Eosinophilic cystitis mimics bladder tumor: A rare case report.

Eosinophilic cystitis is a rare inflammatory condition of the bladder characterized by eosinophils infiltrating the bladder wall. It affects people of all ages and with no gender difference. Eosinophilic cystitis can mimic bladder tumors and other chronic cystitis, which makes it a challenging condition to diagnose. In this article, we will discuss the causes, symptoms, diagnosis, and treatment of eosinophilic cystitis, as well as how it might be mistaken for bladder tumors.

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies.

Sodium acetate and sodium butyrate attenuate diarrhea in yak calves by regulating gut microbiota and metabolites.

Diarrhea is a severe issue in calves that causes fertility problems and economic issues worldwide. Sodium acetate/sodium butyrate (SA/SB) alleviates diarrhea in mice; however, little information is available about the preventive effect of SA/SB on diarrheic yak calves living on the Tibet plateau. Yak calves (n = 19) of age ≥4 months and weight 37 ± 2 Kg were randomly divided into control (C, n = 10) and supplement groups (S, n = 9). Yaks belonging to the supplement group were given sodium butyrate (10 g/kg) and sodium acetate (5 g/kg) for 28 days, along with normal feed, seasonal grasses, pasture, and water. The blood and fecal samples from yak calves were collected for assessment of antioxidant capacity, inflammatory cytokines, microbiome, and short-chain fatty acids (SCFAs) concentration analysis. Results of this study revealed that a lower diarrhea rate, higher weight, and net weight gain were recorded in yaks belonging to group S supplemented with SA/SB. Similarly, increased antioxidant capacity with higher levels of T-AOC, SOD, and GSH-px and decreased inflammatory reactions by decreasing both TNF-α and IL-1ß concentrations were recorded in yaks of group S. The concentration of SCFAs was significantly higher (p < 0.05) in yaks from group S than group C. Microbiome analysis revealed that 8 phyla and 54 genera were significantly different (p < 0.05) in both yak groups, with increased probiotics (Akkermansia, Oscillospira), SCFAs producing genera (Oscillospira, ASF356, Anaerosporobacter and Phascolarctobacterium), and decreased inflammatory related genus (Flavonifractor, Fournierella) and harmful bacteria (Oscillibacter, Achromobacter) in group S. In conclusion, the results demonstrated that SA and SB could decrease diarrhea rates in yak calves on the plateau via increasing antioxidant ability and SCFAs, while decreasing inflammatory responses in yaks by moderating gut microbiota. The current results provide new insights for the prevention and treatment of diarrhea in yaks.

Microbiome analysis reveals the differences in gut fungal community between Dutch Warmblood and Mongolian horses.

Similar to gut bacterial community, gut fungal community are also an important part of the gut microbiota and play crucial roles in host immune regulation and metabolism. However, most studies have focused on the gut bacterial community, and research on the gut fungal community has been limited. Dutch Warmblood (DWH) and Mongolian horses (MGH) are important equine breeds, but little research has been done on their gut fungal community. Here, we assessed differences in gut fungal community between two horse species. Results showed that a total of 2159 OTUs were found in the Dutch Warmblood and Mongolian horses, of which 308 were common. Between-group analyzes of microbial diversity showed no differences in the alpha and beta diversity of gut fungal community between the two horse species. Microbiological taxonomic surveys showed that the dominant fungal phyla (Neocallimastigomycota and Ascomycota) and genera (unclassified_Neocallimastigaceae and Anaeromyces) were the same without being affected by species. Although the types of dominant fungal phyla did not change, the abundances of some fungal genera changed significantly. Results of Metastats analysis showed that there were a total of 206 fungal genera that were significantly different between the two horses, among which 78 genera showed an increase and 127 genera significantly decreased in Dutch Warmblood horses compared with Mongolian horses. In conclusion, this study investigated the composition and structure of the gut fungal community of Dutch Warmblood and Mongolian horses and found significant differences in gut fungal community between both breeds. Notably, this is the first exploration of the differences in the gut fungal community of both breeds, which may help to understand the distribution characteristics of the gut fungal community of different breeds of horses and reveal the differences in the traits of different horses.

