Day For 4weeks Research Articles

Hypoactivity and neurochemical alterations in the basal ganglia of female Sprague-Dawley rats after repeated exposure to atrazine.

The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100mg ATR/kg or a vehicle every other day for 2weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST)has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25mg/kg per day for 4weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

High-intensity interval training using electrical stimulation ameliorates muscle fatigue in chronic kidney disease-related cachexia by restoring mitochondrial respiratory dysfunction.

Exercise, especially high-intensity interval training (HIIT), can increase mitochondrial respiratory capacity and enhance muscular endurance, but its systemic burden makes it difficult to safely and continuously prescribe for patients with chronic kidney disease (CKD)-related cachexia who are in poor general condition. In this study, we examined whether HIIT using electrical stimulation (ES), which does not require whole-body exercise, improves muscle endurance in the skeletal muscle of 5/6 nephrectomized rats, a widely used animal model for CKD-related cachexia. Male Wistar rats (10weeks old) were randomly assigned to a group of sham-operated (Sham) rats and a group of 5/6 nephrectomy (Nx) rats. HIIT was performed on plantar flexor muscles in vivo with supramaximal ES every other day for 4weeks to assess muscle endurance, myosin heavy-chain isoforms, and mitochondrial respiratory function in Nx rats. A single session was also performed to identify upstream signaling pathways altered by HIIT using ES. In the non-trained plantar flexor muscles from Nx rats, the muscle endurance was significantly lower than that in plantar flexor muscles from Sham rats. The proportion of myosin heavy chain IIa/x, mitochondrial content, mitochondrial respiratory capacity, and formation of mitochondrial respiratory supercomplexes in the plantaris muscle were also significantly decreased in the non-trained plantar flexor muscles from Nx rats than compared to those in plantar flexor muscles from Sham rats. Treatment with HIIT using ES for Nx rats significantly improved these molecular and functional changes to the same degrees as those in Sham rats. Furthermore, a single session of HIIT with ES significantly increased the phosphorylation levels of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), pathways that are essential for mitochondrial activation signaling by exercise, in the plantar muscles of both Nx and Sham rats. The findings suggest that HIIT using ES ameliorates muscle fatigue in Nx rats via restoration of mitochondrial respiratory dysfunction with activation of AMPK and p38 MAPK signaling. Our ES-based HIIT protocol can be performed without placing a burden on the whole body and be a promising intervention that is implemented even in conditions of reduced general performance status such as CKD-related cachexia.

Protective effect of curcumin on testicular damage caused by carbon tetrachloride exposure in rats.

Context Carbon tetrachloride (CCl4 ) is a chemical that is still widely used in industry and has been shown to cause structural defects in rat testicles through oxidative stress. Aims In our study, the effect of curcumin on CCl4 -mediated testicular damage was investigated. Methods Twenty-four adult Wistar albino male rats weighing 300-350g were divided into four groups: control group (olive oil was applied by gavage every consecutive day for 3weeks); curcumin and CCl4 +curcumin groups (200mg/kg curcumin dissolved in olive oil was given by gavage once a day, every consecutive day for 3weeks); and CCl4 and CCl4 +curcumin groups (0.5mL/kg CCl4 was dissolved in olive oil at a ratio of 1/1 and given by i.p. injection every other day for 3weeks). Tissue samples were examined histopathologically, histomorphometrically, immunohistochemically and biochemically. Key results CCl4 disrupted both testicular morphology and testosterone synthesis, whereas curcumin treatment resulted in an improvement in testicular morphology and biochemical parameters, as well as a decrease in caspase-3 and tumour necrosis factor-α expression. Conclusions Curcumin has a protective effect on testicular tissue damage caused by CCl4 with its anti-inflammatory, antiapoptotic and antioxantioxidant properties. Implications Curcumin can prevent testicular damage due to CCl4 , an environmental pollutant.

Idiographic bidirectional associations of stressfulness of events and negative affect in daily life as indicators for mental health: An experience sampling study.

