Acute Response Research Articles

Acute Antioxidant Response to Two Types of Exercises: 2000 M Run vs. Burpee Test.

Physical activity results in oxidative stress, as evidenced by the increased production of reactive oxygen, nitrogen species, and inflammatory mediators. The management of these components is instrumental for antioxidant adaptation to exercise and post-exercise recovery. Therefore, the present report aims to study the antioxidant response to two types of exercise (a 2000 m run and a burpee test) in healthy volunteers after a long period of inactivity (1-2 months). Antioxidant enzyme activities and oxidative stress markers (protein carbonyls and malondialdehyde content) were measured in neutrophils, peripheral blood mononuclear cells, and plasma. These parameters were determined under basal conditions and immediately post-exercise. Compared to those in basal state, neutrophil superoxide dismutase (28.3 vs. 22.9 pkat/109 cells), glutathione peroxidase (147.5 vs. 120.1 nkat/109 cells), and catalase (106.3 vs. 57.9 k/109 cells) were activated significantly (p < 0.05) after the burpee test. Peripheral blood mononuclear cells exhibited only significant (p < 0.05) catalase activation (113.6 vs. 89.4 k/109 cells) after the burpee test. Other enzymes, such as glutathione reductase and myeloperoxidase, tended to increase post-exercise, although the differences from baseline were not significant. Finally, compared to basal conditions, the protein carbonyl (24.5 vs. 14.5 mmol/L) and malondialdehyde (39.6 vs. 18.3 mmol/L) contents increased significantly (p < 0.05) in neutrophils and in plasma (115.1 vs. 97.8 and 130.2 vs. 123.4 μmol/L, respectively) after the burpee test. In conclusion, high-intensity exercise seems to induce immediate oxidative stress in inactive individuals, and the acute antioxidant response was slightly greater after the burpee test than after the 2000 m run. Glutathione-dependent antioxidant systems are activated immediately as protective mechanisms.

Characterization of immune responses and immunopathology in turkeys experimentally infected with clostridial dermatitis-producing strains of Clostridium septicum

Clostridium septicum is one of the major causative agents of clostridial dermatitis (CD), an emerging disease of turkeys, characterized by sudden deaths and necrotic dermatitis. Despite its economic burden on the poultry industry, the immunopathological changes and pathogen-specific immune responses are poorly characterized. Here, we used three strains of C. septicum, namely Str. A1, Str. B1 and Str. C1, isolated from CD field outbreaks, to experimentally infect turkeys to evaluate local (skin and muscle) and systemic (spleen) pathological and immunological responses. Results showed that while all three strains produced an acute disease, Str. A1 and B1 caused significantly higher mortality when compared to Str. C1. Gross and histopathology evaluation showed that birds infected with Str. A1 and B1 had severe inflammatory, edematous, granulomatous and necrotic lesions in the skin, muscle and spleen, while these lesions produced by Str. C1 were relatively less severe and mostly confined to skin and/or muscle. Immune gene expression in these tissues showed that Str. B1-infected birds had significantly higher expression of interleukin (IL)−1β, IL-6 and interferon (IFN)γ genes compared to uninfected control, suggesting a robust inflammatory response both locally as well as systemically. The transcription of IL-1β and IFNγ in the muscle or spleen of Str. A1-infected birds and IL-1β in the skin of Str. C1-infected group was also significantly higher than control. Additionally, Str. A1 or B1-infected groups also had significantly higher IL-4 transcription in these tissues, while birds infected with all three strains developed C. septicum-specific serum antibodies. Furthermore, splenic cellular immunophenotyping in the infected turkeys showed a marked reduction in CD4+ cells. Collectively, it can be inferred that host responses against C. septicum involve an acute inflammatory response along with antibody production and that the disease severity seem to depend on the strain of C. septicum involved in CD in turkeys.

