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El objetivo de este trabajo fue evaluar el efecto de la asociación de Leucaena leucocephala, y su co-inoculación con una cepa del hongo micorrízico arbuscular (HMA) Claroideoglomus claroideum y un aislado local de rizobio, sobre el comportamiento de las gramíneas asociadas (Bouteloua gracilis, Bouteloua curtipendula y Setaria macrostachya). Se estudiaron las estructuras micorrízicas y la nodulación. Se realizaron tres experimentos independientes, uno por cada gramínea, en asociación con L. leucocephala co-inoculada y sin inocular, o sola (como testigo). Los pastos asociados con L. leucocephala co-inoculada produjeron mayor cantidad de tallos que aquellos asociados con L. leucocephala sin inocular. B. gracilis y B. curtipendula acumularon mayor biomasa cuando se asoció con L. leucocephala co-inoculada. Las concentraciones de clorofilas a, b y totales en S. macrostachya y la de clorofila b en B. gracilis se vieron favorecidas por la asociación con L. leucocephala. La co-inoculación promovió el desarrollo de estructuras micorrízicas en la rizósfera y el número de nódulos en raíces de L. leucocephala, aunque el porcentaje de nódulos efectivos no reflejó diferencias entre tratamientos. En conclusión, la asociación de gramíneas con L. leucocephala y su inoculación con HMA y aislados de rizobios locales no solo promueve el desarrollo de estructuras micorrízicas y la nodulación, sino también aumenta el crecimiento y el contenido de pigmentos fotosintéticos en las gramíneas asociadas

Objectives: This prospective, open-label, single-arm, multicenter study evaluated the use of differential target multiplexed (DTM) spinal cord stimulation (SCS) therapy for chronic upper limb pain (ULP)., Materials and Methods: A total of 58 candidates for SCS who had chronic ULP were enrolled at 11 sites in the USA. The safety and effectiveness of DTM SCS for treating chronic intractable ULP were evaluated over 12 months. The primary end point was the percentage of responders (≥50% ULP relief versus baseline) to treatment at three months after device activation. This study also evaluated the extent of disability, patient satisfaction, and patient global impression of change with DTM SCS therapy., Results: The mean baseline pain score (10-cm visual analog scale [VAS-10]) for ULP was 7.2 cm, with a mean age of 56 years and mean ULP duration of ten years; 47 subjects were assessed at the primary end point. The percentage of ULP responders was 92% at three months, which was consistent at six (91%) and 12 months (86%). Significant ULP relief (81% reduction in VAS-10) was observed at the primary end point and sustained throughout the study duration. Significant improvements in disability in addition to high levels (>95%) of satisfaction and feelings of improvement were reported. Frequency of study-related anticipated adverse events was in line with expectations of SCS therapy., Conclusion: In this patient population with difficult-to-treat conditions with limited clinical evidence of the effectiveness of SCS, subjects reported significant reduction in chronic ULP in response to treatment with DTM SCS., Competing Interests: Conflict of Interest Wilson Almonte, Richard Bundschu, Amr El-Naggar, Gennady Gekht, Mayank Gupta, Yoann Millet, Andrew Will, and Kenneth Wu report institutional grant support from SGX Nova. Aaron Calodney reports grant support from Stryker, Boston Scientific, Saluda Medical, and Vivex, and consulting fees from Medtronic, Companion Spine, PainTeq, and Vertos. David L. Cedeño reports institutional grant support from Medtronic, consulting fees from SGX Medical, ownership of SGX Medical, and being coinventor of patents assigned to Medtronic. Harold Cordner and Rafael Justiz report institutional grant support from SGX Nova and consulting fees from Medtronic. Michael Fishman reports institutional grant support from SGX Nova, consulting fees from Medtronic and Saluda Medical, honoraria for speaker engagements for Medtronic and Mainstay Medical, and stock options from Brixton Biosciences, Celeri Health, and Aurora Spine. Philip Kim reports institutional grant support from SGX Nova, Medtronic, Biotronik, Abbott, Saluda Medical, and Boston Scientific, consulting fees from Medtronic and Biotronik, and honoraria for speaker engagements for Medtronic. Wesley Park reports employment with SGX Medical. David Schultz discloses participation in the advisory board for SynerFuse Inc. Ricardo Vallejo reports institutional grant support from Medtronic, consulting fees from SGX Medical and Medtronic, ownership of SGX Medical, and being coinventor of patents assigned to Medtronic. Thomas