CTR Group Research Articles

Application of the "echo-synch protocol" to advance pregnancy onset in ewe lambs at the first reproductive season.

This study assessed the efficacy and economic impact of a reproductive protocol based on repeated ultrasound scanning (US) associated with the use of GnRH to advance pregnancy onset in ewe lambs. Prepubertal ewe lambs (n = 133) were divided into three weight groups (High: HW n = 35; Medium: MW n = 65; Low: LW n = 33). Thereafter, animals were randomly allocated into two subgroups: GnRH, ewe lambs treated with GnRH analog and then exposed to rams; CTR, ewe lambs exposed to rams only. CTR groups were joined with rams as a single flock. GnRH groups were kept separate from rams receiving a single dose of gonadorelin (40 μg/head) and then were evaluated after a week of US. Animals showing corpora lutea received an injection of PGF2α analog (100 μg/head) and then were joined with rams. The remaining ewe lambs received a second dose of gonadorelin and were kept separate from the rams. After another week, animals were checked again and the ones showing corpora lutea were injected with the PGF2α analog, while the others received a third injection of gonadorelin. On the same day, all the animals were joined with rams. Pregnancies were confirmed within 30 days by US. The efficacy of the protocol was determined by assessing differences in the number of days required to achieve pregnancy rates of 25, 50, and 75% and in the total costs and incomes from birth to the end of first lactation within the groups. The GnRH-MW group showed the best performances in reaching the threshold pregnancy rates of 25, 50, and 75%, but the effect of treatment was significant only at the 25% threshold (p < 0.01). Both low groups displayed an overall poorer performance at 50 and 75% thresholds than medium and high-weight groups (p = 0.01 and p < 0.01, respectively). The GnRH administration did not advance pregnancy onset in GnRH-HW compared with CTR-HW. In the balance between costs and income, the HW-CTR and MW-GnRH groups showed higher gross margins than the other groups. Using the US/GnRH protocol in ewe lambs appears technically and economically effective in animals that have not reached the optimal weight at the first breeding season, advancing ewe lambs' pregnncies and increasing farm profitability.

Effects of γ-Irradiated Date (Phoenix dactylifera) Fruit on Growth, Immunological and Antioxidant Parameters of Goldfish (Carassius auratus)

The aim of this study was to evaluate the potential effects of γ-irradiated date palm fruit (Phoenix dactylifera), which is rich in phenolic acids and has important and varied biological bioactivities, on growth performance, mucosal immunity and liver antioxidant status in goldfish (Carassius auratus). The antioxidant activity, alongside the phenolic and flavonoid contents, were also determined in irradiated palm fruit extracts (IPFE). The results showed that IPFE5 had a higher antioxidant activity as well as heightened phenolic and flavonoid contents compared to IPFE10 and IPFE0. Meanwhile, goldfish specimens were randomly divided into three groups with three replicates in each. Subsequently, skin immunity and antioxidant activity in the livers of the goldfish were studied. The growth rates of fish fed with IPFE5 and IPFE10 were significantly higher (p &lt; 0.05) compared to the CTR group. In addition, fish fed with the IPFE5 diet demonstrated increased mucosal immunity compared to the CTR group (p &lt; 0.05). Lipid peroxidation levels as well as antioxidant enzyme activities were also higher in all the IPFE-fed groups compared to the CTR group (p &lt; 0.05). These data showed that 40-day dietary administration of γ-irradiated date extract, especially IPFE5, improved growth performance, mucosal immunity, and liver antioxidant capacity in goldfish. The suitability of administrating this additive in the diet of farmed fish is discussed.

Effect of modified clivoaxial angle on surgical decision making and treatment outcomes in patients with Chiari malformation type 1.

