treatment differences were observed on several reading scales (eg, total reading: χ2 = 17.96, P = .006), in which the highest modality HRT group (mean [M] =119.87) outperformed the untreated group (M = 99.88). In the postnatal analysis, we observed a significant effect of treatment on basic skills (P = .01). Despite equal HRT status, males with FLDs (M = 105.79) exhibited reduced total reading skills compared with those in the no FLD group (P = 0.0006). CONCLUSION: Our findings in this pilot study reveal that the most optimal reading trajectory is associated with a prenatal diagnosis, absence of FLDs, and the highest modality HRT.

Optical Monitoring of Breathing Patterns and Tissue Oxygenation: A Potential Application in COVID-19 Screening and Monitoring.

The worldwide outbreak of the novel Coronavirus (COVID-19) has highlighted the need for a screening and monitoring system for infectious respiratory diseases in the acute and chronic phase. The purpose of this study was to examine the feasibility of using a wearable near-infrared spectroscopy (NIRS) sensor to collect respiratory signals and distinguish between normal and simulated pathological breathing. Twenty-one healthy adults participated in an experiment that examined five separate breathing conditions. Respiratory signals were collected with a continuous-wave NIRS sensor (PortaLite, Artinis Medical Systems) affixed over the sternal manubrium. Following a three-minute baseline, participants began five minutes of imposed difficult breathing using a respiratory trainer. After a five minute recovery period, participants began five minutes of imposed rapid and shallow breathing. The study concluded with five additional minutes of regular breathing. NIRS signals were analyzed using a machine learning model to distinguish between normal and simulated pathological breathing. Three features: breathing interval, breathing depth, and O2Hb signal amplitude were extracted from the NIRS data and, when used together, resulted in a weighted average accuracy of 0.87. This study demonstrated that a wearable NIRS sensor can monitor respiratory patterns continuously and non-invasively and we identified three respiratory features that can distinguish between normal and simulated pathological breathing.

Applications of near-infrared spectroscopy in epilepsy, with a focus on mitochondrial disorders.

Mitochondrial diseases are inherited disorders that impede the mitochondria's ability to produce sufficient energy for the cells. They can affect different parts of the body, notably the brain. Neurological symptoms and epilepsy are prevalent in patients with mitochondrial disorders. The epileptogenicity of mitochondrial disorder is a complex process involving the intricate interplay between abnormal energy metabolism and neuronal activity. Several modalities have been used to detect seizures in different disorders including mitochondrial disorders. EEG serve as the gold standard for diagnosis and localization, commonly complemented by additional imaging modalities to enhance source localization. In the current work, we propose the use of functional near-infrared spectroscopy (fNIRS) to identify the occurrence of epilepsy and seizure in patients with mitochondrial disorders. fNIRS proves an advantageous imaging technique due to its portability and insensitivity to motion especially for imaging infants and children. It has added a valuable factor to our understanding of energy metabolism and neuronal activity. Its real-time monitoring with high spatial resolution supplements traditional diagnostic tools such as EEG and provides a comprehensive understanding of seizure and epileptogenesis. The utility of fNIRS extends to its ability to detect changes in Cytochrome c oxidase (CcO) which is a crucial enzyme in cellular respiration. This facet enhances our insight into the metabolic dimension of epilepsy related to mitochondrial dysfunction. By providing valuable insights into both energy metabolism and neuronal activity, fNIRS emerges as a promising imaging technique for unveiling the complexities of mitochondrial disorders and their neurological manifestations.

Review of Applications of Near-Infrared Spectroscopy in Two Rare Disorders with Executive and Neurological Dysfunction: UCD and PKU.