Acute Response of the Noninfarcted Myocardium and Surrounding Tissue Assessed by T2 Mapping After STEMI

BackgroundST-segment elevation myocardial infarction (STEMI) is associated with a systemic and local inflammatory response with edema. However, their role at the tissue level is poorly characterized. ObjectivesThis study aims to characterize T2 values of the noninfarcted myocardium (NIM) and surrounding tissue and to investigate prognostic relevance of higher NIM T2 values after STEMI. MethodsA total of 171 consecutive patients with STEMI without prior cardiovascular events who underwent cardiac magnetic resonance after primary percutaneous coronary intervention were analyzed in terms of standard infarct characteristics. Edema of the NIM, liver, spleen, and pectoralis muscle was assessed based on T2 mapping. Follow-up was available for 130 patients. The primary endpoint was major adverse cardiac events (MACE), defined as cardiovascular death, myocardial infarction, unplanned coronary revascularization or rehospitalization for heart failure. The median time from primary percutaneous coronary intervention to cardiac magnetic resonance was 3 days (IQR: 2-5 days). ResultsHigher (above the median value of 45 ms) T2 values in the NIM area were associated with larger infarct size, microvascular obstruction, and left ventricular dysfunction and did not correlate with C-reactive protein, white blood cells, or T2 values of the pectoralis muscle, liver, and spleen. At a median follow-up of 17 months, patients with higher (>45 ms) NIM T2 values had increased risk of MACE (P < 0.001) compared with subjects with NIM T2 values ≤45 ms, mainly caused by a higher rate of myocardial reinfarction (26.3% vs 1.4%; P < 0.001). At multivariable analysis, higher NIM T2 values independently predicted MACE (HR: 2.824 [95% CI: 1.254-6.361]; P = 0.012). ConclusionsHigher NIM T2 values after STEMI are independently associated with worse cardiovascular outcomes, mainly because of higher risk of myocardial infarction.

Biological Effects of Small Sized Graphene Oxide Nanosheets on Human Leukocytes.

Since the discovery of graphene, there has been a wide range of the literature dealing with its versatile structure and easy binding of biomolecules as well as its large loading capacity. In the emerging field of immunotherapy, graphene and its derivatives have potential uses as drug delivery platforms directly into tumour sites or as adjuvants in cancer vaccines, as they are internalized by monocytes which in turn may activate adaptive anti-tumoral immune responses. In this study, we expose cells of the innate immune system and a human acute monocytic leukemia cell line (THP-1) to low doses of small-sized GO nanosheets functionalized with bovine serum albumin (BSA) and fluorescein isothiocyanate (FITC), to study their acute response after internalization. We show by flow cytometry, uptake in cells of GO-BSA-FITC reaches 80% and cell viability and ROS production are both unaffected by exposure to nanoparticles. On the contrary, GO-BSA nanosheets seem to have an inhibitory effect on ROS production, probably due to their antioxidant properties. We also provided results on chemotaxis of macrophages derived from peripheral blood monocytes treated with GO-BSA. In conclusion, we showed the size of nanosheets, the concentration used and the degree of functionalization were important factors for biocompatibility of GO in immune cells. Its low cytotoxicity and high adaptability to the cells of the innate immune system make it a good candidate for deployment in immunotherapy, in particular for delivering protein antigens to monocytes which activate adaptive immunity.

Involvement of Extracellular Vesicles in the Proinflammatory Response to Clozapine: Implications for Clozapine-Induced Agranulocytosis.

Most idiosyncratic drug reactions (IDRs) appear to be immune-mediated, but mechanistic events preceding severe reaction onset remain poorly defined. Damage-associated molecular patterns (DAMPs) may contribute to both innate and adaptive immune phases of IDRs, and changes in extracellular vesicle (EV) cargo have been detected post-exposure to several IDR-associated drugs. To explore the hypothesis that EVs are also a source of DAMPs in the induction of the immune response preceding drug-induced agranulocytosis, the proteome and immunogenicity of clozapine- (agranulocytosis-associated drug) and olanzapine- (non-agranulocytosis-associated drug) exposed EVs were compared in two preclinical models: THP-1 macrophages and Sprague-Dawley rats. Compared with olanzapine, clozapine induced a greater increase in the concentration of EVs enriched from both cell culture media and rat serum. Moreover, treatment of drug-naïve THP-1 cells with clozapine-exposed EVs induced an inflammasome-dependent response, supporting a potential role for EVs in immune activation. Proteomic and bioinformatic analyses demonstrated an increased number of differentially expressed proteins with clozapine that were enriched in pathways related to inflammation, myeloid cell chemotaxis, wounding, transforming growth factor-β signaling, and negative regulation of stimuli response. These data indicate that, although clozapine and olanzapine exposure both alter the protein cargo of EVs, clozapine-exposed EVs carry mediators that exhibit significantly greater immunogenicity. Ultimately, this supports the working hypothesis that drugs associated with a risk of IDRs induce cell stress, release of proinflammatory mediators, and early immune activation that precedes severe reaction onset. Further studies characterizing EVs may elucidate biomarkers that predict IDR risk during development of drug candidates. SIGNIFICANCE STATEMENT: This work demonstrates that clozapine, an idiosyncratic drug-induced agranulocytosis (IDIAG)-associated drug, but not olanzapine, a safer structural analogue, induces an acute proinflammatory response and increases extracellular vesicle (EV) release in two preclinical models. Moreover, clozapine-exposed EVs are more immunogenic, as measured by their ability to activate inflammasomes, and contain more differentially expressed proteins, highlighting a novel role for EVs during the early immune response to clozapine and enhancing our mechanistic understanding of IDIAG and other idiosyncratic reactions.

