Severe morbidity among hospitalised adults with acute influenza and other respiratory infections: 2014-2015 and 2015-2016.

Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014-2015 and 2015-2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0-2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2-0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2-1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0-2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.

Progress and Advances in Porous Silica-based Scaffolds for Enhanced Solid-state Hydrogen Storage: A Systematic Literature Review.

Hydrogen plays a crucial role in the future energy landscape owing to its high energy density. However, finding an ideal storage material is the key challenge to the success of the hydrogen economy. Various solid-state hydrogen storage materials, such as metal hydrides, have been developed to realize safe, effective, and compact hydrogen storage. However, low kinetics and thermodynamic stability lead to a high working temperature and a low hydrogen sorption rate of the metal hydrides. Using scaffolds made from porous materials like silica to confine the metal hydrides is necessary for better and improved hydrogen storage. Therefore, this article reviews porous silica-based scaffolds as an ideal material for improved hydrogen storage. The outcome showed that confining the metal hydrides using scaffolds based on porous silica significantly increases their storage capacities. It was also found that the structural modifications of the silica-based scaffold into a hollow structure further improved the storage capacity and increased the affinity and confinement ability of the metal hydrides, which prevents the agglomeration of metal particles during the adsorption/desorption process. Hence, the structural modifications of the silica material into a fibrous and hollow material are recommended to be crucial for further enhancing the metal hydride storage capacity.

Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus).

The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.

Clinically significant red blood cell antibodies in chronically transfused patients: a survey of Chinese thalassemia major patients and literature review.

BACKGROUND: Red blood cell (RBC) alloimmunization is reported to occur at an incidence of 5.2% to 23.5% among patients with thalassemia requiring chronic transfusion. With very limited data on alloimmunization among the Chinese population, a territory-wide study has been performed to look at its prevalence among Chinese thalassemia major patients. STUDY DESIGN AND METHODS: A retrospective study was conducted by reviewing RBC request records for patients with thalassemia major in Hong Kong from 2006 to 2009. Demographic information and serologic data were retrieved for analysis. RESULTS: A total of 382 patients were identified and consisted of 190 males and 192 females with a median age of 23 ± 10.4 (range, 0.25 to 52) years. Eighty-eight patients (23.0%) were reported to have RBC antibodies. Of them, 114 alloantibodies, 18 autoantibodies, and 19 unidentified antibodies were identified. Anti-E (42, 39.3%), anti-Mi(a)/Mur (33, 30.85%), anti-c (14, 13.1%), and anti-Jk(a) (seven, 6.55%) were the commonest antibodies reported. However, one case of anti-K (0.9%) and two cases of anti-Fy(b) (1.9%) were reported. Seven of the 18 patients with autoantibodies contained a total of 13 alloantibodies. They were anti-E (five, 38.4%), anti-Mi(a)/Mur (four, 30.8%), anti-Jk(a) (two, 15.4%), anti-c (one, 7.7%), and anti-Fy(b) (one, 7.7%). CONCLUSION: It is the first comprehensive study on Chinese thalassemia major patients. Clinically significant alloantibodies are different from those observed in the Western population, although antibodies developed against Rh antigens are still common. Chinese patients are less likely to have antibodies against Kell and Duffy blood group antigens, but are more prone to develop antibodies against the Miltenberger antigens.

Validation of a prediction rule for development of rheumatoid arthritis in patients with early undifferentiated arthritis.

OBJECTIVE: To validate a model which predicts progression from undifferentiated arthritis (UA) to RA, in a Canadian UA cohort. METHODS: The prediction rule, comprising variables which are scored from 0 to 13, with higher scores reflecting an increased risk of RA, was applied to baseline characteristics of all patients with UA. Progression to RA was determined at 6 months. RESULTS: 105 patients were identified. By 6 months, 80 (76%) had developed RA while 25 (24%) had developed another diagnosis. Number of tender and swollen joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide positivity, poor functional status and high disease activity were associated with development of RA (p<0.01). Median prediction score was 8.0 for progressors, 5.0 for non-progressors. With these cut-off points, 18 (72%) patients with scores < or =5 did not develop RA, while 35 (97%) with scores > or =8 did develop RA. CONCLUSIONS: High scores in our cohort predicted those who progressed to RA by 6 months. Baseline scores > or =8 corresponded with higher rates of progression.