Economic and Health Care Resource Use Burden of Systemic Sclerosis.

OBJECTIVE: To describe the health care resource use (HCRU) and costs of patients with systemic sclerosis (SSc) prior to and after diagnosis. METHODS: This retrospective study used a claims data set (Merative MarketScan; 2015-2019). Eligible patients with SSc were identified by diagnosis codes and required at least 24 months of enrollment without an SSc diagnosis before their first SSc claim and at least 12 months of enrollment thereafter. Total HCRU and costs were reported for three intervals: 2 years and 1 year before and 1 year after index diagnosis. A general population cohort without SSc was matched 1:1 to the SSC cohort on age and sex for comparison. RESULTS: Eligibility criteria identified 902 patients with SSc (mean age: 54 years old; 85% female). Mean per-member per year costs increased each year from $22,383 to $29,708 to $47,095, 2 years before, 1 year before, and 1 year after index diagnosis versus $10,232 to $9656 to $9714 in the general population cohort. Outpatient settings represented the largest proportion of cost 1 year after SSc diagnosis ($16,392), followed by prescription drugs ($10,692), physician office ($10,523), and inpatient ($9448) settings. CONCLUSION: Patients with SSC accrued greater costs and required more services than a general population cohort. These elevated expenditures and HCRU were observed at least 2 years before an SSc diagnosis and increased over time, reflecting both the progressive, multisystem nature of SSc and potential challenges in diagnosis. These findings suggest that SSc poses a substantial burden on the US health care system and highlights the need for early diagnosis and effective therapies.

The EDC4-XRN1 interaction controls P-body dynamics to link mRNA decapping with decay.

Deadenylation-dependent mRNA decapping and decay is the major cytoplasmic mRNA turnover pathway in eukaryotes. Many mRNA decapping and decay factors are associated with each other via protein-protein interaction motifs. For example, the decapping enzyme DCP2 and the 5'-3' exonuclease XRN1 interact with the enhancer of mRNA-decapping protein 4 (EDC4), a large scaffold that has been reported to stimulate mRNA decapping. mRNA decapping and decay factors are also found in processing bodies (P-bodies), evolutionarily conserved ribonucleoprotein granules that are often enriched with mRNAs targeted for decay, yet paradoxically are not required for mRNA decay to occur. Here, we show that disrupting the EDC4-XRN1 interaction or altering their stoichiometry inhibits mRNA decapping, with microRNA-targeted mRNAs being stabilized in a translationally repressed state. Importantly, we demonstrate that this concomitantly leads to larger P-bodies that are responsible for preventing mRNA decapping. Finally, we demonstrate that P-bodies support cell viability and prevent stress granule formation when XRN1 is limiting. Taken together, these data demonstrate that the interaction between XRN1 and EDC4 regulates P-body dynamics to properly coordinate mRNA decapping with 5'-3' decay in human cells.

A computational study of structural analysis of Class I human glucose-6-phosphate dehydrogenase (G6PD) variants: Elaborating the correlation to chronic non-spherocytic hemolytic anemia (CNSHA).

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect that affects more than 500 million people worldwide. Individuals affected with G6PD deficiency may occasionally suffer mild-to-severe chronic hemolytic anemia. Chronic non-spherocytic hemolytic anemia (CNSHA) is a potential result of the Class I G6PD variants. This comparative computational study attempted to correct the defect in variants structure by docking the AG1 molecule to selected Class I G6PD variants [G6PDNashville (Arg393His), G6PDAlhambra (Val394Leu), and G6PDDurham (Lys238Arg)] at the dimer interface and structural NADP+ binding site. It was followed by an analysis of the enzyme conformations before and after binding to the AG1 molecule using the molecular dynamics simulation (MDS) approach, while the severity of CNSHA was determined via root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen bonds, salt bridges, radius of gyration (Rg), solvent accessible surface area analysis (SASA), and principal component analysis (PCA). The results revealed that G6PDNashville (Arg393His) and G6PDDurham (Lys238Arg) had lost the direct contact with structural NADP+ and salt bridges at Glu419 - Arg427 and Glu206 - Lys407 were disrupted in all selected variants. Furthermore, the AG1 molecule re-stabilized the enzyme structure by restoring the missing interactions. Bioinformatics approaches were also used to conduct a detailed structural analysis of the G6PD enzyme at a molecular level to understand the implications of these variants toward enzyme function. Our findings suggest that despite the lack of treatment for G6PDD to date, AG1 remains a novel molecule that promotes activation in a variety of G6PD variants.

