Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials.

OBJECTIVE: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA). METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence. RESULTS: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty). CONCLUSIONS: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function.

Interface Engineering Enables Multilevel Resistive Switching in Ultra-Low-Power Chemobrionic Copper Silicate.

Memristor is assuming prominence due to its exceptionally low power consumption, adaptable, and parallel signal processing capabilities that address the limitations of the von Neumann architecture to meet the growing demand for advanced technologies such as artificial intelligence, Internet of Things (IoTs), and neuromorphic computation. In this work, we demonstrate resistive switching in copper silicate-based hollow tube-forming self-organized membrane structures belonging to the category of chemobrionics or chemical gardens to demonstrate cost-effective and highly efficient memristor devices. The device architecture is configured as ITO/PEDOT:PSS/active layer (copper silicate)/PMMA/Ag, an arrangement that serves to stabilize current-voltage hysteresis and exhibit a low SET voltage ∼0.2 V with a 0.8 nJ power consumption while manifesting robust data endurance and multilevel resistive switching. The inherent self-rectifying behavior, characterized by a high rectification ratio of 60, underscores the potential utility of these devices across a spectrum of electronic applications. To emulate the functionality of biological synapses, fundamental synaptic characteristics are assessed, including paired-pulse facilitation (PPF) and potentiation and depression (P&D). We validate the potential of copper silicate chemical garden-based memristor devices for applications that require real-time synaptic processing. Importantly, the fabrication of these devices was accomplished through a comprehensive solution-based, low-temperature process conducted under ambient environmental conditions, obviating the need for specialized glovebox facilities.

Adhesions After Hip Arthroscopy Are Associated With Revision But Show Poorly Defined Criteria for Diagnosis and Operative Management: A Systematic Review.

PURPOSE: To evaluate the current body of evidence surrounding the diagnosis, management, and clinical outcomes of adhesions that developed after hip arthroscopy (HA). METHODS: A systematic search of the MEDLINE, Embase, Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was designed and conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Eligible studies included patients with confirmed adhesions after HA that reported one or more of the following: (1) diagnostic procedures and criteria used; (2) indications for and details surrounding surgical management; and (3) clinical outcomes after the operative management of adhesions (e.g., patient-reported outcome measures). RESULTS: Nineteen studies involving a total of 4,145 patients (4,211 hips; 38% female sex) were included in this review. The quality of evidence was found to be fair for both comparative studies (mean, 17; range, 13-21) and noncomparative studies (mean, 10; range, 5-12) according to the Methodological Index for Non-randomized Studies (MINORS) instrument, with the level of evidence ranging from IIB to IV. Adhesions were often diagnosed intraoperatively at the time of revision surgery (10 of 19 studies, 53%), with only 3 studies specifying the criteria used to adjudicate adhesions. The most common indication for operative management (i.e., release or lysis of adhesions) was persistent pain (9 of 19, 47%), but this was often grossly stated for revision HA rather than being specific to adhesions. Patient-reported outcome measures were the most reported postoperative outcomes (9 of 19, 47%) and generally showed significant improvement from preoperative assessment across the short-term follow-up period (range, 24.5-38.1 months). There was a paucity of objective measures of clinical improvement (3 of 19, 16%) and of mid- and long-term follow-up (i.e., 5-7 years and ≥10 years, respectively). CONCLUSIONS: Despite the growing body of evidence suggesting that adhesions are highly contributory to revision HA, there is ambiguity in the diagnostic approach and indications for operative management of adhesions. Additionally, although the operative management of adhesions after HA has shown satisfactory clinical outcomes in the short term, there is a paucity of research elucidating the mid- to long-term outcomes, as well as minimal use of objective assessment of clinical improvement (e.g., biomechanics). LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

Risk factors for prolonged opioid consumption following hip arthroscopy: A secondary analysis of the Femoroacetabular Impingement RandomiSed controlled Trial and embedded cohort study.

