Brugia malayi, an etiological agent of human lymphatic filariasis. While acetylcholine-gated ion channels are intensely studied as targets of existing anthelmintics, comparatively little is known about metabotropic receptor contributions to parasite cholinergic signaling. Using multivariate phenotypic assays in microfilariae and adults, we show that nicotinic and muscarinic compounds disparately affect parasite fitness traits. We identify a putative G protein-linked acetylcholine receptor of B. malayi (Bma-GAR-3) that is highly expressed across intramammalian life stages and adapt spatial RNA in situ hybridization to map receptor transcripts to critical parasite tissues. Tissue-specific expression of Bma-gar-3 in Caenorhabditis elegans  enabled receptor deorphanization and pharmacological profiling in a nematode physiological context. Finally, we developed an image-based feeding assay as a reporter of pharyngeal activity to facilitate GPCR screening in parasitized strains. We expect that these receptor characterization approaches and improved knowledge of GARs as putative drug targets will further advance the study of GPCR biology across medically important nematodes.The diversification of anthelmintic targets and mechanisms of action will help ensure the sustainable control of nematode infections in response to the growing threat of drug resistance. G protein-coupled receptors (GPCRs) are established drug targets in human medicine but remain unexploited as anthelmintic substrates despite their important roles in nematode neuromuscular and physiological processes. Bottlenecks in exploring the druggability of parasitic nematode GPCRs include a limited helminth genetic toolkit and difficulties establishing functional heterologous expression. In an effort to address some of these challenges, we profile the function and pharmacology of muscarinic acetylcholine receptors in the human parasite  Wuchereria bancrofti, Brugia malayi, and Brugia timori) that migrate to and develop in human lymphatic systems  are highly druggable and are the targets of over one-third of all FDA-approved drugs in human medicine . Despite24–30–37–Caenorhabditis elegans (–C. elegans genome encodes three known G protein-linked acetylcholine receptors (GARs)  and its receptor targets are essential for growth, development, and neuromuscular function in the clade V model nematode  elegans , 43. The elegans –50, but s (GARs) –54 that  (GARs) –, 55 and  (GARs) –, 56–58. esponses , 59, andarasites , justifyB. malayi, Bma-GAR-3. We examine the effects of muscarinic compounds on microfilariae and adult Brugia parasites using multivariate phenotyping approaches and determine temporal and spatial gene expression patterns for Bma-gar-3. Building on previous work  and pharmacologic characterization. Finally, we validate a high-throughput assay that enables screening of Bma-GAR-3 expressed in the C. elegans pharynx. These approaches circumvent some of the challenges associated with the study of GPCRs in difficult helminth systems and are likely extensible to many other parasitic nematodes and receptors.Here, we focus our efforts on the characterization of a phylum-conserved muscarinic acetylcholine receptor in ous work , 61–64, C. elegans G protein-linked acetylcholine receptors (GARs) were used to identify closely related biogenic amine receptors across six parasitic nematode species. Phylogenetic analysis of putative GARs revealed that B. malayi possessed one-to-one orthologs of C. elegans GAR-2 (Cel-GAR-2) and GAR-3, but not GAR-1  across intramammalian life cycle stages . Bma-gar-3 was constitutively expressed across all life cycle stages and was much more highly expressed than Bma-gar-2 , atropine (ATR), arecholine (ARE), carbachol (CAR), oxotremorine M (OXO), nicotine (NIC), and levamisole (LEV). ACh leads to a slow increase in baseline movement after prolonged exposure (24 and 48 h), attributable to inefficient penetration of the cuticle . Tr. TrBrugi cuticle .Cel-GAR-2 is unaffected by the muscarinic agonists ARE and OXO or the antagonist ATR  elicits a range of subtle-to-large effects on motility. ATR and ARE immediately decrease motility in male and female worms (100 μM) and CAR decreases motility in male worms (10 μM and 100 μM), in agreement with previous work . Cel-GARnist ATR , 65, sug at 24 h ; LEV is  elegans .−4 M) and low (>10−7 M) concentrations, respectively (−2 M) in the 24- to 48-h time frame. The morphologies of mf at 48 h varied among treatments, suggesting effects not fully captured by motility. LEV, NIC, and OXO treatment caused worms to become flaccid, much like heat-killed (HK) control worms, while ACh-treated worms maintained the posture of untreated controls. Some cell death was noticeable for all treatments, except acetylcholine, at high concentrations (>1 mM) at 48 h  to measure the effects of cholinergic compounds on motility and cell death. NIC and LEV both caused immediate inhibition of mf motility, at high . Individual sections were captured sequentially from the anterior tip (216 sections) of a single adult female B. malayi worm, and RNAScope was used to localize Bma-gar-3 transcripts within sections, allowing the reconstruction of expression patterns down the anterior-posterior axis of the head region   7578, suggeB. malayi GPCRs through functional expression in discrete C. elegans tissues. Pharmacological profiling of parasite GPCRs in this heterologous system requires that the receptors are properly folded and exported to the membrane, that they signal through endogenous G proteins, and that their activation in response to exogenous ligands can be measured through convenient phenotypic endpoints. Building on previous work leveraging C. elegans as a heterologous expression platform for the expression of human GPCRs ] genetic background. We employed simple plate-based assays to verify proper cell surface expression of B. malayi GAR-3 and to deorphanize the receptor by confirming activation by the putative ligand ACh. Activation of the C. elegans ASH neuron by noxious stimuli results in a well-characterized avoidance response wherein worms reverse their movement. We hypothesized that the successful activation of parasite GPCRs expressed in this neuron should lead to increased reversal frequency. We adapted an aversion assay (Bma-GAR-3 in the ASH neuron (sra-6p::Bma-gar-3) exhibited strong aversion responses to ACh (100 mM) and the selective muscarinic agonist oxotremorine M (100 mM) ] strains demonstrated aversion to ACh or OXO, but all strains maintained consistent responses to negative (water) and positive (4 M fructose) controls.To limit background signaling, transgenic lines were created in a on assay , 82 thaton assay . Worms e(100 mM) . OXO hasel-GAR-2 , 53, 66.Bma-GAR-3 in the body wall muscle (myo-3p::Bma-gar-3), predicting that the buildup of ACh at the receptor synapse would lead to flaccid paralysis of this parasitized C. elegans strain. We adapted a protocol  on worms expressing protocol  that inv strains  and D. CC. elegans expressing Bma-GAR-3 in the pharyngeal muscle (myo-2p::Bma-gar-3), hypothesizing that the expression and activation of parasite acetylcholine receptors in the pharynx and the body wall would alter baseline and drug-induced pharyngeal pumping activity. Pharyngeal pumping activity can be directly measured by observing terminal bulb inversions  are commonly used to elevate baseline pumping frequency  or B. malayi GAR-3 (myo-2p::Bma-gar-3 strain) in the pharynx (L1 assays carried out on OP50 plates confirmed that this food stimulant did not saturate pumping responses or mask expected drug effects. The inhibitory effect of arecoline could be measured in strains expressing either  pharynx . A dynam pharynx . Assays Cel-GAR-3 agonist oxotremorine M. OXO increased the pumping frequency in L1-stage (~41%) and adult-stage (~26%) N2 worms  strain (We next used these optimized L1 and adult-stage assays  to confiN2 worms  and D. K profile . In adul) strain .gar-3(gk305) and gar-3(gk305); myo-2p::Bma-gar-3 strains.Although it is known that pharyngeal pumping can be modulated by cholinergic signaling in both tissue types, the precise mechanism by which the body wall and pharynx communicate is unclear , 94, 95.Bma-GAR-3 expression in the body wall and pharynx of young-adult C. elegans worms. We recorded individual worms for 2 min after a 20-min drug incubation period, mirroring the visual counting assay  and gar-3(gk305); myo-2p::Bma-gar-3 worms, respectively  background  incubation. We tested two concentrations of BODIPY to help minimize background fluorescence and ensure that the dye was not a limiting reagent. We tested the inclusion of 5-HT and HB101 as feeding stimulants for the duration of the drug exposure, as well as the inclusion of HB101 in the BODIPY incubation period. Assays using at least 90 ng/mL BODIPY (2×) generated the best conditions to detect both pharyngeal stimulation (5-HT and HB101) and inhibition (NIC)  . The incon (NIC) .gar-3(gk305) and gar-3(gk305); myo-2p::Bma-gar-3 animals. We treated worms with cholinergic compounds, followed by BODIPY incubation. An image-processing pipeline was established to identify transgene (+) worms via pharyngeal GFP expression. OXO caused an increase in dye uptake in wild-type worms compared to the uptake in nontreated controls , consistent with the increased pumping frequency observed in visual counting assays. OXO decreased dye uptake in the gar-3(gk305) background, which was rescued by the expression of Bma-gar-3 in the pharynx  that was highly expressed throughout the intramammalian life stages and developed a spatial RNAScope protocol to map receptor transcripts in multiple tissue types in the adult stage. Multivariate phenotypic assays of cholinergic effects on microfilariae and adult parasites revealed differential effects of nicotinic and muscarinic agents. We showed that muscarinic compounds affected motility in both adult- and mf-stage parasites, some of which were likely to be mediated by GAR-3. We predict that sampling a broader array of muscarinic compounds will likely reveal other overt and subtle-but-important phenotypes that are relevant to potential anthelmintic mechanisms of action.We identified a Bma-gar-3 in the C. elegans body wall muscle, pharynx, and sensory neurons. Different phenotypic endpoints were optimized to measure receptor activity across these parasitized strains. Simple plate-based assays allowed the deorphanization of Bma-GAR-3 expressed in the body wall and sensory neurons. We focused primarily on pharyngeal expression, given its amenability to a range of visual, electrophysiological, and imaging assays. While visual observations of pharyngeal pumping and electropharyngeogram recordings provided different measurements of Bma-GAR-3 perturbation, these assays were ultimately low in throughput. To enable more facile and higher-throughput screening of pharynx-expressed receptors, we deployed a microtiter-plate imaging assay that measured the accumulation of lipophilic dye as a reporter of pharyngeal pumping. We show that this feeding assay can be used to detect activation of Bma-GAR-3 within the pharynx.Building upon previous work , 61–64, 61–The suitability of these approaches for a given parasite GPCR will depend on the complement of related receptors and endogenous ligands that signal in targeted tissues. We show that transgenic strains can be created in various genetic knockout backgrounds to help mitigate some of these concerns. While expression in scalable single-cell systems will remain an important objective for high-throughput screening (HTS) against GPCR targets, functional parasite receptor assays in a more native nematode cell and physiological environment can provide important baseline pharmacological data and transgenic whole-organism assays can conceivably be adapted for high-throughput screening and anthelmintic discovery.B. malayi and Brugia pahangi adults extracted from the