Infrared Thermography as a Potential Non-Invasive Tool for Estrus Detection in Cattle and Buffaloes.

The productivity of dairy animals has significantly increased over the past few decades due to intense genetic selection. However, the enhanced yield performance of milk animals caused a proportional increase in stress and compromised reproductive efficiency. Optimal reproductive performance is mandatory for the sustainable production of dairy animals. Reproductive efficiency is marked by proper estrus detection and precise breeding to achieve maximum pregnancies. The existing conventional methods of estrus detection are somewhat labor intensive and less efficient. Similarly, the modern automated methods that rely on detecting physical activity are expensive, and their efficiency is affected by factors such as type of housing (tie stall), flooring, and environment. Infrared thermography has recently emerged as a technique that does not depend on monitoring physical activity. Furthermore, infrared thermography is a non-invasive, user-friendly, and stress-free option that aids in the detection of estrus in dairy animals. Infrared thermography has the potential to be considered a useful non-invasive tool for detecting temperature fluctuations to generate estrus alerts without physical contact in cattle and buffaloes. This manuscript highlights the potential use of infrared thermography to understand reproductive physiology and practical implementation of this technique through discussing its advantages, limitations, and possible precautions.

Synthesis of Chitosan-TiO2 Nanocomposite for Efficient Cr(VI) Removal from Contaminated Wastewater Sorption Kinetics, Thermodynamics and Mechanism.

A photolysis method was used to prepare a nanocomposite adsorbent (Chitosan-TiO2) and was tested for Cr(VI) removal from aqueous solution. The produce nanocomposite was investigated using, XRD, BET, FTIR, FESEM-EDX and TEM before and after Cr(VI) adsorption. The XRD results shows prepared anatase phase of TiO2 with 12 nm. According to BET measurements, the surface area of the TiO2/chitosan nanocomposite was lower and archived to 26 m2/g, while the TEM and FESEM images show a uniform distribution of TiO2 throughout the chitosan matrix. Adsorption and kinetic experiments were run in batch system under different conditions of pH, contact time, adsorbent dosage and temperature. Experimental Cr(VI) adsorption equilibrium and kinetics data fitted well to Langmuir model. The calculated Langmuir maximum adsorption capacity (qmax) value of nanocomposite was 488 mg/g. Moreover, the highest quantity of Cr(VI) uptake was achieved of pH = 2 and 45℃ and TiO2 and CS-TiO2 had respective removal efficiencies of 94 and 87.5%. The thermodynamic parameters of Cr(VI) adsorption by nanocomposite affirm the spontaneous and endothermic nature of process. Chromium adsorption mechanism by CS-TiO2 nanocomposite were proposed and discussed.

Response to COVID-19 in Lebanon: update, challenges and lessons learned.

The COVID-19 pandemic remains a public health problem threatening national and global health security. The socio-economic impact of COVID-19 was more severe on developing countries including Lebanon, especially due to the fragile healthcare system, weak surveillance infrastructure and lack of comprehensive emergency preparedness and response plans. Lebanon has been struggling with plethora of challenges at the social, economic, financial, political and healthcare levels prior to the COVID-19 pandemic. The COVID-19 pandemic in Lebanon revealed gaps and challenges across the spectrum of preparedness and response to emergencies. Despite these challenges, the Lebanese response was successful in delaying the steep surge of COVID-19 cases and hospitalisations through imposing strict public health and social measures. The deployment of the national vaccination plan in Lebanon in February 2021 coincided with the reduction in the number of cases and hospitalisation rates. The aim of this manuscript is to advance the epidemiologic evolution of COVID-19 in Lebanon pre- and post-vaccination, the challenges affecting the response and recovery, and the lessons learned.

