Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI). Morphine exposure uniquely decreased antiretroviral concentrations in anterior cerebral (primary motor and somatosensory) cortices, corpus collosum (anterior forceps), caudoputamen, nucleus accumbens, and posterior regions including the hippocampus, corpus callosum (main body), cerebral cortex (somatosensory and auditory cortices), thalamus, and hypothalamus. Interestingly, male mice experienced greater morphine-associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in antiretroviral concentrations were linked with inflammation in astroglia, assessed through the measurement of astroglial activation using glial fibrillary acidic protein (GFAP) as a marker. Alterations in antiretroviral concentrations co-registering with areas of astroglial activation exhibited sex-specific treatment differences. This study highlights the intricate interplay between HIV, opioids, and antiretroviral drugs within the CNS, elucidating distinct regional and sex variations in responsiveness. Our findings emphasize the identification of vulnerabilities within the neural landscape and underscore the necessity of carefully monitoring opioid use to maintain the efficacy of antiretroviral therapies.

Preventable trauma deaths in the Western Cape of South Africa: A consensus-based panel review.

Injury causes 4.4 million deaths worldwide annually. 90% of all injury-related deaths occur in low-and-middle income countries. Findings from expert-led trauma death reviews can inform strategies to reduce trauma deaths. A cohort of trauma decedents was identified from an on-going study in the Western Cape Province of South Africa. For each case, demographics, injury characteristics, time and location of death and postmortem findings were collected. An expert multidisciplinary panel of reviewed each case, determined preventability and made recommendations for improvement. Analysis of preventable and non-preventable cases was performed using Chi-square, Fisher's exact, and Wilcoxon signed rank tests. A rapid qualitative analysis of recommendations was conducted and descriptively summarized. 138 deaths (48 deceased-on-scene and 90 pre- or in-hospital deaths) were presented to 23 panelists. Overall, 46 (33%) of deaths reviewed were considered preventable or potentially preventable. Of all pre- and in-hospital deaths, late deaths (>24 hours) were more frequently preventable (22, 56%) and due to multi-organ failure and sepsis, compared to early deaths (≤24 hours) with 32 (63%) that were non-preventable and due to central nervous system injury and haemorrhage. 45% of pre and in-hospital deaths were preventable or potentially preventable. The expert panel recommended strengthening community based primary prevention strategies for reducing interpersonal violence alongside health system improvements to facilitate high quality care. For the health system the panel's key recommendations included improving team-based care, adherence to trauma protocols, timely access to radiology, trauma specialists, operative and critical care.

Fentanyl dysregulates neuroinflammation and disrupts blood-brain barrier integrity in HIV-1 Tat transgenic mice.

Opioid overdose deaths have dramatically increased by 781% from 1999 to 2021. In the setting of HIV, opioid drug abuse exacerbates neurotoxic effects of HIV in the brain, as opioids enhance viral replication, promote neuronal dysfunction and injury, and dysregulate an already compromised inflammatory response. Despite the rise in fentanyl abuse and the close association between opioid abuse and HIV infection, the interactive comorbidity between fentanyl abuse and HIV has yet to be examined in vivo. The HIV-1 Tat-transgenic mouse model was used to understand the interactive effects between fentanyl and HIV. Tat is an essential protein produced during HIV that drives the transcription of new virions and exerts neurotoxic effects within the brain. The Tat-transgenic mouse model uses a glial fibrillary acidic protein (GFAP)-driven tetracycline promoter which limits Tat production to the brain and this model is well used for examining mechanisms related to neuroHIV. After 7 days of fentanyl exposure, brains were harvested. Tight junction proteins, the vascular cell adhesion molecule, and platelet-derived growth factor receptor-ß were measured to examine the integrity of the blood brain barrier. The immune response was assessed using a mouse-specific multiplex chemokine assay. For the first time in vivo, we demonstrate that fentanyl by itself can severely disrupt the blood-brain barrier and dysregulate the immune response. In addition, we reveal associations between inflammatory markers and tight junction proteins at the blood-brain barrier.

High-Performance Wearable Organic Photodetectors by Molecular Design and Green Solvent Processing for Pulse Oximetry and Photoplethysmography.