PURPOSE: The purpose of the study was to identify prognostic risk factors for prolonged opioid use at 2 and 6 weeks after hip arthroscopy using data from the Femoroacetabular Impingement RandomiSed controlled Trial and its external validation cohort study. METHODS: Opioids were prescribed for postoperative pain management at the surgeon's discretion, with a majority being prescribed a combination of oxycodone and paracetamol (5/325 mg). Prolonged opioid use was defined as the ongoing use of any dosage of opioids reported at either 2 or 6 weeks after surgery to treat femoroacetabular impingement, as recorded in the patient's study medication log. Multivariable logistic regressions were performed to evaluate patient and surgical characteristics, such as preoperative opioid use, type of surgical procedure and intraoperative cartilage state that may be associated with prolonged opioid use at either 2 and 6 weeks postoperatively. RESULTS: A total of 265 and 231 patients were included for analysis at 2 and 6 weeks postoperatively, respectively. The median age of participants was 35 years (interquartile range [IQR]: 27-42) and 33% were female. At 2 weeks postoperatively, female sex (odds ratio [OR]: 2.56; 95% confidence interval: [CI] 1.34-4.98, p = 0.005), higher body mass index (BMI) (OR: 1.10; 95% CI: 1.02-1.18, p = 0.009), active tobacco use (OR: 4.06; 95% CI: 1.90-8.97, p < 0.001), preoperative opioid use (OR: 10.1; 95% CI: 3.25-39.1, p < 0.001) and an Outerbridge classification of ≥3 (OR: 2.33; 95% CI: 1.25-4.43, p = 0.009) were significantly associated with prolonged opioid use. At 6 weeks postoperatively, only preoperative opioid use was significantly associated with prolonged opioid consumption (OR: 10.6; 95% CI: 3.60-32.6, p < 0.001). CONCLUSION: Preoperative opioid use was significantly associated with continued opioid use at 2 and 6 weeks postoperatively. Specific patient factors including female sex, higher BMI, active tobacco use and more severe cartilage damage should be considered in developing targeted strategies to limit opioid use after surgery. LEVEL OF EVIDENCE: Level III.

Development of an antimicrobial, 3D printable denture base material with K18 quaternary ammonium silane-functionalized methyl methacrylate and filler.

STATEMENT OF PROBLEM: Denture base materials are highly susceptible to microbial colonization, which can lead to denture stomatitis. In addition, patients who sleep with their dentures have an increased chance of contracting pneumonia. Commercially available antimicrobial denture base materials to prevent or combat microbial colonization are lacking. PURPOSE: The purpose of this in vitro study was to determine the effects of K18 quaternary ammonium methacryloxy silane-functionalized filler (K18-Filler) and methyl methacrylate (K18-MMA) on the polymerization of 3D printed denture base material and its esthetic, mechanical, and antimicrobial properties. MATERIAL AND METHODS: K18-Filler (0%, 10%, 20% w/w) and K18-MMA (0%, 5%, 12.5% w/w) were added to a 3D printable denture base resin (Denture Base Resin, Original Pink; Formlabs Inc) and 3D printed. Specimens were tested by using the Rockwell15T hardness, near infrared FTIR monomer-to-polymer degree of conversion (DoC), transparency parameter (TP), color shift, and 3-point bend and by counting colony forming units against Streptococcus aureus, Streptococcus sanguinis and Candida albicans tests. Data were analyzed using analysis of variance with the Tukey-Kramer HSD post hoc test. RESULTS: Control resins had significantly higher Rockwell15T hardness than most of the K18 groups (P<.05) but had comparable DoC with all K18 groups except one, showing that all groups were well polymerized. Controls had significantly higher TP than most K18 groups, but most K18 groups had ΔE<3.3, so the color shift was not noticeable. However, the 12.5% K18-MMA with 10% and 20% K18-Filler groups, which were also the groups used to test for antimicrobial activity, had ΔE>8. All K18 groups had comparable or greater moduli than the controls, but the controls had significantly higher ultimate transverse strengths than most K18 groups (P<.05). All 12.5% K18-MMA with K18-Filler groups had significant antimicrobial activity against S. aureus, S. sanguinis, and C. albicans. CONCLUSIONS: 12.5% K18-MMA and K18-Filler produced 3D printable denture materials with comparable polymerization properties and significant antimicrobial properties against S. mutans, S. sanguinis, and C. albicans. High K18-MMA and K18-Filler concentrations caused significant color shifts and reductions in ultimate strengths.