Chiari malformation type 1 (CM1), a complex pathological developmental disorder of the craniovertebral junction, is typically characterized by herniation of the cerebellar tonsils from the foramen magnum. Treatment using posterior fossa decompression alone without taking the ventral cervico-medullary compression into consideration may lead to unsatisfactory treatment outcomes. The current study evaluated the utility of the modified clivoaxial angle (MCAA) in assessing ventral compression and also examined its effect on treatment outcomes. This retrospective study included 215 adult patients who underwent surgical treatment for CM1 at one medical center over a 10-year period. The following surgical techniques were used to decompress the posterior fossa: (a) PFD: bone removal only; (b) PFDwD: bone removal with duraplasty; and (c) CTR: cerebellar tonsil resection. The morphometric measurements of the craniovertebral junction (including MCAA) were recorded using preoperative images, and the postoperative clinical status was evaluated using the Chicago Chiari outcome scale (CCOS). MCAA was positively correlated with the CCOS score and also independently predicted treatment outcome. To enable Receiver operating characteristic (ROC) curve analysis of CCOS scores, the patients were divided into three groups based on the MCAA cut-off values, as follows: (a) severe (n = 43): MCAA ≤ 126; (b) moderate (n = 86): 126 < MCAA ≤ 138; and (c) mild (n = 86): MCAA > 138. Group a exhibited severe ventral cervico-medullary compression (VCMC), and their CCOS scores for the PFD, PFDwD, and CTR groups were 11.01 ± 1.2, 11.24 ± 1.3, and 13.01 ± 1.2, respectively (p < 0.05). The CCOS scores increased with widening of the MCAA angle in all surgical groups (p < 0.05). Furthermore, patients with mild MCAA (>138°) exhibited 78% regression of syringomyelia, and this was significantly greater than that observed in the other groups. MCAA can be used in the selection of appropriate surgical techniques and prediction of treatment outcomes, highlighting the importance of preoperative evaluation of ventral clivoaxial compression in patients with CM1.

Randomized Clinical Trial of Intermittent Calorie Restriction in People with Multiple Sclerosis: Effects on Immunometabolic and Cognitive Measures

Abstract BACKGROUND: Intermittent calorie restriction (iCR) reduces inflammation in preclinical models and in people with Multiple Sclerosis (pwMS). Mechanisms could be related to changes in levels of adipose tissue-derived adipokines with reduced systemic inflammation and gut microbiota composition. AIMS: Evaluate the effects of iCR on adipokines levels, metabolic and immune/inflammatory biomarkers compared to a control unrestricted diet (Ctr) in pwMS. METHODS: PwMS (relapsing Remitting MS) were randomly assigned to the iCR or Ctr groups for 12 weeks. Blood was collected at baseline, 6 and 12 weeks. Leptin and adiponectin levels, peripheral blood metabolic and immunologic profiling, anthropometric and total body fat measures, and clinical and cognitive measures were evaluated. Differences between iCR and Ctr were examined using a linear, repeated measures mixed model and adjusted for baseline levels, age, sex and DMTs. RESULTS: 42 pwMS were randomized (iCR=22 and Ctr=20). 34 pwMS completed the study (iCR=17 and Ctr=17). PwMS on iCR showed a significant reduction of anthropometric (weight and BMI) and body adiposity measures (waist circumference and fat mass) over the 12 weeks. Leptin levels decreased and were significantly lower in the iCR group at 6 weeks and approaching significance at 12 weeks. Adiponectin increased from baseline in the iCR group at 6 and 12 weeks. The iCR group showed a significant decrease in Th1 cells and an increase in CD45RO+ regulatory T cells after 6 weeks. Cognitive testing using symbol digit modality test showed significantly greater improvement in the iCR group versus Ctr at 12 weeks. CONCLUSIONS: Short term iCR is safe and feasible in pwMS, and it can ameliorate metabolic, immunologic, and cognitive profiles. National Multiple Sclerosis Society # RG-1607-25158

Ferroptosis inhibition shields house ear institute-organ of corti 1 cells from free fatty acids-induced inflammatory injuries

Background Free fatty acids (FFAs) could induce inflammatory responses via various pathways. Ferroptosis is characterized by the accumulation of lipid peroxidation products and fatal reactive oxygen species derived from iron accumulation, which may be an upstream event in the inflammatory injuries. Objectives To investigate the involvement of ferroptosis during the FFAs-induced pathological hair cell inflammatory injuries and its underlying mechanisms. Material and Methods We utilized House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line as an in vitro model. The palmitate acid (PA) was utilized as a substitute for FFA, with cotreatment with ferroptosis inducer RSL3 and ferroptosis inhibitor Fer-1. Cell viability, lactase dehydrogenase (LDH) release, the expressions of ferroptosis-related factors such as glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), as well as toll-like receptor 4 (TLR4), ferric ion and reactive oxygen species (ROS), and partial inflammatory cytokines were measured. Results PA treatment might induce ferroptosis in HEI-OC1 cells, manifested as decreased cell viability, upregulated LDH release, iron overload, and ROS accumulation. Several inflammatory cytokines including IL-1β, IL-6, IL-1β, IL-6, TNF-α, MCP-1, IL-13, IL-12 p40, CCL5, G-CSF, and GM-CSF were upregulated compared to the Ctr group, while GPX4 and SLC7A11 were downregulated. The expression of TLR4 in the inflammatory pathway was also upregulated. Besides, these changes were further exacerbated by RSL3 cotreatment and abolished by Fer-1 cotreatment. Conclusions and Significance Ferroptosis inhibition could alleviate the PA-induced inflammatory injuries via inactivation of TLR4 signaling pathway in HEI-OC1 cell line.

