Treatment Dose Research Articles

The Effect of doses of Natural Super Phospate Fertilizer and Potassium on the Growth and Yield of Peanut Plants (Arachis hypogaea L.)

The purpose of the study was to determine the proper dosage of natural phosphate and potash fertilizers for peanut growth and yield. This research was conducted in Tanjung Village, Darul Hasanah District, Southeast Aceh Regency from October to December 2020. This study used 3x3 factorial randomized block design (RBD) with 3 repeats. The results showed that the dose of Natural Super Phosphat fertilizer had a significant effect on the weight of 100 dry seeds of peanut plants. The highest growth and soaking of dried peanut seeds tends to be obtained at a dose of Natural Super Phospat 100 kg P205 I ha. The dose of potash fertilizer had no significant effect on plant height at the age of 15, 30 and 45 watersheds, the number of well-fused pods per clump, the number of empty pods per clump, the weight of dry pods per clump, the weight of 100 dry seeds, the weight of dry seeds per net plot and the weight of dry seeds per hectare. Better growth and yield of dry seeds in peanut plants tend to be obtained with a dose of potash fertilizer of 75 kg K20 I ha. There is an insignificant interaction between the dose treatment of Natural Super Phosphate fertilizer and the dose of potassium fertilizer.

The role of nutrient solutions on Phosphate-solubilizing bacteria population, Phosphorus availability, Phosphorus uptake, growth and yield of Red Chili (Capsicum annuum L.)

Red chili consumption in Indonesia has increased every year. However, with large chili production to meet large consumption, land conversion for various purposes has reduced the harvested area. The efforts to increase the harvested area of chili using Inceptisols soil by providing nutrient solutions to overcome the infertility of the soil using its nutrients. This experiment aims to determine the effect of nutrient solution application on the population of phosphate-solubilizing bacteria, phosphorus availability, phosphorus uptake, growth, and yield of Red Chili (Capsicum annuum L.) in Inceptisols. The experiment was conducted from August 2023 to February 2024 at Ciparanje Experimental Field, Faculty of Agriculture, Padjadjaran University, and the analysis process was conducted at the Laboratory of Soil Biology and Soil Chemistry and Plant Nutrition, Department of Soil Science and Land Resources, Faculty of Agriculture, Universitas Padjadjaran., using a factorial randomized block design with two factors, nutrient solutions concentrates (1200, 1600, 2000 ppm) and nutrient solutions doses (200, 400, 600 mL), resulting in nine treatments and three replications. The results showed that the treatment of nutrient solution concentration and dose increased the number of fruits per plant, fruit weight per plant, and yield of chili with grade A. Treatment with 2000 ppm concentrate + 600 mL dose gave the best results on the number of fruits per plant (44.7 fruits), fruit weight per plant (725g), and grade A chili yield (73 fruits).

Impact of Laboratory-Measured Euthyroid Hashimoto's Thyroiditis on Reproductive Hormone Profile in Women with Obesity.

Introduction: Hashimoto's thyroiditis is a common endocrinological disorder that often coexists with obesity. Thyroid hormones interact with the regulation of sex steroids, and thyroid autoimmunity has a negative impact on female fertility. There are studies showing when euthyroid state is achieved with hormone replacement therapy (HRT), the reproductive hormone profile is improved but they usually compare the reproductive hormones before and after HRT in the same individuals. Studies comparing patients with Hashimoto's thyroiditis in an euthyroid state receiving HRT with individuals having normal thyroid function are limited. Here, it was aimed to search the impact of euthyroid Hashimoto's thyroiditis on reproductive hormone profile in women living with obesity. Materials and Methods: Sixty-one randomly selected female patients with Hashimoto's thyroiditis were included as the case group and 60 patients without Hashimoto's thyroiditis were included as the control group, from our obesity center. The case group included patients who had menstrual cycles and were euthyroid under l-thyroxine treatment for at least 6 months. Data on weight, height, body mass index (BMI), waist circumference (WC), free thyroxine (fT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), cortisol, insulin, prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (prog), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) levels, l-thyroxine treatment dosage (for case group), and accompanying diseases were recorded. The results were evaluated using SPSS. Results: A total of 121 patients were included in the study. Mean age was 41.8 ± 8.5 years in case and 38.6 ± 8.9 years in control group. There was no significant difference in weight, height, BMI, WC, or accompanying diseases between Hashimoto's thyroiditis and control group. fT4, anti-TPO, cortisol levels were higher in Hashimoto's thyroiditis group when compared with control group, but there was no significant difference for TSH, insulin, FSH, LH, E2, prog, T, DHEAS, or PRL. Conclusion: In women living with obesity, it is important to screen for Hashimoto's thyroiditis and achieve euthyroidism through effective LT4 treatment to promote a healthy reproductive system and improve fertility rates.

