Kilogram Of Body Weight Research Articles

Bridging the gap: aligning physical work capacity testing with actual endurance performance in military settings

Physical fitness tests are essential for evaluating the endurance capabilities of military personnel. In many armed forces, including the Czech Republic’s, the Physical Working Capacity at a heart rate of 170 beats per minute (PWC 170) test is used to predict performance on the 12-min Cooper run, a widely accepted measure of endurance. However, concerns exist regarding the accuracy of the currently used conversion between PWC 170 test results, specifically W170/kg (watts per kilogram of body weight), and actual 12-min run performance. This study directly investigates the relationship between W170/kg and 12-min run times among military recruits and students (military personnel) from a university with a military program. Utilizing regression analysis, we found a significant positive correlation between W170/kg and 12-min run performance. However, the currently used conversion significantly underestimated actual 12-min run performance across all analyzed groups. These findings highlight a critical need to revise the existing conversion standard between W170/kg and 12-min run performance to ensure a more accurate and effective assessment of endurance capabilities in military personnel.

The association between initial defibrillation dose and outcomes following adult out-of-hospital cardiac arrest resuscitation: a retrospective, multi-agency study.

Effective defibrillation is essential to out-of-hospital cardiac arrest (OHCA) survival. International guidelines recommend initial defibrillation energies between 120 and 360 Joules, which has led to widespread practice variation. Leveraging this natural experiment, we aimed to explore the association between initial defibrillation dose and outcome following OHCA. The ESO Data Collaborative (2018-2022) was used for this nationwide, retrospective study of adult (18-80 years of age) non-traumatic OHCA patients who presented with an initially shockable ECG rhythm. We excluded patients if they had ROSC prior to initial defibrillation, a resuscitation-limiting advanced directive, or were residents in a healthcare institution. The primary exposure was initial defibrillation dose, defined as Joules per kilogram of body weight, and the primary outcome was return of spontaneous circulation (ROSC). We included survival to discharge as a secondary outcome. We used multivariable logistic regression modeling to assess the relationship between defibrillation dose and outcome. We analyzed data from 21,121 patients. Of the 12,160 patients linked to a defibrillator manufacturer, 7,240 (59.5%) were treated using a biphasic truncated exponential (BTE) waveform and 4,920 (40.5%) were treated using a rectilinear biphasic (RLB) waveform. Defibrillation dose (per 1 J/kg increase) was not associated with ROSC (BTE aOR: 0.97 [0.92, 1.01], n=7,240; RLB aOR: 1.00 [0.92, 1.09], n=4,920; all aOR: 1.01 [0.98, 1.04], 21,121) or survival (BTE aOR: 0.98 [0.87, 1.10], n=1,245; RLB aOR: 0.89 [0.70, 1.12], n=775; all aOR: 1.00 [0.92, 1.08], n=2,981). Initial defibrillation dose was not associated with outcome in this nationwide cohort.

Analysis of serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol in patients with heart failure with reduced ejection fraction: a pilot study in routine health care

ABSTRACT Background The cardioselective β-1 receptor antagonist metoprolol is used to treat heart failure. It is metabolized in the liver, primarily by cytochrome 2D6. Research design and methods In this study, trough serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol were measured in patients with heart failure with reduced ejection fraction. Results Concentrations were 1.3–122.9 µg/L for metoprolol and 1.3–125.7 µg/L for α-hydroxymetoprolol, metabolic ratios were 0.11–98.32. The median weight-adjusted apparent clearance of metoprolol was 53.07 (range 3.24–500.0). Metoprolol and α-hydroxymetoprolol concentrations correlated with both daily dose and dose per kilogram of body weight. However, metoprolol concentrations at the same daily dose showed a wide variability. Patients taking 100 mg/day had significantly lower NT-proBNP values than those taking 25 or 50 mg/day. Patients with LVEF ≤ 35% versus > 35% used significantly lower daily doses and doses per kilogram of body weight, although metoprolol concentrations did not differ. A poor cytochrome 2D6 metabolizer phenotype was detected in two patients. Conclusions Metoprolol concentrations showed a wide interindividual variability at the same daily dose. Simultaneous determination of metoprolol and α-hydroxymetoprolol concentrations could identify patients at risk of possible accumulation of metoprolol leading to intoxication or, conversely, patients at risk of underdosing.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma

BackgroundTalquetamab (anti–G protein–coupled receptor family C group 5 member D) and teclistamab (anti–B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class–exposed relapsed or refractory multiple myeloma.MethodsWe conducted a phase 1b–2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study. Talquetamab at a dose of 0.8 mg per kilogram of body weight plus teclistamab at a dose of 3.0 mg per kilogram every other week was selected as the recommended phase 2 regimen. The primary objective was to evaluate adverse events and dose-limiting toxic effects.ResultsA total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months. Three patients had dose-limiting toxic effects (including grade 4 thrombocytopenia in 1 patient with the recommended phase 2 regimen). Across all dose levels, the most common adverse events were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of the patients. Grade 3 or 4 infections occurred in 64% of the patients. With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease); across all dose levels, a response occurred in 78%. The likelihood of patients continuing in response at 18 months was 86% with the recommended phase 2 regimen (82% among those with extramedullary disease) and 77% across all dose levels.ConclusionsThe incidence of grade 3 or 4 infections with talquetamab plus teclistamab was higher than has been observed with either therapy alone. A response was observed in a high percentage of patients across all dose levels, with durable responses with the recommended phase 2 regimen. (Funded by Janssen Research and Development; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.)

Optimization of Nanobentonite-CuO Adsorption for Reducing 3-MCPDE, Free Fatty Acids, and Peroxide Values in Bulk Cooking Oil: A Study of Adsorption Efficacy and Isotherm Modeling

Indonesia is the largest palm oil producing country in the world. A factor that affects the quality of cooking oil is the presence of diglycerides and free fatty acids. Diglycerides in palm oil serve as precursors for the carcinogenic chemical 3-Monochloropropane-1,2-diol ester (3-MCPDE), whilst elevated concentrations of free fatty acids (ALB) might compromise oil stability. Numerous investigations indicate that the cooking oil present in the population includes the 3-MCPDE molecule at levels ranging from 8,150 to 58,140 ug/kg. The maximum permissible amount is 2 ug of 3-MCPDE per kilogram of body weight per day. The pillarization process involves the amalgamation of Cu(NO3)2 and NaOH inside an activated bentonite solution. The adsorption analysis of 3-MCPDE employing nanobentonite-CuO was performed using Gas Chromatography Mass Spectrometry (GC-MS) in accordance with the AOCE Cd 29a-2013 method, while free fatty acid and peroxide values were evaluated by a titration method that accounted for temporal variations. The peak efficacy of Nanobentonite-CuO in adsorbing the 3-MCPDE molecule was seen at 15 minutes, with an adsorption efficiency of 52.4%. Peroxide numbers achieved ideal performance at 45, 60, and 75 minutes, with an adsorption efficiency of 80%, whilst free fatty acids reached top performance at 75 minutes with an adsorption efficiency of 76.69%. The adsorption of 3-MCPDE compounds, free fatty acids, and peroxide content by Nanobentonite-CuO, as indicated by Adsorption Isotherm modeling, conforms to the Freundlich Isotherm, implying a physical adsorption mechanism.

Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.

Severe hemophilia A is managed with factor VIII replacement or hemostatic products that stop or prevent bleeding. Data on gene therapy with hematopoietic stem-cell (HSC)-based expression of factor VIII for the treatment of severe hemophilia A are lacking. We conducted a single-center study involving five participants 22 to 41 years of age with severe hemophilia A without factor VIII inhibitors. Autologous HSCs were transduced with CD68-LV-ET3 - a lentiviral vector including a new F8 transgene (ET3) with a myeloid-directed CD68 promoter - either without transduction enhancer (group 1) or with transduction enhancer (group 2). Transduced HSCs were transplanted into recipients after myeloablative conditioning. The treatment was assessed for safety (engraftment and regimen-related toxic effects) and efficacy (factor VIII activity and annualized bleeding rate). Participants received CD68-ET3-LV-transduced autologous CD34+ HSCs at doses of 5.0×106 to 6.1×106 per kilogram of body weight. The vector copy numbers in the final drug product were 1.0 and 0.6 copies per cell for the two participants in group 1 and 1.5, 0.6, and 2.2 copies per cell for the three participants in group 2. The duration of severe neutropenia was 7 to 11 days and of severe thrombocytopenia was 1 to 7 days. The median factor VIII activity level, measured with the use of a one-stage assay, after day 28 until the last follow-up visit was 5.2 IU per deciliter (range, 3.0 to 8.7) and 1.7 IU per deciliter (range, 1.0 to 4.0) with a peripheral-blood vector copy number of 0.2 and 0.1 copies per cell, respectively, in the two group 1 participants, and 37.1 IU per deciliter (range, 18.3 to 73.6), 19.3 IU per deciliter (range, 6.6 to 34.5), and 39.9 IU per deciliter (range, 20.6 to 55.1) with a peripheral-blood vector copy number of 4.4, 3.2, and 4.8 copies per cell, respectively, in the three group 2 participants. The annualized bleeding rate was zero for all five participants over a cumulative follow-up of 81 months (median follow-up, 14 months; range, 9 to 27). Gene therapy for hemophilia A with the use of lentiviral vector-transduced autologous HSCs resulted in stable factor VIII expression, with factor VIII activity correlating to vector copy number in the peripheral blood. (Funded by the Ministry of Science and Technology, Government of India, and others; ClinicalTrials.gov number, NCT05265767; Clinical Trials Registry-India number, CTRI/2022/03/041304.).