Maternal treatment with pegbovigrastim influences growth performance and immune-metabolic status of calves during the pre-weaning period

This study aimed to investigate the immune-metabolic status and growth performance of Simmental calves born from cows subjected to pegbovigrastim administration 7 days before calving. Eight calves born from cows subjected to pegbovigrastim administration (PEG group) and 9 calves born from untreated cows (CTR group) were used. Growth measurements and blood samples were collected from birth to 60 d of age. The PEG group had lower body weight from 28 up to 60 d of age (P < 0.01), lower heart girth (P < 0.05), lower weekly and total average daily gain values (P < 0.05) than the CTR group throughout the monitoring period. A decrease in milk replacer (MR) intake was observed in the PEG group compared with the CTR group around 20–28 d of age (P < 0.01). The PEG group had lower values of γ-glutamyl transferase (GGT) at d 1 of age (P < 0.05), Zn at 21 and 28 d of age (P < 0.05), hemoglobin, MCH and MCHC at 54 and 60 d of age (P < 0.01), and higher urea concentration at 21 and 28 d of age (P < 0.05) compared with the CTR group. Lower values of retinol (P < 0.05), tocopherol (P < 0.01), mean myeloperoxidase index (P < 0.05) and higher total reactive oxygen metabolites (P < 0.05) and myeloperoxidase (P < 0.05) were also detected in the PEG group. In light of the results gathered in the current study, it can be speculated that activation of the cow's immune system by pegbovigrastim could have influenced the immune competence, growth performance as well as the balance between oxidant and antioxidant indices of the newborn calf.

Effect of Ouabain on Glutamate Transport in the Hippocampus of Rats with LPS-Induced Neuroinflammation.

A lipopolysaccharide (LPS)-induced neuroinflammation rat model was used to study the effects of ouabain (OUA) at low concentrations, which can interact with the Na,K-ATPase, causing the modulation of intracellular signalling pathways in the Central Nervous System. Our study aimed to analyse the effects of OUA on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation. Adult male Wistar rats were divided into four groups: OUA (1.8 µg/kg), saline (CTR), LPS (200 µg/kg), and OUA + LPS (OUA 20 min before LPS). The animals were sacrificed after 2 h, and the hippocampus was collected for analysis. After treatment, we determined the activities of Na,K-ATPase and glutamine synthetase (GS). In addition, expression of the α1, α2, and α3 isoforms of Na,K-ATPase and the glutamate transporters, EAAT1 and EAAT2, were also analysed. Treatment with OUA caused a specific increase in the α2 isoform expression (~20%), whereas LPS decreased its expression (~22%), and treatment with OUA before LPS prevented the effects of LPS. Moreover, LPS caused a decrease of approximately 50% in GS activity compared with that in the CTR group; however, OUA pre-treatment attenuated this effect of LPS. Notably, it was found that treatment with OUA caused an increase in the expression of EAAT1 (~30%) and EAAT2 (~25%), whereas LPS caused a decrease in the expression of EAAT1 (~23%) and EAAT2 (~25%) compared with that in the CTR group. When treated with OUA, the effects of LPS were abrogated. In conclusion, the OUA pre-treatment abolished the effect caused by LPS, suggesting that this finding may be related to the restoration of the interaction between FXYD2 and the studied membrane proteins.

Bacillus subtilis DSM29784 attenuates Clostridium perfringens-induced intestinal damage of broilers by modulating intestinal microbiota and the metabolome.

