Kilogram Of Body Weight Research Articles

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 < 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.

Subchronic Toxicity of Ethanol Extract of Mangosteen Rind (Garcinia Mangostana L.) on Kidney Function in Wistar Rats

Mangosteen (Garcinia mangostana L.) is a fruit that possesses antioxidant, antibacterial, antihistamine, anti-inflammatory, and antidiabetic properties. Before this, an acute toxicity test was conducted on the ethanol extract of mangosteen rind. However, further testing is required, specifically the subchronic toxicity test, to identify any hazardous effects that may not have been found in the previous study. The objective of this study is to evaluate the amount of toxicity based on the mortality rate, alterations in the relative weight of the kidneys, and changes in renal function as shown by levels of urea and creatinine. This study is an experimental investigation that employs the Post-test Only Control Group Design methodology, with a sample of 40 rats. The rats were categorized into two groups: the control group and the treatment group. The treatment group was divided into three subgroups, each receiving a dosage of 250 mg/kg body weight. The doses were 500 milligrams per kilogram and 1000 milligrams per kilogram of body weight, respectively. The control group received simply water and feed. The duration of the treatment was 28 days. Observations were conducted over 28 days, which involved monitoring animal mortality. On the 29th day, a surgical procedure was carried out to assess the comparative weight of the kidneys and collect blood samples for analyzing the levels of urea and creatinine. The findings demonstrated no mortality in the test subjects, although there was an elevation in the relative mass of the kidneys and an increase in urea concentrations. The increase in urea levels was observed in female rats using the Kruskal–Wallis test (P = 0.019). The study was further conducted using the post-hoc Mann–Whitney test. Control female rats exhibited notable disparities when administered dosages of 250 mg/kgBW and 500 mg/kgBW. The repeated administration of an ethanolic extract derived from the peel of the mangosteen fruit had a detrimental impact on the functioning of the kidneys, as evidenced by a rise in urea concentrations. Keywords: mangosteen, toxicity test, subchronic, kidney

Formulation of Complementary Feeding Food Using Pearl Millet and Its Sensory Evaluation

Infancy is a period of rapid development. As a result, the energy consumption per kilogram of body weight is higher than in adults. After birth, exclusive breastfeeding is recommended for at least 4-6 months. Supplemental feeding should begin after six months, when the body's needs increase. Supplementary mixes offered on the market and given through various systems are often cereal-based. When millet is used in supplemental feeding foods, it is often ground into a fine powder to make it easier for newborns to consume. Using complementary feeding meals containing millet can help introduce your baby to new textures and flavors while also delivering the nutrients they need for healthy growth and development. However, millets have the same calorific value as grains with higher mineral content. Combining these two-three grain foods improves protein and nutritional density in later food products. Probably because of their high nutritional content, this study evaluates several studies in the literature on the utilization of these crops to generate composite food products. In the majority of underdeveloped countries, complementary foods are made from staple cereals or root crops. As a result, the current study aimed to create a supplementary mix that included pearl millet, mung beans, and pigeon peas. Sensory evaluation was conducted using composite scoring to determine the best accepted supplemental mix.

The Top 5 Can't-Miss Sport Supplements.

Background/Objectives: Sports supplements have become popular among fitness enthusiasts for enhancing the adaptive response to exercise. This review analyzes five of the most effective ergogenic aids: creatine, beta-alanine, nitrates, caffeine, and protein. Methods: We conducted a narrative review of the literature with a focus on the sport supplements with the most robust evidence for efficacy and safety. Results: Creatine, one of the most studied ergogenic aids, increases phosphocreatine stores in skeletal muscles, improving ATP production during high-intensity exercises like sprinting and weightlifting. Studies show creatine supplementation enhances skeletal muscle mass, strength/power, and muscular endurance. The typical dosage is 3-5 g per day and is safe for long-term use. Beta-alanine, when combined with the amino acid histidine, elevates intramuscular carnosine, which acts as a buffer in skeletal muscles and delays fatigue during high-intensity exercise by neutralizing hydrogen ions. Individuals usually take 2-6 g daily in divided doses to minimize paresthesia. Research shows significant performance improvements in activities lasting 1-4 min. Nitrates, found in beetroot juice, enhance aerobic performance by increasing oxygen delivery to muscles, enhancing endurance, and reducing oxygen cost during exercise. The recommended dosage is approximately 500 milligrams taken 2-3 h before exercise. Caffeine, a central nervous system stimulant, reduces perceived pain while enhancing focus and alertness. Effective doses range from 3 to 6 milligrams per kilogram of body weight, typically consumed an hour before exercise. Protein supplementation supports muscle repair, growth, and recovery, especially after resistance training. The recommended intake for exercise-trained men and women varies depending on their specific goals. Concluions: In summary, creatine, beta-alanine, nitrates, caffeine, and protein are the best ergogenic aids, with strong evidence supporting their efficacy and safety.

Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B

BackgroundFidanacogene elaparvovec, an adeno-associated virus (AAV) gene-therapy vector for hemophilia B containing a high-activity human factor IX variant (FIX-R338L/FIX-Padua), was associated with sustained factor IX activity in a phase 1–2a study.MethodsWe conducted a phase 3 open-label study of fidanacogene elaparvovec at a dose of 5×1011 vector genome copies per kilogram of body weight. Men 18 to 65 years of age with hemophilia B and a factor IX level of 2% or less were eligible for screening if they had received at least 6 months of therapy with prophylactic factor IX concentrate. The primary end point, tested for noninferiority, was the annualized bleeding rate (treated and untreated bleeding episodes) from week 12 to month 15 after treatment with fidanacogene elaparvovec as compared with the prophylaxis lead-in period. Superiority, additional efficacy end points, and safety were also assessed.ResultsOf 316 men who underwent screening for the lead-in study, 204 (64.6%) were not eligible; 188 (59.5%) of those were ineligible owing to the presence of anti-AAV neutralizing antibodies. Of the 45 participants who received fidanacogene elaparvovec, 44 completed at least 15 months of follow-up. The annualized rate of bleeding for all bleeding episodes decreased by 71%, from 4.42 (95% confidence interval [CI], 1.80 to 7.05) at baseline to 1.28 (95% CI, 0.57 to 1.98) after gene therapy, a treatment difference of −3.15 episodes (95% CI, −5.46 to −0.83; P=0.008). This result shows the noninferiority and superiority of fidanacogene elaparvovec to prophylaxis. At 15 months, the mean factor IX activity was 26.9% (median, 22.9%; range, 1.9 to 119.0) by one-stage SynthASil assay. A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days. No infusion-related serious adverse events, thrombotic events, development of factor IX inhibitors, or malignant conditions were observed.ConclusionsFidanacogene elaparvovec was superior to prophylaxis for the treatment of participants with hemophilia B, leading to reduced bleeding and stable factor IX expression. (Funded by Pfizer; BENEGENE-2 ClinicalTrials.gov number, NCT03861273.)

Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease

BackgroundColony-stimulating factor 1 receptor (CSF1R)–dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.MethodsIn this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%.ResultsA total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group.ConclusionsTargeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.)

Reliability, Objectivity, Validity, and Reference Levels of the Austrian Pole Climbing Test (APCT)-A Novel Monitoring Tool for Assessing General Fitness in Children, Adolescents, and Young Adults.

Climbing is an activity involving many major muscle groups and, therefore, it is suitable for assessing general physical fitness. The Austrian pole climbing test (APCT) was developed as a reliable and valid test for the assessment of general fitness levels in children, adolescents, and young adults. In this cross-sectional pilot study, 677 participants (aged 6 to 19 years) were assessed via the APCT. Subsequently, test quality criteria (reliability and objectivity) were assessed, and the test's validity was evaluated through comparisons with other established fitness tests (hand grip strength, standing long jump, and pull- and push-ups). Additionally, age- and gender-specific reference values were generated. The reliability (ICC2.1 = 0.97, 95%CI 0.95 to 0.98) and objectivity (ICC2.1 = 0.99, 95%CI 0.99 to 0.99) of the APCT were found to be excellent. The APCT results correlated strongly with the hand strength per kilogram of body weight (right: r = 0.58; left: r = 0.53), number of pull-ups (with upper grip: r = 0.74; with lower grip: r = 0.69) and standing long jump (r = 0.61); a moderate correlation with the push-up test was observed (r = 0.44). The APCT is reliable, objective, and suitable for children, adolescents, and young adults with an affinity for sports. It offers a novel opportunity to assess fitness without time pressure, considering the anthropometric requirements.

