A RANDOMIZED CLINICAL TRIAL OF 2-WEEK METHOTREXATE DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS VACCINATED WITH INACTIVATED SARS-COV-2 VACCINE

Objectives: To evaluate the effect on immunogenicity and safety of 2-week methotrexate(MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in rheumatoid arthritis(RA) patients. Methods: This was a single-center, prospective, randomized, investigator-blinded, intervention study (#NCT04754698, CoronavRheum), including adult RA patients(stable CDAI<10, prednisone<7.5mg/day), randomized(1:1) to withdraw MTX(MTX-hold) for 2 weeks after each vaccine dose or maintain MTX(MTX-maintain), evaluated at D0, D28 and D69. Co-primary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion(SC) and neutralizing antibody(NAb) positivity at D69. Secondary outcomes were GMT and changes in disease activity scores. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those unable to hold MTX twice(CDAI>10 at D28). Results: Randomization included 138 patients with 9 exclusions(5 COVID-19, 4 protocol violations). Safety evaluation included 60(MTX-hold) and 69(MTX-maintain) patients. Further exclusions consisted of 27 patients[13(21.7%) vs. 14(20.3%),p=0.848] with positive baseline IgG/NAb and 10 patients(21.3%) in MTX-hold with CDAI>10 at D28. At D69, a higher increase in SC[29(78.4%) vs 30(54.5%),p=0.019] was observed in MTX-hold(n=37) in comparison to MTX-maintain(n=55), with parallel augmentation in GMT[34.2(25.2-46.4) vs 16.8(11.9-23.6),p=0.006]. No differences were observed for NAb positivity[23(62.2%) vs 27(49.1%),p=0.217]. Longitudinal variations in disease activity scores were alike in both groups(CDAI,p=0.144; DAS28-CRP,p=0.718). Conclusion: We provided novel data that 2-week MTX withdrawal after each vaccine dose improves anti-SARS-CoV-2 immunogenicity. The comparable longitudinal variations of disease activity in both groups suggest that discontinuation is a feasible and efficient strategy in well-controlled RA patients, and may be even safer for vaccines with longer interval between doses or single dose schedules.

Cardiac Autonomic Modulation in Response to Muscle Fatigue and Sex Differences During Consecutive Competition Periods in Young Swimmers: A Longitudinal Study

Objective: To study the differences in cardiac autonomic modulation in response to muscle fatigue caused by high-intensity exercise during two consecutive competition periods in young swimmers.Methods: Twenty-six competitive swimmers, selected by their training volume, were separated in two groups, females (n = 12 [46%], age: 13.5 ± 1.4 years) and males (n = 14 [54%], age: 13.9 ± 1.7 years), aged between 10 and 16 years, were evaluated five times as follow: (i) 21 days before the first competition (t-0); (ii) two days before (t-1; t-3); and (iii) two days after (t-2; t-4) of the first and second competitions. Morphological measurements (body mass, percentage of total body fat and height), blood pressure, power, and resting heart rate variability (RR with Polar band) were recorded before and after Wingate test at each time.Results: Body fat was higher in females compared to males. However, no differences were found in other morphological parameters. An intra-subject analysis grouped by sex in cardiovascular parameters shows longitudinal variations in systolic pressure and mean pressure among females. Additionally, females depicted higher, very low frequency (VLF, which is intrinsically generated by the heart and strongly associated with emotional stress) after physical fatigue compared to males at t-1. Further, before the competition, the high frequency (HF) component of HRV (parasympathetic drive) was higher in males than females at t-0 and t-4.Conclusion: Our data revealed that males displayed greater parasympathetic reactivity after an anaerobic muscle fatigue test during their competition periods. Contrarily, females had a less cardiac autonomic modulation when comparing the pre-post Wingate test after two consecutive competition periods.