White-light detection from the visible to the near-infrared region is central to many applications such as high-speed cameras, autonomous vehicles, and wearable electronics. While organic photodetectors (OPDs) are being developed for such applications, several challenges must be overcome to produce scalable high-detectivity OPDs. This includes issues associated with low responsivity, narrow absorption range, and environmentally friendly device fabrication. Here, an OPD system processed from 2-methyltetrahydrofuran (2-MeTHF) sets a record in light detectivity, which is also comparable with commercially available silicon-based photodiodes is reported. The newly designed OPD is employed in wearable devices to monitor heart rate and blood oxygen saturation using a flexible OPD-based finger pulse oximeter. In achieving this, a framework for a detailed understanding of the structure-processing-property relationship in these OPDs is also developed. The bulk heterojunction (BHJ) thin films processed from 2-MeTHF are characterized at different length scales with advanced techniques. The BHJ morphology exhibits optimal intermixing and phase separation of donor and acceptor moieties, which facilitates the charge generation and collection process. Benefitting from high charge carrier mobilities and a low shunt leakage current, the newly developed OPD exhibits a specific detectivity of above 1012  Jones over 400-900 nm, which is higher than those of reference devices processed from chlorobenzene and ortho-xylene.

Additive-free molecular acceptor organic solar cells processed from a biorenewable solvent approaching 15% efficiency.

We report on the use of molecular acceptors (MAs) and donor polymers processed with a biomass-derived solvent (2-methyltetrahydrofuran, 2-MeTHF) to facilitate bulk heterojunction (BHJ) organic photovoltaics (OPVs) with power conversion efficiency (PCE) approaching 15%. Our approach makes use of two newly designed donor polymers with an opened ring unit in their structures along with three molecular acceptors (MAs) where the backbone and sidechain were engineered to enhance the processability of BHJ OPVs using 2-MeTHF, as evaluated by an analysis of donor-acceptor (D-A) miscibility and interaction parameters. To understand the differences in the PCE values that ranged from 9-15% as a function of composition, the surface, bulk, and interfacial BHJ morphologies were characterized at different length scales using atomic force microscopy, grazing-incidence wide-angle X-ray scattering, resonant soft X-ray scattering, X-ray photoelectron spectroscopy, and 2D solid-state nuclear magnetic resonance spectroscopy. Our results indicate that the favorable D-A intermixing that occurs in the best performing BHJ film with an average domain size of ∼25 nm, high domain purity, uniform distribution and enhanced local packing interactions - facilitates charge generation and extraction while limiting the trap-assisted recombination process in the device, leading to high effective mobility and good performance.

Application of infrared matrix-assisted laser desorption electrospray ionization mass spectrometry for morphine imaging in brain tissue.

Here, we present a method developed for the analysis of spatial distributions of morphine in mouse brain tissue using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to a Q Exactive Plus mass spectrometer. The method is also capable of evaluating spatial distributions of the antiretroviral drug abacavir. To maximize sensitivity to morphine, we analyze various Orbitrap mass spectrometry acquisition modes utilizing signal abundance and frequency of detection as evaluation criteria. We demonstrate detection of morphine in mouse brain and establish that the selected ion monitoring mode provides 2.5 times higher sensitivity than the full-scan mode. We find that distributions of morphine and abacavir are highly correlated with the Pearson correlation coefficient R = 0.87. Calibration showed that instrument response is linear up to 40 pg/mm2 (3.8 µg/g of tissue).

Elucidating Design Rules toward Enhanced Solid-State Charge Transport in Oligoether-Functionalized Dioxythiophene-Based Alternating Copolymers.

