Trial Period Research Articles

#1179 Early change of eGFR predicts long-term renal event in patients with hypertensive chronic kidney disease using a RAS blocker

Abstract Background and Aims The renin-angiotensin-aldosterone inhibitor (RASI) is one of the important medications for chronic kidney disease (CKD) with potential decrease of glomerular filtration rate (GFR) after initiation. There are few studies about the effect of GFR change by the RASI on variations of GFR and albuminuria. Method This observational cohort study was the extension of an open-label, case-controlled randomized clinical trial (NCT01552954) including adult hypertensive CKD patients with estimated GFR ≥30 ml/min/1.73 m2 and random urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine. In the trial phase, the angiotensin receptor blocker (ARB: Olmesartan 40 mg/day) was prescribed to participants after cessation of RASIs for 8 weeks of screening phase. (0-week). Participants had the second visit at 8 weeks after initiation of ARB (8-week) with randomization into the intensive education for low salt diet and the conventional education. Third visit was conducted at 16 weeks after 0-week (16-week). After 27 (19∼38) months later, we recruited participants for the cohort observation and finished at 38 (29∼48) months after 0-week visit. We grouped patients by tertiles of percent change of initial GFR during the first 8 weeks (from 0-week to 8-week) (pcGFRi) and compared the change of UACR from 24-hour urine and estimated GFR during trial and observational period. Results We analyzed data from 174 people finished 38-month observation among 235 participants enrolled for the trial phase. Initial GFR and 24-h urine UACR were 67 ± 24 ml/min/1.73 m2 and 829 ± 829 mg/g cr, respectively. There were −16.0 (−41.5∼−8.1) %, −2.8 (−7.3∼1.6) %, and 8.3 (1.8∼28.4) % pcGFRi in the first tertile group (group 1), the second tertile group (group 2), and the third tertile group (group 3), respectively. There were no differences in age, gender, GFR, 24-hour UACR, and 24-hour sodium excretion among the tertile groups at 0-week visit. The pcGFRi and the tertile group showed positive correlation with GFR change during 16 weeks of the trial, however, were not related to the percent change of 24-hour UACR during the trial phase. They were also positively correlated to the percent change of GFR during whole study period of 38 months (factor B = 8.180 and p-value< 0.001 for the group and factor B = 0.801 and p-value< 0.001 for pcGFRi), although, they did not show relationships with the percent change of 24-hour UACR during whole study period and UACR at last visit. The GFR slopes per year during 38 (29∼48) months were −2.9 (−4.0∼ −1.8), −1.3 (−2.4∼-0.3), and 0.1 (−1.0∼1.2) ml/min/1.73 m2/year in group 1, group 2, and group 3, respectively (p = 0.001 by the ANCOVA test). The relative risks to estimate GFR decrease ≥ 30% during whole study period were 0.237 (0.07∼0.798) (p = 0.020) and 0.035 (0.004∼0.302) (p = 0.035) in group 2 and group 3 compared to group 1, respectively. The AUC to estimate GFR decline ≥ 30% by the pcGFRi was 0.787 (0.685∼0.889, p< 0.001). The cut-off value 7.25% of pcGFRi estimates GFR decline ≥ 30% with 71.4% sensitivity and 70.9% specificity. Conclusion The decline of GFR by initiation of RASI predicts long-term renal event of GFR decline ≥ 30% in users of RASI, strongly. We need to compare the renal outcomes between RASI users with initial decrease of GFR and non-users to make guideline adjusting RASI usage according to initial change of GFR with RASI prescription.

The Safer Driver App Decreases Mobile Phone Induced Distracted Driving: Evidence From a Randomized Controlled Trial

When using a mobile phone while driving, people are more at risk of causing or being in a crash. To address distracted driving behaviours related to mobile phone use, we developed a mobile coaching app, Safer Driver. The app collects data on a person's driving behaviour and implements behavioural change techniques to help people make smart changes to reduce their distracted driving behaviour. Initially 814 participants were randomly assigned to a 30-day trial period of the Safer Driver app (intervention group, n=573) or the control app (control group, n=241). The control app did not provide any coaching and only collected driving behaviour data. We measured the relative distraction duration score as a proximal outcome. Only participants who were assessed as distracted drivers at the start of the trial were included in our main analysis. This resulted in 182 distracted drivers in the intervention condition who interacted with the Safer Driver app and 86 distracted drivers in the control condition. In line with our hypothesis, the relative distraction duration score was significantly lower at the end of the trial period for distracted drivers who received digital coaching via the Safer Driver app, compared to distracted drivers who received the control app. The findings from this trial indicate that digital coaching via a smartphone application has the potential to decrease mobile phone usage while driving. Digital coaching is a promising way of changing people's behaviour towards safer driving habits.

