Safety Data Timelines for Pregnant Individuals with HIV on Antiretroviral Therapy.

Antiretrovirals are often approved by the Food and Drug Administration without sufficient safety data regarding their use in pregnancy. To quantify this delay, we calculated the interval from the approval date to their inclusion in the Antiretroviral Pregnancy Registry prospective analysis (≥ 200 first trimester exposures); median delay was six years.

Concurrent detection of the mitochondrial DNA copy number and the +35G/C polymorphism in the mitochondrial transcription factor A gene in endometriosis.

BACKGROUND AND AIM: Endometriosis is a chronic gynecological inflammatory disease. The mitochondrial DNA copy number (mtDNA CN) and mitochondrial transcription factor A (TFAM) are known to contribute to human pathologies and cancer. Therefore, this study aims to reveal the association of mtDNA CN and TFAM+35G/C (rs1937) polymorphism with the risk of endometriosis in Egyptian females. MATERIALS AND METHODS: This case-control study involved 160 Egyptian females divided into two groups: 80 endometriosis cases and 80 controls. The mtDNA CN was quantified using a real-time quantitative PCR (qPCR), and the TFAM +35G/C SNP (rs1937) was genotyped using the TaqMan allelic discrimination assay technique. RESULTS: The mtDNA CN was markedly decreased in endometriosis cases compared to controls (P < 0. 001). TFAM rs1937 genotypes and allele distributions were all in Hardy-Weinberg equilibrium. The GC genotype and the 'C' allele frequency (P = 0.015 and P = 0.017, respectively) were substantially greater in endometriosis cases. CONCLUSION: Decreased mtDNA CN and the GC genotype of TFAM +35G/C polymorphism were significantly associated with the risk of endometriosis in Egyptian females.

Efficacy and Safety of Ketamine-Dexmedetomidine Versus Ketamine-Propofol Combination for Periprocedural Sedation: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: The combination of ketamine with propofol and dexmedetomidine has gained popularity for sedation and general anesthesia in different populations. In our meta-nalysis, we helped the anesthesiologists to know the efficiency and the efficacy of both combinations in adult and pediatric patients. METHODS: We searched PubMed, CENTRAL, Web of Science, and Scopus from inception to August 1, 2023. Our outcome parameters for efficacy were recovery time, pain score, and physician satisfaction while for safety were the related cardiorespiratory, neurological, and gastrointestinal adverse events. RECENT FINDINGS: Twenty-two trials were included with a total of 1429 patients. We found a significantly longer recovery time in the ketadex group of 7.59 min (95% CI, 4.92, 10.26; I2 = 94%) and a significantly less pain score of - 0.72 (95% CI, - 1.10, - 0.34; I2 = 0%). Adults had a significantly better physician satisfaction score with the ketofol group, odds ratio of 0.29 (95% CI, 0.12, 0.71; I2 = 0%). Recovery agitations were higher in the ketofol group with an odds ratio of 0.48 (95% CI, 0.24, 0.98; I2 = 36%). Furthermore, we found a significant difference between the combinations with a higher incidence in the ketadex group with pooled odds ratio of 1.75 (95% CI, 1.06, 2.88; I2 = 15%). Ketadex was associated with lower pain scores, hypoxic events and airway obstruction, and emergence agitation. At the same time, ketofol had much more clinician satisfaction which might be attributed to the shorter recovery time and lower incidence of nausea and vomiting. Therefore, we suppose that ketadex is the better combination in periprocedural sedation for both adult and pediatric patients who are not at greater risk for postoperative nausea and vomiting.

A holistic mitigation model for net zero emissions in the palm oil industry.

