CS Treatment Research Articles

Overuse of corticosteroids in patients with immune thrombocytopenia (ITP) between 2011 and 2017 in the United States.

Corticosteroids (CSs) are standard first-line therapy for immune thrombocytopenia (ITP). Prolonged exposure is associated with substantial toxicity; thus guidelines recommend avoidance of prolonged CS treatment and early use of second-line therapies. However, real-world evidence on ITP treatment patterns remains limited. We aimed to assess real-world treatment patterns in patients with newly-diagnosed ITP, using two large US healthcare databases (Explorys and MarketScan) between January 1, 2011 and July 31, 2017. Adults with ITP, ≥12 months of database registration prior to diagnosis, ≥1 ITP treatment, and ≥1 month enrollment following initiation of first ITP treatment were included (n = 4066 Explorys; n = 7837 MarketScan). Information on lines of treatment (LoTs) was collected. As expected, CSs were the most common first-line treatment (Explorys, 87.9%; MarketScan, 84.5%). However, CSs remained by far the most common treatment (Explorys ≥77%; MarketScan ≥85%) across all subsequent LoTs. Second-line treatments such as rituximab (12.0% Explorys; 24.5% MarketScan), thrombopoietin receptor agonists (11.3% Explorys; 15.6% MarketScan), and splenectomy (2.5% Explorys; 8.1% MarketScan) were used much less frequently. CS use is widespread in the US in patients with ITP across all LoTs. Quality improvement initiatives are needed to reduce CS exposure and bolster use of second-line treatments.

Cool- and Warm-Season Turfgrass Irrigation with Subsurface Drip and Sprinkler Methods Using Different Water Management Strategies and Tools

This study compared the performances of subsurface drip irrigation (SDI) to sprinkler irrigation (SI) of cool-season turf mix (CS) and warm-season (WS) turfgrass species while investigating their response to different irrigation scheduling strategies. Moreover, the suitability of crop water stress index (CWSI) for monitoring water stress and scheduling irrigation was tested. Irrigation was applied up to the field capacity when 30%, 50% and 70% of total available water was consumed. All parameters, including color, quality, fresh yield, dry matter yield, irrigation water productivity, water productivity, vegetation height and mowing, differed significantly for different irrigation methods and water supply strategies for both species. The best visual turf was maintained under non-limiting soil moisture conditions (30%) in all main and sub-treatments. At this irrigation threshold, maximum and minimum amounts of irrigation water were applied in SI CS treatment (523.5 mm) and SDI WS treatment (298.6 mm), respectively. Warm-season turf required up to 40% less water than cool-season turf mix. In the water-scarce regions, 50% treatment for cool-season and 70% treatment for warm-season can be suggested for acceptable visual quality, lower water consumption and less frequent clipping. The mean CWSI before irrigation, representing irrigation threshold, ranged between 0.22–0.70.

Regulating charge carrier recombination in Cu2ZnSn(S,Se)4 solar cells via cesium treatment: bulk and interface effects

Cs treatment in a CZTSSe system could enhance device performance by affecting defect characteristics and carrier–transport properties.

The interplay between Cs and K in Pseudanabaena catenata; from microbial bloom control strategies to bioremediation options for radioactive waters

Pseudanabaena dominates cyanobacterial blooms in the First-Generation Magnox Storage Pond (FGMSP) at a UK nuclear site. The fission product Cs is a radiologically significant radionuclide in the pond, and understanding the interactions between Cs and Pseudanabaena spp. is therefore important for determining facility management strategies, as well as improving understanding of microbiological responses to this non-essential chemical analogue of K. This study evaluated the fate of Cs following interactions with Pseudanabaena catenata, a laboratory strain most closely related to that dominating FGMSP blooms. Experiments showed that Cs (1 mM) exposure did not affect the growth of P. catenata, while a high concentration of K (5 mM) caused a significant reduction in cell yield. Scanning transmission X-ray microscopy elemental mapping identified Cs accumulation to discrete cytoplasmic locations within P. catenata cells, indicating a potential bioremediation option for Cs. Proteins related to stress responses and nutrient limitation (K, P) were stimulated by Cs treatment. Furthermore, selected K+ transport proteins were mis-regulated by Cs dosing, which indicates the importance of the K+ transport system for Cs accumulation. These findings enhance understanding of Cs fate and biological responses within Pseudanabaena blooms, and indicate that K exposure might provide a microbial bloom control strategy.