Trace level quantification of N-nitrosorasagiline in rasagiline tablets by LC-TQ-MS/MS.

Parkinson's disease is a chronic, progressive neurological disease that currently affects about more than 10 million population worldwide. Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease. Rasagiline tablets have been recalled from market due to the presence of unacceptable levels of nitrosamine impurity. European Medical Agency has set up very stringent limit 100ng/day of N-nitrosorasagiline (NSRG) in drug product based on its mutagenicity. The analytical methods need to be sufficiently sensitive in order to adequately detect and quantify trace levels of NSRG. A highly sensitive LC-MS/MS method for determination of NSRG in rasagiline tablet formulation was developed by effectively separating on zorbax eclipse XDB C18 column using 0.1% formic acid in mixture of water and acetonitrile (35:65 v/v) in an isocratic mode at 0.5mL/min flow rate. The measurement of NSRG was performed using triple quadrupole mass detection accompanied by electrospray ionization in the multiple reaction monitoring mode. The validation of the method was comprehensive, demonstrating strong linearity across the concentration spectrum of 2 to 200ng/mL for NSRG. The obtained correlation coefficient exceeded 0.998, signifying a robust relationship. Recoveries spanning from 80.0% to 120.0% for NSRG were deemed satisfactory. The developed method was able to detect and quantitate NSRG at a concentration level of 1 to 2ng/mL respectively (1 to 2ppm with respect to 1mg/mL of rasagiline tablet sample concentration). The developed and validated method can be employed for routine quality control testing of rasagiline tablets.

Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress.

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can be passed on to the offspring epigenetically. We investigated the effects of gestational chronic variable stress (CVS) in rats using restraint and social isolation stress in the parental F0 generation and its transgenerational transmission across three generations of female offspring (F1-F3). A subset of F1 rats was housed in an enriched environment (EE) to mitigate the adverse effects of CVS. We found that CVS is transmitted across generations and induces inflammatory changes in the uterus. CVS did not alter any gestational lengths or birth weights. However, inflammatory and endocrine markers changed in the uterine tissues of stressed mothers and their offspring, suggesting that stress is transgenerationally transmitted. The F2 offspring reared in EE had increased birth weights, but their uterine gene expression patterns remained comparable to those of stressed animals. Thus, ancestral CVS induced changes transgenerationally in fetal programming of uterine stress markers over three generations of offspring, and EE housing did not mitigate these effects.

The quality of diagnostic studies used for the diagnostic criteria of periprosthetic joint infections.

BACKGROUND: Although periprosthetic joint infection (PJI) is a serious complication following a total joint arthroplasty procedure, there remains uncertainty regarding the diagnosis of PJI due to the lack of a globally accepted, standardized definition. The goal of this review is to critically analyze the quality of the evidence used for the novel 2018 MSIS PJI definition and identify gaps and limitations with using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. METHODS: References from the modified 2018 MSIS definition for PJI by Parvizi et al. were retrieved and manually reviewed. A total of 11 studies were assessed using a validated QUADAS-2 tool. RESULTS: Many included studies had an unclear or high risk of bias for the Index Test domain due to a lack of blinding and lack of prespecified thresholds. A majority of studies utilized Youden's J statistic to optimize the thresholds which may diminish external validity. Likewise, several studies were assessed to have an unclear and high risk of bias for the Flow and Timing domain primarily due to a lack of reporting and a large number of exclusions. Overall, there was a low risk of bias for the choice of reference standard, its conduct and interpretation, as well as for the Patient Selection domain. CONCLUSION: Although the literature used for the MSIS 2018 PJI definition is fraught with potential sources of bias, there may be a trend toward an improvement in the quality of evidence when compared to the earlier definition of PJI.