Meriones unguiculatus infection system (NIH/NIAID Filariasis Research Reagent Resource Center) (l-glutamine (Sigma-Aldrich) supplemented with fetal bovine serum (FBS)  and penicillin-streptomycin  at 37°C with 5% CO2 unless otherwise specified. Brugia microfilariae isolated from the same system were maintained in RPMI 1640 medium supplemented with l-glutamine (Sigma-Aldrich) and penicillin-streptomycin  at 37°C with 5% CO2 unless otherwise specified. Center)  were maiThe chemicals used in the assays included serotonin , arecoline , atropine , nicotine , levamisole , carbachol , acetylcholine , oxotremorine M , and aldicarb .C. elegans GARs. This initial list of GARs was expanded with homology-based searches against the C. elegans predicted proteome, and a broader list of C. elegans  that survived a reciprocal BLASTp search against C. elegans were retained. This list was combined with human muscarinic receptors for phylogenetic inference and annotation. Receptors were aligned with MAFFT  per well. The parasites were incubated overnight, after which individual parasites were transferred to new plates with 750 μL incomplete medium (RPMI 1640 plus penicillin/streptomycin). Compound stocks (100×) were made fresh daily in H2O. Plates were recorded for 15 s, compound was added, and plates were immediately recorded again. Recordings were taken 1 h posttreatment and 24 h posttreatment, prior to transferring parasites to a new preloaded drug plate. The final recordings were taken 48 h posttreatment. Three biological replicates from separate batches of parasite infection cohorts were assayed with four worms per treatment. Videos were analyzed with the optical flow (motility) module of wrmXpress , and each well was imaged with transmitted light at 2× with an ImageXpress Nano system (Molecular Devices). Images of progeny were segmented as previously described  in batches of 500,000 (mf), 300 to 500 (L3), or 3 (adults). Three independent samples originating from different batches of animal infections were collected for each stage . Freeze-thawed samples were homogenized using a compact bead mill , and RNA was extracted using the Zymo Direct-zol RNA miniprep kit . RNA integrity and concentration were assessed via NanoDrop, and cDNA was generated with the SuperScript III kit  using equal amounts of oligo(dT) and random hexamer primers for first-strand synthesis. qPCR primers for Bma-gar-2  and Bma-gar-3  were designed with Primer3 (TC) values were calculated with the system’s automatic threshold.Parasites were flash frozen in liquid N Primer3  and opti Primer3  were useB. malayi females were cultured overnight and separated in 10-cm petri dishes, dipped in 70% ethanol, and spatially embedded in 1% Bacto-agar. The blocks of Bacto-agar were dehydrated for 5 min in 25%, 50%, and 70% ethanol sequentially and stored in 100% ethanol overnight. The Bacto-agar-embedded tissue was processed into a paraffin block, and agar was trimmed from the anterior tip of the agar block before embedding for cross-sectioning. Blocks were sectioned at 8 μm, and sections were arranged sequentially on slides, keeping all sections.Adult Bacillus subtilis) as a negative control and two highly-expressed B. malayi genes as positive controls: Bma-Bm4733  and Bma-cdc-42 . Our Bma-GAR-3 target probe targeted positions 400 to 1501 of the sequence with accession number XM_043081323.1 (20ZZ). The standard RNAScope 2.5 HD assay-red kit (ACD Bio) protocol was followed with an adjusted length of 8 min for retrieval using a steamer and 45 min for amp 5. Imaging was done in bright-field microscopy with a 40× Nikon Plan Apo objective on a Nikon Eclipse80i. The presence of red punctate staining, indicating target gene expression, was quantified by manual annotation by two independent observers. Annotation and alignment were carried out with Fiji (The hybridization probes used for the RNAScope assays (ACD Bio) included DapB  was selected for study based on manual assessment and alignment with homologous GARs. This isoform is supported by long-read RNA-sequencing data (myo3p::Bma-gar-3::unc-54-3′UTR). pMZ0012 (sra-6p::Bma-gar-3::unc-54-3′UTR) was created by subcloning Bma-gar-3 into sra-6p::ChR2*YFP (a gift from Shawn Lockery ), ZAM10 (gar-3(gk305) V, maz10Ex), and ZAM11 (gar-3(gk305) V, maz11Ex), created as described previously (gar-3(gk305) along with fluorescent markers (unc-122p::GFP or myo-2p::GFP) and empty vector (pPD95.75) to create a final concentration of 100 ng/μL. ZAM19 ([myo-2p::GFP]) and ZAM20 (gar-3(gk305) V [myo-2p::GFP]) were created by injecting 10 ng/μL of a fluorescent marker (myo-2p::GFP) and empty vector (pPD95.75) to create a final concentration of 100 ng/μL. VC657(gar-3(gk305) V) was sourced from the C. elegans Gene Knockout Consortium  and pipetted onto unseeded 6-cm plates. To assemble the assay plate, a copper ring  was soaked in a test compound with fast green dye as a visual marker and placed in the center of the plate. One microliter of 1:1,000-diluted diacetyl (attractant) was combined with 1 μL fast green and added outside the ring. Plates were used immediately after assembly. The copper ring was removed after 1 min to allow the test compound to soak into the agar. Individual worms were picked without bacteria to the center of the compound ring on assay plates and monitored for reversals in response to test compounds. Three biological replicates from three independent bleaches were run using four worms per treatment per strain. Observations were made until either the worm crossed the compound ring or six attempts to cross the compound ring occurred without the worm crossing. Water was used as a negative control, and 4 M d-fructose was used as a positive control.Bleach-synchronized adult worms were rinsed three times in M9 buffer  in NGM. Plates were stored at 4°C and used within 30 days. Thirty L4-stage animals from each strain were picked to OP50-seeded plates and cultured at 20°C overnight until they reached the young-adult stage. Aldicarb plates were acclimated to room temperature on the morning of the assay. Four copper rings  were dipped in 70% ethanol and briefly flamed before placement onto a single aldicarb plate to form quadrants. Ten microliters of OP50 from an overnight liquid culture was spotted into the center of each of the copper rings and allowed to dry for 30 min. A minimum of 10 worms per strain were picked to the center of a quadrant, allowing the testing of four strains per plate. Four biological replicates were carried out across strains. After 30 min and every 10 min thereafter, each worm was tapped 3 times on the head and tail, the paralyzed worms were removed, and the remaining worms were tallied. This process continued until the 2-h mark.For L1-stage assays, gravid worms were bleached and embryos were hatched on unseeded 10-cm NGM plates overnight . L1s were washed from plates into 1.5-mL tubes and treated with drug for 20 min. Five hundred microliters of the treated worm mixture was then transferred to an unseeded 10-cm NGM plate and allowed to dry for 5 min. Individual transgene (+) worms were then picked to seeded 6-cm NGM assay plates and given 10 min to acclimate. Adult assays required minor modifications of the L1 protocol. Young adults were developed on seeded 10-cm NGM plates, drug-treated worms were transferred to 10-cm plates with no drying period, and transgene (+) worms were picked to unseeded 6-cm NGM assay plates. For optimization and cholinergic assays, an average of 8 worms were visually phenotyped for each strain-condition combination. Pumps were measured by the motion of the terminal bulb grinder over a 30-s (L1s) or 10-s (adults) interval using a Zeiss Axio Vert.A1 at ×10 magnification with differential interference contrast (DIC) optics.Electropharyngeograms (EPGs) were recorded with the ScreenChip system (InVivo Biosystems). Briefly, worms were bleach synchronized and embryos were hatched and developed on seeded 10-cm NGM plates. Young-adult worms were washed 3 times with M9 in 1.5-mL tubes. Worms were treated for 20 min before loading them into the ScreenChip40 microfluidic chamber. Each worm was vacuumed into the channel, acclimated for 30 s, and recorded for 2 min using the NemaAcquire 2.1 software. Worms from three biological replicates representing independent bleaches were assayed for optimization (minimum of 15 worms per condition), and one replicate was assayed for the cholinergic panel (minimum of 5 worms per condition). Analysis was done using NemaAnalysis 0.2 with default settings found under customize analysis. Filtering of data was done by modifying “parameters left” for signal-to-noise ratio (SNR), E and R high-pass cutoffs, and the minimum absolute threshold, followed by visually ensuring all pumps were identified and background noise was ignored.E. coli HB101 bacterial food . Worms were incubated for 48 h at 20°C with shaking at 180 RPM until reaching adult stage . Nonworm objects and contaminating fluorescence were further filtered with size thresholds and outlier pruning (TxRed fluorescence units [FLU] Z score of >3). Total fluorescent dye uptake for GFP-positive worms was quantified using the StdIntensity parameter.Bleach-synchronized larval-stage worms (L1) were aliquoted into 96-well plates at a titer of 50 L1 animals per well along with lt stage . For thelt stage , 131. Sehttps://github.com/zamanianlab/Bm-GAR-ms.All primary data  and pipelines for statistical analysis and data visualization are available at


The correlation results showed that technical performance in the continuous and fractional regimes was related to agility, horizontal jump, and height, while biological maturation was only related to technical performance in the fractional regimen of SSGs. Perceived enjoyment showed a negative relationship with weight, height, BMI, and WC. Conclusion: The fractional and continuous regimens of SSGs implemented in this study induced similar technical demands and enjoyment. Furthermore, the results suggest that physical fitness, anthropometric profile, and biological maturation may influence the technical performance and enjoyment of SSGs.The objective is to determine the relationship between physical fitness, anthropometric measures, and biological maturation as they relate to technical performance in small-sided games (SSGs) of continuous and fractioned regimes. Methodology: A crossover-design study in which 12 children participated in two regimens of SSG . At the beginning of the study, all children were evaluated using physical fitness tests , anthropometric profile , and waist circumference (WC)), and biological maturation (peak years of growth velocity). All sessions were recorded and analyzed with the Performance Assessment in Team Sports instrument, and at the end of each game each child was asked to answer a scale of enjoyment for physical activity. Results: The results of the paired samples t-test showed no significant differences in the measures of technical performance and perceived enjoyment for the continuous and fractional regimens of SSGs ( The World Health Organization recommends that children and adolescents should engage in at least 60 min a day of moderate to vigorous physical activity (MVPA) and should incorporate at least three days a week of exercises that strengthen muscles and bones . HoweverIn particular, schools’ physical education (PE) classes could offer a great opportunity to favor the development of physical fitness and motor skills in children and adolescents , encouraThe implementation of teaching models appropriate to the needs of students and the context can be key to the development of physical literacy . TraditiIn this sense, small-sided games (SSGs) are widely used in pedagogical models that favor the practice, offering the integration of skills in contextualized situations ,11 in whPreviously, different systematic reviews have proposed that regimen type or participant characteristics should be considered when planning