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The worldwide HIV cases were 39.0 million (33.1–45.7 million) in 2022. Due to genetic variations, HIV-1 is more easily transmitted than HIV-2 and favours CD4 + T cells and macrophages, producing AIDS. Conventional HIV drug therapy has many drawbacks, including adherence issues leading to resistance, side effects that lower life quality, drug interactions, high costs limiting global access, inability to eliminate viral reservoirs, chronicity requiring lifelong treatment, emerging toxicities, and a focus on managing infections. Conventional dosage forms have bioavailability issues due to intestinal P-glycoprotein (P-gp) efflux, which can reduce anti-retroviral drug efficacy and lead to resistance. Use of phyto-constituents with P-gp regulating actions has great benefits for semi-synthetic modification to create formulations with greater bioavailability and reduced toxicity, which improves drug effectiveness. Lipid-based nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanocarriers, and inorganic nanoparticles may inhibit P-gp efflux. Employing potent P-gp inhibitors within nanocarriers as a Trojan horse approach can enhance the intracellular accumulation of anti-retroviral drugs (ARDs), which are substrates for efflux transporters. This technique increases oral bioavailability and offers lower-dose options, boosting HIV patient compliance and lowering costs. Molecular docking of the inhibitor with P-gp may anticipate optimum binding and function, allowing drug efflux to be minimised. [ABSTRACT FROM AUTHOR]

Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone. A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, "Cochrane Central Register of Controlled Trials," Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received. From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating "high concerns" for bias. Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs. [ABSTRACT FROM AUTHOR]

AbstractUp to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria. [ABSTRACT FROM AUTHOR]

AbstractConventional systemic cancer therapy often causes numerous adverse events. However, discovering overexpressed folate receptors in solid tumours has paved the way for targeted chemotherapy. Folic acid (FA), a ligand for these receptors, is frequently combined with chemotherapeutic drugs to improve their effectiveness. Carbon nanotubes have emerged as a versatile and promising method for delivering these folate-conjugated nano-systems, ensuring targeted delivery of therapeutic agents to cancerous cells. When FA-conjugated nanotubes dissociate, they release the drug-loaded nanotubes inside the malignant cells, reducing off-target effects. These nanotubes can also be used for combination therapies, producing synergistic effects. This review aims to comprehensively gather and critically evaluate the latest methods for delivering therapeutics using FA-conjugated nanovehicles. Additionally, it seeks to enhance our comprehension of the pertinent chemistry and biochemical pathways involved in this approach. [ABSTRACT FROM AUTHOR]

Nanotechnology has significantly impacted human life, particularly in overcoming the limitations associated with neurodegenerative diseases (NDs). Various nanostructures and vehicle systems, such as polymer nanoparticles, carbon nanotubes (CNTs), nanoliposomes, nano-micelles, lipid nanoparticles, lactoferrin, polybutylcyanoacrylate, and poly lactic-co-glycolic acid, have been shown to enhance drug efficacy, reduce side effects, and improve pharmacokinetics. NDs affect millions worldwide and are challenging to treat due to the blood-brain barrier (BBB), which hinders drug delivery to the central nervous system (CNS). Research suggests that natural ingredients can be formulated into nanoparticles, offering a promising approach for ND treatment. This review examines the advantages and disadvantages of herbal-based nanoformulations, highlighting their potential effectiveness when used alone or in combination with other medications. Herbal nanoparticles provide benefits over synthetic ones due to their biocompatibility, reduced toxicity, and potential for synergistic effects. The study's findings can be applied to develop more efficient drug delivery systems, improving the treatment of NDs by enhancing drug penetration across the BBB and targeting affected CNS areas more precisely. [ABSTRACT FROM AUTHOR]

AbstractChitosan oligosaccharides are biopolymers with a wide range of potential applications in various fields. This biopolymer is diverse and promising, and current research is investigating its capabilities for improved drug delivery. As chitosan oligosaccharide has the potential to be used as a drug delivery option, the purpose of this study was to examine its physicochemical characteristics and its potential for drug delivery. In this study, the pharmacokinetic properties of chitosan oligosaccharide were studied through Insilco investigation, which revealed that it is an extremely soluble and effective drug delivery candidate because it does not inhibit CYP isoenzymes and has a log Kp of −12.10 cm/s. It belongs to toxicity class 6 for acute oral toxicity, with an average similarity of 87.5% and a prediction accuracy of 70.97%. Additionally, XRD peak analysis revealed that the material was amorphous, as the peak appeared at 2θ = 24.62°, indicating the absence of well-defined crystalline areas. This characteristic makes the material more suitable for customization in many applications such as drug delivery and tissue engineering. FTIR, SEM, and TGA analysis were performed to gain a better understanding. These findings also emphasize the distinctive qualities and benefits of the oligosaccharides in this domain. Application of chitosan oligosaccharides in the development of efficient drug delivery systems. In the future, it would be more effective, targeted, and safe, with potent therapeutic efficacy for drug delivery. [ABSTRACT FROM AUTHOR]