Are Functional Outcomes of a Total Hip Arthroplasty Predictive of a Contralateral Total Hip Arthroplasty: A Retrospective Cohort Study.

BACKGROUND: Current literature suggests that 8%-35% of patients undergoing total hip arthroplasty (THA) undergo a subsequent contralateral THA. This study aims to determine if functional outcomes after primary THA predict outcomes in the subsequent primary THA of the contralateral side. METHODS: A retrospective cohort of patients undergoing staged bilateral primary THA was reviewed. The Oxford Hip Score (OHS) was utilized as the functional outcome measurement tool and was assessed preoperatively and at one year postoperatively. The minimal clinically important difference (MCID) was assessed. Based on the first-side THA one-year outcomes, the odds of maintaining an MCID, or not, for the second-side THA were determined. RESULTS: The study cohort consisted of 551 patients and 1102 primary THAs. The average postoperative OHSs were similar after the first and second THA. Patients achieving the MCID with the first-side surgery were 2.6 times (95% confidence interval 1.0 to 6.64, P = .04) more likely to achieve the MCID for the second-side surgery than patients failing to reach the MCID for their first-side surgery. After the first THA, 29 (5.3%) patients failed to reach the predefined MCID for the OHS compared with 54 (9.8%) patients undergoing their second THA (odds ratio: 1.96 [95% confidence interval: 1.23 to 3.1], χ2 = 8.14, P = .005). CONCLUSIONS: Functional outcomes after the first THA are predictive of functional outcomes of the second THA. Patients are more likely to achieve a clinically significant improvement after their first THA related to higher preoperative OHSs before the second THA.

The role of strontium ranelate and guided bone regeneration in osteoporotic and healthy conditions.

BACKGROUND/ OBJECTIVES: SR is a chemical agent developed for the treatment of osteoporosis. In vitro, SR enhanced replication of osteoprogenitor cells and bone formation. In vivo, in ovariectomized rats SR prevented the biomechanical deterioration of bone while in non-ovariectomized rats, enhanced bone architecture and increased trabecular and cortical bone mass. The aim of this study was to evaluate the effect of SR on bone healing of calvarial critical size defects treated with a deproteinized bovine bone mineral (DBBM) and a collagen barrier (CM), in healthy and osteoporotic rats. MATERIAL AND METHODS: Sixty-four, 4-month-old Wistar female rats were used. Osteoporosis was induced by ovariectomy and calcium-deficient diet in half of them. Sixteen ovariectomized (OSR) and 16 healthy (HSR) rats were treated with SR while no medication was administered in the remaining 16 healthy (H) and 16 ovariectomized (O) rats. At 6 weeks after ovariectomy, a 5mm defect was created in each parietal bone of every animal. One defect was treated with DBBM and CM, while the contralateral was left untreated. Qualitative and quantitative histological analysis was performed at 30 and 60 days of healing. A generalized estimating equations test was performed to evaluate the effect of SR and osteoporosis, on new bone formation (NB). RESULTS: After 30 days of healing, NB in the untreated defects was 3.4%±1.7%, 4.3%±6.2%, 3.2±4.5%, 15.9±23.5% in O, OSR, H and HSR groups, respectively; after 60 days, NB was 4.7%±4.3%, 11.3%±7%, 7.1%±13.2, 12.1%±13.5%, respectively. In the GBR-treated defects, after 30 days, NB was 2.6%±1.4%, 2.4%±1.6%, 4.5%±4.1%, 10.3%±14.4% in O, OSR, H and HSR groups, respectively; after 60 days, NB was 2.2%±1.6%, 4.3%±4.2%, 7%±5.1%, 10.8%±17.4%, respectively. Osteoporosis (p=0.008) and the absence of strontium ranelate treatment (p=0.01) had a negative impact on NB. CONCLUSION: SR may promote bone formation in calvarial defects in healthy and osteoporotic rats, albeit in a moderate extent.

Emergency Nurses' Experiences in Treating Patients With Mental Illness: A Qualitative, Interpretive Metasynthesis.