White reports institutional grant support from SGX Nova, consulting fees and honoraria from Medtronic, and ownership of North Pines Surgery Center. Justin Sirianni reports no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with persistent spinal pain syndrome with previous spinal surgery (PSPS-T2) or ineligible for it (PSPS-T1). This study reports 24-month efficacy and safety of DTM SCS vs. conventional medical management (CMM) in PSPS-T1 subjects across four European countries., Methods: This is a prospective, multicenter, open-label, randomized, controlled trial with optional crossover. Subjects randomized 1:1 to DTM SCS or CMM. Primary endpoint was responder rate (% subjects reporting ≥50% CLBP relief) at 6 months. A superiority test compared responder rates between treatments. CLBP and leg pain levels, functional disability, quality of life (QoL), patient satisfaction and global impression of change were evaluated for 24 months. A Composite Responder Index (CRI) was obtained using CLBP relief, disability and QoL. Incidence of study-related adverse events evaluated safety., Results: A total of 55 and 57 subjects were randomized to DTM SCS and CMM respectively. DTM SCS was superior, with CLBP responder rates ≥80% and CLBP relief >5.6 cm (>70% reduction) through the 24-month follow-up. Improvements with DTM SCS in other outcomes were sustained. The CRI was >80% for DTM SCS through 24 months. Opioid medication intake decreased in subjects treated with DTM SCS. Most patients treated with DTM SCS felt satisfied and improved at the end of the study. Safety was congruent with other studies., Conclusion: DTM SCS is efficacious and safe during 24 months for the treatment of CLBP and leg pain in PSPS-T1 patients ineligible for spine surgery., Significance Statement: This randomized controlled trial shows that Differential Target Multiplexed SCS (DTM SCS) is an effective and safe long-term treatment for PSPS type 1 patients suffering from axial low back pain with or without leg pain and who are ineligible for spinal surgery. Currently, CMM treatments are their only option and provide limited benefits. Besides superior pain relief, DTM SCS provides significant improvements in functional disability, quality of life, high levels of satisfaction and perceived impression of change., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Tuberculosis (TB) is a major health threat for humans and for non-human primates used for toxicology or research purposes. Emerging mycobacterial species represent a major challenge for diagnosis and surveillance programs. Here, we report a natural outbreak of Mycobacterium caprae in imported cynomolgus macaques ( Macaca fascicularis ) that occurred at AnaPath Research S.A.U. (APR). The macaques underwent repeated negative intradermal tuberculin tests (IDT) before importation and at the European quarantine station. Exhaustive TB screening was started at APR after confirmation of one positive case at another facility. The animal in question belonged to the same colony received at APR. Diagnostic approaches included clinical examination, PCR, culture, spoligotyping, IDT testing, interferon-γ release assay (IGRA), and thoracoabdominal ultrasound (US). Three regulatory toxicity studies and stock animals were affected. The macaques lacked clinical signs, except for one showing a fistulizing nodule in the right inguinal area, which tested positive for the Mycobacterium tuberculosis complex by PCR. All animals were necropsied and 10 macaques (n=114) showed gross and histologic findings compatible with TB confirmed by PCR and culture. M. caprae was identified as the etiological agent by Direct Variable Repeat spacer oligonucleotide typing (DVR spoligotyping). The infection was traced to Asia via the SB1622 spoligotype involved, confirming that the animals were infected prior to their import into Europe. Tuberculin skin test (TST), IGRA, and US were only sensitive in detecting advanced cases of M. caprae infection. One staff member showed a positive TST reaction, which was handled in accordance with the Spanish government's health regulations. All the sanitary measures implemented were effective in eradicating the disease., Competing Interests: There are no conflicts of interest for the coauthors from APR or APS, and the CRO wants to publish information on the scope of such a dangerous infection and how to deal with it. The co-authors of the Secció de Ramaderia i Sanitat Animal de Barcelona Catalunya and CReSA do not have a COI. R. Hartelust, CEO of the affected quarantine station, was interested in publishing data on the damage caused., (©2024 The Japanese Society of Toxicologic Pathology.)

Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1)., Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients., Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%-90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23-6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups., Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients., Competing Interests: One or more of the authors declare financial or professional relationships on ICMJE-NASSJ disclosure forms., (© 2024 The Author(s).)

Objectives: The aim of this study was to a) explore barriers and facilitators associated with medication-taking habit formation, and b) elicit feedback on the components of an intervention designed to help form strong habits for long-term medication adherence., Design: The study design was qualitative; we conducted semistructured interviews between September 2021 and February 2022., Setting: The interviews were conducted online, with 27 participants recruited at the Cedars-Sinai Medical Center in Los Angeles, California., Participants: A purposive sample of 20 patients who were over 18 years of age, had been diagnosed with hypertensive disorder (or reported high blood pressure; >140/90 mm Hg) and who were prescribed antihypertensive therapy at the time of recruitment, along with seven providers were interviewed., Results: Contextual factors included frequent changes to prescription for regimen adjustment, and polypharmacy. Forgetfulness, perceived need for medication, and routine disruptions were identified as possible barriers to habit formation. Facilitators of habit formation included identification of stable routines for anchoring, planning, use of external reminders (including visual reminders) and pillboxes for prescription management, and extrinsic motivation for forming habits. Interestingly, experiencing medication side effects was identified as a possible barrier and a possible facilitator of habit formation. Feedback on study components included increasing text size, and visual appeal of the habit leaflet; and imparting variation in text message content and adjusting their frequency to once a day. Patients generally favoured the use of conditional financial incentives to support habit formation., Conclusion: The study sheds light on some key considerations concerning the contextual factors for habit formation among people with hypertension. As such, future studies may evaluate the generalisability of our findings, consider the role of visual reminders in habit formation and sustenance, and explore possible disruptions to habits., Trial Registration Number: NCT04029883., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Spinal cord stimulation (SCS) provides pain relief for some patients with persistent spinal pain syndrome type 2 (PSPS 2), but the precise mechanisms of action and prognostic factors for a favorable pain response remain obscure. This in vivo human genome-wide association study provides some pathophysiological clues., Methods: We performed a high-density oligonucleotide microarray analysis of serum obtained from both PSPS 2 cases and pain-free controls who had undergone lower back spinal surgery at the study site. Using multivariate discriminant analysis, we tried to identify different expressions between mRNA transcripts from PSPS 2 patients relative to controls, SCS responders to non-responders, or SCS responders to themselves before starting SCS. Gene ontology enrichment analysis was used to identify the biological processes that best discriminate between the groups of clinical interest., Results: Thirty PSPS 2 patients, of whom 23 responded to SCS, were evaluated together with 15 pain-free controls. We identified 11 significantly downregulated genes in serum of PSPS 2 patients compared with pain-free controls and two significantly downregulated genes once the SCS response became apparent. All were suggestive of enhanced inflammation, tissue repair mechanisms and proliferative responses among the former. We could not identify any gene differentiating patients who responded to SCS from those who did not respond., Conclusions: This study points out various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response, inflammation and restorative processes., Competing Interests: Competing interests: RV, MD, PhD: Consultant for Medtronic., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Death initiates a cascade of physiological and biochemical alterations in organs and tissues, resulting in microscopic changes that challenge the histopathological evaluation. Moreover, the brain is particularly susceptible to artifacts owing to its unique composition and its location