Necrotic enteritis (NE), especially subclinical NE (SNE), without clinical symptoms, in chicks has become one of the most threatening problems to the poultry industry. Therefore, increasing attention has been focused on the research and application of effective probiotic strains as an alternative to antibiotics to prevent SNE in broilers. In the present study, we evaluated the effects of Bacillus subtilis DSM29784 (BS) on the prevention of subclinical necrotic enteritis (SNE) in broilers. A total of 480 1-day-old broiler chickens were randomly assigned to four dietary treatments, each with six replicates pens of twenty birds for 63 d. The negative (Ctr group) and positive (SNE group) groups were only fed a basal diet, while the two treatment groups received basal diets supplemented with BS (1 × 109 colony-forming units BS/kg) (BS group) and 10mg/kg enramycin (ER group), respectively. On days 15, birds except those in the Ctr group were challenged with 20-fold dose coccidiosis vaccine, and then with 1 ml of C. perfringens (2 × 108) at days 18 to 21 for SNE induction. BS, similar to ER, effectively attenuated CP-induced poor growth performance. Moreover, BS pretreatment increased villi height, claudin-1 expression, maltase activity, and immunoglobulin abundance, while decreasing lesional scores, as well as mucosal IFN-γ and TNF-α concentrations. In addition, BS pretreatment increased the relative abundance of beneficial bacteria and decreased that of pathogenic species; many lipid metabolites were enriched in the cecum of treated chickens. These results suggest that BS potentially provides active ingredients that may serve as an antibiotic substitute, effectively preventing SNE-induced growth decline by enhancing intestinal health in broilers.

Evaluation of coronary function in female rats with severe type 1 diabetes: Effects of combined treatment with insulin and pyridoxamine.

This study aimed to evaluate the coronary function, myocardium, and epicardial adipose tissue (EAT) in female rats with severe type 1 diabetes and the effects of combined treatment with insulin and pyridoxamine (AGEs inhibitor). Female Wistar rats were divided into groups: control (CTR, n=13), type 1 diabetes (DM1, n=12), type 1 diabetes treated with insulin (DM1+INS, n=11), and type 1 diabetes treated with insulin and pyridoxamine (DM1+INS+PDX, n=14). The vascular responsiveness was performed in the septal coronary artery and the protein expressions of AGE, RAGE, GPER, NF-kB was evaluated in the left ventricle (LV), as well as the reactive oxygen species (ROS) was measured in LV and in EAT. We analyzed plasma levels of glucose, estradiol, Nε-carboxymethylisine (CML), thiobarbituric acid reactive substances (TBARS), catalase (CAT), and superoxide dismutase (SOD). The maximal responses to ACh were reduced in the DM1 compared with the CTR group, accompanied by an increase in circulating glucose, CML, and TBARS. Additionally, the expression of NF-kB in LV and generation of ROS in the presence of MnTMPyP (SOD mimetic) were increased in the DM1 group compared with CTR. Only the combined treatment was effective for fully re-establish ACh relaxation response, NF-kB protein expression, ROS generation, and increased SOD activity in the DM1+INS+PDX group. The reduction of the endothelium-dependent relaxation response in the septal coronary artery of female rats with severe type 1 diabetes was normalized with the combined treatment with insulin and pyridoxamine, associated with reduced inflammation and oxidative stress in the myocardium and increased circulating antioxidant activity.

Treatment with 2 commercial antibiotics reduced clinical and systemic signs of pneumonia and the abundance of pathogenic bacteria in the upper respiratory tract of preweaning dairy calves

The aim of this study was to evaluate the effect of therapeutically administered tildipirosin or florfenicol + flunixin meglumine for the treatment of bovine respiratory disease (BRD) accompanied by fever in calves before weaning compared with diseased and untreated animals. As specific objectives, we evaluated the composition of the bacterial microbiota of the upper respiratory tract (URT) and blood and health parameters of the animals. Preweaning Holstein female calves diagnosed with naturally acquired pneumonia were randomly assigned to one of the following experimental groups on the day of diagnosis (d 0): (1) TLD (n = 36): single subcutaneous injection with 4 mg/kg tildipirosin; (2) FLF (n = 33): single subcutaneous injection with an antimicrobial (40 mg/kg florfenicol) combined with a nonsteroidal anti-inflammatory drug (2.2 mg/kg flunixin meglumine); and (3) NEG (n = 35): no treatment within the first 5 d following enrollment. The NEG treatment group was closely monitored for 5 d, and calves were removed from the study following a standardized late treatment protocol, when necessary, to minimize health concerns. Healthy untreated calves (CTR; n = 31) were also selected for the study and used as controls. Blood samples used for biochemical analysis and nasopharyngeal swabs used for evaluation of URT microbiota were collected daily from d 0 until d 5 and then weekly until weaning. Next-generation sequencing of the 16S rRNA gene was used to assess the URT microbiota at the phylum and genus levels. Clinical signs associated with pneumonia and otitis media were assessed daily, as was the need for antibiotic interventions. Calves in the TLD and FLF groups had faster recovery from fever within the first 5 d after enrollment. In addition, antibiotic-treated calves reached the same serum haptoglobin levels as healthy calves on d 2 after diagnosis, whereas calves in the NEG group had higher haptoglobin levels than the CTR group until at least d 5 after BRD diagnosis. Calves in the TLD and FLF groups had a lower risk of treatment for pneumonia (FLF = 22.8%; TLD = 27.7%) from d 5 to weaning than calves in the NEG group (54.7%). Furthermore, FLF treatment had a significantly lower risk of nasal discharge, otitis media, and treatment failure compared with the NEG group, but did not differ from the TLD group. Differences in the composition of the URT microbiota were found between groups, and the genus Mycoplasma was the most abundant in samples collected from the URT of calves with and without pneumonia. Both drugs were effective in reducing the mean relative abundance (MRA) of important genera associated with pneumonia (Mannheimia and Pasteurella), although an increase in Mycoplasma MRA was observed for tildipirosin-treated calves. In conclusion, both drugs were effective in reducing the inflammatory signs of pneumonia and the need for antimicrobial treatment after enrollment compared with no treatment. In addition, both TLD and FLF were effective in reducing the MRA of important bacterial genera associated with pneumonia; however, TLD treatment was associated with increased Mycoplasma MRA compared with healthy and untreated calves.

