Racial Disparities and Mental Health Effects Within Prostate Cancer.

Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.

Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2.

Influenza A virus's (IAV's) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV's genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem-loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term 'programmable antivirals', with implications for antiviral prophylaxis and post-exposure therapy.

Chronic Lymphocytic Leukemia With Leptomeningeal Involvement Presenting as an Acute Encephalopathy.

Introduction Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Extramedullary involvement in the central nervous system (CNS) is a rare complication of the disease, and less than 200 cases have been reported. We report a case of leptomeningeal involvement of CLL that presented as an acute encephalopathy. Case presentation A 76-year-old man with treatment-naïve, Rai stage 0 CLL presented with altered mental status. Cerebrospinal-fluid studies, including flow cytometry, confirmed the leptomeningeal involvement of the previously diagnosed CLL. Surveillance imaging and lab studies showed no evidence of disease progression or Richter's transformation. One-time intrathecal methotrexate resulted in transient improvement of his mental status. Conclusion CLL patients with new-onset neurologic manifestations should be evaluated for the CNS involvement of the neoplasm via brain imaging and cerebrospinal-fluid flow cytometry. This CNS involvement of CLL is associated with poor clinical outcomes. Intrathecal treatment with methotrexate, cytarabine, and steroid may improve neurologic symptoms.

Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.

Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.

Ionic Liquid Aqueous Two-Phase Systems for the Enhanced Paper-Based Detection of Transferrin and Escherichia coli.

Aqueous two-phase systems (ATPSs) have been widely utilized for liquid-liquid extraction and purification of biomolecules, with some studies also demonstrating their capacity as a biomarker concentration technique for use in diagnostic settings. As the limited polarity range of conventional polymer-based ATPSs can restrict their use, ionic liquid (IL)-based ATPSs have been recently proposed as a promising alternative to polymer-based ATPSs, since ILs are regarded as tunable solvents with excellent solvation capabilities for a variety of natural compounds and proteins. This study demonstrates the first application of IL ATPSs to point-of-care diagnostics. ATPSs consisting of 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) and sodium phosphate salt were utilized to quickly concentrate biomarkers prior to detection using the lateral-flow immunoassay (LFA). We found the phase separation speed of the IL ATPS to be very rapid and a significant improvement upon the separation speed of both polymer-salt and micellar ATPSs. This system was successfully applied to both sandwich and competitive LFA formats and enhanced the detection of both Escherichia coli bacteria and the transferrin protein up to 8- and 20-fold, respectively. This system's compatibility with a broad range of biomolecules, rapid phase separation speed, and tunability suggest wide applicability for a large range of different antigens and biomarkers.

A one-pot, isothermal DNA sample preparation and amplification platform utilizing aqueous two-phase systems.

Infectious diseases remain one of the major causes of death worldwide in developing countries. While screening via conventional polymerase chain reaction (PCR) is the gold standard in laboratory testing, its limited applications at the point-of-care have prompted the development of more portable nucleic acid detection systems. These include isothermal DNA amplification techniques, which are less equipment-intensive than PCR. Unfortunately, these techniques still require extensive sample preparation, limiting user accessibility. In this study, we introduce a novel system that combines thermophilic helicase-dependent amplification (tHDA) with a Triton X-100 micellar aqueous two-phase system (ATPS) to achieve cell lysis, lysate processing, and enhanced nucleic acid amplification in a simple, one-step process. The combined one-pot system was able to amplify and detect a target gene from whole-cell samples containing as low as 102 cfu/mL, and is the first known application of ATPSs to isothermal DNA amplification. This system's ease-of-use and sensitivity underlie its potential as a point-of-care diagnostic platform to detect for infectious diseases. Graphical abstract ᅟ.

A Combined Aqueous Two-Phase System and Spot-Test Platform for the Rapid Detection of Escherichia coli O157:H7 in Milk.

Foodborne illnesses are a public health concern in the United States and worldwide. Recent outbreaks of Escherichia coli O157:H7 have brought to light the need for improved ways to detect foodborne pathogens and minimize serious outbreaks. Unfortunately, current methods for the detection of foodborne pathogens are time intensive and complex. In this study, we designed a spot immunoassay that uses a UCON-potassium phosphate salt aqueous two-phase system (ATPS) for the preconcentration of O157:H7. This platform was tested with samples of O157:H7 spiked in phosphate-buffered saline and milk. The ATPS was found to improve the detection limit of the spot test, yielding detection at 106 cfu/mL within 30 min. This is the first known application of ATPSs to spot immunoassays. Moreover, detection was successfully achieved without upstream processing or dilution of the sample prior to testing, thereby further simplifying the detection process. This technology's ease of use, sensitivity, and short time to result highlight its potential to advance the spot test as a viable diagnostic tool for foodborne pathogens.

Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery.

We demonstrate for the first time the application of an endoscopic fluorescence lifetime imaging microscopy (FLIM) system to the intraoperative diagnosis of glioblastoma multiforme (GBM). The clinically compatible FLIM prototype integrates a gated (down to 0.2 ns) intensifier imaging system with a fiber-bundle (fiber image guide of 0.5 mm diameter, 10,000 fibers with a gradient index lens objective 0.5 NA, and 4 mm field of view) to provide intraoperative access to the surgical field. Experiments conducted in three patients undergoing craniotomy for tumor resection demonstrate that FLIM-derived parameters allow for delineation of tumor from normal cortex. For example, at 460±25-nm wavelength band emission corresponding to NADH/NADPH fluorescence, GBM exhibited a weaker fluorescence intensity (35% less, p-value<0.05) and a longer lifetime τGBM-Amean=1.59±0.24 ns than normal cortex τNC-Amean=1.28±0.04 ns (p-value<0.005). Current results demonstrate the potential use of FLIM as a tool for image-guided surgery of brain tumors.