The global COVID-19 pandemic, caused by SARS-CoV-2, has created an urgent need for novel antiviral agents, as it has led to a devastating loss of lives worldwide. In response, numerous vaccines were developed in 2022, with ongoing efforts for more candidates. Despite significant progress, reports of vaccine-related issues and side effects have emerged. The effectiveness of COVID-19 vaccines has been challenged by new viral variants, a lack of well-designed in vivo experiments, and randomised controlled trials. Currently, no clinically approved antiviral medications exist for treating COVID-19. However, a few broad-spectrum antiviral drugs have shown promising outcomes in clinical studies. Many scientists believe that natural compounds derived from herbal medicines and mushrooms could offer substantial benefits to COVID-19 patients. Ganoderma, known for its traditional use in promoting health and longevity, has a rich history of therapeutic applications and dietary supplementation. Numerous epidemiological and clinical studies have demonstrated that Ganoderma and its derivatives can enhance innate and adaptive immune responses against various pathogens, including viruses, in laboratory settings and living organisms. Therefore, the secondary metabolites in Ganoderma, such as triterpenoids, polysaccharides, and glycoproteins, hold significant potential for developing novel antiviral drugs. These compounds have demonstrated various antiviral mechanisms, including inhibition of viral replication, modulation of immune responses, and direct virucidal effects. Given the ongoing search for effective treatments against COVID-19, Ganoderma and its bioactive compounds stand out as promising candidates for further research and development. Their multifaceted antiviral mechanisms make them suitable for exploration as therapeutic agents against SARS-CoV-2, potentially contributing to developing novel antiviral drugs and enhancing the effectiveness of existing treatments. [ABSTRACT FROM AUTHOR]

High placebo responses in clinical trial could reduce the treatment effect leading to the failure of a promising drug. Several strategies have been developed to minimize high placebo responses, including the sequential parallel comparison design (SPCD). For a study with binary outcome, the existing statistical methods to test the drug effectiveness always rely on the asymptotic limiting distribution. When a study's sample size is small to medium, the asymptotic approaches do not have satisfactory performance with regard to type I error rate and statistical power. For that reason, we propose utilizing exact conditional approach to calculate sample size based on the existing test statistics to order the sample space. The proposed method controls the type I error rate under the unconditional framework. We compare the proposed exact sample sizes using different test statistics and the sample size for a randomized parallel study. We would recommend using exact sample sizes for the SPCD with small- to medium sample sizes and the SPCD with extreme response rates. [ABSTRACT FROM AUTHOR]

The most commonly used intervention for opioid overdoses is naloxone. With naloxone soon to be sold over-the-counter in the United States, the goal of this paper is to categorize frequently asked questions (FAQs) and answers about naloxone using internet sources in a cross-sectional fashion. Terms "narcan" and "naloxone" were searched on a clean Google Chrome browser using the "People also asked" tab to find FAQs and their answer sources. We classified questions and sources and assessed each website's quality and credibility grading with JAMA benchmark criteria. The Kruskal-Wallis H test was used to determine variance of mean JAMA score by source type and Post-Hoc Dunn's test with Bonferroni corrected alpha of 0.005 used to compare source types. Of the 305 unique questions, 202 (66.2%) were classified as facts, 78 (25.6%) were policy, and 25 (8.2%) were value. Of the 144 unique answer sources, the two most common included 55 (38.2%) which were government entities and 47 (32.6%) which were commercial entities. Ninety-two (of 144, 63.9%) sources met three or more JAMA benchmark criteria. Statistical analysis showed a significant difference between the JAMA benchmark scores by source type H(4) = 12.75, p = 0.0126 and between the mean rank of academic and government sources (p = 0.0036). We identified FAQs and their citations about naloxone, highlighting potential lack of understanding and knowledge of this important intervention. We recommend updating websites to accurately reflect current and useful information for those that may require naloxone. [ABSTRACT FROM AUTHOR]

The author comments on banning puberty-pausing medications and how such endangers transgender adolescents. Topics covered include the prescribed treatment of gender-dysphoria in adolescents, how such types of medications are also used in a variety of other medical contexts and implication of legislation attacking the provision of puberty-pausing medications.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC). Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared. The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p =.001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p =.011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p <.001). Less neutropenia (26.0% vs. 70.0% [p <.001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p =.009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort. p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a common gynecological malignancy, and improving cisplatin sensitivity has become a hot topic in CC chemotherapy research. Polyphyllin I (PPI), a potent bioactive compound found in Rhizoma Paridis, known for its anticancer properties, remains underexplored in CC resistance. In this study, we evaluated PPI's impact on cisplatin-resistant CC cells and elucidated its underlying mechanism. Our findings reveal that PPI enhances the sensitivity of cisplatin-resistant CC cells to the drug, promotes apoptosis, and inhibits cell migration. Mechanistically, PPI was found to regulate p53 expression and its target genes, and suppressing p53 expression reverses PPI's sensitizing effect in drug-resistant CC cells. In conclusion, PPI showed promise in sensitizing cisplatin-resistant human CC cells to cisplatin treatment, suggesting that it could serve as a potent adjunct therapy for cervical cancer, particularly for cases that have developed resistance to cisplatin, thereby providing a promising basis for further clinical investigation into PPI for enhancing the efficacy of existing chemotherapy regimens in resistant cervical cancer. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment. [ABSTRACT FROM AUTHOR]

Biopolymers have the utmost significance in biomedical applications and blending synthetic polymers has shown favorable characteristics versus individual counterparts. The utilization of the blends can be restricted through the use of toxic chemical agents such as initiators or crosslinkers. In this regard, a chemical agent-free ionizing irradiation is a beneficial alternative for preparing the hydrogels for biomedical applications. In this study, carboxymethyl chitosan (CM-CS), guar gum (GG), and poly(vinylpyrrolidone) (PVP) based ternary blends (TB) were crosslinked using various doses of ionizing irradiation to fabricate hydrogels. The prepared hydrogels were characterized for physicochemical properties, swelling analysis, biological assays, and drug delivery applications. Swelling analysis in distilled water revealed that the hydrogels exhibit excellent swelling characteristics. An in vitro cytocompatibility assay showed that the hydrogels have greater than 90% cell viability for the human epithelial cell line and a decreasing cell viability trend for the human alveolar adenocarcinoma cell line. In addition, the prepared hydrogels possessed excellent antibacterial characteristics against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). Finally, the release studies of anti-inflammatory Quercus acutissima (QA) loaded hydrogels exhibited more than 80% release in phosphate-buffered saline (pH = 7.4). These findings suggest that TB hydrogels can be used as suitable carrier media for different release systems and biomedical applications. [ABSTRACT FROM AUTHOR]