This study investigates the solid-state charge transport properties of the oxidized forms of dioxythiophene-based alternating copolymers consisting of an oligoether-functionalized 3,4-propylenedioxythiophene (ProDOT) copolymerized with different aryl groups, dimethyl ProDOT (DMP), 3,4-ethylenedioxythiophene (EDOT), and 3,4-phenylenedioxythiophene (PheDOT), respectively, to yield copolymers P(OE3)-D, P(OE3)-E, and P(OE3)-Ph. At a dopant concentration of 5 mM FeTos3, the electrical conductivities of these copolymers vary significantly (ranging between 9 and 195 S cm-1) with the EDOT copolymer, P(OE3)-E, achieving the highest electrical conductivity. UV-vis-NIR and X-ray spectroscopies show differences in both susceptibility to oxidative doping and extent of oxidation for the P(OE3) series, with P(OE3)-E being the most doped. Wide-angle X-ray scattering measurements indicate that P(OE3)-E generally demonstrates the lowest paracrystallinity values in the series, as well as relatively small π-π stacking distances. The significant (i.e., order of magnitude) increase in electrical conductivity of doped P(OE3)-E films versus doped P(OE3)-D or P(OE3)-Ph films can therefore be attributed to P(OE3)-E exhibiting both the highest carrier ratios in the P(OE3) series, along with good π-π overlap and local ordering (low paracrystallinity values). Furthermore, these trends in the extent of doping and paracrystallinity are consistent with the reduced Fermi energy level and transport function prefactor parameters calculated using the semilocalized transport (SLoT) model. Observed differences in carrier ratios at the transport edge (ct) and reduced Fermi energies [η(c)] suggest a broader electronic band (better overlap and more delocalization) for the EDOT-incorporating P(OE3)-E polymer relative to P(OE3)-D and P(OE3)-Ph. Ultimately, we rationalize improvements in electrical conductivity due to microstructural and doping enhancements caused by EDOT incorporation, a structure-property relationship worth considering in the future design of highly electrically conductive systems.

Combined Endoscopic Robotic Surgery for Complex Colon Polyps.

BACKGROUND: Combined endoscopic robotic surgery is a surgical technique that modifies traditional endoscopic laparoscopic surgery with robotic assistance to aid in the removal of complex colonic polyps. This technique has been described in the literature but lacks patient follow-up data. OBJECTIVE: This study aimed to evaluate the safety and outcomes of combined endoscopic robotic surgery. DESIGN: A retrospective review of a prospective database. SETTING: East Jefferson General Hospital, Metairie, Louisiana. PATIENTS: Ninety-three consecutive patients who underwent combined endoscopic robotic surgery from March 2018 to October 2021 were included in the study. MAIN OUTCOME MEASURES: Operative time, intraoperative complication, 30-day postoperative complication, hospital length of stay, and follow-up pathology report results were the main outcome measures. RESULTS: Combined endoscopic robotic surgery was completed in 88 of 93 participants (95%). Among the 88 participants who completed combined endoscopic robotic surgery, the average age was 66 years (SD = 10), BMI was 28.8 kg/m 2 (SD = 6), and history of previous abdominal surgeries was 1 (SD = 1). Median operative time was 72 minutes (range, 31-184 minutes) and polyp size was 40 mm (range, 5-180 mm). The most common polyp locations were the cecum, ascending colon, and transverse colon (31%, 28%, 25%). Pathology mainly demonstrated tubular adenoma (76%). Data on 40 patients who underwent follow-up colonoscopy were available. The average follow-up time was 7 months (range, 3-22 months). One patient (2.5%) had polyp recurrence at the resection site. LIMITATIONS: Limitations for our study include a lack of randomization and follow-up rate to assess for recurrence. The low compliance rate may be due to procedure cancelations/difficulty scheduling because of changing coronavirus disease 2019 guidelines. CONCLUSIONS: Compared to literature-reported statistics for its laparoscopic counterpart, combined endoscopic robotic surgery was associated with decreased operation times and resection site polyp recurrence. See Video Abstract at http://links.lww.com/DCR/C208 . CIRUGA ROBTICA ENDOSCPICA COMBINADA PARA PLIPOS DE COLON COMPLEJOS: ANTECEDENTES:La cirugía robótica endoscópica combinada es una técnica quirúrgica que modifica la cirugía laparoscópica endoscópica tradicional con asistencia robótica para ayudar en la extracción de pólipos colónicos complejos. Esta técnica está previamente descrita en la literatura, pero carece de datos de seguimiento de los pacientes.OBJETIVO:Evaluar la seguridad y los resultados de la cirugía robótica endoscópica combinada.DISEÑO:Revisión retrospectiva de una base de datos prospectiva.AJUSTE:Hospital General East Jefferson, Metairie LouisianaPACIENTES:Noventa y tres pacientes consecutivos y sometidos a cirugía robótica endoscópica combinada por un solo cirujano colorrectal desde marzo de 2018 hasta octubre de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Tiempo operatorio, complicación intraoperatoria, complicación posoperatoria a los 30 días, duración de la estancia hospitalaria y resultados del informe patológico de seguimiento.RESULTADOS:La cirugía robótica endoscópica combinada se completó en 88 de 93 (95%). Entre los 88 participantes que completaron la cirugía robótica endoscópica combinada, la edad promedio fue de 66 años (desviación estándar = 10), índice de masa corporal de 28,8 (desviación estándar = 6) y el historial de cirugías abdominales previas de 1 (desviación estándar = 1). La mediana del tiempo operatorio y el tamaño de los pólipos fueron 72 minutos (rango 31-184 minutos) y 40 milímetros (rango 5-180 milímetros), respectivamente. Las ubicaciones de pólipos más comunes fueron el ciego, colon ascendente y transverso (31%, 28%, 25%). La patología demostró principalmente adenoma tubular (76%). Los datos de 40 pacientes sometidos a una colonoscopia de seguimiento estaban disponibles. El tiempo medio de seguimiento fue de 7 meses (rango 3-22 meses). Un paciente (2,5%) presentó recurrencia polipoidea en el sitio de resección.LIMITACIONES:Las limitaciones de nuestro estudio incluyeron la falta de aleatorización y la tasa de seguimiento para evaluar la recurrencia. La baja tasa de seguimiento puede deberse a la renuencia del paciente en hacerse una colonoscopia o cancelaciones de procedimientos por la dificultad para programar debido a cambios de COVID-19.CONCLUSIÓN:En comparación con las estadísticas reportadas en la literatura para su contraparte laparoscópica, la cirugía robótica endoscópica combinada se asoció con reducción en tiempos de operación y recurrencia de pólipos en el sitio de resección. Consulte Video Resumen en http://links.lww.com/DCR/C208 . (Traducción - Dr. Fidel Ruiz Healy ).

