Baseline Day Research Articles

Effectiveness of video-assisted teaching programme and mobile application on knowledge, attitude, and practices regarding management of common minor discomforts of pregnancy among primigravida mothers– A pilot study from South India

Pregnancy might lead to various physiological changes that may end up in a diversity of symptoms and frequently to gastrointestinal complaints, such as heartburn, nausea, vomiting, or constipation. With adequate information and timely care, the majority of mild problems that arise during pregnancy can be reduced.The main aim is to to evaluate the efficacy of video-assisted teaching programme and mobile applicationin improving primigravida women' knowledge, attitudes, and practices about how to handle common pregnancy discomforts.A quantitative research approach with the one group pre-test and post-test design was adopted to conduct this pilot study among a total of 20 primigravida mothers attending the PHC Centre by purposive sampling technique who were administered with video-assisted teaching having the contents on knowledge, attitude, and practice aspects regarding management of various minor discomforts of pregnancy. Knowledge, attitude, and practice were measured using structured tools at the baseline (day 1) and after the administration of video-assisted teaching with mobile app-based follow-up education on day 15. We analysed the data with descriptive to describe the variables, paired t-test to test the effectiveness, Karl Pearson’s correlation for the relationship, and Chi-square to find the association. Knowledge, attitude, and practice all showed statistically significant improvements following the implementation of the video-assisted teaching program and mobile application.The research findings indicated that video-assisted teaching along with a mobile app in their own language was found useful method of educating primigravida mothers to increase their knowledge and to generate favorable attitudes regarding the management of minor discomforts during pregnancy.

Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health.

The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings. The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease-free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty-six NG participants age-matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead-based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2-way analysis of variance (ANOVA) with a post-hoc Tukey's test. Our findings showed that EG had a greater gingival index than NG and was healthy (p<0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p<0.001), CCL3 (p<0.05), and IL-1B (p<0.001) than NG. In contrast, NG had increased levels of MIF (p<0.05), Fractalkine (p<0.001), angiogenin (p<0.05), C3a (p<0.001), BMP-2 (p<0.001), OPN (p<0.05), RANKL (p<0.001), and MMP-13 (p<0.001) than EG. Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG.

Assessment of Wearable Device Adherence for Monitoring Physical Activity in Older Adults: Pilot Cohort Study.

Physical activity has emerged as a modifiable behavioral factor to improve cognitive function. However, research on adherence to remote monitoring of physical activity in older adults is limited. This study aimed to assess adherence to remote monitoring of physical activity in older adults within a pilot cohort from objective user data, providing insights for the scalability of such monitoring approaches in larger, more comprehensive future studies. This study included 22 participants from the Boston University Alzheimer's Disease Research Center Clinical Core. These participants opted into wearing the Verisense watch as part of their everyday routine during 14-day intervals every 3 months. Eighteen continuous physical activity measures were assessed. Adherence was quantified daily and cumulatively across the follow-up period. The coefficient of variation was used as a key metric to assess data consistency across participants over multiple days. Day-to-day variability was estimated by calculating intraclass correlation coefficients using a 2-way random-effects model for the baseline, second, and third days. Adherence to the study on a daily basis outperformed cumulative adherence levels. The median proportion of adherence days (wearing time surpassed 90% of the day) stood at 92.1%, with an IQR spanning from 86.9% to 98.4%. However, at the cumulative level, 32% (7/22) of participants in this study exhibited lower adherence, with the device worn on fewer than 4 days within the requested initial 14-day period. Five physical activity measures have high variability for some participants. Consistent activity data for 4 physical activity measures might be attainable with just a 3-day period of device use. This study revealed that while older adults generally showed high daily adherence to the wearable device, consistent usage across consecutive days proved difficult. These findings underline the effectiveness of wearables in monitoring physical activity in older populations and emphasize the ongoing necessity to simplify usage protocols and enhance user engagement to guarantee the collection of precise and comprehensive data.