A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0-4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality.

The moisturizing effect of Capparis spinosa fruit extract targeting filaggrin synthesis and degradation.

Small molecular natural products, such as betaine, have unique moisturizing advantages. Capparis spinosa L. fruit is rich in quaternary ammonium alkaloids such as betaine and stachydrine. However, few studies investigated its efficacy and mechanism on human skin. Polysaccharides-free C. spinosa fruit extract (CS) was obtained to study its moisturizing effect and mechanisms focusing on filaggrin (FLG) synthesis and degradation. The clinical moisturizing test was carried out on human arms, calves, and faces after CS treatment for 0.5-6h. The change in the level of FLG, caspase 14, loricrin, and transglutaminase 5 (TGM 5) was measured by immunofluorescence after CS treatment for 4 and 24 h in a reconstructed epidermis model. Also, the content of pyrrolidone carboxylic acid (PCA) in the stratum corneum was tested by high-performance liquid chromatography (HPLC) both in the epidermis model and human calves. Compared with glycerin (positive control), 5% CS showed a strong skin hydration effect on arms and calves when applied for 0.5-6h. Also, the face hydration increased at 0.5 and 4 h. In addition, 3% CS applied to the recombinant epidermis model under low humidity promoted the immunodetected levels of caspase 14 and PCA content but reduced the levels of FLG at 4h, however, the levels of FLG, loricrin, and TGM 5 were promoted at 24 h. Meanwhile, CS treatment for 4h in human calves increased the PCA content in the stratum corneum by 29.9%. Topical application of CS on human skin showed an instant and long-lasting increase in skin hydration by regulating the FLG network. It promoted FLG degradation to form PCA at 4h both in vivo and in vitro, increasing FLG synthesis after 24 h, potentially reforming the FLG monomer reservoir to alleviate the skin's dry condition.

Comparisons of different regeneration approaches on soil respiration of Chamaecyparis obtusa planted in pine wilt disease-disturbed stands

ABSTRACT Changes in the abiotic and biotic factors created by forest regeneration can have a major influence on soil respiration, which is an important component of the forest carbon (C) cycle. This study was performed to determine the soil respiration rates caused by regeneration approaches in Chamaecyparis obtusa planted in pine wilt disease (PWD)-disturbed stands in South Korea. In 2007, four-year-old C. obtusa seedlings were planted with two regeneration approaches, clearcutting (CS) of infected pine trees or underplanting following selective cutting (DS) of infected pine trees in disturbed pine stands. Soil respiration rates were assessed in two regeneration approaches and an undisturbed pine stand (NS) for two years. The mean soil respiration rates were significantly lower in the DS (1.07 µmol m−2 s−1) treatment than in the NS (1.87 µmol m−2 s−1) treatment, whereas there was no significant difference between the CS (1.44 µmol m−2 s−1) treatment and the NS or DS treatment. The three treatments showed exponential relationships between soil respiration rates and soil temperature (R 2 = 0.57–0.81). The annual soil respiration rates were significantly higher in the CS (6.49 Mg C ha−1 year−1) treatment than in the DS (3.98 Mg C ha−1 year−1) treatment. The Q 10 values were lowest in the DS (2.00–2.03) treatment, followed by the CS (2.23–2.62) and NS (2.74–3.07) treatments. These results reveal that DS approaches in PWD-disturbed stands are one for the critical drivers of reducing annual soil respiration rates.

