Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer's disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.

Interleukin 9 alterations linked to alzheimer disease in african americans.

OBJECTIVE: Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life or whether race modifies other AD-related biomarkers such as inflammatory proteins. METHODS: We performed multiplex cytokine analysis in a healthy middle-aged cohort with family history of AD (n = 68) and an older cohort (n = 125) with normal cognition (NC), mild cognitive impairment, or AD dementia. After determining baseline interleukin (IL)-9 level and AD-associated IL-9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL-9 in brains of African Americans and Caucasians (n = 38), and analyzed postmortem IL-9-related gene expression profiles in the publicly available Mount Sinai cohort (26 African Americans and 180 Caucasians). RESULTS: Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p-Tau181 , and IL-9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL-9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed perivascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL-9 upregulation only in African Americans but not Caucasians. INTERPRETATION: Baseline and AD-associated IL-9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and nongenetic factors need to be considered in future AD research involving unique populations. ANN NEUROL 2019;86:407-418.

SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

OBJECTIVE: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons. STUDY DESIGN: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized. RESULTS: Results were similar across the two seasons. Among infants with community-acquired RSVH (N = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge. CONCLUSION: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.

Structural Organization of the Laryngeal Motor Cortical Network and Its Implication for Evolution of Speech Production.

The laryngeal motor cortex (LMC) is essential for the production of learned vocal behaviors because bilateral damage to this area renders humans unable to speak but has no apparent effect on innate vocalizations such as human laughing and crying or monkey calls. Several hypotheses have been put forward attempting to explain the evolutionary changes from monkeys to humans that potentially led to enhanced LMC functionality for finer motor control of speech production. These views, however, remain limited to the position of the larynx area within the motor cortex, as well as its connections with the phonatory brainstem regions responsible for the direct control of laryngeal muscles. Using probabilistic diffusion tractography in healthy humans and rhesus monkeys, we show that, whereas the LMC structural network is largely comparable in both species, the LMC establishes nearly 7-fold stronger connectivity with the somatosensory and inferior parietal cortices in humans than in macaques. These findings suggest that important "hard-wired" components of the human LMC network controlling the laryngeal component of speech motor output evolved from an already existing, similar network in nonhuman primates. However, the evolution of enhanced LMC-parietal connections likely allowed for more complex synchrony of higher-order sensorimotor coordination, proprioceptive and tactile feedback, and modulation of learned voice for speech production. SIGNIFICANCE STATEMENT: The role of the primary motor cortex in the formation of a comprehensive network controlling speech and language has been long underestimated and poorly studied. Here, we provide comparative and quantitative evidence for the significance of this region in the control of a highly learned and uniquely human behavior: speech production. From the viewpoint of structural network organization, we discuss potential evolutionary advances of enhanced temporoparietal cortical connections with the laryngeal motor cortex in humans compared with nonhuman primates that may have contributed to the development of finer vocal motor control necessary for speech production.

SENTINEL1: An Observational Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

Objective SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season. Study Design This is a noninterventional, observational, cohort study. Results A total of 702 infants were hospitalized with community-acquired RSV disease, of whom an estimated 42% were admitted to the intensive care unit (ICU) and 20% required invasive mechanical ventilation (IMV). Earlier gestational age and younger chronologic age were associated with an increased frequency of RSV-confirmed hospitalization (RSVH), ICU admission, and IMV. Among infants 29 to 32 wGA and < 3 months of age, 68% required ICU admission and 44% required IMV. One death occurred of an infant 29 wGA. Among the 212 infants enrolled for in-depth analysis of health care resource utilization, mean and median RSVH charges were $55,551 and $27,461, respectively, which varied by intensity of care required. Outpatient visits were common, with 63% and 62% of infants requiring visits before and within 1 month following the RSVH, respectively. Conclusion Preterm infants 29 to 35 wGA are at high risk for severe RSV disease, which imposes a substantial health burden, particularly in the first months of life.

Receipt of palivizumab before birth hospitalization discharge among preterm infants in the United States.

