Upper extremity weakness: A novel risk factor for non-cardiovascular mortality among community-dwelling older adults.

BACKGROUND: Aging-associated upper extremity weakness has been shown to be associated with adverse health outcomes in older adults, but less is known about the association between impaired upper extremity function and cause-specific mortalities. METHODS: Among the 5512 prospective community-based longitudinal Cardiovascular Health Study participants, 1438 had difficulty with one of the three upper extremity functions of lifting, reaching, or gripping. We assembled a propensity score-matched cohort in which 1126 pairs of participants with and without difficulty with upper extremity function, balanced on 62 baseline characteristics including geriatric and functional variables such as physical and cognitive function. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortalities associated with upper extremity weakness were estimated in the matched cohort. RESULTS: Matched participants had a mean age of 73.1 years, 72.5% were women, and 17.0% African American. During 23 years of follow-up, all-cause mortality occurred in 83.7% (942/1126) and 81.2% (914/1126) of participants with and without upper extremity weakness, respectively (HR, 1.11; 95% CI, 1.01-1.22; p = 0.023). Upper extremity weakness was associated with a higher risk of non-cardiovascular mortality, occurring in 595 (52.8%) and 553 (49.1%) of participants, respectively (HR, 1.17; 95% CI, 1.04-1.31; p = 0.010), but had no association with cardiovascular mortality (30.8% vs 32.1% in those with and without upper extremity weakness, respectively; HR, 1.03; 95% CI, 0.89-1.19; p = 0.70). CONCLUSION: Among community-dwelling older adults, upper extremity weakness had a weak, albeit independent, significant association with all-cause mortality, which was primarily driven by a higher risk of non-cardiovascular mortality. Future studies need to replicate these findings and understand the underlying reasons for the observed associations.

Direct Integration of Perovskite Solar Cells with Carbon Fiber Substrates.

Integrating photovoltaic devices onto the surface of carbon-fiber-reinforced polymer substrates should create materials with high mechanical strength that are also able to generate electrical power. Such devices are anticipated to find ready applications as structural, energy-harvesting systems in both the automotive and aeronautical sectors. Here, the fabrication of triple-cation perovskite n-i-p solar cells onto the surface of planarized carbon-fiber-reinforced polymer substrates is demonstrated, with devices utilizing a transparent top ITO contact. These devices also contain a "wrinkled" SiO2 interlayer placed between the device and substrate that alleviates thermally induced cracking of the bottom ITO layer. Devices are found to have a maximum stabilized power conversion efficiency of 14.5% and a specific power (power per weight) of 21.4 W g-1 (without encapsulation), making them highly suitable for mobile power applications.

Effects of New Zealand Blackcurrant Extract on Sequential Performance Testing in Male Rugby Union Players.

Previous studies on performance effects by New Zealand blackcurrant (NZBC) extract used mainly a single exercise task. We examined the effects of NZBC extract in a battery of rugby union-specific tests including speed, agility and strength testing. University male rugby union players (n = 13, age: 21 ± 2 years, height: 182 ± 6 cm, body mass: 87 ± 13 kg) completed two full familiarisations and two experimental visits in an indoor facility. The study had a double blind, placebo-controlled, randomised, crossover design. For the experimental visits, participants consumed NZBC extract (210 mg/day of anthocyanins for 7 days) or placebo with a 7-day wash-out. Testing order was the running-based anaerobic sprint test, the Illinois agility test, seated medicine ball (3 kg) throw, and handgrip strength. With NZBC extract, there may have been an effect for average sprint time to be faster by 1.7% (placebo: 5.947 ± 0.538 s, NZBC extract: 5.846 ± 0.571 s, d = -0.18 (trivial), p = 0.06). However, with NZBC extract there may have been reduced slowing of sprint 2 (d = -0.59 (moderate), p = 0.06) and reduced slowing for sprint 6 (d = -0.56 (moderate), p = 0.03). In the Illinois agility test, there may have also been an effect for the mean time to be faster by 1.6% (placebo: 18.46 ± 1.44 s, NZBC extract: 18.15 ± 1.22 s, d = -0.24 (small), p = 0.07). The correlation between the %change in average sprint time and %change in mean agility time was not significant (Pearson R2 = 0.0698, p = 0.383). There were no differences for the seated medicine ball throw distance (p = 0.106) and handgrip strength (p = 0.709). Intake of NZBC extract in rugby union players seems to improve tasks that require maximal speed and agility but not muscle strength. NZBC blackcurrant extract may be able to enhance exercise performance in team sports that require repeated movements with high intensity and horizontal change of body position without affecting muscle strength.