within the cranial vault. The aim of this study was to compile and illustrate the microscopic changes in the central nervous system (CNS) of rats subjected to delayed postmortem fixation. It also scrutinizes the influence of exsanguination and cooling methods on the initiation and progression of these alterations. Twenty-four Wistar Han outbred rats (RccHan ™ : WIST) were sacrificed and stored either at room temperature (18-22°C) or under refrigeration (2-4°C). Necropsies were conducted at different time points postmortem (i.e., 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h, 36 h, 48 h, 7 days and 14 days). Brain sections underwent simultaneous digital evaluation by 14 pathologists until a consensus was reached on terminology, key findings, and intensity levels. Microscopic observations varied among cell types. Glial cells were similarly affected throughout the CNS and showed pericellular halo, chromatin condensation and nuclear shrinkage. Neurons showed two types of postmortem changes as most of them showed progressive shrinkage, cytoplasmic dissolution and karyorrhexis whereas others acquired a dark-neuron-like appearance. Neuronal changes showed marked differences among neuroanatomical locations. Additional postmortem changes encompassed: granulation and microcavitation in neuropil and white matter; retraction spaces; detachment of ependyma, choroid plexus, and leptomeninges. Severity of findings after 48 h at room temperature was higher than after seven days under refrigeration and similar to or slightly lower than after 14 days under refrigeration. No clear differences were observed related to the sex or weight of the animals or their exsanguination status. This work elucidates the onset and progression of autolytic changes in the brains of Wistar Han rats, offering insights to accurately identify and enhance the histopathological evaluation., Competing Interests: Authors KW, KK, RK, YO, PO, LP, TR, OR, RS, NW, RV, RD were employed by AnaPath Services GmbH. Authors AD, FM, RS were employed by AnaPath Research S.A.U., (Copyright © 2024 Weber, Domènech, Kegler, Kreutzer, Mayoral, Okazaki, Ortega, Polledo, Razinger, Richard, Sanchez, Warfving, Vallejo and de Miguel.)

Background: There are limited therapeutic options to treat complex regional pain syndrome (CRPS). Spinal cord stimulation and dorsal root ganglion stimulation are proven therapies for treating chronic low limb pain in CRPS patients. There is limited evidence that stimulation of dorsal nerve roots can also provide relief of lower limb pain in these patients., Objectives: To demonstrate that electrical stimulation of dorsal nerve roots via epidural lead placement provides relief of chronic lower limb pain in patients suffering from CRPS., Study Design: Prospective, open label, single arm, multi-center study., Setting: The study was performed at the Center for Interventional Pain and Spine (Exton, PA), Millennium Pain Center (Bloomington, IL), and the Carolinas Pain Center (Huntersville, NC). It was approved by the Western Institutional Review Board-Copernicus Group Institutional Review Board and is registered at clinicaltrials.gov (NCT03954080)., Methods: Sixteen patients with intractable chronic severe lower limb pain associated with CRPS were enrolled in the study. A standard trial period to evaluate a patients' response to stimulation of the dorsal nerve roots was conducted over 3 to 10-days. Patients that obtained 50% or greater pain relief during the trial period underwent permanent implantation of a neurostimulation system. The primary outcome was the evaluated pain level after 3 months of device activation, based on NRS pain score relative to baseline. Patients were followed up for 6 months after activation of the permanently implanted system., Results: At the primary endpoint, patients reported a significant (P = 0.0006) reduction in pain of 3.3 points, improvement in quality of life, improved neuropathic pain characteristics, improved satisfaction, and an overall perception of improvement with the therapy. Improvements were sustained throughout the duration of the study up to the final 6-month visit., Limitations: Due to the COVID-19 pandemic occurring during patient enrollment, only 16 patients were enrolled and trialed, with 12 being permanently implanted. Nine were able to complete the end of study evaluation at 6 months., Conclusions: The results of this short feasibility study confirm the functionality, effectiveness, and safety of intraspinal stimulation of dorsal nerve roots in patients with intractable chronic lower limb pain due to CRPS using commercially approved systems and conventional parameters.