OBJECTIVE: This study aims to determine predischarge palivizumab receipt prevalence among infants ≤ 36 weeks' gestational age. STUDY DESIGN: This retrospective cohort study used hospital discharge records from the Premier Perspective database (Premier Inc., Charlotte, NC) of infants ≤ 36 weeks' gestational age who were discharged home after birth hospitalization during the November-March respiratory syncytial virus (RSV) seasons from 2006 to 2011. Descriptive statistics were performed and logistic regression was employed to identify differences in categorical variables. RESULTS: Among infants ≤ 36 weeks' gestational age discharged home during the RSV seasons, 21.4 to 27.0% had a record of palivizumab receipt before discharge. Among infants ≤ 30 weeks' gestational age, palivizumab receipt was 82.3 to 88.8%. Receipt varied considerably at the hospital level, from 0 to 100%. CONCLUSION: This study improves our understanding of characteristics associated with predischarge palivizumab administration. The identified gaps in recommended care can help inform future implementation of palivizumab and other interventions to help improve the health of high-risk preterm infants in the United States.

What's special about task in dystonia? A voxel-based morphometry and diffusion weighted imaging study.

Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex, and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task specificity in dystonia remained limited. We used high-resolution magnetic resonance imaging (MRI) with voxel-based morphometry and diffusion weighted imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer's cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. A direct comparison between both dystonia forms indicated that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, and occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in the non-task-specific group were limited to the left cerebellum (lobule VIIa) only, whereas white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule, and middle cingulate gyrus. Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers.

Isolation, expression and characterization of a minor allergen from Penicillium crustosum.

A ribosomal P1 protein, Pen b 26 from Penicillium brevicompactum, was previously identified as a major allergen. A homolog protein was isolated and characterized from Penicillium crustosum which is not known to be allergenic mold. A cDNA library of P. crustosum was constructed and screened using a probe based on the DNA sequence of Pen b 26. A positive clone was isolated, expressed in Escherichia coli, purified and characterized by comparing its immunological and physical properties to Pen b 26. It was designated as Pen cr 26 and had a 321 nt ORF corresponding to 107 amino acids with a MW of 11 kDa. Pen cr 26 had strong sequence homology to Pen b 26 (92% for nucleotides and 86% for amino acids) and its physical and predicted structural properties were similar to the latter. The level of expression of Pen cr 26 was much lower than that of Pen b 26 in the same expression vector. Both proteins were recognized equally well by the IgG class specific antibodies, but Pen cr 26 was poorly recognized by Penicillium-sensitive atopic sera (IgE), suggesting striking antigenic difference in IgE epitopes, i.e., 87% were positive for Pen b 26 while only 23% were positive for Pen cr 26. The allergenicity of Pen cr 26 seems to be minor in nature and it could be a hypoallergenic variant of Pen b 26.

Self-catalyzed site-specific depurination of G residues mediated by cruciform extrusion in closed circular DNA plasmids.

A major variety of "spontaneous" genomic damage is endogenous generation of apurinic sites. Depurination rates vary widely across genomes, occurring with higher frequency at "depurination hot spots." Recently, we discovered a site-specific self-catalyzed depurinating activity in short (14-18 nucleotides) DNA stem-loop-forming sequences with a 5'-G(T/A)GG-3' loop and T·A or G·C as the first base pair at the base of the loop; the 5'-G residue of the loop self-depurinates at least 10(5)-fold faster than random "spontaneous" depurination at pH 5. Formation of the catalytic intermediate for self-depurination in double-stranded DNA requires a stem-loop to extrude as part of a cruciform. In this study, evidence is presented for self-catalyzed depurination mediated by cruciform formation in plasmid DNA in vitro. Cruciform extrusion was confirmed, and its extent was quantitated by digestion of the plasmid with single strand-specific mung bean endonuclease, followed by restriction digestion and sequencing of resulting mung bean-generated fragments. Appearance of the apurinic site in the self-depurinating stem-loop was confirmed by digestion of plasmid DNA with apurinic endonuclease IV, followed by primer extension and/or PCR amplification to detect the endonuclease-generated strand break and identify its location. Self-catalyzed depurination was contingent on the plasmid being supercoiled and was not observed in linearized plasmids, consistent with the presence of the extruded cruciform in the supercoiled plasmid and not in the linear one. These results indicate that self-catalyzed depurination is not unique to single-stranded DNA; rather, it can occur in stem-loop structures extruding from double-stranded DNA and therefore could, in principle, occur in vivo.

