estradiol +levonorgestrel (Fem7 Plus / HRT, Merck)

Variability in HIV viral load quantification in real-world service delivery settings: findings from an observational cohort study in Rwanda.

Murenzi Gad G, Brazier Ellen E, Rutwaza Marie Gertrude MG, Mivumbi Jean Paul JP et al.

While developments in HIV viral load (VL) testing technologies have improved detection of low-level viremia, there is substantial variation in the quantitative results of available polymerase chain reaction tests, particularly around assay lower limits of quantification (LLOQ). We aimed to describe testing results for paired specimens from the same participants reported by two laboratories in Rwanda using different assays, characterize discordancy in VL quantification, and identify factors associated with quantifiable VL results at a threshold of 40 copies/mL. In an observational cohort study of people living with HIV (PWH), aged ≥ 40 years enrolled in HIV care, we used two laboratories to process paired research specimens. We used Kappa statistics and plots to examine between-lab agreement at the LLOQs for assays used by the two labs (Lab A: 20 copies/mL for COBAS AmpliPrep/Taqman and Abbott Alinity-m HIV1 assays; Lab B: 40 copies/mL for Abbott RealTime assay and at thresholds of 200, 1000 and 2000 copies/mL. We used Poisson regression to examine participant characteristics independently associated with unsuppressed viral loads (≥ 200 copies/mL). 593 results were reported by both laboratories for 572 unique participants. The mean age of study participants was 54.4 years, and 58% were female. Median time on antiretroviral therapy was 16 years, 93.7% were on dolutegravir-based regimens, and 96.9% had CD4 cell counts of > 200 cells/mm3. For Lab A, 29.2% of specimens had quantifiable VLs at assay LLOQs of 20 copies/mL and 22.1% had quantifiable VLs at a common threshold of 40 copies/mL, compared with 4.7% of specimens processed by Lab B (LLOQ 40 copies/mL). Kappa statistics showed poor to moderate between-lab agreement below a threshold of 200 copies/mL, with high agreement at thresholds of 1000 and 2000 copies/mL and differences by assay type. CD4 cell counts < 200 cells/mm3 were associated with unsuppressed VLs reported by each laboratory. While VL quantification differed substantially between assays and laboratories used in a real-world service delivery setting, there was high agreement at cut-offs generally used in clinical decision-making. Our findings support the use of higher viral suppression cut-offs used in UNAIDS' 95-95-95 targets because lower thresholds are vulnerable to misclassification.

Neurokinin pathway botanical antagonist for menopausal vasomotor symptoms: A randomized, double-blind, placebo-controlled study.

Lederman Samuel S, Minkin Mary Jane MJ, Doyle Audra Lisa AL, Rubio Jevaneeh J et al.

Vasomotor symptoms (VMS) are a prevalent and disruptive manifestation of menopause, and many women prefer nonhormonal, nonpharmacologic treatment options. This study evaluated the efficacy of a patented multi-ingredient botanical neurokinin inhibitor (BNI) on VMS and other patient-reported outcome measures. A randomized, double-blind, placebo-controlled trial was performed in menopausal women with 5 or more moderate to severe hot flashes daily. Participants were enrolled from community medical practices in the United States and randomized to BNI or placebo for 12 weeks. BNI is a novel formulation of plant extracts that attenuates neurokinin receptor signaling in vivo. Primary endpoints were changes in daily VMS frequency and score on the Hot Flash Related Daily Interference Scale (HFRDIS). Secondary endpoints included changes in Menopause-Specific Quality of Life (MENQOL) and Pittsburgh Sleep Quality Index (PSQI). Serum estrogen and liver function were assessed in a subgroup of patients. Of 74 randomized participants, 68 completed the trial (BNI, n = 32; placebo, n = 36). BNI supplementation reduced VMS frequency by 2.2 hot flashes per day more than placebo (p = 0.003), corresponding to a 47.7% relative decrease. HFRDIS was improved in the BNI group (p = 0.037), with significant reduction on all subscales. No significant differences were observed in global menopause symptoms (MENQOL) or sleep quality (PSQI). No changes in serum estradiol or liver function abnormalities were detected. BNI was well tolerated, with no difference in adverse events between groups. A combination of botanically derived neurokinin inhibitors produces significant and sustained relief of vasomotor symptoms in menopausal women. gov registration: NCT05813067.

Steryl glucosides as a novel chemosensitizer: Enhancing doxorubicin response in estrogen receptor-positive breast cancer.

Cavalcanti-Neto Marinaldo Pacífico MP, Brauer Verônica Soares VS, Rella Antonella A, Shamseddine Achraf A et al.

Estrogen receptor-positive (ER+) breast cancer is the most prevalent breast cancer subtype, and doxorubicin is a key systemic therapeutic drug. However, its use is limited by toxicity and mechanisms of drug resistance. Steryl glucosides are bioactive glycolipids with potential anticancer and immunomodulatory properties, but their role as chemotherapy-sensitizing agents remains undefined. Here, we investigated whether a soybean-derived steryl glucoside preparation (SG) enhances doxorubicin activity primarily in the MCF-7 ER+ breast cancer model. SG co-treatment increased doxorubicin-associated cytotoxicity and reduced cell viability of MCF-7. Dose-response matrix analysis and exploratory Bliss independence modeling identified concentration-dependent regions of greater-than-expected combined activity, supporting pharmacological potentiation but not definitive synergy. SG co-treatment also increased γ-H2AX-positive nuclei, consistent with enhanced doxorubicin-associated DNA damage signaling. Fluorescence-based extraction analysis showed increased doxorubicin-associated intracellular fluorescence in SG co-treated cells, while ABCB1 qRT-PCR revealed concentration-dependent transcriptional changes. These findings suggest altered intracellular drug exposure or transport-associated responses, although functional efflux activity was not directly assessed. In an ovariectomized, estradiol-supplemented MCF-7 xenograft model, the SG-doxorubicin group showed the lowest mean tumor-growth trajectory, reduced cumulative tumor burden, lower terminal tumor weight, reduced Ki-67 staining, and increased tumor necrosis. However, the longitudinal tumor-volume analysis did not establish unequivocal superiority over doxorubicin monotherapy. Exploratory T47D data indicated weaker responsiveness, suggesting that the effect may be model-dependent. This study provides proof-of-concept evidence that SG can enhance doxorubicin-associated antitumor activity mainly in the MCF-7 model. Further studies are required to define functional transport mechanisms, model generalizability, toxicity, and formal dose-sparing potential. This study provides proof-of-concept evidence that a soybean-derived steryl glucoside preparation can enhance doxorubicin-associated cytotoxicity, DNA damage signaling, and antitumor activity primarily in the MCF-7 estrogen receptor-positive breast cancer model. The findings support further investigation of SG as a candidate chemotherapy-sensitizing adjuvant, while highlighting the need for functional transport assays, broader model validation, comprehensive toxicity assessment, and formal dose-sparing studies before translational conclusions can be drawn.

False-positive Neisseria gonorrhoeae results on the Abbott Alinity m STI assay caused by Neisseria meningitidis: two cases from Australia.

Maskell Janelle J, O'Connor Michael M, Lahra Monica M MM, Whiley David M DM et al.