Studying rare diseases, particularly those with neurological dysfunction, is a challenge to researchers and healthcare professionals due to their complexity and small population with geographical dispersion. Universal and standardized biomarkers generated by tools such as functional neuroimaging have been forged to collect baseline data as well as treatment effects. However, the cost and heavily infrastructural requirement of those technologies have substantially limited their availability. Thus, developing non-invasive, portable, and inexpensive modalities has become a major focus for both researchers and clinicians. When considering neurological disorders and diseases with executive dysfunction, EEG is the most convenient tool to obtain biomarkers which can correlate the objective severity and clinical observation of these conditions. However, studies have also shown that EEG biomarkers and clinical observations alone are not sensitive enough since not all the patients present classical phenotypical features or EEG evidence of dysfunction. This article reviews disorders, including two rare disorders with neurological dysfunction and the usefulness of functional near-infrared spectroscopy (fNIRS) as a non-invasive optical modality to obtain hemodynamic biomarkers of diseases and for screening and monitoring the disease.

Novel Neurocognitive Profile in a Minority of Boys with 47,XXY (Klinefelter Syndrome).

INTRODUCTION: 47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal variation (1:660). The neurocognitive profile of boys with 47,XXY, in addition to verbal abilities, language skills, and general intelligence, has been explored in this study. METHODS: Fifty-five participants with 47,XXY were segregated into groups according to their performance on the Wechsler Intelligence Scale for Children (WISC): (1) those with a higher performance intelligence quotient (PIQ) in comparison with their verbal IQ (VIQ) and (2) those with a higher VIQ compared with their PIQ. Two-tailed independent t tests were completed to analyze group differences. RESULTS: Our study results demonstrate novel findings that one-third of subjects have higher verbal capabilities than perceptual skills. Those participants who showed the typical presentation of 47,XXY with increased PIQ in comparison with their VIQ excelled on perceptual and visual spatial subtests on the WISC and on nonverbal IQ on the Leiter International Performance Scale-III. In addition, it was found that expressive and receptive vocabulary skills were commensurate in both groups, which has not been reported previously. DISCUSSION: To the best of our knowledge, this is the first study to identify an alternative profile of 47,XXY with increased verbal capabilities in comparison with perceptual skills. In addition, previous research has found that boys with 47,XXY often show increased receptive vocabulary skills in comparison with their expressive vocabulary skills early in life. Therefore, our findings of commensurate expressive and receptive vocabulary skills suggest that age may be an impactful factor in vocabulary development. Further research is necessary to determine individualized treatment options for these patients, focusing on the specific cognitive profile they present.

Case Report: A Case Study on the Neurodevelopmental Profile of a Child With Pallister-Killian Syndrome and His Unaffected Twin.

Pallister-Killian syndrome is an uncommon genetic disorder that has broad developmental and multisystemic effects. While medical complications are widely reported throughout the literature, research on the neurodevelopmental profile has been limited. Case reports make up the majority of the few existing studies regarding the neurodevelopmental phenotype associated with this disorder. The current case report describes a 3-year-old male with Pallister-Killian syndrome (AF), reports the neurodevelopmental evaluation of his unaffected twin brother (MF), and outlines the results of an optical imaging study on both boys. AF presents with severe developmental delays, however, he ambulates with support and engages in conversation using his communication device. Most severely impaired was AF's speech and expressive language, with childhood apraxia of speech (CAS) as a possible explanation for these severe deficits. MF, the sibling, demonstrated neurotypical abilities and often advanced scores for his age. Both subjects completed a functional near-infrared spectroscopy (fNIRS) study, revealing decreased temporal and frontal lobe function in AF and typical functioning in MF. This case report expands on the existing literature on PKS by describing variances in fraternal twin presentation and novel reporting on fNIRS findings in both boys.

An fNIRS Study of Brain Lateralization During Observation and Execution of a Fine Motor Task.