A minimal physiologically-based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti-LAG-3 monoclonal antibody.

In oncology drug development, measuring drug concentrations at the tumor site and at the targeted receptor remains an ongoing challenge. Positron emission tomography (PET)-imaging is a promising noninvasive method to quantify intratumor exposure of a radiolabeled drug (biodistribution data) and target saturation by treatment doses invivo. Here, we present the development and application of a minimal physiologically-based pharmacokinetic (mPBPK) modeling approach to integrate biodistribution data in a quantitative platform to characterize and predict intratumor exposure and receptor occupancy (RO) of BI 754111, an IgG-based anti-lymphocyte-activation gene 3 (LAG-3) monoclonal antibody (mAb). Specifically, calibration and qualification of the predictions were performed using 89Zr-labeled BI 754111 biodistribution data, that is, PET-derived intratumor drug concentration data, tumor-to-plasma ratios, and data from Patlak analyses. The model predictions were refined iteratively by the inclusion of additional biological processes into the model structure and the use of sensitivity analyses to assess the impact of model assumptions and parameter uncertainty on the predictions and model robustness. The developed mPBPK model allowed an adequate description of observed tumor radioactivity concentrations and tumor-to-plasma ratios leading to subsequent adequate prediction of LAG-3 RO at different dose levels. In the future, the developed model could be used as a platform for the prediction and analysis of biodistribution data for other mAbs and may ultimately support dose optimization by identifying dosages resulting in saturated RO.

Study of Relationship between Heparin and Platelets in Hemodialysis Patients

Platelets are considered one of the most important components of blood that contribute to the coagulation process, and they also play an important role in the blood clotting process. Platelets may be exposed to some types of anticoagulant drugs, such as heparin, which increases the risk of thrombocytopenia, especially in dialysis patients who receive heparin periodically in the extracorporeal circuit in the dialysis unit; thrombocytopenia may develop due to receiving heparin in every dialysis session, which has been confirmed for patients in previous research. This research, aims to find the relationship between heparin and platelets among dialysis patients. Some parameters were carried on for hemodialysis patients of (Al-Jamil - Raqdalin - Zuwara) hemodialysis centers to support the study of the relationship between them, (CBC, PT, PTT, CT, and BT), also a questionnaire has been collected from the patients for further information. The results showed that there is an inverse relationship between the dose of heparin and platelets at α (0.5), meaning that the higher the dose of heparin, the greater the thrombocytopenia. We also found that there is an inverse relationship between the duration of dialysis and platelets, meaning that the longer the duration of dialysis, the lower the platelet count. The results showed also the presence of clots in the dialysis machine in varying proportions. We can conclude that there are no effects on the types of treatment doses on the platelets. Also, heparin dose and Platelets count have an inverse significant relationship. We can conclude also that there are no significant differences between the average platelets due to the types of heparin at the level of significance.

Outcome of lupus nephritis patients treated with an anti-CD40 monoclonal antibody according to kidney biopsy features.

