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The charge radius of the proton, the simplest nucleus, is known from electron-scattering experiments only with a surprisingly low precision of about 2%. The poor knowledge of the proton charge radius restricts tests of bound-state quantum electrodynamics (QED) to the precision level of about 6 × 10 –6 , although the experimental data themselves (1S Lamb shift in hydrogen) have reached a precision of 2 × 10 –6 . The determination of the proton charge radius with an accuracy of 10 –3 is the main goal of our experiment, opening a way to check bound-state QED predictions to a level of 10 –7 . The principle is to measure the 2S–2P energy difference in muonic hydrogen (µ – p) by infrared laser spectroscopy. The first data were taken in the second half of 2003. Muons from our unique very-low-energy muon beam are stopped at a rate of ~100 s –1 in 0.6 mbar H 2 gas where the lifetime of the formed µp(2S) atoms is about 1.3 µs. An incoming muon triggers a pulsed multistage laser system that delivers ~0.2 mJ at λ ≈ 6 µm. Following the laser excitation µp(2S) → µp(2P) we observe the 1.9 keV X-rays from 2P–1S transitions using large area avalanche photodiodes. The resonance frequency, and, hence, the Lamb shift and the proton radius, is determined by measuring the intensity of these X-rays as a function of the laser wavelength. A broad range of laser frequencies was scanned in 2003 and the analysis is currently under way. PACS Nos.: 36.10.Dr, 14.20.Dh, 42.62.Fi

Plague is a deadly zoonosis that still poses a threat in many regions of the world. We combined epidemiologic, host, and vector surveillance data collected during 1961-1980 from the Araripe Plateau focus in northeastern Brazil with ecologic, geoclimatic, and Yersinia pestis genomic information to elucidate how these factors interplay in plague activity. We identified well-delimited plague hotspots showing elevated plague risk in low-altitude areas near the foothills of the plateau's concave sectors. Those locations exhibited distinct precipitation and vegetation coverage patterns compared with the surrounding areas. We noted a seasonal effect on plague activity, and human cases linearly correlated with precipitation and rodent and flea Y. pestis positivity rates. Genomic characterization of Y. pestis strains revealed a foundational strain capable of evolving into distinct genetic variants, each linked to temporally and spatially constrained plague outbreaks. These data could identify risk areas and improve surveillance in other plague foci within the Caatinga biome.

In this set of four phase 1 studies, a recombinant vesicular stomatitis virus (rVSV)–based Ebola vaccine induced Ebola virus–specific immune responses and was associated with side effects that included fever and transient arthritis, rash, and VSV viremia. In August 2014, after the outbreak of Ebola virus disease was declared a public health emergency of international concern by the World Health Organization (WHO), the Canadian government donated 800 vials of the replication-competent recombinant vesicular stomatitis virus (rVSV)–vectored Zaire ebolavirus (rVSV-ZEBOV) candidate vaccine to the WHO. The VSV Ebola Consortium (VEBCON) was created under the auspices of the WHO to initiate phase 1 studies to facilitate rapid progression to phase 2 and 3 trials in affected countries. 1 Live replicating viral vaccines elicit humoral and cellular immune responses against viral pathogens. 2 , 3 A single injection of 10 million plaque-forming units . . .

The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV-GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study. Our data confirm the acceptable safety and immunogenicity profile of the 2 × 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. Pan African Clinical Trials Registry PACTR201411000919191.

Background Although clinical practice guidelines recommend pain education as the first-line option for the management of chronic musculoskeletal pain, there is a lack of pain education programmes in healthcare. Thus, digital health programmes can be an effective tool for implementing pain education strategies for public health. This trial will aim to analyse the implementation and effectiveness outcomes of three online pain science education strategies in the Brazilian public health system (SUS) for individuals with chronic musculoskeletal pain. Methods We will conduct a hybrid type III effectiveness-implementation randomised controlled trial with economic evaluation. We will include adult individuals with chronic musculoskeletal pain, recruited from primary healthcare in the city of Guarapuava, Brazil. Individuals will be randomised to three implementation groups receiving a pain science education intervention ( EducaDo r) but delivered in different modalities: group 1) synchronous online; group 2) asynchronous videos; and group 3) interactive e-book only. Implementation outcomes will include acceptability, appropriateness, feasibility, adoption, fidelity, penetration, sustainability, and costs. We will also assess effectiveness outcomes, such as pain, function, quality of life, sleep, self-efficacy, and adverse effects. Cost-effectiveness and cost-utility analyses will be conducted from the SUS and societal perspectives. The evaluations will be done at baseline, post-intervention (10 weeks), and 6 months. Discussion This study will develop and implement a collaborative intervention model involving primary healthcare professionals, secondary-level healthcare providers, and patients to enhance self-management of chronic pain. In addition to promoting better pain management, this study will also contribute to the field of implementation science in public health by generating important insights and recommendations for future interventions. Trial registration ClinicalTrials.gov (NCT05302180; 03/29/2022).

Background/Objectives: The acute phase of stroke is marked by inflammation and mobility changes that can compromise nutritional status. This study was a randomized, double-blind, placebo-controlled trial evaluating the effectiveness of creatine supplementation for older people during seven days of hospitalization for stroke compared to usual care. Method: The primary outcome measures were changes in functional capacity, strength, muscle mass, and muscle degradation. The secondary outcomes were changes in serum biomarkers related to inflammation, fibrosis, anabolism, and muscle synthesis. In addition, a follow-up 90 days after the stroke verified functional capacity, strength, quality of life, and mortality. Following admission for an acute stroke, participants received either creatine (10 g) or a visually identical placebo (10 g) orally twice daily. Both groups received supplementation with protein to achieve the goal of 1.5 g of protein/kg of body weight/day and underwent daily mobility training during seven days of hospitalization. Results: Thirty older people were included in two similar groups concerning baseline attributes (15—treatment/15—placebo). Conclusions: Creatine supplementation did not influence functional capacity, strength, or muscle mass during the first 7 days or outcomes 90 days after stroke. There were no serious adverse events associated with creatine supplementation. However, it decreased progranulin levels, raising a new possibility of creatine action. This finding needs further exploration to understand the biological significance of creatine–progranulin interaction.