Neuroprotection Afforded by an Enriched Mediterranean-like Diet Is Modified by Exercise in a Rat Male Model of Cerebral Ischemia.

Ischemic stroke is an important cause of mortality and disability worldwide. Given that current treatments do not allow a remarkably better outcome in patients after stroke, it is mandatory to seek new approaches to preventing stroke and/or complementing the current treatments or ameliorating the ischemic insult. Multiple preclinical and clinical studies highlighted the potential beneficial roles of exercise and a Mediterranean diet following a stroke. Here, we investigated the effects of a pre-stroke Mediterranean-like diet supplemented with hydroxytyrosol and with/without physical exercise on male rats undergoing transient middle cerebral artery occlusion (tMCAO). We also assessed a potential synergistic effect with physical exercise. Our findings indicated that the diet reduced infarct and edema volumes, modulated acute immune response by altering cytokine and chemokine levels, decreased oxidative stress, and improved acute functional recovery post-ischemic injury. Interestingly, while physical exercise alone improved certain outcomes compared to control animals, it did not enhance, and in some aspects even impaired, the positive effects of the Mediterranean-like diet in the short term. Overall, these data provide the first preclinical evidence that a preemptive enriched Mediterranean diet modulates cytokines/chemokines levels downwards which eventually has an important role during the acute phase following ischemic damage, likely mediating neuroprotection.

A single dose multi-ingredient pre-workout supplement enhances upper body resistance exercise performance.

Multi-ingredient pre-workout supplements (MIPS) are commonly used by individuals looking to enhance exercise performance and augment adaptations to training. However, the efficacy of commercially available MIPS is largely dependent on the ingredient profile, and new formulations should be investigated to determine their effectiveness. Therefore, the purpose of this study was to examine the effects of a commercially available MIPS product on performance during an upper body resistance exercise protocol. Twenty resistance-trained participants (10 men, 10 women) volunteered to complete this double-blind, placebo-controlled, crossover study consisting of 3 visits. Visit 1 consisted of body composition, 1-repetition maximum (1RM) testing, and familiarization. Visits 2 and 3 consisted of supplementation with either MIPS or placebo (PLA) 1 h prior to completion of an upper body resistance exercise workout during which power output, repetitions completed, rating of perceived exertion (RPE), and perceived recovery were recorded. Assessments of reaction time, isometric mid-thigh pull, and perceived levels of focus, energy, fatigue, and "muscle pump" were also completed before supplementation, 1 h after supplementation, and immediately after exercise. Statistical analysis revealed significant main effects of trial for reaction time (p < 0.001) and bench press peak power (p = 0.026) indicating better performance during the MIPS trial. Furthermore, total number of repetitions completed significantly increased (p = 0.003) during the MIPS (96.90 ± 21.31 repetitions) trial compared to PLA (89.50 ± 18.37 repetitions). Additionally, overall session RPE was significantly lower (p = 0.002) during the MIPS (7.6 ± 1.2) trial compared to PLA (8.3 ± 0.9). These findings suggest that acute supplementation with this MIPS improved upper body resistance exercise performance while reducing participant RPE. Further research should investigate the efficacy of chronic supplementation with this MIPS as the acute response provided an ergogenic benefit.

