Post-Covid Conditions and their Effects on the Cardiovascular System.

Background: Rising global concerns about COVID-19 recently gained more research attention due to the ease of person-to-person transmission, various symptoms after healing, and the shortage of effective antiviral therapy. The study aims to analyze post-COVID conditions and clinical manifestations of cardiovascular lesions in patients recovering from COVID-19 infection. Methods: A practical examination of post-COVID conditions manifestation was conducted in a prospective cohort study, involving 250 patients diagnosed with COVID-19 between June 1, 2021, and August 31, 2021. The study specifically focused on analyzing the cardiovascular effects of COVID-19, utilizing data from a subgroup of 200 patients previously discharged from the hospital with elevated troponin levels. The cardiovascular variables assessed included tachycardia, ischemia, heart attack, myocarditis, hypertension, blood clots, and heart failure. Results: It has been observed that among surviving patients, the following symptoms persisted: anosmia/ageusia (59%), severe dyspnea (36.7%), palpitations and complaints related to the cardiovascular sys-tem (15.8%), headaches (13.2%), arthralgia (11.7%), myalgia (9.8%), and hair problems (≥5%). By the 60th day, a reduction in symptoms by 5-10% was noted, and by the 90th day, a decrease in activity by 25-35% was observed. Patients aged 40-60 years exhibited the highest percentage of cardiovascular diseases (75%). Conclusions: Consequently, the SARS-CoV-2 virus underscores the critical importance of cardiological attention in patient care. Cardiac screening results in individuals with COVID-19 reveal a significant prevalence of serious heart problems, affecting over half of the patients. This emphasizes the necessity for heightened vigilance and specialized cardiac care when managing patients with COVID-19.

Effect of a graded running race on lower limb muscle damage, jump performance and muscle soreness in men and women.

PURPOSE: Delayed structural and functional recovery after a 20 km graded running race was analyzed with respect to the sex effect. METHODS: Thirteen female and 14 male recreational runners completed the race and three test sessions: one before (PRE) and two after, once on Day 1 or 2 (D1-2) and then on Day 3 or 4 (D3-4). Muscle damage was assessed indirectly using ultrasonography to quantify changes in cross-sectional area (CSA) of 10 lower-limb muscles. Delayed onset of muscle soreness (DOMS) was assessed for three muscle groups. Functional recovery was quantified by kinetic analysis of a squat jump (SJ) and a drop jump (DJ) test performed on a sledge ergometer. Linear mixed models were used to assess control group reproducibility and recovery patterns according to sex. RESULTS: Regardless of sex, DOMS peaked at D1-2 for all muscle groups and resolved at D3-4. CSA was increased in each muscle group until D3-4, especially in the semimembranosus muscle. A specific increase was found in the short head of the biceps femoris in women. Regardless of sex, SJ and DJ performances declined up to D3-4. Depending on the muscle, positive and/or negative correlations were found between structural and functional changes. Some of these were sex-specific. CONCLUSION: Structural and functional recovery was incomplete in both sexes up to D3-4, although DOMS had disappeared. More emphasis should be placed on hamstring muscle recovery. Highlighting the intermuscular compensations that can occur during multi-joint testing tasks, the structural-functional relationships were either positive or negative, muscle- and sex-dependent.

Recognizing Myopathy in Patients with Muscle Weakness or Pain.

Muscle weakness and pain can be seen in orthopedic, rheumatologic, cardiac, and musculoskeletal conditions in addition to neurologic disorders. Myopathy, which describes a heterogenous group of hereditary and acquired disorders that affect muscle channels, structure, and metabolism, is one possible cause. This review focuses on essential information to support primary care providers as they assess patients with muscle weakness and pain for myopathy. As with most neurologic disorders, a thorough clinical history and physical examination are essential first steps. These findings will then guide diagnostic testing and facilitate appropriate management or referral for further neuromuscular care.

Effects of far-infrared radiation lamp therapy on recovery from a simulated soccer-match in elite female soccer players.