Abstract PO1-16-02: Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC)

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC &amp;lt; 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were &amp;lt; 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p&amp;lt; 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P&amp;lt; 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (&amp;lt; 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs &amp;lt; 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-02.

Correlation of C-Reactive Proteins With Chronic Periodontitis. A Prospective Study

Abstract Context: The C-reactive protein (CRP) is an acute-phase reactant protein that is produced in response to various inflammatory and noxious stimuli that include exposure to heat, traumatic conditions, varieties of infectious processes, and conditions of hypoxia. Estimation of CRP levels in serum samples helps in providing important information related to the diagnosis, monitoring, and treatment of inflammatory processes and various associated diseases. Materials and Methods: This prospective longitudinal study was designed to evaluate serum CRPs in subjects who were selected for study participation after fitting into inclusion criteria, which were as follows: a) study participants who were clinically diagnosed with chronic generalized periodontitis along with periodontal pocket depths of ≥5 mm and also radiographic alveolar bone loss; b) subjects within the age range of 35 to 55 years; and c) no smoking habit or use of tobacco in any other form. Results: Patients were assessed for clinical parameters such as gingival index, sulcular bleeding index, mean depth of periodontal pocket, and loss of clinical attachment. Blood was collected at required visits, and CRP was evaluated. Study evaluation periods were baseline (day 0), day 14 (2nd appointment), and day 45 (3rd appointment). Results: Statistically significant reductions in both clinical and serum CRP levels were obtained at subsequent appointments. Conclusion: This study has demonstrated and supported the evidence that serum CRPs act as a biomarker in determining the prognosis of chronic periodontitis patients after nonsurgical periodontal treatment.

Bilateral Sutureless Application of Human Dehydrated Amniotic Membrane with a Specialised Bandage Contact Lens for Moderate-to-Severe Dry Eye Disease: A Prospective Study with 1-Month Follow-Up.

To assess changes in symptoms and ocular surface signs following a bilateral sutureless treatment of dehydrated amniotic membrane (dAM) under a specialised bandage contact lens (sBCL) in patients with moderate-to-severe dry eye disease (DED). In this prospective pre-post interventional study, 35 patients diagnosed with moderate-to-severe DED, with an Ocular Surface Disease Index (OSDI) score >30 on current treatment, were enrolled. Assessments were conducted at baseline (day -30), after 30 days run-in with no additional treatment (day 0 - control), and 30 days post sBCL+dAM treatment (day 30 - treatment). Intervention involved two successive bilateral 4-5 day sutureless applications of dAM (17mm diameter, with a 6 mm central aperture, Omnigen® VIEW) under an 18mm sBCL (OmniLenz®). Symptomatology and ocular signs were measured using OSDI, Dry Eye Questionnaire-5 (DEQ-5), Symptom Assessment iN Dry Eye (SANDE), and other ocular surface health indicators including non-invasive breakup time, corneal and conjunctival staining, and lid wiper epitheliopathy length and width (LWE). While symptomatology remained stable during the 30-day no-treatment run-in, 1-month post-dAM treatment, there was a significant reduction in OSDI scores (from 55.8 to 32.3, p<0.001), DEQ-5 (from 14.6 to 10.0, p<0.001), SANDE frequency (from 65.2 to 43.6, p<0.001), and SANDE severity (from 59.8 to 41.1, p<0.001). Additionally, there was a notable decrease in the width of LWE staining, from grade 2 (50-75% of the lid wiper) to grade 1 (25-50% of the lid wiper) (p=0.011). A bilateral 8-10-day treatment duration with dAM applied with sBCL demonstrated a 31 to 42% improvement in symptomatology and a decrease in ocular surface signs of mechanical stress. This innovative bilateral treatment approach offers a promising treatment modality for patients with refractory moderate-to-severe DED.

Dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models over periods of time

BackgroundDental casts made utilising digital workflow are becoming more common because to their speed and cost savings. However, studies on their dimensional accuracy over time with diverse designs are missing.ObjectiveThe aim of this in vitro study was to assess the dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models with 50-micrometer resolution over 1 day, 14 days, and 28 days using surface matching software.MethodsScanned edentulous and fully dentate maxillary typodont models were used as references. The models were scanned by a desktop lab scanner of 15-micrometer accuracy (D900, 3Shape). Then, the files were used in designing software (Meshmixer, Autodesk) to create hollowed maxillary casts. Fifteen edentulous and 15 fully dentate (total of 30) models were printed using a DLP lab printer (Cara print 4.0, Kulzer). The 3D-printed models were scanned using the same desktop lab scanner of 15-micrometer accuracy at intervals of baseline days, 1 day, 14 days, and 28 days to assess the effect of aging (n = 120). The dimensional changes were quantified and compared using the root mean square (RMS) method, expressed in micrometres (µm). The study employed repeated measures analysis of variance (ANOVA) to assess and compare the root mean square (RMS) values across the variables. The data was analysed using SPSS (26, Chicago, Illinois, USA).ResultsThe RMS of the edentulous models rapidly increased from a mean value of 0.257 at the beginning of the study to 0.384 after twenty-eight days. However, the mean RMS values for the dentate models did not change much over the four intervals. It varied only from 0.355 to 0.347. The mean values for edentulous patients increased from 0.014 to 0.029 during the period from baseline to twenty-eight days. However, the mean average values decreased for the dentate models from 0.033 to 0.014 during this period. By utilizing ANOVA, mean RMS values increased insignificantly till one day but significantly to fourteen and twenty-eight days. Dentate model mean values differed insignificantly across four intervals. Repeated measures ANOVA for combined and separated data showed no significant differences across edentulous, dentate, and total models over times.ConclusionThe study revealed changes in the dimensions of 3D-printed edentulous models over a span of 3 and 4 weeks. Caution should be applied when using 3D-printed dental master models for constructing definitive prostheses on edentulous models over a period of 3 to 4 weeks.

Daily intake of baru (Dipteryx alata Vog.), a Cerrado native almond, promotes changes in the intestinal microbiota of individuals with obesity: A pilot study

The Brazilian Cerrado biome is rich in plant biodiversity, with fruits that have unique sensory characteristics and high nutritional quality. Among the various fruits, baru (Dipteryx alata Vog.) has attracted the attention of researchers because of its high lipid, protein, carbohydrate, fiber, and micronutrient (minerals and vitamins) contents. The present study evaluated the effects of regular consumption of baru almonds for over 60 days on the biochemical and anthropometric profiles and fecal microbiota of obese individuals. A pilot study was conducted on 15 individuals with obesity who were instructed to consume a 20-gram portion of baru almonds throughout the day. The body composition was assessed using anthropometric measurements. Blood pressure, glucose levels, lipid profile, serum insulin and iron contents, and fecal microbiota composition were determined at baseline (day 0) and after 60 days. Baru almond consumption contributed to changes in biochemical parameters, improved HDL cholesterol levels, and reduced total and LDL cholesterol levels. Some positive changes in the microbiota composition after consuming baru almonds include a decrease in the Faecalibacterium family and an increase in the Provotella genus. Therefore, ingesting baru almonds can modulate gut microbiota of individuals with obesity.

Adipose-derived Stem Cells Therapy for Moderate Chronic Obstructive Pulmonary Disease in Adult Subjects: A Phase III Randomized, Multicenter Trial: RESPIRE Protocol

Introduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and has a prevalence of 11.7%. Current treatment focuses on reducing symptoms and exacerbations, as no definitive intervention exists. Regenerative treatments such as mesenchymal stem cell (MSCs) therapy have shown promise in preclinical and clinical studies. This article presents a study protocol to evaluate the efficacy of adipose-derived (AD) MSCs therapy in improving FEV-1 in COPD patients. Methods: A phase III, multicenter, randomized, double-blind, placebo-controlled study is proposed to test the clinical safety and efficacy of AD-MSC therapy in patients with COPD. The population is subjects with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 (50%≤FEV1&lt;80% predicted) and Group D (two exacerbations or one hospitalization and mMRC&gt;2 or CAT&gt;10). This study aims to evaluate the improvement of FEV1 from baseline to 90 days after AD-MSC infusion. The primary outcome is FEV1-improvement (%) over the baseline for the treatment and placebo groups, assessed on study day 90 vs. baseline (day 0). For the primary outcome, the statistical analysis will use the Mann-Whitney U test to analyze the FEV1 for the treatment and control groups at 90 days against the baseline. Discussion: Aside from symptomatic relief, there is a growing demand for a curative treatment for COPD. The potential of novel AD-MSCs therapies for COPD improvement is currently in early development. Preclinical, phase I, and a few phase II studies for AD-MSCs as a COPD treatment have proven optimistic results. This phase III, randomized, multicenter trial proposes evaluating an alternative treatment for this condition that may improve lung function.

Assessment of Efficacy and Safety of Dr.Ortho Capsules in Managing Musculoskeletal Disorders: A Phase IV Post-Marketing Surveillance Study

Objectives: This study aimed to evaluate the potential efficacy and safety of Dr. Ortho capsules in managing various musculoskeletal conditions, including knee pain, joint stiffness, arthritis, bulky shoulders, joint inflammation, acute sports injuries, strains, and sprains. Methods: The study was a single centric, open-label, non-randomized, post-marketing surveillance study involving 120 subjects. Subjects were selected based on inclusion and exclusion criteria. The study assessed changes in pain intensity and disability levels after the administration of Dr. Ortho capsules, employing the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. Additionally, safety was evaluated through physical examinations, vital sign monitoring, and laboratory safety parameters. Results: The study revealed significant reductions in pain intensity and disability levels among the participants. Pain intensity, as measured by VAS, decreased significantly (p&lt; 0.0001) from a mean score of 4.84 at baseline (day 1) to 0.38 at the end of the study (day 30). Disability levels, indicated by ODI, significantly improved (p&lt;0.0001) from a mean score of 14.73% at baseline to 1.88% at the end of the study. There were no reported adverse events during the study, and all safety parameters remained within normal ranges. Conclusion: The findings of the study suggest that Dr. Ortho capsules may offer effective relief for individuals with musculoskeletal conditions, reducing pain intensity and improving functional abilities. The absence of adverse events and the maintenance of normal safety parameters indicate the safety of Dr. Ortho capsules for human consumption.

Sleep and Thermoregulation in Birds: Cold Exposure Reduces Brain Temperature but Has Little Influence on Sleep Time and Sleep Architecture in Jackdaws (Coloeus monedula).

Birds have an electrophysiological sleep state that resembles mammalian rapid-eye-movement (REM) sleep. However, whether its regulation and function are similar is unclear. In the current experiment, we studied REM sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Eight jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a thermistor to record cortical brain temperature. Recordings covered a three-day period starting with a 24 h baseline day at an ambient temperature of 21 °C, followed by a 12 h cold night at 4 °C, after which the ambient temperature was restored to 21 °C for the remaining recovery period. Cold exposure at night caused a significant drop in brain temperature of 1.4 °C compared to the baseline night. However, throughout the cold night, jackdaws expressed NREM sleep and REM sleep levels that were not significantly different from the baseline. Also, EEG spectral power during NREM sleep was unaffected by cold exposure. Thus, while cold exposure had a clear effect on brain temperature in jackdaws, it did not have the same REM sleep suppressing effect reported for mammals. These findings suggest that the REM-sleep-like state in birds, unlike REM sleep in mammals, is protected against the influence of low temperature.