A phase II trial tested different doses of the anti-CD40 monoclonal antibody BI655064 as add-on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post-hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well-known role in LN pathogenesis. 101 renal biopsies of LN patients enrolled in the BI655064 trial were scored centrally. eGFR and spot urine protein/urine creatinine ratio (UP/UC) and Complete Renal Response (CRR) were evaluated over 52 weeks. Patients were divided according to a "Better" or "Worse" performance than the average of all patients in the cohort, predicted by a mixed model for repeated measurements. Logistic regression models adjusted for potential confounders assessed the association between different treatment doses and outcomes according to the presence or absence of monocytes. A higher BI655064 dose (180/240mg) was associated with better outcomes of UP/UC and CRR when glomerular monocytes were present in kidney biopsies (OR 3.66[1.09-12.3], P=0.04; OR 4.58[1.24-16.9], P=0.02). A trend toward improved eGFR was also observed in these patients (P 52-weeks=0.08). In LN kidney biopsies with glomerular monocytes, high-dose BI655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsies without glomerular monocytes. Histologic features may guide the choice of treatment for individual LN patients.

Interactional Effects of Soil and Foliar Application of Manganese Combined with Soil Stabilizer on Cd Accumulation in Rice

Crucial environmental and health problems occur in acidic paddy fields contaminated by cadmium （Cd）. Alkaline stabilizers and manganese （Mn） fertilizers are often applied to soil to reduce Cd pollution in rice. However, the bioavailability of Mn may also be affected by stabilizers and cannot effectively reduce Cd accumulation in rice. In this study, an alkaline compound stabilizer containing organic matter and silica-calcium was used in combination with a soil application of Mn antagonist （Mn-sulfate）, and organic Mn-fertilizer （EDTA-Mn, amino acid-bound Mn） was sprayed on the leaves of rice at the booting stage and filling stage to elucidate the effectiveness and mechanism of the combined treatments. In the pot experiment, three types of treatments were selected： soil application of stabilizer/Mn fertilizer （T）, Mn foliar spray （Y）, and the combination of soil stabilizer/Mn fertilizer and Mn foliar spray （T+Y）, and a total of 12 treatments were performed. In the field experiment, two types of treatments were selected： Mn foliar spray （Y） and the combination of soil stabilizer/Mn fertilizer and Mn foliar spray （T+Y）, and nine treatments were performed in total. The pot experiment results showed that, compared with that in CK, the Cd content in brown rice treated with the single applications of stabilizer, Mn-sulfate, and 1/2 stabilizer+1/2 Mn-sulfate were decreased by 19.1%, 44.0%, and 51.9%, respectively. On the basis of 1/2 stabilizer+1/2 Mn-sulfate, the Mn foliar spray of EDTA-Mn and amino acid-bound Mn further reduced Cd in brown rice by 46.1% and 46.9%, respectively. Field experiment results showed that, compared with that in CK, Mn foliar spray with EDTA-Mn and amino acid-bound Mn combined with 1/2 stabilizer + 1/2 Mn-sulfate reduced Cd in brown rice by 86.9% and 83.6%, respectively, and the Cd bioconcentration factor were both reduced to 0.05. A single application of stabilizer significantly increased the pH of the soil in the pot experiment and reduced the soil CaCl2-extractable Cd. However, the single application of stabilizer significantly inhibited the formation of Mn plaque on the root surface, while 1/2 stabilizer+1/2 Mn sulfate significantly increased the iron-Mn plaque on the root surface, and more Cd was also fixed on root surface. The addition of Mn foliar spray significantly reduced Cd transport from the stem and leaves to the rice grains. The field experiment showed that the 1/2 stabilizer+1/2 Mn-sulfate combined with Mn foliar spray significantly reduced Cd transport from the stem and leaves to the rice grains, though this combined treatment did not increase soil pH and reduce CaCl2-Cd as much as the treatment of the full dose of stabilizer. In summary, pot and field experiments consistently showed that 1/2 stabilizer+1/2 Mn-sulfate combined with organic Mn foliar spray could inhibit the uptake and transport of Cd in whole soil-plant systems and effectively reduce the Cd accumulation in brown rice.