We investigated the effects of far-infrared radiation (FIR) lamp therapy on changes in muscle damage and performance parameters following six sets of 15-min Loughborough intermittent shuttle test (LIST), a simulated soccer match. Twenty-four elite female soccer players (20-24 y) were assigned into FIR or sham treatment group (n = 12/group). The participants received a 60-min FIR or sham treatment (30 min per muscle) over knee extensors (KE) and flexors (KF) at 2, 25, 49, 73, and 97 h post-LIST. Maximal voluntary isometric contraction (MVC) torque and muscle soreness of the KE and KF, plasma creatine kinase (CK) activity as muscle damage markers, and several performance parameters including countermovement jump (CMJ) and Yo-Yo intermittent recovery test level 1 (YYIR1) were measured before and 1, 24, 48, 72, 96, and 120 h post-LIST. Changes in the measures were compared between groups by a mixed-design two-way ANOVA. The running distance covered during LIST and changes in the measures at 1-h post-LIST (before the treatment) were similar (p = 0.118-0.371) between groups. Changes in muscle damage markers at 24-120 h post-LIST were smaller (p < 0.05, η2 = 0.208-0.467) for the FIR (e.g., MVC-KE torque decrease at 48-h post-LIST: -1 ± 2%, peak KE soreness: 16 ± 10 mm, peak CK: 172 ± 42 IU/L) than sham group (-11 ± 9%, 33 ± 7 mm, 466 ± 220 IU/L, respectively). Performance parameters recovered faster (p < 0.05, η2 = 0.142-0.308) to baseline for the FIR (e.g., decreases at 48-h post-LIST; CMJ: 0 ± 1%, YYIR1: 0 ± 1%) than sham group (-6 ± 2%, -9 ± 6%, respectively). These results suggest that the FIR lamp therapy was effective for enhancing recovery from a soccer match.

Healthcare experiences of fibromyalgia patients and their associations with satisfaction and pain relief. A patient survey.

OBJECTIVES: The etiology of fibromyalgia (FM) is disputed, and there is no established cure. Quantitative data on how this may affect patients' healthcare experiences are scarce. The present study aims to investigate FM patients' pain-related healthcare experiences and explore factors associated with high satisfaction and pain relief. METHODS: An anonymous, online, and patient-administered survey was developed and distributed to members of the Norwegian Fibromyalgia Association. It addressed their pain-related healthcare experiences from both primary and specialist care. Odds ratios for healthcare satisfaction and pain relief were estimated by binary logistic regression. Directed acyclic graphs guided the multivariable analyses. RESULTS: The patients (n = 1,626, mean age: 51 years) were primarily women (95%) with a 21.8-year mean pain duration and 12.7 years in pain before diagnosis. One-third did not understand why they had pain, and 56.6% did not know how to get better. More than half had not received satisfactory information on their pain cause from a physician, and guidance on how to improve was reported below medium. Patients regretted a lack of medical specialized competence on muscle pain and reported many unmet needs, including regular follow-up and pain assessment. Physician-mediated pain relief was low, and guideline adherence was deficient. Only 14.8% were satisfied with non-physician health providers evaluating and treating their pain, and 21.5% were satisfied (46.9% dissatisfied) with their global pain-related healthcare. Patients' knowledge of their condition, physicians' pain competence and provision of information and guidance, agreement in explanations and advice, and the absence of unmet needs significantly increased the odds of both healthcare satisfaction and pain relief. CONCLUSIONS: Our survey describes deficiencies in FM patients' pain-related healthcare and suggests areas for improvement to increase healthcare satisfaction and pain relief. (REC# 2019/845, 09.05.19).

Immunogenicity and safety of SARS-CoV-2 recombinant protein subunit vaccine (IndoVac) adjuvanted with alum and CpG 1018 in Indonesian adults: A phase 3, randomized, active-controlled, multicenter trial.