Introduction: Seladelpar (MBX-8025) is a once-daily administered highly specific PPAR-δ agonist in Phase 3 and extension trials for use in patients with primary biliary cholangitis (PBC). Areas covered: This review provides background on current treatment options for PBC, and summarizes clinical trial data regarding the safety and effectiveness of seladelpar within the context of these treatments. Expert opinion: Clinical trials results demonstrate the safety and tolerability of seladelpar use for PBC, including in patients with cirrhosis. The primary composite endpoint (ALP <1.67 times ULN, decrease ≥ 15% from baseline, and TB ≤ULN) was met in 61.7% of the patients treated with seladelpar and in 20% receiving placebo (p < 0.001). Moreover, pruritus – a cardinal and often intractable symptom of PBC – was improved with seladelpar treatment, as were overall quality of life measurements. Improvements in markers of inflammation were likewise observed. These biochemical and clinical findings therefore represent landmark developments in PBC treatment and offer a therapeutic option for PBC. [ABSTRACT FROM AUTHOR]

Introduction: Acute gastroenteritis (AGE) is the consequence of a disturbed gastro-intestinal microbiome. Certain probiotic strains (Lacticaseibacillus rhamnosus, Saccharomyces boulardii CNCM I-745, Limosilactobacillus reuteri (L. reuteri) DSM 17,938, the combination of L. rhamnosus 19070–2 and L. reuteri DSM 12,246) reduce the duration and severity of diarrhea. Areas covered: Relevant literature was sourced from PubMed and CINAHL. Important reviews until 2021 were summarized in tables. New evidence for pro-, pre-, syn- and postbiotics in AGE was searched for. Postbiotics offer advantages regarding product stability and show accumulating evidence. Heterogeneity in studies regarding the in- and exclusion criteria, primary and secondary endpoints, type, dose, timing and duration of biotic administration limits the evidence. Expert opinion: Development of a core outcome set for children with AGE would be beneficial, as its application would increase the homogeneity of the available evidence. The vast majority of the 'biotics' is registered as food supplement. Regulations for food supplements prioritize safety over efficacy, making them considerably more tolerant compared to the regulation for registration as medication. We recommend that at least one randomized controlled trial is published with the commercialized product before marketing the product, despite the fact that legislation regarding food supplements requires only safety data. [ABSTRACT FROM AUTHOR]

Immunotherapies have revolutionized cancer treatment, but often fail to produce desirable therapeutic outcomes in all patients. Due to the inter-patient heterogeneity and complexity of the tumor microenvironment, personalized treatment approaches are gaining demand. Researchers have long been using a range of in-vitro assays including 2D models, organoid co-cultures, and cancer-on-a-chip platforms for cancer drug screening. A comparative analysis of these assays with their suitability, high-throughput capacity, and clinical translatability is required for optimal translational use. The review summarized in-vitro platforms with their comparative advantages and limitations including construction strategies, and translational potential for immuno-oncology drug efficacy assessment. We also discussed end-point analysis strategies so that researchers can contextualize their usefulness and optimally design experiments for personalized immunotherapy efficacy prediction. Researchers developed several in-vitro platforms that can provide information on personalized immunotherapy efficacy from different angles. Image-based assays are undoubtedly more suitable to gather a wide range of information including cellular morphology and phenotypical behaviors but need significant improvement to overcome issues including background noise, sample preparation difficulty, and long duration of experiment. More studies and clinical trials are needed to resolve these issues and validate the assays before they can be used in real-life scenarios. [ABSTRACT FROM AUTHOR]

Cannabis Use Disorder (CUD) has no FDA-approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for their potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Seventeen participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N = 12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N = 4, all females), anorexia (N = 3), and irritability (N = 2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE = 0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Lorcaserin was well tolerated in males but not females, suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. [ABSTRACT FROM AUTHOR]

Skin disorders have an important psychosocial impact on the life of the affected patient. Skin disorders are usually treated by using topical drug delivery systems like creams and gels. These conventional topical drug delivery systems display various adverse effects (burning, itching, inflammation, etc.) reducing the therapeutic efficacy of drugs. Therefore, pharmaceutical scientists are trying to develop new delivery vehicles to treat dermatological disorders. Polymeric microsponges have shown their potential to deliver various therapeutic agents effectively through the topical route in the last decade. Their physicochemical properties like size, high drug entrapment (%), and extended drug release make them superior to other microcarriers explored for topical delivery. This present review discloses about methods of preparation, characterization parameters, and the role of polymeric microsponges for the topical delivery of a variety of drugs. The literature investigation for this review was done by exploring search engines like Google Scholar and Pubmed. This review will be useful for the researchers involved in the work of the development of new delivery vehicles for the topical route. [ABSTRACT FROM AUTHOR]