Delays in fibrosis staging reduce the likelihood of achieving hepatitis C treatment and cure.

BACKGROUND: Updated 2021 hepatitis C virus (HCV) treatment guidelines no longer recommend fibrosis staging for treatment-naïve patients without cirrhosis; however, numerous US state Medicaid plans continue to restrict initiation of HCV therapy by fibrosis stage. The study objective was to determine whether delays from HCV diagnosis to fibrosis staging impact the likelihood of initiating/completing HCV treatment and achieving sustained virologic response (SVR). METHODS: A retrospective cohort study was performed among patients diagnosed with chronic HCV by an urban US emergency department who subsequently underwent fibrosis staging. Time elapsed from HCV diagnosis to hepatic fibrosis staging was evaluated on the likelihood of treatment initiation, treatment completion and SVR. RESULTS: Among fibrosis staging modalities, hepatic ultrasounds occurred more quickly following HCV diagnosis (3.5 months, IQR = 12.4 months), compared to FibroSure (8.5 months, IQR = 20.4 months) and FibroScan (9.9 months, IQR = 18.0 months) (p<.001). Each six-month delay in fibrosis staging decreased the likelihood of initiating treatment by 5% (adjusted relative risk (aRR)=0.95; 95% confidence interval (CI)=0.91-0.998; p=.04) and the likelihood of SVR by 7% (aRR = 0.93; 95% CI = 0.87-0.995; p=.04) after adjusting for insurance, race/ethnicity and history of HIV testing. CONCLUSIONS: Delays in hepatitis fibrosis staging were significantly associated with decreased likelihood of HCV treatment initiation and SVR.

Importance of Electric-Field-Independent Mobilities in Thick-Film Organic Solar Cells.

In organic solar cells (OSCs), a thick active layer usually yields a higher photocurrent with broader optical absorption than a thin active layer. In fact, a ∼300 nm thick active layer is more compatible with large-area processing methods and theoretically should be a better spot for efficiency optimization. However, the bottleneck of developing high-efficiency thick-film OSCs is the loss in fill factor (FF). The origin of the FF loss is not clearly understood, and there a direct method to identify photoactive materials for high-efficiency thick-film OSCs is lacking. Here, we demonstrate that the mobility field-dependent coefficient is an important parameter directly determining the FF loss in thick-film OSCs. Simulation results based on the drift-diffusion model reveal that a mobility field-dependent coefficient smaller than 10-3 (V/cm)-1/2 is required to maintain a good FF in thick-film devices. To confirm our simulation results, we studied the performance of two ternary bulk heterojunction (BHJ) blends, PTQ10:N3:PC71BM and PM6:N3:PC71BM. We found that the PTQ10 blend film has weaker field-dependent mobilities, giving rise to a more balanced electron-hole transport at low fields. While both the PM6 blend and PTQ10 blend yield good performance in thin-film devices (∼100 nm), only the PTQ10 blend can retain a FF = 74% with an active layer thickness of up to 300 nm. Combining the benefits of a higher JSC in thick-film devices, we achieved a PCE of 16.8% in a 300 nm thick PTQ10:N3:PC71BM OSC. Such a high FF in the thick-film PTQ10 blend is also consistent with the observation of lower charge recombination from light-intensity-dependent measurements and lower energetic disorder observed in photothermal deflection spectroscopy.