Thermoregulatory sudomotor dysfunction and diabetic neuropathy develop in parallel in at-risk feet.

AIMS: To establish the longitudinal relationship of foot complications to neuropathy based on a 4-year follow-up of diabetic patients stratified by sudomotor dysfunctions. METHODS: One hundred and nineteen Type 2 diabetic patients and 36 non-diabetic subjects were initially registered in the prospective cohort study. Plantar skin temperature and sympathetic skin response (SSR) were used to monitor sympathetic mediated thermoregulation and sudomotor function. Peripheral somatic and central autonomic functions were studied using clinical, nerve conduction and cardiovascular reflex tests. At enrolment, the diabetic patients were classified into one of three groups by the progressive stages of sudomotor dysfunction: SSR+ (SSR present; 49 patients), SSR- (SSR absent; 41 patients) and at-risk group (SSR absent but with cracked skin involving partial thickness of the dermis; 29 patients). RESULTS: The at-risk group had 13.4 times (95% confidence interval 1.4-125.7) higher plantar ulceration rates than the other two patient groups during the 4 years. Skin temperature elevation occurred in parallel with development of foot sweating problems. There were no significant differences between the three patient groups in the ratios of abnormal heart rate variation, orthostatic test and clinical neuropathy score at follow-up. After 4 years of follow-up, nerve conduction abnormalities were more frequent in the at-risk and SSR- groups than in the SSR+ group. CONCLUSIONS: Early deterioration of small sympathetic fibres could not be quantified accurately by the clinical, somatic and autonomic tests. Assessing skin integrity and sudomotor function in at-risk individuals identifies early peripheral sympathetic neuropathy, even if the patients have no overt clinical symptoms.

Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue.

A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer.

Pulse electroplating of copper film: a study of process and microstructure.

Copper films with high density of twin boundaries are known for high mechanical strength with little tradeoff in electrical conductivity. To achieve such a high density, twin lamellae and spacing will be on the nanoscale. In the current study, 10 microm copper films were prepared by pulse electrodeposition with different applied pulse peak current densities and pulse on-times. It was found that the deposits microstructure was dependent on the parameters of pulse plating. Higher energy pulses caused stronger self-annealing effect on grain recrystallization and growth, thus leading to enhanced fiber textures, while lower energy pulses gave rise to more random microstructure in the deposits and rougher surface topography. However in the extremes of pulse currents we applied, the twin densities were not as high as those resulted from the medium or relatively high pulse currents. The highest amount of nanoscale twinning was found to form from a proper degree of self-annealing induced grain structure evolution. The driving force behind the self-annealing is discussed.

Effect of dynamic compression on in vitro chondrocyte metabolism.

BACKGROUND: Chondrocytes can detect and respond to the mechanical environment by altering their metabolism. This study was designed to explore the effects of dynamic compression on chondrocyte metabolism. METHODS: Chondrocytes were harvested from newborn Wistar rats. After 7 days of expansion, chondrocytes embedded in agarose discs underwent uniaxial unconfined dynamic compression loads at different amplitudes (5%, 10%, and 15%) and frequencies (0.5 Hz, 1.0 Hz, 2.0 Hz, and 3.0 Hz) with a duration of 24 hours. The delayed effects on the chondrocytes were studied at 1, 3, and 7 days after the experiment. RESULTS: The results showed that at 10% strain, higher-frequency compression pressure can enhance the proliferation of chondrocytes. The synthesis of glycosaminoglycan (GAG) increased at 10%-15% strain and a 1-Hz load. The synthesis of nitric oxide (NO) increased at the 0.5-Hz load; while decreasing at the 15% strain. With 10% strain, 1 Hz dynamic compression, the proliferation of chondrocytes and GAG synthesis increased and persisted for 7 days, and NO synthesis decreased at the third and seventh days of culture. CONCLUSIONS: This study showed that chondrocytes respond metabolically to compressive loading, which is expected to modulate the growth and the resultant biomechanical properties of these tissue-engineered constructs during culture.

Strongly exchange-coupled and surface-state-modulated magnetization dynamics in Bi2Se3/yttrium iron garnet heterostructures.

