Effective therapies that enable precise drug delivery and integrated monitoring are urgently needed for fertility-sparing management of endometrial cancer (EC). Although calcium channel blockers (CCBs) exhibit anti-proliferative potential in EC, their poor tumor selectivity and systemic toxicity limit clinical translation. To overcome these limitations, a nanoparticle-mediated sonodynamic therapy (SDT) strategy is employed to deliver CCBs while integrating real-time imaging. This study develops MPA-RSP/Ce6/MDP, medroxyprogesterone (MPA)-modified nanoparticles based on a reactive oxygen species (ROS)-sensitive polymer (RSP), co-incorporating the sonosensitizer chlorin e6 (Ce6) and CCB manidipine (MDP). Upon ultrasound activation, Ce6 generates cytotoxic ROS, which trigger degradation of the ROS-responsive shell and release of MDP. The combination of ROS generation and calcium influx inhibition synergistically induces severe endoplasmic reticulum stress, thereby triggering immunogenic cell death and subsequent activation of antitumor immunity. This SDT approach further synergizes with PD-1 checkpoint inhibition, significantly enhancing therapeutic outcomes in vivo. Additionally, single-photon emission computed tomography (SPECT) imaging with co-assembled MPA-RSP/[99m]Tc-RSP confirms efficient tumor accumulation. In summary, this study introduces an ultrasound-responsive nanoparticle that integrates calcium-homeostasis disruption, sonodynamic therapy, and immune activation for non-surgical treatment of endometrial cancer. This strategy shifts from sustained hormonal exposure to spatiotemporally controlled physical intervention, thereby establishing a multimodal foundation for EC fertility-preservation treatment.

Reproductive efficiency in goats is essential for improving productivity, with estrus synchronization and artificial insemination (AI) being strategic reproductive tools. Although post-AI GnRH administration has been proposed to improve luteal function and fertility, its effectiveness under different synchronization protocols in goats remains unclear. Therefore, this study evaluated the effect of GnRH administration five days after AI on the reproductive response of goats synchronized using short- and long-term protocols. A total of 39 Creole goats were distributed according to protocol type (short-term: n = 26; long-term: n = 13) and treatment (control: n = 18; GnRH: n = 21). In both groups, intravaginal sponges containing medroxyprogesterone acetate were inserted on Day 0. Artificial insemination was performed 64 h after device removal, and the depth of cervical semen deposition was recorded. Estrus expression was concentrated between 24 and 48 h after device removal in both protocols, with greater synchrony in the long-term protocol. No significant differences were observed in pregnancy rate between protocols (57.7 vs. 53.8%) or treatments (57.1 vs. 55.6%). Intermediate cervical semen deposition resulted in a greater pregnancy rate (69.2%) than superficial deposition (25.0%). Multiple correspondence analysis revealed associations between reproductive variability, insemination depth, and estrus expression patterns. In conclusion, neither post-AI GnRH administration nor protocol duration affected pregnancy rate. However, reproductive performance appeared to depend more on insemination-related factors than on hormonal treatments under field conditions in Creole goats subjected to cervical artificial insemination programs.

Barrier protection provided by vaginal stratified squamous epithelium (SSE) is supported by estrogen (E)-mediated stimulation of ephrin-Eph signaling that promote desmosome expression and function. Conversely, loss of E induced by use of the contraceptive depot-medroxyprogesterone acetate (DMPA) or menopause reduces desmosome expression and weakens this epithelial barrier. We previously reported treating mice with DMPA lowers expression of the desmosomal cadherin desmoglein-1 (DSG1) in vaginal SSE by dampening EFNA3-mediated signaling whereas these effects are partially reversed by intravaginal administration of recombinant EFNA3 (rEFNA3) protein. Herein we extended these results, developing an EFNA3-mimetic agonist peptide (EFNA3-MAP) that engages the EphA2 receptor in vitro. In vivo, EFNA3-MAP penetrated vaginal SSE more effectively than rEFNA3 and restored DSG1 levels and vaginal epithelial thickness in DMPA-treated mice. It also reduced susceptibility of these mice to genital infection with bacterial and viral pathogens. In separate studies, we showed that EFNA3-MAP bioactivity depended on G-H loop aromatic residues and EphA2 engagement and that topical EFNA3-MAP restored vaginal epithelial thickness and DSG1 expression in DMPA-treated rhesus macaques. Together, current studies establish EFNA3-EphA2 signaling as a key regulator of vaginal SSE health and offer strong rationale to explore if EFNA3-MAP similarly enhances cutaneous SSE barrier function.

Several investigations have reported on the increased risk of meningioma following depot medroxyprogesterone acetate (DMPA) treatment. An extensive PubMed search was conducted evaluate systematic reviews, propensity-matched studies and case-control studies on the topics of DMPA use and meningioma risk from 2018-2026. Primarily, the studies have reported that the risk of a meningioma is exacerbated by prolonged use of DMPA, which confers sustained and higher systemic exposure to progestin. Despite the documented risk of meningioma from case-control studies, the actual number of meningioma cases associated with DMPA is extremely low. While patients should be aware of the risks associated with enduring use of DMPA, one should also consider the therapeutic benefits, namely the drug's use as a treatment for endometriosis, dysmenorrhea and the secondary effects of reducing the risk for endometrial and ovarian cancers. Additional research that evaluates the clinical risk-benefit ratio associated with DMPA use is warranted.