DIRECT PULP CAPPING IN CARIOUS EX POSED PERMANENT TEETH ASSESSING THE SUPERIORITY BETWEEN BIODENTIN AND MINERAL TRIOXIDE AGGREGATE

Direct pulp capping is an essential technique in endodontic therapy, where it is used to preserve the vitality and functionality of the dental pulp when it has been exposed due to caries or trauma. Objective: The study aims to find the direct pulp capping in carious exposed permanent teeth, assessing the superiority between biodentin and mineral trioxide aggregate. Methods: This randomised control trial was conducted at Sardar Begum Dental College/Hospital Peshawar from January 2023 to June 2023. Data was collected from 112 patients. A total of 112 patients with carious-exposed permanent teeth requiring direct pulp capping were included in the study. Participants in Group A underwent direct pulp capping using Biodentine, while those in Group B received direct pulp capping with MTA. Experienced endodontists performed the procedures following standardised protocols. Pre-operative and post-operative assessments included clinical examination, pulp vitality testing, and radiographic evaluation. Results: Data were collected from 112 patients according to the study's methodology. A 24-month trial period of carrier and MTA proved that they could consistently have high clinical success rates of direct pulp cap for the carious surface of the permanent tooth. In the first 6 months, Biodentine was more successful, 85%, than MTA, 78%, but similar results were presented in 12 months (80% compared to 78%). The radiographic evaluation was done for the healt of periapical healing in the dentine to MTA, which revealed no statistical differences in all the radiographic follow-up intervals. Biodentine and Mineral Trioxide Aggregate (MTA) groups across all follow-up intervals. At 6 months, Biodentine demonstrated a mean healing score of 4.2 ± 0.8, slightly higher than MTA's 4.0 ± 0.7. Conclusion: It is concluded that both Biodentine and Mineral Trioxide Aggregate (MTA) exhibit comparable effectiveness in direct pulp capping of carious-exposed permanent teeth, with high clinical success rates and favourable periapical healing outcomes observed in both groups.

Effects of Breaking Up Sitting on Gut Hormone Responses and Subsequent Compensatory Behaviors in Physically Inactive Adults.

The effects of breaking up sitting on gut hormone responses and free-living energy compensatory behaviors are still unclear in people of Asian ethnicity. Twenty-six Asians including 13 lean individuals (Lean) and 13 individuals with centrally overweight/obesity (OW), aged between 20 and 45 yr, completed a randomized crossover study with either 5.5-h uninterrupted sitting (SIT) or 5.5-h sitting with 2-min walking at 6.4 km·h -1 every 20 min (ACTIVE) in the laboratory. Blood samples were collected at regular time points to examine postprandial glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) concentrations. Free-living physical activity and energy intake were recorded using wearable devices and weighed food diaries outside the laboratory until midnight. Paired t -tests were conducted to compare responses between trials. Postprandial GLP-1 and PYY incremental area under the curve values were higher in the ACTIVE trial versus SIT in both Lean and OW groups (all, P < 0.05), but there was no difference in GIP in either group (both, P > 0.05). There were no differences in free-living physical activity (volume and intensity) or energy intake (total and macronutrients) between trials in either group (all, P > 0.05), resulting in greater total physical activity over the 24-h monitoring period in ACTIVE trial versus SIT trial (both, P < 0.05). Breaking up sitting increases postprandial GLP-1 and PYY concentrations in Asians, but does not induce subsequent behavioral compensation, resulting in greater 24-h physical activity levels and lower relative energy intake, in inactive individuals irrespective of bodyweight status.

