Manual Therapy and Exercise Have Similar Outcomes to Corticosteroid Injections in the Management of Patients With Subacromial Pain Syndrome: A Systematic Review and Meta-Analysis.

Subacromial pain syndrome (SAPS) is the most frequent diagnosis in patients with shoulder pain presenting with persistent pain and significant functional decline. Although exercise and manual therapy (EMT) and corticosteroid injections provide first-line treatment options, evidence for the best management of SAPS remains inconclusive. We aimed to evaluate the effectiveness of EMT compared with corticosteroid injections on disability, recovery rates, and pain in patients with SAPS through a systematic review and meta-analysis approach. PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), ScienceDirect, the Cochrane Library, and grey literature databases were searched. Only randomized controlled trials evaluating the effectiveness of EMT alone or as an additive intervention compared to corticosteroid injections were included. Methodological quality was evaluated with the PEDro score and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. In total, 8 trials with 946 patients were included. EMT presented no difference in disability compared with corticosteroid injections at very short- (standardized mean difference {SMD}: 0.19; 95%CI: -0.20, 0.58), short- (SMD: -0.16; 95%CI: -0.58, 0.25), mid- (SMD: -0.14; 95%CI: -0.44, 0.16), and long-term (SMD: 0.00; 95%CI: -0.25, 0.25) follow-up. No difference was found between the comparators in self-perceived recovery at very short- (risk ratio: 0.93; 95%CI: 0.71, 1.21) and mid- (risk ratio: 0.98; 95%CI: 0.90, 1.07) follow-up and in pain rating at very short- (SMD: -0.18; 95%CI: -0.73, 0.38), short- (SMD: 0.05; 95%CI: -0.26, 0.37), and long-term (SMD: 0.04; 95%CI: -0.26, 0.34) follow-ups. The addition of corticosteroid injections to EMT provided no better results in shoulder disability compared with EMT (SMD: 0.45; 95%CI: -0.47, 1.37) or corticosteroid injections alone (MD: 2.70; 95%CI: -7.70, 13.10) in the mid-term. Based on very low to moderate certainty of evidence, EMT has similar effects to corticosteroid injections on improving all outcomes in patients with SAPS at all follow-up periods. Based on low certainty of evidence the combination of both interventions does not change the treatment outcome compared with each intervention alone.

Low-Intensity Blood Flow Restriction Exercises Modulate Pain Sensitivity in Healthy Adults: A Systematic Review.

Low-intensity exercise with blood flow restriction (LIE-BFR) has been proposed as an effective intervention to induce hypoalgesia in both healthy individuals and patients with knee pain. Nevertheless, there is no systematic review reporting the effect of this method on pain threshold. We aimed to evaluate the following: (i) the effect of LIE-BFR on pain threshold compared to other interventions in patients or healthy individuals; and (ii) how different types of applications may influence hypoalgesic response. We included randomized controlled trials assessing the effectiveness of LIE-BFR alone or as an additive intervention compared with controls or other interventions. Pain threshold was the outcome measure. Methodological quality was assessed using the PEDro score. Six studies with 189 healthy adults were included. Five studies were rated with 'moderate' and 'high' methodological quality. Due to substantial clinical heterogeneity, quantitative synthesis could not be performed. All studies used pressure pain thresholds (PPTs) to assess pain sensitivity. LIE-BFR resulted in significant increases in PPTs compared to conventional exercise at local and remote sites 5 min post-intervention. Higher-pressure BFR results in greater exercise-induced hypoalgesia compared to lower pressure, while exercise to failure produces a similar reduction in pain sensitivity with or without BFR. Based on our findings, LIE-BFR can be an effective intervention to increase pain threshold; however, the effect depends on the exercise methodology. Further research is necessary to investigate the effectiveness of this method in reducing pain sensitivity in patients with pain symptomatology.

Wrist Extensor Training With Blood Flow Restriction for the Management of Lateral Elbow Tendinopathy: A Case Report.