β2-Adrenoceptors activation regulates muscle trophic-related genes following acute resistance exercise in mice.

Resistance exercise (RE) training and pharmacological stimulation of β2-Adrenoceptors (β2-ARs) alone can promote muscle hypertrophy and prevent muscle atrophy. Although the activation of the sympathetic nervous system (SNS) is a well-established response during RE, the physiological contribution of the endogenous catecholamines and β2-ARs to the RE-induced changes on skeletal muscle protein metabolism remains unclear. This study investigated the effects of the β2-ARs blockade on the acute molecular responses induced by a single bout of RE in rodent skeletal muscles. Male C57BL6/J mice were subjected to a single bout of progressive RE (until exhaustion) on a vertical ladder under β2-AR blockade with ICI 118,551 (ICI; 10mgkg-1, i. p.), or vehicle (sterile saline; 0.9%, i. p.), and the gene expression was analyzed in gastrocnemius (GAS) muscles by qPCR. We demonstrated that a single bout of RE acutely increased the circulating levels of stress-associated hormones norepinephrine (NE) and corticosterone (CORT), as well as the muscle phosphorylation levels of AMPK, p38 MAPK and CREB, immediately after the session. The acute increase in the phosphorylation levels of CREB was followed by the upregulation of CREB-target genes Sik1, Ppargc1a and Nr4a3 (a central regulator of the acute RE response), 3h after the RE session. Conversely, β2-AR blockade reduced significantly the Sik1 and Nr4a3 mRNA levels in muscles of exercised mice. Furthermore, a single bout of RE stimulated the mRNA levels of the atrophic genes Map1lc3b and Gabarapl1 (autophagy-related genes) and Mstn (a well-known negative regulator of muscle growth). Unexpectedly, the gene expression of Igf-1 or Il-6 were not affected by RE, while the atrophic genes Murf1/Trim63 and Atrogin-1/Mafbx32 (ubiquitin-ligases) were increased only in muscles of exercised mice under β2-AR blockade. Interestingly, performing a single bout of RE under β2-AR blockade increased the mRNA levels of Mstn in muscles of exercised mice. These data suggest that β2-ARs stimulation during acute RE stimulates the hypertrophic gene Nr4a3 and prevents the overexpression of atrophic genes such as Mstn, Murf1/Trim63, and Atrogin-1/Mafbx32 in the first hours of postexercise recovery, indicating that he SNS may be physiologically important to muscle adaptations in response to resistance training.

Transcranial Direct Current Stimulation (tDCS) Ameliorates Stress-Induced Sleep Disruption via Activating Infralimbic-Ventrolateral Preoptic Projections.

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutamatergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 min, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 h post-stimulation, persisting up to 16-24 h. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS's sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS's effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy.

Evaluation of the efficacy of adjuvant radiotherapy versus chemoradiotherapy in patients with salivary gland tumors.

The aim of this study was to compare the efficacy of adjuvant radiotherapy (RT) versus adjuvant chemoradiotherapy (CRT) in patients with salivary gland tumors (SGTs). Data from patients who underwent adjuvant RT for a diagnosis of SG cancer at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital between September 01, 2009 and September 01, 2022 were analysed retrospectively. We evaluated the efficacy of RT alone versus CRT in these patients in terms of acute response, treatment tolerance, overall survival (OS), and disease-free survival (DFS). Fifty-five patients who underwent RT between September 14, 2009 and August 04, 2022 at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital were included in this study. Eight patients who did not meet the study criteria were excluded; thus, the analysis was performed for 47 patients. The median follow-up period was 60 months (range: 6-160 months). The median patient age was 53 years (range: 18-86 years). Thirty-nine patients (83%) had parotid tumors and eight patients (17%) had submandibular cancer. The time from surgery to RT was 48 days (range: 20-126 days). Intensity-modulated radiotherapy was administered to all patients and the median RT dose was 66 Gy (range: 52-70 Gy). Concomitant chemotherapy (CCT) (40 mg/m 2 of cisplatin weekly) was administered to 13 patients (27.7%). Acute adverse events were observed in 17 patients (36.2%). Interruption of RT was noted for only six patients (12.8%), and this proportion did not differ significantly between the CRT and RT-only arms ( P = 0.538). Acute side effects were observed in 17 patients (36.2%), and there were no significant relationships between acute side effects and the administration of CCT ( P = 0.112). Recurrence was observed in 10 patients (21.3%). All recurrences were locoregional and no distant metastases were observed during the follow-up period. The median DFS of the patients was 48 months (range: 4-160 months), 1-year DFS was 86%, 2-year DFS was 83.5%, and 5-year DFS was 77.9%. There was no statistically significant difference in DFS between the adjuvant CRT and RT-alone arms ( P = 0.114). At the date of last follow-up, 14 patients (29.8%) had died. The median OS of the patients was 58.5 months (range: 6-160 months), 1-year OS was 91.4%, 2-year OS was 86.8%, and 5-year OS was 78%. There was no statistically significant difference in OS between the adjuvant CRT and RT-only arms ( P = 0.453). Stage was identified as the most important prognostic factor for DFS and OS. No significant differences in OS, DFS, or acute side effects were observed between the CRT and RT-only arms. Additional studies are needed to identify the subgroup of SGT patients for which CRT is most warranted.