Physiological Responses and Tolerance of Halophyte Sesuvium portulacastrum L. to Cesium

Cesium (Cs) is a soil contaminant and toxic to the ecosystem, especially the plant species. In this study, we have assessed the potential of a halophyte Sesuvium portulacastrum for its Cs tolerance and accumulation. Thirty days old S. portulacastrum plants were subjected to different concentrations of Cs (0, 5, 10, 25, 50, and 150 mg·L−1 Cs) using cesium chloride. The biomass and photosynthetic pigments were not affected up to 25 mg·L−1 Cs treatment while a significant decline in pigment levels was observed at higher concentrations. The Cs treatments increased protein content at low concentrations while higher concentrations were inhibitory. Under Cs exposure, significant induction of antioxidant enzymes such as ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), and superoxide dismutase (SOD) was observed. The antioxidant enzyme activities were upregulated up to 50 mg·L−1 Cs but decreased significantly at 150 mg·L−1. The accumulation of Cs was dose and tissue-dependent as evidenced by a higher accumulation of Cs in leaves (536.10 μg·g−1) as compared to stem (413.74 μg·g−1) and roots (284.69 μg·g−1). The results suggest that S. portulacastrum is a hyper-accumulator of Cs and could be useful for the phytoremediation of Cs-contaminated soils.

Prenatal thermal stress affects acute-phase proteins, heat shock protein 70, and circulating corticosterone in developing broiler embryos and neonates

Higher or lower incubation temperature may impose some degree of stress on developing poultry embryos. This study was designed to delineate the effects of prenatal thermal stress on serum levels of acute-phase proteins (APPs), namely ceruloplasmin (CPN) and alpha-1-acid glycoprotein (AGP), the regulation of brain mRNA levels of heat shock protein (Hsp) 70, and serum levels of corticosterone (CORT) in embryos and neonatal chicks. Hatching eggs were subjected to three thermal treatments; (i) standard optimum temperature throughout (SS: 37.8 °C and 56 % RH), (ii) heat stress for 12 h daily (HS: 40.0 °C and 56 % RH), and (iii) cold stress for 12 h daily 18 (CS: 30.2 °C and 56 % RH). The heat and cold stress treatments were imposed from the 10th to the 18th day of incubation (ED). Results showed that thermal stress had a negligible effect on hatchability rate and body temperatures of neonatal chicks. The CS treatment was detrimental to embryonic growth. The HS treatment elevated AGP (ED 16, ED 18, and post-hatch day 1), CPN (on post-hatch day 1), and CORT (ED 14). On the contrary, the CS embryos had reduced AGP (ED14, ED16, ED18, and post-hatch day 1), CPN (ED 16), and CORT (ED 14, ED 16, ED 18). The brain mRNA levels of Hsp70 were upregulated throughout the experimental period in both the HS and CS embryos and chicks. Based on these modifications, AGP, together with Hsp70 mRNA expression, could be considered effective biomarkers useful to evaluate the magnitude and the time response of embryos and neonatal chicks to prenatal thermal stress. It is concluded that developing chicken embryos have the ability to evoke APPs, Hsp70 and CORT reactions which are important to cope with thermal stress.

Effect of Chlorella vulgaris on the Growth and Phytochemical Contents of “Red Russian” Kale (Brassica napus var. Pabularia)

Kale is a prominent leafy vegetable because of its high content of bioactive compounds and various health benefits. Microalgae have been suggested as a biostimulator that can replace chemical fertilizers by enhancing crop yield and supporting soil carbon sequestration. In this study, the effect of Chlorella vulgaris as a plant biostimulant on the growth and secondary metabolite contents of “Red Russian” kale (Brassica napus var. Pabularia) with green leaves and purple veins has been demonstrated. Three Chlorella treatments were used: CS, C. vulgaris suspension; CB, C. vulgaris biomass; and CFS, filtered C. vulgaris-free supernatant. The plant growth rates, phytochemical contents, and individual glucosinolate and anthocyanin contents were determined. There was no significant difference under the CS and CB treatments, while CFS negatively influenced on kale growth with 37% reduction of dried weight. In contrast, metabolite production differed according to Chlorella treatments. Total contents of chlorophyll and carotenoid were increased by 1.57 and 1.41 folds by CS treatment, whereas total contents of phenol and flavonoids were enhanced by 1.30 and 1.22 folds by CFS treatment. Totally, seven glucosinolates and four anthocyanins were characterized and quantified individually. Notably, CFS treatment increased gluconasturtiin and all anthocyanins the most, 10.28-fold and 5.90-fold, respectively.