BACKGROUND: Bio Farma has developed a recombinant protein subunit vaccine (IndoVac) that is indicated for active immunization in population of all ages. This article reported the results of the phase 3 immunogenicity and safety study in Indonesian adults aged 18 years and above. METHODS: We conducted a randomized, active-controlled, multicenter, prospective intervention study to evaluate the immunogenicity and safety of IndoVac in adults aged 18 years and above. Participants who were SARS-CoV-2 vaccine-naïve received two doses of either IndoVac or control (Covovax) with 28 days interval between doses and were followed up until 12 months after complete vaccination. RESULTS: A total of 4050 participants were enrolled from June to August 2022 and received at least one dose of vaccine. The geometric mean ratio (GMR) of neutralizing antibody at 14 days after the second dose was 1.01 (95 % confidence interval (CI) 0.89-1.16), which met the WHO non-inferiority criteria for immunobridging (95 % CI lower bound > 0.67). The antibody levels were maintained through 12 months after the second dose. The incidence rate of adverse events (AEs) were 27.95 % in IndoVac group and 32.15 % in Covovax group with mostly mild intensity (27.70 %). The most reported solicited AEs were pain (14.69 %) followed by myalgia (7.48 %) and fatigue (6.77 %). Unsolicited AEs varied, with each of the incidence rate under 5 %. There were no serious AEs assessed as possibly, probably, or likely related to vaccine. CONCLUSIONS: IndoVac in adults showed favourable safety profile and elicited non-inferior immune response to Covovax. (ClinicalTrials.gov: NCT05433285, Indonesian Clinical Research Registry: INA-R5752S9).

Effects of triceps surae exercise-induced delayed onset muscle soreness on control of body stability in different postures.

This research aimed to determine whether triceps surae delayed onset muscle soreness (DOMS) affects stability while performing different postural control tasks requiring upright and landing stabilization. Twenty-four participants who self-reported as healthy were recruited. Pre and 48 h after a protocol to induce DOMS in the triceps surae, participants were evaluated for DOMS perception, pressure pain threshold, and postural control (assessed by the center of pressure, CoP) during different standing and landing stabilization tasks. We found higher DOMS perception and lower pressure pain threshold 48 h after the exercise. Mediolateral CoP displacement was more sensitive to DOMS across different postural tasks, but no effects were found for bilateral standing. The landing time to stabilization elicited high individual variability in the presence of DOMS. Effects of DOMS in the performance of less challenging tasks, such as bipedal standing, were not found. We conclude that DOMS in the triceps surae impairs mediolateral postural control during challenging tasks such as unilateral standing and body forward lean. It highlights the need for caution and individualized approaches when incorporating movements requiring frontal plane control in training and rehabilitation sessions under the presence of DOMS.

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition: A Randomized Crossover Clinical Trial.