Longitudinal variations of noontime thermospheric winds in response to IMF Bz temporal oscillations: broken mean circulation and standing feature

The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

Macro- and Trace-Element Intake from Human Milk in Australian Infants: Inadequacy with Respect to National Recommendations

Longitudinal variations of macro- and trace elements in human milk (HM) are not well characterised, and therefore, the recommendations for intake for Australian infants require more evidence to ensure accuracy. We aimed to investigate the longitudinal variation of HM macro- and trace-element concentrations (1–12 months) and infant intake (1–6 months) and to investigate the relationships between intake and infant growth parameters at 3 and 6 months, and determine if intake was sufficient when compared to national guidelines. HM samples were collected monthly for the first 6 months and then at 9 and 12 months postpartum from mother–infant dyads (n = 83). Test–weighing was used to determine the volume of HM consumed daily. Element concentrations (Na, Ca, K, Mg, P, I, Se, Zn, Cu, Mn, Mo, and Fe) were measured using ICP-MS, and intake was calculated using the measured concentrations and the volume of HM consumed. The average intake of HM was 776.3 ± 24.0 mL for the infants. Changes in concentration from months 1 to 12 postpartum were observed for all the measured micronutrients (all p < 0.05). The calculated intakes of all the macro- and trace elements showed that 0% to 82% of infants met the current adequate recommendations at varying periods of lactation. The calculated macro- and trace-element intakes were below the adequate intake recommendations, suggesting that they are not reflective of healthy infant requirements. These findings suggest the need for larger studies using sensitive analytical techniques and the revision of current recommendations for breastfed infants.

The influence of changing reward of electronic consumer goods on burglary and theft offences in Western market-based countries in the years prior to and during the crime drop

It is widely recognised that burglary and theft offence trends have broadly moved in parallel in ‘Western’ market-based countries since the 1950s. Most researchers have focussed on the trend from the early 1990s onwards, when burglary and theft offence rates plummeted. One major proposed explanation for this trend, relates to improved security. This paper draws on the longitudinal variations in reward of electronic consumer goods to propose a complementary account. This argument is supported by criminological theory, empirical evidence, and historical trends of specific property crime offences. The paper concludes by explaining that reward and security operate in partnership to influence the opportunity for crime, which provides an optimal account for burglary and theft offence trends over the last 40 years.

Longitudinal variations in the gastrointestinal microbiome of the white shrimp, Litopenaeus vannamei

The shrimp gut is a long digestive structure that includes the Foregut (stomach), Midgut (hepatopancreas) and Hindgut (intestine). Each component has different structural, immunity and digestion roles. Given these three gut digestive tract components’ significance, we examined the bacterial compositions of the Foregut, Hindgut, and Midgut digestive fractions. Those bacterial communities’ structures were evaluated by sequencing the V3 hypervariable region of the 16S rRNA gene, while the functions were predicted by PICRUSt2 bioinformatics workflow. Also, to avoid contamination with environmental bacteria, shrimp were maintained under strictly controlled conditions. The pairwise differential abundance analysis revealed differences among digestive tract fractions. The families Rhodobacteraceae and Rubritalaceae registered higher abundances in the Foregut fraction, while in the Midgut, the families with a higher proportion were Aeromonadaceae, Beijerinckiaceae and Propionibacteriaceae. Finally, the Cellulomonadaceae family resulted in a higher proportion in the Hindgut. Regarding the predicted functions, amino acid and carbohydrate metabolism pathways were the primary functions registered for Foregut microbiota; conversely, pathways associated with the metabolism of lipids, terpenoids and polyketides, were detected in the Midgut fraction. In the Hindgut, pathways like the metabolism of cofactors and vitamins along with energy metabolism were enriched. Structural changes were followed by significant alterations in functional capabilities, suggesting that each fraction’s bacteria communities may carry out specific metabolic functions. Results indicate that white shrimp’s gut microbiota is widely related to the fraction analyzed across the digestive tract. Overall, our results suggest a role for the dominant bacteria in each digestive tract fraction, contributing with a novel insight into the bacterial community.