Dietary astaxanthin (Lucantin® Pink) mitigated oxidative stress induced by diazinon in rainbow trout (Oncorhynchus mykiss).

The potential of commercial astaxanthin on growth, biochemical factors, and antioxidant-related gene expression following a challenge with diazinon were studied in rainbow trout (Oncorhynchus mykiss). Fish (~ 20.70 g) were fed diets containing commercial astaxanthin (ASX) at 0.00 (CTR and ASX0), 0.50 (ASX1), 2.00 (ASX2), and 5.00 (ASX3) g kg-1 for 60 days. Afterwards, the treated fish (ASX1, ASX2, ASX3) as well as the fish in ASX0 group were challenged with diazinon (0.11 mg L-1) for 96 hr whereas fish in the CTR group was not challenged with diazinon. Results showed that growth pattern improved significantly with all enriched diets compared to the ASX0 group. Metabolic enzyme activities, including alanine aminotransferase and alkaline phosphatase decreased in ASX2 and ASX3 groups with respect to the ASX0 group. Serum antioxidant status also showed the same pattern with enhancement in the fish fed with the ASX2 and ASX3 supplemented diets. Feeding the fish with astaxanthin, particularly in the ASX3 group, up-regulated the expression of some antioxidant-relevant genes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and nuclear factor erythroid-2 related factor 2 (Nrf2) in the kidney and liver. Besides, the histopathological damages in kidneys and liver induced by diazinon were less pronounced in the ASX2 and ASX3 groups compared to the ASX0 group. In conclusion, commercial astaxanthin, especially at 5.00 g kg-1, enhanced the growth performance and ameliorated the oxidative stress induced by diazinon in rainbow trout.

Eficácia da profilaxia antibiótica na extração de terceiros molares

Abstract Introduction Third molar extraction surgery is a common dental procedure, often challenging with increased post-operative complications. The need for antibiotic prophylaxis in these cases remains debated. Objective The aim of this study was to evaluate the effect of antibiotic prophylaxis on the postoperative clinical course of third molar extraction surgeries. Material and method Sixty-three patients were randomly allocated into two groups after extraction of the four third molars. ATB group (N = 33) the patients received 1g of amoxicillin one hour before the surgical procedure, CTR group (N = 30) the patients did not receive antibiotic prophylaxis. Clinical analyses were performed at 3, 7, 14, and 30 days after the surgical procedure. These analyses consisted of assessing oedema, variation in mouth opening, and soft tissue healing. Furthermore, patient-centered analyses were also carried out through the application of the visual analogue scale (VAS) to assess pain, inflammation, bleeding, difficulty opening the mouth, and chewing. Result No influence of antibiotic prophylaxis was observed on the evolution of clinical parameters of healing, oedema, and mouth opening. Patients did not notice differences regarding their comfort during the postoperative period. Conclusion The incidence of complications observed in the present study was low and was not related to infectious processes. The use of prophylactic antibiotic therapy has no beneficial effects on the postoperative clinical course in third molar extraction.