Spectroscopic investigations, concentration dependent SERS, and molecular docking studies of a hydroxybenzylidene derivative.

Spectroscopic analysis, density functional theory (DFT) studies and surface enhanced Raman scattering (SERS) of (E)-N'-(5-chloro-2-hydroxybenzylidene)-4-trifluoromethyl) benzohydrazide (CHTB) have been studied on different silver colloids in order to know the particular chemical species responsible for the spectra. Very significant shifts are observed for Raman and SERS wavenumbers. Observed changes in the υ-ring modes may be due to surface interaction of the π-electrons and the presence of this suggested that RingII is more tilted in both cases than RingI and the molecule assumes a tilted orientation for the concentration 10-3 M. Orientation changes are seen in concentration dependent SERS spectra. The molecular electrostatic potential has also been constructed to determine the electron rich and poor site of CHTB. The molecular docking studies indicate that the binding affinity and hydrogen bond interactions with the receptors may be supporting evidence for further studies in designing other pharmaceutical applications of CHTB.Communicated by Ramaswamy H. Sarma.

Conformational analysis and quantum descriptors of two new imidazole derivatives by experimental, DFT, AIM, molecular docking studies and adsorption activity on graphene.

1-[2-(2-hydroxy-3-methoxy-5-(4-methoxyphenylazo)benzaldeneamino)ethyl]-3-methyl-3H-imidazole (HMY) and 1-[2-(2-hydroxy-3-methoxy-5-(4-methylphenylazo)benzaldene amino)ethyl]-3-methyl-3H-imidazole (HMM) were synthesized and characterized using spectral analysis. Conformational analysis has been achieved using potential energy scan for different rotable bonds for obtaining the lowest energy conformer. Conformer with minimum energy is obtained along the dihedral angle N30-C31-C34-N37. QTAIM analysis gives nature and strength of hydrogen bonding interactions. UV-Vis, electrostatic potential and chemical descriptors are analyzed. Interaction of HMY and HMM with graphene is analyzed in terms of SERS activity. Chemical reactivity descriptors were investigated for graphene-drug systems. NLO activity of parent drugs and its graphene complexes show good activity. The wavenumber downshift of different modes is noted. Title molecules exhibit inhibitory activity against cytochrome C peroxidase. Interactions with graphene sheets are theoretically predicted for the title compounds.

Spectral characterization, thermochemical studies, periodic SAPT calculations and detailed quantum mechanical profiling various physico-chemical properties of 3,4-dichlorodiuron.

A set of experimental and computational techniques have been applied for the understanding of fundamental spectroscopic and reactive properties of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron) compound. Experimental techniques employed in this study encompassed spectroscopic characterization via IR and Raman approaches, while optical properties were studied by measurements of UV/Vis spectra. The thermogravimetric analysis was also studied in order to analyze the stability of diuron. Aside from the determination of reactive properties, DFT calculations on isolated molecules were also used to thoroughly visualize and analyze spectroscopic properties such as IR and UV/Vis. MD simulations were used in order to understand interactions with water, while periodic DFT calculations were used in order to analyze band structure and density of states of the diuron crystal structure. Since the crystal structure of diuron is known, it was used in order to extract the relevant molecular pairs and investigate interactions between them by DFT and symmetry adapted perturbation theory approaches (SAPT).

Baseline Results: The Association Between Cardiovascular Risk and Preclinical Alzheimer's Disease Pathology (ASCEND) Study.

BACKGROUND: The rate of AD for African Americans (AAs) is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress, and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs. OBJECTIVE: Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race. METHODS: We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound, and cognitive testing. RESULTS: While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less cerebrospinal fluid tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, race significantly modified the relationship between total tau, phospho-tau, and Trails B, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs. CONCLUSION: In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.

Expression and characterization of Pen b 26 allergen of Penicillium brevicompactum in Escherichia coli.

