Accurate detection and characterization of cancers is key for providing timely intervention and effective treatments. Current imaging technologies are particularly limited when it comes to detecting very small tumors in vivo, i.e. very early cancers or metastases, differentiating viable tumor from surrounding dead tumor tissue, and evaluating tumor metabolism within tissue. Optoacoustic imaging offers potential solutions to these imaging problems because of its ability to image optical absorption properties of both intrinsic tissue chromophores and exogenous contrast agents without the involvement of ionizing radiation. Optoacoustic imaging uses pulsed laser to induce localized thermoelastic expansion that generates acoustic waves detectable by an ultrasound transducer. To date, Multispectral optoacoustic tomography (MSOT) has primarily been utilized in preclinical research; however, its use in translational and clinical research is expanding. This review focuses on the current and emerging applications of optoacoustic imaging for the molecular imaging of cancer using both exogenous and endogenous contrast agents and sheds light on potential future clinical applications.

Despite significant efforts to translate nanotechnology for cancer application, lack of identification of biodistribution/accumulation of these nanovehicles in vivo remains a substantial barrier for successful implementation of theranostic nanoparticles in the clinic. The purpose of the study was to develop a tumor targeted-theranostic nanovehicle for pancreatic cancer detectable by multispectral optoacoustic tomography (MSOT). To improve the tumor specificity of our mesoporous silica nanoparticle (MSN), we utilized a dual targeting strategy: 1) an elevated tumor receptor, urokinase plasminogen activator receptor (UPAR), and 2) the acidic tumor microenvironment. The tumor specificity of the MSN particle was improved with the addition of both chitosan, targeting acidic pH, and urokinase plasminogen activator (UPA), targeting UPAR. Drug release assays confirmed pH responsive release of gemcitabine in vitro. The UPAR specific binding of MSN-UPA nanoparticles was confirmed by reduction in fluorescence signal following MSN-UPA nanoparticle treatment in UPAR positive cells blocked with a UPAR-blocking antibody. Based upon indocyanine green encapsulation within the nanoparticles, UPA ligand targeted MSNs demonstrated increased intensity compared to untargeted MSNs at both pH 7.4 (7X) and 6.5 (20X); however the signal was much more pronounced at a pH of 6.5 using tissue phantoms (p<0.05). In vivo, MSN-UPA particles demonstrated orthotopic pancreatic tumor specific accumulation compared to liver or kidney as identified using multispectral optoacoustic tomography (p<0.05) and confirmed by ex vivo analysis. By tracking in vivo nanoparticle biodistribution with MSOT, it was shown that pH responsive, ligand targeted MSNs preferentially bind to pancreatic tumors for payload delivery.

Maintenance of the corpus luteum (CL) during pregnancy is essential for continuing the elevated circulating progesterone (P4) that is required to maintain pregnancy. The mechanisms that protect the CL during early pregnancy when the non-pregnant animal would typically undergo CL regression have been extensively investigated. It is clear uterine prostaglandin F2α (PGF) causes regression of the CL in non-pregnant ruminants and that maintenance of the CL during early pregnancy is dependent upon secretion of interferon-tau (IFNT) from the elongating embryo. A number of specific mechanisms appear to be activated by IFNT. Most studies indicate that there is an inhibition of oxytocin-induced secretion of uterine PGF. There is also evidence for increased resistance to PGF action, perhaps due to secretion of PGE2 and PGE1 or direct endocrine actions of circulating IFNT. These mechanisms occur concurrently and each may help to maintain the CL during the first month of pregnancy. However, during the second month of pregnancy, IFNT is no longer secreted by the embryo. Attachment of the embryo to the uterus and subsequent placentome development have been linked to silencing of expression from the IFNT gene. In addition, there is some evidence that oxytocin responsiveness of the uterus returns during the second month of pregnancy leading to substantial basal secretion of PGF and perhaps PGF pulses. There is also no evidence that the CL during the second month of pregnancy is resistant to the actions of PGF as observed during the first month. Thus, this manuscript attempts to compare the mechanisms that maintain the CL during the first and second months of pregnancy in ruminants and provides a new, speculative, physiological model for maintenance of the CL during month two of pregnancy that is distinct from the previously-described mechanisms that maintain the CL during the first month of pregnancy.