Proprioceptive contribution to oculomotor control in humans.

Stretch receptors in the extraocular muscles (EOMs) inform the central nervous system about the rotation of one's own eyes in the orbits. Whereas fine control of the skeletal muscles hinges critically on proprioceptive feedback, the role of proprioception in oculomotor control remains unclear. Human behavioural studies provide evidence for EOM proprioception in oculomotor control, however, behavioural and electrophysiological studies in the macaque do not. Unlike macaques, humans possess numerous muscle spindles in their EOMs. To find out whether the human oculomotor nuclei respond to proprioceptive feedback we used functional magnetic resonance imaging (fMRI). With their eyes closed, participants placed their right index finger on the eyelid at the outer corner of the right eye. When prompted by a sound, they pushed the eyeball gently and briefly towards the nose. Control conditions separated out motor and tactile task components. The stretch of the right lateral rectus muscle was associated with activation of the left oculomotor nucleus and subthreshold activation of the left abducens nucleus. Because these nuclei control the horizontal movements of the left eye, we hypothesized that proprioceptive stimulation of the right EOM triggered left eye movement. To test this, we followed up with an eye-tracking experiment in complete darkness using the same behavioural task as in the fMRI study. The left eye moved actively in the direction of the passive displacement of the right eye, albeit with a smaller amplitude. Eye tracking corroborated neuroimaging findings to suggest a proprioceptive contribution to ocular alignment.

Nonplanar Spray-Coated Perovskite Solar Cells.

Spray coating is an industrially mature technique used to deposit thin films that combines high throughput with the ability to coat nonplanar surfaces. Here, we explore the use of ultrasonic spray coating to fabricate perovskite solar cells (PSCs) over rigid, nonplanar surfaces without problems caused by solution dewetting and subsequent "run-off". Encouragingly, we find that PSCs can be spray-coated using our processes onto glass substrates held at angles of inclination up to 45° away from the horizontal, with such devices having comparable power conversion efficiencies (up to 18.3%) to those spray-cast onto horizontal substrates. Having established that our process can be used to create PSCs on surfaces that are not horizontal, we fabricate devices over a convex glass substrate, with devices having a maximum power conversion efficiency of 12.5%. To our best knowledge, this study represents the first demonstration of a rigid, curved perovskite solar cell. The integration of perovskite photovoltaics onto curved surfaces will likely find direct applications in the aerospace and automotive sectors.

Oculomotor Synkinesis (Aberrant Reinnervation of the Third Cranial Nerve) Associated with Atypical Tolosa-Hunt Syndrome.

A 70-year-old woman with systemic lupus erythematosus developed a painful pupil-involving right third nerve palsy, ipsilateral fourth nerve palsy, and periorbital paraesthesia. Magnetic resonance imaging demonstrated enhancement and thickening of the right third nerve, and she was diagnosed with presumed Tolosa-Hunt syndrome. Repeated imaging seven months later showed resolution of the enhancing thickened oculomotor nerve, but the patient developed signs of oculomotor synkinesis. This presentation demonstrates a rare case of oculomotor synkinesis secondary to inflammation.

Catalytically Active Single-Chain Polymeric Nanoparticles: Exploring Their Functions in Complex Biological Media.

Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media. The ability of SCPNs to act as catalysts in biological media was first assessed by investigating their potential for reactive oxygen species generation. With porphyrins covalently attached to the SCPNs, singlet oxygen was generated upon irradiation with light, inducing spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based SCPNs were prepared and these catalysts were screened in vitro and studied in cellular environments for the carbamate cleavage reaction of rhodamine-based substrates. This is a model reaction for the uncaging of bioactive compounds such as cytotoxic drugs for catalysis-based cancer therapy. We observed that the rate of the deprotection depends on both the organometallic catalysts and the nature of the protective group. The rate reduces from in vitro to the biological environment, indicating a strong influence of biomolecules on catalyst performance. The Cu(I)-based SCPNs in combination with the dimethylpropargyloxycarbonyl protective group showed the best performances both in vitro and in biological environment, making this group promising in biomedical applications.

Performance variation due to stiffness in a tuna-inspired flexible foil model.

Tuna are fast, economical swimmers in part due to their stiff, high aspect ratio caudal fins and streamlined bodies. Previous studies using passive caudal fin models have suggested that while high aspect ratio tail shapes such as a tuna's generally perform well, tail performance cannot be determined from shape alone. In this study, we analyzed the swimming performance of tuna-tail-shaped hydrofoils of a wide range of stiffnesses, heave amplitudes, and frequencies to determine how stiffness and kinematics affect multiple swimming performance parameters for a single foil shape. We then compared the foil models' kinematics with published data from a live swimming tuna to determine how well the hydrofoil models could mimic fish kinematics. Foil kinematics over a wide range of motion programs generally showed a minimum lateral displacement at the narrowest part of the foil, and, immediately anterior to that, a local area of large lateral body displacement. These two kinematic patterns may enhance thrust in foils of intermediate stiffness. Stiffness and kinematics exhibited subtle interacting effects on hydrodynamic efficiency, with no one stiffness maximizing both thrust and efficiency. Foils of intermediate stiffnesses typically had the greatest coefficients of thrust at the highest heave amplitudes and frequencies. The comparison of foil kinematics with tuna kinematics showed that tuna motion is better approximated by a zero angle of attack foil motion program than by programs that do not incorporate pitch. These results indicate that open questions in biomechanics may be well served by foil models, given appropriate choice of model characteristics and control programs. Accurate replication of biological movements will require refinement of motion control programs and physical models, including the creation of models of variable stiffness.

Nutritional Optic Neuropathy Caused by Copper Deficiency After Bariatric Surgery.

A 47-year-old woman developed severe bilateral visual loss 4 years after a Roux-en-Y gastric bypass and 24 years after vertical banded gastroplasty. Her serum copper level was 35 µg/dL (normal, 80-155 µg/dL). She was prescribed elemental copper tablets. Because her methylmalonic acid was slightly elevated, she received vitamin B12 injections as well. Five weeks later, she reported that her vision had improved and, at 10 months, her vision had recovered from 20/400 bilaterally to 20/25 in each eye. This case highlights the importance of checking copper levels in addition to the "more routine" vitamin levels, such as B1, B6, B12, E, and serum folate in patients with suspected nutritional optic neuropathy after bariatric surgery, particularly if it involved a bypass procedure.

PCNA appears in two populations of slow and fast diffusion with a constant ratio throughout S-phase in replicating mammalian cells.

DNA replication is a fundamental cellular process that precedes cell division. Proliferating cell nuclear antigen (PCNA) is a central scaffold protein that orchestrates DNA replication by recruiting many factors essential for the replication machinery. We studied the mobility of PCNA in live mammalian cells using single-particle tracking in combination with photoactivated-localization microscopy (sptPALM) and found two populations. The first population which is only present in cells with active DNA replication, showed slow diffusion and was found to be located in replication foci. The second population showed fast diffusion, and represents the nucleoplasmic pool of unbound PCNA not involved in DNA replication. The ratio of these two populations remained constant throughout different stages of S-phase. A fraction of molecules in both populations showed spatially constrained mobility. We determined an exploration radius of ~100 nm for 13% of the slow-diffusing PCNA molecules, and of ~600 nm for 46% of the fast-diffusing PCNA molecules.

Surface water retardation around single-chain polymeric nanoparticles: critical for catalytic function?