Brain activity in the action observation network (AON) is lateralized during action execution, with greater activation in the contralateral hemisphere to the side of the body used to perform the task. However, it is unknown whether the AON is also lateralized when watching another person perform an action. In this study, we use fNIRS to measure brain activity over the left and right cortex while participants completed actions with their left and right hands and watched an actor complete action with their left and right hands. We show that while activation is lateralized when the participants themselves are moving, brain lateralization is not affected by the side of the body when the participant is observing another person's action. In addition, we demonstrate that individual differences in hand preference and dexterity between the right and left hands are related to brain lateralization patterns.

Characterizing the Action-Observation Network Through Functional Near-Infrared Spectroscopy: A Review.

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that has undergone tremendous growth over the last decade due to methodological advantages over other measures of brain activation. The action-observation network (AON), a system of brain structures proposed to have "mirroring" abilities (e.g., active when an individual completes an action or when they observe another complete that action), has been studied in humans through neural measures such as fMRI and electroencephalogram (EEG); however, limitations of these methods are problematic for AON paradigms. For this reason, fNIRS is proposed as a solution to investigating the AON in humans. The present review article briefly summarizes previous neural findings in the AON and examines the state of AON research using fNIRS in adults. A total of 14 fNIRS articles are discussed, paying particular attention to methodological choices and considerations while summarizing the general findings to aid in developing better protocols to study the AON through fNIRS. Additionally, future directions of this work are discussed, specifically in relation to researching AON development and potential multimodal imaging applications.

Non-invasive transabdominal measurement of placental oxygenation: a step toward continuous monitoring.

This study aimed to assess transabdominal placental oxygenation levels non-invasively. A wearable device was designed and tested in 12 pregnant women with an anterior placenta, 5 of whom had maternal pregnancy complications. Preliminary results revealed that the placental oxygenation level is closely related to pregnancy complications and placental pathology. Women with maternal pregnancy complications were found to have a lower placental oxygenation level (69.4% ± 6.7%) than those with uncomplicated pregnancy (75.0% ± 5.8%). This device is a step in the development of a point-of-care method designed to continuously monitor placental oxygenation and to assess maternal and fetal health.

Cerebral hemodynamic response during a live action-observation and action-execution task: A fNIRS study.

Although many studies have examined the location of the action observation network (AON) in human adults, the shared neural correlates of action-observation and action-execution are still unclear partially due to lack of ecologically valid neuroimaging measures. In this study, we aim to demonstrate the feasibility of using functional near infrared spectroscopy (fNIRS) to measure the neural correlates of action-observation and action execution regions during a live task. Thirty adults reached for objects or observed an experimenter reaching for objects while their cerebral hemodynamic responses including oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) were recorded in the sensorimotor and parietal regions. Our results indicated that the parietal regions, including bilateral superior parietal lobule (SPL), bilateral inferior parietal lobule (IPL), right supra-marginal region (SMG) and right angular gyrus (AG) share neural activity during action-observation and action-execution. Our findings confirm the applicability of fNIRS for the study of the AON and lay the foundation for future work with developmental and clinical populations.

Review of the efficacy of infrared thermography for screening infectious diseases with applications to COVID-19.

Purpose: The recent coronavirus disease 2019 (COVID-19) pandemic, which spread across the globe in a very short period of time, revealed that the transmission control of disease is a crucial step to prevent an outbreak and effective screening for viral infectious diseases is necessary. Since the severe acute respiratory syndrome (SARS) outbreak in 2003, infrared thermography (IRT) has been considered a gold standard method for screening febrile individuals at the time of pandemics. The objective of this review is to evaluate the efficacy of IRT for screening infectious diseases with specific applications to COVID-19. Approach: A literature review was performed in Google Scholar, PubMed, and ScienceDirect to search for studies evaluating IRT screening from 2002 to present using relevant keywords. Additional literature searches were done to evaluate IRT in comparison to traditional core body temperature measurements and assess the benefits of measuring additional vital signs for infectious disease screening. Results: Studies have reported on the unreliability of IRT due to poor sensitivity and specificity in detecting true core body temperature and its inability to identify asymptomatic carriers. Airport mass screening using IRT was conducted during occurrences of SARS, Dengue, Swine Flu, and Ebola with reported sensitivities as low as zero. Other studies reported that screening other vital signs such as heart and respiratory rates can lead to more robust methods for early infection detection. Conclusions: Studies evaluating IRT showed varied results in its efficacy for screening infectious diseases. This suggests the need to assess additional physiological parameters to increase the sensitivity and specificity of non-invasive biosensors.