Two kinds of traditional Chinese medicine prescriptions reduce thymic inflammation levels and improve humoral immunity of finishing pigs.

In animal husbandry, traditional Chinese medicine (TCM) as a reasonable alternative to antibiotics has attracted more and more concerns to reduce microbial resistance. This study was aimed to investigate the effects of dietary supplementation with TCM prescriptions on serum parameters and thymus inflammation responses in finishing pigs. Thirty finishing pigs were randomly divided into three groups, which included the Con group (basal diet), the TCM1 group (basal diet supplemented with Xiao Jian Zhong prescriptions), and the TCM2 group (basal diet supplemented with Jingsananli-sepsis). The results showed that the contents of C3 and C4 in the serum were significantly increased in both the TCM1 and TCM2 groups compared to the Con group on day 30. Similarly, the levels of IgA, IgG, and IgM were increased in the TCM2 group, and only the level of IgM in TCM1 was increased on day 30. Meanwhile, the levels of classical swine fever virus (CSFV) and respiratory syndrome virus (PRRSV) antibodies had a notable increase in the TCM1 and TCM2 groups. Both TCM1 and TCM2 inhibited the levels of TLR4/MyD88/NF-κB signaling pathway-related mRNA (TLR4, MyD88, NF-κB, IL6, IL8, and TNF-α) and protein (p-IκBα and p-P65) expression levels in the thymus. In conclusion, dietary supplementation with TCM could reduce thymic inflammation levels and improve humoral immunity of finishing pigs.

Molecular characterization of multi-drug-resistant Staphylococcus aureus in mastitis bovine milk from a dairy farm in Anhui, China.

Mastitis is an economically important disease in the dairy industry, which is caused by various infectious pathogens. There is limited information known about the situation of drug resistance and virulence factors of Staphylococcus aureus (S. aureus) in mastitis bovine milk in Anhui. Therefore, a total of 125 fresh milk samples from clinically mastitis-positive bovine animals were collected. The bacteria pathogens were identified via bacterial culture, Gram staining, biochemical analysis, DNA extraction, 16s rRNA amplification, and phylogenetic analysis. Drug resistance analyses were performed through drug-resistant genes and virulence genes amplification. Results showed that a total of 24.8% (31/125) bacterial isolates were isolated and identified as S. aureus by Gram straining, biochemical reactions, and 16 s rRNA genes blasting. Multiple sequence alignment analysis found that the current isolates were highly similar (96.9-100.0%) to previous isolates. Phylogenetic analysis demonstrated that S. aureus was similar with MK809241.1 isolated from food in China and wCP030426.1 isolated from a person in the United States. The bacterial isolates were detected resistant to 11 antibiotics, such as Penicillin G, SXT, Ciprofloxacin, Norfloxacin, Polymyxin B, Levofloxacin, Chloramphenicol, Clindamycin, Clarithromycin, Erythromycin, and Spectinomycin. Drug-resistant genes of blaZ, ermC, rpoB, and ant (4')-la were successfully amplified. Virulence genes of hla, nuc, clfa, and eta were found in S. aureus bacteria. The current study isolated S. aureus from milk samples and revealed its drug-resistant situation, drug-resistant genes, and virulence genes. Hence, regular monitoring of S. aureus in milk samples from dairy cows may contribute to the prevention and treatment of public health concerns causing bacteria in this region.

A metagenomic insight into the Yangtze finless porpoise virome.

The Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis) inhabiting the Yantze River, China is critically endangered because of the influences of infectious disease, human activity, and water contamination. Viral diseases are one of the crucial factors that threatening the health of Yangtze finless porpoise. However, there are few studies which elaborate the viral diversity of Yangtze finless. Therefore, this study was performed to investigate the viral diversity of Yangtze finless by metagenomics. Results indicated that a total of 12,686,252 high-quality valid sequences were acquired and 2,172 virus reads were recognized. Additionally, we also obtained a total of 10,600 contigs. Phages was the most abundant virus in the samples and the ratio of DNA and RNA viruses were 69.75 and 30.25%, respectively. Arenaviridae, Ackermannviridae and Siphoviridae were the three most predominant families in all the samples. Moreover, the majority of viral genus were Mammarenavirus, Limestonevirus and Lambdavirus. The results of gene prediction indicated that these viruses play vital roles in biological process, cellular component, molecular function, and disease. To the best of our knowledge, this is the first report on the viral diversity of Yangtze finless porpoise, which filled the gaps in its viral information. Meanwhile, this study can also provide a theoretical basis for the establishment of the prevention and protection system for virus disease of Yangtze finless porpoise.

Hexavalent Chromium Exposure Induces Intestinal Barrier Damage via Activation of the NF-κB Signaling Pathway and NLRP3 Inflammasome in Ducks.

Hexavalent chromium [Cr(VI)] is a dangerous heavy metal which can impair the gastrointestinal system in various species; however, the processes behind Cr(VI)-induced intestinal barrier damage are unknown. Forty-eight healthy 1-day-old ducks were stochastically assigned to four groups and fed a basal ration containing various Cr(VI) dosages for 49 days. Results of the study suggested that Cr(VI) exposure could significantly increase the content of Cr(VI) in the jejunum, increase the level of diamine oxidase (DAO) in serum, affect the production performance, cause histological abnormalities (shortening of the intestinal villi, deepening of the crypt depth, reduction and fragmentation of microvilli) and significantly reduced the mRNA levels of intestinal barrier-related genes (ZO-1, occludin, claudin-1, and MUC2) and protein levels of ZO-1, occludin, cand laudin-1, resulting in intestinal barrier damage. Furthermore, Cr(VI) intake could increase the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) but decrease the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione reductase (GR), as well as up-regulate the mRNA levels of TLR4, MyD88, NF-κB, TNFα, IL-6, NLRP3, caspase-1, ASC, IL-1ß, and IL-18 and protein levels of TLR4, MyD88, NF-κB, NLRP3, caspase-1, ASC, IL-1ß, and IL-18 in the jejunum. In conclusion, Cr(VI) could cause intestinal oxidative damage and inflammation in duck jejunum by activating the NF-κB signaling pathway and the NLRP3 inflammasome.

Investigation on Immune-Related Protein (Heat Shock Proteins and Metallothionein) Gene Expression Changes and Liver Histopathology in Cadmium-Stressed Fish.

Heat shock proteins (HSP) are highly conserved in their structure and released in case of stress. Increased metallothionein (MT) synthesis is associated with increased capacity for binding heavy metals. Healthy juveniles of grass carp were exposed to sublethal dose (1.495 mg L-1) of cadmium for 28 days. Simultaneously, a control group was also run to compare difference of total RNA expression levels in cadmium-treated and control groups. The cadmium levels in the tissues of treated fish recorded were 1.78 ± 0.10 mg L-1, 1.60 ± 0.04 mg L-1, and 2.00 ± 0.05 mg L-1, respectively. Several histological alterations including edema, hemorrhage, dilated sinusoids, hypertrophy, hyperplasia, congestion of central vein, and nuclear alterations were observed in cadmium-exposed fish. Stress gene (metallothionein and heat shock proteins) mRNA transcription levels were studied by mRNA extraction and cDNA preparation by using PCR. The expression level of heat shock protein gene was higher as compared to metallothionein and beta-2-microglobulin gene after cadmium exposure. This study reports various stress-related immune-responsive changes of immune proteins, heat shock proteins, metallothionein, and histopathological changes in fish due to cadmium toxicity that make the fish immunocompromised which may be considered as the biomarkers of cadmium toxicity in other experimental species.