Rheological behaviour, setting time, compressive strength and microstructure of mortar incorporating supplementary cementitious materials and nano-silica.

The setting time of the paste and the rheological properties and microstructure of the mortar after replacing OPC cement with silica fume (SF), fly ash cenosphere (FAC) and nano-silica are studied as a reference for shotcrete applications. The suggested contents of SF, FAC and nano-silica are around 5-7.5%, higher than 20% and 1-3%, respectively, to meet the initial setting time specification. Viscosity and yield stress of mortar are highly dependent on water/cement ratio and paste/sand ratio. At the higher water/cement ratio, viscosity is more based on the paste itself. For SF of 2.5-10%, viscosity and yield stress increase, and the flowability of the mixture decreases. For FAC of 5-25%, viscosity and yield stress increase with a lower rate than SF, and flowability increases at 5% and then decreases as FAC content increases, which, however, is at the same level as the control. When SF and FAC are both added, a tortuous behavior of viscosity is shown. As nano-silica is further added, significant increases in viscosity and yield stress are shown. The compressive strengths of mortar with different supplementary cementitious materials (SCMs) at early ages are close. The difference in compressive strength after 28 days of standard curing is significant. The SF5-FAC15 group exhibits the largest increase in strength for 32.82%. At the age of 2.5 h, the macropore areas distribution of SF5-FAC25-NS1.5 test groups were 31.96%, indicating the lowest macropore area distribution. The secondary hydration reaction of supplementary cementitious materials (SCMs) continuously generates products that fill the pores, and the ultrafine filling effect of nanomaterials improves the compactness of the mortar microstructure and reduces the macropore area distribution. The mercury intrusion test results of the SF5-FAC25-NS1.5 group show that the pores are concentrated within the range of 0.01 to 0.05 μm, and the most probable pore size is significantly smaller than that of the CTR group. As the overall replacement level of SCMs increases, the diffraction peak of calcium hydroxide gradually weakens.

Discriminatory Brain Processes of Native and Foreign Language in Children with and without Reading Difficulties.

The association between impaired speech perception and reading difficulty has been well established in native language processing, as can be observed from brain activity. However, there has been scarce investigation of whether this association extends to brain activity during foreign language processing. The relationship between reading skills and neuronal speech representation of foreign language remains unclear. In the present study, we used event-related potentials (ERPs) with high-density EEG to investigate this question. Eleven- to 13-year-old children typically developed (CTR) or with reading difficulties (RD) were tested via a passive auditory oddball paradigm containing native (Finnish) and foreign (English) speech items. The change-detection-related ERP responses, the mismatch response (MMR), and the late discriminative negativity (LDN) were studied. The cluster-based permutation tests within and between groups were performed. The results showed an apparent language effect. In the CTR group, we found an atypical MMR in the foreign language processing and a larger LDN response for speech items containing a diphthong in both languages. In the RD group, we found unstable MMR with lower amplitude and a nonsignificant LDN response. A deficit in the LDN response in both languages was found within the RD group analysis. Moreover, we observed larger brain responses in the RD group and a hemispheric polarity reversal compared to the CTR group responses. Our results provide new evidence that language processing differed between the CTR and RD groups in early and late discriminatory responses and that language processing is linked to reading skills in both native and foreign language contexts.

Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism.

Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case-control study to evaluate the occurrence of RDV-related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2-5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (-8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb (β = 0.772, p < 0.001) and bALT (β = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.

Diet supplemented with olive cake as a model of circular economy: Metabolic and endocrine responses of beef cattle

IntroductionIntegrating by-products into livestock diet represents a great opportunity for implementing the concept of circular economy while reducing feed costs. Olive cake (OC) is considered an agro-industrial waste, but the high content of valuable metabolites makes it a promising feed integration. Therefore, this study investigated the effect of OC integration in beef cattle diet on different blood parameters.MethodsForty-eight young growing fattening Limousines-−24 bulls (body weight 350 ± 15 kg) and 24 heifers (280 ± 10 kg)—, aged 240 ± 20 days, were randomly allocated to 1 of 3 dietary treatments: concentrate at 0% (Control group: CTR), 10% (Low-olive cake group: L-OC), or 15% (High-olive cake group: H-OC) of OC inclusion. Blood samples and body weights were collected before administrating the supplemented diet (0 d), at the end of the stocker growing phase (56 d), and at the end of the fattening (147 d). After being slaughtered, animal carcasses were weighted. A linear regression model was fitted for each blood parameter with the 0 d as covariate and diet, time, sex, diet × time, and diet × sex as fixed effects.ResultsIn males, body weight was highest in CTR, but carcass weight was similar in all the groups. All the blood parameters were within physiological ranges, independently from the animal diet. CTR group showed the highest alanine aminotransferase (ALT, P = 0.0027) and creatine kinase (P = 0.0119), whereas total bilirubin (P = 0.0023) was higher in H-OC than in CTR. Moreover, ALT was highest in CTR at 56 d, becoming similar in all the groups at 147 d (P = 0.0280). Instead, the increase observed in total cholesterol from 56 to 147 d was lower in H-OC compared with CTR and L-OC (P = 0.0451). A significant effect of diet × sex interaction was observed on triglycerides, urea, liver enzymes, and insulin. These data support the OC inclusion of up to 15% of the concentrate with no detrimental effect on beef cattle metabolic status.DiscussionIn conclusion, OC can be considered as a component in beef diet giving an opportunity to improve agriculture sustainability.