Importance: Many patients with post-COVID condition (PCC) experience persistent fatigue, muscle pain, and cognitive problems that worsen after exertion (referred to as postexertional malaise). Recommendations currently advise against exercise in this population to prevent symptom worsening; however, prolonged inactivity is associated with risk of long-term health deterioration. Objective: To assess postexertional symptoms in patients with PCC after exercise compared with control participants and to comprehensively investigate the physiologic mechanisms underlying PCC. Design, Setting, and Participants: In this randomized crossover clinical trial, nonhospitalized patients without concomitant diseases and with persistent (≥3 months) symptoms, including postexertional malaise, after SARS-CoV-2 infection were recruited in Sweden from September 2022 to July 2023. Age- and sex-matched control participants were also recruited. Interventions: After comprehensive physiologic characterization, participants completed 3 exercise trials (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order. Symptoms were reported at baseline, immediately after exercise, and 48 hours after exercise. Main Outcomes and Measures: The primary outcome was between-group differences in changes in fatigue symptoms from baseline to 48 hours after exercise, assessed via the visual analog scale (VAS). Questionnaires, cardiopulmonary exercise testing, inflammatory markers, and physiologic characterization provided information on the physiologic function of patients with PCC. Results: Thirty-one patients with PCC (mean [SD] age, 46.6 [10.0] years; 24 [77%] women) and 31 healthy control participants (mean [SD] age, 47.3 [8.9] years; 23 [74%] women) were included. Patients with PCC reported more symptoms than controls at all time points. However, there was no difference between the groups in the worsening of fatigue in response to the different exercises (mean [SD] VAS ranks for HIIT: PCC, 29.3 [19.5]; controls, 28.7 [11.4]; P = .08; MICT: PCC, 31.2 [17.0]; controls, 24.6 [11.7]; P = .09; ST: PCC, 31.0 [19.7]; controls, 28.1 [12.2]; P = .49). Patients with PCC had greater exacerbation of muscle pain after HIIT (mean [SD] VAS ranks, 33.4 [17.7] vs 25.0 [11.3]; P = .04) and reported more concentration difficulties after MICT (mean [SD] VAS ranks, 33.0 [17.1] vs 23.3 [10.6]; P = .03) compared with controls. At baseline, patients with PCC showed preserved lung and heart function but had a 21% lower peak volume of oxygen consumption (mean difference: -6.8 mL/kg/min; 95% CI, -10.7 to -2.9 mL/kg/min; P < .001) and less isometric knee extension muscle strength (mean difference: -37 Nm; 95% CI, -67 to -7 Nm; P = .02) compared with controls. Patients with PCC spent 43% less time on moderate to vigorous physical activity (mean difference, -26.5 minutes/d; 95% CI, -42.0 to -11.1 minutes/d; P = .001). Of note, 4 patients with PCC (13%) had postural orthostatic tachycardia, and 18 of 29 (62%) showed signs of myopathy as determined by neurophysiologic testing. Conclusions and Relevance: In this study, nonhospitalized patients with PCC generally tolerated exercise with preserved cardiovascular function but showed lower aerobic capacity and less muscle strength than the control group. They also showed signs of postural orthostatic tachycardia and myopathy. The findings suggest cautious exercise adoption could be recommended to prevent further skeletal muscle deconditioning and health impairment in patients with PCC. Trial Registration: ClinicalTrials.gov Identifier: NCT05445830.

[Neurotrophin-associated mechanisms of delayed-onset muscle soreness: research progress and perspective].

Delayed-onset muscle soreness (DOMS) is a common phenomenon that occurs following a sudden increase in exercise intensity or unfamiliar exercise, significantly affecting athletic performance and efficacy in athletes and fitness individuals. DOMS is characterized by allodynia and hyperalgesia, and their mechanisms remain unclear. Recent studies have reported that neurotrophic factors, such as nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF), are involved in the development and maintenance of DOMS. This article provides a review of the research progress on the signaling pathways related to the involvement of NGF and GDNF in DOMS, hoping to provide novel insights into the mechanisms underlying allodynia and hyperalgesia in DOMS, as well as potential targeted treatment.

Pregabalina preoperatoria previene las fasciculaciones y mialgias inducidas por succinilcolina: metaanálisis de ensayos aleatorizados / Preoperative pregabalin prevents succinylcholine-induced fasciculations and myalgias: A meta-analysis of randomized trials

La succinilcolina es el bloqueador neuromuscular de referencia para la inducción de secuencia rápida. Sin embargo, su uso se asocia a fasciculaciones y mialgias. Se realizó una revisión sistemática y un metaanálisis. Se incluyeron ensayos clínicos controlados aleatorizados comparando gabapentinoides frente a placebo, para la prevención de fasciculaciones y mialgias inducidas por succinilcolina. Se incluyeron seis estudios clínicos aleatorizados. El número total de pacientes fue de 481, de los cuales 241 se incluyeron en el grupo de intervención y 240 en el grupo de placebo. Los gabapentinoides redujeron la incidencia de mialgia inducida por succinilcolina (RR=0,69; IC95%: 0,56-0,84; p<0,001), que siguió siendo estadísticamente significativa para pregabalina (RR=0,71; IC95%: 0,54-0,93; p=0,013) y gabapentina (RR=0,61; IC95%: 0,45-0,82; p=0,001) por separado. No hubo diferencia entre los grupos en cuanto a fasciculaciones (RR=0,92; IC95%: 0,82-1,03; p=0,148). El uso preoperatorio de gabapentinoides se asocia a una menor incidencia de mialgias inducidas por succinilcolina dentro de las primeras 24horas posteriores al procedimiento. (AU)