Study on Various Luteal Characteristics Using Doppler Ultrasonography for Early Pregnancy Diagnosis in Nili-Ravi Buffaloes.

The objective of current study was to assess the trend in various luteal characteristics viz luteal size (LS), plasma progesterone (P4) concentration, and luteal blood flow (LBF) using color Doppler imaging (CDI) and power Doppler imaging (PDI) modes in pregnant and nonpregnant Nili-Ravi buffaloes. Lactating, cyclic, and healthy Nili-Ravi buffaloes (n = 09) without any reproductive abnormality were selected in present study. Buffaloes were synchronized using Ov-Synch, and fixed-time artificially insemination was performed (day = 0). Pregnancy was diagnosed on 30-day post-AI using B-mode ultrasonography based on presence or absence of embryonic heartbeat. Ovaries of all animals were scanned from day 5 till 21 post-AI using both B-mode and Doppler ultrasonography to measure LS and LBF. After each ovarian ultrasound examination, blood samples were collected via jugular venipuncture to determine plasma P4 concentration. According to results, LBF using CDI and PDI was significantly higher (P ≤ 0.05) in pregnant buffaloes on days 13 and 15 post-AI, respectively. The mean LS and plasma P4 concentration did not differ (P ≥ 0.05) between pregnant and nonpregnant animals until day 15 post-AI. However, a significant difference (P ≤ 0.05) was noticed for both on day 17 and onwards. It is concluded that LBF is a more sensitive luteal character as compared to LS and P4 for earlier pregnancy diagnosis in Nili-Ravi buffaloes when ascertained through CDI.

Acetochlor Affects Bighead Carp (Aristichthys Nobilis) by Producing Oxidative Stress, Lowering Tissue Proteins, and Inducing Genotoxicity.

Acetochlor is persistently used in the agroproduction sector to control broadleaf weeds. Due to frequent and continuous applications, this herbicide can reach nearby water bodies and may induce deleterious changes in aquatic life. Therefore, investigation of harmful impacts of different environmental pollutants, including herbicides, is vital to knowing the mechanisms of toxicity and devising control strategies. The current experiment included bighead carp (n = 80) to estimate adverse impacts. Fish were randomly placed in 4 different experimental groups (T0-T3) and were treated for 36 days with acetochlor at 0, 300, 400, and 500 µg/L. Fresh blood without any anticoagulant was obtained and processed for nuclear and morphological changes in erythrocytes. At the same time, various visceral organs, including the gills, liver, brain, and kidneys, were removed and processed on days 12, 24, and 36 to determine oxidative stress and various antioxidant biomarkers. Comet assays revealed significantly increased DNA damage in isolated cells of the liver, kidneys, brain, and gills of treated fish. We recorded increased morphological and nuclear changes (P ≤ 0.05) in the erythrocyte of treated fish. The results on oxidative stress showed a higher quantity of oxidative biomarkers and a significantly (P ≤ 0.05) low concentration of cellular proteins in the gills, liver, brain, and kidneys of treated fish compared to unexposed fish. Our research findings concluded that acetochlor renders oxidative stress in bighead carp.

Effects of 25(OH)D3 supplementation during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets.

The purpose of this study was to investigate the effects of diet type (normal or low Ca and P diets) and 25(OH)D3 supplementation (with or with not 2000 IU/kg 25(OH)D3 ) during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets. A total of 40 sows, which are at their 7th parity, were divided into four groups: control group (standard diet), low Ca group, 25(OH)D3 group and low Ca plus 25(OH)D3 group respectively (10 in each group). The blood of sows on day 100 and 114 of gestation and newborn piglets was collected for serum biochemical analyses. Results showed that the reproductive performance of sows was not influenced by diet type or 25(OH)D3 supplementation (p > 0.05). And the addition of 25(OH)D3 to diet low Ca group caused that the content of serum TG in sows on day 100 of gestation was not different from that of the control group (p > 0.05). The addition of 25(OH)D3 significantly decreases the content of serum TG in sows on day 114 of gestation (p < 0.05). The addition of 25(OH)D3 significantly increased the content of serum UREA and CREA in newborn piglets (p < 0.05). Overall, feeding 2000 IU/kg 25(OH)D3 to aged sows at late gestation had no effects on reproductive performance, but partly contributed to keeping serum TG balance in sows and may indicate increased pressure on kidneys in newborn piglets.

