24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status

Background: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients. Methods: A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L'Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients' contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated. Results: Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing. Conclusion: Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression

24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status

BackgroundSleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.MethodsA total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7–35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L’Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients’ contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated.ResultsOf the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03–82%)] and HR/LF [median: 3.75 (interquartile range 3.19–5.05)] were elevated, independent from the wake–sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.ConclusionOur findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression

Truly form-factor–free industrially scalable system integration for electronic textile architectures with multifunctional fiber devices

Funding Information: This work was supported by the European Commission (H2020, 1D-NEON, grant agreement ID: 685758). J.M.K. and L.G.O. acknowledge the support from the U.K. Research and Innovation (EPSRC, EP/P027628/1). We thank Y. Bernstein and J. Faulkner for helping with grammar check. Funding Information: Acknowledgments Funding:ThisworkwassupportedbytheEuropeanCommission(H2020,1D-NEON,grant agreementID:685758).J.M.K.andL.G.O.acknowledgethesupportfromtheU.K.Researchand Innovation(EPSRC,EP/P027628/1).W ethankY .BernsteinandJ.Faulknerforhelpingwith grammarcheck.Authorcontributions:S.L.andJ.M.K.conceivedtheproject.S.L.,L.G.O.,P .B., R.Martins,andJ.M.K.supervisedtheproject.S.L.andH.L.developedF-PD.S.L.,Y .-W .L., G.-H.A., D.-W .S., J.I.S.,andS.C.developedF-SC.C.L.F ., A.S.,R.I.,P .B., andR.Martinsdevelopedfiber transistor.S.L.,H.L.,andS.C.developedF-LED.ThefiberdeviceswereevaluatedbyS.L.,H.W .C., D.-W .S., H.L.,S.J.,S.D.H.,S.Y .B., S.Z.,W .H.-C., Y .-H.S., X.-B.F ., T .H.L., J.-W .J., andY .K. The developmentofweavingprocesswasconductedbyS.L.,H.W .C., F .M.M., P .J., andV .G.C. Thelaser interconnectionwasdevelopedbyS.L.,H.W .C., K.U.,M.E.,andM.S.Thetextiledemonstrations werecharacterizedbyS.L.,H.W .C., D.-W .S., J.Y ., S.S.,U.E.,S.N.,A.C.,A.M.,R.Momentè,J.G.,N.D., S.M.,C.-H.K.,M.L.,A.N.,D.J.,M.C.,andY .C. ThismanuscriptwaswrittenbyS.L.andJ.M.K.and reviewed by H.W .C., D.-W .S., M.C.,L.G.O., P .B., E.F ., and G.A.J.A. All authors discussed the results andcommentedonthemanuscript.Competinginterests:Theauthorsdeclarethattheyhave nocompetinginterests.Dataandmaterialsavailability:Alldataneededtoevaluatethe conclusionsinthepaperarepresentinthepaperand/ortheSupplementaryMaterials. Publisher Copyright: Copyright © 2023 The Authors, some rights reserved.An integrated textile electronic system is reported here, enabling a truly free form factor system via textile manufacturing integration of fiber-based electronic components. Intelligent and smart systems require freedom of form factor, unrestricted design, and unlimited scale. Initial attempts to develop conductive fibers and textile electronics failed to achieve reliable integration and performance required for industrial-scale manufacturing of technical textiles by standard weaving technologies. Here, we present a textile electronic system with functional one-dimensional devices, including fiber photodetectors (as an input device), fiber supercapacitors (as an energy storage device), fiber field-effect transistors (as an electronic driving device), and fiber quantum dot light-emitting diodes (as an output device). As a proof of concept applicable to smart homes, a textile electronic system composed of multiple functional fiber components is demonstrated, enabling luminance modulation and letter indication depending on sunlight intensity.publishersversionpublishe

New Insights into Properties of Methanol Transport in Sulfonated Polysulfone Composite Membranes for Direct Methanol Fuel Cells

Methanol crossover through a polymer electrolyte membrane has numerous negative effects on direct methanol fuel cells (DMFCs) because it decreases the cell voltage due to a mixed potential (occurrence of both oxygen reduction and methanol oxidation reactions) at the cathode, lowers the overall fuel utilization and contributes to long-term membrane degradation. In this work, an investigation of methanol transport properties of composite membranes based on sulfonated polysulfone (sPSf) and modified silica filler is carried out using the PFG-NMR technique, mainly focusing on high methanol concentration (i.e., 5 M). The influence of methanol crossover on the performance of DMFCs equipped with low-cost sPSf-based membranes operating with 5 M methanol solution at the anode is studied, with particular emphasis on the composite membrane approach. Using a surface-modified-silica filler into composite membranes based on sPSf allows reducing methanol cross-over of 50% compared with the pristine membrane, making it a good candidate to be used as polymer electrolyte for high energy DMFCs

<i>PHF21A</i> Related Disorder: Description of a New Case

PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki–Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype–phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder

Identification of a Novel Missense Mutation of <i>POLR3A</i> Gene in a Cohort of Sicilian Patients with Leukodystrophy

Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD

Ligation of Prostate Cancer Cell Surface GRP78 Activates a Proproliferative and Antiapoptotic Feedback Loop: A ROLE FOR SECRETED PROSTATE-SPECIFIC ANTIGEN*

GRP78, a well characterized chaperone in the endoplasmic reticulum, is critical to the unfolded protein response. More recently, it has been identified on the cell surface, where it has many roles. On cancer cells, it functions as a signaling receptor coupled to proproliferative/antiapoptotic and promigratory mechanisms. In the current study, we demonstrate that ligation of prostate cancer cell surface GRP78 by its natural ligand, activated α2-macroglobulin (α2M*), results in a 2–3-fold up-regulation in the synthesis of prostate-specific antigen (PSA). The PSA is secreted into the medium as an active proteinase, where it binds to native α2M. The resultant α2M·PSA complexes bind to GRP78, causing a 1.5–2-fold increase in the activation of MEK1/2, ERK1/2, S6K, and Akt, which is coupled with a 2–3-fold increase in DNA and protein synthesis. PSA is a marker for the progression of prostate cancer, but its mechanistic role in the disease is unclear. The present studies suggest that PSA may be involved in a signal transduction-dependent feedback loop, whereby it promotes a more aggressive behavior by human prostate cancer cells