Harnessing the spin-momentum locking of topological surface states in conjunction with magnetic materials is the first step to realize novel topological insulator-based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron garnet (YIG) bilayers manifested as large interfacial in-plane magnetic anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance. The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3 film approaches its two-dimensional limit, indicating that topological surface states play an important role in the magnetization dynamics of YIG. Temperature-dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the magnetic proximity effect of TC as high as 180 K, an emerging low-temperature perpendicular magnetic anisotropy competing the high-temperature IMA, and an increasing exchange effective field of YIG steadily increasing toward low temperature. Our study sheds light on the effects of topological insulators on magnetization dynamics, essential for the development of topological insulator-based spintronic devices.

High-quality thulium iron garnet films with tunable perpendicular magnetic anisotropy by off-axis sputtering - correlation between magnetic properties and film strain.

Thulium iron garnet (TmIG) films with perpendicular magnetic anisotropy (PMA) were grown on gadolinium gallium garnet (GGG) (111) substrates by off-axis sputtering. High-resolution synchrotron radiation X-ray diffraction studies and spherical aberration-corrected scanning transmission electron microscope (Cs-corrected STEM) images showed the excellent crystallinity of the films and their sharp interface with GGG. Damping constant of TmIG thin film was determined to be 0.0133 by frequency-dependent ferromagnetic resonance (FMR) measurements. The saturation magnetization (Ms) and the coercive field (Hc) were obtained systematically as a function of the longitudinal distance (L) between the sputtering target and the substrate. A 170% enhancement of PMA field (H⊥) was achieved by tuning the film composition to increase the tensile strain. Moreover, current-induced magnetization switching on a Pt/TmIG structure was demonstrated with an ultra-low critical current density (jc) of 2.5 × 106 A/cm2, an order of magnitude smaller than the previously reported value. We were able to tune Ms, Hc and H⊥ to obtain an ultra-low jc of switching the magnetization, showing the great potential of sputtered TmIG films for spintronics.

Metallic Nanoislands on Graphene for Monitoring Swallowing Activity in Head and Neck Cancer Patients.

There is a need to monitor patients with cancer of the head and neck postradiation therapy, as diminished swallowing activity can result in disuse atrophy and fibrosis of the swallowing muscles. This paper describes a flexible strain sensor comprising palladium nanoislands on single-layer graphene. These piezoresistive sensors were tested on 14 disease-free head and neck cancer patients with various levels of swallowing function: from nondysphagic to severely dysphagic. The patch-like devices detected differences in (1) the consistencies of food boluses when swallowed and (2) dysphagic and nondysphagic swallows. When surface electromyography (sEMG) is obtained simultaneously with strain data, it is also possible to differentiate swallowing vs nonswallowing events. The plots of resistance vs time are correlated to specific events recorded by video X-ray fluoroscopy. Finally, we developed a machine-learning algorithm to automate the identification of bolus type being swallowed by a healthy subject (86.4%. accuracy). The algorithm was also able to discriminate between swallows of the same bolus from either the healthy subject or a dysphagic patient (94.7% accuracy). Taken together, these results may lead to noninvasive and home-based systems for monitoring of swallowing function and improved quality of life.

The incidence and risk factors for the development of vitreomacular interface abnormality in diabetic macular edema treated with intravitreal injection of anti-VEGF.

PurposeTo report the incidence and associated factors for the development of vitreomacular interface abnormality (VMIA) in patients with diabetic macular edema (DME) who received intravitreal injection (IVI) of anti-VEGF (Bevacizumab and Ranibizumab) treatment.MethodsA retrospective observational study. Patients with DME followed at least 6 months were reviewed. Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT) and final BCVA, CRT in eyes with and without VMIA were compared. Multiple logistic regression was also used to investigate the risk factors of VMIA formation in patients with DME treated by anti-VEGF.ResultsA total of 201 eyes in 142 patients met the inclusion criteria of the study. VMIA developed in 44 eyes (21.89%) of patients during a mean follow-up period of 40.84 months. The estimated mean incidence of VMIA formation was 6.43% per year. Poor baseline BCVA was found to be a risk factor for VMIA development (P=0.001, odds ratio=5.299, 95% confidence interval: 1.972 to 14.238). There was no difference between eyes with and without VMIA formation in improving BCVA (P=0.557) and lowering the macular edema (eyes without VMIA formation: -107.72±171.91 µm; eyes with VMIA formation: -155.02±212.27 µm, P=0.133).ConclusionsThis study revealed the incidence of VMIA formation in IVI anti-VEGF treated DME eyes was 6.43%. Poor baseline BCVA was found to be a risk factor for VMIA formation. Both eyes with and without VMIA development had favorable response to anti-VEGF treatment.

Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis.

Monospecific antikeratin antisera and specific complementary DNA probes were used to analyze expression of keratin genes in newborn mouse skin and skin papillomas and carcinomas by indirect immunofluorescence, immunoblotting, and in situ hybridization. Tumors were induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Type I epidermal keratin K14 protein (Mr 55,000) is found in all living layers of the newborn skin but is most abundant in the lower strata. K1 (Mr 67,000) and K10 (Mr 59,000) proteins are predominantly suprabasal and K1 is processed in the stratum corneum. Transcripts for K14 were confined largely to the basal cell layer by in situ hybridization. Transcripts for K1 and K10 were highly expressed in suprabasal cells including the granular cell layer. In benign tumors, distribution of K14 protein is similar to that in newborn skin, while the abundance of K1 and K10 appears to be somewhat reduced although the tissue distribution remains suprabasal. Transcription of K14 is aberrant in benign tumors and transcripts persist throughout much of the suprabasal cell layers. Transcripts of K1 and K10 are normally distributed in papillomas but grain density is less intense than in newborn epidermis. Keratin expression in carcinomas is highly disturbed. K14 protein and transcripts are highly expressed in all strata in carcinomas while protein and transcripts for K1 and K10 are essentially absent. These results suggest that papilloma cells fail to respond to or generate signals to regulate K14 expression in the differentiating suprabasal cell layers and may not fully express their suprabasal cell keratins. Carcinomas fail to express suprabasal cell keratins and this is regulated at the transcriptional level. The loss of suprabasal keratin expression may provide a marker for malignant conversion in the mouse skin carcinogenesis model.

Differential role of PR-A and -B isoforms in transcription regulation of human GnRH receptor gene.

The presence of progesterone response element (PRE) in the 5'-flanking region of the human GnRH receptor (GnRHR) suggests the possible regulation of this gene by progesterone (P). In the present study, we examined the effects of P in transcriptional regulation of human GnRHR gene expression at the pituitary and placenta levels since the GnRHR has been detected in both tissues. By the use of transient transfection assays, a differential regulation of human GnRHR promoter activity by P was observed. P treatment resulted in a decrease in promoter activity in the pituitary alphaT3-1 cells, suggesting a P-mediated inhibitory action. Interestingly, P is found to have a stimulatory role at the placental expression of this gene. Addition of RU486 to, or inhibition of endogenous P production by, the placental JEG-3 cells leads to a decrease in promoter activity, which is reversed by the replacement of P. Further studies have identified a putative PRE, namely human GR-PRE (located between -535 and -521, related to translation start site), that may be responsible for the P action since the mutation of these motifs reversed the P-mediated effects. The binding of PR to this element is confirmed by antibody supershift assays. The physiological effects of P are mediated through two PR isoforms, namely PR-A and PR-B. In the present study, overexpression of human PR-A resulted in a decrease in human promoter activity in both pituitary and placental cells. Interestingly, overexpression of PR-B exhibits a cell-dependent transcriptional activity, whereby it functions as a transcription activator in the placenta but as a transcription repressor in the pituitary. In summary, our results demonstrated a differential usage of PR-A and PR-B in transcriptional regulation of human GnRHR gene expression by P at the pituitary and placenta levels.

Ultra-slow frequency bands reflecting potential coherence between neocortical brain regions.