Anal and Oral Sex Behaviors Among Young Black Men Who Have Vaginal Sex: Evidence of the Need for Extragenital Testing for Chlamydia and Gonorrhea.

BACKGROUND: Unprotected oral and anal sex may result in extragenital sexually transmitted infections. The purposes of this study were to describe sexual behaviors, barrier use, and chlamydia/gonorrhea (Ct/GC) positivity among young Black men who have sex with women, and to examine the potential influence of extragenital infections on genital infections. METHODS: Young Black men who had vaginal sex were screened for Ct/GC in New Orleans, LA, from August 14, 2019, to February 29, 2020. Audio/computer-assisted self-interviews were used to collect data on demographics and sexual behaviors. χ2 /Fisher exact or t test/Wilcoxon rank tests were used to assess differences in behaviors by Ct/GC positivity. RESULTS: Among 373 men studied, 619 female partnerships were reported in the past 2 months. Vaginal sex was reported in all partnerships per study protocol, receiving fellatio in 42.7%, performing cunnilingus in 35.7%, and penile-anal sex in 5.9%. Although 31.4% of the men consistently used condoms for vaginal sex with all partners, consistent barrier use was low during cunnilingus (0.5%) and fellatio (5.1%). Urethral infection rates among all men in the sample were 12.6% for Ct and 1.6% for GC. There was no significant difference in Ct/GC rates between those using and not using condoms consistently during vaginal sex ( P = 0.38). CONCLUSIONS: Unprotected oral sex with female partners was common. The high rate of genital infection among men who used condoms consistently for vaginal sex suggests that oral infections could be serving as a reservoir of genital infection. Testing at all sites of exposure for youth who engage in heterosexual sex is merited.

Independent actions by HIV-1 Tat and morphine to increase recruitment of monocyte-derived macrophages into the brain in a region-specific manner.

Despite advances in the treatment of human immunodeficiency virus (HIV), approximately one-half of people infected with HIV (PWH) experience neurocognitive impairment. Opioid use disorder (OUD) can exacerbate the cognitive and pathological changes seen in PWH. HIV increases inflammation and immune cell trafficking into the brain; however, less is known about how opioid use disorder affects the recruitment of immune cells. Accordingly, we examined the temporal consequences of HIV-1 Tat and/or morphine on the recruitment of endocytic cells (predominantly perivascular macrophages and microglia) in the dorsal striatum and hippocampus by infusing multi-colored, fluorescently labeled dextrans before and after exposure. To address this question, transgenic mice that conditionally expressed HIV-1 Tat (Tat+), or their control counterparts (Tat-), received three sequential intracerebroventricular (i.c.v.) infusions of Cascade Blue-, Alexa Fluor 488-, and Alexa Fluor 594-labeled dextrans, respectively infused 1 day before, 1-day after, or 13-days after morphine and/or Tat exposure. At the end of the study, the number of cells labeled with each fluorescent dextran were counted. The data demonstrated a significantly higher influx of newly-labeled cells into the perivascular space than into the parenchyma. In the striatum, Tat or morphine exposure increased the number of endocytic cells in the perivascular space, while only morphine increased the recruitment of endocytic cells into the parenchyma. In the hippocampus, morphine (but not Tat) increased the influx of dextran-labeled cells into the perivascular space, but there were too few labeled cells within the hippocampal parenchyma to analyze. Collectively, these data suggest that HIV-1 Tat and morphine act independently to increase the recruitment of endocytic cells into the brain in a region-specific manner.

Iron(III) Dopant Counterions Affect the Charge-Transport Properties of Poly(Thiophene) and Poly(Dialkoxythiophene) Derivatives.