Variability of marine epifauna assemblages in response to the microhabitat type and thermal stress

Anthropogenic activities like overfishing, urban and industrial developments, and coastal pollution are some of the stressors affecting the marine environment. Thermal pollution from coastal industries like power plants represents the main cause of increased temperatures in water bodies, which can affect the marine community structure and function. The aim of this study was: 1) to compare the epifaunal communities associated with three different types of microhabitats: articulated coralline algae around coral colonies (CWC), articulated coralline algae in the absence of coral colonies and other benthic organisms (CNB), and the seaweed Ecklonia cava (ECK); and 2) to determine the potential changes in epifaunal communities in acute response to the increased water temperature resulting from coastal power plant activities in Jeju Island, South Korea. Our findings revealed a strong association between epifaunal abundance and microhabitat type, with CNB exhibiting the highest abundance while ECK showed the lowest. Additionally, an increase in temperature of 0.5–1.5 °C was observed to not alter the overall abundance of epifauna at the impact site, however, it did lead to a shift in the community composition. There was a notable decline in the abundance of amphipods-caprellids, polychaetes, gastropods, and bivalves with their densities nearly halving in response to thermal stress. Furthermore, there was a shift in dominant taxa, transitioning from amphipods-caprellids to amphipods-non-caprellids. Conversely, other taxonomic groups such as isopods and copepods showed a remarkable surge in abundance following the temperature rise. These findings highlight the relationship between rising temperatures and epifaunal community composition while emphasizing taxa’s different responses to thermal stress.

Inflammation gene signature to predict survival outcomes in hepatocellular carcinoma (HCC): A machine-learning approach.

551 Background: Inflammation is closely associated with HCC tumorigenesis. Understanding transcriptomic features of inflammatory response will elucidate potential therapeutic targets that could improve survival outcomes. Herein, we study the association between inflammation-based genes and survival outcomes in early-stage HCC. Methods: Transcriptomic and clinical data of 249 patients with resectable stage I and II HCC were obtained from The Cancer Genome Atlas. 132 genes associated with acute and chronic inflammatory response were identified from the molecular signature database. Those were then used in a principal component analysis (PCA) to cluster patients into high and low inflammation groups using the median of the first PCA. Inflammation related differentially expressed genes (DEGs) between the two groups were then identified &amp; were fit in Least Absolute Shrinkage and Selection Operator model to reduce the multicollinearity. Uni- and multi-variate Cox proportional hazard model was used to find the independent predictors of survival. PCA was applied to significant genes to calculate the inflammation score (IS) and the optimal cut-off point was chosen based on survival. Log-rank test and Kaplan Meier curves were used to correlate the IS with overall survival (OS) &amp; disease-free survival (DFS). Pearson’s Chi-squared, Wilcoxon rank sum, and Fisher’s exact tests were used to correlate the inflammation groups with clinical variables. Gene set variation analysis was performed to investigate enriched pathways between groups using the cancer hallmark gene sets. Results: We identified 6 inflammation-related DEGs associated with survival including: ADAM8, CCR7, FFAR3, S100A9, TNF, and TREM1. Two of those were independent predictors of survival: TREM1 &amp; FFAR3. Based on IS cut off of 0.29 we have grouped patients into inflammation high (n=91) and inflammation low (n=158) groups. The low-inflammation group had significantly better OS &amp; DFS (P=0.00039, P=0.039) respectively. No significant association was found between the inflammation groups and multiple variables including hepatitis B and C, alcohol and non-alcohol fatty liver disease. Stage I HCC patients had low-inflammation scores and better survival outcomes compared to stage II, indicative of an association between inflammation and HCC evolution. Pathway enrichment analysis notably showed significant enrichment in signal transduction pathways in the high inflammation group including Wnt/β-catenin, Notch, PI3K-AKT-mTOR, Hedgehog, TGFβ and upregulated KRAS signaling. Conclusions: Findings from this analysis highlight the close association between inflammation and survival outcomes in early-stage HCC and support the utility of an inflammation-based gene signature to predict survival in this disease setting. Our work also sheds light on potentially targetable pathways linked to IS that deserve further exploration.