Herein, we investigated the effect of fish oil supplementation combined with a strength-training protocol, for 6 weeks, on muscle damage induced by a single bout of strength exercise in untrained young men. Sixteen men were divided into two groups, supplemented or not with fish oil, and they were evaluated at the pre-training period and post-training period. We investigated changes before and 0, 24, and 48 h after a single hypertrophic exercise session. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities, plasma interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the redox imbalance were increased in response to the single-bout session of hypertrophic exercises at baseline (pre-training period) and decreased during the post-training period in the control group due to the repeated-bout effect (RBE). The fish oil supplementation exacerbated this reduction and improved the redox state. In summary, our findings demonstrate that, in untrained young men submitted to a strength-training protocol, fish oil supplementation is ideal for alleviating the muscle injury, inflammation, and redox imbalance induced by a single session of intense strength exercises, highlighting this supplementation as a beneficial strategy for young men that intend to engage in strength-training programs.

Background: Little has been reported in terms of clinical outcomes to confirm the benefits of nebulized bronchodilators during mechanical ventilation (MV). Electrical Impedance Tomography (EIT) could be a valuable method to elucidate this gap. Objective: The purpose of this study is to evaluate the impact of nebulized bronchodilators during invasive MV with EIT by comparing three ventilation modes on the overall and regional lung ventilation and aeration in critically ill patients with obstructive pulmonary disease. Method: A blind clinical trial in which eligible patients underwent nebulization with salbutamol sulfate (5 mg/1 mL) and ipratropium bromide (0.5 mg/2 mL) in the ventilation mode they were receiving. EIT evaluation was performed before and after the intervention. A joint and stratified analysis into ventilation mode groups was performed, with p < 0.05. Results: Five of nineteen procedures occurred in controlled MV mode, seven in assisted mode and seven in spontaneous mode. In the intra-group analysis, the nebulization increased total ventilation in controlled (p = 0.04 and ⅆ = 2) and spontaneous (p = 0.01 and ⅆ = 1.5) MV modes. There was an increase in the dependent pulmonary region in assisted mode (p = 0.01 and ⅆ = 0.3) and in spontaneous mode (p = 0.02 and ⅆ = 1.6). There was no difference in the intergroup analysis. Conclusions: Nebulized bronchodilators reduce the aeration of non-dependent pulmonary regions and increase overall lung ventilation but there was no difference between the ventilation modes. As a limitation, it is important to note that the muscular effort in PSV and A/C PCV modes influences the impedance variation, and consequently the aeration and ventilation values. Thus, future studies are needed to evaluate this effort as well as the time on ventilator, time in UCI and other variables.

Connective tissue graft (CTG), which is considered to be among the best techniques for treating gingival recession, has presented stable long-term results. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. A previous study reports that photobiomodulation (PBM) using a dosage of 15 J/cm 2 may improve wound healing and the patient’s postoperative comfort. However, no other studies in the literature provide the best application dosage or comparisons between protocols for this purpose. The aim of this study is to compare two power densities of PBM on the wound-healing process of the donor palatine area after CTG removal. In this study, 51 patients presenting buccal gingival recession were randomized into one of the following groups: group 1: CTG procedure for root coverage and PBM application at the donor site using a 60 J/cm 2 dose; group 2: CTG and PBM application using a 30 J/cm 2 dose; or group 3: CTG and sham application. The evaluated parameters were the wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D), evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Group 1 presented statistically significant smaller wounds at day 7 ( p  > 0.05). None of the patients presented scars at the operated area, and all of the patients reported mild discomfort, with low consumption of analgesic pills. We concluded that the protocol of 60 J/cm 2 provided faster wound healing 7 days after removing the connective tissue graft for root coverage. Trial registration: ClinicalTrial.org (NCT02580357) https://clinicaltrials.gov/ct2/show/NCT02580357 .

This study investigated the local effect of photobiomodulation (PBM) for the treatment of periodontal pockets in patients with periodontitis and type 2 diabetes. Thirty-eight periodontal pockets presenting probing depth (PD) and clinical attachment level (CAL) ≥ 5 mm were selected from 19 patients (two pockets/patient). The selected periodontal pockets were randomly assigned to receive mechanical debridement only (control group) or mechanical debridement with PBM (PBM group). Clinical measures, such as PD, CAL, bleeding on probing (BoP), and presence of supragingival biofilm (PI), were collected and compared at baseline, 3, 6, and 12 months. After 12 months, no statistically difference was observed for mean PD and mean CAL when control and PBM groups were compared. The frequency of pockets with PD 5–6 mm was significantly lower for the PBM group at 6 months when compared to the control group. Pockets with PD ≥ 7 mm changed significantly between baseline and 3, 6, and 12 months for the PBM group, while for the control group, statistical significance was only observed between baseline and 6 months. The PBM protocol used in this study did not provide significant changes for PD and CAL in periodontal pockets when compared to mechanical therapy only. However, PBM was more effective in reducing the percentage of moderate periodontal pockets at 6 months in patients with type 2 DM.