Pen b 26 is one of the allergens produced by Penicillium brevicompactum which is one of the most prevalent in door airborne fungi and a major source of respiratory problems, including asthma. Pen b 26 wa scloned and expressed as an N-terminal as well as a C-terminal His6 tagged fusion protein in Escherichia coli. This allergen was purified by immobilized Ni2+-affinity chromatography. The purified Pen b 26 was characterized by immunological, biochemical and biophysical methods. C-His6 tagged Pen b 26 produced several fold greater yield than N-His6 tagged Pen b 26. The affinity of C-His6 tagged Pen b 26 for the specific antibody was also 2.75 times higher than N-His6 tagged Pen b 26

One-step synthesis of eco-friendly boiled rice starch blended polyvinyl alcohol bionanocomposite films decorated with in situ generated silver nanoparticles for food packaging purpose.

The study reports a one-step preparation of polyvinyl alcohol/boiled rice starch blend film fabricated with in situ generated silver nanoparticles (PVA/BRS/sAgNPs) formed in the presence of sunlight irradiation. The bionanocomposite appeared to have dark brown color with a characteristic surface plasmon resonance peak at 439 nm. Further characterization has confirmed the presence of physical interactions among the components PVA, BRS and sAgNPs. Compared to the control PVA, the nanocomposites showed improved mechanical and optical properties with decreased water sensitivity. Presence of boiled rice starch and sAgNPs were also found to influence the light transmittance of composite film. Moreover, PVA/BRS/sAgNPs film was found to have superior barrier property against environmental microorganisms. Biodegradation of the composite films was studied by indoor soil burial test and was assessed by visual appearance, weight loss and FTIR analysis. Interestingly, both the PVA/BRS and PVA/BRS/sAgNPs films proved to be biodegradable and hence have promising application as cost effective food packaging material with the latter having marked antimicrobial property.

Detailed quantum mechanical, molecular docking, QSAR prediction, photovoltaic light harvesting efficiency analysis of benzil and its halogenated analogues.

The structural, spectroscopic various physico-chemical and biological characteristics of the organic molecule benzil (BZL) and derivatives, 1,2-bis(4-methylphneyl)-1,2-ethanedione (DMB), 4,4'-difluorobenzil (DFB), 4,4'-dichlorobenzil (DCB) and 4,4'-dibromobenzil (DBB) have been studied by various computational methods. The experimental and scaled simulated Raman and IR spectra were compared and found close agreement. Assignments of important peaks are also presented. Detailed information pertaining to the local and global reactivity and other properties like electrophilic and nucleophilic characteristics were analysed. The hyperactive pressure was measured in terms of polarizability and corresponding biological properties were validated to identity reactive sites. Prediction of Activity Spectral Studies (PASS) predicts the biological activity of the compounds and it is found that the candidate molecules can be used as feruloyl esterase inhibitor, bisphosphoglycerate phosphatase inhibitor and Prolylaminopeptidase inhibitor. The crystals structures of those receptors are taken from the protein data bank and docking studies indicates stable complex with the receptors and candidate molecules. Light harvesting efficiency, followed by photovoltaic modelling shows that DMB is the best compound to be used in the DSSC to get the best output.

Cost savings associated with timely treatment of botulism with botulism antitoxin heptavalent product.

BACKGROUND: Botulism is a rare, serious, and sometimes fatal paralytic illness caused by exposure to neurotoxins produced by Clostridium botulinum bacteria. Patients with documented or suspected exposure to botulinum toxin serotypes A-G can be treated with BAT® [Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)] product, which was approved in 2013 in the United States (US). Patients with botulism have demonstrated greater clinical benefit with early BAT product treatment (≤2 days from symptom onset) versus late treatment (>2 days). OBJECTIVE: Economic outcomes associated with improved clinical outcome benefits of BAT product treatment have not yet been reported. This ad hoc analysis aimed to estimate and compare costs associated with hospitalization, intensive care unit stay, and mechanical ventilation for patients with botulism administered BAT product treatment early or late. METHODS: Clinical outcomes data for early and late BAT product treatment were obtained from a patient registry conducted between October 2014 and July 2017. Total per patient mean daily costs were estimated based on information from published literature. Total population costs per group were calculated by multiplying estimated mean cost per patient by the average annual number of non-infant botulism cases in the US. RESULTS: Mean per patient costs were 2.5 times lower for patients treated with BAT product early versus late. On average in the US, early BAT product treatment could save greater than $3.9 million per year versus late treatment. CONCLUSION: Substantial economic savings can be achieved with early BAT product treatment. The findings support the recommendation for public health authorities to ensure antitoxin treatment is readily available in sufficient quantities to manage botulism cases, including sporadic outbreaks and potential mass exposure biological attacks.