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction, however, its use is associated with fasciculations and myalgias. A systematic review and meta-analysis including randomized controlled clinical trials was performed comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included. The total number of patients was 481, of which 241 were in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR=.69; 95%CI: .56-.84; P<.001), which remained statistically significant for pregabalin (RR=.71; 95%CI: .54-.93; P=.013) and gabapentin (RR=.61; 95%CI: .45-.82; P=.001) separately. There was no difference between the groups in fasciculations (RR=.92; 95%CI: .82-1.03; P=.148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24hours after the procedure. (AU)

Genetic Variations in Susceptibility to Traumatic Muscle Injuries and Muscle Pain among Brazilian High-Performance Athletes.

Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes' performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (ACTN3 rs1815739, FAAH rs324420, PPARGC1A rs8192678, ADRB2 rs1042713, NOS3 rs1799983, and VDR rs731236), none was significantly associated with TMI. Regarding MP after exercise, ACTN3 rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01-3.57) and FAAH rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08-4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of ACTN3 rs1815739 and FAAH rs324420. This could have implications for prophylactic interventions to improve athletes' quality of life.

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

Recovery following exercise-induced fatigue: Influence of a single heart rate clamped cycling session under systemic hypoxia.

We investigated whether a single heart rate clamped cycling session under systemic hypoxia affects the recovery of physical and psycho-physiological responses from residual fatigue compared to normoxia. On separate occasions, twelve trained males performed a 3-d acute training camp scenario. On days 1 and 3, participants cycled for 60 min at a constant heart rate (80% of ventilatory threshold). On day 2, fatigue was induced through a simulated team game circuit (STGC), followed by a 60-min intervention of either: (1) heart rate clamped cycling in normoxia; (2) heart rate clamped cycling in hypoxia (simulated altitude ~ 3500 m); or (3) no cycling. Countermovement jump height and leg stiffness were assessed before and after every session. Perceptual fatigue was evaluated daily. Compared to baseline, jump height decreased at all timepoints following the STGC (all p < 0.05). Leg stiffness and cycling power output only decreased immediately following the STGC, with a 48% further decrease in cycling power output in hypoxia compared to normoxia (p < 0.05). Perceived fatigue, decreased sleep quality, and increased muscle soreness responses occurred on day 3 (p < 0.05). A single heart rate-clamped cycling session in hypoxia reduced mechanical output without affecting recovery of physical performance and perceptual measures from residual fatigue induced through team sport activity.

Venlafaxine-Associated Rhabdomyolysis: A Literature Review.

PURPOSE: This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis. METHODS: A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine. RESULTS: A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care. CONCLUSIONS: Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.

Temporomandibular involvement in children and adolescents with juvenile idiopathic arthritis: a 2-year prospective cohort study.

This study aimed to clinically evaluate temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) and the ability to identify and/or predict development of TMJ-deformities over time using cone beam computed tomography (CBCT). The predictive value of self-reported TMJ pain was also assessed. A prospective longitudinal cohort study comprising 54 children with JIA, 39 girls and 15 boys, was performed. All children had active disease at baseline, 50% with the subtype oligoarthritis. Repeated clinical orofacial and CBCT examinations were performed over a two-year period. At baseline, 39% had radiographic TMJ deformities (24% unilateral, 15% bilateral), at 2-year follow-up, 42% (p > 0.05). Both progressing and improving TMJ deformities were observed. An association was found between TMJ-deformities and self-reported TMJ pain at baseline (p = 0.01). Maximum unassisted mouth opening (MUO) was smaller for children with TMJ-deformities (p < 0.05). The prevalence of palpatory muscle pain was high (48-59%) but not predictive of development of TMJ-deformities. TMJ noises increased over time and crepitations were associated with TMJ-deformities (p < 0.05). In conclusion, in children with JIA, self-reported TMJ pain and dysfunction were common and predictive of TMJ deformities. TMJ deformities were associated with smaller MUO and palpatory TMJ pain as well as crepitations. Trial registration. ClinicalTrials.gov Protocol id: 2010/2089-31/2.