Inhibition of matrix metalloproteinase-9 by 10-MDP and its calcium salt contributes to improved dentin-bonding durability

The activation of matrix metalloproteinases (MMPs) is responsible for degradation of the hybrid layer. The effect of 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) on biodegradation of the hybrid layer remains unknown. This study aimed to evaluate the effects of 10-MDP and its Ca salt on MMP-9 activity and dentin-bonding durability. 10-MDP-Ca salt was synthesized and characterized by X-ray diffraction (XRD) and nuclear magnetic resonance (NMR). The effects of chlorhexidine (CHX), 10-MDP, and 10-MDP-Ca salt on MMP activity were evaluated by in-situ zymography, MMP-9 inhibition assay, and hydroxyproline (HYP) assay. Dentin-resin bonded specimens were fabricated with using CHX or 10-MDP, including Single Bond 2 (Ctr), CHX + Single Bond 2 (CHX), 10-MDP + Single Bond 2 (10-MDP), and SBU (SBU). Micro-tensile bond strength (μTBS) and nanoleakage tests were performed after 24-h or two-years water storage. XRD and NMR confirmed the presence of 10-MDP-Ca salt. The relative inhibition percentages of recombinant MMP-9 for 10-MDP and 10-MDP-Ca salt were 8.04 ± 0.83% and 55.96 ± 1.82% respectively. HYP assay showed that 10-MDP, CHX, and 10-MDP-Ca salt conditioning decreased collagen degradation. Water storage weakened μTBS of all the groups, with the Ctr and CHX groups showing more significant decreases (P < 0.05). After aging, the Ctr and CHX groups also presented more nanoleakage, and the CHX group showed more in-situ zymography fluorescence than the 10-MDP and SBU groups. The capacity to inhibit MMP-9 activity, decrease HYP release, and reduce nanoleakage of 10-MDP and its salt contribute to improvement of dentin-bonding durability.

Atranorin, a Secondary Metabolite of Lichens, Exhibited Anxiolytic/Antidepressant Activity in Wistar Rats.

Atranorin (ATR) is one of lichens' many known secondary metabolites. Most current studies have investigated the various effects of ATR in vitro and only sporadically in vivo. The latest data indicate that ATR may have anxiolytic/antidepressive effects. This study aimed to analyze the potential of ATR in a depression-like state in male Wistar rats. Pregnant females were stressed by restricting their mobility in the final week of pregnancy three times a day for 45 min each, for three following days. After birth, progeny aged 60 days was stressed repeatedly. The male progeny was divided into three groups as follows: CTR group as a healthy control (n = 10), DEP group as a progeny of restricted mothers (n = 10), and ATR group as a progeny of restricted mothers, treated daily for one month with ATR (n = 10; 10 mg/kg of body weight, p.o.). Our results show that ATR acts as an antioxidant and markedly changes animal behavior. Concomitantly, hippocampal neurogenesis increases in the hilus and subgranular zone, together with the number of NeuN mature neurons in the hilus and CA1 regions. Our results indicate a potential antidepressant/anxiolytic effect of ATR. However, further studies in this area are needed.

Antinociceptive Effect of a Sacro-Coccygeal Epidural of Morphine and Lidocaine in Cats Undergoing Ovariohysterectomy.