The present study was conducted to investigate the effects of Ocimum basilicum L. (OB) extract on learning and memory impairment in aged rats. Male rats were divided into the following experimental groups: Group 1 (control): including 2 months old rats, Group 2 (aged) including 2 years old rats, Groups 3–5 (aged-OB): including 2 years old rats received 50, 100, and 150 mg/kg OB for 8 weeks by oral gavage. Aging increased the delay to find the platform but, however, decreased the time spent in the target quadrant when tested by Morris water maze (MWM). Aging also reduced the latency to enter the dark chamber in the passive avoidance (PA) test compared to the control group. Moreover, interleukin-6 (IL-6) and malondialdehyde (MDA) levels were raised in the hippocampus and cortex of aged rats. In contrast, thiol levels and enzymatic activity of superoxide dismutase (SOD) and catalase (CAT) significantly reduced. In addition, aging significantly reduced BDNF expression. Finally, OB administration reversed the mentioned effects. The current research showed that OB administration improves learning/memory impairment induced by aging. It also found that this plant extract protects the brain tissues from oxidative damage and neuroinflammation. [ABSTRACT FROM AUTHOR]

Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20–24] years and 23 [20–26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10–32] months vs. 12 [8–21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7–2.1] nmol/L vs. 13.0 [6.0–17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8–28.1] ng/ml vs. 11.8 [7.9–18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL. [ABSTRACT FROM AUTHOR]

Premenstrual syndrome is a common disorder in women of reproductive age characterized by a variety of cyclical symptoms with a great impact on their lifestyle. Available pharmacological options include both antidepressants and oral contraceptives, both of which have side effects, are expensive and not always effective. Vitamins, minerals and plant extracts have been proven to alleviate the symptomatology of the premenstrual syndrome. For this reason, the purpose of this study was to test the effectiveness of a commercial phytotherapeutic dietary supplement (PREMEN-CALM®: γ-aminobutyric acid, Rhodiola rosea L., Vitex agnus-castus, vitamin B6 and melatonin) as an alternative treatment for this condition. A randomized, double-blind, and placebo-controlled pilot study was performed. Participants (n = 42) were assessed before and after 3 months of taking the supplement (n = 21) or the placebo (n = 21). Outcome measures include antioxidant and inflammatory biomarkers, body composition, subjective sleep quality, mood state profile, quality of life, and certain characteristics of the menstrual cycle. The within-group analysis revealed a significant improvement in the total antioxidant status (1.49 ± 0.34 vs reference value 1, p = 0.002), mood state profile (p = 0.02), and affective symptoms (p = 0.01) in the women receiving the commercial phytotherapeutic dietary supplement PREMEN-CALM®. On the contrary, the between-group analysis showed no statistical differences, suggesting a plausible placebo effect. The phytotherapeutic supplement PREMEN-CALM® might be effective in treating or alleviating the symptoms of the premenstrual syndrome without adverse events. Integrative medicine approaches in the clinical practice may help improve the health of women suffering from this and other gynecological conditions. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a functional gastrointestinal condition. Probiotics and other nutraceutical compounds can have specific indications in the context of IBS. A retrospective analysis was conducted on 123 IBS patients in order to evaluate the effects of an oral probiotic-based dietary supplement (Colicron, one cps/day for 4 wk) on stool consistency and pain intensity. Different time points were defined as follows: baseline (T0), 2 wk of treatment (T2), and 4 wk of treatment (T4). Stool consistency was assessed by using the Bristol Stool Scale. Pain intensity was evaluated by the Visual Analogue Scale (VAS). Patients who were initially categorized as normal retained regular bowel movements throughout the study. Both patients with constipation and diarrhea showed an improvement in the Bristol Stool Scale. The score increased from 1.5 ± 0.5 to 3.3 ± 0.7 (p < 0.001) and decreased from 6.5 ± 0.7 to 4.3 ± 0.9 (p < 0.001) at T4, respectively, compared to T0. The VAS score for pain in the pooled IBS patients improved from 6.7 ± 2.2 to 2.8 ± 1.9 at T0 vs T4 (p < 0.001), with a similar trend also observed when patients were categorized based on stool consistency: normal (from 5.2 ± 1.9 to 2.9 ± 1.7), constipation (from 7.5 ± 1.3 to 3.2 ± 2.2), and diarrhea (6.7 ± 2.3 to 2.5 ± 1.9) (p < 0.001). Colicron could be useful in symptom relief, reducing abdominal pain and improving stool consistency of IBS patients. However, further controlled clinical trials are needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

The incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) have been significantly increasing in China. Indole-3-carbinol (I3C), a naturally occurring component in cruciferous vegetables, is an effective cancer therapy. Yet, its effect and action mechanism in ESCC are still not fully understood. This study explored the role of I3C in ESCC in vitro and in vivo by focusing on the Wnt/β-catenin signaling pathway. MTT and flow cytometry were used to assess cell viability and apoptosis in EC18 and TE1 cells, while wound healing and transwell assays were used to investigate cell migration and invasion in vitro. Expression of β-catenin, c-myc, and cyclin D1 was determined by Western blot; LiCl (an agonist of the canonical Wnt signaling that inhibits GSK3β activity) was used to assess the role of I3C on the Wnt/β-catenin signaling pathway. For in vivo experiments, nude BALB/c mice bearing EC18 xenografts were treated with I3C and/or LiCl. I3C promoted ESCC apoptosis and inhibited cell migration and invasion by downregulating β-catenin, c-myc, and cyclin D1 in vitro and decreased the tumor growth in vivo; this process was reversed by LiCl treatment. In summary, I3C inhibits ESCC malignant behavior by suppressing the Wnt/β-catenin signaling pathway, thus deeming it a promising drug for ESCC treatment. [ABSTRACT FROM AUTHOR]