Transient Anti-TCRβ mAb Treatment Induces CD4+ T Cell Exhaustion and Prolongs Survival in a Mouse Model of Systemic Lupus Erythematosus.

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Chronic T cell receptor (TCR) signalling induces T cell exhaustion, characterised by reduced capacity to induce tissue damage. Here, we investigated the therapeutic potential of the anti-TCRβ (H57-597) monoclonal antibody (mAb) in a mouse model of SLE. Four-month-old MRL/lpr mice exhibiting SLE phenotypes received 5 weekly doses of anti-TCRβ mAb or phosphate-buffered saline (PBS) vehicle control. Subsequently, mouse survival was monitored daily. On day 1 post the final dose of treatment, SLE pathogenesis was determined using histological staining and spot urine test. T and B cell states in the brain, kidney, and secondary lymphoid organs were determined by flow cytometry. Transient treatment of anti-TCRβ mAb significantly prolonged the survival of MRL/lpr mice. Accordingly, MRL/lpr mice in the anti-TCRβ mAb group exhibited decreased proteinuria scores and minimal renal pathological damage compared to the PBS control group. Flow cytometric analysis revealed that anti-TCRβ mAb treatment resulted in a reduction in the frequencies of CD4+ T cells and CD138+B220lo/- plasma cells, plus an increase in Foxp3+ regulatory T cell frequency. Furthermore, CD4+ T cells from anti-TCRβ mAb treated mice exhibited elevated expression levels of PD-1 and TIM-3, with reduced IFN-γ production, indicative of an exhaustion-like phenotype. Therefore, transient administration of anti-TCRβ mAb treatment induces an exhaustion-like phenotype in CD4+ T cells, resulting in prolonged survival of MRL/lpr mice. Inducing autoreactive T-cell exhaustion holds promise as an attractive therapeutic approach for SLE.

Assessment of dimethoate and malathion mediated toxicity on Solanum lycopersicum L.

Nowadays organophosphate-based chemicals are most commonly used insecticides worldwide which are applicable to a wide range of crop plants. In this study, the effect of organophosphate insecticides, dimethoate (DM) and malathion (MT), was investigated on Solanum lycopersicum L. The seeds were germinated under in vivo conditions and after 1month of germination, they were transferred to separate pots. Insecticides were applied in three different concentrations (X, 2X, and 4X) using a nozzle spray at 7-day intervals for 21days where X was the recommended dose. After 21days of treatment, the toxicological responses of plants were confirmed by evaluating the growth patterns, anatomical, photosynthetic pigments, expression of proteins, and antioxidant enzymes catalase (CAT), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX). The study findings demonstrated that both DM and MT treatment resulted in adverse growth effects even at the initial recommended dose (X) of application. However, compared to MT, at 4X concentrations of DM, maximum decrease in plant height (43.43%), leaf length (43.16%), leaf width (41.09%), and total numbers of leaves per plant (50.57%) was observed. Plants subjected to higher doses of DM and MT showed a gradual reduction in chlorophyll a, chlorophyll b, total chlorophyll, and carotenoids (67.25, 50.00, 62.03, and 41.04%, respectively, for DM and 61.75, 55.72, 59.87, and 41.04%, respectively, for MT). In addition, higher doses of these insecticides greatly disturbed micromorphology and protein contents. At high dose (4X) of treatment, the activities of CAT, GPX, and APX were found to increase by 14.01, 3.62, and 2.21 times the control value, respectively, for DM and 5.17, 2.53, and 1.46 times, respectively, for MT. Additionally, increased isoenzymes of CAT, GPX, and APX were demonstrated by nondenaturing PAGE and were also dependent on the concentrations of DM and MT. These results suggest that the isoforms of the antioxidant enzymes newly developed due to DM and MT excess may be used as biochemical markers for other crop plants grown under insecticide stress. This study provides insights into the biochemical mechanism associated with the toxicity caused to plants by the test insecticides.