Safety of an inactivated COVID-19 vaccine (CoronaVac) in children aged 7-14 years in Taizhou, China.

Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children.

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

A taxonomy of threat and soothing influences in rheumatic and musculoskeletal diseases and central sensitivity syndromes / Una taxonomía de amenazas e influencias calmantes en enfermedades reumáticas y musculoesqueléticas y síndromes de sensibilidad central

Background: An imbalance in affect regulation, reflected by a hyperactive threat system and hypoactive soothing system, may impact physical symptoms in people with rheumatic and musculoskeletal diseases (RMD) and central sensitivity syndromes (CSS), including chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome. This study aimed to identify and structure comprehensive overviews of threat and soothing influences that may worsen or alleviate physical symptoms in people with RMD or CSS. Method: A concept mapping procedure was used. An online open-question survey (N = 686, 641 [93.4%] women) yielded comprehensive sets of 40 threats and 40 soothers that were individually sorted by people with RMD or CSS (N = 115, 112 [97.4%] women). Results: Hierarchical cluster analyses generated eight threat clusters: environmental stimuli, physical symptoms, food and drugs, inactivity, demands, effort, invalidation, and emotional stress. Ten soother clusters were identified: social emotional support, rest and balance, pleasant surroundings, illness understanding, positive mindset and autonomy, spirituality, leisure activity, wellness, treatment and care, and nutrition and treats. Conclusions: Our study provided a comprehensive taxonomy of threats and soothers in people with RMD or CSS. The results can be used in experimental research to label threat and soothing stimuli and in clinical practice to screen and monitor relevant treatment targets.(AU)

Effects of Percussive Massage Treatments on Symptoms Associated with Eccentric Exercise-Induced Muscle Damage.

Percussive massage (PM) is an emerging recovery treatment despite the lack of research on its effects post-eccentric exercise (post-EE). This study investigated the effects of PM treatments (immediately, 24, 48, and 72 h post-EE) on the maximal isometric torque (MIT), range of motion (ROM), and an 11-point numerical rating scale (NRS) of soreness of the nondominant arm's biceps brachii from 24-72 h post-EE. Seventeen untrained, college-aged subjects performed 60 eccentric elbow flexion actions with their nondominant arms. Nine received 1 minute of PM, versus eight who rested quietly (control [CON]). In order, NRS, ROM, and MIT (relative to body mass) were collected pre-eccentric exercise (pre-EE) and after treatment (AT) at 24, 48, and 72 h post-EE. NRS was also collected before treatment (BT). Electromyographic (EMG) and mechanomyographic (MMG) amplitudes were collected during the MIT and normalized to pre-EE. There were no interactions for MIT, EMG, or MMG, but there were interactions for ROM and NRS. For ROM, the PM group had higher values than the CON 24-72 h by ~6-8°, a faster return to pre-EE (PM: 48 h, CON: 72 h), and exceeded their pre-EE at 72 h by ~4°. The groups' NRS values did not differ BT 24-72 h; however, the PM group lowered their NRS from BT to AT within every visit by ~1 point per visit, which resulted in them having lower values than the CON from 24-72 h by ~2-3 points. Additionally, the PM group returned their NRS to pre-EE faster than the CON (PM: BT 72 h, CON: never). In conclusion, PM treatments may improve ROM without affecting isometric strength or muscle activation 24-72 h post-EE. Although the PM treatments did not enhance the recovery from delayed onset muscle soreness until 72 h, they consistently provided immediate, temporary relief when used 24-72 h post-EE.