Study of a PST-trained voice-enabled artificial intelligence counselor for adults with emotional distress (SPEAC-2): Design and methods

BackgroundNovel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms. MethodsTo further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen after the trial period. Participants will be assessed at baseline and 18 weeks. The primary aim is to confirm neural target engagement by testing whether compared with waitlist controls, Lumen participants will show significantly greater improvements from baseline to 18 weeks in the a priori neural target for cognitive control, right dorsal lateral prefrontal cortex engaged by the go/nogo task (primary superiority hypothesis). A secondary hypothesis will test whether compared with human-coached PST participants, Lumen participants will show equivalent improvements (i.e., noninferiority) in the same neural target from baseline to 18 weeks. The second aim is to examine (1) treatment effects on depression and anxiety symptoms, psychosocial functioning, and quality of life outcomes, and (2) relationships of neural target engagement to these patient-reported outcomes. ConclusionsThis study offers potential to improve the reach and impact of psychotherapy, mitigating access, cost, and stigma barriers for people with depression and/or anxiety.Clinicaltrials.gov #: NCT05603923

Microencapsulated essential oils alleviate diarrhea in weaned piglets by modulating the intestinal microbial barrier as well as not inducing antibiotic resistance: a field research.

Microencapsulated essential oils (MEO)have been used as antibiotic alternatives that can be applied to alleviate diarrhea in weaning piglet. We examined a large group of weaned piglets and incorporated essential oil containing thymol (2%), carvacrol (5%) and cinnamaldehyde (3%) in the feed of weaned piglets on an intensive production farm. The piglets were divided into four groups; Control (no additions) and chlortetracycline (Chl), essential oil (EO) and microencapsulated essential oil (MEO) were fed ad libitum over a 28-day trial period. We found MEO significantly reduced the incidence of diarrhea in the piglets that was also accompanied by increased average daily weight gains from days 14-28 (p < 0.05). MEO enhanced the antioxidant capacity in the piglets and serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-px) levels were significantly increased (p < 0.05). MEO also significantly reduced expression of genes related to ileal inflammation (IL-6, TNF-α and TGF-β1) (p < 0.05) and significantly (p < 0.05) increased in sIgA antibody levels. MEO influenced the composition of the intestinal microbiome and reduced Bacteroidota (p < 0.05) and thus altered the Firmicutes/Bacteroidota ratio. However, none of the treatments produced significant changes in the most common tetracycline resistance genes (p > 0.05). Metagenomic analysis indicated that MEO impacted DNA expression, virulence factors, antioxidant activity and antimicrobial activity. Metabolomic analysis of the intestinal content also indicated that MEO impacted tyrosine metabolism and primary bile acid biosynthesis suggesting improved intestinal health and nutrient absorption. This study paves the way for further research into the development and optimization of MEO-based interventions aimed at improving piglet health and performance while also providing a reference for reducing reliance on antibiotics in animal agriculture.

Protective effects of butyric acid during heat stress on the survival, immune response, histopathology, and gene expression in the hepatopancreas of juvenile pacific shrimp (L. Vannamei)

This study looked at the effects of adding butyric acid (BA) to the diets of juvenile Pacific shrimp and how it affected their response to survival, immunity, histopathological, and gene expression profiles under heat stress. The shrimp were divided into groups: a control group with no BA supplementation and groups with BA inclusion levels of 0.5 %, 1 %, 1.5 %, 2 %, and 2.5 %. Following the 8-week feeding trial period, the shrimp endured a heat stress test lasting 1 h at a temperature of 38 °C. The results showed that the control group had a lower survival rate than those given BA. Interestingly, no mortality was observed in the group receiving 1.5 % BA supplementation. Heat stress had a negative impact on the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the control group. Still, these activities were increased in shrimp fed the BA diet. Similar variations were observed in AST and ALT fluctuations among the different groups. The levels of triglycerides (TG) and cholesterol (CHO) increased with high temperatures but were reduced in shrimp-supplemented BA. The activity of an antioxidant enzyme superoxide dismutase (SOD) increased with higher BA levels (P < 0.05). Moreover, the groups supplemented with 1.5 % BA exhibited a significant reduction in malondialdehyde (MDA) content (P < 0.05), suggesting the potential antioxidant properties of BA. The histology of the shrimp's hepatopancreas showed improvements in the groups given BA. Conversely, the BA significantly down-regulated the HSPs and up-regulated MnSOD transcript level in response to heat stress. The measured parameters determine the essential dietary requirement of BA for shrimp. Based on the results, the optimal level of BA for survival, antioxidant function, and immunity for shrimp under heat stress is 1.5 %.