A library of water-soluble dynamic single-chain polymeric nanoparticles (SCPN) was prepared using a controlled radical polymerisation technique followed by the introduction of functional groups, including probes at targeted positions. The combined tools of electron paramagnetic resonance (EPR) and Overhauser dynamic nuclear polarization (ODNP) reveal that these SCPNs have structural and surface hydration properties resembling that of enzymes.

Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review.

OBJECTIVE: To establish the number of outbreaks of extended spectrum beta-lactamase (ESBL) producing organisms in neonatal intensive care units (NICUs), to determine causes, mortality rates, proportions of infants colonised and infected and the interventions that terminated outbreaks. METHODS: A systematic review of the literature in English, Spanish and French was undertaken with searches in four databases. The review conformed to the PRISMA guidelines, and the data extraction was modelled on the ORION criteria for studies of nosocomial infection. RESULTS: 75 studies fulfilled the inclusion criteria. There were 1185 cases of colonisation, 860 infections and 139 deaths. The median outbreak duration was 6.2 months (IQR 2.0-7.5 months). Klebsiella pneumoniae was the most frequently implicated pathogen. Understaffing was the most frequent risk factor for outbreaks. The most commonly identified source was admission of an ESBL-colonised infant with subsequent horizontal dissemination. The main interventions described were improved infection-control procedures and screening of staff and the environment. 26 studies were included in the quantitative analysis. Random effects meta-analysis indicated high mortality rates in infants who developed infection (31%, 95% CI 20% to 43%). CONCLUSION: ESBL outbreaks in NICUs are associated with significant mortality and prolonged disruption. Understaffing is a major risk factor, but is infrequently addressed by interventions. Poor infection-control procedures are frequently implicated as contributing to ESBL spread. Better reporting of outbreaks may help clarify the role for routine ESBL screening in NICUs.

Hydrodynamic function of biomimetic shark skin: effect of denticle pattern and spacing.

The structure of shark skin has been the subject of numerous studies and recently biomimetic shark skin has been fabricated with rigid denticles (scales) on a flexible substrate. This artificial skin can bend and generate thrust when attached to a mechanical controller. The ability to control the manufacture of biomimetic shark skin facilitates manipulation of surface parameters and understanding the effects of changing denticle patterns on locomotion. In this paper we investigate the effect of changing the spacing and arrangement of denticles on the surface of biomimetic shark skin on both static and dynamic locomotor performance. We designed 3D-printed flexible membranes with different denticle patterns and spacings: (1) staggered-overlapped, (2) linear-overlapped, and (3) linear-non-overlapped, and compared these to a 3D-printed smooth-surfaced control. These 3D printed shark skin models were then tested in a flow tank with a mechanical flapping device that allowed us to either hold the models in a stationary position or move them dynamically. We swam the membranes at a frequency of 1 Hz with different heave amplitudes (from ±1 cm to ±3 cm) while measuring forces, torques, self-propelled swimming speed, and cost of transport (COT). Static tests revealed drag reduction of denticle patterns compared to a smooth control at low speeds, but increased drag at speeds above 25 cm s(-1). However, during dynamic (swimming) tests, the staggered-overlapped pattern produced the fastest swimming speeds with no significant increase in the COT at lower heave values. For instance, at a heave frequency of 1 Hz and amplitude of ±1 cm, swimming speed of the staggered-overlapped pattern increased by 25.2% over the smooth control. At higher heave amplitudes, significantly faster self-propelled swimming speeds were achieved by the staggered-overlapped pattern, but with higher COT. Only the staggered-overlapped pattern provides a significant swimming performance advantage over the smooth control and the other two denticle patterns. Quantitative hydrodynamic comparisons among skin models where control over manufacture allows alteration of design parameters provides a useful experimental tool for future work on the considerable natural diversity of shark skin denticles both among species and on different body locations.

Effects of non-uniform stiffness on the swimming performance of a passively-flexing, fish-like foil model.