Achieving net zero emissions to ensure a sustainable future has become increasingly urgent in light of climate change. The palm oil industry in Malaysia plays a significant role in the country's economy but has faced criticism for its environmental impact, particularly in terms of sustainability and greenhouse gas emissions. While the government has implemented policies and initiatives to promote sustainable palm oil production and reduce emissions, there remains a need for a comprehensive and integrated mitigation strategy to help make an informed decision to improve the performance. To address the limitations of the current framework, this study proposes an Integrated Mitigation Strategy Model which incorporates established frameworks of Palm Oil Mill Carbon Accounting (POMCFA) and Sustainability Index (POMSI). This model has been developed based on the superstructure approach, considering a set of mitigation options to improve weak indicators identified through assessments. The selection of these options is informed by a theoretical review of existing literature on factor changes and their impact on emissions reduction. The model is further validated through case studies, ensuring its robustness and reliability. Based on the case study, it reveals that palm oil mill effluent, diesel consumption, and water consumption contribute the most to carbon dioxide equivalent emissions. In terms of sustainability scoring, the environmental aspect obtains the lowest scores compared to social and economic aspects. Weaknesses identified include dust concentration, palm oil mill effluent, and boiler emissions. Using the heuristics of factor changes equation, the mitigation model suggests implementing high-technology boilers as the optimal solution for these weaknesses. With the theoretical and empirical support behind the choice of variables, our model provides a valuable tool for decision-making in achieving net-zero emissions and sustainable palm oil production.

Polymeric nanofibers for the removal of Cr(III) from tannery waste water.

We demonstrate the use of cysteine-modified polymer nanofibers for the rapid and efficient removal of Cr(III) from real tannery waste water samples. Various parameters such as pH, load of nanofibers and time of exposure were optimized to achieve maximum removal. The optimum parameters were found to be 0.1 mg of nanofibers per mL of tannery waste water with a pH of 5.5 and an exposure time of 45 min. Almost 99% Cr(III) was removed at these ideal conditions thus demonstrating the efficacy of our material. The maximum removal capacity at these ideal conditions was estimated to be approximately 1.75 g of chromium/gram of polymeric material. This is probably due to a variety of factors including the apparent high surface to volume ratio exhibited by these nanofibers and also due to the availability of numerous cysteine groups that are known to have high binding affinities with heavy metal ions. These nanoscale polymeric materials show great potential towards the removal of heavy metal cations from waste waters.

Greenness assessment of two chromatographic methods developed for the determination of Mupirocin in two binary mixtures along with its impurity.

Two simple, accurate and precise chromatographic methods have been developed and validated for estimating Mupirocin (MUP) in two binary mixtures. Mixture (1); with Fluticasone propionate (FLU) together with two of their impurities, namely; Pseudomonic acid-D (Pseud-D) and Fluticasone impurity C (FIC). Mixture (2); with Mometasone furoate (MF) along with Pseud-D impurity. High performance thin layer chromatography (HPTLC-densitometry) and high performance liquid chromatography (RP-HPLC) were the two proposed methods. In the HPTLC method, good separation of both mixtures was achieved by using HPTLC plates pre-coated with silica gel 60 F254 as stationary phase and the mobile phase consisted of toluene: chloroform: ethanol at a ratio of (5: 4: 2, by volume). The detection was carried out at 220 nm for MUP and 254 nm for FLU, MF, Pseud-D and FIC. In the HPLC method, chromatographic separation was carried out using Agilent Eclipse XDB (250 mm×4.6 mm, 5 µm) C18 column. For mixture (1), a mobile phase of methanol: sodium di-hydrogen phosphate (pH 3.0) was applied in stepwise gradient elution starting at ratios of (50: 50, v/v) and then switching to (80: 20, v/v) after 7 min at a flow rate of 1 mL.min- 1. Detection was performed using diode array detector at 220 nm for MUP and Pseud-D and 240 nm for FLU and FIC. For mixture (2), the same mobile phase was used, but in isocratic elution in the ratio (80: 20, v/v) at flow rate of 1 mL.min- 1 and detection at 220 nm for MUP and Pseud-D and 248 nm for MF. The two methods successfully separated the cited drugs and were used to determine the drugs in pure form as well as pharmaceutical dosage forms. Validation was done as per International Council on Harmonization guidelines. Furthermore, the greenness of the proposed methods compared to the reported method, was evaluated as per the National Environmental Method Index, analytical Eco scale, Green Analytical Procedure Index and Analytical Greenness metric approaches.

Fabrication and evaluation of antimicrobial cellulose/Arabic gum hydrogels as potential drug delivery vehicle.

