Sex disparities of human neuromuscular decline in older humans.

Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex-specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low- to mid-level contractions (P < 0.05) without sex × level interactions. Females had smaller cross-sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex-specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex-based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. KEY POINTS: Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty. In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age-matched males. Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females. These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health-sex paradox.

Mid-Infrared, Optically Active Black Phosphorus Thin Films on Centimeter Scale.

Black phosphorus (BP) is a narrow bandgap (∼0.3 eV) semiconductor with a great potential for optoelectronic devices in the mid-infrared wavelength. However, it has been challenging to achieve a high-quality scalable BP thin film. Here we present the successful synthesis of optically active BP films on a centimeter scale. We utilize the pulsed laser deposition of amorphous red phosphorus, another allotrope of phosphorus, followed by a high-pressure treatment at ∼8 GPa to induce a phase conversion into BP crystals. The crystalline quality was improved through thermal annealing, resulting in the observation of photoluminescence emission at mid-infrared wavelengths. We demonstrate high-pressure conversion on a centimeter scale with a continuous film with a thickness of ∼18 nm using a flat-belt-type high-pressure apparatus. This synthesis procedure presents a promising route to obtain optical-quality BP films, enabling the exploration of integrated optoelectronic device applications such as light-emitting devices and mid-infrared cameras on a chip scale.

Post-operative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: a split body randomised control trial.

INTRODUCTION: Significant losses of muscle mass and function occur after major abdominal surgery. Neuromuscular electrical stimulation (NMES) has been shown to reduce muscle atrophy in some patient groups, but evidence in post-operative patients is limited. This study assesses the efficacy of NMES for attenuating muscle atrophy and functional declines following major abdominal surgery in older adults. METHODS: Fifteen patients undergoing open colorectal resection completed a split body randomised control trial. Patients' lower limbs were randomised to control (CON) or NMES (STIM). The STIM limb underwent 15 minutes of quadriceps NMES twice daily on post-operative days (PODs) 1-4. Ultrasound measurements of Vastus Lateralis cross-sectional area (CSA) and muscle thickness (MT) were made preoperatively and on POD 5, as was dynamometry to determine knee extensor strength (KES). Change in CSA was the primary outcome. All outcomes were statistically analysed using linear mixed models. RESULTS: NMES significantly reduced the loss of CSA (-2.52 versus -9.16%, P < 0.001), MT (-2.76 versus -8.145, P = 0.001) and KES (-10.35 versus -19.69%, P = 0.03) compared to CON. No adverse events occurred, and patients reported that NMES caused minimal or no discomfort and felt that ~90-minutes of NMES daily would be tolerable. DISCUSSION: NMES reduces losses of muscle mass and function following major abdominal surgery, and as such, may be the promising tool for post-operative recovery. This is important in preventing long-term post-operative dependency, especially in the increasingly frail older patients undergoing major abdominal surgery. Further studies should establish the efficacy of bilateral NMES for improving patient-centred outcomes.

The role of resistance exercise training for improving cardiorespiratory fitness in healthy older adults: a systematic review and meta-analysis.

BACKGROUND: Declines in cardiorespiratory fitness (CRF) and muscle mass are both associated with advancing age and each of these declines is associated with worse health outcomes. Resistance exercise training (RET) has previously been shown to improve muscle mass and function in the older population. If RET is also able to improve CRF, as it has been shown to do in younger populations, it has the potential to improve multiple health outcomes in the expanding older population. METHODS: This systematic review aimed to identify the role of RET for improving CRF in healthy older adults. A search across CINAHL, MEDLINE, EMBASE and EMCARE databases was conducted with meta-analysis performed on eligible papers to identify improvements in established CRF parameters (VO2 peak, aerobic threshold (AT), 6-minute walking distance test (6MWT) following RET intervention. Main eligibility criteria included older adults (aged over 60), healthy cohorts (disease-specific cohorts were excluded) and RET intervention. RESULTS: Thirty-seven eligible studies were identified. Meta-analysis revealed a significant improvement in VO2 peak (MD 1.89 ml/kg/min; 95% confidence interval (CI) 1.21-2.57 ml/kg/min), AT (MD 1.27 ml/kg/min; 95% CI 0.44-2.09 ml/kg/min) and 6MWT (MD 30.89; 95% CI 26.7-35.08) in RET interventions less than 24 weeks. There was no difference in VO2 peak or 6MWT in interventions longer than 24 weeks. DISCUSSION: This systematic review adds to a growing body of evidence supporting the implementation of RET in the older population for improving whole-body health, particularly in time-limited timeframes.