Combining network pharmacology, RNA-seq, and metabolomics strategies to reveal the mechanism of Cimicifugae Rhizoma - Smilax glabra Roxb herb pair for the treatment of psoriasis

BackgroundPsoriasis is a prevalent chronic inflammatory skin condition marked by immune cell infiltration and keratinocyte abnormal proliferation. Cimicifugae Rhizoma - Smilax glabra Roxb (CS) herb pair, the main component of Shengma Detoxification Decoction, has been proven effective for the treatment of psoriasis. However, the mechanism is yet to be deciphered. PurposeTo explore the mechanism of CS for the treatment of psoriasis. MethodsThe imiquimod-induced psoriasis-like lesion mouse model was used to identify the targets and the molecular mechanisms of CS. Network pharmacology combined with RNA-seq strategy was employed to predict the targets and mechanisms of CS for psoriasis. Metabolomics approaches were used to demonstrate the complexity of CS for the treatment of psoriasis. Finally, a compound-response-enzyme-gene network was constructed based on the multi-omics results to elucidate potential connections. ResultsThe CS herb pair could significantly improve psoriatic lesions and reduce the inflammatory cell infiltration and proliferation of keratinocytes in skin lesions. Network pharmacology predicted that TNF, JNK, IL-6, and IL-1β could be potential targets. RNA-seq data revealed that CS could significantly regulate genes and signaling pathways associated with Th17 responses, such as IL-36, IL-1β, CCl2, CXCL16, keratin 14, keratin 5, and antimicrobial peptides S100A8 and S100A9 well as MAPK, mTOR, and other signaling pathways. Further experimental data validated that CS treatment remarkably reduced the expression of inflammatory cytokines and factors, such as CCL2, CCL7, IL1F6, IL-17, IL-23, IL-1β, TNF-α, and IL-6, and inhibited the phosphorylation of p38 and ERK1/2. This indicated that CS exerts its therapeutic effect by inhibiting the MAPK signaling pathways. In addition, metabolomic analyses demonstrated that CS treatment improved seven metabolic pathways, these included phenylalanine, tyrosine, pyruvate metabolism, carnitine metabolism, etc. Four key metabolites (L-Arginine, L-Phenylalanine, L-Carnitine, O-Acetylcarnitine) and nine differential genes (CMA1, PCBD2, TPSAB1, TPSB2, etc.) were identified that affected amino acid metabolism, carnitine metabolism, and other pathways contributing to the infiltration of Th17 cells in psoriatic lesions. ConclusionCS could alleviate IMQ-induced psoriasis-like dermatitis by reducing the expression of cytokines and chemokines mediated by the MAPK pathway, and improved amino acid and carnitine metabolism in vivo. Our study is the first to demonstrate the complex mechanism of CS for the treatment of psoriasis and provides a new paradigm to elucidate the pharmacological effects of Traditional Chinese Medicine (TCM) drugs for psoriasis from multiple perspectives.