INTRODUCTION: Each year, emergency departments are seeing an increase in the number of patients with mental illness. Nurses often do not feel equipped with the knowledge or skills for this patient population while caring for them. Although there is published literature about nurses caring for patients with mental illness, there is a gap in knowledge about the lived experiences of these frontline workers. METHODS: To gain a better understanding of the experiences of emergency nurses in treating patients presenting with psychiatric issues, a qualitative interpretive metasynthesis of 5 qualitative articles was conducted. RESULTS: Three themes emerged from the synthesis: (1) feeling unprepared and unqualified, (2) feeling anxious and hesitant, and (3) the need to keep the patient environment safe. DISCUSSION: The overarching finding in our QIMS was the prevalent feeling of general concern regarding treating patients with mental illness despite the nurses' own preconceptions and apprehensions. It is important to understand the lived experiences of nurses treating patients with mental illness to learn be better prepared for future encounters.

Unique and overlapping effects of triiodothyronine (T3) and thyroxine (T4) on sensory innervation of the chick cornea.

Multiple aspects of cornea development, including the innervation of the cornea by trigeminal axons, are sensitive to embryonic levels of thyroid hormone (TH). Although previous work showed that increased TH levels could enhance the rate of axonal extension within the cornea in a thyroxine (T4)-dependent manner, details underlying the stimulatory effect of TH on cornea innervation are unclear. Here, by examining the effects throughout all stages of cornea innervation of the two main THs, triiodothyronine (T3) and T4, we provide a more complete characterization of the stimulatory effects of TH on corneal nerves and begin to unravel the underlying molecular mechanisms. During development, trigeminal axons are initially repelled at the corneal periphery and encircle the cornea in a pericorneal nerve ring prior to advancing into the corneal stroma radially from all along the nerve ring. Overall, exogenous T3 led to pleiotropic effects throughout all stages of cornea innervation, whereas the effects of exogenous T4 was confined to timepoints following completion of the nerve ring. Specifically, exogenous T3 accelerated the formation of the pericorneal nerve ring. By utilizing in vitro neuronal explants studies we demonstrated that T3 acts as a trophic factor to directly stimulate trigeminal nerve growth. Further, exogenous T3 caused disorganized and precocious innervation of the cornea, accompanied by the downregulation of inhibitory Robo receptors that normally act to regulate the timing of nerve advancement into the Slit-expressing corneal tissues. Following nerve ring completion, the growth rate and branching behavior of nerves as they advanced into and through the cornea were found to be stimulated equally by T3 or T4. These stimulatory influences of T3/T4 over nerves likely arose as secondary consequences brought on by TH-mediated modulations to the corneal extracellular matrix. Specifically, we found that the levels of nerve-inhibitory keratan- and chondroitin-sulfate containing proteoglycans and associated sulfation enzymes were dramatically altered in the presence of exogenous T3 or T4. Altogether, these findings uncover new roles for TH on corneal development and shed insight into the mechanistic basis of both T3 and T4 on cornea innervation.

Benzylic Hydroperoxidation via Visible-Light-Induced Csp3-H Activation.

A highly efficient benzylic hydroperoxidation has been realized through a visible-light-induced Csp3-H activation. We believe that this reaction undergoes a direct HAT mechanism catalyzed by eosin Y. This approach features the use of a metal-free catalyst (eosin Y), an energy-economical light source (blue LED), and a sustainable oxidant (molecular oxygen). Primary, secondary, and tertiary hydroperoxides as well as silyl, benzyl, and acyl peroxides were successfully prepared with good yields and excellent functional group compatibility.

Changes in forward light scatter parameters as a function of refractive error in young adults.