an SSG for desired responses ,15,16. HConsidering the increased use of SSGs in non-competitive contexts and the limited evidence about the effect that regimen type or individual characteristics might have on technical performance or enjoyment during SSGs, this research aimed to determine the relationship between physical fitness, anthropometric measures, and biological maturation with technical performance and perceived enjoyment in untrained children during continuous- and fractional-regimen small-sided games.A crossover experimental design study was carried out in which 12 children participated in 4 sessions of small-sided games, two sessions of fractional regimens , and two continuous regimens (1 match of 16 min). Participants were assigned to a team of 3 participants and always faced the same opposing team in each of the 4 experimental sessions. Each team played only 1 SSG regimen per session and they were performed alternately see .The research was approved by the ethics committee of the Adventist University of Chile Nº 2021-17). All parents and children signed their respective informed consent or assent. All procedures were carried out following the principles described in the Helsinki declaration for human studies [. All parParticipantsTwelve untrained children (11.5 ± 1.33 years) were invited to participate in the study. All children were from a recreational soccer school that trained once a week and resumed activities after 16 months of suspension of activities due to confinement during the COVID-19 pandemic. Inclusion criteria were: (i) boys between 11 and 14 years of age; (ii) informed consent and assent signed by each guardian responsible for the schoolchild; (iii) no participation in structured training during the last 6 months; and (iv) health compatible with the practice of physical activity. Exclusion criteria: (i) reporting an injury or severe muscle pain during the data collection sessions; (ii) history of musculoskeletal injuries in the last 6 months; (iii) motor or intellectual disability that does not allow him/her to perform team sports; or (iv) failure to comply with instructions during evaluations or soccer sessions.ProceduresA member of the research team informed the participants and their legal guardians of the objectives of the research project, the days, the schedule, and the place where the sessions would take place. Data collection was carried out for 3 weeks. In the first week anthropometric and sociodemographic evaluations were performed, followed by jumping tests: horizontal and vertical jump, T-test agility test, and YO-YO intermittent recovery test. In the second and third weeks, the experimental sessions were carried out, allowing a 24 h recovery period between each session. During the SSG sessions, each participant wore a Polar H10 brand heart band  connecteSmall-sided games Intervention (SSG)All experimental sessions began with a targeted, staged warm-up. The SSGs consisted of 3 vs. 3 formats in two types of regimes; the first was the “continuous regime” which was a 16 min one-half match, while the other mode of play was the “fractional regime”, which was composed of 4 halves, lasting 4 min each, with a 2 min break for each half. At both ends of the court there were members of the research groups, who had balls available for each kick of the participants, to provide greater fluidity to the game. The rules used for these reduced games were as follows: the goal is valid when all participants pass half court; throw-ins and corner kicks were performed with the foot; and after each goal, the game was resumed at half court. As for the playing surface, the area was delimited with cones, measuring 17 m long by 9 m wide, while the goal was 78 cm high by 2.9 m wide.Instruments® scale, model 803; Seca® stadiometer, model 213; and CESCORF® anthropometric tape). Body Mass Index (BMI) and years at peak growth velocity (APHV) were calculated [Anthropometric measurements: Body mass, height, sitting height, and waist circumference were measured with standardized protocols using shorts and polo shirt , according to the protocol proposed by Krustrup et al. (2003) . The tes® Boscosystem, Barcelona, Spain) and participants were asked to lower their center of gravity to a self-selected depth and then perform a vertical jump, always with their hands on their hips. The same verbal prompts were delivered before each attempt, “jump as high as you can in 3, 2, 1 go” [Muscular fitness measurements: These were evaluated using a vertical jump with countermovement (CMJ) and a horizontal jump (SH), performing three attempts each. The CMJ was evaluated with a contact mat .Agility test: To measure agility, each participant performed three attempts of the agility test T-test (TT) . The TT Measures of performance and enjoyment during the SSG: Performance during the SSG was evaluated by observing video records using the Performance Assessment in Team Sports instrument . In addiIndividual performance assessment: Each player was observed during the games, and various actions that occurred during each game were recorded based on the Performance Assessment in Team Sports instrument . The actEnjoyment Scale (PACES): At the end of each SSG, participants completed the Physical Activity Enjoyment Scale (PACES) , which cStatistical proceduresResults are presented as means and standard deviation (SD) for descriptive data. The normality analysis of data distribution was tested with the Shapiro–Wilk test. The results of the reduced sets with continuous (2) and fractional (2) regimes were averaged for comparison and correlations.Differences between continuous and fractional regimes for measures of game performance, physiological responses, and perceptual responses were performed with paired samples t-tests. In addition, Cohen’s d effect size with 95%CI was calculated and classified as trivial (<0.2), small (0.2–0.6), moderate (0.6–1.2), or large (>1.2).p < 0.05.Pearson product-moment correlation coefficients tested the relationships between performance during reduced play with anthropometric and fitness variables. The magnitude of the correlation is reported for all variables and supplemented as 95% confidence intervals and r2 when a significant correlation was found between variables. The magnitude of the correlation between variables was assessed with the following thresholds: <0.1, trivial; 0.1–0.3, small; 0.3–0.5, moderate; 0.5–0.7, large; 0.7–0.9, very large; and >0.9, near perfect . All anaThe anthropometric and physical fitness characteristics of the study participants are presented in The results for the measures of technical performance, perceived enjoyment, and physiological response for the continuous and fractional regimens are presented in p = 0.04), while years to APHV was positively correlated with successful shots  and efficiency index .The correlation coefficients between technical performance and enjoyment during SSG with anthropometric and fitness measures are presented in p = 0.01 and R = −0.75, 95%CI (−0.27:−0.93); R2 = 0.56; p = 0.008), weight ; R2 = 0.67; p = 0.002 and R = 0.84, 95%CI (−0.48:−0.96); R2 = 0.71; p = 0.001), body mass index ; R2 = 0.61; p = 0.005 and R = −0.82, 95%CI (−0.44:−0.95); R2 = 0.67; p = 0.002), and waist circumference ; R2 = 0.67; p = 0.002 and R = −0.90, 95%CI (−0.67:0.98); R2 = 0.81; p < 0.001).In addition, a relationship was found between PACES scores, during continuous and fractional SSGs, with height ; R2 = 0.53; p = 0.036), efficiency index ; R2 = 0.45; p = 0.02), and overall performance ; R2 = 0.42; p = 0.02). Furthermore, a negative correlation was found between agility test execution time with the number of successful shots ; R2 = 0.40; p = 0.03) and the efficiency index ; R2 = 0.40; p = 0.03).The results of the relationship between physical fitness and continuous SSGs showed a positive correlation between horizontal jumping and offensive balls ; R2 = 0.36; p = 0.04) and the efficacy index ; R2 = 0. 36; p = 0.04), while the results in the agility test correlated with balls conquered ; R2 = 0.41; p = 0.03), balls received ; R2 = 0.40; p = 0.01), offensive balls ; R2 = 0.62; p = 0.003), successful shots ; R2 = 0.53; p = 0.007), volume of play ; R2 = 0.41; p = 0.008), efficiency index ; R2 = 0.46; p = 0.02), and overall performance ; R2 = 0.67; p = 0.001).In fractional SSGs, the horizontal jump score correlated with successful shots ; R2 = 0.36; The purpose of this study was to determine the relationship between physical fitness, anthropometric measures, and biological maturation as they relate to performance in small-sided games of continuous and fractional regimens in untrained children. Results showed no differences between regimens with respect to technical performance or perceived enjoyment during SSGs. Correlation analysis found that height and APHV were related to efficiency rate and successful shots in fractional SSGs, but not in continuous SSGs. Physical fitness measures, mainly horizontal jump and agility, correlated with technical performance measures in both SSG modalities. In addition, perceived enjoyment during continuous and fractional SSGs was related to weight, height, BMI, and waist circumference.Our study implemented SSGs in continuous and fractional regimens, without finding significant differences in technical performance or perceived enjoyment during the game. Previously, systematic reviews have reported a relationship between physical fatigue and technical performance ; therefoPrevious research has reported that technical performance during SSGs could be influenced by the individual characteristics of the participants ,31. The In trained populations, it has been found that locomotor demands can vary according to the regime or duration of the series ,32. PartOur results showed that biological maturation measured by the APHV had a moderate relationship with technical performance only for the fractional regime but not in the continuous regime, showing that those with a higher maturational status had higher performance in successful shots and in the efficiency index. Interestingly, technical performance during the fractional regime showed a greater influence of performance in the agility test, a skill that is related to maturational status . On the The SSG is proposed as a resource associated with a high level of enjoyment, with the potential to be applied in different contexts, such as school, sports, or health promotion programs ,38. In aThe SSG is considered a methodological resource for teaching sports , and difThe results of this research are important to understand how untrained children and adolescents respond to SSGs, and thus, to understand the different variables that determine the performance and experience associated with SSGs in contexts such as school, recreational sports workshops, or health programs that use this type of resource. However, it should be taken into consideration that the sample size is small, so future research should cover a larger sample size to achieve a more precise understanding of the influence of physical fitness and anthropometric variables on the technical performance in and enjoyment of SSGs.The fractional- and continuous-regimen SSGs implemented in this study induced similar technical demands and enjoyment. In addition, the results showed that better results in the agility test, horizontal jump, and the height of the participants were related to better technical performance, but only the anthropometric profile constituted by height, weight, Body Mass Index, and waist circumference was related to enjoyment. Biological maturation could be related to technical performance in fractional regimes. Therefore, considering the importance of offering enriching sports experiences, teachers or coaches should use continuous or fractional reduced games, considering the anthropometric profile and physical fitness of the participants in the planning of SSGs intended for untrained children and adolescents.