Physiological adaptability of three gramineae plants under various vegetation restoration models in mining area of Qinghai-Tibet Plateau

Large-scale coal mining activities on the QTP have affected the natural grassland ecosystem which will take decades to recover. Therefore, looking for an effective vegetation restoration method is the most effective way to restore the ecosystem. In this study, we explored the effects of three vegetation restoration modes (coal mine spoils planting (CK), organic fertilizer planting (OF), and cover soil planting (CS)) on the five cold-resistance related physiological indices of three native Gramineae plants (Elymus nutans, Poa crymophila and Festuca sinensis) growing in three different habitats (shady slope, sunny slope, and flat slope). The higher contents of soluble sugar (SS) in the Elymus nutans (213.46 mg/g) and Festuca sinensis (202.84 mg/g) were recorded under the CS treatment in the sunny slope habitat. The FP contents of Elymus nutans (421.31 μg/g), Poa crymophila (310.06 μg/g), and Festuca sinens (288.45 μg/g) were higher under the CK treatment in the flat ground habitat. The higher (P < 0.05) content of chlorophyll (Chl) was recorded in the Elymus nutans (2.13 mg/g) under the CS treatment in the sunny slope habitat compared to the other two plants. We observed lower MDA contents in the Elymus nutans (3.19 nmol/g) and Festuca sinensis (3.56 nmol/g) under the CK treatment growing in the shady slope habitat. In the shady slope habitat, the H2O2 contents of Elymus nutans (15.86 μmol/g), Poa crymophila (6.78 μmol/g), and Festuca sinensis (8.76 μmol/g) under the CS treatment were significantly lower compared to other treatments. Based on membership function method, the low-temperature adaptability order of the three restoration plants from strong to weak was Elymus nutans > Festuca sinensis > Poa crymophila. While the effectiveness order of the three vegetation restoration models in alpine mining areas from good to bad was CS > OF > CK. This study will provide a theoretical and guiding significance to evaluate the effectiveness of different restoration methods, formulate optimal restoration strategies and guide the sustainable restoration of the damaged ecosystems of the alpine mining areas.

Cromolyn Sodium differentially regulates human mast cell and mouse leukocyte responses to control allergic inflammation

BackgroundCromolyn Sodium (CS) has been used in the past as an anti-allergy drug owing to its mast cell (MC) stabilizing properties that impair histamine release. However, additional mechanisms for its clinical actions are likely and might help to identify new roles for MCs and leukocytes in regulating inflammation. Here, using human cord blood-derived MCs (CBMCs), mouse bone marrow-derived MCs (BMMCs) and eosinophils (BMEos), and in vivo mouse models of allergic inflammation (AI), additional actions of CS on MCs were determined. MethodsThe in vitro effects of CS on IgE-activated human and mouse MCs were assessed by measuring the levels of pro-inflammatory (tryptase, LTC4, IL-8, CD48) and pro-resolution effectors (IL-10, CD300a, Annexin A1) before and after CS treatment. The in vivo effects of daily CS injections on parameters of inflammation were assessed using mouse models of allergic peritonitis (AP) (Ovalbumin/Alum- or Ovalbumin/S. aureus enterotoxin B) and allergic airways inflammation (AAI) (house dust mite (HDM)). ResultsIn vitro, CS did not affect pro-inflammatory effectors but significantly increased the anti-inflammatory/pro-resolution CD300a levels and IL-10 release from IgE-activated CBMCs. BMMCs were not affected by CS. In vivo, CS injections decreased total cell and Eos numbers in the peritoneal cavity in the AP models and bronchoalveolar lavage and lungs in the AAI model. CS reduced EPX release from PAF-activated BMEos in vitro, possibly explaining the in vivo findings. ConclusionTogether, these results demonstrate immunomodulatory actions for CS in AI that are broader than only MC stabilization.