This study investigates the charge-transport properties of poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly(ProDOT-alt-biEDOT) (PE2) films doped with a set of iron(III)-based dopants and as a function of dopant concentration. X-ray photoelectron spectroscopy measurements show that doping P3HT with 12 mM iron(III) solutions leads to similar extents of oxidation, independent of the dopant anion; however, the electrical conductivities and Seebeck coefficients vary significantly (5 S cm-1 and + 82 µV K-1 with tosylate and 56 S cm-1 and +31 µV K-1 with perchlorate). In contrast, PE2 thermoelectric transport properties vary less with respect to the iron(III) anion chemistry, which is attributed to PE2 having a lower onset of oxidation than P3HT. Consequentially, PE2 doped with 12 mM iron(III) perchlorate obtained an electrical conductivity of 315 S cm-1 and a Seebeck coefficient of + 7 µV K-1. Modeling these thermoelectric properties with the semilocalized transport (SLoT) model suggests that tosylate-doped P3HT remains mostly in the localized transport regime, attributed to more disorder in the microstructure. In contrast perchlorate-doped P3HT and PE2 films exhibited thermally deactivated electrical conductivities and metal-like transport at high doping levels over limited temperature ranges. Finally, the SLoT model suggests that PE2 has the potential to be more electrically conductive than P3HT due to PE2's ability to achieve higher extents of oxidation and larger shifts in the reduced Fermi energy levels.

Closing the hepatitis C treatment gap: United States strategies to improve retention in care.

The hepatitis C virus (HCV) treatment landscape is shifting given the advent of direct-acting antivirals and a global call to action by the World Health Organization. Eliminating HCV is now an issue of healthcare delivery. Treatment is limited by the complexity of the HCV care continuum, expensive therapy and competing health burdens experienced by an underserved HCV population. The objective of this literature review was to assess strategies to improve retention in HCV care, with particular focus on those implemented in the United States. We identified barriers in HCV care retention and propose solutions to increase HCV treatment delivery. The following recommendations are herein described: improving the cohesion of health services through localized care and integrated case management, expanding the supply of non-specialist HCV treatment providers, leveraging patient navigators and care coordinators, improving adherence through directly observed therapy and reducing cost barriers through value-based payment and pharmaceutical subscription models.

Emergency department versus community screening on hepatitis C follow-up care.

OBJECTIVES: Emergency department (ED) hepatitis C virus (HCV) screening programs are proliferating, and it is unknown whether EDs are more effective than traditional community screening at promoting HCV follow-up care. The objective of this study was to investigate whether patients screened HCV seropositive (HCV+) in the ED are linked to care and retained in treatment more successfully than patients screened HCV+ in the community. METHODS: A retrospective cohort study was performed including patients screened HCV+ at twelve screening facilities in New Orleans, LA from March 1, 2015 to July 31, 2017. Treatment outcomes, including retention and time to follow-up care, were assessed using the HCV continuum of care model. RESULTS: ED patients (n = 3008) were significantly more likely to achieve RNA confirmation (aRR = 1.91, 95% CI = 1.54-2.37), initiate HCV therapy (aRR = 2.23 [1.76-2.83]), complete HCV therapy (aRR = 1.77 [1.40-2.24]), and achieve HCV functional cure (aRR = 2.80 [1.09-7.23]) compared to community-screened patients (n = 322). ED screening was associated with decreased likelihood of fibrosis staging (aRR = 0.65 [0.51-0.82]) and no difference in linkage to specialty care (aRR = 1.03 [0.69-1.53]). In time to follow up, RNA confirmation occurred at faster rates in the ED (aHR = 2.26 [1.86-2.72]), although these patients completed fibrosis staging at slower rates (aHR = 0.49 [0.38-0.63]) than community patients. CONCLUSIONS: Compared to community screening, HCV screening in the ED was associated with higher rates of disease confirmation, treatment initiation/completion, and cure. Our findings provide new evidence that EDs may be the most effective setting to screen patients for HCV to promote follow-up care.

A rapid and robust method for amino acid quantification using a simple N-hydroxysuccinimide ester derivatization and liquid chromatography-ion mobility-mass spectrometry.