Evidence suggests that complex micro-dynamics occurring in daily life underly the development of mental distress. We aimed to (1) study the cross-lagged association between stressful events and negative affect (NA), (2) show that there is substantial between-person variability in idiographic associations and (3) show that idiographic associations are indicative of mental health. Experience sampling study assessing perceived stressfulness of events (PSE) and NA four times per day for 2weeks in a non-clinical convenience sample (N=70, mean age=22.9, 61% female, 69% German). Bivariate vector autoregressive model implemented in dynamic structural equation modelling to model the associations between stressful events and NA and obtain idiographic associations. Stressfulness of events and NA were significantly reciprocally associated. Autocorrelations and cross-lagged associations from PSE to NA showed substantial variability and were significantly related with trait measures of depression, anxiety, well-being, and perceived stress. Contrary to expectations, cross-lagged associations from NA to stressfulness of events were not related to trait mental health. The approach outlined in this article is useful for studying idiographic dynamics in daily life. The findings increase our understanding of micro-dynamics underlying mental health and individual differences in these processes.

Multi-frequency electromagnetic radiation induces anxiety in mice via inflammation in the cerebral cortex.

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65GHz radiofrequency radiation at 4 W/kg for 2h per day for 4weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1β, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.

Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice.

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4°C) for 3h per day for 3weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1β (IL-1β), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.

Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial.

Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. Fifty-six MMT cases (< 75mg/day methadone, > 3months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4mg/day) once a day for 2weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. The dose of 4mg/day naloxone was excluded from the study due to severe OWS. The precipitantsof groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2mg/day groups, respectively, withdrew from the study due to OWS. Oral naloxone at doses of 0.5 and 2mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4mg induced intolerable OWS.

MRNA biomarkers sensitive and specific to micro-dose erythropoietin treatment at sea level and altitude.

Recombinant human erythropoietin (rhEPO) is prohibited by the World Anti-Doping Agency. rhEPO abuse can be indirectly detected via the athlete biological passport (ABP). However, altitude exposure challenges interpretation of the ABP. This study investigated whether 5'-aminolevulinate synthase 2 (ALAS2) and carbonic anhydrase 1 (CA1) in capillary dried blood spots (DBSs) are sensitive and specific markers of rhEPO treatment at altitude. ALAS2 and CA1 expression was monitored in DBS collected weekly before, during, and after a 3-week period at sea level or altitude. Participants were randomly assigned to receive 20 IU kg bw-1 epoetin alpha (rhEPO) or placebo injections every second day for 3weeks while staying at sea level (rhEPO, n = 25; placebo, n = 9) or altitude (rhEPO, n = 12; placebo, n = 27). ALAS2 and CA1 expression increased up to 300% and 200%, respectively, upon rhEPO treatment at sea-level and altitude (P-values <0.05). When a blinded investigator interpreted the results, ALAS2 and CA1 expression had a sensitivity of 92%. Altitude did not confound the interpretation. Altitude affected ALAS2 and CA1 expression less than actual ABP markers when compared between sea level and altitude results. An individual athlete passport-like approach simulation confirmed the biomarker potential of ALAS2 and CA1. ALAS2 and CA1 were sensitive and specific biomarkers of micro-dose rhEPO treatment at sea level and altitude. Altitude seemed less a confounding factor for these biomarkers, especially when they are combined. Thus, micro-dose rhEPO injections can be detected in a longitudinal blinded setting using mRNA biomarkers in DBS.

The role of bidirectional communication between the adipokines and the endogenous opioid system in an experimental mouse model of colitis-associated colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of death globally. Multiple factors may contribute to the pathogenesis of CRC, including the abnormalities in the functioning of the endogenous opioid system (EOS) or adiponectin-related signaling. The aim of our study was to evaluate if differences in the expression of opioid receptors (ORs) influence the development of CRC and if modulation of adiponectin receptors using AdipoRon, a selective AdipoR1 receptor agonist, affects colorectal carcinogenesis. Naltrexone, an opioid receptor antagonist, was injected intraperitoneally every second day for 2weeks, at the dose of 1mg/kg in healthy Balb/C mice to induce changes in ORs expression. CRC was induced by a single intraperitoneal injection of azoxymethane (AOM) and the addition of dextran sodium sulfate (DSS) into drinking water in three-week cycles. The development of CRC was assessed using macro- and microscopic scoring and molecular analysis (RT qPCR, ELISA)after 14 weeks. Naltrexone significantly increased the mRNA expression of Oprm1, Oprd1, and Oprk1 in the mouse colon and in the brain (non-significantly). The pretreatment of mice with naltrexone aggravated the course of CRC (as indicated by tumor area, colon thickness, and spleen weight). The level of circulatory adiponectin was lowered in mice with CRC and increased in the colon as compared with healthy mice. The β-endorphin level was increased in the plasma of mice with CRC and decreased in the colon as compared to healthy mice. AdipoRon, AdipoR1 agonist, worsened the CRC development, and pretreatment with naltrexone enhanced this negative effect in mice. CRC did not affect the expression of the Adipor1 gene, but the Adipor1 level was increased in mice pretreated with naltrexone (AOM/DSS and healthy mice). AdipoRon did not influence the expression of opioid receptors at the mRNA level in the colon of mice with CRC. The mRNA expression of Ptgs2, Il6, Nos2, Il1b, Il18, Gsdmd, and Rela was increased in mice with CRC as compared to the healthy colon. AdipoRon significantly decreased mRNA expression of Ptgs2, Il6, Il1b, and Il18 as compared to CRC mice. EOS and adiponectin-related signaling may play a role in the pathogenesis of CRC and these systems may present some additivity during carcinogenesis.