This article aims to assess the highly potent antimicrobial hydrogels composed of cellulose and Arabic gum containing sulfadiazine drug (sulfadiazine-loaded Cel/AG) as drug-targeting carriers. ATR-IR, SEM/ EDS, XRD, and XPS methods were used to investigate the hydrogel. The highest water absorption % was 489.93 ± 4.5 at pH 7.4. Pseudo-second order and Fickian diffusion govern the swelling behavior. The maximal sulfadiazine loading percent was 82.291 ± 74. The in-vitro drug release exhibited significant responses in physiologically simulated pH values. The maximum cumulative release percent was 66.42 ± 0.6 % at pH 7.4. The drug release is predicted by the first order and Korsmeyer-Peppas models. The first diffusion coefficient was (Di = 9.207 ± 47 × 10-3 cm2/h) and the late one was (DL = 5.64 ± 9.0 × 10-2 cm2/h) at pH 7.4. That hydrogel is well-thought-out a potential drug delivery vehicle. The thermal stability of the Cel/AG hydrogel drug carrier has been enhanced by the incorporation of sulfadiazine which is evidenced by increasing the total activation approximately two-fold. The total activation energy of Cel/AG and sulfadiazine-loaded Cel/AG hydrogels were -0.07362 and -0.2092 J/mol. The sulfadiazine medication's inhibitory effect was markedly enhanced when it was incorporated into the Cel/AG hydrogel films.

Normal-Phase TLC and Gradient Reversed-Phase HPLC for the Simultaneous Determination of Enrofloxacin and Bromhexine HCl in Presence of Two of Their Official Impurities.

In this work, two chromatographic methods are developed and validated for the determination of enrofloxacin and bromhexine (BRM) HCl in the presence of two of their specified impurities, ciprofloxacin and BRM impurity C. The suggested chromatographic methods included the use of thin layer chromatography (TLC-densitometry) and high-performance liquid chromatography (HPLC). In case of TLC-densitometry, good separation was achieved by using mobile phase of n.butanol:acetone:water:glacial acetic acid:triethylamine (10:3:1:0.5:0.5, by volume) on silica gel stationary phase at 254-nm detection. The developed HPLC method used BDS HYPERSIL C18 column with a mobile phase of water:acetonitrile:methanol:triflouroacetic acid. A linear gradient elution of 75-10%, 20-50% and 5-40% for water, acetonitrile and methanol, respectively, was applied in 13 min at a flow rate of 1.5 mL min-1. These methods were sufficient to separate the four substances simultaneously, and they are validated as per International Conference on Harmonization guidelines.

Lactoferrin alleviates cyclophosphamide induced-nephropathy through suppressing the orchestration between Wnt4/ß-catenin and ERK1/2/NF-κB signaling and modulating klotho and Nrf2/HO-1 pathway.

AIMS: Cyclophosphamide is an alkylating agent with vast arrays of therapeutic activity. Currently, its medical use is limited due to its numerous adverse events, including nephrotoxicity. This study aimed to follow the molecular mechanisms behind the potential renoprotective action of lactoferrin (LF) against cyclophosphamide (CP)-induced renal injury. MATERIALS AND METHODS: For fulfillment of our aim, Spragw-Dwaly rats were orally administrated LF (300 mg/kg) for seven consecutive days, followed by a single intraperitoneal injection of CP (150 mg/kg). KEY FINDINGS: Treatment of CP-injured rats with LF significantly reduced the elevated creatinine and blood urea nitrogen (BUN), markedly upregulated Nrf2/HO-1 signaling with consequent increase in renal total antioxidant capacity (TAC) and decrease in renal malondialdehyde (MDA) level. Furthermore, LF treatment significantly reduced the elevated renal p-ERK1/2 expression, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB) levels in CP-treated animals. Interestingly, LF treatment downregulated Wnt4/ß-catenin signaling and increased both renal klotho gene expression and serum klotho level. Furthermore, LF treatment reduced apoptosis in kidney tissue via suppressing GSK-3ß expression and modulating caspase-3 and Bcl2 levels. Histopathological examination of kidney tissue confirmed the protective effect of LF against CP-induced renal injury. SIGNIFICANCE: The present findings document the renoprotective effect of LF against CP-induced nephropathy, which may be mediated via suppressing ERK1/2/ NF-κB and Wnt4/ß-catenin trajectories and enhancing klotho expression and Nrf2/HO-1 signaling.

Morin post-treatment surpassed calpeptin in ameliorating 3-NP-induced cortical neurotoxicity via modulation of glutamate/calpain axis, Kidins220, and BDNF/TrkB/AKT/CREB trajectory.