The opioid epidemic and limited access to treatment for opioid withdrawal (OW) and opioid use disorder (OUD) has led individuals to seek alternative treatments. This narrative review aims to educate clinicians on the mechanisms of action, toxicity, and applications of psychoactive plant-based substances patients may be using to self-treat OUD and OW. We specifically discuss ayahuasca, ibogaine, and kratom as they have the most evidence for applications in OUD and OW from the last decade (2012-2022). Evidence suggests these substances may have efficacy in treating OW and OUD through several therapeutic mechanisms including their unique pharmacodynamic effects, rituals performed around ingestion, and increased neuroplasticity. The current evidence for their therapeutic application in OUD and OW is primarily based on small observational studies or animal studies. High-quality, longitudinal studies are needed to clarify safety and efficacy of these substances in treatment of OW and OUD. [ABSTRACT FROM AUTHOR]

Background: Data on the characteristics and treatment outcomes of super-responders and non-superresponders in psoriasis under adalimumab treatment are limited. Methods: A retrospective analysis from psoriatic patients treated with adalimumab was compared to characterize super-responders vs non-super-responders’ groups, identify factors associated with super response, and assess treatment outcomes after switching. Results: 15 out of 70 (21.4%) patients were categorized as super-responder. The proportion of patients achieving a PASI 100 response was significantly higher in super-responders than non-super-responders at weeks 12, 24, and 52. Female sex and Charlson Co-morbidity Index were significantly associated with super-responders. A high level of high-density lipoprotein was independently associated with PASI 90 response at weeks 24 and 52. Additionally, nearly 35%–43% of non-super-responders switching to interleukin-17A (IL-17A) inhibitors may achieve a PASI 100 response at week 12. In contrast, all super-responders switching to IL-17A inhibitors achieved a PASI 100 response at week 4. Conclusions: Super-responders treated with adalimumab have a higher rate of being female and fewer comorbidities. And super-responders have better PASI responses than non-super-responders, whether the patients were treated with adalimumab or switched to IL-17A inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). Methods: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. Results: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p=0.006) and a slower decline in eGFR (WMD = 0.90mL/min/1.73 m2, 95% CI 0.31-1.48, p=0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD=-0.21, 95% CI -0.41 to -0.01, p=0.042). Conclusion: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout. Systematic review registration: PROSPERO CRD42021272591 [ABSTRACT FROM AUTHOR]

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7–9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 μM and compounds 1, 9–11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively. [ABSTRACT FROM AUTHOR]

Propolis is a natural resinous compound produced by bees, mixed with their saliva and wax, and has a range of biological benefits, including antioxidant and anti-inflammatory effects. This article reviews the in vivo transformation of propolis flavonoids and their potential influence on drug efficacy. Despite propolis is widely used, there is little research on how the active ingredients of propolis change in the body and how they interact with drugs. Future research will focus on these interactions and the metabolic fate of propolis in vivo. [ABSTRACT FROM AUTHOR]

AbstractDrug combinations are increasingly used in cancer treatment to enhance drug effectiveness through synergistic therapeutic effects. However, determining the optimal biological dose combination (OBDC) in small-scale drug combination trials presents challenges due to the increased complexity of the dose space. To effectively optimize the dose combination of combined drugs, we propose a model-assisted design by extending the single-agent Bayesian optimal interval phase I/II (BOIN12) design. Our approach incorporates a utility function to balance the tradeoff between risk and benefit and directly models the utility of each dose by constructing a quasi-beta-binomial model. A key advantage of our design is the simplification of decision-making during interim periods by considering all possible outcomes and pre-including the decision rule in the protocol. Additionally, we present a time-to-event (TITE) version of our design, employing an approximate likelihood approach to mitigate potential late-onset effects. We demonstrate that our proposed design exhibits robust and desirable operating characteristics across various scenarios through extensive simulation studies. [ABSTRACT FROM AUTHOR]

The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under hypoxic conditions has led to the development of oral drugs, HIF-Prolyl Hydroxylase inhibitors (HIF-PHIs), that constantly activate erythropoietin by inhibiting prolyl hydroxylase. HIF-PHIs have gained rapid approval in Asian countries, including Japan, with six distinct types entering clinical application. This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat. A phase 3, randomized, open-label, clinical trial (PRO2TECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNO2VATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies. [ABSTRACT FROM AUTHOR]

Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale. [ABSTRACT FROM AUTHOR]

Nano-drug delivery systems have opened new pathways for tumor treatment by overcoming some of the limitations of conventional drugs, such as physiological degradation, short half-life, and rapid release. Liposomes are promising nanocarrier systems due to their biocompatibility, low toxicity, and high inclusivity, as well as their enhanced drug bioavailability. Various strategies for active targeting of liposomal formulations have been investigated to achieve the highest drug efficacy. This review aims to summarize current developments in novel liposomal formulations, particularly ligand-targeted liposomes (such as folate, transferrin, hyaluronic acid, antibodies, aptamer, and peptide, etc.) used for the therapy of various cancers and provide an insight on the challenges and future of liposomes for scientists and pharmaceutical companies. [ABSTRACT FROM AUTHOR]