BACKGROUND/AIMS: Some aspects of visual performance worsen with increasing myopia. Whilst the underlying causes are not always clear, reduction in retinal image quality is often attributed to structural changes in the posterior myopic eye. Forward light scatter, originating principally from the cornea and lens, is known to produce veiling glare which subsequently reduces retinal image contrast. It is therefore of interest to investigate whether forward light scatter varies with refractive error. METHODS: Thirteen young-adult subjects (18-25 years), with mean spherical errors (MSE ± sd, D) RE, - 1.69 ± 2.02 (range 0.38 to - 4.75); LE, - 1.91 ± 1.94 (range 0.50 to - 4.63) underwent binocular assessment of forward light scatter using the AVOT light scatter test. Five glare annuli, with effective eccentricities ranging from 2 to 10°, were used to estimate parameters, k and n, which define the light scatter function of the eye. These were then used to calculate the area under the light scatter function (k') and the total volume of light scatter (k″). RESULTS: Significant correlation was found between increasing myopia and k' values (RE, p < 0.05; r = 0.64; LE, p < 0.05, r = 0.66). Neither the 'volume' of light scatter (k″), the parameter, n, which controls the angular distribution of light scatter, or the straylight parameter constant, k, were significantly correlated with refractive error (p > 0.05 for both eyes). Axial length was also not correlated with any of the light scatter parameters measured. CONCLUSION: The preliminary data from this study provide evidence that some light scatter parameters may be correlated with refractive error. Further studies are needed to characterize how changes in the anterior media of the eye, and inclusion of a wider range of refractive errors, may affect forward light scatter.

Developmental Impacts of Epigenetics and Metabolism in COVID-19.

Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.

Transition Needs Among Veterans Living With Chronic Pain: A Systematic Review.

INTRODUCTION: A third of Canadian Armed Forces veterans report difficulty adjusting to post-military life. Moreover, an estimated 40% of Canadian veterans live with chronic pain, which is likely associated with greater needs during the transition from military to civilian life. This review explores challenges and transition needs among military personnel living with chronic pain as they return to civilian life. METHODS: We searched MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to July 2022, for qualitative, observational, and mixed-method studies exploring transition needs among military veterans released with chronic pain. Reviewers, working independently and in duplicate, conducted screening and used a standardized and pilot-tested data collection form to extract data from all included studies. Content analysis was used to create a coding template to identify patterns in challenges and unmet needs of veterans transitioning to civilian life, and we summarized our findings in a descriptive manner. RESULTS: Of 10,532 unique citations, we identified 43 studies that reported transition challenges and needs of military personnel; however, none were specific to individuals released with chronic pain. Most studies (41 of 43; 95%) focused on military personnel in general, with one study enrolling individuals with traumatic brain injury and another including homeless veterans. We identified military-to-civilian challenges in seven areas: (1) identity, (2) interpersonal interactions/relationships, (3) employment, (4) education, (5) finances, (6) self-care and mental health, and (7) accessing services and care. CONCLUSIONS: Military personnel who transition to civilian life report several important challenges; however, the generalizability to individuals released with chronic pain is uncertain. Further research is needed to better understand the transition experiences of veterans with chronic pain to best address their needs and enhance their well-being.

Control-Etched Ti3C2Tx MXene Nanosheets for a Low-Voltage-Operating Flexible Memristor for Efficient Neuromorphic Computation.

Hardware neural networks with mechanical flexibility are promising next-generation computing systems for smart wearable electronics. Overcoming the challenge of developing a fully synaptic plastic network, we demonstrate a low-operating-voltage PET/ITO/p-MXene/Ag flexible memristor device by controlling the etching of aluminum metal ions in Ti3C2Tx MXene. The presence of a small fraction of Al ions in partially etched MXene (p-Ti3C2Tx) significantly suppresses the operating voltage to 1 V compared to 7 V from fully Al etched MXene (f-Ti3C2Tx)-based devices. Former devices exhibit excellent non-volatile data storage properties, with a robust ∼103 ON/OFF ratio, high endurance of ∼104 cycles, multilevel resistance states, and long data retention measured up to ∼106 s. High mechanical stability up to ∼73° bending angle and environmental robustness are confirmed with consistent switching characteristics under increasing temperature and humid conditions. Furthermore, a p-Ti3C2Tx MXene memristor is employed to mimic the biological synapse by measuring the learning-forgetting pattern for ∼104 cycles as potentiation and depression. Spike time-dependent plasticity (STDP) based on Hebb's Learning rules is also successfully demonstrated. Moreover, a remarkable accuracy of ∼95% in recognizing modified patterns from the National Institute of Standards and Technology (MNIST) data set with just 29 training epochs is achieved in simulation. Ultimately, our findings underscore the potential of MXene-based flexible memristor devices as versatile components for data storage and neuromorphic computing.