Correlation between body fat percentage and aerobic capacity in various athletes

Introduction: The Body Fat Percentage is an indicator of the Body's fitness level and its effects on VO2max and thus the cardiovascular status of the athletes. Physical exercise can help to improve a healthy life interestingly. Aims: This study aims to understand the relationship between Body Fat Percentage and Aerobic Capacity of different athletes. Methods: A total of 150 athletes were randomly selected as the subjects for the present study. In the present study VO2max was measured by Step test in millimeters of oxygen per kilogram of body weight per minute (ml.kg-1.min-1) and Fat percentage was measured by Skinfold Calliper in Millimeters (mm). The collected data were inferential statistics and an independent t-test was applied to check the level of significance. The significance level was set at p < .05. Descriptive and for the relationship appropriate multiple relation statistical tools will be used for the analysis of gathering data. Results: In between fat percentage and Step Test Pulse rate (b/min) coefficient of correlation (r = .441) and level of significance (p = .00) indicated statistical significance with a small positive correlation. At the time relationship between fat percentage and VO2max (ml/kg/min) (r = -.450) and level of significance (p = .00) indicated a statistically significant and medium negative correlation. Conclusion: The relationship between body fat percentage variables and VO2max was statistically significant and indicated a negative correlation but step pulse rate and fat percentage were statistically significant with a small positive correlation.

The effect of human umbilical cord-derived mesenchymal stem cell transplantation on the reparative properties of muscle-aponeurotic defect reconstruction in the anterior abdominal wall of rats

Postoperative ventral hernias represent a significant challenge in modern surgery, arising as complications following abdominal operations due to weakness or defects in the musculoaponeurotic structure of the anterior abdominal wall. Mesenchymal stem cells (MSCs) possess high reparative potential due to their paracrine ability to stimulate the regeneration of damaged recipient tissues. Objective. To investigate the effect of intraperitoneal transplantation of human umbilical cord-derived MSCs on the regeneration of muscle fibers in the area of musculoaponeurotic defect repair in the anterior abdominal wall of rats. Materials and Methods. A surgical model of a musculoaponeurotic defect (2 cm in diameter) in the anterior abdominal wall was created in 72 white rats. Animals were divided into four groups based on the method of defect correction: 1) repair with autologous tissues; 2) repair with autologous tissues combined with MSC injection; 3) repair using a polypropylene mesh; 4) repair using a polypropylene mesh combined with MSC injection. Human umbilical cord-derived MSCs were isolated using enzymatic methods, validated by flow cytometry for surface marker expression, and administered intraperitoneally at a dose of 1 million cells per kilogram of body weight. On the 10th and 30th days, histological analysis of tissue samples from the repair site was conducted, assessing the presence of granulation tissue, collagen fibers, newly formed connective tissue, and cellular infiltration. Morphometric comparisons included the relative areas of granulation and fibrous reticular tissue, microcirculatory vessels, and counts of neutrophilic leukocytes, lymphohistiocytic elements, and fibroblasts per square millimeter of section. Results. In Group 1, the repair area demonstrated loose connective tissue rich in fibroblasts and histiocytes. In Group 2, a significantly reduced cellular reaction was observed, along with the formation of denser connective tissue bundles; transverse striation of muscle fibers was more clearly visualized at the sites of damage. On day 10, the granulation tissue area was 34.6% smaller, and the microcirculatory vessel area was 15.9% smaller compared to Group 1, and 28.1% and 57.2% smaller, respectively, compared to Group 3. In Group 3, granulation tissue formed at sites of necrosis and muscle fiber destruction. The best results were observed with the combination of polypropylene mesh and MSCs, where complete resolution of the inflammatory response and scar tissue formation was recorded. In Group 4, on day 10, the granulation tissue area was 2.5 times smaller than in Group 1 and 1.3 times smaller than in Group 2. The relative area of microcirculatory vessels was 1.8 times smaller than in Group 1 and 1.3 times smaller than in Group 2, whereas the fibrous reticular tissue area was 3.2 and 1.2 times larger, respectively. By day 30, granulation tissue, microcirculatory vessels, and leukocytes were no longer detected. The fibrous reticular tissue area was the largest among all groups at this time point. Conclusion. Intraperitoneal transplantation of human umbilical cord-derived MSCs in conjunction with polypropylene mesh repair of musculoaponeurotic defects in the anterior abdominal wall of rats improves regeneration at the defect site and promotes faster healing.