Lateral elbow tendinopathy (LET) is a common overuse injury with complex underlying pathophysiological mechanisms. Although several modes of exercise with or without passive interventions have been recommended as the first-line treatment option of the condition, their effectiveness remains inconclusive. The aim of this case report is to evaluate the effect of wrist extensor exercises with blood flow restriction (BFR) as an add-on intervention to a multi-modal physiotherapy programme to improve outcomes in a patient with LET. A 51-year-old male patient presented with a history of right LET for six months. Interventions included wrist extension exercise with BFR, a two-stage progressive loading training programme of the upper limb, soft-tissue massage, education and a home exercise programme for six weeks (12 visits). A substantial improvement in pain intensity, pain-free grip strength, Patient Rated Tennis Elbow Evaluation score and self-perceived recovery was reported at three-, six-, and 12-week follow-up measurements. A 21% reduction in pressure pain thresholds at the lateral epicondyle was found immediately after wrist extensor exercise with BFR. Based on our findings, adding wrist extensor exercises with BFR to a multimodal physiotherapy programme seems a promising approach to improve the treatment outcome in LET. Nonetheless, further research is needed to confirm the present results.

Cross-Cultural Adaptation, Reliability, and Validity of the Greek Version of the Upper Extremity Functional Index.

Introduction The Upper Extremity Functional Index (UEFI) is a region-specific questionnaire for patients with upper extremity disorders including patients with rotator cuff-related pain (RCRP). We aimed to translate and cross-culturally adapt the UEFI into Greek (UEFI-Gr) and evaluate its reliability and validity in a Greek-speaking population with RCRP. Methods Published guidelines for translation and cross-cultural adaptation of patient-rated outcome measures were followed. One hundred two patients were asked to complete the Greek versions of the UEFI; Disability of the Arm, Shoulder, and Hand (DASH) questionnaire; and RAND 36-Item Health Survey. Internal consistency, test-retest reliability, measurement error, content validity, concurrent validity, and ceiling and floor effects were evaluated. Results Minor linguistic discrepancies were identified and adopted in the Greek language. The UEFI-Gr presented high internal consistency (Cronbach's alpha: 0.93), excellent test-retest reliability (intraclass correlation coefficient: 0.91; 95% confidence interval {CI}: 0.79-0.95), and acceptable measurement error (standard error of measurement: 4.9 points; minimal detectable change {MDC}: 13.8 points). No ceiling or floor effects were detected. Strong correlations were found with the Greek versions of the Disability of the Arm, Shoulder, and Hand questionnaire (r=0.629; p<0.001) and weak to moderate correlations with most subdomains of RAND 36-Item Health Survey (r=0.30-0.59; p<0.05). Conclusions The UEFI-Gr is a comprehensive, reliable, and valid self-reported instrument to evaluate symptoms in patients with RCRP. Further research on the responsiveness of the questionnaire is necessary.

Nanocrystal synthesis, µfluidic sample dilution and direct extraction of single emission linewidths in continuous flow.

The rational design of semiconductor nanocrystal populations requires control of their emission linewidths, which are dictated by interparticle inhomogeneities and single-nanocrystal spectral linewidths. To date, research efforts have concentrated on minimizing the ensemble emission linewidths, however there is little knowledge about the synthetic parameters dictating single-nanocrystal linewidths. In this direction, we present a flow-based system coupled with an optical interferometry setup for the extraction of single nanocrystal properties. The platform has the ability to synthesize nanocrystals at high temperature <300 °C, adjust the particle concentration after synthesis and extract ensemble-averaged single nanocrystal emission linewidths using flow photon-correlation Fourier spectroscopy.

Continuous Multistage Synthesis and Functionalization of Sub-100 nm Silica Nanoparticles in 3D-Printed Continuous Stirred-Tank Reactor Cascades.

The controlled and continuous production of nanoparticles (NPs) with functionalized surfaces remains a technological challenge. We present a multistage synthetic platform, consisting of 3D-printed miniature continuous stirred-tank reactor (CSTR) cascades, for the continuous synthesis and functionalization of SiO2 NPs. The use of the CSTR platform provides ideal and rapid mixing of precursor solutions, precise injection of additional reagents for multistep reactions, and facile operation when using viscous solutions and handling of syntheses with longer reaction times. To exemplify the use of such custom-designed CSTR cascades, amine- and carbohydrate-functionalized SiO2 NPs are chosen as model reaction systems. In particular, the intensified flow reactor units allowed for the reproducible formation of SiO2 NPs with diameters less than 100 nm and narrow size distributions (3-8%). Most importantly, by assembling various 3D-printed CSTR cascades, we synthesized gluconolactone-capped polyethylenimine-modified silica NPs in a fully continuous manner. The inherent control over NP surface charge, reactor scalability, and the significant shortening of processing times (less than 10 min) compared to batch methodologies (several days) strongly indicate the ability of the reactor technology to accelerate continuous nanomanufacturing. In general, it provides a simple route for the reproducible preparation of functionalized NPs, thus expanding the gamut of flow reactors for material synthesis.