Combined Accentuated Eccentric Loading and Rest Redistribution in High-Volume Back Squat: Acute Stimulus and Fatigue.

Chae, S, Long, SA, Lis, RP, McDowell, KW, Wagle, JP, Carroll, KM, Mizuguchi, S, and Stone, MH. Combined accentuated eccentric loading and rest redistribution in high-volume back squat: Acute stimulus and fatigue. J Strength Cond Res 38(4): 648-655, 2024-The purpose of this study was to examine acute stimulus and fatigue responses to combined accentuated eccentric loading and rest redistribution (AEL + RR). Resistance-trained men ( n = 12, 25.6 ± 4.4 years, 1.77 ± 0.06 m, and 81.7 ± 11.4 kg) completed a back squat (BS) 1 repetition maximum (1RM) and weight releaser familiarization session. Three BS exercise conditions (sets × repetitions × eccentric-concentric loading) consisted of (a) 3 × (5 × 2) × 110/60% (AEL + RR 5), (b) 3 × (2 × 5) × 110/60% (AEL + RR 2), and (c) 3 × 10 × 60/60% 1RM (traditional sets [TS]). Weight releasers (50% 1RM) were attached to every first repetition of each cluster set (every first, third, fifth, seventh, and ninth repetition in AEL + RR 5 and every first and sixth repetition in AEL + RR 2). The AEL + RR 5 resulted in greater total volume load (sets × repetitions × eccentric + concentric loading) (6,630 ± 1,210 kg) when compared with AEL + RR 2 (5,944 ± 1,085 kg) and TS (5,487 ± 1,002 kg). In addition, AEL + RR 5 led to significantly ( p < 0.05) greater rating of perceived exertion (RPE) after set 2 and set 3 and lower blood lactate (BL) after set 3 and 5, 15, and 25 minutes postexercise than AEL + RR 2 and TS. There was a main effect of condition for BL between AEL + RR 5 (5.11 ± 2.90 mmol·L -1 ), AEL + RR 2 (6.23 ± 3.22 mmol·L -1 ), and TS (6.15 ± 3.17 mmol·L -1 ). In summary, AEL + RR 5 results in unique stimulus and fatigue responses. Although it may increase perceived exertion, coaches could use AEL + RR 5 to achieve greater back squat total volume load while reducing BL accumulation.

Impacts of trace mineral source and ancillary drench on steer performance during a 60-day backgrounding phase