Developmental refinements to neural attentional state during semantic memory retrieval through adolescence

Despite the fact that attention undergoes protracted development, little is known about how it may support memory refinements in childhood and adolescence. Here, we asked whether people differentially focus their attention on semantic or perceptual information over development during memory retrieval. First, we trained a multivoxel classifier to characterize whole-brain neural patterns reflecting semantic versus perceptual attention in a cued attention task. We then used this classifier to quantify how attention varied in a separate dataset in which children, adolescents, and adults retrieved autobiographical, semantic, and episodic memories. All age groups demonstrated a semantic attentional bias during memory retrieval, with significant age differences in this bias during the semantic task. Trials began with a preparatory picture cue followed by a retrieval question, which allowed us to ask whether attentional biases varied by trial period. Adults showed a semantic bias earlier during the picture cues, whereas adolescents showed this bias during the question. Adults and adolescents also engaged different brain regions—superior parietal cortex and ventral visual regions, respectively—during preparatory picture cues. Our results demonstrate that retrieval-related attention undergoes refinement beyond childhood. These findings suggest that alongside expanding semantic knowledge, attention-related changes may support the maturation of factual knowledge retrieval.

Editorial

We are pleased to introduce the first issue of 2024’s Studies in Communication Sciences (SComS). Following a two-year trial period, the thrice-yearly publication rhythm is now firmly established. Thanks to our reviewers and additional efforts of the whole editorial team, it permits us to accommodate the growing number of submissions. The General Section includes an article by Konstantin Schätz and Susanne Kirchhoff from the University of Salzburg. Combining conceptual metaphor analysis and qualitative frame analysis, they explore how Austrian newspapers portrayed the initial outbreak of COVID-19 in March 2020. Building on the distinction between rhetorical and technical devices of journalistic framing, the article suggests considering metaphors as an additional “reasoning device.” Thus, ontological metaphors emphasized the fragility of the collective “we,” needing to stand together while guarding the distance. The analysis reveals a consistent journalistic framing in a neutral tone that may have favored a responsible public discussion during the crisis.

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

PSVI-16 Inclusion of dietary micelle silymarin on production performance, egg quality, storage capacity, and blood profile Sin Hy-line brown laying hens

Abstract Silymarin is known to have immunomodulating, anti-inflammatory and antioxidant effects. This study aimed to investigate the effects of micelle silymarin (MS) supplementation on production performance, egg quality, egg water loss, and blood profile in Hy-line brown laying hens. For 12 wk, a total of 288, 28-wk-old laying hens were randomly allocated into one of three treatment groups. The dietary treatments were control (CON) a basal diet and a basal diet supplemented with 0.03, and 0.06% of MS. All hens were housed in an individual cage with 38 cm width × 50 cm length × 40 cm height. Growth performance was recorded at d 1, wk 6, and wk 12. The egg production and feed conversion ratio were recorded at the end of every week. The egg quality and water loss were measured at the end of wk 4, 8, and 12. At initial and at the end of wk 12, 5 mL of blood was collected to analyze aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), triglycerides, albumin, and cholesterol concentrations. All data were analyzed by the GLM procedure of SAS. The polynomial orthogonal contrasts of increasing dietary MS supplementation were examined by linear and quadratic effects. The inclusion of MS supplement in laying hen diet did not exhibit significant impact on growth performance. However, MS group showed linear improvement in egg weight, Haugh Units, and eggshell strength throughout the trial period (P &amp;lt; 0.05). Additionally, egg yolk color and eggshell thickness indicated linear improvements particularly at wk 4 and 8 (P &amp;lt; 0.05). While albumen height and egg water in MS group were linearly increased at wk 12 (P &amp;lt; 0.05). Compared with CON, laying hens fed MS supplement has linearly decreased the ALP and cholesterol concentrations in the serum (P &amp;lt; 0.05). Based on the findings, we inferred that the inclusion of 0.04 to 0.06% MS in the laying hen diet would not only increase the production performance, egg quality, and egg water loss traits but also to improve laying hens’ health.