Mutations in the PIK3C2B, ERBB3, KIT, and MLH1 Genes and Their Relationship with Resistance to Temozolomide in Patients with High-Grade Gliomas

Introduction. The treatment for patients with high-grade gliomas includes surgical resection of tumor, radiotherapy, and temozolomide chemotherapy. However, some patients do not respond to temozolomide due to a methylation reversal mechanism by the enzyme O6-methylguanine-DNA-methyltransferase (MGMT). In patients receiving treatment with temozolomide, this biomarker has been used as a prognostic factor. However, not all patients respond in the same way, which suggests the existence of other proteins involved in resistance to temozolomide chemotherapy. Methods. A group of thirty-one patients was recruited who were clinically and pathologically diagnosed with high-grade gliomas. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment. Results. According to the Stupp protocol and metronomic dose of the temozolomide treatment, the mutated genes related to the second relapse of patients with high-grade glioma were PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. Considering the results obtained, we suggest that mutations in the four genes and methylation of the gene promoter that codes for the MGMT protein could be related to response to treatment with temozolomide.

The Effectiveness of Early Treatment With Intense Pulsed Light Combined With Fractional Erbium Laser in Preventing Post-traumatic Hypertrophic Scar Formation.

Once scars form and begin to proliferate, treatment becomes challenging. Traditional methods of scar treatment often provide suboptimal results. Therefore, early intervention has become widely accepted, with a focus on prevention during the wound-healing phase rather than later treatment. Here, the authors evaluate the effectiveness of early treatment with intense pulsed light (IPL) combined with fractional erbium laser in preventing the formation of post-traumatic hypertrophic scars. A total of 120 patients who underwent emergency cosmetic suture surgery for facial trauma between January 2019 and December 2021 were selected for the study. The control group received conventional antiscar therapy (pressure therapy or antiscar medication), while the observation group received IPL combined with fractional erbium laser in addition to the conventional treatment. The specific treatment doses were adjusted based on the patient's age, scar color, texture, and thickness. A treatment course consisted of 3 to 5 sessions, with 4-week intervals between treatments. Follow-up was conducted within 1 year after treatment to assess the improvement in scar appearance before and after therapy. After IPL combined with fractional erbium laser treatment, patients in the observation group showed significantly lower scores in color, thickness, vascular distribution, softness, and total scores on the Vancouver Scar Scale (VSS) compared with the control group. During the follow-up, 3 complications were observed: 2 cases of skin blisters and 1 case of pigmentation. No immediate skin lesions, depigmentation, infections, ulcers, or other adverse reactions were reported. For patients with early-stage superficial scars following trauma surgery, early treatment with IPL combined with fractional erbium laser not only leads to significant improvements in appearance and effectively prevents hypertrophic scar formation but also promotes rapid recovery with few complications. This approach has clinical value.

P48 Maintenance response of guselkumab in the Chinese population: an interim analysis of an observational study