Myrtenol Inhalation Mitigates Asthma-Induced Cognitive Impairments: an Electrophysiological, Behavioral, Histological, and Molecular Study.

Asthma is an inflammatory disorder with significant health problems. It generally affects the lungs but can also impact brain performance via several mechanisms. Some investigations have proposed that asthma impairs cognition. This study assessed the impacts of myrtenol as a monoterpene on cognitive disorders following asthma at behavioral, molecular, and synaptic levels. Asthma was induced by injection and inhalation of ovalbumin (OVA). Male Wistar rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Myrtenol (8mg/kg) or budesonide (160μg/kg) was administered through inhalation once a day for 1week, and at the end of the inhalation period, behavioral tests (MWM and Open Field), field potential recording, hippocampal brain-derived neurotrophic factor (BDNF), IL1β (ELISA), and NFκB measurement (Western blot) were performed to evaluate cognitive performance. Moreover, H&E (hematoxylin and eosin) staining was used for hippocampus histological evaluation. Myrtenol improved spatial learning, memory, LTP (long-term potentiation) impairments, and anxiety-like behaviors following asthma. Myrtenol inhalation increased the BDNF level and decreased the IL1β level and NFκB expression in the hippocampus of the asthmatic rats. The neuronal damage in the hippocampus following allergic asthma was alleviated via myrtenol administration. Myrtenol, as an herbal extract, protects the hippocampus from asthma consequences. Our observations revealed that myrtenol can improve spatial learning, memory, synaptic plasticity impairments, and anxiety-like behaviors following asthma. We believe that these ameliorating effects of myrtenol can be attributed to inflammation suppression and increased BDNF in the hippocampus.

Effect of Vastus Medialis Oblique Strengthening Versus Mulligan Knee Taping Technique (Mcconnell Tape) on Patellofemoral Pain Syndrome: A Comparative Study.

This study aims to determine the effectiveness of Vastus medialis oblique (VMO) strengthening and conventional therapy treatment (group A) andMulligan knee taping technique(McConnell tape) and conventional therapy treatment (group B) in patients with patellofemoral pain syndrome by VAS for pain andKPS for anterior knee pain scale is to compare VMO strengthening Versus Mulligan knee taping technique using McConnell tape in patellofemoral pain syndromeusing VAS for assessing pain and Kujala patellofemoral scale to assess knee pain and function. The most frequent cause of knee discomfort with retro patellar orperipatellar pain is patellofemoral pain syndrome (PFPS). The need for further studies to better understand the causes and treatment of PFPS is essential to provideoptimal care for individuals experiencing pain in the knee. Physical therapy is considered the most effective treatment for PFPS, but more research is needed todetermine each individual's best course of action. Proper diagnosis is the key to successful treatment and prevention of PFPS. Early intervention is also important forbetter outcomes. Patellofemoral pain syndrome (PFPS), which is often used interchangeably with "anterior knee pain" or "runner's knee," is the clinical entity ofstiffness or pain or both on prolonged sitting with the knees flexed and pain with activities that load the patellofemoral joint, such as climbing or descending stairs,squatting, running and kneeling. Varieties of conservative treatments are suggested, like quadriceps strengthening, stretching, braces and straps, electrotherapy, footorthosis, patellar taping, etc. Hence, a comparison between the vastus medialis obliqus muscle strengthening and patellar taping was undertaken to determine theireffectiveness concerning pain and function. A well-organized research study was conducted over 12 months to investigate the impact of strengthening the vastusmedialis oblique muscle and applying conventional therapy treatment. Group A received this combination of treatments, while Group B was assigned a treatmentprotocol involving the use of McConnell tape along with conventional therapy treatment. After taking informed and written consent, 30 subjects diagnosed withunilateral or bilateral PFPS were randomly selected and allocated into two groups - Group A (VMO muscle strengthening and conventional therapy treatment) andGroup B (Mulligan knee taping technique (McConnell tape) and conventional therapy treatment). Both groups received 6 therapy sessions every alternate day for 6weeks. The visual analog scale (VAS) and Kujala patellofemoral scale (KPS) measured pre and post-pain and function. "T-Test" was used for statistical analysis. Therewas a significant improvement in pain and function in patients with Patellofemoral pain syndrome at the end of 6 weeks regarding VAS and KPS within both groups,i.e., groups A and B (p&lt;0.01). But there was no significant difference regarding improvement in pain and functional status in patients with Patellofemoral painsyndrome at the end of 6 weeks in terms of VAS and KPS between groups. The effect of conventional therapy treatment along with VMO muscle strengthening issimilar to the conventional therapy treatment along with patellar taping in improving pain and functional level in patients with patellofemoral pain syndrome at theend of 6 weeks.