Purpose/Objective(s) To establish the prevalence of SARS-CoV-2 in asymptomatic patients scheduled to receive radiation therapy and its impact on management decisions. Materials/Methods Between April 2020 and July 2020, patients without influenza-like-illness (ILI) symptoms at four radiation oncology departments (2 academic university hospitals and 2 community hospitals) underwent polymerase chain reaction (PCR) testing for SARS-CoV-2 prior to the initiation of treatment. Patients were tested either prior to radiotherapy simulation or after simulation but prior to treatment initiation. Patients tested for indications of ILI symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. Results Over a three-month period, a total of 385 tests were performed in 336 asymptomatic patients either prior to simulation (n=75), post-simulation, prior to treatment (n=230), or on-treatment (n=49). A total of 5 patients tested positive for SARS-CoV-2, for a pre-treatment prevalence of 1.3% (2.6% in North/Central NJ and 0.4% in Southern NJ/Southeast PA). The median age of positive patients was 58 years (range: 38-78 years). All positive patients were white and were relatively equally distributed with regard to gender (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was 5. All 5 patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of re-testing for 4 patients, while one patient was treated without delay but with additional infectious-disease precautions. Conclusion Broad-based pre-treatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Mechanisms of bovine corpus luteum (CL) maintenance during the second month of pregnancy have not been adequately investigated, despite significant reproductive losses. In the first month, interferon-tau is believed to suppress oxytocin-stimulated prostaglandin F2α (PGF) production, yet there are conflicting reports of circulating PGF metabolite (PGFM). In this study, characterization of PGFM and P4 occurred through continuous bihourly blood sampling in cows undergoing CL regression (day 18–21, n = 5), and during the first (day 18–21, n = 5) and second month (day 47–61; n = 16) of pregnancy. Cattle in the second month were assigned to control (n = 8) or oxytocin treatment (n = 8; three pulses to mimic luteolysis) to evaluate if oxytocin receptors were active. All cows but one (which had elevated PGFM prior to oxytocin treatment) maintained the pregnancy. Basal PGFM concentrations were low (11.6 ± 0.7 pg/mL) in the first month but increased 2.54-fold in the second month. Few (0.26 ± 0.12 pulses/day) PGFM pulses with low peak concentrations (28.8 ± 3.1 pg/mL) were observed during the first month of pregnancy, similar to cows not undergoing regression. However, in the second month, frequency (1.10 ± 0.26 pulses/day) and peak concentration (67.2 ± 5.0 pg/mL) of PGFM pulses increased, displaying similar frequency but lower peak PGFM than seen in regression (1.44 ± 0.14 pulses/day; 134.5 ± 18.9 pg/mL). Oxytocin treatment increased likelihood of PGFM pulses post-treatment and increased peak concentration (89.7 ± 10.1 pg/mL) in cows during the second month. Thus, cows have more PGFM pulses during second than first month of pregnancy, possibly induced by endogenous oxytocin, indicating suppression of PGF production is an important mechanism for CL maintenance during first but not second month of pregnancy.

The acquisition of dominance and ovulatory capacity was evaluated in follicles from cows that were carriers or half-sibling noncarriers of the Trio allele. Follicle size at acquisition of follicular dominance was determined by evaluating whether follicles ovulate after GnRH challenge (ovulatory capacity-experiment 1) and by determination of intrafollicular concentrations of estradiol and free insulin like growth factor 1 (IGF1) and relative mRNA expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), luteinizing hormone/choriogonadotropin receptor (LHCGR), and pappalysin 1 (PAPPA, previously known as pregnancy-associated plasma protein A, pappalysin 1) in granulosa cells from follicles of different sizes (experiment 2). Ovulatory capacity developed in follicles at 8.3 mm (50% ovulatory capacity) in noncarriers but at smaller sizes (5.5 mm) in Trio carriers. Similarly, in experiment 2, follicles of Trio carriers acquired a dominant phenotype, as determined by intrafollicular estradiol and CYP19A1, LHCGR, and PAPPA mRNA expression in granulosa cells, at significantly smaller sizes but at a similar time after wave emergence. Overall, dominance/ovulatory capacity was acquired when follicles of Trio carriers were ∼30% the size (volume basis) of follicles in noncarriers. In addition, follicles in Trio carriers appear to acquire dominance in a hierarchal manner, as demonstrated by the progressively greater number of follicles with a dominant phenotype between days 2 and 4 after wave emergence. Thus, results from this study provide further support for a physiological model in which selection of multiple follicles in Trio allele carriers is characterized by acquisition of dominance at a smaller follicle size but at a similar time in the follicular wave with multiple follicles acquiring dominance in a hierarchal sequence.

In lactating dairy cattle, the corpus luteum (CL) is a dynamic endocrine tissue vital for pregnancy maintenance, fertility, and cyclicity. Understanding processes underlying luteal physiology is therefore necessary to increase reproductive efficiency in cattle. A common technique for investigating luteal physiology is reversetranscription quantitative PCR (RT-qPCR), a valuable tool for quantifying gene expression. However, reference-gene-based RT-qPCR quantification methods require utilization of stably expressed genes to accurately assess mRNA expression. Historically, selection of reference genes in cattle has relied on subjective selection of a small pool of reference genes, many of which may have significant expression variation among different tissues or physiologic states. This is particularly concerning in dynamic tissues such as the CL, with its capacity for rapid physiologic changes during luteolysis, and likely in the less characterized period of CL maintenance during pregnancy. Thus, there is a clear need to identify reference genes well suited for the bovine CL over a wide range of physiological states. Whole-transcriptome RNA sequencing stands as an effective method to identify new reference genes by enabling the assessment of the expression profile of the entire pool of mRNA transcripts. We report the identification of 13 novel putative reference genes using RNA sequencing in the bovine CL throughout early pregnancy and luteolysis: RPL4,

Our objective was to determine the effect of route of administration of dinoprost tromethamine 7 d after treatment with GnRH on circulating 13,14-dihydro-15-keto-prostaglandin F2α (PGFM) and progesterone (P4) concentrations in lactating dairy cows. Multiparous Holstein cows fitted with indwelling jugular catheters were randomized 7 d after the last GnRH of an Ovsynch protocol (G2, d 0) to receive 25 mg of dinoprost tromethamine either intramuscularly (IM) or subcutaneously (SC). The SC cows had greater circulating PGFM concentrations 15 to 90 min after treatment than the IM cows; however, circulating P4 concentrations during induced luteolysis did not differ at any time based on route of administration.