Abstract Maintenance treatment with biologics is recommended for the treatment of moderate-to-severe psoriasis; however, treatment withdrawal occurs frequently in the real world. In a post-approval commitment (PAC) study (NCT04914429), guselkumab demonstrated efficacy in Chinese patients with moderate-to-severe plaque psoriasis. Here, we report interim analysis results from the observational post-PAC study evaluating health-related quality of life (HRQoL) and psoriasis relapse within 24 weeks following guselkumab withdrawal. This prospective, observational study enrolled patients who achieved a psoriasis area and severity index (PASI) 75 response at Week 44 in the PAC study. In the framework of a decentralized clinical trial design, patients utilized an electronic patient-reported outcome system to report on HRQoL, psoriasis status, and administration of systemic treatment for psoriasis. HRQoL was assessed by the dermatology life quality index (DLQI) at baseline, then every 12 weeks through Week 48. Psoriasis relapse was defined as the initiation of a new systemic treatment for psoriasis. Off-treatment duration (OTD) was defined as the time between the last guselkumab administration at Week 44 in the PAC study and the date of the first dose of any systemic treatment for psoriasis, loss to follow-up, death, or end of the study. A planned interim analysis was conducted when all patients had completed questionnaires 24 weeks after guselkumab withdrawal. The data cut-off (DCO) date was 3 June 2024. A total of 243 patients were enrolled. As of DCO, two patients withdrew from the study due to loss of follow-up. Most patients were male [n = 194 (79.8%)] and mean [standard deviation (SD)] age was 41.2 (12.3) years. At baseline, nearly all patients had PASI <3 [94.2% (229/243)] and Investigator’s Global Assessment 0/1 [91.4% (222/243)]. DLQI scores gradually increased after guselkumab withdrawal, from a mean (SD) of 4.8 (4.4) on the index date to 5.2 (4.6) at Week 12 and 7.2 (6.0) at Week 24 [mean (SD) change: 0.4 (4.5) at Week 12; 2.5 (6.2) at Week 24]. Overall, 5.8% (14/241) of patients had a psoriasis relapse. The mean (SD) OTD was 157.6 (1.1) days; the median OTD was not reached. Patients in this post-PAC study in China experienced gradual deterioration of HRQoL after guselkumab withdrawal. Only a small proportion of patients experienced a psoriasis relapse during 24 weeks of follow-up, suggesting treatment response was generally maintained after guselkumab withdrawal. Results from the planned interim analysis were not conclusive due to the limited duration of follow-up; long-term data analysis will be conducted upon study completion at Week 48.

Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors.

The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi. A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment. We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]). There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.

Circadian Rhythm Enhances mTORC1/AMPK Pathway-Mediated Milk Fat Synthesis in Dairy Cows via the Microbial Metabolite Acetic Acid.

Livestock may respond differently to circadian rhythms, leading to differences in the composition of the animal products. Nevertheless, the circadian effects on rumen microorganisms and animal products are poorly understood. In the study, it was found that dairy cows exhibited increased milk fat levels, decreased acetic acid concentrations in the rumen fluid, and elevated acetic acid levels in the blood during the night compared to those of the day. Correlational analyses suggested a high association between Succiniclasticum, Lactobacillus, Prevotellacene NK3B31_group, Muribaculaceae_unclassified, etc., which were significantly enriched in rumen fluid at night, and milk fat levels. The differential metabolite Vitamin B6, significantly elevated at night, promoted the translocation of acetic acid into the circulation by increasing the level of rumen epithelial MCT1 protein expression. In addition, we found that both acetic acid treatment time and dose modulated the expression of lipid metabolism transcription factors (PPARγ, PPARα, and SREBP1c) and downstream genes (FASN, SCD1, ACCα, and CPT1A). Additionally, the mTORC1 and AMPK pathways were responsible for the effects of acetic acid on transcription factors and genes involved in lipid metabolism. Differences in rumen microbial taxa were observed between the day and night. Microbial metabolite (acetic acid) was found to be absorbed into the bloodstream and entered the mammary gland at night at a significantly elevated level. This regulation impacted the expression of lipid metabolism-related transcription factors (PPARγ, PPARα, and SREBP1c), as well as downstream genes through the mTORC1 and AMPK signaling pathways, ultimately affecting milk fat synthesis. These findings provide a new perspective for the microbial regulation of milk synthesis.

Comparative effectiveness of kilo- and megavoltage energies in low-dose radiotherapy for painful degenerative musculoskeletal diseases: asystematic review and meta-analysis.