A multicenter, open-label, single-arm trial of the long-term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE-02).

Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01. The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02. Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis. Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

PSIII-2 Evaluation of medium-chain fatty acids on just-weaned piglet performance and diarrhea scores: A nursery trial

Abstract Weaning is one of the most stressful events for commercial pigs. The transition from mother’s milk (animal proteins) to a solid diet based on plant proteins, the reduction in lactose intake and the decline in HCl secretion by the digestive system of the piglet result in a sudden and significant increase in stomach pH as well as an increased risk of post-weaning diarrhea. The aim of this trial was to evaluate whether the use of a blend of medium-chain fatty acids (MCFAs) on top-off conventional nursery diets would improve zootechnical performance and intestinal problems in just-weaned piglets. Piglets [n = 624, 21-d of age, 6.5 kg body weight (BW), (♂ Fast Duroc x ♀ Fast 275)] were housed in 26 pens of an experimental nursery. Each pen (24 pigs/pen, with a starting density of 3.0 ft2/pig) was equipped with a height-adjustable water sucker, a water bowl and fitted with a single feeder-bin. Females and males were allocated to each pen, according to 3 BW categories (heavy, medium, and light). During a 46-d period of trial, the piglets (13 replicated pens per treatment) were allotted to a conventional 5 phases feeding program with 2 kg/MT of chlortetracycline (22%) and 400 g/MT of tiamuline (1.78%; CON). These basal diets contained 2,500 ppm Zn in Phases #1, 2, and only 2,000 ppm Zn in phase #3. Phases #1 to 3 were also supplemented with Ca-butyrate (1 kg/MT) and a blend of protected acidifiers (1 kg/MT). The treated group consisted to the basal diet (CON) supplemented with a blend of medium-chain fatty acids (MCFAs) at 1.0 or 0.75 kg/MT for Phases #1, 2,3 and Phases #4, 5, respectively and supplying of a proprietary blend of caprylic, capric, and lauric acids. Daily feed consumption, weekly pig pen BW, dead and removed pigs and daily diarrhea evaluation index were completed. Data are analyzed by an ANOVA model including treatment and pen as fixed and random effects, respectively. Pairwise comparisons were completed with a Chi-square test. The overall results are presented in Table 1. At the end of wk 2 and 3, animals receiving MCFAs had a better average daily gain (ADG; P &amp;lt; 0.05) than CON. Therefore, at wk 2, 3 and 4, MCFAs animals BW were heavier than CON ones (P &amp;lt; 0.05). Average daily feed intake (ADFI) was not significantly different for the overall duration of the trial (P &amp;gt; 0.05). However, at weeks 2 and 3, MCFAs piglets had a greater ADFI than CON ones (P &amp;lt; 0.05). The daily diarrhea index of the MCFAs group was less than CON at wk 3 (P &amp;lt; 0.05). In this trial, the significant improvement of diarrhea index on just-weaned MCFAs treated piglets could explain the significant better growth during the first 3 wk of nursery.

Effects of herbal dregs supplementation of Salvia miltiorrhiza and Isatidis Radix residues improved production performance and gut microbiota abundance in late-phase laying hens.