The quest for eco-friendly antifungal compounds from natural sources has surged, seeking alternatives to synthetic fungicides. In this study, we explored Cupressus sempervirens organic extracts antifungal potential against Botrytis cinerea, a destructive fungus causing grey mold disease in crops. Extracts from various phenological stages were evaluated for their antifungal activities. The dichloromethanolic extract from the flowering stage exhibited the highest efficacy, completely inhibiting B. cinerea mycelial growth, at 250 μg/mL and preventing conidia germination at 500 μg/mL. Bioguided fractionation and chromatography, led to the identification of isoquercetin as the active compound responsible for the antifungal effects. These findings present promising possibilities for the development of sustainable biofungicides to combat grey mould disease in agriculture. Further investigations into isoquercetin's potential as a biofungicide are warranted. [ABSTRACT FROM AUTHOR]

According to epidemiological research, as the population ages, neurological illnesses are becoming a bigger issue. Despite improvements in the treatment of these diseases, there are still widespread worries about how to find a long-lasting remedy. Several neurological diseases can be successfully treated with natural substances. As a result, current research has been concentrated on finding effective neuroprotective drugs with improved efficacy and fewer side effects. Naringenin is one potential treatment for neurodegenerative diseases. Many citrus fruits, tomatoes, bergamots, and other fruits are rich in naringenin, a flavonoid. This phytochemical is linked to a variety of biological functions. Naringenin has attracted a lot of interest for its ability to exhibit neuroprotection through several mechanisms. In the current article, we present evidence from the literature that naringenin reduces neurotoxicity and oxidative stress in brain tissues. Also, the literatures that are currently accessible shows that naringenin reduces neuroinflammation and other neurological anomalies. Additionally, we found several studies that touted naringenin as a promising anti-amyloidogenic, antidepressant, and neurotrophic treatment option. This review's major goal is to reflect on advancements in knowledge of the molecular processes that underlie naringenin's possible neuroprotective effects. Furthermore, this article also provides highlights of Naringenin with respect to its chemistry and pharmacokinetics. [ABSTRACT FROM AUTHOR]

Rho kinase (ROCK) inhibitors (RKIs) have been available commercially as topical ocular hypotensive agents for approximately a decade. RKIs have promise as their presumed mechanism of action is increased trabecular meshwork (TM) outflow, the presumed primary site of pathology in open-angle glaucoma. We reviewed recent literature on netarsudil, ripasudil, H-1337, and VVN539 as monotherapy and in combination with other topical ocular hypotensive agents. With a unique primary mechanism of increase in trabecular outflow, these agents target the glaucomatous pathology in aqueous humor dynamics. The ocular hypotensive efficacy of netarsudil, once-daily (q.d.), is in the range of non-cardioselective beta-adrenoceptor antagonists. Ripasudil, given twice-daily (b.i.d.), is somewhat less effective. H-1337 and VVN539, at an early development stage, both seem to have efficacy in the range of netarsudil. Conjunctival hyperemia is an adverse event common to all RKIs tested to date. The greater adoption of RKIs in therapy may be limited by financial considerations, at least in the U.S. We searched PubMed for the keywords netarsudil (AR13324), ripasudil (K-115), H-1337, and VVN539 as of November 2023. We found 349 citations which we reviewed for consideration in this review. Herein we summarize primary research reports, excluding news stories or meeting abstracts. We also searched to find new trials of interest. [ABSTRACT FROM AUTHOR]

Chloroquine (CQ) is the drug of choice for treating uncomplicated Plasmodium vivax (P.vivax) malaria in India. The knowledge about the exact burden of CQ resistance in P. vivax in India is scarce. Therefore, this systematic review aimed to assess the prevalence of CQ resistance in reported P.vivax cases from India. PubMed, EMBASE, and Web of Science, were searched using the search string: 'Malaria AND vivax AND chloroquine AND (resistance OR resistant) AND India'. We systematically reviewed in-vivo and in-vitro drug efficacy studies that investigated the CQ efficacy of P. vivax malaria between January 1995 and December 2022. Those studies where patients were followed up for at least 28 days after initiation of treatment were included. We identified 12 eligible CQ therapeutic efficacy studies involving 2470 patients, Of these 2329 patients were assessed by in-vivo therapeutic efficacy methods and the remaining 141 were assessed by in-vitro methods. CQ resistance was found in 25/1787 (1.39%) patients from in-vivo and in 11/141 (7.8%) patients from in-vitro drug efficacy studies. Based on the available studies, the prevalence of CQ resistance in P.vivax was found to be relatively lower in India. However, continued surveillance and monitoring are crucial to identify the emergence of CQ resistance. [ABSTRACT FROM AUTHOR]

Chronic low back pain is a leading cause of disability worldwide. A clinical model for its cause is lacking. Defining a cause based clinical model and a framework of understanding back pain in terms of peripheral structural and central functional pain is essential for optimal management. We describe the results of the largest published audit of 41 chronic low back pain patients, receiving outpatient sublingual ketamine therapy for defined central functional pain along with conventional peripheral structural pain management. Our clinical model assigns Movement Dysfunction as the primary cause for low back pain symptoms and restores it with Movement Therapy focused rehabilitation which is also defined. Patients were derived from a tertiary single neurosurgical specialist practice in Brisbane Australia over a three year period. Severe pain and disability measurements more than halved and only 13% of patients ceased ketamine prematurely due to predominantly non-sinister side effects common to all pharmaceutical therapies. All other surveyed metrics of utility were highly favourable in this challenging cohort of chronic back pain patients biased to poor outcomes. Outpatient ketamine maintains high efficacy and safety used in conjunction with a unique clinical model that describes chronic low back pain. This paper builds on our previous publications that describe the disease of movement dysfunction as an integral factor to the development of a cause based clinical model for the condition of chronic low back pain symptoms. Our clinical application of this model, applying the necessary dual approach of controlling symptoms arising from peripheral structural pain and central functional pain in conjunction with elimination of root causation has shown favourable outcomes in patients with high levels of pain and disability based on their tertiary referral origin and high Oswestry Disability Scores. Removing chronic low back pain from its position as one of the world's leading causes of pain and disability is more likely if the rehabilitation industry can replicate and test treatment algorithms based around established clinical models of disease which is the important subject of this paper. [ABSTRACT FROM AUTHOR]