This study aimed to assess the impact of different energy levels on the effectiveness of low-dose radiotherapy (LDRT) for treating painful degenerative musculoskeletal diseases, as comparative efficacy data are currently lacking. Asystematic review was conducted in PubMed, Embase, and the Cochrane Library databases to identify studies with response information on the energy used (kilovoltage [kV] vs. megavoltage [MV]). The primary endpoint was the overall response rate (ORR), and the secondary endpoint was the complete response rate (CRR). Exploratory subgroup analyses included treatment site, study period, study design, country, and dose per fraction. Atotal of 33studies involving 12,143patients were analyzed. Short-term follow-up (up to 6months) showed apooled ORR of 64% (95% CI 46-78%) for kV and of 62% (95% CI 54-70%) for MV. Long-term follow-up (at least 12months) revealed apooled ORR of 85% (95% CI 65-95%) for kV and of 69% (95% CI 62-75%) for MV. Subgroup analysis indicated no significant differences in ORR for energy level stratified by treatment site and other factors. Regarding dose per fraction (0.5 Gy vs.1.0 Gy), comparable ORRs were demonstrated between the two energies. No clinical side effects were noted. This meta-analysis suggests that the known effectiveness of LDRT in painful degenerative musculoskeletal disease may not depend on the energy used. Additional studies using standardized evaluation methods are warranted to establish consistency and enhance the comprehensiveness of research. Further research is also needed to explore treatment modality selection considering disease-specific biology.

The influences of X-rays irradiation on sensory attributes and physicochemical properties of shiitake mushrooms during storage

Shiitake mushrooms (Lentinus edodes) are edible mushrooms with unique flavor and high nutritional value that are is highly perishable and prone to rapid quality deterioration post-harvest. This research evaluated the efficiency of X-rays irradiation to maintain the sensory attributes and physicochemical properties of shiitake mushrooms. Changes in postharvest quality were monitored in irradiated (0.5, 1.0, and 1.5 kGy) mushrooms stored for 35 days. Results indicated that X-rays irradiation effectively mitigated the deterioration in appearance, color and texture of shiitake mushrooms during storage. Electronic nose (E-nose) assay revealed that 0.5 kGy X-rays delayed the aroma fading of shiitake mushrooms while higher doses of X-rays treatment changed the odor profile. After X-rays treatment, the microorganism growth was inhibited, the electrolyte leakage and malondialdehyde (MDA) accumulation were alleviated, and the contents of soluble proteins, reducing sugars, ascorbic acid (AA), and total phenols (TP) were maintained. Notably, 0.5 kGy X-rays irradiation performed superior efficacy in maintaining sensory scores and tissue structure. The study suggests that 0.5 kGy X-rays irradiation can be used as shiitake mushrooms preservation method to retain the perceptual attributes and protect against spoilage.

Effect of Using Fern Leaf Extract (Diplazium esculentum) in Raw Fish Feed on Growth and Feed Conversion Ratio of Mud Crab (Scylla serrata)

Mangrove crab or known as Scylla sp. is one of the biota whose habitat is in coastal waters, especially in mangrove forest areas. The need for mangrove crabs still largely relies on natural catches that are fluctuating. For this reason, it is necessary to cultivate mangrove crabs in a controlled manner that can support an effective, efficient and economically profitable mangrove crab farming business. Cultivation can increase mangrove crab production to meet domestic and foreign market demand. An alternative that can be chosen for mangrove crab cultivation is an apartment system that is arranged vertically in the form of a storage rack. The water medium used in this apartment system cultivation uses a recirculation system. One of the efforts to accelerate the growth of crabs is by using steroid hormones. Ecdysteroid is the main steroid hormone that has the main function as a skin replacement hormone. In addition, this hormone also regulates physiological functions, such as growth, metamorphosis, and reproduction. Therefore, this study was conducted to determine the effect of using fern leaf extract (Diplazium esculentum) in raw fish feed with different doses on growth and feed conversion ratio in mud crabs. This research method uses a field experimental method with a completely randomized design (CRD) consisting of 5 treatments and 3 replicates with different percentage doses, namely: PA: Percentage of 0 ml/Kg, PB: Percentage of 100 ml/Kg, PC: Percentage of 125 ml/Kg, PD: Percentage of 150 ml/Kg, PE: 175 ml/Kg percentage. The results showed that the use of fern leaf extract in mangrove crab (Scylla serrata) feed had a significant effect on the growth of absolute weight, Absolute Length, SGR (Specific Growth Rate) and FCR (Feed Conversion Ratio) where the most influential treatment was treatment E which was the highest dose of 175 ml/Kg. This indicates that treatment E is the best dose treatment for growth and feed conversion ratio of mud crab (Scylla serrata).