Body Composition and Dietary Intake of Women Attending an Infertility Clinic-Polish Observational Study.

We aimed to assess the body composition and dietary intake of female patients attending one of the Polish infertility clinics. Additionally, we evaluated if there were any relationships between dietary intake and body composition parameters. The study involved 51 women who met the inclusion criteria. For the nutritional assessment, we used 3-day dietary records. Weight, height, waist and hip circumferences, and body composition were assessed. The participants were divided into three groups, with low (I, n = 12), normal (II, n = 27), and high (III, n = 12) fat tissue content, and then compared in terms of dietary intake. The lowest protein intake per kilogram of body weight was observed in group III (p < 0.001). In group I, we reported the highest consumption of plant protein in general (p = 0.03) and per kg of body weight (p < 0.001). Higher protein intake per kg body mass was associated with lower values of BMI (r = -0.681; p < 0.001), fat mass (r = -0.641; p < 0.001), waist-hip ratio (r = -0.391; p = 0.005), and abdominal fat index (r = -0.653; p < 0.001). Our findings suggest that targeted nutritional counseling focused on optimizing protein intake and emphasizing plant-based sources may improve body composition and potentially support fertility outcomes in women undergoing infertility treatment.

Tocilizumab for the management of corticosteroid-resistant GO combined with OMG: a case series

PurposeTo highlight the safety and efficacy of tocilizumab (TCZ) in Graves’ ophthalmopathy (GO) combined with ocular myasthenia gravis (OMG) patients refractory to steroids and cholinesterase inhibitor (CEI).MethodsThis was retrospective case series. We reviewed the health records of patients with GO combined with OMG, ten of whom were refractory to corticosteroids and CEI treatment and received intravenous injection of TCZ. Ten patients were treated with four injections of TCZ (intravenously, 8 mg per kilogram of body weight, once a month). We analyzed the efficacy and safety of TCZ treatment for this subset of patients with GO and OMG.ResultsThe main outcomes including quality of life questionnaire in Graves’ orbitopathy (GO-QoL) score, Clinical Activity Score (CAS), Myasthenia Gravis Activities of Daily Living profile (MG-ADL) score, proptosis, diplopia and ptosis were assessed at 3 time points: “Baseline” (before the TCZ injection), “4th month” (after fourth time TCZ injection), “Follow up” (Last follow-up). Comparing parameters at 4th month vs. at baseline, all indicators improved at 4th month including GO-QoL score of visual functioning subscale (82.29 ± 13.71 vs. 35.98 ± 20.66, P < 0.001), GO-QoL score of the appearance subscale (80 ± 8.75 vs. 40.63 ± 17.95, P < 0.001), CAS (1.3 ± 0.46 vs. 4.5 ± 0.81, P < 0.001), MG-ADL (2.5 ± 1.56 vs. 5.11 ± 1.14, P < 0.001). Furthermore, proptosis decreased from 19.73 ± 2.84 to 17.93 ± 2.26 mm at 4th month (P < 0.0001). Diplopia and ptosis were also resolved at 4th month. After following up for a minimum of 11 months, the patients had no signs of relapse. In addition, we observed that all analyzed patients exhibited no significant drug reactions following the administration of TCZ.ConclusionTocilizumab maybe a useful therapeutic option in refractory GO coexisting with OMG. However, considering the limitation of a retrospective study, short follow up period and small sample size of this study, randomized controlled studies are needed to validate our results.