Nutritional approaches to optimize cattle health and performance during the receiving period are warranted. This experiment evaluated the impacts of supplementing organic complexed Cu, Co, Mn, and Zn on productive and health responses of high-risk beef cattle during a 60-day backgrounding phase. Crossbred steers (120) were purchased at auction and transported to the experimental facility, where BW was recorded (day−1; initial shrunk BW = 227.7 ± 1.3 kg). On day 0, steers were ranked by BW and allocated to one of eight groups and housed in drylot pens equipped with GrowSafe automated feeding systems (Model 8000; two bunks/pen). Groups were randomly assigned to receive a total mixed ration containing: (1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 40); (2) organic complexed sources of the same minerals (AAC; Zinpro Availa 4 based on a metal:amino acid complex ratio of 1:1 for Zn, Cu, and Mn in addition to cobalt glucoheptonate; Zinpro Corp., Eden Prairie, MN; n = 40); or (3) AAC and an organic complexed trace mineral drench (APF; 30 mL/hd; Zinpro ProFusion, Zinpro Corp.) on day 0 and with morbidity treatment (n = 40). Diets provided the same daily amount of all nutrients and minerals based on 7 g/steer daily of Zinpro Availa 4. Steers were assessed for bovine respiratory disease (BRD) signs daily. Liver biopsies were performed on days 0, 28 and 60. Blood samples were collected on days 0, 2, 6, 10, 13, 21, 28 and 45. No treatment differences were detected (P ≥ 0.23) for feed intake, final BW, average daily gain, or BRD incidence. Mean liver Co concentrations were greater (P = 0.02) in AAC and APF compared to INR steers. Mean liver Cu was greater (P = 0.02) in APF compared to AAC steers. Liver Zn tended to be greater (P = 0.10) on day 28 but less (P = 0.05) on day 60 for INR compared to AAC and APF steers. Plasma cortisol was lowest (P = 0.05) for AAC steers on day 6, whereas AAC steers tended to have greater (P = 0.09) plasma cortisol on day 13 compared with APF. Plasma haptoglobin tended to be greater (P ≤ 0.10) for INR steers on days 28 and 45 compared to AAC and APF. While supplementing cattle with AAC or INR results in similar animal performance and clinical disease, AAC and APF reduce stress and acute phase protein responses.

Transcriptional response to mild therapeutic hypothermia in noise-induced cochlear injury.

Prevention or treatment for acoustic injury has been met with many translational challenges, resulting in the absence of FDA-approved interventions. Localized hypothermia following noise exposure mitigates acute cochlear injury and may serve as a potential avenue for therapeutic approaches. However, the mechanisms by which hypothermia results in therapeutic improvements are poorly understood. This study performs the transcriptomic analysis of cochleae from juvenile rats that experienced noise-induced hearing loss (NIHL) followed by hypothermia or control normothermia treatment. Differential gene expression results from RNA sequencing at 24 h post-exposure to noise suggest that NIHL alone results in increased inflammatory and immune defense responses, involving complement activation and cytokine-mediated signaling. Hypothermia treatment post-noise, in turn, may mitigate the acute inflammatory response. This study provides a framework for future research to optimize hypothermic intervention for ameliorating hearing loss and suggests additional pathways that could be targeted for NIHL therapeutic intervention.

Endemic Human Coronavirus-Specific Nasal Immunoglobulin A and Serum Immunoglobulin G Dynamics in Lower Respiratory Tract Infections.

Endemic human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 cause respiratory infection. Following infection, a virus-specific serum antibody rise is usually observed, coinciding with recovery. In some cases, an infection is not accompanied by an immunoglobulin G (IgG) antibody rise in serum in the first month after HCoV infection, even though the infection has cleared in that month and the patient has recovered. We investigated the possible role of nasal immunoglobulin A (IgA). We measured spike (S) and nucleocapsid (N)-specific nasal IgA during and after an HCoV lower respiratory tract infection (LRTI) and compared the IgA responses between subjects with and without a significant IgG rise in serum (IgG responders (n = 31) and IgG non-responders (n = 14)). We found that most IgG responders also exhibited significant nasal IgA rise in the first month after the infection, whereas such an IgA rise was lacking in most IgG non-responders. Interestingly, the serum IgG non-responders presented with a significantly higher nasal IgA when they entered this study than during the acute phase of the LRTI. Our data suggest that nasal IgA could be part of a fast acute response to endemic HCoV infection and may play a role in clearing the infection.

Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial

BackgroundA single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery.MethodsIn this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18–80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions.DiscussionAnalgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial.Trial registrationChinese Clinical Trial Registry (https://www.chictr.org.cn/) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.

Bergamot Byproducts: A Sustainable Source to Counteract Inflammation.

