Vaccine hesitancy in the refugee, immigrant, and migrant population in the United States: A systematic review and meta-analysis.

Refugees, immigrants, and migrants (RIM) in the United States (US) have been identified as an underimmunized population prior to the COVID-19 pandemic. Vaccine acceptance is critical to combat the public health threat incited by COVID-19 and other vaccine-preventable disease. To better understand escalating vaccine hesitancy among US RIM, a comprehensive evaluation of the problem and solutions is necessary. In this systematic review, we included 57 studies to describe vaccination rates, barriers, and interventions addressing vaccine hesitancy over the past decade. Meta-analysis was performed among 22 studies, concluding that RIM represent an underimmunized population compared to the general US population. Narrative synthesis and qualitative methods were used to identify critical barriers, including gaps in knowledge, poor access to medical care, and heightened distrust of the medical system. Our results demonstrate the need for effective, evidence-based interventions to increase vaccination rates among diverse RIM populations.

Human health risk evaluation of selected VOC, SVOC and particulate emissions from scented candles.

Airborne compounds in the indoor environment arise from a wide variety of sources such as environmental tobacco smoke, heating and cooking, construction materials as well as outdoor sources. To understand the contribution of scented candles to the indoor load of airborne substances and particulate matter, candle emission testing was undertaken in environmentally controlled small and large emission chambers. Candle emission rates, calculated on the basis of measured chamber concentrations of volatile and semi-volatile organic compounds (VOC, SVOC) and particulate matter (PM), were used to predict their respective indoor air concentrations in a standard EU-based dwelling using 2 models: the widely accepted ConsExpo 1-box inhalation model and the recently developed RIFM 2-box indoor air dispersion model. The output from both models has been used to estimate more realistic consumer exposure concentrations of specific chemicals and PM in candle emissions. Potential consumer health risks associated with the candle emissions were characterized by comparing the exposure concentrations with existing indoor or ambient air quality guidelines or, where not existent, to established toxicity thresholds. On the basis of this investigation it was concluded that under normal conditions of use scented candles do not pose known health risks to the consumer.

The microtubule-active antitumor compound TTI-237 has both paclitaxel-like and vincristine-like properties.

PURPOSE: To compare TTI-237 (5-chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1, 2, 4]triazolo[1,5-a]pyrimidin-7-amine butanedioate) with paclitaxel and vincristine in order to better understand the properties of this new anti-microtubule agent. METHODS: Tubulin polymerization and depolymerization were followed by turbidimetric assays. Effects of compounds on the binding of [(3)H]guanosine triphosphate ([(3)H]GTP) to tubulin were studied by competition binding assays. Effects of compounds on the phosphorylation of a panel of intracellular proteins were determined by flow cytometry using phosphoprotein-specific antibodies. RESULTS: At low molar ratios of TTI-237:tubulin heterodimer (about 1:30), TTI-237 enhanced depolymerization kinetics in response to low temperature, but stabilized the aggregates at higher ratios (about 1:4). Similarly, the aggregates induced in microtubule protein by TTI-237 were depolymerized by excess Ca(++) at low TTI-237:tubulin-heterodimer molar ratios, but were stable at higher ratios. TTI-237 inhibited the exchange of [(3)H]GTP at the exchangeable nucleotide site of the tubulin heterodimer, and was similar to vincristine in its effects on the phosphorylation of eight intracellular proteins in HeLa cells. CONCLUSIONS: TTI-237 has properties that distinguish it from typical vinca-site and taxoid-site ligands, and therefore it may exemplify a new class of microtubule-active compounds.

TTI-237: a novel microtubule-active compound with in vivo antitumor activity.

5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine butanedioate (TTI-237) is a microtubule-active compound of novel structure and function. Structurally, it is one of a class of compounds, triazolo[1,5a]pyrimidines, previously not known to bind to tubulin. Functionally, TTI-237 inhibited the binding of [(3)H]vinblastine to tubulin, but it caused a marked increase in turbidity development that more closely resembled the effect observed with docetaxel than that observed with vincristine. The morphologic character of the presumptive polymer is unknown at present. When applied to cultured human tumor cells at concentrations near its IC(50) value for cytotoxicity (34 nmol/L), TTI-237 induced multiple spindle poles and multinuclear cells, as did paclitaxel, but not vincristine or colchicine. Flow cytometry experiments revealed that, at low concentrations (20-40 nmol/L), TTI-237 produced sub-G(1) nuclei and, at concentrations above 50 nmol/L, it caused a strong G(2)-M block. The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC(50) of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively. TTI-237 was not recognized by the MRP or MXR transporters. TTI-237 was active in vivo in several nude mouse xenograft models of human cancer, including LoVo human colon carcinoma and U87-MG human glioblastoma, when dosed i.v. or p.o. Thus, TTI-237 has a set of properties that distinguish it from other classes of microtubule-active compounds.