Within the realm of archaeology, the analysis of biomolecules assumes significant importance in elucidating historical dietary patterns and their implications for contemporary contexts. To achieve this, knowledge and tools of both chemistry and archaeology are essential to yield objective outcomes and conduct analyses of archaeological materials for the detection of biomolecules. Usually, only minuscule remnants of ceramic fragments are retrieved from excavations, which limits the feasibility of comprehensive laboratory analysis. This study aimed to establish a protocol for analyzing fatty acids and starch from archaeological food utensils with minimal sample quantities. Various experiments were conducted to replicate preparations that might have occurred in archaeological vessels, aiming to establish the optimal protocol. The analyses were performed using clay griddles, subjecting vegetable oil to varying temperatures for fatty acid assessment. For starch analysis, a series of experiments encompassed diverse forms of potato preparations (pulp, chuño , tortilla, carbonization, and freeze-drying) and maize (flour, tortilla, and carbonization). The verification of the experiments was confirmed by conducting identical analyses, as developed in the current study, on authentic archaeological fragments. The principal outcomes of this investigation include the successful extraction of both types of biomolecules using only 0.25 g of the sample, obtained through direct scraping from the vessel. Soxhlet extraction was identified as the most efficient strategy to recover fatty acids. Additionally, a comprehensive protocol for the identification of starch extraction was developed. This study has, for the first time, elucidated two detailed methodologies for the extraction of fatty acids and starch in scenarios in which researchers can obtain limited quantities of archaeological food utensil fragments.

Glomus tumors are a rare, benign neoplasm arising from the neuroarterial structure known as the glomus body, which is a specialized arteriovenous shunt involved in temperature regulation. They account for less than 2% of soft tissue tumors and between 1% and 4.5% of tumors in the hand.. Despite their first descriptions appearing almost 100 years ago, late and missed diagnoses are common, leading to significant suffering. The classic diagnostic triad includes spontaneous pain, a sensation of pressure and tenderness, and cold hypersensitivity. Magnetic resonance imaging remains the most useful imaging modality. The abolition of pain after inflating a blood pressure cuff above the systolic blood pressure level (ischemia test) is highly diagnostic.Therefore, we suggest the routine use of this simple test in cases of upper limb pain of unclear etiology . Surgical excision is the treatment of choice and is curative., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Introduction: Low back pain is the leading cause of disability worldwide, with sacroiliac joint pain comprising up to 30% of cases of axial lower back pain. Conservative therapies provide only modest relief. Although placebo-controlled trials show efficacy for sacral lateral branch cooled radiofrequency ablation, there are no comparative effectiveness studies., Methods: In this randomized, multicenter comparative effectiveness study, 210 patients with clinically suspected sacroiliac joint pain who obtained short-term benefit from diagnostic sacroiliac joint injections and prognostic lateral branch blocks were randomly assigned to receive cooled radiofrequency ablation of the L5 dorsal ramus and S1-S3 lateral branches or standard medical management consisting of pharmacotherapy, injections and integrative therapies. The primary outcome measure was mean reduction in low back pain score on a 0-10 Numeric Rating Scale at 3 months. Secondary outcomes included measures of quality of life and function., Results: 3 months post-treatment, the mean Numeric Rating Scale pain score for the cooled radiofrequency ablation group was 3.8±2.4 (mean reduction 2.5±2.5) compared with 5.9±1.7 (mean reduction 0.4±1.7) in the standard medical management group (p<0.0001). 52.3% of subjects in the cooled radiofrequency ablation group experienced > 2 points or 30% pain relief and were deemed responders versus 4.3% of standard medical management patients (p<0.0001). Comparable improvements favoring cooled radiofrequency ablation were noted in Oswestry Disability Index score (mean 29.7±15.2 vs 41.5+13.6; p<0.0001) and quality of life (mean EuroQoL-5 score 0.68±0.22 vs 0.47±0.29; p<0.0001)., Conclusions: In patients with sacroiliac joint pain, cooled radiofrequency ablation provided statistically superior improvements across the spectrum of patient outcomes compared with standard medical management., Trial Registration Number: NCT03601949., Competing Interests: Competing interests: All authors received institutional research funding. SPC, LKa, LKo, SL, DPB and MJD are consultants for Avanos (which makes radiofrequency equipment). Currently, SPC is the editorial board member of RAPM., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)