Thiol-Disulfide Homeostasis in Noise-Induced Hearing Loss in Rats.

This study was designed to assess if thiol-disulfide homeostasis could be used as diagnostic biomarker in noise-induced hearing loss (NIHL) in a laboratory animal model. The study was carried out with a total of 28 female albino rats in 4 groups: group 1 (control group) included rats that were not exposed to noise or any study treatment; in group 2, following noise exposure, rats received 2 mg of dexamethasone per kilogram of body weight via the intramuscular route for 5 days; in Group 3, rats were exposed to noise and received a saline solution for 5 days, in a volume (0.15 cc) matched to that of dexamethasone administered in group 2; and in group 4, rats were exposed to noise, and blood samples were collected during the early phase to assess thiol-disulfide homeostasis without administering any treatment. Rats in groups 2, 3, and 4 were exposed to 120 dB noise in the 4 kHz octave band for 4 hours. The auditory brainstem response (ABR) test was performed in all groups on day 1 after noise exposure and was repeated in groups 1, 2, and 3 on day 5. Auditory brainstem response thresholds were recorded at 8, 12, 16, 20, and 32 kHz frequencies. Groups 1, 2, and 3 rats were sacrificed on day 5, and group 4 rats were sacrificed by exsanguination on day 1 after noise exposure. Venous blood samples collected from the caudal vena cava were centrifuged and sent to the corresponding laboratory for thiol-disulfide homeostasis studies. After sacrificing the rats, the right and left temporal bones of each rat were removed and stained with hematoxylin eosin for histological studies to explore any pyknotic changes in spiral ganglion cells. Intergroup comparisons by frequency on day 5 of noise exposure showed statistically significantly lower responses in ABR measurements at 8 kHz, 12 kHz, and 16 kHz in group 2 compared to group 3 (P = .003, P=.006, and P=.002). Improvements were observed with dexamethasone administered for therapeutic purposes, particularly if the hearing loss was induced by low-frequency noise. In the assessment of the parameters of thiol-disulfide homeostasis, disulfide/native thiol and disulfide/total thiol ratios and ischemia-modified albumin (IMA) levels were higher in group 4 than in other groups, although only the differences between group 1 and group 4 reached statistical significance. According to this study, thiol-disulfide homeostasis and IMA can be shown as diagnostic biomarkers in NIHL, especially in the early period. The results from our study suggest that these markers may be used as adjunctive diagnostic tools in NIHL, in addition to audiological studies. However, this issue can be clarified with further clinical studies.

Systemic Toxicity of Recombinant Adeno-Associated Virus Gene Therapy Vectors.

Recombinant adeno-associated virus (rAAV) vectors have emerged as a promising tool for gene therapy. However, the systemic administration of rAAV vectors is not without risks, particularly for dose levels >1 × 1014 viral genome per kilogram of body weight (vg/kg). rAAV-associated toxicities can variably manifest either acutely or in a delayed manner. Acute toxicities often present shortly after administration and can include severe immune responses, hepatotoxicity, and thrombotic microangiopathy (TMA). Delayed toxicities, on the other hand, may emerge weeks to months post-treatment, potentially involving chronic liver damage or prolonged immune activation. Thrombotic microangiopathy is often associated with complement activation and endothelial damage. The activation of the complement system can additionally trigger a cascade of inflammatory responses, exacerbating systemic toxicity. While many of these toxicities are reversible with appropriate medical intervention, there have been instances where the adverse effects were severe enough to lead to fatalities. Both human and animal studies have reported these adverse effects, highlighting the critical importance of thorough preclinical testing. However, a differential toxicity profile associated with systemic AAV administration exists between humans and nonhuman primates (NHPs), in which certain toxicities reported in humans are yet to be observed in NHPs, and vice versa. This review aims to explore the recent literature on systemic rAAV toxicities, focusing on dose levels, the role of the complement activation pathway, endothelial injury, TMA, hepatotoxicity, and the bidirectional translational safety profiles from both human and animal studies.

Influence of Baduanjin on cardiopulmonary function in long-term practitioners and beginners.