Intravenous injection of tumor extracellular vesicles suppresses tumor growth by reducing the regulatory T cell phenotype.

Colorectal cancer is a disease of unmet medical need. Although extracellular vesicles (EVs) have been implicated in anti-tumor responses, discrepancies were observed among studies. We analyzed the role of tumor-derived EVs (TEVs) in tumor progression in vivo by focusing on regulatory T (Treg) cells, which play essential roles in tumor development and progression. A mouse model of colorectal cancer lung metastasis was generated using BALB/c mice by tail vein injection of the BALB/c colon adenocarcinoma cell line Colon-26. TEVs derived from Colon-26 and BALB/c lung squamous cell carcinoma ASB-XIV were retrieved from the culture media supernatants. A TEV equivalent to 10µg protein was injected every other day for 2weeks. Histology and immunohistochemistry studies revealed that lung tumors reduced in the Colon-26-EV group when compared to the phosphate-buffered saline (PBS) group. The population of CD4 + FoxP3 + cells in the lung was upregulated in the PBS group mice when compared to the healthy mice (P < 0.001), but was significantly downregulated in the Colon-26-EV group mice when compared to the PBS group mice (P < 0.01). Programmed cell death protein 1, glucocorticoid-induced TNFR-related protein, and CD69 expression in lung Treg cells were markedly upregulated in the PBS group when compared to the healthy mice, but downregulated in the Colon-26-EV group when compared to the PBS group. The changes in expression were dose-dependent for Colon-26-EVs. ASB-EVs also led to significantly downregulated Treg cell expression, although non-cancer line 3T3-derived EVs did not. Our study suggests that TEVs possess components for tumor suppression.

Specificity of affective dynamics of bipolar and major depressive disorder.

Here, we examine whether the dynamics of the four dimensions of the circumplex model of affect assessed by ecological momentary assessment (EMA) differ among those with bipolar disorder (BD) and major depressive disorder (MDD). Participants aged 11-85years (n=362) reported momentary sad, anxious, active, and energetic dimensional states four times per day for 2weeks. Individuals with lifetime mood disorder subtypes of bipolar-I, bipolar-II, and MDD derived from a semistructured clinical interview were compared to each other and to controls without a lifetime history of psychiatric disorders. Random effects from individual means, inertias, innovation (residual) variances, and cross-lags across the four affective dimensions simultaneously were derived from multivariate dynamic structural equation models. All mood disorder subtypes were associated with higher levels of sad and anxious mood and lower energy than controls. Those with bipolar-I had lower average activation, and lower energy that was independent of activation, compared to MDD or controls. However, increases in activation were more likely to perpetuate in those with bipolar-I. Bipolar-II was characterized by higher lability of sad and anxious mood compared to bipolar-I and controls but not MDD. Compared to BD and controls, those with MDD exhibited cross-augmentation of sadness and anxiety, and sadness blunted energy. Bipolar-I is more strongly characterized by activation and energy than sad and anxious mood. This distinction has potential implications for both specificity of intervention targets and differential pathways underlying these dynamic affective systems. Confirmation of the longer term stability and generalizability of these findings in future studies is necessary.

'Physically it was fine, I'd eat what normal people do. But it's never like this in my head': A qualitative diary study of daily experiences of life in recovery from an eating disorder.