IgG4-related diseases (IgG4-RDs) are known to disrupt the functioning of multiple organs and are usually associated with mass lesions. Periaortitis, an inflammation of the adventitia and tissues surrounding the aorta, is an example of an IgG4-RD. In ophthalmology, an enlargement of the lacrimal gland is a well-known IgG4-RD, and scleritis has also been reported to be an IgG4-RD although it is rare. We report our findings in a case with periaortitis and posterior scleritis that were present at the same time, and they responded well to systemic steroid therapy.A 79-year-old man with dementia and Lewy bodies was referred to our hospital because of uveitis in both eyes that did not respond to topical steroid therapy.We found anterior scleritis in the right eye and uveitis with shallow anterior chambers in both eyes. B-mode echography showed choroidal detachments (CDs) and a T sign in the right eye. The CDs were assumed to have progressed to the posterior scleritis which then caused the severe vision reduction. The patient was referred to the Internal Medicine Department because the systemic inflammatory disease was suspected due to the high levels of C-reactive protein (CRP) and the fast erythrocyte sedimentation rate. Systemic CT scans showed periaortitis only at the lumbar region. Because of the high levels of IgG4, the patient was diagnosed with IgG4-RD.The patient received intravenous and oral steroid therapy. The first 125 mg of methylprednisolone (mPSL) for 3 days was intravenous, after which it was switched to oral prednisolone (PSL) therapy and the dosage was gradually reduced.The posterior scleritis and periaortitis responded well to the systemic steroid therapy. One year and a half after the onset of the disease, the patient is still taking 5 mg of PSL.Scleritis with multiple CDs and periaortitis were strongly suspected to be due to IgG4-RD although no definitive diagnosis was made by biopsy of the lesions. Clinicians should be aware that IgG4-RD should be considered as one of the causes of posterior scleritis. Periaortitis, an inflammation of the adventitia and tissues surrounding the aorta, is an example of a condition associated with IgG4-RD. In ophthalmology, a lacrimal gland enlargement is known to be associated with IgG4-RD, and its clinical manifestations include an enlargement of the trigeminal nerve and the external ocular muscles. Posterior scleritis has also been reported to be an IgG4-RD although it is rare.,5Posterior scleritis is an inflammation of the posterior sclera and has a variety of properties including the rapid spread of the inflammation to the adjacent cornea, uvea, optic nerve, external ocular muscles, and eyelids. Thus, posterior scleritis should be diagnosed as quickly as possible to prevent the spread of the inflammation.,5 Because of the rapid spread of posterior scleritis, diagnostic steroid treatment is usually performed because a delay can result in poor visual acuity. In spite of the seriousness of IgG4-RD, there is very little information about its characteristics and treatment.The inflammatory spread of posterior scleritis to the choroid can cause choroidal detachments (CDs), which then hasten the shallowing of the anterior chamber. The signs in these eyes then resemble those of the Vogt-Koyanagi-Harada (VKH) syndrome. Because the treatment protocols of posterior scleritis and VKH syndrome differ, it is important to differentiate them. In addition, the severe CDs with inflammation can make it difficult to differentiate them from choroidal infections and malignant tumors.Thus, the purpose of this study was to determine the characteristics of a case with periaortitis and posterior scleritis that were present at the same time. Our results showed that both responded well to systemic steroid therapy.The patient was a 79-year-old man. Two months before his first visit to our clinic, he visited his local ophthalmologist with complaints of decreased vision in both eyes, hyperemia, and pain in the right eye. He was treated with topical and subconjunctival injections of steroids for the uveitis of both eyes. However, there was a rapid deterioration of vision and a shallowing of the anterior chamber in the right eye. He then underwent cataract surgery on the right eye but the shallow anterior chamber did not improve. The patient was then referred to our hospital for further examinations and treatments.At our initial examination, the right eye had only light perception and the visual acuity of the left eye was 20/63. There was conjunctivitis and anterior scleritis in the right eye and very shallow anterior chambers with posterior synechia in both eyes. Detailed evaluations of the fundus were difficult, and OCT images could not be obtained because of vitreous opacities and miosis. B-mode echography detected choroidal detachments (CDs) and a thickening of the sclera with fluid collecting in the posterior episcleral space that extended around the optic nerve, the T sign, of the right eye.The patient was referred to the Internal Medicine Department on the same day because systemic inflammatory disease was suspected due to the high levels C-reactive protein (CRP) and fast erythrocyte sedimentation rate (ESR). Systemic CT scan showed only periaortitis at the lumbar region. There were no signs of any other infections.At the time of the initial examination, there were CDs in only the right eye, but 7 days later, they were also present in the left eye and the visual acuity was also reduced in the left eye Fig. . At thisNineteen days after the initial examination, his right eye did not have light perception and the visual acuity of the left eye was reduced to light perception. Although we suspected a choroidal or orbital tumor initially, we believed that it was more likely to be posterior scleritis because of the subfoveal area of the choroid was less solid and appeared more serous.We then decided to treat the patient with steroids. Because of the age of the patient, he was treated with intravenous 125 mg of methylprednisolone (mPSL) for 3 days initially and was then switched to 40 mg of oral PSL, and the dose was reduced by 5 mg every week with frequent examinations looking for any signs of a relapse. Then, there was a gradually increase in the examination interval to 2 weeks and then to 1 month, and the treatment has not been completely stopped at this time. In spite of the reduction of the steroid therapy, there were no signs of the scleritis or new CDs.After beginning the treatment with the corticosteroids, there was a rapid response with the level of c-reactive protein (CRP) decreasing to normal levels after 4 days, and the erythrocyte sedimentation rate (ESR) and IgG4 levels were within normal limits after 1 month. In addition, the inflammation of the aorta was not detected in the CT scan taken after 1 month of steroid therapy.During the course of the disease process, various examinations were performed to confirm the diagnosis and that no other abnormalities were present. B-mode echography showed improvements of the CDs, and the visual acuity gradually improved to normal levels Fig. .Five months after the onset of the signs and symptoms of posterior scleritis, OCT imaging became possible because of the disappearance of the vitreous opacities. The OCT images showed subretinal deposits and serous retinal detachment in the right eye Fig. A. No cho In ophthalmology, Mikulicz disease was first reported to be an IgG4-RD in 2004. In 2011, the Ministry of Health, Labor and Welfare of Japan developed the comprehensive diagnostic criteria of IgG4-RDs.Patients with IgG4-RD present with tissue infiltration and formation of IgG4-positive plasma cells that form masses in various organs of the body. This disease was initially diagnosed as autoimmune pancreatitis in 2001. An enlargement of the lacrimal gland is a well-known IgG4-related ocular disease (IgG4-ROD), but posterior scleritis, uveitis, and optic neuropathy have also been reported although they are relatively rare.,3 Scleritis and uveitis due to IgG4-ROD was first reported in 2012.The pancreas is the organ most common affected by IgG4-RD followed by the salivary glands, kidneys, lacrimal glands, periaortitis, bile ducts, and lungs. but there have been only a few reports of IgG4-related scleritis in the PubMed data base.Philippakis et al reported the first case of conjunctival carcinoma in a patient with IgG4-RD scleritis, In our case, no definitive diagnosis was made by biopsy of the sclera and the periaortic tissue because of its difficulty but IgG4-RD was strongly suspected based on the imaging and serological findings.Although lacrimal gland enlargement is a well-known IgG4-ROD, it was reported that 52.3% of patients with IgG4-ROD have lesions in organs other than the lacrimal glands.,13 and IgG4-RD was suspected in our case. When scleritis is accompanied by multiple CDs and shallow anterior chamber, it is difficult to differentiate it from VKH disease. B-scan ultrasonography was important in the differential diagnosis of posterior scleritis because the images showed the pathognomonic T-sign due to fluid collecting in the posterior episcleral space and extending around the optic nerve (Fig.  In our case, the T-sign was present from the time of the initial examination especially in the right eye, and even after the improvement of the anterior scleritis, vitreous opacity, and CDs, the T-sign was still present. We assumed that the right eye was more affected by the severe scleritis than the left eye, and this may be the reason why the visual acuity of his right eye improved more slowly.Autoimmune diseases have been reported to be the cause of many diseases,rve Fig. .[14] In  Early systemic search and cooperation with the Internal Medicine Department is important because IgG4-RD is a chronic inflammatory condition that may involve nearly every organ system. It should be noted that not only a monitoring of local recurrences but also screening intertemporal development in other organs would be important.The scleritis with the CDs was strongly suspected to be an IgG4-ROD because of the presence of high levels IgG4, scleritis, and periaortits at same time, although no definitive diagnosis was made by biopsy of leasions. IgG4-RD should be considered as one of the possible causes of the posterior scleritis although it is relatively rare. And it is also important to consider that posterior scleritis may also be a subretinal or choroidal mass, and it may be difficult to differentiate inflammatory lesions from an intraocular tumor based on imaging alone.We thank Professor Emeritus Duco Hamasaki of the Bascom Palmer Eye Institute of the University of Miami for critical discussion and final manuscript revisions.Yoko Mase: Conceptualization, Writing-Original draft preparation; Akiko Kubo: Conceptualization, Writing-Reviewing and Editing; Akane Matsumoto: Writing-Reviewing and Editing; Kosuke Masuda: Visualization, Writing-Reviewing and Editing; Masatoshi Kadoya: Writing-Reviewing and Editing; Kan Koizumi: Writing-Reviewing and Editing; Chie Sotozono: Writing-Reviewing and Editing; Mineo Kondo: Project administration, Writing-Reviewing and Editing.