Chronic inflammation is the result of an acute inflammatory response that fails to eliminate the pathogenic agent or heal the tissue injury. The consequence of this failure lays the foundations to the onset of several chronic ailments, including skin disorders, respiratory and neurodegenerative diseases, metabolic syndrome, and, eventually, cancer. In this context, the long-term use of synthetic anti-inflammatory drugs to treat chronic illnesses cannot be tolerated by patients owing to the severe side effects. Based on this, the need for novel agents endowed with anti-inflammatory effects prompted to search potential candidates also within the plant kingdom, being recognized as a source of molecules currently employed in several therapeutical areas. Indeed, the ever-growing evidence on the anti-inflammatory properties of dietary polyphenols traced the route towards the study of flavonoid-rich sources, such as Citrus bergamia (bergamot) and its derivatives. Interestingly, the recent paradigm of the circular economy has promoted the valorization of Citrus fruit waste and, in regard to bergamot, it brought to light new evidence corroborating the anti-inflammatory potential of bergamot byproducts, thus increasing the scientific knowledge in this field. Therefore, this review aims to gather the latest literature supporting the beneficial role of both bergamot derivatives and waste products in different models of inflammatory-based diseases, thus highlighting the great potentiality of a waste re-evaluation perspective.

Evaluation and comparison of the results of the Alvarado scoring system with acute inflammatory response score in the diagnosis of acute appendicitis based on the pathological evidence

Introduction: Although appendectomy is the most common reason for abdominal surgery, acute appendicitis (AA) diagnosis remained a challenging issue using various scoring systems. Objectives: The current study aims to investigate the diagnostic value of the Alvarado scoring system versus the acute inflammatory response score (AIRS) in the diagnosis of AA. Patients and Methods: The current cross-sectional study was conducted on 120 patients who underwent appendectomy between 2019 and 2020. The on-admission Alvarado and AIRS scores were evaluated for the patients. Besides, the histopathological study of the resected tissues was considered the gold standard. The receiver operating characteristics (ROC) curve was depicted for the scoring systems, and sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), and area under the curve (AUC) were calculated. Results: The sensitivity, specificity, NPV, and PPV of Alvarado criteria for scores &gt;4 equaled 89.3%, 23.5%, 35.2%, and 89.3%, respectively. These amounts were calculated as 96.1%, 82.3%, 77.7%, and 97% for the AIRS, respectively. Moreover, at cut-points &gt;8, the sensitivity of 32.1%, specificity of 100%, PPV of 100%, and NPV of 15.7% have been measured for AIRS compared with 41.7%, 88.2%, 97.1%, and 29.4% for Alvarado, respectively. The measured AUC for AIRS and Alvarado criteria accounted for 0.81 and 0.72, respectively (P value &lt;0.05). Besides, 17 (14.16%) ones had a negative appendectomy. Conclusion: Based on the current study’s findings, both AIRS and Alvarado scoring systems were reliable means to diagnose appendicitis; however, AIRS was relatively superior considering its higher specificity and PPV in scores &gt;8 and higher sensitivity and NPV in scores &gt;4.

Neutrophil-Lymphocyte Ratio in Patients With Acute Schizophrenia.

Introduction Schizophrenia symptom severity is linked to neuroinflammation. Certain blood cell indexes such as neutrophil-lymphocyte ratio (NLR) and neutrophil-albumin ratio (NAR) have been used as biomarkers in various diseases, including schizophrenia. In acute clinical practice, it is challenging to decide whether to provide intravenous antipsychotic treatment in some cases due to the lack of objective biomarkers of psychiatric symptoms. The NLR of individuals with schizophrenia is thought to be associated with disease severity, and changes in NLR may reflect a patient's response to antipsychotic treatment. We investigated the application of NLR as a biomarker for identifying acute severity and determining acute treatment response in patients withschizophrenia. Methods We retrospectively examined 251 inpatients diagnosed with schizophrenia and classified them according to treatment (intravenous haloperidol vs. oral antipsychotic medication during the acute phase) and investigated their NLR and NAR while receiving inpatient care. Results A total of 48 inpatients were given intravenous haloperidol to manage their acute symptoms; 208 were given oral antipsychotics. The intravenous haloperidol group experienced more severe symptoms, such as agitation and disorganized thinking, during the acute phase. Further, those who received intravenous haloperidol had significantly higher Clinical Global Impression-Severity (CGI-S) scores than the oral antipsychotic group. NLR and NAR were also significantly higher in the haloperidol intravenous group. Conclusion Elevated NLR and NAR could be easily measured in patients with psychomotor agitation who should be treated at any facility. Further, they are useful biomarkers for determining disease severity and the effects of treatment on psychomotor excitement in patients who require intravenous haloperidol.