Incidence and outcomes of in-hospital nutritional decline: A prospective observational cohort study in adult patients

Background and AimsHospital malnutrition is associated with higher healthcare costs and worse outcomes. Only a few prospective studies have evaluated trends in nutritional status during an acute stay, but these studies were limited by the short timeframe between nutrition assessments. The aim of this study was to investigate changes in nutritional status, incidence of hospital-acquired malnutrition (HAM), and the associated risk factors and outcomes in acute adult patients admitted for >14 days. MethodsA prospective observational cohort study was conducted in two medical and two surgical wards in a tertiary hospital in Brisbane, Australia. Nutrition assessments were performed using the Subjective Global Assessment at baseline (day eight) and weekly until discharge. Nutritional decline was defined as a change from well-nourished to moderate/severe malnutrition (HAM) or from moderate to severe malnutrition (further decline) >14 days after admission. ResultsOne hundred and thirty patients were included in this study (58.5% male; median age 67.0 years (IQR 24.4), median length of stay 23.5 days (IQR 14)). At baseline, 70.8% (92/130) of patients were well-nourished. Nutritional decline occurred in 23.8% (31/130), with 28.3% (26/92) experiencing HAM. Of the patients with moderate malnutrition on admission (n = 30), 16% (5/30) continued to decline to severe malnutrition. Improvement in nutritional status from moderate and severe malnutrition to well-nourished was 18.4% (7/38). Not being prescribed the correct nutrition care plan within the first week of admission was an independent predictor of in-hospital nutritional decline or remaining malnourished (OR 2.3 (95% CI 1.0–5.1), p = 0.039). In-hospital nutritional decline was significantly associated with other hospital-acquired complications (OR 3.07 (95% CI 1.1–8.9), p = 0.04) and longer length of stay (HR 0.63 (95% CI 0.4–0.9), p=0.044). ConclusionThis study found a high rate of nutritional decline in acute patients, highlighting the importance of repeated nutrition screening and assessments during hospital admission and proactive interdisciplinary nutrition care to treat or prevent further nutritional decline.

East Meets West: Effect of Acupuncture on Lactation and Maternal Quality of Life.

Objective: To evaluate the impact of acupuncture as part of a traditional Chinese medicine (TCM) treatment plan on lactation and maternal well-being in pump-dependent mothers of hospitalized neonates during the first 30 days after delivery. Study Design: This single-center study was conducted in a level IV regional neonatal intensive care unit with access to integrative health services. Sixty-six mothers were prospectively enrolled in two nonparallel groups: (1) Standard lactation support and (2) standard lactation support augmented with acupuncture. Daily pump volumes were documented. Participants completed a quality-of-life (QOL) survey at baseline and neonatal day of life 30. A linear model was constructed, adjusting for increased milk production over time. Results: Acupuncture was associated with increased milk production at all time points: Day 10 (p = 0.0002), day 14 (p < 0.0001), day 21 (p < 0.0001), and day 30 (p < 0.0001). Acupuncture was associated with an increase in three of five QOL components: psychological/child's health (p = 0.0006), family/friend relationship (p = 0.0006), and health/functioning (p = 0.02). Conclusion: Mothers receiving acupuncture reported enhanced milk supply and improved QOL. The limited sample size restricts the broad applicability of the results; nonetheless, this study paves the way for further research on the advantages of merging Eastern and Western treatments to enhance human lactation.

Abstract 5180: Pharmacodynamic biomarker analysis of gastrointestinal cancer patients treated with metronomic chemotherapy in the Italian COMET Trial

