A Third Pandemic is on the Horizon

The emergence of the novel SARS-CoV-2 virus and the resultant COVID-19 pandemic has brought the world to a standstill. In the United States, the morbidity and mortality associated with COVID-19 infection has disproportionately impacted Black, Indigenous and People of Color (BIPOC) communities, highlighting an underlying “second pandemic” perpetuated by the deeply-rooted health care inequities and social determinants of health. In this manuscript, we warn about a “Third Pandemic” on the horizon which could be driven by federal policies that fail to ensure equitable access to COVID-specific therapeutics for BIPOC communities, and the potential inequitable implementation of such policies that could further perpetuate disparities in health outcomes

Characterisation and Mechanical Testing of Hydrothermally Treated HA/ZrO2 Composites

Hydrothermal treatment is traditionally employed to improve the sinterability of powder compacts by reducing porosity and increasing apparent density. The effect of hydrothermal treatment on green powder compacts has been assessed in order to better understand how treatment may affect the sinter ability of the bodies. Laboratory synthesized nano sized hydroxyapatite (HA) and a commercial zirconia (ZrO2) powder have been ball milled together to create composite mixtures containing 0-5 wt% ZrO2 loadings. Disc shaped bodies have been formed using uniaxial and subsequent isostatic pressure. The resultant coherent samples were subjected to hydrothermal treatment at either 120 or 250°C for 10 h in order to assess the effect of this processing technique on the physical, mechanical and microstructural properties of the green composites. ZrO2 loadings up to 3 wt% increased apparent density from 90 to 92%, whereas increased loading to 5 wt% increased flexural strength, from 6 to 9 MPa. Increasing the hydrothermal treatment temperature increased open porosity, from ~44 to ~48% and reduced biaxial flexural strengths of the treated bodies compared to those of their room temperature isostatically pressed counterparts (~10 to ~6 MPa). © 2009 Springer Science+Business Media, LLC

Tetraaquabis(3-fluoropyridine-4-carboxylato-\u3cem\u3eκN\u3c/em\u3e)zinc(II) dihydrate

In the title compound, [Zn(C6H3FNO2)2(H2O)4]·2H2O, the ZnII atom is octahedrally coordinated in a ZnO4N2 environment by two 3-fluoropyridine-4-carboxylate (3-fpy4-cbx) ligands and four water molecules. The [Zn(3-fpy4-cbx)2(H2O)4] molecules form a three-dimensional network through strong O-HO and weak O-HF hydrogen bonds between 3-fpy4-cbx and water molecules. The crystal used for data collection was a twin, with the twin law corresponding to a 180° rotation about the real-space [001] axis. The major twin fraction refined to 0.795 (1)

Intra-articular anesthesia and knee muscle response

Background: Many receptors located within the intra-articular knee structures contribute to the neuromuscular responses of the knee. The purpose was to compare the automatic postural response induced by a perturbation at the foot before and after an intra-articular injection of a local anesthetic (bupivicaine), after a saline (sham) injection, and after no intra-articular injection (control) in the knee. Methods: Muscle onset latencies and automatic response magnitudes for the vastus medialis, vastus lateralis, biceps femoris, medial hamstrings, tibialis anterior, and gastrocnemius were measured using electromyography (EMG) when anteriorly directed perturbations were applied to the feet of 30 subjects. All subjects then received a lidocaine skin injection followed by: an intra-articular bupivicaine injection (treatment group); an intra-articular saline injection (sham group); or no injection (control group), depending on their randomized group assignment. The perturbation tests were then repeated. Findings: Muscle onset latencies and automatic response magnitudes did not change as a result of the intra-articular injections. Latencies were significantly greater for the vastus medialis and vastus lateralis when compared to the medial hamstrings, biceps femoris and tibialis anterior (P \u3c 0.001). Automatic response magnitudes for the tibialis anterior were significantly greater than those of the hamstrings, which were greater than those of the quadriceps (P \u3c 0.001). Interpretation: There were no differences in muscle response when anteriorly directed perturbations were applied to the foot with or without an injection of local anesthetic in the knee. Intra-articular receptors were either unaffected by the anesthetic or the extra-articular receptors or receptors of the other joints were able to compensate for their loss

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

<b>Background:</b> Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.<p></p> <b>Objective:</b> To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.<p></p> <b>Design, setting, and participants:</b> RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.<p></p> <b>Outcome measurements and statistical analysis:</b> We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.<p></p> <b>Results and limitations:</b> We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.<p></p> <b>Conclusions:</b> RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.<p></p&gt

Tetra­aqua­bis(3-fluoro­pyridine-4-carboxyl­ato-κN)zinc(II) dihydrate

In the title compound, [Zn(C6H3FNO2)2(H2O)4]·2H2O, the ZnII atom is octa­hedrally coordinated in a ZnO4N2 environment by two 3-fluoro­pyridine-4-carboxyl­ate (3-fpy4-cbx) ligands and four water mol­ecules. The [Zn(3-fpy4-cbx)2(H2O)4] mol­ecules form a three-dimensional network through strong O—H⋯O and weak O—H⋯F hydrogen bonds between 3-fpy4-cbx and water mol­ecules. The crystal used for data collection was a twin, with the twin law corresponding to a 180° rotation about the real-space [001] axis. The major twin fraction refined to 0.795 (1)