Differences of hip involvement in systemic and non-systemic juvenile idiopathic arthritis

Systemic corticosteroids are continued to be administered in juvenile idiopathic arthritis (JIA) patients, especially in systemic JIA (sJIA), despite the ability of biologic therapy. One of the complications of long-term CS treatment is delayed hip arthritis development with risk of secondary hip osteoarthritis formation and total hip arthroplasty (THA).We compared different types of hip joint lesions in JIA, especially, secondary hip osteoarthritis development and THA rates in systemic and non-systemic JIA, and evaluate systemic corticosteroids contribution to those complications.The study included 753 JIA patients. They were divided into 2 groups: patients with sJIA and non-systemic JIA (nsJIA). Clinical and demographic characteristics, CS treatment regimens were compared.Results. Hip arthritis was found equally often in both groups, but both secondary hip osteoarthritis (19% vs 5,3%) and THA (8.6% vs 1.6%) prevailed in the sJIA. Patients with sJIA had delayed hip involvement (57.9% vs 30.6%; p=0.019), earlier secondary hip osteoarthritis development (4.5 vs 5.1 years after the JIA onset) with younger age of secondary hip osteoarthritis achievement (13.7 vs 15.2 years; р=0.045), they also had higher inflammatory activity, greater systemic corticosteroids administration (94.8% vs 56.1%; р=0.0000001) and higher cumulative systemic corticosteroids dose (3085 mg vs 2000 mg; p=0,005). More than half patients (56.1%) with nsJIA had systemic corticosteroids treatment and impaired calcium-phosphorus metabolism.Conclusion. Systemic corticosteroid treatment and delayed hip involvement are independent predictors of secondary hip osteoarthritis in all JIA categories. Calcium and phosphate metabolism disturbances are additional predictor for secondary hip osteoarthritis in non-systemic JIA categories

Undecomposed litter mixed in the soil can increase interrill erosion on hillslopes: A laboratory study

Soil-litter mixing has been found to affect soil erosion. However, previous studies did not distinguish the effects of litter exposed on the soil surface and that buried in the soil resulting from soil-litter mixing processes. This causes an unclear understanding of the effect of soil-litter mixing on soil erosion. In this research, we hypothesized that after mixing, the exposed litter would decrease soil erosion, while the litter buried in the soil would increase soil erosion. To test this hypothesis, soil boxes were filled with three treatments: soil-litter mixing with surface-exposed litter (CS), soil-litter mixing without surface-exposed litter (S), and soil surface cover (C) at four litter rates (0, 0.10, 0.20, and 0.35 kg m−2). Laboratory rainfall experiments were performed under a soil box slope of 10° and at a rainfall intensity of 80 mm h−1. The results of this study showed that the CS and C treatments reduced runoff velocity, and their velocities changed similarly depending on the surface cover of litter. However, in the S treatment, the litter rate increasedid not change runoff velocity significantly, indicating that runoff velocity was mostly controlled by the litter on the soil surface. Under the same surface cover, the C treatment reduced sediment yield by up to 39%; while the S treatment was found to increase sediment yield by up to 43% compared with the bare soil. The sediment yield of the CS treatment showed a decreasing trend as the litter rate increased. When the litter increased to 0.35 kg m−2, the sediment in CS treatment was 19% lower than in the bare soil. These results demonstrate a counteracting effect of surface litter and buried litter. The promoting effect of the buried litter on sediment yield was explained by the undecomposed litter creating an oversaturated condition and introducing a deforming force that decreased soil resistance to erosion. This study suggests that it is necessary to isolate the effect of exposed litter and buried litter on soil erosion, particularly in the early period after soil-litter mixing when litter is undecomposed.

Prospective epidemiological study of juvenile-onset systemic lupus erythematosus in the UK and Republic of Ireland.