Abstract Metronomic, or continuous low-dose, chemotherapy produces antitumor effects through multiple mechanisms. These include inhibition of angiogenesis and activation of the immune system. At AACR 2017 we presented a small, proof-of-concept, multiplex analysis of 14 cytokines specifically chosen by their association with activation of the immune system. The 14 cytokines were evaluated in 31 out of 38 patients with advanced refractory gastrointestinal tumors, enrolled in a phase II clinical trial of metronomic UFT (a 5-fluorouracil prodrug; 100 mg/twice per day p.o.) and cyclophosphamide (500 mg/mq2 i.v. bolus on day 1 and then 50 mg/day p.o.) plus celecoxib (200 mg/twice a day p.o.); the Italian COMET trial (Clinical Trial ID NCT02926911; Allegrini et al. Angiogenesis 2012: 15(2):275-86). We evaluated baseline (day 0) plasma levels with levels at days 28 and 56, and tested for correlations with observed Progression Free Survival, which we then reported (Valenzuela et al. Clin Exp Med. 2021: 21(1):149-159). We now present a comprehensive analysis of 75 cytokines in 34 of the 38 patients. Furthermore we extend the analysis to include baseline (day 0), days 28 and 56, and days 84 and 112 of the COMET trial, and we also correlated specific cytokines levels with Overall Survival. After an estimation of optimal cut-off points of plasma levels of the cytokines, survival analysis was performed, and log-rank tests and cox regression analyses were applied. We show that pre-treatment plasma level &amp;lt;435.46pg/ml of macrophage-derived chemokine (MDC), was a predictive marker for those patients with better progression-free survival at 3 and 6 months (log-rank test p=0.0046; Cox regression analysis p=0.016). Moreover, baseline plasma levels of three cytokines, including monocyte chemoattractant protein 2 (MCP-2), monocyte chemoattractant protein 4 (MCP-4) and TNF-related apoptosis-inducing ligand (TRAIL), were associated with an improved overall survival. MCP-2 values &amp;gt;26.21pg/ml (log-rank test p=0.0012; Cox regression analysis p=0.007), MCP-4 &amp;gt;72.97pg/ml (log-rank test p=0.012; Cox regression analysis p=0.019) and TRAIL &amp;gt;60.73pg/ml (log-rank test p=0.0059; Cox regression analysis p=0.011) were predictive markers for subjects with a better overall survival at 6 and 9 months. These results indicate that a methodology based on the detection of optimal cut-off points and survival analysis allowed the selection of potential biomarkers, such as MDC or MCPs. We propose that the systematic use of these statistical strategies, aimed at detecting potential biomarkers, could help to identify those patients that are likely to benefit from metronomic chemotherapy schedules. This would allow the stratification of such patients for future metronomic chemotherapy trials, and the potential identification of patients that should instead be offered alternative therapeutic strategies. Citation Format: Maria L. Manca, Diana Prospero, Saeedeh Darvishi, Arianna Bandini, Marta Banchi, Paola Orlandi, Hector Padilla, Alejandro Sanchez, Claire E. Perucho, Nydia de Avila, Hazel Padilla, Brianna E. Ortega, Ryley D. Stewart, Magdiel Santillan, Valeria Lopez, Robert Kirken, Giacomo Allegrini, Guido Bocci, Giulio Francia. Pharmacodynamic biomarker analysis of gastrointestinal cancer patients treated with metronomic chemotherapy in the Italian COMET Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5180.

Serdexmethylphenidate/dexmethylphenidate for children with attention-deficit/hyperactivity disorder: dose optimization from a laboratory classroom study.

To evaluate treatment responder rate using the Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) score based on optimized dose level of serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) and changes in ADHD severity in children (aged 6-12 years) with ADHD. During a 21-day dose-optimization phase, 155 patients initiated treatment with 39.2/7.8 mg SDX/d-MPH in the first week and then were titrated to an optimum dose; 5 patients were downtitrated to 26.1/5.2 mg, 76 were uptitrated to 52.3/10.4 mg, and 69 remained at 39.2/7.8 mg during the following 2 weeks. Responder threshold values were 30% and 50% based on the percent change from baseline (day 0) to days 7, 14, and 21 in the ADHD-RS-5 score. The Conners 3rd Edition-Parent score was used to assess weekly changes in ADHD severity during the dose-optimization and treatment phases. Of the 5 subjects whose dose was optimized at 26.1/5.2 mg, ≥80% across all days had ≥50% responder rate. Of the 69 subjects whose dose was optimized at 39.2/7.8 mg, 81.2% had ≥50% responder rate by day 21. Of the 76 subjects whose dose was optimized to 52.3/10.4 mg, 72.4% had ≥50% responder rate by day 21. Changes in ADHD severity, based on mean Conners 3rd Edition-Parent scores, improved from baseline at each visit during dose optimization for each subscale. At the dose-optimization phase, Conners 3rd Edition-Parent scores improved from baseline for SDX/d-MPH in all subscales. A high percentage of subjects were responders upon reaching their final optimized dose. SDX/d-MPH demonstrated significant reductions in ADHD severity in children based on the Conners 3rd Edition-Parent scores. Determining the optimal dosage of SDX/d-MPH and its effect on ADHD severity could enable the development of a more clinically relevant treatment regimen in children with ADHD.