Depth dependence of coherent hemodynamics in the human head.

We report a near-infrared spectroscopy (NIRS) study of coherent hemodynamic oscillations measured on the human forehead at multiple source-detector distances (1 to 4 cm). The physiological source of the coherent hemodynamics is arterial blood pressure oscillations at a frequency of 0.1 Hz, induced by cyclic inflation (to a pressure of 200 mmHg) and deflation of two thigh cuffs wrapped around the subject's thighs. To interpret our results, we use a recently developed hemodynamic model and a phasor representation of the oscillations of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations in the tissue (phasors O, D, and T, respectively). The increase in the phase angle between D and O at larger source-detector separations is assigned to greater flow versus volume contributions and to a stronger blood flow autoregulation in deeper tissue (brain cortex) with respect to superficial tissue (scalp and skull). The relatively constant phase lag of T versus arterial blood pressure oscillations at all source-detector distances was assigned to competing effects from stronger autoregulation and smaller arterial-to-venous contributions in deeper tissue with respect to superficial tissue. We demonstrate the application of a hemodynamic model to interpret coherent hemodynamics measured with NIRS and to assess the different nature of shallow (extracerebral) versus deep (cerebral) tissue hemodynamics.

Swept-Source OCT Angiography of Serpiginous Choroiditis.

PURPOSE: To examine and quantify choriocapillaris lesions in active and quiescent serpiginous choroiditis (SC) using swept-source optical coherence tomography angiography (SS-OCTA) and en-face image analysis. DESIGN: Prospective observational case series. PARTICIPANTS: Patients with a clinical diagnosis of SC. METHODS: A SS-OCTA prototype was used to image active and quiescent serpiginous lesions longitudinally before and after anti-inflammatory treatment. En-face slabs of choriocapillaris flow (CC-slab) or outer nuclear layer structure (ONL-slab) were generated from OCTA and OCT data, respectively. MAIN OUTCOME MEASURES: Qualitative and quantitative analyses on lesion boundary and area using a semi-automated MATLAB algorithm. Lesions were also compared to traditional multimodal imaging. RESULTS: Six eyes of three patients were imaged. Choroidal lesions were identified and analyzed in four of six eyes. Lesions with well-defined boundaries were identified in the CC-slab in areas of both active and inactive choroiditis. CC-slab lesion size and shape showed good correlation with lesions identified on indocyanine green angiography. CC-slab lesion area increased with disease activity and decreased with corticosteroid treatment. During active disease, the CC-slab lesion area was larger than both the ONL-slab and fundus autofluorescence lesion areas. Active CC-slab lesions not associated with corresponding abnormal autofluorescence resolved without clinical scarring after treatment. In inactive scars, the areas of retinal and choriocapillaris lesions were similar and did not change over time. CONCLUSIONS: En-face analysis of SS-OCTA choriocapillaris flow voids provide a non-invasive method for the detection of lesions in patients with SC. The presence of lesions in the choriocapillaris in the absence of retinal pigment epithelium and outer retinal abnormalities supports the hypothesis that choriocapillaris is the primary site of pathology in SC, and may be a sensitive early sign of disease activity. We propose a simple grading system of SC lesions based on SS-OCTA and fundus autofluorescence findings. SS-OCTA is a promising non-invasive method for monitoring patients with SC.

Laser speckle contrast imaging is sensitive to advective flux.