The present study was designed to evaluate the effect of a mixture of Chinese medicinal residues (CMRs) consisting of Salvia miltiorrhiza residues (SMR) and Isatidis Radix residues (IRR) on productive performance, egg quality, serum lipid and hormone levels, liver and blood antioxidant capacity, oviduct inflammation levels, and gut microbiota in the late-laying stage. A total of 288 fifty-four-week-old BaShang long-tailed hens were divided into four groups. The feed trial period was 8 weeks. The control group was fed the basic diet as a CCMR group, supplemented with 3, 4, and 6% for the experimental groups LCMR, MCMR, and HCMR. The egg production rate of the MCMR group was 8.1% higher than that of the CCMR group (p < 0.05). Serum triglyceride (TG) levels of hens of the CMR-supplemented group were significantly decreased than those of the CCMR group (p < 0.05). The group supplemented with different levels of CMR had significantly higher serum HDL-C levels compared with the control group (p < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were remarkably increased for the LCMR and MCMR groups and significantly decreased for the HCMR group compared to CCMR (p < 0.05). Serum and liver glutathione peroxidase (GSH-PX) activities were significantly increased, and malondialdehyde (MDA) levels were significantly decreased in the MCMR group compared to the CCMR group (p < 0.05). The expression levels of tubal inflammatory factor markers (IL-4, IL-1β, TNF-α) in the MCMR and HCMR groups were consistent with the pathological findings of the sections. As for cecal microbiota, supplementation with CMR affected the alpha diversity of the cecum microbiome at the genus level. The Shannon index was significantly higher in the MCMR group than in the CCMR and HCMR groups (p < 0.05). Supplementation with different levels of CMR mainly regulated the ratio of intestinal Firmicutes to Bacteroidetes and the abundance of phyla such as Proteobacteria. In addition, CMR supplementation at different levels in the diet enriched lipid-metabolizing bacteria, such as Bacteroides and Ruminococcus_gnavus_group. Furthermore, according to linear discriminant analysis (LDA) effect size (LEfSe) analysis, the MCMR group showed an increase in the number of short-chain fatty acid-producing bacteria Romboutsia and fiber-degrading specialized bacteria Monoglobus. Therefore, supplementation of appropriate amounts of CMR to the diet of laying hens enhanced reproductive hormone levels, hepatic antioxidant capacity, and lipid metabolism, alleviated the levels of oviductal inflammatory factors, and modulated the abundance structure of bacterial flora to improve the late-laying performance and egg quality. The results of the current study showed that CMR is a beneficial feed supplement for chickens when added in moderation.

The Effects of Digital Educational Games on Secondary School Students’ Attitudes Towards Elective English Class and on Increasing Their English Listening Skills and Vocabulary

The purpose of this study was to investigate the impact of digital educational games on secondary school students' attitudes towards elective English lessons, as well as the influence of digital educational games on the development of EFL listening skills and vocabulary learning. The study group included 40 students in two classes of 6th grade elective English course from a secondary school in Samsun province of Türkiye during the academic year 2022-2023. A quasi-experimental model with a pretest-posttest control group was used in the study. A total of six weeks, namely two hours of instruction each week, made up the trial period. Digital instructional games meeting certain criteria set by the study were used to teach the experimental group. In the control group, no digital educational games were employed, and the same teaching strategies as before the experiment were used. An academic achievement exam covering vocabulary and listening and the "Middle School English Course attitude scale" were utilized as data gathering tools. The study revealed that digital educational games had a favourable impact on secondary school students' views about the elective English class. Additionally, it was noted that the pupils in the experimental group improved their vocabulary and listening skills more than those in the control group. In conclusion, considering the positive outcomes of using digital educational games in both foreign languages and other disciplines, we can say that their integration into education will have positive effects on academic achievement and may positively affect students' attitudes towards that course by providing them with a fun learning environment. This makes the case for the potential use of digital educational games as a tool for learning-reinforcing activities in elective English and other elective classes.

The efficacy of transcranial direct current stimulation in the treatment of anorexia nervosa: a randomized double-blind clinical trial.

Anorexia nervosa (AN) is a life-threatening disease with a low effectiveness of treatment. The high relapse and mortality rate indicate new treatment approaches are needed. Here, we represent the protocol for randomized clinical trial (RCT) of transcranial direct current stimulation (tDCS) efficiency in the AN treatment. The main purpose of the 3-week RCT is to determine the effect of tDCS on the mental state and advances in nutritional rehabilitation in patients with AN. 50 female inpatients (13-25 years old, body mass index (BMI) 17.5 kg/m2 or less) will be randomly allocated into groups: active (n=25) and sham (n=25) tDCS. Thirty 25-minute tDCS sessions (applied current at 2mA) will be given to DLPFC (F3 anode/F4 cathode) twice a day for 3 weeks on working days parallel to treatment as usual. The primary outcome measures include changes in symptoms related to eating disorders, as assessed by the Eating Attitudes Test (EAT-26), following tDCS sessions over a 3-week trial period. The secondary outcome measures include changes in: brain bioelectric activity, anthropometric measurements, mood, nutritional status, neurocognition, psychological symptoms, selected biological markers related to stress, food intake, inflammation and neurotrophins. This paper describes the evaluation of a 3-week tDCS-based intervention for AN patients. The study design was developed by a multidisciplinary research team to assess the treatment effect, taking into account various types of variables. This approach could help in better understanding the potential therapeutic tDCS strategy in AN. www.ClinicalTrials.gov, identifier NCT05814458.