Conformational profile, vibrational assignments, NLO properties and molecular docking of biologically active herbicide1,1-dimethyl-3-phenylurea.

1,1-Dimethyl-3-phenylurea (known as fenuron) which is a phenyl urea-based widely used herbicide exhibits interesting structural and conformational properties and a notable biological activity. A detailed analysis on the vibrational, molecular and electronic characteristics of fenuron has been carried out. Potential energy scans (PESs) performed at the B3LYP/6-311++G(d,p) level of theory predicted two possible minima corresponding to the optimized anti and synforms resulting from the internal rotation about the N-C bond. The presence of an auxochrome together with the interaction with DMSO solvent exhibited a blue shift corresponding to the C=O orbitals. Delocalization of HOMO and LUMO orbital facilitated the charge transfer effect in the molecule. The calculated HOMO-LUMO energies, chemical potential, energy gap and global hardness suggested a low softness value for the compound while its biological activity was described by the value of electrophilicity. Chlorine substitution in the phenyl ring influenced the orbital delocalization for ortho and para substitutions but that of meta remained unaffected. NLO properties were noticed to increase due to chlorine substitution in the parent molecule. The docking results suggested that the compound exhibits an inhibitory activity against mitochondrial ubiquinol-cytochrome-c reductase and can be developed as a potential anticancer agent.

Impact of Respiratory Syncytial Virus-Confirmed Hospitalizations on Caregivers of US Preterm Infants.

This study assessed the impact of respiratory syncytial virus-confirmed hospitalizations (RSVH) on caregivers of high-risk preterm infants. Caregivers for infants born at 29 to 35 weeks' gestational age and hospitalized for confirmed RSV disease responded to measures of self-rated and perceived infant stress (1-7; 7 = very stressful), perceived infant health (0-100; 100 = best imaginable health), and productivity impairment. Data were collected at hospital discharge through 1 month post-discharge. Caregiver responses indicated high stress levels, poor health, and productivity loss were reported at discharge; however, steady improvements were seen through 1 month post-discharge: caregiver-rated stress (from 6 to 2), infant stress (5 to 1), caregiver-perceived infant health (64 to 84), and productivity loss (mothers: 91% to 31%; fathers: 81% to 18%). Qualitative results indicated emotional impact, family routine disruption, financial concerns, and medical concerns persisted at 1 month post-discharge. This study found the caregiver burden of RSVH persists at least 1 month beyond discharge.

Connectivity profiles of the insular network for speech control in healthy individuals and patients with spasmodic dysphonia.

The importance of insula in speech control is acknowledged but poorly understood, partly due to a variety of clinical symptoms resulting from insults to this structure. To clarify its structural organization within the speech network in healthy subjects, we used probabilistic diffusion tractography to examine insular connectivity with three cortical regions responsible for sound processing [Brodmann area (BA) 22], motor preparation (BA 44) and motor execution (laryngeal/orofacial primary motor cortex, BA 4). To assess insular reorganization in a speech disorder, we examined its structural connectivity in patients with spasmodic dysphonia (SD), a neurological condition that selectively affects speech production. We demonstrated structural segregation of insula into three non-overlapping regions, which receive distinct connections from BA 44 (anterior insula), BA 4 (mid-insula) and BA 22 (dorsal and posterior insula). There were no significant differences either in the number of streamlines connecting each insular subdivision to the cortical target or hemispheric lateralization of insular clusters and their projections between healthy subjects and SD patients. However, spatial distribution of the insular subdivisions connected to BA 4 and BA 44 was distinctly organized in healthy controls and SD patients, extending ventro-posteriorly in the former group and anterio-dorsally in the latter group. Our findings point to structural segregation of the insular sub-regions, which may be associated with the different aspects of sensorimotor and cognitive control of speech production. We suggest that distinct insular involvement may lead to different clinical manifestations when one or the other insular region and/or its connections undergo spatial reorganization.