Multistage Microfluidic Platform for the Continuous Synthesis of III-V Core/Shell Quantum Dots.

We present a fully continuous chip microreactor-based multistage platform for the synthesis of quantum dots with heterostructures. The use of custom-designed chip reactors enables precise control of heating profiles and flow distribution across the microfluidic channels while conducting multistep reactions. The platform can be easily reconfigured by reconnecting the differently designed chip reactors allowing for screening of various reaction parameters during the synthesis of nanocrystals. III-V core/shell quantum dots are chosen as model reaction systems, including InP/ZnS, InP/ZnSe, InP/CdS and InAs/InP, which are prepared in flow using a maximum of six chip reactors in series.

Pick a Color MARIA: Adaptive Sampling Enables the Rapid Identification of Complex Perovskite Nanocrystal Compositions with Defined Emission Characteristics.

Recent advances in the development of hybrid organic-inorganic lead halide perovskite (LHP) nanocrystals (NCs) have demonstrated their versatility and potential application in photovoltaics and as light sources through compositional tuning of optical properties. That said, due to their compositional complexity, the targeted synthesis of mixed-cation and/or mixed-halide LHP NCs still represents an immense challenge for traditional batch-scale chemistry. To address this limitation, we herein report the integration of a high-throughput segmented-flow microfluidic reactor and a self-optimizing algorithm for the synthesis of NCs with defined emission properties. The algorithm, named Multiparametric Automated Regression Kriging Interpolation and Adaptive Sampling (MARIA), iteratively computes optimal sampling points at each stage of an experimental sequence to reach a target emission peak wavelength based on spectroscopic measurements. We demonstrate the efficacy of the method through the synthesis of multinary LHP NCs, (Cs/FA)Pb(I/Br)3 (FA = formamidinium) and (Rb/Cs/FA)Pb(I/Br)3 NCs, using MARIA to rapidly identify reagent concentrations that yield user-defined photoluminescence peak wavelengths in the green-red spectral region. The procedure returns a robust model around a target output in far fewer measurements than systematic screening of parametric space and additionally enables the prediction of other spectral properties, such as, full-width at half-maximum and intensity, for conditions yielding NCs with similar emission peak wavelength.

Exploration of Near-Infrared-Emissive Colloidal Multinary Lead Halide Perovskite Nanocrystals Using an Automated Microfluidic Platform.

Hybrid organic-inorganic and fully inorganic lead halide perovskite nanocrystals (NCs) have recently emerged as versatile solution-processable light-emitting and light-harvesting optoelectronic materials. A particularly difficult challenge lies in warranting the practical utility of such semiconductor NCs in the red and infrared spectral regions. In this context, all three archetypal A-site monocationic perovskites-CH3NH3PbI3, CH(NH2)2PbI3, and CsPbI3-suffer from either chemical or thermodynamic instabilities in their bulk form. A promising approach toward the mitigation of these challenges lies in the formation of multinary compositions (mixed cation and mixed anion). In the case of multinary colloidal NCs, such as quinary Cs xFA1- xPb(Br1- yI y)3 NCs, the outcome of the synthesis is defined by a complex interplay between the bulk thermodynamics of the solid solutions, crystal surface energies, energetics, dynamics of capping ligands, and the multiple effects of the reagents in solution. Accordingly, the rational synthesis of such NCs is a formidable challenge. Herein, we show that droplet-based microfluidics can successfully tackle this problem and synthesize Cs xFA1- xPbI3 and Cs xFA1- xPb(Br1- yI y)3 NCs in both a time- and cost-efficient manner. Rapid in situ photoluminescence and absorption measurements allow for thorough parametric screening, thereby permitting precise optical engineering of these NCs. In this showcase study, we fine-tune the photoluminescence maxima of such multinary NCs between 700 and 800 nm, minimize their emission line widths (to below 40 nm), and maximize their photoluminescence quantum efficiencies (up to 89%) and phase/chemical stabilities. Detailed structural analysis revealed that the Cs xFA1- xPb(Br1- yI y)3 NCs adopt a cubic perovskite structure of FAPbI3, with iodide anions partially substituted by bromide ions. Most importantly, we demonstrate the excellent transference of reaction parameters from microfluidics to a conventional flask-based environment, thereby enabling up-scaling and further implementation in optoelectronic devices. As an example, Cs xFA1- xPb(Br1- yI y)3 NCs with an emission maximum at 735 nm were integrated into light-emitting diodes, exhibiting a high external quantum efficiency of 5.9% and a very narrow electroluminescence spectral bandwidth of 27 nm.