Baduanjin, a traditional Chinese exercise for health enhancement and chronic disease prevention, has been practiced for millennia. However, studies on the exercise intensity of Baduanjin are limited. Most existing studies focus on its general health benefits rather than quantifying its specific intensity levels. This study aims to measure and compare the exercise intensity indices of long-term Baduanjin practitioners and beginners, providing insights into its mechanisms for disease prevention and treatment and supporting the scientific formulation of clinical exercise prescriptions. Twenty healthy adults aged 35-45 years old and the mean BMI was 24.45 were recruited and divided into a beginner group (A group, no prior practice, 10 participants) and a skilled group (B group, practice duration ≥3 years, 10 participants). The Italian Cosmed/K5 wireless portable cardiopulmonary testing system was used to measure indicators during the practice. Within-group analysis revealed statistically significant differences in oxygen consumption (VO2), oxygen consumption per kilogram of body weight (VO2/kg), metabolic equivalent (METs), heart rate (HR), oxygen pulse (VO2/HR), respiratory rate (RR), and minute ventilation (VE) between exercise and resting states in both the B and A groups (P < 0.001). In between-group comparisons, resting HR was significantly lower in the B group compared to the A group (P < 0.01). During Baduanjin practice, significant between-group differences were found in METs, HR (P < 0.01), and RR (P < 0.05), with the A group exhibiting higher values for METs, HR, and RR than the B group. Baduanjin positively impacts cardiovascular function and exercise performance, with long-term practitioners showing significantly better cardiovascular recovery and overall function.

Analgesic Effects of Magnesium Sulphate In Patients Undergoing Laparoscopic Cholecystectom

Objective: To assess the effectiveness of intraoperative administration of MgSO4 in achieving satisfactory postoperative pain relief following laparoscopic surgery. Study Design: Quasi-experimental research. Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, Apr to Sep 2021. Methodology: A total of 200 patients gave their informed consent before being split into two groups of 100. Patients were given Tablet Alprazolam 0.25mg and Omeprazole 20mg the night before surgery and again on the morning of surgery, and were asked for NPO for 8 hours before to surgery. Group 1 got 50 mg/kg of magnesium sulphate diluted in 250 ml of isotonic 0.9% normal saline intravenously during surgery, while Group 2 received the same volume of isotonic 0.9% normal saline. Results: Administering intravenous magnesium sulphate at an intravenous dose of 50 milligrams per kilogram of body weight before laryngoscopy and intubation significantly reduces the need for post-operative pain medication by reducing post-operative pain and delaying its onset. Additionally, it reduces the amount of pain medication required after surgery. Therefore, overall, pretreatment with magnesium sulphate has a significant impact on post-operative pain management. Conclusion: Magnesium sulphate is an excellent analgesic for people undergoing laparoscopic cholecystectomy.

Oral Infigratinib Therapy in Children with Achondroplasia.

Achondroplasia is a genetic skeletal condition that results in disproportionately short stature and medical complications throughout life. Infigratinib is an orally bioavailable FGFR1-3 selective tyrosine kinase inhibitor in development for achondroplasia. In this phase 2 dose-finding study, we evaluated the safety and efficacy of oral infigratinib in children with achondroplasia between the ages of 3 and 11 years. A total of 72 children were enrolled in five sequential cohorts to receive daily infigratinib at doses of 0.016 mg per kilogram of body weight (cohort 1), 0.032 mg per kilogram (cohort 2), 0.064 mg per kilogram (cohort 3), 0.128 mg per kilogram (cohort 4), and 0.25 mg per kilogram (cohort 5) for 6 months, followed by 12 months of extended treatment in which the dose in cohorts 1 and 2 could be escalated to the next ascending level at months 6 and 12. The primary safety outcome was the incidence of adverse events that led to a decrease in the dose or discontinuation of infigratinib. The primary efficacy outcome was the change from baseline in the annualized height velocity. During treatment, all the children had at least one adverse event, most of which were mild or moderate in severity; none resulted in treatment discontinuation. In cohort 5, an increased annualized height velocity was observed, which persisted throughout the duration of the study, with a mean change from baseline at 18 months of 2.50 cm per year (95% confidence interval [CI], 1.22 to 3.79; P = 0.001). The mean change from baseline in height z score was 0.54 (95% CI, 0.35 to 0.72) relative to an untreated achondroplasia reference population at 18 months; the mean change from baseline in the upper-to-lower body segment ratio was -0.12 (95% CI, -0.18 to -0.06). The administration of oral infigratinib did not result in any apparent major safety signal and increased the annualized height velocity and z score and decreased the upper-to-lower body segment ratio at 18 months of treatment in cohort 5. (Funded by BridgeBio Pharma; PROPEL2 ClinicalTrials.gov number, NCT04265651.).