The primary objective was to define the incidence of JSLE in children <16 years of age in the UK and Republic of Ireland (ROI). The secondary objective was to describe presenting features, classification criteria, initial management and disease damage in newly presenting JSLE patients. A prospective JSLE epidemiological study was undertaken between September 2017 and September 2019 with support of the British Paediatric Surveillance Unit and other professional groups involved in diagnosis and management of JSLE patients. Treating consultants reported all cases of JSLE seen. A follow-up study at 1 year examined management and progression of disease and treatment. There were 124 incident cases included in the final analysis. Incidence was estimated using ACR-1997 classification criteria (0.36/100 000), SLICC-2012 classification criteria (0.41/100 000) and clinician expert opinion (0.46/100 000). A high disease burden was seen, with 71.0% of patients requiring ongoing systemic CS treatment at 1 year; 98.2% receiving immunomodulatory treatment; and 20.4% accruing damage in the year following diagnosis (predominantly neuropsychiatric-related), with substantial involvement from multiple speciality teams. The minimum UK and ROI incidence of JSLE is between 0.36 and 0.46/100 000, depending on the case definition used. Challenges in classification of patients with JSLE are highlighted, but overall this study supports the use of SLICC-2012 classification criteria. The high levels of disease damage and ongoing CS use 1 year after diagnosis is concerning, highlighting the need for further interventions to improve outcomes in JSLE.

Alteration of the α5 GABA receptor and 5HTT lead to cognitive deficits associated with major depressive-like behaviors in a 14-day combined stress rat model

Introduction: Current models used to study the pathophysiology of major depressive disorder (MDD) are laborious and time consuming. This study examined the effect of a 14-day combined stress model (CS; corticosterone injection and restraint stress) in male Sprague-Dawley rats and also compare the effect of CS versus 28-day corticosterone treatment on depressive-like behaviour and cognitive deficits. Materiel and methods: Depressive-like behaviours and cognitive deficits were assessed in the forced swim test (FST), sucrose preference (SPT), Morris water maze (MWM) and novel object recognition (NORT) tests. Real-time PCR and ELISA were respectively used to detect expression of the serotonin transporter (5-HTT), serotonin 1 A receptor (5-HT1A), α5 GABAA receptor, and the concentrations of corticosterone (plasma), GABA and acetylcholinesterase (AChE) in the hippocampus and Prefrontal cortex (PFC). Results CS group showed increased immobility time in the FST, time to reach the MWM platform, higher corticosterone level, and increased expressions of hippocampal and PFC 5-HT1A and α5 GABAA receptors, and AChE compared to their control groups. In contrast, reductions in SPT ratio, discrimination index in NORT, time in target quadrant, and hippocampal 5-HTT expression was noted relative to their control group. Compared to the 28-day corticosterone only group, PFC 5-HT1A, Hippocampal 5-HTT were reduced, while PFC 5-HTT, Hippocampal α5 GABAA receptors, and AChE concentrations were higher in the CS group. Conclusion: Our CS model induced depressive-like behaviour with early cognitive deficits in rats affecting both hippocampus and PFC. The CS model may be useful in investigating new and comprehensive treatment strategies for MDD.

Prediction of clinical response to corticosteroid or platelet-rich plasma injection in plantar fasciitis with MRI: A prospective, randomized, double-blinded study

PurposeThe purpose of this study was to identify association between magnetic resonance imaging (MRI) features and clinical data at baseline and six months following platelet-rich plasma (PRP) or corticosteroid (CS; cortivazol) injection in patients with plantar fasciitis, and to identify initial MRI criteria associated with a favorable clinical response to treatment. Material and methodsThe study was registered on ClinicalTrials.gov (NCT03857334). MRI examinations of 36 patients with plantar fasciitis lasting more than 3 months who were randomly assigned to receive ultrasound-guided PRP (PRP group, 20 patients) or CS (CS group, 18 patients) injection were quantitatively and qualitatively analyzed with respect to plantar fascia thickness, plantar fascia hyperintensity on T2-weighted STIR (HSTIR) images, calcaneal bone marrow and surrounding soft tissues. Clinical evaluation including visual analytic scale (VAS) assessment and MRI examinations were obtained before and 6 months after treatment. Good clinical response was defined as pain VAS decrease > 50% at 6 months. ROC curves with AUC measurements were used to determine cut-off points. ResultsIn the whole study population, an association was found between MRI features (deep soft tissue and calcaneal bone marrow HSTIR) and pain VAS scores for the first steps of the day (P = 0.028 and P = 0.007, respectively). No significant radioclinical associations on post-treatment MRI examinations were found in either group. Initial coronal thickness of plantar fascia was associated with a good clinical response in the CS group (P < 0.01). ROC curve analysis found that 7-mm or thicker plantar aponeurosis at initial MRI was predictive of good clinical response in patients with CS treatment (Youden index = 0.6). PRP infiltrations were effective regardless of fascia thickness (73% of patients with ≤ 7 mm aponeurosis and 67% for thicker ones). ConclusionInitial facia thickness (> 7 mm) is predictive of good clinical response six months after CS injection, whereas PRP injection shows effectiveness regardless of fascia thickness.