Glucocorticoid doses according to tissue/organ involvement in ANCA-associated vasculitis

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are a group of disorders that include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), renal-limited vasculitis, and eosinophilic granulomatosis with polyangiitis (EGPA). Infections and cardiovascular diseases are the main causes of death in patients with AAV. New treatment regimens with low-dose glucocorticoidsare proposed to reduce the frequency of side effects. Studies related to the use of glucocorticoids in AAV patients were searched in the literature and results were summarized. Low-dose steroid protocols are not inferior to standard dose treatment and have fewer side effects. Although their effectiveness appears to be similar and their side effects appear to be less, the long-term results of low-dose regimens should also be evaluated.New studies are needed for alternative treatment regimens.

Synergistic potential of lopinavir and azole combinational therapy against clinically important Aspergillus species.

Aspergillus fumigatus is a widely distributed pathogen responsible for severe infections, particularly in immunocompromised individuals. Triazoles are the primary treatments options for Aspergillus infections; however, the emergence of acquired resistance to this antifungal class is becoming a growing concern. In this study, we investigated the potential of the antiviral drug, lopinavir (LPV) to restore the susceptibility of A. fumigatus strains to a set of azoles, while also reducing the required azole dosage for treatment of susceptible isolates. The combination of LPV with either itraconazole (ITC) or posaconazole (POS) demonstrated potent synergistic interactions against 16 out of 23 (~70%) and 21 out of 23 (~91%) A. fumigatus isolates, respectively. Moreover, the combination showed synergistic activity against other clinically important Aspergillus species, including A. niger, A. flavus, and A. brasiliensis. The fractional inhibitory concentration index (FICI) for the combinations ranged from 0.18 to 0.313 for ITC and 0.091 to 0.313 for POS, indicating strong synergistic effects. Further investigation revealed that efflux pump inhibition contributed to the synergy observed between azole and LPV. Morphological examination of the fungal cells subjected to this combinational therapy at sub-inhibitory doses showed the presence of carbohydrate granules/patches. The identification of LPV as a promising adjunct therapy holds promise for addressing the emerging challenge of azole resistance in Aspergillus species and improving treatment outcomes for patients.

Prenatal Diagnosis and Management of Generalized Arterial Calcification of Infancy

BACKGROUND: Generalized arterial calcification of infancy is a rare genetic disorder that was first reported in 1899. Since then, slightly more than 200 cases have been documented. This rare autosomal recessive disorder occurs when the homozygous ENPP1 gene mutation is associated with abnormal calcification in the medium and large arteries in the fetus. Overall mortality in individuals with generalized arterial calcification of infancy is high (55%) before the age of 6 months, with 24.4% dying in utero. Due to the high mortality rate, there is a critical need for additional reports and research regarding generalized arterial calcification of infancy. CASE: We submit a case report of a child with generalized arterial calcification of infancy—a unique instance in which the diagnosis was established prenatally and treatment was initiated in utero. Patient care was continued through a multidisciplinary approach coordinated between specialists across India, Australia, and the United States. There was an almost complete resolution of the calcification, with near-normal development and intellectual capacity of the child for age. CONCLUSION: Clear guidelines are needed regarding prenatal use of bisphosphonate therapy, timing, dosage, and duration of treatment for fetuses with ENPP1 gene mutations to minimize disease progression and improve neonatal health at birth. This case further illustrates how involving well-informed parents in decision making can help tailor the appropriate treatment. Our report also describes the possibility of new, ongoing clinical trials that may pave the way for a cure for this child and others.