Addressing recurrent cervical cancer poses a substantial challenge. Osimertinib, an FDA-approved EGFR inhibitor, has emerged as a promising option. Our study examined its potential to enhance paclitaxel's efficacy against cervical cancer. Osimertinib effectively hindered cancer cell growth and induced apoptosis across multiple cell lines. Combined with paclitaxel, it exhibited synergy in suppressing cervical cancer cells. Importantly, osimertinib's inhibitory effect was EGFR-independent; it targeted Mnk phosphorylation, reducing eIF4E activity. In mice, the combined osimertinib-paclitaxel treatment surpassed individual drugs in inhibiting cancer growth. These preclinical findings suggest osimertinib's repurposing as a means to improve paclitaxel's effectiveness in cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Primary dose reduction (PDR) in the first course of chemotherapy is an empirical practice, commonly used in older population. Patients over 70 years old receiving a first course of chemotherapy for a solid tumor were enrolled. A total of 179 patients were included. Standard dose was used in 69.8% of patients, while 30.2% received PDR of chemotherapy. Only 29.6% received a standardized geriatric assessment. Patients receiving standard doses presented 83.2% of toxicities, while 68% of toxicities were reported in patients receiving PDR. The toxicity rate was significantly decreased in patients treated with reduced first-cycle dose of chemotherapy. [ABSTRACT FROM AUTHOR]

Ethosomes, which are liposomes like structures, mainly composed primarily of ethanol, have attracted considerable attention due to their potential to enhance the drug permeation via skin. The article discusses the formulation and preparation methods of ethosomes, offering insights into the various factors that influence their size, shape, and stability. Moreover, it explores the techniques used to assess the physicochemical properties of ethosomes and their impact on drug delivery effectiveness. The article also elucidates the mechanism by which ethosomes enhance skin permeation, emphasising their ability to modify the lipid structure and fluidity of the stratum corneum. Additionally, the review investigates the applications of ethosomes in diverse drug delivery scenarios, including the delivery of small molecules, peptides, and phytoconstituents. It highlights the potential of ethosomes to improve drug bioavailability, extend drug release, and achieve targeted delivery to specific skin layers or underlying tissues. [ABSTRACT FROM AUTHOR]

Cranberries have a long history of use in the prevention of urinary tract infections. Cranberry products vary in proanthocyanidin content, a compound implicated in preventing the adhesion of uropathogenic Escherichia coli (E. coli) to uroepithelial cells. Testing is routinely done by cranberry product formulators to evaluate in vitro bacterial anti-adhesion bioactivity, shelf-life, and potential efficacy of cranberry products for consumer use to maintain urinary tract health. Hemagglutination assays evaluate the anti-adhesion bioactivity of cranberry products by determining how effectively the products prevent agglutination of specific red blood cells with E. coli expressing P-type and Type 1 fimbriae. The current study sought to improve upon an established anti-adhesion assay method by expanding the number of E. coli strains used to broaden potential in vivo efficacy implications and presenting results using photomicrographic data to improve accuracy and build databases on products that are routinely tested. Different lots of cranberry powder ingredient and two formulated products were tested independently for anti-adhesion activity using the established method and the improved method. Positive harmonization of results on the same samples using rigorous controls was achieved and provides the substantiation needed for the cranberry industry to utilize the improved, rapid in vitro testing method to standardize cranberry products for sufficient anti-adhesion bioactivity and maintain consumer confidence. [ABSTRACT FROM AUTHOR]

Prostate inflammation is often treated with drugs which are ineffective. Antibacterial agents fail to reach the prostate epithelium, and the blood-prostate barrier (BPB) may affect the drug transport process. Factors affecting drug efficacy remain unclear. Rats were categorised into groups A and B, corresponding to adulthood and puberty, respectively. Group C included the model of chronic prostate infection. Dialysates of levofloxacin and cefradine were collected from the prostate gland and jugular vein and evaluated. Pharmacokinetic analysis was conducted. The free concentrations of antimicrobials in the prostate and plasma samples of all groups peaked at 20 min, then gradually decreased. The mean AUC0-tprostate/AUC0-tplasma ratio in the levofloxacin group were 0.86, 0.53, and 0.95, and the mean values of AUC0-∞prostate/AUC0-∞plasma ratio were 0.85, 0.63, and 0.97. The corresponding values in the cefradine group were 0.67, 0.30 and 0.84, and 0.66, 0.31, and 0.85, respectively. The mean values in group B were lower than those in group A, and those in group C were higher than those in group B. The maturity of the prostate may affect the ability of the drug to cross the BPB. Infection may disrupt the BPB, affecting drug permeability. [ABSTRACT FROM AUTHOR]