Does decentralisation of surgical management improve outcomes for paediatric testicular torsion?

INTRODUCTION: In testicular torsion (TT), delayed emergency scrotal exploration (ESE) increases the risk of orchidectomy. Transfer of a patient with suspected TT from a district general hospital (DGH) to a paediatric surgical centre (PSC) delays ESE and potentially puts them at increased risk of testicular loss. Prior to 1st January 2017, all boys under aged <16 years presenting to a DGH within the East Midlands Clinical Network (EMCN) would be referred to the PSC. From this date, it was agreed within the EMCN that boys aged ≥5 years with suspected TT presenting to a network DGH would be managed locally, barring exceptional circumstances. Boys aged <5 years would be referred to the PSC for management. AIM: This study aimed to assess the impact of decentralisation of ESE for suspected TT on orchidectomy rates in the EMCN. METHODS: All patients who underwent ESE under the care of paediatric surgery in the PSC, and all patients <16 years old who underwent ESE in 4 EMCN DGHs between January 2017 and December 2019 were identified. Neonatal cases and inpatient referrals were excluded. Comparison was made with published data on ESE performed in the PSC over the 9 years 2008-2016 prior to decentralisation. RESULTS: In the 9 years prior to decentralisation, there were 110 cases of TT in the PSC. In the subsequent 3 years, there were 40 in the PSC and 37 in the DGHs. The orchidectomy rate of boys with TT presenting to DGHs and undergoing exploration locally (16%, 6/37) contrasts with the rate in those transferred from DGHs to the PSC for exploration (58%, 15/26). The difference is highly significant (p = 0.00059, RR 0.28 [95% CI 0.13-0.63]) and indicates that in the EMCN, avoiding hospital transfer and performing ESE at the presenting DGH reduces the risk of orchidectomy by 72%. CONCLUSION: Decentralisation of the provision of ESE in boys with TT has resulted in a significantly lower orchidectomy rate in boys undergoing ESE in the presenting hospital than when transferred to the PSC. This study reinforces existing literature that demonstrates the effect of delayed ESE on orchidectomy rate, and supports the recommendations of national guidelines in the UK that transfer of boys to a PSC for ESE should only occur in exceptional circumstances.

Band Engineering of Large-Twist-Angle Graphene/h-BN Moiré Superlattices with Pressure.

Graphene interfacing hexagonal boron nitride (h-BN) forms lateral moiré superlattices that host a wide range of new physical effects such as the creation of secondary Dirac points and band gap opening. A delicate control of the twist angle between the two layers is required as the effects weaken or disappear at large twist angles. In this Letter, we show that these effects can be reinstated in large-angle (∼1.8°) graphene/h-BN moiré superlattices under high pressures. A graphene/h-BN moiré superlattice microdevice is fabricated directly on the diamond culet of a diamond anvil cell, where pressure up to 8.3 GPa is applied. The band gap at the primary Dirac point is opened by 40-60 meV, and fingerprints of the second Dirac band gap are also observed in the valence band. Theoretical calculations confirm the band engineering with pressure in large-angle graphene/h-BN bilayers.

Non-Occlusive Retinal Vascular Inflammation and Role of Red Blood Cell Deformability in Birdshot Chorioretinopathy.

Purpose: To investigate differences in red blood cell (RBC) deformability between birdshot chorioretinopathy (BCR) subjects and matched controls, and to postulate its relationship with lack of vascular occlusion in BCR. Methods: In a single center, prospective, non-randomized mechanistic study, blood samples were collected from eight healthy controls and nine BCR patients, and subjected to biochemical and hematological tests, as well as RBC indices assessment using dual-beam optical tweezers. Results: The mean age of the controls was 52.37 ± 10.70 years and BCR patients was 53.44 ± 12.39 years. Initial cell size (Io) for the controls was 8.48 ± 0.25 µm and 8.87 ± 0.31 µm for BCR RBCs (p = 0.014). The deformability index (DI) for the controls was 0.066 ± 0.02 and that for BCR RBCs was 0.063 ± 0.03 (p = 0.441). Conclusion: There was no statistically significant difference in DI between RBCs from BCR and healthy controls. This may explain the rare occurrence of retinal vascular occlusion despite the underlying vasculitic pathophysiology of BCR.

A microscopic Kapitza pendulum.