Recent studies of electromagnetic ultra-slow waves (⩽0.1Hz) have suggested that they play a role in the integration of otherwise disassociated brain regions supporting vital functions (Ackermann and Borbely, 1997; Picchioni et al., 2010; Knyazev, 2012; Le Bon et al., 2012). We emphasize this spectral domain in probing sensor coherence issues raised by these studies using Hilbert phase coherences in the human MEG. In addition, we ask: will temporal-spatial phase coherence in regional brain oscillations obtained from the ultraslow spectral bands of multi-channel magnetoencephalograms (MEG) differentiate resting, "task-free" MEG records of normal control and schizophrenic subjects? The goal of the study is a comparison of the relative persistence of intra-regional phase locking values (PLVs), among 10, region-defined, sensors in examined in the resting multichannel, MEG records as a function of spectral frequency bands and diagnostic category. The following comparison of Hilbert-transform-engendered relative phases of each designated spectral band was made using their pair-wise PLVs. This indicated the proportion of shared cycle time in which the phase relations between the index location and reference leads were maintained. Leave one out, bootstrapping of the PLVs via a support vector machine (SVM), classified clinical status with 97.3% accuracy. It was generally the case that spectral bands ⩽1.0Hz generated the highest values of the PLVs and discriminated best between control and patient populations. We conclude that PLV analysis of the oscillatory patterns of MEG recordings in the ultraslow frequency bands suggest their functional significance in intra-regional signal coherence and provide a higher rate of classification of patients and normal subjects than the other spectral domains examined.

Regulated synthesis of low-molecular-weight antigens in keratinocyte cell cultures.

Proteins from mouse epidermis cytosol extracts react on immunoblots with a polyclonal rabbit antiserum raised against rat skin calcium-binding protein (SCaBP), a parvalbumin of the panniculus carnosus. Three mouse epidermal proteins with molecular weights between 10-12K, which are distinct from SCaBP, are recognized by the antiserum. The synthesis of these proteins in keratinocyte culture is modulated by Ca++, as is the differentiation of the keratinocytes. Proliferating mouse keratinocytes in medium containing 0.07 mM Ca++ (low Ca++) undergo terminal differentiation when the Ca++ concentration is elevated to 1.8 mM (high Ca++). Synthesis of the 3 antigens can be demonstrated when soluble extracts of keratinocytes labeled with [35S]methionine in low Ca++ medium are immunoprecipitated with anti-SCaBP serum. These antigens are not synthesized in cultures of dermal fibroblasts. When keratinocytes are switched to high Ca++ medium, synthesis of these antigens is greatly diminished over the course of 48-72 h. However, the antigens persist in differentiating cells. When proliferating keratinocytes in low Ca++ medium are exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), differentiation is induced in a subpopulation of cells, and specific antigen synthesis is transiently inhibited. The inhibition correlates with the time when many cells are differentiating in response to TPA. When proliferating keratinocytes are pulse-labeled with 32PO4, the 11K antigen is phosphorylated and the phosphorylation is not enhanced by TPA exposure. All 3 antigens are synthesized in a reticulocyte lysate preparation with added newborn mouse epidermis messenger RNA or mRNA from keratinocytes cultured in low Ca++ medium. Thus, these antigens are likely to represent unique proteins rather than processed or degraded ones. The coordinately regulated expression of these antigens associated with the differentiation state of the keratinocytes suggests that these proteins are important in keratinocyte proliferation and differentiation.

Expression of keratin genes in mouse epidermis and normal and malignantly transformed epidermal cells in culture.

Complementary DNA (cDNA) clones constructed to the 55, 59 and 67 kilodalton (K) keratins, the major keratins synthesized in newborn mouse epidermis, were used as molecular hybridization probes to examine the expression of these genes in newborn epidermis and normal and malignantly transformed epidermal cells in culture. Transcripts of these three keratin genes are abundant in newborn epidermis. However, primary cultures of epidermal cells contain very low levels of these RNAs. The decreased expression of these keratin genes in primary cells appears to be due to factors within the culture system. Unlike primary-cell cultures, the malignantly transformed cell line Pam 212 synthesizes keratin proteins and mRNAs similar to newborn epidermis, including the 67 K keratin. However, synthesis of the 67 K keratin in Pam 212 cells is modulated by culture factors. Keratin gene expression in another Pam line, 321, differs from that of Pam 212 cells in that decreased expression of these three keratin genes occurs. These results indicate that keratin genes that are normally expressed in vivo in epidermis may be expressed in malignant epidermal cells under conditions that do not permit expression of these genes in nonmalignant primary epidermal cells.