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions. We randomly assigned patients with previously untreated advanced melanoma, in a 1:1:1 ratio, to one of the following regimens: nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks; nivolumab (3 mg per kilogram) every 2 weeks plus placebo; or ipilimumab (3 mg per kilogram) every 3 weeks for four doses plus placebo. Treatment was continued until the occurrence of disease progression, unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to BRAF mutation status, metastasis stage, and programmed death ligand 1 expression. Here, we report the final, 10-year results of this trial, including results for overall survival and melanoma-specific survival, as well as durability of response. With a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) for nivolumab plus ipilimumab as compared with ipilimumab and was 0.63 (95% CI, 0.52 to 0.76) for nivolumab as compared with ipilimumab. Median melanoma-specific survival was more than 120 months with nivolumab plus ipilimumab (not reached, with 37% of the patients alive at the end of the trial), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab. The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma. (Funded by Bristol Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

394 Cover crops for efficient grazing systems

Abstract Grazing of cool-season cover crops provides a sustainable solution for extending the grazing season while potentially reducing the environmental impact of conventional row-crop farming practices. The primary objective of this study was to evaluate how different mixtures of cover crops affect stocker performance when grazed. The study was conducted across 18 paddocks that were sown with grass [‘Coker’ oat (Avena sativa)], grass + legume [‘Dixie’ crimson clover (Trifolium incarnatum)], or grass + legume + brassica [‘Turnip’ brassica (Brassica rapa subsp.; rapa)] at the Wiregrass Research and Extension Center in Headland, AL. These paddocks were randomly assigned to either grazed or un-grazed conditions (n = 3). In this study, yearling beef steers with an average body weight (BW) of 266 ± 44 kg were grazed in paddocks using the put and take method to maintain a forage allowance of 1 kg dry matter per kilogram of BW. Forage samples were collected biweekly to analyze biomass, botanical composition, and forage nutritive value. Grazing occurred from January 17 to March 22, 2023 (65 d). Steer BW were recorded at the beginning and end of the grazing season to calculate average daily gain. The data were subjected to analysis as a two-way ANOVA using Glimmix in SAS 9.4 (SAS Institute, Cary, NC), harvest date was considered a repeated measure. No treatment × grazing interaction was observed on forage yield performance [average (AVG) forage yield kg DM/ha; P = 0.460]. In addition, no difference was observed among the different cover crop mixtures (AVG forage yield kg DM/ha; P = 0.670). Grazed paddocks had a greater crude protein when compared with ungrazed paddocks (Grazed vs. Ungrazed %; P = 0. 017). However, there was no effect of cover crop mixture on crude protein (CP) concentration (AVG CP %; P = 0.670 for treatment effect). These results indicate that cool-season annual cover crops can provide sufficient forage yield and quality to support sufficient animal gains, even during the relatively short grazing season. Incorporating cover crops not only improves agricultural sustainability but can also enhance the resilience and long-term health of the agroecosystem.

Evaluation of the Effect of the Injected Dose and Body Mass Index on the Signal-to-Noise Ratio (SNR) Detected using a PET/CT Scan.

This study aims to investigate, using patient studies, the impact of Injected Dose (ID), Body Mass Index (BMI), and image noise assessments in PET imaging. This study included 59 liver cancer patients weighing between 45 and 107 kg. After intravenously injecting 0.1 millicurie (mCi) of 18F-FDG per kilogram of body weight, PET scans were obtained for 1, 1.5, and 3 min/bed position based on the patient's weight. Weight, height, and body mass index were calculated using a spreadsheet. Five regions of interest (ROIs) were placed at the same site in the liver, which was considered to have a homogeneous metabolism, in five successive slices of PET/CT scans to determine the mean uptake (signal) values and their standard deviation (noise). The ratio of both gives the liver's Signal-to-Noise Ratio (SNR). Graphs were created to determine the relationship between these characteristics. The plots demonstrated that the dose injected increased when body weight and/or BMI increased, and that the SNR fell even as the dose administered increased. This is owing to the fact that heavier patients having a higher administered dose and, have a lower SNR even when greater 18F-FDG doses are delivered. These data indicate that the image quality, as measured by the SNR, is inferior in heavier persons compared to those who are thinner.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn

BackgroundIn early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti–neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.MethodsIn an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks’ gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks’ gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%).ResultsLive birth at 32 weeks’ gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks’ gestation or later and one fetus before fetal loss at 22 weeks and 5 days’ gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity.ConclusionsNipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.)

Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A

BackgroundOnce-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited.MethodsWe conducted a phase 3, open-label study involving previously treated patients younger than 12 years of age with severe hemophilia A. Patients received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. The primary end point was the occurrence of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary end points included annualized rates of treated bleeding episodes, bleeding treatment, safety, and pharmacokinetics.ResultsA total of 74 male patients were enrolled (38 with an age of <6 years and 36 with an age of 6 to <12 years). No factor VIII inhibitors developed. Most adverse events were nonserious. No serious adverse events that were assessed by the investigator as being related to efanesoctocog alfa were reported. In the 73 patients treated according to the protocol, the median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. A total of 47 patients (64%) had no treated bleeding episodes, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints. A total of 41 of 43 bleeding episodes (95%) resolved with one injection of efanesoctocog alfa. Mean factor VIII activity at steady state was more than 40 IU per deciliter for 3 days and more than 10 IU per deciliter for almost 7 days after dose administration. The geometric mean terminal half-life was 40.0 hours.ConclusionsIn children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa provided high sustained factor VIII activity in the normal to near-normal range (>40 IU per deciliter) for 3 days and more than 10 IU per deciliter for almost 7 days after administration, leading to effective bleeding prevention. Efanesoctocog alfa was associated with mainly nonserious adverse events. (Funded by Sanofi and Sobi; XTEND-Kids ClinicalTrials.gov number, NCT04759131.)

Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer

BackgroundRecurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy.MethodsWe conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival.ResultsA total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects.ConclusionsIn patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.)

Association of physical activity patterns with nocturnal hypoglycemia events in youth with type 1 diabetes.

This study sought to elucidate the interactions among physical activity (PA) patterns, mean glucose concentrations, and the incidence of nocturnal hypoglycemia events in children and adolescents with type 1 diabetes, examining the moderating influence of daily dosage on these associations. Eighty-two participants aged 6 to 18 years (43.9% girls) from the Diactive-1 Cohort Study, diagnosed with type 1 diabetes, were included. Data collection involved continuous glucose monitoring, accelerometry to assess real-world PA, as well as documentation of daily insulin doses and carbohydrate counting over the same seven days. A total of 19 participants experienced at least one nocturnal hypoglycemia event over a span of 574 measurement days (106 days with and 451 days without nocturnal hypoglycemia). Higher levels of vigorous PA (VPA) were associated with lower same-day mean glucose levels (p = 0.014). Additionally, higher levels of moderate PA (p = 0.023), VPA (p = 0.011), and moderate-to-vigorous PA (p = 0.010) were associated with a greater number of nocturnal hypoglycemia events. Specifically, a significant association was identified between VPA and nocturnal hypoglycemia events when the daily insulin dose were at or above 1.04 units per kilogram of body weight per day (p = 0.016). Daily VPA is associated with glucose reductions, potentially leading to more hypoglycemic episodes, particularly when there's an excess of daily insulin. This highlights the need for careful insulin management in children and adolescents with type 1 diabetes engaging in VPA.

CASE SERIES: EFFICACY OF THROMBOLYSIS USING INTRAVENOUS ALTEPLASE IN ACUTE ISCHEMIC STROKE WITH ONSET LESS THAN 6 HOURS (CODE STROKE)

Background: The gold standard therapy for acute ischemic stroke is timely reperfusion of ischemic brain tissue. Intravenous thrombolysis with tPA is the only proven medical therapy for acute ischemic stroke within 4.5 hours of symptom onset using intravenous alteplase at a dose of 0.9 mg per kilogram of body weight. Hemorrhagic transformation is one of the complications of thrombolytic therapy and East Asian population having a higher prevalence of cerebral hemorrhage. This study will examine several cases of ischemic stroke that were treated with thrombolysis using a standard dose (0.9 mg/kg) of intravenous alteplase in acute ischemic stroke with an onset of less than 6 hours in the Special Region of Yogyakarta, especially at the UGM Academic Hospital. Objective: To determine the efficacy of standard dose thrombolysis using intravenous alteplase (rTPA-recombinant tissue plasminogen activator) in acute ischemic stroke with an onset of less than 6 hours through activation of the Code Stroke. Methods: Descriptive research design using a case series, the hyperacute stroke patients with an onset of less than 6 hours who received intravenous alteplase which were then assessed by the National Institutes of Health Stroke Scale (NIHSS) score at initial admission, 24 hours post-alteplase and 30 days post -alteplase. The study took place and was conducted from May to October 2022 by administering intravenous alteplase at a dose of 0.9 mg/kg body weight in acute ischemic stroke patients at UGM RSA who are eligible for thrombolysis therapy with a maximum administration time of 6 hours after stroke onset with the maximum dose of alteplase is 50 mg. Results: The study sample was 8 patients with acute ischemic stroke who were treated between May to October 2022. There were 2 patients who died before completing the 3-month follow-up. One of the patients died within the second week of treatment from sepsis which may have occurred from a pre-existing pneumonia. Another patient died from ileus that occurred 1 month after tissue plasminogen activator (tPA). However, the patient with this ileus showed clinical improvement at the 24-hour post-tPA follow-up, i.e. the initial NIHSS score of 12 improved to an NIHSS score of 6. Conclusion: The modified Alteplase dose, which is 0.9 mg/kg body weight with a maximum dose of 50 mg, at the onset of stroke less than 6 hours can be an option to maximize thrombolytic therapy while still considering the efficiency of treatment costs.