Pyotr Kapitza studied in 1951 the unusual equilibrium features of a rigid pendulum when its point of suspension is under a high-frequency vertical vibration. A sufficiently fast vibration makes the top position stable, putting the pendulum in an inverted orientation that seemingly defies gravity. Kapitza's analytical method, based on an asymptotic separation of fast and slow variables yielding a renormalized potential, has found application in many diverse areas. Here we study Kapitza's pendulum going beyond its typical idealizations, by explicitly considering its finite stiffness and the dissipative interaction with the surrounding medium, and using similar theoretical methods as Kapitza. The pendulum is realized at the micrometre scale using a colloidal particle suspended in water and trapped by optical tweezers. Though the strong dissipation present at this scale prevents the inverted pendulum regime, new ones appear in which the equilibrium positions are displaced to the side, and with transitions between them determined either by the driving frequency or the friction coefficient. These new regimes could be exploited in applications aimed at particle separation at small scales.

Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique.

A pilot cross sectional study was conducted to investigate the role of red blood cells (RBC) deformability in type 2 diabetes mellitus (T2DM) without and with diabetic retinopathy (DR) using a dual optical tweezers stretching technique. A dual optical tweezers was made by splitting and recombining a single Nd:YAG laser beam. RBCs were trapped directly (i.e., without microbead handles) in the dual optical tweezers where they were observed to adopt a "side-on" orientation. RBC initial and final lengths after stretching were measured by digital video microscopy, and a Deformability index (DI) calculated. Blood from 8 healthy controls, 5 T2DM and 7 DR patients with respective mean age of 52.4 yrs, 51.6 yrs and 52 yrs was analysed. Initial average length of RBCs for control group was 8.45 ± 0.25 µm, 8.68 ± 0.49 µm for DM RBCs and 8.82 ± 0.32 µm for DR RBCs (p < 0.001). The DI for control group was 0.0698 ± 0.0224, and that for DM RBCs was 0.0645 ± 0.03 and 0.0635 ± 0.028 (p < 0.001) for DR group. DI was inversely related to basal length of RBCs (p = .02). DI of RBC from DM and DR patients was significantly lower in comparison with normal healthy controls. A dual optical tweezers method can hence be reliably used to assess RBC deformability.

Size evolution of highly amphiphilic macromolecular solution assemblies via a distinct bimodal pathway.

The solution self-assembly of macromolecular amphiphiles offers an efficient, bottom-up strategy for producing well-defined nanocarriers, with applications ranging from drug delivery to nanoreactors. Typically, the generation of uniform nanocarrier architectures is controlled by processing methods that rely on cosolvent mixtures. These preparation strategies hinge on the assumption that macromolecular solution nanostructures are kinetically stable following transfer from an organic/aqueous cosolvent into aqueous solution. Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent. The unexpected micelle growth evolves through a distinct bimodal distribution separated by multiple fusion events and critically depends on solution agitation. Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule and protein systems. Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure.

A simple approach to characterizing block copolymer assemblies: graphene oxide supports for high contrast multi-technique imaging.

Block copolymers are well-known to self-assemble into a range of 3-dimensional morphologies. However, due to their nanoscale dimensions, resolving their exact structure can be a challenge. Transmission electron microscopy (TEM) is a powerful technique for achieving this, but for polymeric assemblies chemical fixing/staining techniques are usually required to increase image contrast and protect specimens from electron beam damage. Graphene oxide (GO) is a robust, water-dispersable, and nearly electron transparent membrane: an ideal support for TEM. We show that when using GO supports no stains are required to acquire high contrast TEM images and that the specimens remain stable under the electron beam for long periods, allowing sample analysis by a range of electron microscopy techniques. GO supports are also used for further characterization of assemblies by atomic force microscopy. The simplicity of sample preparation and analysis, as well as the potential for significantly increased contrast background, make GO supports an attractive alternative for the analysis of block copolymer assemblies.

L-Proline Functionalized Polymers Prepared by RAFT Polymerization and Their Assemblies as Supported Organocatalysts.

We have prepared a range of well-defined copolymers of styrene and L-proline functionalized styrene (5-11 kDa) using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques and explored their use in supported catalysis. Upon deprotection of the L-proline functionalities, the solution self-assembly of these copolymers was investigated in mixed solvent systems. The resulting assemblies were characterized by dynamic light scattering, transmission electron microscopy (on graphene oxide substrates, along with cryo-TEM and tomography), and scanning electron microscopy. The application of these functional assemblies as supported catalysts for the aldol condensation reaction was explored using cyclohexanone and 4-nitrobenzaldehyde. The rate and selectivity of solution catalysis in our self-assembled system were comparable to those of L-proline, and a significant advantage of our system was that the polymer support could be utilized at lower catalyst loadings with comparable activity and also could be recycled a number of times while maintaining activity and selectivity.