In this work, we report on flexible toluene diisocyanate (TDI)-based polyurethane foams (FPUFs) chemically modified by POSS moieties, i.e., octa (3-hydroxy-3-methylbutyldimethylsiloxy) POSS (OCTA-POSS) and 1,2-propanediolizo-butyl POSS (PHI-POSS). The influence of silsesquioxane on the PU foaming process, structure, morphology, physicochemical, and mechanical properties, as well as flammability, was examined. FT-IR analysis provided evidence for the chemical incorporation of the nanofiller into the foam structure. It was found that the addition of POSS increases the apparent density of the foam and its compressive strength. The XRD and SEM-EDS techniques showed the uniform distribution of POSS in the FPUF with agglomeration depending on the kind and content of the introduced POSS moieties. The analysis of the thermogravimetric and microcalorimetry data revealed an improved resistance to the burning of FPUFs containing reactive POSS, as evidenced by the reduced rate of heat release (HRR). Importantly, the mechanical properties tests showed that the incorporation of silsesquioxane nanoparticles into the polyurethane structure via covalent bonds strengthens the foam integrity. The second group of pyrolyzates is compounds formed after the degradation of hard segments containing isocyanates and amines, such as 1,3-diisocyanato-2-methyl-benzene, 7-amino-1,3-dihydro-indol-2-one, and 4-(methyleneamino)phenyldimethyl amine . The preThe introduction of POSS to the flexible polyurethane foams influenced the physicochemical and mechanical properties of the hybrid materials. At the synthesis stage, the presence of silsesquioxanes affects the course of the reaction, as evidenced by the dielectric polarization vs. time profiles. A reduced maximum temperature during the foaming process of the hybrids was observed compared to the reference PU foam. For the OCTAPOSS cross-linking agent, core temperature lowering was more intense than for the pendant PHIPOSS modifier. The chemical incorporation of silsesquioxane into the polyurethane structure was confirmed by IR analysis, and elemental analysis maps of FPUF/OCTAPOSS materials revealed an even distribution of silicon on the surface of the tested material. Moreover, the WAXD patterns show only amorphous structures. In foams containing PHIPOSS, some agglomerates were detected, which may be associated with the local accumulation of pendant silsesquioxane cages. The good dispersion of OCTAPOSS particles in the polyurethane matrix caused an increase in the compressive strength of the composites, especially for the material with the highest POSS load. Py-GC/MS analysis allowed for the detection of the main products of the thermal decomposition of the modified foams formed via chain scission or depolymerization reactions, as well as by dehydration. POSS moieties degrade in a two-step process: (i) detachment of organic functional groups and (ii) the decomposition of the Si-O cage structure to form silica residue—the latter supports the formation of a thermal barrier on the materials’ surface. The applied POSS acted as flame retardants and lowered the THR and pHRR parameters in the cone calorimeter tests. The analysis of flammability data showed that the modified flexible polyurethane foams are less prone to fire development compared to the reference foams. POSS during combustion creates a silica layer, as evidenced by Py-GC/MS analysis, which can act as an insulating barrier hindering heat and mass transport.


The permeability of different strength grades of submerged non-dispersible concrete with different granulated slag admixtures in a saline soil environment simulated by different erosion solutions was investigated. The variation patterns of the chloride ion diffusion coefficient and pore characteristics were tested using NEL and MIP. The microscopic morphology of the specimens in different erosion environments and with slag doping was observed using SEM. The results showed that the impermeability of concrete in sulfate and complex salt environments was significantly reduced. The resistance of concrete to chloride ion penetration increased with the increase in strength grade, and the Cl− diffusion coefficient of C35 was 5–30% lower than those of C30 and C25 underwater non-dispersible concrete at 360 d. Meanwhile, the admixture of granulated blast-furnace slag optimized the pore size distribution and improved the matrix compactness and permeability. Underwater non-dispersible concrete (NDC/NUC) refers to self-compacting concrete  that doe42−, Cl− and Mg2+ [− can penetrate reinforced concrete structures to destroy the passivation film on the surface of steel bars and accelerate their corrosion [42− enters the concrete, it absorbs water, crystallizes and expands, leading to concrete cracking and damage [Saline soil is a general term for salinized soil, alkali soil, and salt and alkali soil. At present, China’s saline soil is mainly concentrated in six western provinces and regions, namely, Gansu, Ningxia, Qinghai, Inner Mongolia, Xinjiang and Shaanxi, which cover an area of about 1 million square kilometers ,8. Salinand Mg2+ ,10,11, wand Mg2+ ,13. Cl− orrosion ,15. Afted damage .When a transmission line is constructed in a saline soil area, part of the cast-in-place concrete pile should be poured under water. The replacement of ordinary concrete with underwater non-dispersible concrete for underwater pouring can effectively improve the water scour resistance and anti-dispersibility of the cast-in-place pile . HoweverThis work aimed to study the impermeability of underwater non-dispersible concrete in a saline erosion environment and the modification effect of slag content on its impermeability by simulating a saline soil environment and using a microscopic testing method to explore its microscopic mechanism.3 was used. The coarse aggregate was limestone with an apparent density of 2740 kg/m3 and particle size of 5~20 mm; the fine aggregate was natural river sand with an apparent density of 2.69 g/cm3 and fineness modulus of 2.80. The UWB-Ⅱ-type flocculant was selected with suspended turbidity < 150 mg/L and pH < 12; polycarboxylate superplasticizer was used with an effective solid content of 20% and water-reducing rate of 25%. The main chemical compositions of raw materials (mass fraction) are shown in P·O 42.5R-type cement from Dalian Onoda Factory was used in this test. S105 granulated blast-furnace slag powder with an apparent density of 605 kg/mC25, C30 and C35  underwater non-dispersible concrete specimens were prepared according to design rules for concrete mix ratios and test rules for underwater non-dispersible concrete. In particular, the standard referenced in the mix proportion design is the industry standard “Ordinary Concrete Mix Proportion Design Regulations” (JGJ55-2011), and the standard referenced in the process of concrete mixing and performance testing is the power industry standard “Underwater Non-dispersible Concrete Test Regulations” (DL/T5117-2000). In order to study the effect of strength grade on the impermeability of concrete, the underwater non-dispersed concrete had three strength grades, namely, C25, C30 and C35, corresponding to three water–binder ratios of 0.50, 0.45 and 0.40. Meanwhile, in order to study the effect of slag powder on the impermeability of underwater non-dispersed concrete, different dosages of slag powder were added to the concrete with the strength grade of C30. Mineral admixtures were mixed by the equal replacement method . The design and compressive strength for the concrete mix ratio are shown in Underwater molding method of the specimen: The test mold was put into a water tank containing fresh water or a salt solution, with the liquid level of the solution being 150 mm higher than the top of the test mold, and concrete was slowly poured in from the water surface to freely fall into the test mold. After pouring, the test mold was removed from the water tank and left to stand for 5 min at room temperature. After that, excess water was discharged by tapping on both sides of the test mold with a wooden hammer. After scraping the surface of the specimen with a spatula, the specimen was put back into water and cured for 48 h before form stripping. The concrete specimens were put back into fresh water (denoted by S), chloride solution (LY), sulfate solution (SY) or compound salt solution (FY) to be cured until the specified age (20~25 °C).2SO4 were selected to prepare three erosion solutions: chloride , sulfate  and their combination . Selecting this concentration of etching solution can not only accelerate corrosion but also prevent the concentration from being too high and deviating from the actual situation. Meanwhile, the three erosive salt solutions were replaced every 15 days.The ion type and concentration of the salt solution were determined in accordance with the relevant technical building codes in the saline soil area (GB/T 50942-2014 and GB 50021-2001). The saline soil in China is widely distributed, and