High eating disorder (ED) relapse rates stress the need for clearer understanding around how recovery is experienced and maintained. Recent research endorses the concept of recovery as a process rather than an endpoint. This study aimed to investigate daily experiences of living in recovery from an ED. Fourteen participants who self-identified as recovered from a formally diagnosed ED were recruited online. A qualitative diary app was used for data collection. Participants completed written or audio open-ended diary entries every other day for 2weeks describing their experiences, thoughts, and feelings. Diaries were analysed using reflexive thematic analysis. Four themes were developed. 'Ever-present eating disordered thoughts' highlights how pervasive these thoughts remain for participants. 'Impact of social discourses' unpacks the challenges of maintaining recovery while surrounded by unhelpful social discourses about food and body image. 'Recovery is precarious' highlights how a combination of stressors can build up to threaten recovery. 'Finding balance in recovery' illustrates the many ways participants try to manage their recovery each day. The findings make it clear that living in recovery from an ED is a complex process that must be navigated daily. Recommendations for treatment and recovery support are discussed.

Celastrol relieves myocardial infarction-induced cardiac fibrosis by inhibiting NLRP3 inflammasomes in rats.

Myocardial infarction (MI) triggers a strong inflammatory response mediating by NLRP3 inflammasome which is associated with cardiac fibrosis. The key players in this response are Interleukin (IL)-1 and IL-18, which are regulated by NLRP3 inflammasomes. Celastrol, a traditional Chinese medicine with strong anti-inflammatory activity, has recently reported as a cardioprotective agent. However, the mechanisms by which celastrol is cardioprotective in MI remain elusive. We hypothesized that Celastrol could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in rats, improve poor heart remodeling, and preserve heart function. Myocardial infarction (MI) was caused by ligating the left anterior descending of male SD rats. Celastrol (1mg/kg) or saline was administered every other day for 4weeks. Heart function and fibrosis were assessed. Inflammatory and fibrotic markers in the myocardia were evaluated with immunohistochemistry, western blot, and ELISA. Molecular docking was employed to predict Celastrol's binding to NLRP3 protein. The effects of Celastrol on the expression of NLRP3 inflammasome and myocardial fibrosis genes were then examined in vitro. Celastrol maintained the left ventricular fractional shortening (FS) and ejection fraction (EF). Fibrosis was significantly reduced in animals treated with 1mg/kg Celastrol (15.17±1.82%) relative to controls (29.88±4.28%). Celastrol also significantly reduced the NLRP3, IL-18, and IL-1β levels, together with macrophage and neutrophil infiltration in the myocardium. Molecular docking predicted that NLRP3 would bind tightly to Celastrol [Docking energy: -8.9 (kcal/mol)]. In vitro experiments showed reduced NLRP3 inflammasome and myocardial fibrosis-associated proteins expression in neonatal rat cardiac fibroblasts treated with Celastrol. In post-MI rats, Celastrol, a naturally occurring active ingredient, was able to reduce myocardial fibrosis and improve cardiac function, according to our study. These effects may result from inhibiting the NLRP3 inflammasome and attenuating the early inflammatory storm after MI, suggesting that Celastrol may be useful in treating acute MI.

A proof-of-concept open-label clinical trial of spleen tyrosine kinase antagonism using fostamatinib in moderate-to-severe hidradenitis suppurativa

Hidradenitis suppurativa (HS) is an autoinflammatory disorder of keratinization with a prominence of B cells and plasma cells. Fostamatinib is a spleen tyrosine kinase inhibitor targeting B cells and plasma cells. To assess the safety, tolerability, and clinical response at week 4 and week 12 of fostamatinib in moderate-to-severe HS. Twenty participants were administered fostamatinib 100mg twice a day for 4weeks, escalating to 150mg twice a day thereafter until week 12. Participants were assessed for adverse events and clinical response assessed by HiSCR (Hidradenitis Suppurativa Clinical Response Score) and IHS4 (International Hidradenitis Suppurativa Severity Score) as well as other outcomes including DLQI (Dermatology Life Quality Index), visual analog scale, and physician global assessment. All 20 participants completed the week 4 and week 12 endpoints. Fostamatinib was well tolerated in this cohort with no grade 2/3 adverse events reported. A total of 85% achieved HiSCR at week 4 and 85% at week 12. The greatest reduction in disease activity was seen at weeks 4/5 with worsening in a proportion of patients thereafter. Significant improvements were seen in pain, itch, and quality of life. Fostamatinib was well tolerated in this HS cohort with no serious adverse events and improvement in clinical outcomes. Targeting B cells/plasma cells may be a viable therapeutic strategy in HS and requires further exploration.

Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia.

To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Patients were randomized to receive lidocaine patches or placebo every day for 4weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

High-intensity interval training in the form of isometric contraction improves fatigue resistance in dystrophin-deficient muscle.

Duchenne muscular dystrophy is a genetic muscle-wasting disorder characterized by progressive muscle weakness and easy fatigability. Here we examined whether high-intensity interval training (HIIT) in the form of isometric contraction improves fatigue resistance in skeletal muscle from dystrophin-deficient mdx52mice. Isometric HIIT was performed on plantar flexor muscles in vivo with supramaximal electrical stimulation every other day for 4weeks (a total of 15sessions). In the non-trained contralateral gastrocnemius muscle from mdx52 mice, the decreased fatigue resistance was associated with a reduction in the amount of peroxisome proliferator-activated receptor γ coactivator 1-α, citrate synthase activity, mitochondrial respiratory complex II, LC3B-II/I ratio, and mitophagy-related gene expression (i.e. Pink1, parkin, Bnip3 and Bcl2l13) as well as an increase in the phosphorylation levels of Src Tyr416 and Akt Ser473, the amount of p62, and the percentage of Evans Blue dye-positive area. Isometric HIIT restored all these alterations and markedly improved fatigue resistance in mdx52muscles. Moreover, an acute bout of HIIT increased the phosphorylation levels of AMP-activated protein kinase (AMPK) Thr172, acetyl CoA carboxylase Ser79, unc-51-like autophagy activating kinase 1 (Ulk1) Ser555, and dynamin-related protein 1 (Drp1) Ser616 in mdx52muscles. Thus, our data show that HIIT with isometric contractions significantly mitigates histological signs of pathology and improves fatigue resistance in dystrophin-deficient muscles. These beneficial effects can be explained by the restoration of mitochondrial function via AMPK-dependent induction of the mitophagy programme and de novo mitochondrial biogenesis. KEY POINTS: Skeletal muscle fatigue is often associated with Duchenne muscular dystrophy (DMD) and leads to an inability to perform daily tasks, profoundly decreasing quality of life. We examined the effect of high-intensity interval training (HIIT) in the form of isometric contraction on fatigue resistance in skeletal muscle from the mdx52mouse model of DMD. Isometric HIIT counteracted the reduced fatigue resistance as well as dystrophic changes in skeletal muscle of mdx52mice. This beneficial effect could be explained by the restoration of mitochondrial function via AMP-activated protein kinase-dependent mitochondrial biogenesis and the induction of the mitophagy programme in the dystrophic muscles.

Multimodal analgesia did not improve post-operative pain scores, reduce opioid consumption or reduce length of stay following hip arthroscopy.

To determine whether different regimens of multimodal analgesia will reduce postoperative pain scores, opioid consumption, costs and hospital length-of-stay following hip arthroscopy. From 2018 to 2021, 132 patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) were included in this prospective, single-center randomized controlled trial. Patients were randomized into four treatment groups: (1) Group 1-Control: opioid medication (oxycodone-acetaminophen 5mg/325mg, 1-2 tabs q6H as needed), Heterotopic ossification prophylaxis-Naprosyn 500mg twice daily × 3weeks); (2) Group 2-Control + postoperative sleeping aid (Zopiclone 7.5mg nightly × 7days); (3) Group 3-Control + preoperative and postoperative Gabapentin (600mg orally, 1h preoperatively; 600mg postoperatively, 8h following pre-op dose); (4) Group 4-Control + pre-medicate with Celecoxib (400mg orally, 1h preoperatively) The primary outcome was pain measured with a visual analog scale, monitored daily for the first week and every other day for 6weeks. Secondary outcomes included opioid consumption, healthcare resource use, and hospital length of stay. Patient characteristics were similar between groups. There were no statistically significant differences in pain scores between groups at any timepoint after adjusting for intra-operative traction time, intra-operative opioid administration and preoperative pain scores (p > 0.05). There were also no significant differences in the number of days that opioids were taken (n.s.) and the average daily morphine milligram equivalents consumed (n.s.). Similarly, there were no statistically significant differences in length of stay in the experimental groups, compared with the control group (n.s.). Finally, there were no differences in cost between groups (n.s.). The routine use of Zopiclone, Celecoxib and Gabapentin did not improve postoperative pain control or reduce length-of-stay following hip arthroscopy. Therefore, these medications are not recommended for routine postoperative pain control following hip arthroscopy. l.