Standardisation of Curcuminoids into More Bioavailable form (CurcuminAura™) and Its Pharmacokinetics

Curcuminoids are naturally occurring phytocompound extracted from the turmeric rhizome Curcuma longa, a member of the ginger (Zingiberaceae) family. Through the development of a trademark product called Bio-Curcumin, this study seeks to increase the bioavailability and absorption of regular marketed curcumin by 95%. This finding has important implications for the academic and scientific community. The pharmacokinetic study of CurcuminAura™ and its innovation of biocurcuminoids is detailed in detail. Innovation of BioCurcuminoids and its Pharmacokinetic Study of CurcuminAura™ with regular curcuminoids is significantly described which is the need of the hour. This enhanced sunflower lecithin is an effective ingredient in the trademark product CurcuminAuraTM, which was created by Bio-Med Ingredients Pvt.Ltd. Its potency in the market can be increased by lecithin's capacity to efficiently encapsulate active substances, improve bioavailability, and increase absorption. Regular curcumin's weak solubility and poor absorption in its free form. Regular Curcumin due to its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites can greatly limit its utility as a health-promoting agent and dietary supplement. Hence to make it more readily available in the body. CurcuminovaTM is developed will enhance the properties of Curcumin making it more potent in the market. The Evaluation of the Comparative Pharmacokinetic Study of CurcuminAuraTM with Marketed Curcumin 95.0% was carried out through pre-clinical investigations in Sprague Dawley Rats via Oral Route which is the aim of this study with two groups in the study design, with four rats of each sex. Oral administration of CurcuminAuraTM and Curcumin 95.0% was administered to rats in the G1 and G3 groups, respectively. A dosage volume of 10 milliliters per kilogram of body weight was maintained for the oral route. After Dosage, under isofluorane,the blood samples were taken from the retroorbital sinuses after the dose was administered under varying periods of anaesthesia. Animals were split up into two sets for each group, and blood samples were taken at 30-, 2-, and 4-hour intervals. Samples were taken for analysis after being kept at -800C. Designed to increase the bioavailability of curcuminoids, CurcuminAuraTM is standardized to 60.9% total curcuminoids by HPLC, as opposed to marked conventional curcumin 95%. This has been confirmed by HPLC analysis. According to comparison studies, CurcuminAuraTM has a bioavailability that is 3.8 times greater than the reference standard. Additionally, in this study it is shown that the maximum absorption happens in the timeline 3 hrs after feeding the drug.

Pharmacological Screening of Hepatoprotective Activity of Vanillylacetone in Paracetamol Induced Hepatotoxic Rats

Paracetamol is often used as a pain reliever and fever reducer. However, when taken in excessive amounts or used repeatedly, it may result in adverse consequences, such as liver damage. The current study aims to assess the hepatoprotective effects of Vanillylacetone against paracetamol-induced hepatotoxicity in rats, at a dosage of 2g/kg body weight administered orally. A dose of 100 mg/kg of Silymarin was administered orally as a standard reference. On the eleventh day, animals were euthanized and blood samples were collected to assess liver function using liver profile tests including ALT, AST, bilirubin, and total protein levels. The result was also validated by the histopathological examination of liver tissue samples. The administration of 400 mg vanillylacetone per kilogram of body weight per day to group-V rats resulted in a notable reduction in the levels of AST, ALT, direct and total bilirubin, and a considerable rise in total protein levels compared to group-II rats. The hepatoprotective effects of a daily dose of 400 mg vanillylacetone per kilogram were found to be similar to those of a daily dose of 100 mg silymarin per kilogram. Administration of vanillylacetone has effectively restored the aberrant levels of biochemical markers to almost normal levels, with the degree of improvement being depending on the dosage. The current investigation demonstrates that vanillylacetone provides substantial protection against hepatocellular damage generated by paracetamol.