Effect of the sodium-glucose cotransporter-2 inhibitor, DWP16001, as an add-on therapy to insulin for diabetic dogs: A pilot study.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents. This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment. Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n=10) and DWP SID group (n=9). In the DWP TOD group, 0.025mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups. No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p<0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n=5, DWP SID group n=5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001. When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.

Youth Suicide Attempts from the Perspective of Healthcare Professionals: A Qualitative Study, a Case of Turkey

This study was aimed at determining why youth attempt suicides, what the causes of such attempts are, and what methods are used in suicide attempts from the perspective of emergency medicine and mental healthcare professionals. Healthcare professionals provide first aid and treatment for young people who have attempted suicide. In this study, the qualitative research method and phenomenological design were used. In the interviews, a semi-structured interview form was used. According to the participating healthcare professionals’ conclusions at the end of the study, youth is a trial and error period, young people do not always aim to die, they may attempt suicide for manipulative purposes or to call for help, and the method used in the suicide attempt may vary according to the purpose and sex. Healthcare professionals who participated in this study clearly stated that gender-based expectations cause suicide attempts in both male and female youth (both male and female youth to attempt suicide). It is recommended that in future studies, the focus should be on the opinions and experiences of all professionals working in the field of suicide attempts, and that gender-based experiences that may lead youth to attempt suicide should be further addressed.

ANALISIS SWOT DALAM MENENTUKAN PROSES REKRUTMEN DAN SELEKSI KARYAWAN DI JNE EXPRESS CABANG UTAMA KOTA SORONG

This research aims to determine effective recruitment and selection strategies to increase deliveries carried out by JNE Express Sorong City Main Branchthrough SWOT analysis. This research uses qualitative research. Secondary data was collected through observation. Apart from observation, the author also used interviews with HRD and the head of Marketing at JNE Express Main Branch, Sorong City. The data that has been collectedthen analyzed using the SWOT method. The results of the research show that the total IFAS Matrix is 3.29 and the EFAS Matrix is 3.24, with the position in quadrant III showing that the strategy used is the Turn Around (WO) strategy with several strategies, namely inviting a trainer from JNE center to conduct training or seminars to develop employees' knowledge andskills in their field and conduct a trial period for new outsourcing employees.

Assessing the influence of micelle silymarin on laying hens' performance, egg quality, water loss and blood profile.

Micelle silymarin (MS) is known for its various beneficial properties, including antiswelling, antioxidant, hepatoprotective and antidiabetic effects. The primary goal of this research was to investigate how MS impacts the performance, egg quality, water loss and blood profile of laying hens. 288 Hy-Line brown laying hens, 28 weeks in age, were utilized for this experiment. The hens were randomly allocated into three dietary treatment groups, with each group comprising eight replicates of 12 hens, each housed in individual pens with access to feed and water. Over a 12-week feeding trial, the hens were provided with a basal diet supplemented with different levels of MS: 0%, 0.03% and 0.06%. The results indicated that the inclusion of MS in the hens' diet did not have a significant impact on their performance (p > 0.05). However, Haugh units, egg weight and eggshell strength showed a linear improvement (p < 0.05) throughout the entire trial period with MS supplementation. Furthermore, there was a linear decrease in egg yolk colour and eggshell thickness showed linear improvements (p < 0.05), particularly during Week 8, with MS supplementation. Moreover, layers fed diet supplemented with MS showed a linear increased (p < 0.05) in albumen height and eggshell thickness in Week 12. In addition, egg water loss during Week 12, the third day of incubation, linearly decreased as an effect of the increasing level of the MS in the laying hen's diet (p < 0.05). Regarding blood profile parameters, the study revealed a tendency for alkaline phosphatase to decrease, whereas aspartate aminotransferase and cholesterol levels were linearly decreased (p < 0.05). In summary, increasing the level of MS supplementation in the diet of laying hens appeared to be beneficial in improving egg quality, slight improvement for egg water loss and certain aspects of blood profile parameters, without adversely affecting the hens' growth performance.