the ion concentration varies greatly among different regions, but the saline soil in most areas is slightly corrosive. According to the actual situation of saline soil in China, industrial NaCl and Na1.Chloride penetration resistance testSpecimens eroded to a certain age in salt solution were treated with salt using a NEL-VJH vacuum water retention machine, and the chloride diffusion coefficient was measured by a NEL-PDU chloride diffusion coefficient tester. The test block was removed from the solution 7 d before the test. A section with a height of 50 mm was sampled by obtaining a drilling core, and its two end faces were cut and rubbed. Three specimens in each group were tested, and the average value of all data within 15% of each specimen was taken as the measured value. Anti-chloride ion test pieces are presented in 2.Water impermeability testCone specimens with a top diameter, bottom diameter and height of 175 mm, 185 mm and 150 mm were prepared. The water permeability height method was selected, and the water impermeability of the specimens was tested by an HS-40S concrete penetrometer . Water resistance test pieces are presented in 3.SEM and MIP testsA QUANTA 450 scanning electron microscope  and Micromeritics AutoPore Ⅳ9500 Series high-performance automatic mercury porosimeter  were used to analyze the microscopic morphology and pore characteristics of specimens in different erosion environments and with different slag contents.− diffusion coefficient of the C30 strength-grade underwater non-dispersible concrete subjected to erosion by different salt solutions. The results show that the Cl− diffusion coefficient of non-dispersible concrete gradually decreased with the prolongation of curing time. Compared with 28 days, the chlorine permeability resistance coefficient of C30 concrete in fresh water, sulfate, chloride salt and compound salt environments decreased by 38.27%, 30.82%, 36.84% and 28.28%, respectively, after curing for 360 days. At 28 d, the Cl− diffusion coefficient of C30 concrete in different saline and freshwater environments was basically the same. From 90 d to 180 d, the Cl− diffusion coefficient of concrete in sulfate and compound salt environments was higher than that in fresh water and 13.70% and 15.01% higher than that in the freshwater environment at 360 d, respectively. The Cl− diffusion coefficient of concrete in the chloride salt environment was basically the same as that in fresh water.2 production in the concrete in chloride solution (c). Compared with the non-dispersible concrete poured into fresh water (a), the microscopic characteristics are similar. Therefore, it can be seen that Cl− had basically no effect on the Cl− permeability resistance of concrete. In sulfate (b) and compound salt (d) environments, a large amount of acicular ettringite has been produced on the concrete surface, and the cement matrix is dilated and cracked, causing serious damage to the concrete structure. In chloride salts, the solubility of AFt is high, and Cl− reacts with concrete hydration products such as Ca(OH)2 and C3A to generate hydrated chloraluminate, which delays the formation of AFt. The higher the concentration of Cl−, the more significant the effect [42− and other ions in sulfate and compound salts enter the concrete, react with cement hydration products such as CH and C3A to generate dihydrate gypsum, ettringite, etc., and produce high crystallization stress, which promotes the generation and development of matrix cracks and then leads to the decline in the impermeability of concrete [SEM images of concrete at 360 d in fresh water and different salt solutions are shown in e effect . SO42− aconcrete ,28.− diffusion coefficient of concrete decreases with the increase in strength grade. As can be seen in − diffusion coefficient at 28 d in the sulfate environment, the C30 value is 14.87% lower than that of C25 concrete, and the C35 value is 4.86% lower than that of C30 concrete. As can be seen in − diffusion coefficient at 360 d in the chloride salt environment, the C30 value is 18.35% lower than that of C25 concrete, and the C35 value is 29.57% lower than that of C30 concrete. Similarly, for the Cl− diffusion coefficient at 28 d in the composite salt solution, the C30 value is 18.49% lower than that of C25 concrete, and the C35 value is 1.02% lower than that of C30 concrete. It can be seen that the higher the strength grade, the lower the water-to-cement ratio, the higher the contents of cement and admixtures, the higher the amounts of hydration products, the denser the concrete structure, and the less easily erosive ions in the salt solution invade its interior.− diffusion coefficients of underwater non-dispersible concrete with different slag powder contents subjected to erosion by sulfate, chlorine salt and compound salt, respectively. As can be seen in − diffusion coefficient of concrete decreases with the increase in slag powder content. The chloride diffusion coefficient of concrete with 60% slag powder content in the sulfate environment (a) is reduced by 6.49% compared with that without slag powder; at 360 d, the Cl− diffusion coefficient with 80% slag powder content is reduced by 60.23% compared with that without slag powder. However, in the chloride salt environment (b) and compound salt environment (c), the Cl− diffusion coefficient of concrete first decreases with the increase in slag powder content. When the slag powder content reaches 60%, the Cl− diffusion coefficient of concrete is the minimum and increases to some extent when the slag powder content is 80%. This is because the cement content in concrete is reduced due to the high mineral powder content and insufficient strength development in the later stage. In the chloride salt environment, the Cl− diffusion coefficient of concrete with 60% slag powder content is 49.29%, 67.15% and 68.27% lower than that of concrete without slag content at 28 d, 90 d, 180 d and 360 d, respectively. In the compound salt environment, the Cl− diffusion coefficient of concrete with 60% slag powder content is 45.61%, 68.33%, 74.84% and 65.64% lower than that of concrete without slag content at 28 d, 90 d, 180 d and 360 d, respectively.2 and Al2O3 in slag powder, calcium silicate hydrate gel is generated. The binding and adsorption effect of concrete on Cl− is enhanced, the structure is denser, and its impermeability is improved [improved .42− and Cl− invaded and reacted to generate AFt and hydrated calcium chloroaluminate, respectively [ectively , further−, and the aluminum phase in the slag powder can enhance the binding ability of Cl− and cement slurry, reduce the penetration rate of Cl− and improve the impermeability of concrete.(1)In a freshwater environment and salt solution environment, with the increase in age, the chloride ion diffusion coefficient of underwater non-dispersible concrete gradually decreases, and the average water seepage height of concrete gradually decreases.(2)− diffusion coefficient compared to fresh water is less than 5%, and there is no obvious difference in morphology or pore size distribution. Sulfate reduces the impermeability of concrete. The Cl− diffusion coefficient of concrete at 360 d in sulfate and composite salt solutions is 6%~15% higher than that in fresh water.The chloride salt environment has no obvious influence on the impermeability of underwater non-dispersible concrete. The difference in the Cl(3)− diffusion coefficient of C35 is 5%–30% lower than those of C30 and C25 underwater non-dispersible concrete at 360 d.The improvement caused by the increased strength grade is conducive to the enhancement of the impermeability of underwater non-dispersible concrete. The Cl(4)− diffusion coefficient of concrete is the lowest, which is 45%~70% lower than that of the blank sample.The addition of slag powder can significantly improve the impermeability of underwater non-dispersible concrete. The optimal dosage is 60%, and the ClIn this study, a sulfate solution, chlorine salt solution and composite solution of both were used to simulate a saline soil environment to study the microstructures of underwater non-dispersible concrete with different strength grades, in different erosion environments and at different erosion ages, as well as the change rules of chloride ion impermeability, water resistance and porosity. Additionally, this paper also explores the influence of different slag powder contents on the impermeability and resistance to chloride ions of underwater non-dispersible concrete, and the following conclusions are made:In this study, the test volume of the water penetration resistance test of underwater non-dispersed concrete was small, which led to a lack of systematic test data. Concrete with multiple strength grades can be tested to study the effect of strength grades on the water penetration resistance of concrete; different amounts of slag powder can also be added to concrete to study the effect of slag powder content on the water penetration resistance of concrete.