The Effects of Ubiquinone on the Antioxidant System in Male Rats Exposed to Saccharin-Induced the Hepatic Toxicity

Saccharin (Sac) is a widely used artificial sweetener with significant applications in the food industry, pharmaceutical formulations, and tobacco products. Despite its popularity, saccharin has drawn attention due to its potential carcinogenic effects and associations with various health risks, including renal impairment, hepatic dysfunction, obesity, and diabetes. This study aimed to investigate the protective effects of Ubiquinone, or coenzyme Q10 (COQ10), on liver toxicity induced by saccharin, focusing on oxidative stress and antioxidant markers. In this experiment, rats were divided into six groups of ten. The control group received no treatment, while the second group was administered COQ10 at a dosage of 20 mg per kilogram of body weight. The third and fourth groups were given saccharin at 1/10 and 1/20 of the lethal dose 50 (LD50), respectively. The fifth and sixth groups received saccharin at the same dosages as the third and fourth groups, but with additional COQ10 supplementation. All treatments were administered orally for 30 days, after which liver tissues were collected to assess oxidative stress and antioxidant markers. The results revealed that saccharin significantly increased oxidative stress in the liver, as evidenced by elevated levels of malondialdehyde (MDA) and oxidized glutathione (GSSG). Additionally, saccharin-treated groups exhibited a marked decrease in antioxidant markers, including reduced glutathione (GSH) and superoxide dismutase (SOD). However, the groups that received COQ10 alongside saccharin showed significant improvement, with oxidative stress and antioxidant levels nearly returning to those observed in the control group. These findings suggest that saccharin consumption promotes the generation of reactive oxygen species and contributes to liver damage, characterized by necrotic hepatocytes, sinusoidal dilatation, and inflammatory infiltration. The protective effects of COQ10 in mitigating saccharin-induced oxidative stress highlight its potential as a therapeutic agent for preventing liver damage associated with saccharin intake.

Recent data of the biology of the twaite shad, Alosa fallax returning for spawning to the Szczecin Lagoon (southern Baltic Sea)

In 2022–2023 specimens of A. fallax are recorded for the first time in approximately 17 years in Szczecin Lagoon. We collected 11 specimens of juveniles, 9 premature and mature females, and 9 premature and mature males (20.3–40.7 cm of total length, aged from 1+ to 4+). The 2+ aged fish was slightly dominated (34.5% of the whole sample). Females in the Szczecin Lagoon were ready to spawn in the age of 3+ and 4+ years, while males partly in 2+, and in the age of 3+ and 4+. Fulton’s condition factor of this fish was 0.93±0.14 and Clark’s 0.78±0.14. Analysis of correlations between the total length and individual weight of fish revealed that the growth of A. fallax was allometric (b &amp;lt; 3.0). The range of gonadosomatic index (GSI) was 0.12–26.59%, while the mean of the absolute and relative fecundity was 58,756 eggs per female and 139,650 eggs per kilogram of body weight. The obtained results indicate the occurrence of an anadromous population of Alosa fallax in the studied water areas. However, there is still a need to obtain detailed information on the population status and the biology of A. fallax in these areas in order to designate special conservation areas (SACs) for their protection, especially taking into account spawning habitats.

Impact of Intraoperative Blood Transfusion on Cerebral Injury in Pediatric Patients Undergoing Congenital Septal Heart Defect Surgery

Background: The components of donor blood themselves have the potential to initiate a systemic inflammatory response and exacerbate neuroinflammation, resulting in subsequent cerebral injury. The aim of this study was to establish the role of transfusion in the development of cerebral injury during the correction of congenital heart defects in children. Material and Methods: A total of 78 patients aged from 1 to 78 months, with body weights ranging from 3.3 to 21.5 kg, were investigated. Biomarkers of cerebral injury and systemic inflammatory response were studied at three time points. First: prior to the surgical intervention. Second: after the completion of cardiopulmonary bypass. Third: 16 h after the conclusion of the surgery. Results: The strongest correlation was found for S-100-β protein with the volume of transfusion at the second (Rho = 0.48, p = 0.00065) and third time points (Rho = 0.36, p = 0.01330). Neuron-specific enolase demonstrated a similar trend: Rho = 0.41 and p = 0.00421 after the completion of cardiopulmonary bypass. Conclusions: The use of red blood cell suspension and its dosage per kilogram of body weight correlated with the biomarkers of cerebral injury and systemic inflammatory response with moderate to significant strength.