Drug-Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy.

BACKGROUND AND OBJECTIVE: Elagolix is an oral, non-peptide, gonadotropin-releasing hormone receptor antagonist. It is approved for the treatment of moderate-to-severe pain associated with endometriosis and is being investigated for the treatment of heavy menstrual bleeding associated with uterine fibroids. Use of low-dose hormonal add-back therapy can reduce hypoestrogenic effects associated with elagolix, thus there is a need to determine if there is a pharmacokinetic interaction between elagolix and low-dose hormonal add-back therapy. METHODS: Two multiple-dose, open-label, single-sequence, non-randomized studies for elagolix 300 mg twice daily with oral (n = 24) and transdermal (n = 36) low-dose add-back therapy (estradiol [E2]/norethindrone acetate [NETA]; 1 mg/0.5 mg oral and 0.51 mg/4.8 mg transdermal) in healthy postmenopausal women were conducted, with pharmacokinetic sampling for E2, estrone (E1), and NETA up to 72 or 96 h after dosing. Pharmacokinetic parameters for hormones were estimated using noncompartmental methods. RESULTS: No change in norethindrone maximum plasma concentration or area under the concentration-time curve was observed when oral E2/NETA was administered with elagolix. For E2, there was a 2-fold increase in maximum plasma concentration and a 1.5-fold increase in the area under the concentration-time curve, and for E1 there was a 1.7-fold increase in maximum plasma concentration when oral E2/NETA was administered with elagolix. Exposures for norethindrone, E2, and E1 were unchanged when transdermal E2/NETA was applied with elagolix administration. CONCLUSIONS: Although changes in E2/E1 exposures were observed when oral E2/NETA was co-administered with elagolix, these changes are not considered clinically relevant; and no dose adjustments are recommended when elagolix is co-administered with oral or transdermal low-dose add-back therapy.

Cost-benefit analysis of clinical pharmacist intervention in preventing adverse drug events in the general chronic diseases outpatients.

RATIONALE, AIMS, AND OBJECTIVES: Clinical pharmacy services are vital in the prevention of adverse drug events (ADEs) in clinical practice, extending beyond the hospital to chronic disease management in outpatient settings. This study sought to evaluate the cost benefit of a clinical pharmacy intervention in resolving treatment-related problems (TRPs) among hospital outpatients with chronic diseases. METHODS: From the hospital system perspective, the cost-benefit analysis was based on a randomized clinical trial in the general outpatients of the major hospital in Jordan. Eligible patients were randomly assigned to either an intervention or a control group. TRPs were identified in both study groups, but interventions were delivered only to the intervention group via a home medication management review (HMMR) by a clinical pharmacist. A follow-up in both groups took place 3 months after recruitment. The total economic benefit was the sum of (a) cost savings due to intervention and (b) cost avoidance associated with preventable ADEs. The primary outcome measures were the net benefit and benefit-to-cost ratio with the clinical pharmacist-based HMMR. RESULTS: In both groups, 158 TRPs were identified, and 79 interventions were provided in the study group. The monthly cost of intervention was JD764 (US $1078), and the total monthly benefit was JD4570 (US $6444), leading to a benefit-to-cost ratio of 5.98 and an annual net benefit of JD45 669 (US $64 393). Sensitivity analyses confirmed the robustness of results. CONCLUSION: The RCT-based cost-benefit evaluation provided evidence-based insight into the economic benefit of a clinical pharmacist-provided HMMR for preventing ADEs in the general chronic diseases outpatients. This intervention method against the TRPs among outpatients is cost beneficial and offers substantial cost savings to the health care hospital payer in Jordan.