Unveiling the Shape Evolution and Halide-Ion-Segregation in Blue-Emitting Formamidinium Lead Halide Perovskite Nanocrystals Using an Automated Microfluidic Platform.

Hybrid organic-inorganic perovskites and in particular formamidinium lead halide (FAPbX3, X = Cl, Br, I) perovskite nanocrystals (NCs) have shown great promise for their implementation in optoelectronic devices. Specifically, the Br and I counterparts have shown unprecedented photoluminescence properties, including precise wavelength tuning (530-790 nm), narrow emission linewidths (<100 meV) and high photoluminescence quantum yields (70-90%). However, the controlled formation of blue emitting FAPb(Cl1-xBrx)3 NCs lags behind their green and red counterparts and the mechanism of their formation remains unclear. Herein, we report the formation of FAPb(Cl1-xBrx)3 NCs with stable emission between 440 and 520 nm in a fully automated droplet-based microfluidic reactor and subsequent reaction upscaling in conventional laboratory glassware. The thorough parametric screening allows for the elucidation of parametric zones (FA-to-Pb and Br-to-Cl molar ratios, temperature, and excess oleic acid) for the formation of nanoplatelets and/or NCs. In contrast to CsPb(Cl1-xBrx)3 NCs, based on online parametric screening and offline structural characterization, we demonstrate that the controlled synthesis of Cl-rich perovskites (above 60 at% Cl) with stable emission remains a challenge due to fast segregation of halide ions.

Microfluidic Technology: Uncovering the Mechanisms of Nanocrystal Nucleation and Growth.

The controlled and reproducible formation of colloidal semiconductor nanocrystals (or quantum dots) is of central importance in nanoscale science and technology. The tunable size- and shape-dependent properties of such materials make them ideal candidates for the development of efficient and low-cost displays, solar cells, light-emitting devices, and catalysts. The formidable difficulties associated with the macroscale preparation of semiconductor nanocrystals (possessing bespoke optical and chemical properties) result from the fact that underlying reaction mechanisms are complex and that the reactive environment is difficult to control. Automated microfluidic reactors coupled with monitoring systems and optimization algorithms aim to elucidate complex reaction mechanisms that govern both nucleation and growth of nanocrystals. Such platforms are ideally suited for the efficient optimization of reaction parameters, assuring the reproducible synthesis of nanocrystals with user-defined properties. This Account aims to inform the nanomaterials community about how microfluidic technologies can supplement flask experimentation for the ensemble investigation of formation mechanisms and design of semiconductor nanocrystals. We present selected studies outlining the preparation of quantum dots using microfluidic systems with integrated analytics. Such microfluidic reaction systems leverage the ability to extract real-time information regarding optical, structural, and compositional characteristics of quantum dots during nucleation and growth stages. The Account further highlights our recent research activities focused on the development and application of droplet-based microfluidics with integrated optical detection systems for the efficient and rapid screening of reaction conditions and a better understanding of the mechanisms of quantum dot synthesis. We describe the features and operation of fully automated microfluidic reactors and their subsequent application to high-throughput parametric screening of metal chalcogenides (CdSe, PbS, PbSe, CdSeTe), ternary and core/shell heavy metal-free quantum dots (CuInS2, CuInS2/ZnS), and all-inorganic perovskite nanocrystals (CsPbX3, X = Cl, Br, I) syntheses. Critically, concurrent absorption and photoluminescence measurements on millisecond to second time scales allow the extraction of basic parameters governing nanocrystal formation. Moreover, experimental data obtained from such microfluidic platforms can be directly supported by theoretical models of nucleation and growth. To this end, we also describe the use of metamodeling algorithms able to accurately predict optimized conditions of CdSe synthesis using a minimal number of sample parameters. Importantly, we discuss future challenges that must be addressed before microfluidic technologies are in a position to be widely adopted for the on-demand formation of nanocrystals. From a technology perspective, these challenges include the development of novel engineering platforms for the formation of complex architectures, the integration of monitoring systems able to harvest photophysical and structural information, the incorporation of continuous purification systems, and the application of optimization algorithms to multicomponent quantum dot systems.