Using transcranial alternating current stimulation to enhance working memory skills in youths with 22q11.2 deletion syndrome: A randomized double-blind sham-controlled study

Abnormal cognitive development, particularly working memory (WM) deficits, is among the first apparent manifestations of psychosis. Yet, cognitive impairment only shows limited response to current pharmacological treatment. Alternative interventions to target cognition are highly needed in individuals at high risk for psychosis, like carriers of 22q11.2 deletion syndrome (22q11.2DS). Here we applied theta-tuned transcranial alternating current stimulation (tACS) between frontal and temporal regions during a visual WM task in 34 deletion carriers. We conducted a double-blind sham-controlled study over three consecutive days. The stimulation parameters were derived from individual structural MRI scan and HD-EEG data acquired at baseline (Day 1) to model current intensity and individual preferential theta peak. Participants were randomized to either sham or tACS (Days 2 and 3) and then completed a visual WM task and a control task. Our findings reveal that tACS was safe and well-tolerated among participants. We found a significantly increased accuracy in the visual WM but not the control task following tACS. Moreover, this enhancement in WM accuracy was greater after tACS than during tACS, indicating stronger offline effects than online effects. Our study therefore supports the application of repeated sessions of brain stimulation in 22q11.2DS.

Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model.

Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial

Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered β-lactam-β-lactam inhibitor combination widely used in clinical practice). We did a phase 1, single-centre, randomised, parallel-group, active-control trial to evaluate the effect of tebipenem pivoxil hydrobromide on the human gut microbiota. Healthy participants aged 18 years or older with no documented illnesses during recruitment were enrolled at Karolinska University Hospital (Stockholm, Sweden). Study participants were stratified by sex and block-randomised in a 1:1 ratio to treatment with either tebipenem pivoxil hydrobromide (600 mg orally every 8 h) or amoxicillin-clavulanic acid (500 mg amoxicillin and 125 mg clavulanic acid orally every 8 h). The study included 10 days of treatment (days 1-10) and four follow-up visits (days 14, 21, 90, and 180). The trial was open-label for clinical investigators and patients, but masked for microbiology investigators. Faecal samples were collected at all visits. Sequencing of 16S rDNA was used to measure the diversity metrics, and quantitative culture to quantify selected taxa. The primary outcomes were changes in the α and β diversity and log count of colony-forming units for selected taxa between samples compared with baseline (day 1), and whether any changes reverted during the follow-up period. The analyses were done in the intention-to-treat population. This study was registered with ClinicalTrials.gov (NCT04376554). The study was conducted between Jan 23, 2020, and April 6, 2021. 49 volunteers were screened for eligibility, among whom 30 evaluable participants (14 men and 16 women) were assigned: 15 (50%) to the tebipenem pivoxil hydrobromide group and 15 (50%) to the amoxicillin-clavulanic acid group. Baseline characteristics were similar between groups. Complete follow-up was available for all participants, and all participants except one completed treatment as assigned. The diversity metrics showed significant changes from baseline during the treatment period. Significant decreases in richness were observed on days 4-10 (p≤0·0011) in the amoxicillin-clavulanic acid group and on days 4-14 (p≤0·0019) in the tebipenem pivoxil hydrobromide group. Similarly, evenness was significantly decreased during treatment in the amoxicillin-clavulanic acid group (day 4, p=0·030) and the tebipenem pivoxil hydrobromide group (days 4-10, p<0·0001) compared with baseline. Quantitative cultures showed significant decreases in Enterobacterales (days 4-7, p≤0·0030), Enterococcus spp (days 4-14, p=0·025 to p<0·0001), Bifidobacterium spp (days 2-4, p≤0·026), and Bacteroides spp (days 4-10, p≤0·030) in the tebipenem pivoxil hydrobromide group. Similarly, in amoxicillin-clavulanic acid recipients, significant changes were observed in Enterobacterales (days4-10, p≤0·048), Bifidobacterium spp (days 2-4, p≤0·013), and Lactobacillus spp (days 2-4, p≤0·020). Samples from the follow-up period were not significantly different from those at baseline in βdiversity analysis (PERMANOVA, p>0·99). By the end of the study, no significant change was observed compared with baseline in either group. There were no deaths or severe adverse events. The impact of tebipenem pivoxil hydrobromide on the gut microbiome was similar to that of amoxicillin-clavulanic acid. The safety of antibiotic use with regard to the microbiome should be given attention, as dysbiosis is associated with health and disease. Spero Therapeutics.