A commonly described analgesic protocol for ovariohysterectomy (OHE) combines systemic opioids, sedatives, and non-steroidal anti-inflammatory drugs. However, systemic analgesia does not fully prevent perioperative visceral and somatic pain triggered by the surgical stimulus. To compare the analgesic effects and quality of recovery of systemic analgesia with those of a sacrococcygeal epidural injection of lidocaine and morphine in cats undergoing elective OHE. Methods: Twenty domestic female cats were premedicated with dexmedetomidine (0.01 mg kg-1 IM) and alfaxalone (1.5 mg kg-1 IM) and randomly assigned to one of two analgesic protocols: methadone (0.2 mg kg-1 IM) in the control group CTR (n = 10) and methadone (0.1 mg kg-1 IM) + epidural (lidocaine 2% (0.3 mL kg-1) + morphine 1% (0.1 mg kg-1) diluted with NaCl 0.9% to a total volume of 1.5 mL in the SCC-E group (n = 10). General anaesthesia was induced with alfaxalone (1 mg kg-1 IV) and maintained with sevoflurane in 100% oxygen. Non-invasive blood arterial pressure and cardiorespiratory variables were recorded. The quality of recovery was assessed using a simple descriptive scale. Before surgery and 1, 2, 3, 4, 6, and 8 h post-op pain was assessed using the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociception thresholds (MNT). The repeated measures analysis of variance (ANOVA) was used to compare groups over time. Comparison between groups was performed using independent samples t-test if the assumption of normality was verified, or the Mann-Whitney test. The chi-square test of independence and exact Fisher's test were used to compare groups according to recovery quality. Heart rate and systolic arterial pressure increased significantly from baseline values in the CTR group and did not change in the SCC-E group. In the CTR group, MNT and UNESP-Botucatu-MCPS scores increased significantly from baseline for all assessment points and the first 3 h, respectively, whereas this did not occur in the SCC-E group. Based on our results, the SCC-E administration of lidocaine 2% with morphine 1% is a reasonable option to provide perioperative analgesia in cats submitted to OHE, compared to a systemic protocol alone.

Alteration in topological organization characteristics of gray matter covariance networks in patients with prediabetes.

Prediabetes is associated with an increased risk of cognitive impairment and neurodegenerative diseases. However, the exact mechanism of prediabetes-related brain diseases has not been fully elucidated. The brain structure of patients with prediabetes has been damaged to varying degrees, and these changes may affect the topological characteristics of large-scale brain networks. The structural covariance of connected gray matter has been demonstrated valuable in inferring large-scale structural brain networks. The alterations of gray matter structural covariance networks in prediabetes remain unclear. This study aims to examine the topological features and robustness of gray matter structural covariance networks in prediabetes. A total of 48 subjects were enrolled in this study, including 23 patients with prediabetes (the PD group) and 25 age-and sex-matched healthy controls (the Ctr group). All subjects' high-resolution 3D T1 images of the brain were collected by a 3.0 Tesla MR machine. Mini-mental state examination was used to evaluate the cognitive status of each subject. We calculated the gray matter volume of 116 brain regions with automated anatomical labeling (AAL) template, and constructed gray matter structural covariance networks by thresholding interregional structural correlation matrices as well as graph theoretical analysis. The area under the curve (AUC) in conjunction with permutation testing was employed for testing the differences in network measures, which included small world parameter (Sigma), normalized clustering coefficient (Gamma), normalized path length (Lambda), global efficiency, characteristic path length, local efficiency, mean clustering coefficient, and network robustness parameters. The network in both groups followed small-world characteristics, showing that Sigma was greater than 1, the Lambda was much higher than 1, and Gamma was close to 1. Compared with the Ctr group, the network of the PD group showed increased Sigma, Lambda, and Gamma across a range of network sparsity. The Gamma of the PD group was significantly higher than that in the Ctr group in the network sparsity range of 0.12-0.16, but there was no difference between the 2 groups (all P>0.05). The grey matter network showed an increased characteristic path length and a decreased global efficiency in the PD group, but AUC analysis showed that there was no significant difference between groups (all P>0.05). For the network separation measures, the local efficiency and mean clustering coefficient of the gray matter network in the PD group were significantly increased and AUC analysis also confirmed it (P=0.001 and P=0.004, respectively). In addition, network robustness analysis showed that the grey matter network of the PD group was more vulnerable to random damage (P=0.001). The prediabetic gray matter network shows an increased average clustering coefficient and local efficiency, and is more vulnerable to random damage than the healthy control, suggesting that the topological characteristics of the prediabetes grey matter covariant network have changed (network separation enhanced and network robustness reduced), which may provide new insights into the brain damage relevant to the disease.