The Toxic Effect of Bisphenol A on Male Rat Testicles and The Possible Protective Value of Propolis and Vitamin E

This study aimed to examine the impact of propolis (Pro) on various physiological parameters in male rats experiencing induced testicular dysfunction by Bisphenol A. Five groups of ten male rats apiece were created by random selection from the rats. Group 1 the rats, which performed as the group under negative control, received normal food and water. In Group 2, rats were subjected to intraperitoneal administration of 0.2 mL of corn oil, utilized as the vehicle for bisphenol A (BPA), thereby serving as the vehicle control group. For Group 3, rats were administered in corn oil, BPA dissolved at a dosage of 50 mg/kg body weight administered three times a week for three weeks using an intraperitoneal injection. In Group 4rats received a dose of 250 mg/kg body weight of propolis (protected) orally via a gavage needle. Subsequently, intraperitoneal injections are administered to them from BPA delivered three times weekly for three weeks, the dosage is 50 mg per kilogram of body weight dissolved in corn oil. In Group 5, rats received protection with vitamin E orally, at a dose of 100 mg/kg body weight, using a gavage needle. The intraperitoneal injection of BPA, dissolved in corn oil at a dose of 50 mg/kg body weight, was then given three times a week for three weeks. After three weeks, animals were sacrificed, and testes and blood were gathered for additional analysis. Superoxide Dismutase (SOD), Sperm Viability, General motility, Progressive motility, and Morphology, were all significantly reduced in the BPA group compared to the control groups, according to the results. While malondialdehyde (MDA) increased in the BPA group compared to the control groups. In conclusion, propolis enhanced physiological parameters adversely affected by BPA, suggesting its potential as a protective agent against BPA-induced testicular dysfunction.

The Impact of Folic Acid and B12 Administration on Growth, Wool Traits and Some Hormones Concentrations of Male Arabi Lambs

This study aimed to investigate the effects of folic acid and vitamin B12 administration on the growth and wool traits in male lambs. A total of fifteen animals was used from 1st February 2015 to 30th April 2015, divided into three treatment groups. The first group served as a control, the second group received a folic acid dosage equivalent to 0.5 mg per kilogram of body weight per head, and the third group received a vitamin B12 dosage equivalent to 0.1 mg per kilogram of body weight per head. The vitamins were administered orally twice a week. The results showed a significant improvement (P&lt;0.05) in final body weight, daily gain, and total weight gain in the vitamin B12 and folic acid groups compared to the control group. Additionally, there was a significant (P&lt;0.05) increase in all wool characteristics, except for crimp number, in the folic acid group compared to the control group. The study demonstrated significant relationships between body weight and every aspect of wool quality except for fiber length. There was a significant (P&lt;0.05) increase in the concentrations of growth and thyroxine hormones in the vitamin B12 and folic acid groups compared to the control group, particularly in the second and third months of the experiment. No significant difference in insulin hormone concentration among the groups was observed during the 90-day experiment. In conclusion, administering vitamin B12 and folic acid are orally administered twice a week to improve growth, increase hormone concentrations (thyroxine and growth hormone), and improve wool quality

Efficacy of Zingiber Officinale (ZO) in The Treatment of Lead Acetate-induced Hepatopathy in Rabbits: An Ultrastructural Assessment of Sub-acute Trial.

Lead acetate (Pb) is a hazardous heavy metal that is well-known to impair the functions of bodily systems and organs. This present study identifies the histopathological alterations that Pb toxicity causes in the liver of rabbits as well as the efficacy of ginger (Zingiber Officinale, ZO) in mitigating its negative effects. As ZO is a rich source of several antioxidants, this present study examines its ability to decrease Pb toxicity in test animals. A total of 30 rabbits were randomly divided into three groups (n = 10). The Control group was only fed distilled water, the Negative group was only fed a 2% Pb solution, while the Treated group was fed a 2% Pb solution as well as 100 mg of ZO extract per kilogram of body weight daily. Lead acetate (Pb) was found to significantly alter the histopathology of rabbit livers by increasing inflammation, fibrosis, vacuolation, and degeneration; significantly decreasing plasma superoxide dismutase (SOD) and catalase (CAT) enzymatic activities; and increasing plasma malondialdehyde (MDA) concentrations. Furthermore, ZO extract not only significantly decreases the negative hepatic impacts of Pb but also prevents Pb-induced hepatopathy.