Some studies have suggested an increased risk of HIV acquisition or transmission with hormonal contraception and potential drug-antiretroviral therapy (ART) interactions. We conducted a randomized clinical trial among Malawian women with and without HIV who were initiating the levonorgestrel (LNG) implant or depot medroxyprogesterone acetate (DMPA) injectable. Women living with HIV were included to examine contraceptive use in the context of potential contraceptive-ART interactions and the effect of hormonal contraception on HIV genital shedding, and women without HIV were included because of concerns about the potential relationship between hormonal contraception and HIV acquisition. A qualitative sub-study assessed participants' recall and understanding of standardized contraceptive counseling messages.Participants for the qualitative sub-study were purposively sampled from the parent trial based on HIV status, counseling exposure, and contraceptive continuation status, and enrolled after randomization and exposure to counseling messages. Women participated in individual in-depth interviews (IDIs) and/or focus group discussions (FGDs) conducted after trial follow-up visits; interview timing varied across participants.Of 60 eligible women from the parent trial, 41 participated in IDIs and/or FGDs. Most recalled counseling messages emphasizing condom use for HIV and STI prevention among serodiscordant couples. However, none accurately recalled messages about the potential HIV acquisition risk associated with DMPA or the implant, and even when these messages were re-read, they were not accurately interpreted. In contrast, women more frequently recalled messages about potential reduced contraceptive effectiveness of the implant when used with ART. Women who continued their assigned contraceptive method were more likely to accurately recall counseling messages.Improved counseling strategies are needed to support clear communication and understanding of complex and evolving contraceptive and HIV-related risk information.

Intramuscular (IM) injection is the administration of medications deep into specifically selected muscles. Large muscles have an abundant blood supply; therefore, the injected medication rapidly reaches the systemic circulation and its intended site of action while bypassing first-pass metabolism. Intramuscular injection is one of the most common medical procedures performed annually. However, healthcare professionals worldwide continue to demonstrate limited adherence to recommended guidelines and standardized algorithms for administering intramuscular injections. Medications may be administered intramuscularly for prophylactic purposes, including immunization, which accounts for approximately 5% of injections, and curative purposes, which account for more than 95%. The most common medications given by IM route include: Antibiotics: penicillin G, benzathine penicillin, and streptomycin. Biological agents: immunoglobulins, vaccines, and toxoids. Hormonal agents: testosterone and medroxyprogesterone . Any nonirritant and soluble drugs may be given IM during an emergency scenario.

The aim of this study was to develop and psychometrically assess a client-experience-of-care metric tailored for women in Lilongwe, Malawi, using self-administered or provider-administered depot medroxyprogesterone acetate subcutaneous (DMPA-SC) and to assess differences in experiences of care between the two groups. A client exit interview was administered to 400 Malawian women who had self-injected (n = 198) or received provider-administered (n = 202) DMPA-SC within the three months preceding the study. Iterative exploratory factor analysis with a polychoric matrix was performed. Cronbach's alpha was used to assess scale reliability. Bivariate and multivariate generalized linear regression models with robust standard errors were used to test for differences in client experience between self-administered and provider-administered clients. Exploratory factor analysis yielded a two-factor solution, identifying a unifying scale for client experience of care (eight items) and a subscale for empowerment (ten items). The client experience of care scale had moderate construct validity, explaining 40 percent of the variance, high criterion validity with a positive and statistically significant (p < 0.05) correlation coefficient, and low-to-moderate reliability (alpha = 0.68). In adjusted models, statistically significant differences in client experience of care were detected by injection method, with self-injecting clients reporting better experiences of care compared to provider-administered clients.

In 2025, the US Food and Drug Administration (FDA) removed its prior class-wide boxed warnings for menopausal hormone therapy (MHT), paving the way for increased clinical use. Menopause accelerates cardiovascular risk independently of chronological aging, manifesting as a 7.5% increase in carotid-femoral pulse wave velocity within 1 year and a hypertension prevalence of 66.6% in women aged 55-64 years. Risk stratification for MHT hinges on the timing of initiation and the administered formulation. The 2025 Women's Health Initiative secondary analysis suggests that in symptomatic women aged 50-59 years, combination (estrogen-progestogen) MHT maintains atherosclerotic neutrality while reducing vasomotor symptoms by 59%. Conversely, atherosclerotic risk increases in women aged 70-79 years (hazard ratio 3.22 for combined therapy). Route of administration dictates the metabolic effect: oral estrogens undergo hepatic first-pass metabolism, elevating venous thromboembolism risk and increasing triglycerides by 5-15%, whereas transdermal formulations bypass hepatic first-pass metabolism, decrease triglycerides by 5-30%, and carry a neutral thromboembolic risk profile. When concurrent progestogen therapy is required, natural micronized progesterone is favored over synthetic medroxyprogesterone acetate to preserve estrogen-mediated vascular benefits. Oral or transdermal systemic MHT can be considered for vasomotor symptom management in women <60 years or within 10 years of menopause with a 10-year atherosclerotic cardiovascular disease risk of <5% and a coronary artery calcium score of zero.