The neuroprotective capacity of morin hydrate (MH), a potent antioxidant flavonoid, and calpeptin (CP), a calpain inhibitor, was documented against different insults but not Huntington's disease (HD). Accordingly, we aim to assess the neuroprotective potential of MH and/or CP in a 3-nitropropionic acid (3-NP)-induced HD model. The 3-NP-treated rats were post-treated with saline, MH, CP, or MH + CP for a week. Post-treatment with MH and/or CP amended motor function (beam walking test) and short-/ long-term spatial memory (novel object recognition test) and improved cortical microscopic architecture. On the molecular level, MH, and to a lesser extent CP, inhibited the cortical content/expression of glutamate, calpain, and Kidins220 and abated the inflammatory molecules, nuclear factor (NF)-κB, tumor necrosis factor-α, and interleukin-1ß, as well as lipid peroxidation. However, MH, but barely CP, activated the molecules of the neuroprotective trajectory; viz., brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (TrkB), protein kinase B (AKT), and cAMP response element-binding protein (CREB). Compared to the single treatments, the combination regimen mediated further reductions in the cortical contents of glutamate, calpain, and Kidins220, effects that extended to entail the anti-inflammatory/anti-oxidant potentials of MH and to a greater extent CP. However, the combination of MH strengthened the fair effect of CP on the survival signaling pathway BDNF/TrkB/AKT/CREB. In conclusion, MH, CP, and especially their combination, afforded neuroprotection against HD through curbing the glutamate/calpain axis, Kidins220, as well as NF-κB-mediated neuroinflammation/oxidative stress, besides activating the BDNF/TrkB/AKT/CREB hub that was partly dependent on calpain inhibition.

Improving the Quality and Shelf-life of Raw Rabbit Meat During Refrigeration Storage Using Olive/mulberry Leaves Extracts Dipping.

BACKGROUND AND OBJECTIVE: The consumption of fresh rabbit meat has become more popular among consumers in recent years, but they are easily perishable. In this study antioxidant and antimicrobial effects of mulberry (Morus nigra) leaves extract (MLE) and olive (Olea europaea) leaves extract (OLE) dip treatments at 2% w/v on the quality attributes and shelf-life of fresh rabbit meat during chilling storage under aerobic conditions were investigated. MATERIALS AND METHODS: Rabbit meat samples were refrigerated at 4±1°C to be periodically examined for their sensory quality, physicochemical parameters and bacteriological status. RESULTS: Results indicated that as the time of cold storage progressed, the overall mean scores of physicochemical and microbiological parameters were increased, while sensory scores were decreased (p<0.05) irrespective of treatment. Both natural extracts (MLE/OLE) significantly (p<0.05) delayed oxidative quality changes, protein deterioration and proliferation of bacteria noticed during the chilling study. CONCLUSION: Olive leaves extract (OLE; 2%) was more significant (p<0.05) positively affect than mulberry leaves extract (MLE; 2%) in maintaining chemical indices, lipid stability, consumer acceptance, microbial load and can prolonged the expiry of treated rabbit meat by 4 days as compared to control one. Hence, the potential of olive leaves extract to preserve rabbit meat during cold storage has been demonstrated.

Natural Polymeric Nanoparticles for Brain-Targeting: Implications on Drug and Gene Delivery.

There is a broad range of biological, chemical and physical hurdles for drugs to reach the brain. Nanoparticulate drug delivery systems hold tremendous potential for diagnosis and treatment of brain disorders, including the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. Thus, nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti- Alzheimer`s drugs, protease inhibitors, and several macromolecules into the brain. Moreover, nanoparticles may importantly reduce the drug`s toxicity and adverse effects due to an alteration of the body distribution. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable. Therefore, nanocarriers fabricated from natural polymers including polysaccharides and proteins are particularly interesting. Meeting requirements such as low cytotoxicity, abundant surface functional groups, high drug binding capacity and significant uptake into the targeted cells, natural polymer-based nanocarriers represent promising candidates for efficient drug and gene delivery to the brain. The current review highlights the latest advances achieved in developing drug-loaded polysaccharide and protein nanocarriers for brain delivery. The nanoparticles are discussed with respect to their formulation aspects, advantages, limitations, as well as the major outcomes of the in vitro and in vivo investigations. Modification of the nanoparticle surface with specific brain targeting ligands or by coating with certain surfactants for enhanced brain delivery is also reviewed. In addition, the mechanisms of the nanoparticle-mediated drug transport across the BBB are also discussed in this review.