Background: Although small- and medium-sized hospitals comprise most healthcare providers in South Korea, data on antibiotic usage is limited in these facilities. We evaluated the pattern of antibiotic usage and its appropriateness in hospitals with <400 beds in South Korea. Methods: A multicenter retrospective study was conducted in 10 hospitals , with <400 beds in South Korea. We analyzed patterns of antibiotic prescription and their appropriateness in the participating hospitals. Data on the monthly antibiotic prescriptions and patient days for hospitalized patients were collected using electronic databases from each hospital. To avoid the effect of the COVID-19 pandemic, data were collected from January to December 2019. For the evaluation of the appropriateness of the prescription, 25 patients under antibiotic therapy were randomly selected at each hospital over 2 separate periods. Due to the heterogeneity of their characteristics, the orthopedics hospital was excluded from the analysis. The collected data were reviewed, and the appropriateness of antibiotic prescriptions was evaluated by 5 specialists in infectious diseases (adult and pediatric). Data from 2 hospitals were assigned to each specialist. The appropriateness of antibiotic prescriptions was evaluated from 3 aspects: route of administration, dose, and class. If the 3 aspects were ‘optimal,’ the prescription was considered ‘optimal.’ If only the route was ‘optimal,’ and the dose and/or class was ‘suboptimal,’ but not ‘inappropriate,’ it was considered ‘suboptimal.’ If even 1 aspect was ‘inappropriate,’ it was classified as ‘inappropriate.’ Results: The most commonly prescribed antibiotics in long-term care hospitals was fluoroquinolone, followed by β-lactam/β-lactamase inhibitor . In acute-care hospitals, these were third-generation cephalosporin, followed by first-generation cephalosporin and second-generation cephalosporin. The major antibiotics that were prescribed in the orthopedics hospital was first-generation cephalosporin. Only 2.3% of the antibiotics were administered inappropriately. In comparison, 15.3% of patients were prescribed an inappropriate dose. The proportion of inappropriate antibiotic prescriptions was 30.6% of the total antibiotic prescriptions. Conclusions: The antibiotic usage patterns vary between small- and medium-sized hospitals in South Korea. The proportion of inappropriate prescriptions exceeded 30% of the total antibiotic prescriptions.Funding: NoneDisclosures: None


Apesar da gravidade inicial, o trabalho em equipe multidisciplinar foi a chave para o diagnóstico rápido e o início do tratamento personalizado salvavidas, visando inflamação sistêmica e envolvimento de órgãos autoimunes.Aqui relatamos um caso desafiador de uma condição sistêmica rara – doença relacionada à imunoglobulina G4 (IgG4-RD) –que se apresentou com uma rara manifestação cardiovascular. A aortite por IgG4-RD está bem documentada na literatura, mas raramente tem sido relacionada ao envolvimento da árvore arterial coronariana.Uma mulher caucasiana de 56 anos deu entrada no pronto-socorro com dor torácica atípica, dispneia, cansaço e ocasionais surtos de dor abdominal durante a semana anterior. Além disso, foram relatadas mialgias proximais intermitentes de membros inferiores, ondas de calor cervicais, xerostomia e xeroftalmia. A paciente estava afebril, normotensa com taquicardia sinusal (113 batimentos/min) e taquipneia. Ao exame físico notava-se galope S3 e sinais de congestão pulmonar (ausência de edema periférico). A história médica pregressa era notável por rinite alérgica, emagrecimento  e uso continuado de tabaco (27 maços-ano). Há cinco anos, a paciente apresentava cãibras persistentes em membros inferiores há 5 meses, com estudo ultrassonográfico Doppler arterial sem alterações, tratada com terapia não esteroidal.A investigação diagnóstica na emergência revelou níveis ligeiramente elevados de troponina T de alta sensibilidade (73 ng/mL), níveis aumentados de peptídeo natriurético do tipo N-terminal pró-B (NT-proBNP) (3485 pg/mL), bem como uma ligeira elevação da creatina quinase. O eletrocardiograma mostrou extrassístoles ventriculares e alterações inespecíficas da repolarização. A ecocardiografia transtorácica (ETT) foi notável por disfunção sistólica grave do ventrículo esquerdo (VE) (fração de ejeção do VE [FEVE] <30%) com hipocinesia global, padrão de enchimento restritivo e regurgitação valvar aórtica moderada (Vídeo 1).Para excluir doença arterial coronariana e investigar dor abdominal persistente, foi realizada angiotomografia computadorizada (TC) toracoabdominal. Embora não tenha sido observado cálcio na artéria coronária, foi documentada infiltração fibrolipídica difusa da artéria coronária, além de aneurisma proximal da descendente anterior esquerda (DAE) e suboclusão distal da DA. Foi identificada dilatação da aorta ascendente (42 mm) com espessamento concêntrico homogêneo da parede de baixa densidade e aneurisma de aorta abdominal (47 mm) com trombo mural   . A angiA ressonância magnética cardíaca (RMC) diagnosticou disfunção do VE com dilatação grave  e realce tardio subendocárdico difuso por gadolínio. As sequências ponderadas em T2 não mostraram edema miocárdico, embora um sinal hiperintenso ao nível da parede da raiz da aorta Vídeo 2;  .Dada a doença polivascular difusa e a alta suspeita de etiologia não aterosclerótica, foi realizada extensa investigação diagnóstica. Os painéis de investigação de doenças infecciosas e imunológicas  estavam todos dentro da normalidade, exceto para uma alta velocidade de hemossedimentação (VHS) e hipergamaglobulinemia policlonal. Notavelmente, os níveis séricos de IgG4 aumentaram .Um estudo de imagem adicional com tomografia por emissão de pósitrons (PET) - TC mostrou intensa atividade do traçador sobre a aorta ascendente proximal e infrarrenal   .1Em relação à história prévia de rinite alérgica, foi realizada biópsia da mucosa nasal encontrando denso infiltrado linfocitário e discreto aumento de plasmócitos da lâmina própria (CD138+), muitos deles positivos para IgG4+ (razão IgG4+/IgG+ de 0-40% e um número indeterminado de células IgG4+/HPF)   . DianteDessa forma, o paciente foi iniciado com corticoterapia em altas doses  somada a 6 ciclos de infusão de ciclofosfamida e administração subcutânea de metotrexato. Foram iniciados medicamentos modificadores da doença da insuficiência cardíaca e o paciente foi encaminhado ao nosso centro de reabilitação cardíaca. A angio-TC repetida na alta (15 dias após o início do tratamento direcionado) mostrou uma redução significativa no espessamento da parede aórtica (10 a 5 mm)   .No seguimento de um ano, houve melhora da capacidade funcional, avaliada pela classe NYHA e valor de pico V02 , redução nos níveis de NT-proBNP (5260 a 2052 pg/mL) e sinais de remodelação cardíaca reversa (nomeadamente melhoria da FEVE de 30 para 40%). Além disso, houve declínio progressivo dos marcadores de doença inflamatória para valores normais  e resolução completa da atividade metabólica anormal na reavaliação do PET CT   .2 Este caso descreve uma apresentação anedótica e complexa com aortite e arterite coronária concomitante. A arterite crônica é uma apresentação típica de IgG4-RD envolvendo as grandes e, menos frequentemente, as artérias de médio calibre.4 A doença arterial coronariana é raramente relatada e, até onde sabemos, este é o único relato de caso em que a insuficiência cardíaca aguda foi o gatilho para a investigação inicial.6A IgG4-RD é uma condição fibroinflamatória imunomediada de múltiplos órgãos caracterizada por infiltração tecidual difusa de plasmócitos IgG4 positivos, fibrose estoriforme, flebite obliterativa e aumento de IgG sérica4.Os autores afirmam que a origem não aterosclerótica, neste caso, foi suspeitada pela ausência de cálcio coronariano (escore de cálcio 0) – demonstrando o alto valor preditivo negativo para doença calcificada/aterosclerótica clássica; a presença de doença difusa na coronariografia com apenas lesões intermediárias e suboclusão muito distal da DA não explica as alterações cinéticas difusas no ecocardiograma e na RMC. Além disso, contra uma origem aterosclerótica, há LGE subendocárdico difuso na RMC em vez de segmentar. Além disso, a história clínica florida deste caso é mais bem explicada por uma doença multissistêmica, apesar de uma etiologia tipicamente não aterosclerótica.8 no entanto, também repetimos a angio-TC demonstrando uma melhora significativa da aortite. Devido à sua capacidade de realizar avaliação funcional e caracterização tecidual, a RMC permite a avaliação simultânea da atividade da doença e repercussões específicas na função do VE na presença de arterite coronariana.A imagem multimodal aliada à assinatura inflamatória foi essencial para esse desafio diagnóstico e terapêutico. Técnicas de imagem cardiovascular, como ETT, angio-TC, PET-CT e RMC, foram usadas com sucesso para detecção de doenças, avaliação de sintomas e monitoramento. Enquanto a VHS e a hipergamaglobulinemia policlonal levantaram a suspeita de uma possível vasculite, o espessamento da parede aórtica e a doença arterial coronariana não aterosclerótica foram primordiais para orientar a investigação para uma etiologia que não fosse a aterosclerose clássica. PET-CT confirmou a inflamação periarterial e coronária ativa. Além disso, forneceu pistas para correlação clínica, ou seja, explosões de dor abdominal, mialgia proximal dos membros inferiores e ondas de calor cervicais (como observado pela atividade metabólica/inflamatória difusa de todo o corpo). De acordo com um grande estudo retrospectivo, a imagem PET-CT pode ser a única modalidade de imagem útil para avaliar a resposta ao tratamento durante o seguimento,Uma equipe multidisciplinar  foi de extrema importância na investigação da multiplicidade de envolvimento de órgãos e chave para o diagnóstico de IgG4-RD. Após descartar o diagnóstico mais frequente, a equipe multidisciplinar, com base em todos os achados clínicos e laboratoriais, decide assumir a doença relacionada à IgG4. Embora a biópsia não tenha sido totalmente patogênica, ela foi realizada em local não ativamente afetado neste momento (mas na história médica prévia); optamos por não realizar biópsia aórtica ou miocárdica na fase aguda e instável com riscos potencialmente maiores. Embora não tenhamos um diagnóstico confirmador de envolvimento glandular, a reumatologia, essencial neste caso, considera bastante típico o envolvimento de glândulas salivares e xeroftalmia.9 mesmo nos estágios fibróticos avançados.10 As lesões cardiovasculares relacionadas à IgG4 geralmente requerem doses mais altas de corticosteroides,12 muitas vezes melhorando as lesões inflamatórias na TC ou PET.7 Este caso foi ainda mais complicado pelo efeito mineralocorticoide derivado dos corticosteroides, que pode facilitar a descompensação da Insuficiência Cardíaca. Embora dados observacionais possam apoiar essa abordagem, o tratamento inicial com combinação de imunossupressores permanece controverso.13 A ciclofosfamida demonstrou ter bons resultados a longo prazo e menores taxas de recaída.14 Da mesma maneira, rituximabe também foi sugerido para ter efeitos benéficos no IGG4-RD, mas reduziu severamente os sintomas de FEVE e Insuficiência Cardíaca e tuberculose latente, contraindicando seu uso em nosso caso. Diferentemente do caso publicado anteriormente envolvendo artérias coronárias,5 na discussão multidisciplinar, consideramos que a aspirina não teve nenhum papel nesse tipo de acometimento arterial e aumentou o risco de sangramento devido ao tratamento contínuo com esteroides.O bloqueio neuro-hormonal com agentes modificadores da doença é essencial para melhorar a sobrevida em pacientes com Insuficiência Cardíaca e reduzir a FEVE. De acordo com o Consenso Internacional sobre o tratamento de IgG4-RD, os glicocorticoides são os agentes de primeira linha para indução da remissão,6 Além de ser notável por sua rara apresentação, este caso destaca o papel da multimodalidade de imagem e da investigação multidisciplinar como peças-chave no estabelecimento correto de um diagnóstico e na facilitação de um plano de tratamento personalizado.Relatamos um caso desafiador de IgG4-RD apresentando insuficiência cardíaca aguda consequente a arterite coronariana e aortite, com tratamento conservador bem-sucedido, em vez de cirurgia de revascularização miocárdica invasiva como estratégia inicial. 