In this study, twelve drugs used to treat Parkinson's disease were analyzed. To simplify calculations and data analysis, a computer-based computing technique along with the algorithm has been employed. The M-polynomial and their degree-based topological indices derived from the M-polynomial were calculated using MATLAB coding. Linear, quadratic, cubic, logarithmic, inverse, power, compound, s-curve, growth, and exponential regression model analyses were utilized to create QSPR models between the topological indices and eight the Physicochemical properties of the drugs to determine their effectiveness. Confidence intervals at a 95% level were computed for both the slope and intercept of the linear regression models. Also, based on the maximum $ R^{2} $ R 2 , optimal equations for estimating the Boiling point, Enthalpy of vaporization, Molar refractivity, Polarizability, and Molar volume using different indices have been determined, and linear, quadratic, and cubic equations have been specified. Calculated feature values are strongly correlated with actual values, indicating reliable predictive capabilities of the indices. For statistical analysis and to determine if there is a significant difference between the averages of the two groups, we used either an independent T-test or Welch's T-test. The results show that the p-value is less than 0.05, which indicates that the mean difference between the samples is statistically significant. [ABSTRACT FROM AUTHOR]

In many postmenopausal women, quality of life is decreased due to vasomotor symptoms. Efficient and well-tolerated non-hormonal treatment options are needed. The present review summarizes what is known about the etiology of postmenopausal vasomotor symptoms as a rationale for the mechanism of action of Elinzanetant, a new neurokinin (NK)-1/-3 receptor antagonist, as well as its efficacy and side effect profile. Elinzanetant likely exerts an antagonistic effect on the NK-3 receptor in the preoptic thermoregulatory zone, but also an additional antagonistic effect on the NK-1 receptor possibly leading to a reduction in vasodilatation and heat-sensing neuro-activity. Elinzanetant's reported peak drug concentrations are reached within one hour and the terminal elimination half-life is approximately 15 hours. Two phase IIb clinical trials evaluated the safety profile and efficacy of several doses. There were no serious adverse events, which also included a lack of evidence of drug-related hepatotoxicity. Overall, Elinzanetant seems to be well-tolerated. In the SWITCH-1 study, the 120 mg/day and 160 mg/day regimen showed good efficacy for the treatment of vasomotor symptoms and led to significant improvements in quality of life. Thus, 120 mg oral Elinzanetant/day was used in phase III trials, whose results have not yet been published. [ABSTRACT FROM AUTHOR]

Fabry's disease (FD) is a genetic lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) lost/reduced activity. We aim to systematically assess the safety and efficacy of Migalastat, an oral pharmacological chaperone, that has been approved for the treatment of FD in patients with amenable mutations. We conducted literature search following the PRISMA guidelines in major databases up to 4 February 2024, for studies that assessed the clinical outcomes of migalastat in patients with FD. The New Castle Ottawa Scale was used to evaluate the quality of the included studies. A total of 2141 records were identified through database searches and register searches, amongst which 26 records were screened, and 12 of these were excluded. The remaining 14 reports were sought for retrieval. The 12 retrieved articles were assessed for eligibility and their quality was assessed after their inclusion. Amongst the included studies, 5 were of high quality, 6 were of medium quality, and 1 was of low quality. Migalastat showed varied effects on enzyme activity and substrate levels, with gender-specific differences noted in GL-3 substrate activity and eGFR. Overall, it improved cardiac and renal outcomes similarly to enzyme replacement therapy, with a comparable safety profile. [ABSTRACT FROM AUTHOR]

Background: The most important problem in tonsillectomy is pain in the early postoperative period. Objective: We purposed to compare the effects of lidocaine, tetracaine, and articaine application to the peritonsillar bed on post-tonsillectomy pain in children. Methods: The prospective, placebo-controlled study included 80 patients, ages 3–14, who were scheduled for elective tonsillectomy. Patients were randomly divided into four groups. Group 1 received 0.9% NaCl; group 2 received 2% lidocaine; group 3 received 2% tetracaine; and group 4 received 4% articaine to the tonsillary bed for 5 min just after the operation. All patients were evaluated in terms of pain and pain-related adverse events in the postoperative 24 h. Results: All groups that used local anesthetics had significantly lower pain levels than the control group in the first eight hours (p <.001). Furthermore, the articaine group had a lower pain score than the tetracaine group at the eighth hour (p <.05). The articaine group had a lower pain score at the 16th hour than both the control and tetracaine groups (p <.05). There was no significant difference between the groups at the 24th hour (p >.05). Conclusion and significance: We recommend the immediate application of topical articaine to the tonsillar bed following the procedure to enhance postoperative pain management. [ABSTRACT FROM AUTHOR]

Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1–9 years following MDA. A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1–9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. Among 16,142 children aged 1–9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p =.034, or more than 1 h away aOR: 0.31, p =.018) compared with water in the yard. The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma. [ABSTRACT FROM AUTHOR]

Impaired vitamin D status is highly prevalent among women with UFs. The objective of this first-ever systematic review and meta-analysis was to summarize the effect of vitamin D supplementation on the size of uterine fibroids (UFs). We performed a comprehensive literature search for published randomized controlled trials (RCTs) in Medline, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 2022. Five trials including 511 participants (256 cases and 255 controls) were included. Pooling results from five trials, which compared size of UFs between experimental and placebo groups, revealed that vitamin D supplementation could significantly decrease the size of UFs (standardized mean difference [SMD]: −0.48, 95% confidence interval [CI]: −0.66, −0.31) and cause improvement in serum level of vitamin D compared to placebo group (SMD: 3.1, 95% CI: 0.66, 5.55). A significant effect was observed in the subset of trials administering vitamin D supplementation for >8 wk (SMD: −0.62, 95% CI: −0.88, −0.37). In conclusion, vitamin D supplementation significantly increases serum levels of vitamin D and reduces the size of UFs. However, larger, well-designed RCTs are still needed to determine the effect of vitamin D on other parameters of UFs. [ABSTRACT FROM AUTHOR]

To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12–0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11–0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs. [ABSTRACT FROM AUTHOR]