Synthesis and Characterization of Amphiphilic Cyclic Diblock Copolypeptoids from N-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Substituted N-carboxyanhydride.

N-Heterocyclic carbene (NHC)-mediated ring-opening polymerization of N-decylN-carboxylanhydride monomer (De-NCA) has been shown to occur in a controlled manner, yielding cyclic poly(N-decyl-glycine)s (c-PNDGs) with polymer molecular weights (MW) between 4.8 and 31 kg·mol(-1) and narrow molecular weight distributions (PDI < 1.15). The reaction exhibits pseudo-first order kinetics with respect to monomer concentration. The polymer MW increases linearly with conversion, consistent with a living polymerization. ESI MS and SEC analysesconfirm the cyclic architectures of the forming polymers. DSC and WAXS studies reveal that the c-PNDG homopolymers are highly crystalline with two prominent first order transitions at 72-79°C (T(m,1)) and 166-177°C (T(m,2)), which have been attributed to the side chain and main chain melting respectively. A series of amphiphilic cyclic diblock copolypeptoids [i.e.,poly(N-methyl-glycine)-b-poly(N-decyl-glycine) (c-PNMG-b-PNDG)] with variable molecular weight and composition was synthesized by sequential NHC-mediated polymerization of the corresponding N-methyl N-carboxyanhydride (Me-NCA) and De-NCA monomers. (1)H NMR analysis reveals that adjusting the initial monomer to NHC molar ratio can readily control the block copolymer chain length and composition. Time-lapsed light scattering and cryogenic transmission electron microscopy (cryo-TEM) analysis of c-PNDG-b-PNMG samples revealed that the amphiphilic cyclic block copolypeptoids self-assemble into spherical micelles that reorganize into micron-long cylindrical micelles with uniform diameter in room temperature methanol over the course of several days. An identical morphological transition has also been noted for the linear analogs, which occurs more rapidly than for the cyclic copolypeptoids. We tentatively attribute this difference to the different crystallization kinetics of the solvophobic block (i.e., PNDG) in the cyclic and linear block copolypeptoids.

Structural changes in block copolymer micelles induced by cosolvent mixtures.

We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (low interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles.

Homopolymer induced aggregation of poly(ethylene oxide)n-b-poly(butylene oxide)m polymersomes.

We have studied the addition of poly(ethylene oxide) homopolymer (PEO) to a range of polymersome dispersions composed of amphiphilic di- and triblock copolymers. A number of E(n)B(m) E(n)B(m)E(n) and B(m)E(n)B(m) (E = poly(ethylene oxide) B = poly(butylene oxide)) block copolymers of varying molecular weights that spontaneously form polymersomes in water were investigated. This resulted in the aggregation of the dispersed polymersomes by two mechanisms, PEO adsorption or depletion interactions, and is shown to be dependent on PEO concentration. The aggregation kinetics and the resultant structures were analyzed by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM). There is a critical relationship between the polymersome corona thickness t and the PEO radius of gyration R(g), where R(g) must equal t to induce aggregation. This phenomenon has been reported with small self-assembling surfactants such as sodium dodecyl sulfate, but here we show an insight into how this transposes into much larger block copolymer systems which show great promise as biomimetic delivery vectors for controlled release.

Synthesis of well-defined glycopolymers and some studies of their aqueous solution behaviour.

Well-defined polymers with carbohydrate residues pendant to the main chain (glycopolymers) were prepared by reversible addition fragmentation chain transfer (RAFT) polymerisation. Excellent control over molecular weight and narrow polydispersities (1.1-1.2) were achieved over a range of molecular weights. In addition, efficient synthesis of block copolymers by sequential monomer addition with both hydrophilic and hydrophobic non-carbohydrate blocks was demonstrated. The aqueous solution behaviour of amphiphilic block glycopolymers was investigated, revealing the formation of multivalent carbohydrate-bearing aggregates in solution with the capability for the solubilisation of hydrophobic species (a water-insoluble dye). One such amphiphilic glycopolymer shows by TEM the formation of a worm-like micelle phase. Further investigations of these novel bioactive macromolecular assemblies are underway.