Distribution and bulk flow analyses of the intraflagellar transport (IFT) motor kinesin-2 support an "on-demand" model for Chlamydomonas ciliary length control.

Most cells tightly control the length of their cilia. The regulation likely involves intraflagellar transport (IFT), a bidirectional motility of multi-subunit particles organized into trains that deliver building blocks into the organelle. In Chlamydomonas, the anterograde IFT motor kinesin-2 consists of the motor subunits FLA8 and FLA10 and the nonmotor subunit KAP. KAP dissociates from IFT at the ciliary tip and diffuses back to the cell body. This observation led to the diffusion-as-a-ruler model of ciliary length control, which postulates that KAP is progressively sequestered into elongating cilia because its return to the cell body will require increasingly more time, limiting motor availability at the ciliary base, train assembly, building block supply, and ciliary growth. Here, we show that Chlamydomonas FLA8 also returns to the cell body by diffusion. However, more than 95% of KAP and FLA8 are present in the cell body and, at a given time, just ~1% of the motor participates in IFT. After repeated photobleaching of both cilia, IFT of fluorescent kinesin subunits continued indicating that kinesin-2 cycles from the large cell-body pool through the cilia and back. Furthermore, growing and full-length cilia contained similar amounts of kinesin-2 subunits and the size of the motor pool at the base changed only slightly with ciliary length. These observations are incompatible with the diffusion-as-a-ruler model, but rather support an "on-demand model," in which the cargo load of the trains is regulated to assemble cilia of the desired length.

Molecular pathology and therapeutics of the diabetic foot ulcer; comprehensive reviews.

Diabetes mellitus (DM) is a chronic metabolic condition linked to high blood sugar levels. Diabetes causes complications like neuropathy, nephropathy, and retinopathy. Diabetes foot ulcer (DFU) is a significant and serious wound healing issue resulting from uncontrolled DM. The main causes of the development of the DFU are oxidative stress brought on by the NO moiety, release of pro-inflammatory cytokines like tumour necrosis factor (TNF)-α and interleukin (IL-1), cellular dysfunction, and pathogenic microorganisms including staphylococcus and streptococcus species. The two main types of wounds that are prevalent in DFU patients are neuropathic and neuroischemic. If this wound is not properly treated or cared for, a lower limb may have to be amputated. There are several therapy options for DFU, including antibiotics, debridement, dressings, nano formulations, and growth factor preparations like PDGF-BB, to help the wound heal and prevent amputation. Other novel approaches involved the use of nerve taps, microneedle patches, nanotechnology-based formulations and stem cell applications to promote healing. There are possibilities of drug repurposing for the DFU treatment based on targeting specific enzymes. This article summarises the current pathophysiological aspects of DFU and its probable future targets.

Transportation Among Returning Citizens: "You Just Want to Stay Down and Get High".

The United States is releasing more individuals from prisons than ever before. However, returning citizens face numerous challenges transitioning back into community life and many communities remain ill-equipped in successfully supporting them. This study focuses on transportation as in integral component to the success of returning citizens. Rapid and rigorous qualitative data analysis (RADaR technique) is applied to interviews (n = 15) with individuals having returned to their community about the impact of transportation on their reentry. Analysis resulted in three primary themes; interviewees reinforced existing knowledge of the issues with transportation disadvantage, transportation is an extension of freedom, and transportation is directly connected to reentry success. These findings suggest a tiered structure of transportation freedom for returning citizens. This model of transportation will aid future researchers and policymakers in considering how to better resource returning citizens to maximize their success.