Synthesis of Cesium Lead Halide Perovskite Nanocrystals in a Droplet-Based Microfluidic Platform: Fast Parametric Space Mapping.

Prior to this work, fully inorganic nanocrystals of cesium lead halide perovskite (CsPbX3, X = Br, I, Cl and Cl/Br and Br/I mixed halide systems), exhibiting bright and tunable photoluminescence, have been synthesized using conventional batch (flask-based) reactions. Unfortunately, our understanding of the parameters governing the formation of these nanocrystals is still very limited due to extremely fast reaction kinetics and multiple variables involved in ion-metathesis-based synthesis of such multinary halide systems. Herein, we report the use of a droplet-based microfluidic platform for the synthesis of CsPbX3 nanocrystals. The combination of online photoluminescence and absorption measurements and the fast mixing of reagents within such a platform allows the rigorous and rapid mapping of the reaction parameters, including molar ratios of Cs, Pb, and halide precursors, reaction temperatures, and reaction times. This translates into enormous savings in reagent usage and screening times when compared to analogous batch synthetic approaches. The early-stage insight into the mechanism of nucleation of metal halide nanocrystals suggests similarities with multinary metal chalcogenide systems, albeit with much faster reaction kinetics in the case of halides. Furthermore, we show that microfluidics-optimized synthesis parameters are also directly transferrable to the conventional flask-based reaction.

Millisecond-Timescale Monitoring of PbS Nanoparticle Nucleation and Growth Using Droplet-Based Microfluidics.

The early-time kinetics (<1 s) of lead sulfide (PbS) quantum dot formation are probed using a novel droplet-based microfluidic platform, which allows for high-throughput and real-time optical analysis of the reactive process with millisecond time resolution. The reaction platform enables the concurrent investigation of the emission characteristics of PbS quantum dots and a real-time estimation of their size and concentration during nucleation and growth. These investigations reveal a two-stage mechanism for PbS nanoparticle formation. The first stage corresponds to the fast conversion of precursor species to PbS crystals, followed by the growth of the formed particles. The growth kinetics of the PbS nanoparticles follow the Lifshitz-Slyozov-Wagner model for Ostwald ripening, allowing direct estimation of the rate constants for the process. In addition, the extraction of absorption spectra of ultrasmall quantum dots is demonstrated for first time in an online manner. The droplet-based microfluidic platform integrated with online spectroscopic analysis provides a new tool for the quantitative extraction of high temperature kinetics for systems with rapid nucleation and growth stages.

Nanocrystal synthesis in microfluidic reactors: where next?

The past decade has seen a steady rise in the use of microfluidic reactors for nanocrystal synthesis, with numerous studies reporting improved reaction control relative to conventional batch chemistry. However, flow synthesis procedures continue to lag behind batch methods in terms of chemical sophistication and the range of accessible materials, with most reports having involved simple one- or two-step chemical procedures directly adapted from proven batch protocols. Here we examine the current status of microscale methods for nanocrystal synthesis, and consider what role microreactors might ultimately play in laboratory-scale research and industrial production.

Controlled synthesis of fluorescent silica nanoparticles inside microfluidic droplets.

We study the droplet-based synthesis of fluorescent silica nanoparticles (50-350 nm size) in a microfluidic chip. Fluorescein-isothiocyanate (FITC) dye is first chemically linked to aminopropyl triethoxysilane (APTES) in ethanol and this reaction product is subsequently mixed with tetraethyl orthosilicate (TEOS) to yield a fluorescent silicon alkoxide precursor solution. The latter reacts with an aqueous ethanol-ammonia hydrolysing mixture inside droplets, forming fluorescent silica nanoparticles. The droplets are obtained by pinching-off side-by-side flowing streams of alkoxide solution/hydrolysing mixture on a microfluidic chip using a Fluorinert oil continuous phase flow. Synthesis in droplets leads to a faster reaction and allows drastically improved nanoparticle size uniformity (down to 3% relative standard deviation for 350 nm size particles) when compared to conventional bulk synthesis methods, thanks to the precise control of reagent concentrations and reaction times offered by the microfluidic format. Incorporating FITC inside silica nanoparticles using our method leads to reduced dye leakage and increases the dye's stability, as evidenced by a reduced photochemical bleaching compared to a pure FITC solution.