Simple mechanical models emulating fish have been used recently to enable targeted study of individual factors contributing to swimming locomotion without the confounding complexity of the whole fish body. Yet, unlike these uniform models, the fish body is notable for its non-uniform material properties. In particular, flexural stiffness decreases along the fish's anterior-posterior axis. To identify the role of non-uniform bending stiffness during fish-like propulsion, we studied four foil model configurations made by adhering layers of plastic sheets to produce discrete regions of high (5.5 × 10(-5) Nm(2)) and low (1.9 × 10(-5) Nm(2)) flexural stiffness of biologically-relevant magnitudes. This resulted in two uniform control foils and two foils with anterior regions of high stiffness and posterior regions of low stiffness. With a mechanical flapping foil controller, we measured forces and torques in three directions and quantified swimming performance under both heaving (no pitch) and constant 0° angle of attack programs. Foils self-propelled at Reynolds number 21 000-115 000 and Strouhal number ∼0.20-0.25, values characteristic of fish locomotion. Although previous models have emphasized uniform distributions and heaving motions, the combination of non-uniform stiffness distributions and 0° angle of attack pitching program was better able to reproduce the kinematics of freely-swimming fish. This combination was likewise crucial in maximizing swimming performance and resulted in high self-propelled speeds at low costs of transport and large thrust coefficients at relatively high efficiency. Because these metrics were not all maximized together, selection of the 'best' stiffness distribution will depend on actuation constraints and performance goals. These improved models enable more detailed, accurate analyses of fish-like swimming.

Cleaning the Click: A Simple Electrochemical Avenue for Copper Removal from Strongly Coordinating Macromolecules.

We introduce a novel electrochemical method for the purification of complex water-soluble functional polymers contaminated with copper salts originating from copper-catalyzed azide/alkyne ligation chemistry, for which no standard purification protocol is suitable. A triethylene glycol methyl ether methacrylate (TEGMA) star polymer with 2-ureido-4H-pyrimidone (UPy) end groups was prepared via an activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) and copper-catalyzed azide/alkyne cycloaddition (CuAAc) and selected as a model system for electrolysis of an aqueous polymer solution. We systematically investigate the influence of sample concentration, voltage, and time of electrolysis on the quality of the purification. Atom emission spectroscopy (AES) reveals almost quantitative removal of copper, and size exclusion chromatography (SEC) as well as proton nuclear magnetic resonance spectroscopy (1H NMR) ensure the full integrity of the polymer under all selected conditions.

Semi-automated hydrophobic interaction chromatography column scouting used in the two-step purification of recombinant green fluorescent protein.

BACKGROUND: Hydrophobic interaction chromatography (HIC) most commonly requires experimental determination (i.e., scouting) in order to select an optimal chromatographic medium for purifying a given target protein. Neither a two-step purification of untagged green fluorescent protein (GFP) from crude bacterial lysate using sequential HIC and size exclusion chromatography (SEC), nor HIC column scouting elution profiles of GFP, have been previously reported. METHODS AND RESULTS: Bacterial lysate expressing recombinant GFP was sequentially adsorbed to commercially available HIC columns containing butyl, octyl, and phenyl-based HIC ligands coupled to matrices of varying bead size. The lysate was fractionated using a linear ammonium phosphate salt gradient at constant pH. Collected HIC eluate fractions containing retained GFP were then pooled and further purified using high-resolution preparative SEC. Significant differences in presumptive GFP elution profiles were observed using in-line absorption spectrophotometry (A395) and post-run fluorimetry. SDS-PAGE and western blot demonstrated that fluorometric detection was the more accurate indicator of GFP elution in both HIC and SEC purification steps. Comparison of composite HIC column scouting data indicated that a phenyl ligand coupled to a 34 µm matrix produced the highest degree of target protein capture and separation. CONCLUSIONS: Conducting two-step protein purification using the preferred HIC medium followed by SEC resulted in a final, concentrated product with >98% protein purity. In-line absorbance spectrophotometry was not as precise of an indicator of GFP elution as post-run fluorimetry. These findings demonstrate the importance of utilizing a combination of detection methods when evaluating purification strategies. GFP is a well-characterized model protein, used heavily in educational settings and by researchers with limited protein purification experience, and the data and strategies presented here may aid in development other of HIC-compatible protein purification schemes.