Unlike laser Doppler flowmetry, there has yet to be presented a clear description of the physical variables that laser speckle contrast imaging (LSCI) is sensitive to. Herein, we present a theoretical basis for demonstrating that LSCI is sensitive to total flux and, in particular, the summation of diffusive flux and advective flux. We view LSCI from the perspective of mass transport and briefly derive the diffusion with drift equation in terms of an LSCI experiment. This equation reveals the relative sensitivity of LSCI to both diffusive flux and advective flux and, thereby, to both concentration and the ordered velocity of the scattering particles. We demonstrate this dependence through a short series of flow experiments that yield relationships between the calculated speckle contrast and the concentration of the scatterers (manifesting as changes in scattering coefficient), between speckle contrast and the velocity of the scattering fluid, and ultimately between speckle contrast and advective flux. Finally, we argue that the diffusion with drift equation can be used to support both Lorentzian and Gaussian correlation models that relate observed contrast to the movement of the scattering particles and that a weighted linear combination of these two models is likely the most appropriate model for relating speckle contrast to particle motion.

Combined effects of scattering and absorption on laser speckle contrast imaging.

Several variables may affect the local contrast values in laser speckle contrast imaging (LSCI), irrespective of relative motion. It has been suggested that the optical properties of the moving fluid and surrounding tissues can affect LSCI values. However, a detailed study of this has yet to be presented. In this work, we examined the combined effects of the reduced scattering and absorption coefficients on LSCI. This study employs fluid phantoms with different optical properties that were developed to mimic whole blood with varying hematocrit levels. These flow phantoms were imaged with an LSCI system developed for this study. The only variable parameter was the optical properties of the flowing fluid. A negative linear relationship was seen between the changes in contrast and changes in reduced scattering coefficient, absorption coefficient, and total attenuation coefficient. The change in contrast observed due to an increase in the scattering coefficient was greater than what was observed with an increase in the absorption coefficient. The results indicate that optical properties affect contrast values and that they should be considered in the interpretation of LSCI data.

Assessment of incident intensity on laser speckle contrast imaging using a nematic liquid crystal spatial light modulator.

Before laser speckle contrast imaging (LSCI) can be used reliably and quantitatively in a clinical setting, there are several theoretical and practical issues that still must be addressed. In order to address some of these issues, an electro-optical system that utilizes a nematic liquid crystal spatial light modulator (SLM) to mimic LSCI experiments was assembled. The focus of this paper is to address the issue of how incident intensity affects LSCI results. Using the SLM-based system, we systematically adjusted incident intensity on the SLM and assessed the resulting first- and second-order statistics of the imaged speckle to explain the corresponding spatial contrast values in both frozen and time-integrated speckle patterns. The SLM-based system was used to generate speckle patterns with a controlled minimum speckle size, probability intensity distribution, and temporal decorrelation behavior. By eliminating many experimental parameters, this system is capable of serving as a useful intermediary tool between computer simulation and physical experimentation for further developing LSCI as a quantitative imaging modality.

Optical vortex behavior in dynamic speckle fields.

The dynamic behavior of phase singularities, or optical vortices, in the pseudo-phase representation of dynamic speckle patterns is investigated. Sequences of band-limited, dynamic speckle patterns with predetermined Gaussian decorrelation behavior were generated, and the pseudo-phase realizations of the individual speckle patterns were calculated via a two-dimensional Hilbert transform algorithm. Singular points in the pseudo-phase representation are identified by calculating the local topological charge as determined by convolution of the pseudo-phase representations with a series of 2×2 nabla filters. The spatial locations of the phase singularities are tracked over all frames of the speckle sequences, and recorded in three-dimensional space (x,y,f), where f is frame number in the sequence. The behavior of the phase singularities traces 'vortex trails' which are representative of the speckle dynamics. Slowly decorrelating speckle patterns results in long, relatively straight vortex trails, while rapidly decorrelating speckle patterns results in tortuous, relatively short vortex trails. Optical vortex analysis such as described herein can be used as a descriptor of biological activity, flow, and motion.