Efficacy and Side Effects of Low Single Doses of Cloprostenol Sodium or Dinoprost Tromethamine to Induce Luteolysis in Donkeys

Due to the limited literature available evaluating doses of Prostaglandin F2α in donkeys, doses for horses have been extrapolated and used as guidelines. This study aimed to assess the efficacy and side effects of four different cloprostenol sodium and dinoprost tromethamine doses to induce luteolysis in jennies. Sixty-three cycles of seven Jennies (nine cycles per jenny) were used in this study. Seven days after ovulation, jennies randomly received one of the treatments in a crossover design as follows: Control, no treatment was administered; C1, 250 µg of cloprostenol sodium (CS, Estrumate , Merck Animal Health, USA); C2, 125 µg of CS; C3, 65.5 µg of CS, C4, 37.5 µg of CS; DT1, 5 mg of dinoprost tromethamine (DT, Lutalyse, Zoetis, USA); DT2, 2.5 mg of DT; DT3, 1.25 mg of DT; DT4, 0.625 mg of DT. Jennies were monitored for 30 minutes following treatment, and adverse effects were recorded. The measurement of the corpus luteum (CL) and the length of the estrous cycle were recorded. All DT and CS treatment doses were effective (P < .0001) in reducing the estrous cycle length compared to jenny's Control cycle. The CL volume was decreased in all treated groups one day after treatment (P < .05). The adverse effects were reduced as the dose of both Prostaglandin F2α analogs were reduced. In conclusion, a single low dose of dinoprost tromethamine (0.625 mg) or cloprostenol sodium (37.5 µg) can induce luteolysis and shorten the estrous length in jennies producing fewer adverse effects.

Cesium Treatment Depresses Glycolysis Pathway in HeLa Cell.

Cesium (Cs) is an alkali metal element that is of no essential use for humans; it has no known beneficial function that is verified by clinical research. When used as an alternative cancer therapy, it even causes toxicity in high doses. Thus, before using Cs as treatment in clinical settings, it is important to clearly determine its biological effects on cells. However, Cs was found to suppress the proliferation of human cervical cancer cells in a dose-dependent manner, and it was assumed that Cs inhibits the glycolysis pathway. In this study, we clearly determined the step of the glycolysis pathway that is affected by Cs. The glycolytic enzyme expressions, activities, and metabolite concentrations in HeLa cells were measured by PCR, western blotting, and enzymatic methods, after treating the cells with Cs for 3 days. Cs treatment decreased transcriptional and expression levels of hexokinase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase (PK), and lactate dehydrogenase and the activity of PK. Analysis of glycolysis pathway metabolites revealed that Cs treatment reduces lactate level and increases the level of nicotinamide adenine dinucleotide (oxidized form, NAD+); however, it did not affect the levels of pyruvate and nicotinamide adenine dinucleotide (reduced form, NADH). Increase of the [NAD+]/[NADH] ratio and decrease of the [lactate]/[pyruvate] ratio indicate that Cs treatment inhibits the aerobic glycolysis pathway. Cs treatment inhibits PK activity and increases the [NAD+]/[NADH] ratio. Hence, Cs has been determined to inhibit glycolysis, especially the aerobic glycolysis pathway. These results suggest that suppression of HeLa cell proliferation following Cs treatment was caused by inhibition of aerobic glycolysis by Cs.