A modular approach to introduce function into single-chain polymeric nanoparticles.

Here, a modular approach is reported to introduce a specific function into single-chain polymeric nanoparticles (SCPNs). Hereto, an amphiphilic polymer with pendant benzene-1,3,5-tricarboxamide (BTA) units is mixed with a "free" BTA that contains a functional group, either a fluorescent naphthalimide or a catalytically active l-proline. Taking advantage of hydrophobic interactions and self-recognition properties of the BTA units, the "free" BTAs are captured into the interior of the SCPN in water as evidenced by fluorescence studies. To illustrate that function can be readily introduced using a modular approach, l-proline-based BTAs are incorporated to procure a catalytically active SCPN in water. The aldol reaction between p-nitrobenzaldehyde and cyclohexanone shows good conversions at low catalyst loadings and substrate concentrations, and high stereoselectivities are obtained (de = 91% and ee = 98%).

Undulatory locomotion of flexible foils as biomimetic models for understanding fish propulsion.

An undulatory pattern of body bending in which waves pass along the body from head to tail is a major mechanism of creating thrust in many fish species during steady locomotion. Analyses of live fish swimming have provided the foundation of our current understanding of undulatory locomotion, but our inability to experimentally manipulate key variables such as body length, flexural stiffness and tailbeat frequency in freely swimming fish has limited our ability to investigate a number of important features of undulatory propulsion. In this paper we use a mechanical flapping apparatus to create an undulatory wave in swimming flexible foils driven with a heave motion at their leading edge, and compare this motion with body bending patterns of bluegill sunfish (Lepomis macrochirus) and clown knifefish (Notopterus chitala). We found similar swimming speeds, Reynolds and Strouhal numbers, and patterns of curvature and shape between these fish and foils, suggesting that flexible foils provide a useful model for understanding fish undulatory locomotion. We swam foils with different lengths, stiffnesses and heave frequencies while measuring forces, torques and hydrodynamics. From measured forces and torques we calculated thrust and power coefficients, work and cost of transport for each foil. We found that increasing frequency and stiffness produced faster swimming speeds and more thrust. Increasing length had minimal impact on swimming speed, but had a large impact on Strouhal number, thrust coefficient and cost of transport. Foils that were both stiff and long had the lowest cost of transport (in mJ m(-1) g(-1)) at low cycle frequencies, and the ability to reach the highest speed at high cycle frequencies.

Consequences of block sequence on the orthogonal folding of triblock copolymers.

ABA- and BAB-type triblock copolymers possessing pendant, self-assembling motifs in the A and B blocks were synthesized, with 2-ureidopyrimidinone (UPy) and benzene-1,3,5-tricarboxamide (BTA) for the A and B block, respectively. They were investigated to assess if and how the polymer's microstructure influences the self-assembly behavior of the supramolecular motifs and, as a result, the single-chain folding process. BAB-type triblock copolymers were synthesized via atom transfer radical polymerization (ATRP) with molecular weights ranging from 30 to 120 kg mol⁻¹; the BTA and UPy motifs were attached using a post-functionalization approach. The ABA-type triblock copolymers were available from previous work. In highly dilute solutions, both types of triblock copolymers fold into single-chain polymeric nanoparticles (SCPNs) via thermally induced BTA self-assembly and photo-triggered UPy dimerization. Chain collapse induced by intramolecular UPy dimerization was evaluated using size-exclusion chromatography (SEC). The BTA self-assembly was monitored by circular dichroism (CD) spectroscopy. The microstructures of SCPNs were visualized by atomic force microscopy (AFM). SEC analysis indicated a more loose packing for the BAB-type folded nanoparticles than for the ABA-type ones, which implies that topological differences in the polymer architecture do affect the folding behavior, although only slightly. The facile synthetic protocol developed here provides topologically different triblock architectures and opens up the area for single-chain folding technology that is applicable in artificial enzymatic systems with compartmentalized domains.