1 We documented IgG4-RD with diffuse coronary periarteritis, presenting as acute heart failure in this particular case. Despite the initial severity, multidisciplinary teamwork was the key to expeditious diagnosis and initiating tailored life-saving treatment targeting systemic inflammation and autoimmune organ involvement.Here we report a challenging case of a rare systemic condition – immunoglobulin G4-related disease (IgG4-RD) – that presented with a rare cardiovascular manifestation. Aortitis due to IgG4-RD is well-documented in the literature, but rarely has it been related to the involvement of the coronary arterial tree.A 56-year-old Caucasian woman presented to the emergency department with atypical chest pain, dyspnea, tiredness, and occasional abdominal pain bursts during the previous week. In addition, intermittent proximal lower limb myalgia, cervical hot flashes, xerostomy and xerophthalmia were reported. The patient was afebrile, normotensive with sinus tachycardia (113 beats/min) and tachypnea. The physical examination was remarkable for S3 gallop and signs of pulmonary congestion . Past medical history was notable for allergic rhinitis, emaciation  and continued tobacco use (27 pack-year). Five years before, the patient had persistent lower limb cramps for 5 months, with an unremarkable arterial Doppler ultrasound study, treated with non-steroidal therapy.Diagnostic workup at the emergency revealed slightly elevated high sensitivity troponin T levels (73 ng/mL), increased levels of N-terminal pro–B-type natriuretic peptide (NT- proBNP) (3485 pg/mL) as well as a slight elevation of creatine kinase. Electrocardiography showed ventricular extrasystoles and non-specific repolarization abnormalities. Transthoracic echocardiography (TTE) was remarkable for severe left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] <30%) with global hypokinesia, restrictive filling pattern and moderate aortic valve regurgitation (Video 1).In order to exclude coronary artery disease and investigate persistent abdominal pain, a thoracoabdominal computed tomographic (CT) angiography was performed. While no coronary artery calcium was observed, diffuse coronary artery fibrolipidic infiltration was documented, in addition to proximal left anterior descendent (LAD) aneurysm and distal LAD suboclusion. Dilatation of the ascending aorta (42 mm) with concentric homogeneous low-density wall thickening and an abdominal aorta aneurysm (47mm) with mural thrombus was identified   . Corona2) and diffuse subendocardial late gadolinium enhancement. T2-weighed sequences showed no myocardial edema, albeit a hyperintense signal at the aortic root wall level  diagnosed LV dysfunction with severe dilatation  were all within normal range, except for a high erythrocyte sedimentation rate (ESR) and polyclonal hypergammaglobulinemia. Notably, serum levels of IgG4 were increased .An additional imaging study with Positron Emission Tomography (PET) - CT depicted intense tracer activity over the proximal ascending and infra-renal aorta   .1Regarding the previous history of allergic rhinitis, a nasal mucosal biopsy was performed: it found a dense lymphocytic infiltrate and a slight increase in lamina propria plasma cells (CD138+), many of these positive for IgG4+ (an IgG4+/IgG+ ratio of 0-40% and an indeterminate number of IgG4+ cells/HPF)   . Given Accordingly, the patient was started on high-dose corticosteroid therapy  added to 6 cycles of cyclophosphamide infusion and methotrexate subcutaneous administration. Heart failure disease-modifying drugs were initiated, and the patient was referred to our cardiac rehabilitation center. Repeated angio-CT at discharge (15 days after the start of targeted treatment) showed a significant reduction in aortic wall thickening (10 to 5 mm)   .At one year follow-up, there was an improvement in functional capacity, as assessed by NYHA class and peak V02 value (13.8 to 19.9 ml/kg/min), a reduction in NT-proBNP levels (5260 to 2052 pg/mL) and signs of reverse cardiac remodeling (namely LVEF improvement from 30 to 40%). Moreover, there was a progressive decline in inflammatory disease markers towards normal values  and complete resolution of abnormal metabolic activity at PET CT reassessment   .2 This case describes an anecdotally reported and complex presentation with aortitis and concomitant coronary arteritis. Chronic arteritis is a typical presentation of IgG4-RD involving the large and, less frequently, medium-sized arteries.4 Coronary artery disease is seldom reported, and to the best of our knowledge, this is the only case report in which acute heart failure was the trigger for the initial investigation.6IgG4-RD is a multi-organ immune-mediated fibroinflammatory condition characterized by diffuse tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and increased serum IgG4.The authors state that the non-atherosclerotic origin, in this case, was suspected due to the absence of coronary calcium - demonstrating the high negative predictive value for classic calcified/atherosclerotic disease; the presence of diffuse disease on coronary angiography with only intermediate lesions and very distal LAD suboclusion does not explain the diffuse kinetic changes on echocardiography and CMR. Also, against an atherosclerotic origin, there is diffuse subendocardial LGE at CMR rather than segmental. Furthermore, the flowery clinical history of this case is better explained by a multisystemic disease, despite a typically non-atherosclerotic etiology.8 nonetheless, we also repeated Angio- CT demonstrating a significant improvement of aortitis. Due to its capability to perform functional evaluation and tissue characterization, CMR allows simultaneous assessment of disease activity and specific repercussions on LV function when coronary arteritis is present.Multimodality imaging coupled with the inflammatory signature was essential for this diagnostic and therapeutic challenge. Cardiovascular imaging techniques, namely TTE, angio-CT, PET-CT and CMR, were successfully used for disease detection, symptom assessment, and monitoring. While ESR and polyclonal hypergammaglobulinemia raised the suspicion of a possible vasculitis, the aortic wall thickening and non-atherosclerotic coronary artery disease were paramount in guiding the investigation toward an etiology different than classical atherosclerosis. PET-CT confirmed the active periarterial and coronary artery inflammation. Moreover, it provided clues for clinical correlation, namely abdominal pain bursts, proximal lower limb myalgia and cervical hot flashes (as noted by diffuse whole body enhanced metabolic/inflammatory activity). According to a large retrospective study, PET-CT imaging may be the only imaging modality useful for assessing treatment response during follow-up;A multidisciplinary team  was of utmost importance in investigating the multitude of organ involvement and key to achieving the diagnosis of IgG4-RD. After ruling out the most frequent diagnosis, the multidisciplinary team, based on all clinical and laboratory findings, decides to assume the IgG4 - related disease. Although the biopsy was not fully pathogenic, it was performed in a site not actively affected at this moment ; we chose not to perform an aortic or myocardial biopsy in the acute and unstable phase, potentially greater risks. Although we did not have a confirming diagnosis of gland involvement, the rheumatology, essential in this case, considers the involvement of salivary glands and xerophthalmia to be quite typical. Even though the criteria might not be fulfilled, the fact that the patient presented a good response to the IgG4-RD targeted therapy corroborates this hypothesis.9 even in the advanced fibrotic stages.10 IgG4-related cardiovascular lesions usually require higher doses of corticosteroids,12 often improving the inflammatory lesions on CT or PET imaging.7 This case was further complicated by the mineralocorticoid-like effect derived from corticosteroids, which can facilitate Heart Failure decompensation. Although observational data may support this approach, initial treatment with combination immunosuppressors remains controversial.13 Cyclophosphamide has been shown to have good long-term outcomes and lower relapse rates.14 Likewise, rituximab has also been suggested to have beneficial effects in IGG4-RD, yet severely reduced LVEF and Heart Failure symptoms and latent tuberculosis, contra-indicated its use in our case. Unlike the previously published case involving coronary arteries,5 in the multidisciplinary discussion, we consider that aspirin had no role in this type of artery involvement and increased the bleeding risk due to ongoing steroid treatment.Neuro-hormonal blockade with disease-modifying agents is essential to improve survival in patients with Heart Failure and reduce LVEF. According to the International Consensus on the treatment of IgG4-RD, glucocorticoids are the first-line agents for induction of remission,6 Besides being remarkable for its rare presentation, this case highlights the role of multimodality imaging and multidisciplinary workup as key players in correctly establishing a diagnosis and facilitating a tailored treatment plan.We reported a challenging case of IgG4-RD presenting with acute heart failure consequent to coronary arteritis and aortitis, with successful conservative management, rather than invasive coronary bypass graft surgery as an initial strategy.