Immunogenicity and safety of COVID-19 booster vaccination: A population-based clinical trial to identify the best vaccination strategy

BackgroundVarious SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves. MethodsThis multicenter, population-based cohort study included 4697 individuals ≥18 years of age who received a booster vaccination. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variants were assessed at baseline (day of booster vaccination) and after four weeks. Safety was evaluated daily within the first week using a participant-completed electronic diary. Antibody levels were compared across different vaccination strategies, taking into account individual host factors. ResultsOur main model including 3838 participants revealed that individuals who received a booster with mRNA-1273 compared to BNT162b2 vaccine had a significantly higher increase (95 %CI) in anti-RBD-antibody levels (37,707 BAU/mL [34,575–40,839] vs. 27,176 BAU/mL [26,265–28,087]), and of neutralization levels against WT (1,681 [1490–1872] vs. 1141 [1004–1278] and Omicron variant (422 [369–474] vs. 329 [284–374]). Neutralizing antibody titres highly correlated with anti-RBD antibodies, with neutralizing capacity 4.4 fold higher against WT compared to Omicron. No differences in safety were found between the two booster vaccines. ConclusionOur study underlines the superiority of a booster vaccination with mRNA-1273, independent of the primary vaccination and therefore provides guidance on the vaccination strategy.

A study to evaluate the effect of Lactobites bar as a galactagogue to increase the production of milk in lactating women and promote overall healthy recovery of lactating mothers

Breastfeeding is widely acknowledged as the preferred and recommended mode of infant nutrition. However, women who have undergone cesarean deliveries may face an increased risk of inadequate breast milk production, which can be addressed through various techniques, including the use of galactagogues, which stimulate breast milk production. Galactagogues are synthetic or plant molecules that induce, maintain, and increase milk production.In this current real-world evidence study, 53 lactating women were enrolled. During the study, they received lactobites bar for 28 days. The intestinal health of the baby, incidences of formula feeding, the volume of breast milk, baby's anthropometric measures: such as changes in height, changes in the quality of hair and skin of the mother were evaluated. The feeling of wellness in the mother and haemoglobin levels were also assessed during the study.The haemoglobin levels were significantly increased in mothers who were given lactobites bar. A significant increase was observed in hours of night and day sleep, stool frequency per day, vol. of breast milk [baseline vs 28 day: 30.19 ± 34.4 vs 448.06 ± 651.11; P&amp;#60;0.05], no. of diapers per day, height [baseline vs 28th day: 47.39±1.72 vs 50.1±1.62; P&amp;#60;0.05], changes in quality of hair and skin of mother, and the feeling of wellness in mother [baseline vs 28th day: 0.04 ± 0.19 vs 1.88 ± 0.32; P&amp;#60;0.05]. A significant reduction was observed in formula feeding incidence (&amp;#60;0.001). No side effects were reported. Lactobites bar can be used as a galactagogue to increase the human milk volume in lactating women.