The vast majority of mass spectrometry (MS)-based metabolomics studies employ reversed-phase liquid chromatography (RPLC) to separate analytes prior to MS detection. Highly polar metabolites, such as amino acids (AAs), are poorly retained by RPLC, making quantitation of these key species challenging across the broad concentration ranges typically observed in biological specimens, such as cell extracts. To improve the detection and quantitation of AAs in microglial cell extracts, the implementation of a 4-dimethylaminobenzoylamido acetic acid N-hydroxysuccinimide ester (DBAA-NHS) derivatization agent was explored for its ability to improve both analyte retention and detection limits in RPLC-MS. In addition to the introduction of the DBAA-NHS labeling reagent, a uniformly (U) 13C-labeled yeast extract was also introduced during the sample preparation workflow as an internal standard (IS) to eliminate artifacts and to enable targeted quantitation of AAs, as well as untargeted amine submetabolome profiling. To improve method sensitivity and selectivity, multiplexed drift-tube ion mobility (IM) was integrated into the LC-MS workflow, facilitating the separation of isomeric metabolites, and improving the structural identification of unknown metabolites. Implementation of the U-13C-labeled yeast extract during the multiplexed LC-IM-MS analysis enabled the quantitation of 19 of the 20 common AAs, supporting a linear dynamic range spanning up to three orders of magnitude in concentration for microglial cell extracts, in addition to reducing the required cell count for reliable quantitation from 10 to 5 million cells per sample.

Combined endoscopic robotic surgery for complex colonic polyp resection: case series.

BACKGROUND: The study objective was to evaluate combined endoscopic and robotic surgery, a novel surgical technique modifying traditional combined endoscopic laparoscopic surgery through robotic assistance, and characterize a series of patients who underwent the modified operative technique. METHODS: A retrospective case series was performed. The first thirty-seven consecutive patients who underwent combined endoscopic robotic surgery by a single colorectal surgeon from March 2018 to October 2019 were included. Main outcome measures included operative time, intra-operative complication, 30-day post-operative complication, and hospital length of stay. RESULTS: Combined endoscopic and robotic surgery was performed in 37 cases, 32 (86.5%) of which saw the technique through to completion. Median operative room time was 73 min (range 31-184 min). No intraoperative complications occurred and 2 (6.3%) experienced 30-day post-operative complications. Median hospital length of stay was 1.1 days (range 0.2-2.0 days). Median polyp size was 35 mm (range 20-130 mm). Polyps were resected from the following locations: cecum (37.5%), ascending colon (28.1%), transverse colon (21.9%), descending colon (3.1%), sigmoid colon (6.3%), and rectum (3.1%). Pathology demonstrated 77.4% tubular adenoma, 12.9% sessile serrated adenoma, 6.5% dysplasia, and 3.2% signet cell adenocarcinoma. CONCLUSION: Combined endoscopic robotic surgery was associated with decreased operative time, complication rates, and hospital length of stay compared to literature-reported statistics for combined endoscopic laparoscopic surgery. Increased confidence with 3-dimensional visualization and intracorporeal suturing using combined endoscopic and robotic surgery was noted. Additional studies are needed to further define the role of robotics in combined endoscopic surgery.

Current allocations and target apportionment for HIV testing and treatment services for marginalized populations: characterizing PEPFAR investment and strategy.

INTRODUCTION: The United States President's Emergency Plan for AIDS Relief (PEPFAR) is a large bilateral funder of the global HIV response whose policy decisions on key populations (KPs) programming determine the shape of the key populations' response in many countries. Understanding the size and relative share of PEPFAR funds going to KPs and the connection between PEPFAR's targets and resulting programming is crucial for successfully serving key populations. METHODS: Publicly available PEPFAR budgets for key populations' services were assessed by country and geographical region for all 52 countries with budget data in fiscal year (FY) 2020. For the 23 countries which completed a full planning process in FY 2018 and 2019, PEPFAR targets for HIV testing and treatment initiation for key populations were assessed. Expenditures for KP programming were calculated to determine whether shifts in targets translated into programming. Implementing partners were characterized by the level of specialization using the share of assigned targets made up by KPs. The average target per year and implementing partner was calculated for each KP group and indicator. RESULTS: PEPFAR country KP budgets ranged from US$35,000 to $15.2 million, and the proportion of funding to key populations varied by region, with Eastern and Southern African countries having the lowest proportion. Between FY 2018 and 2019, the KP targets for HIV testing and treatment among KPs increased, whereas expenditures on key populations decreased from US$115.4 to $111.0 million. Of the 11 countries with an increase in HIV testing targets, seven had a decrease in KP expenditures. Of the nine countries with an increase in treatment initiation targets, five had a decrease in KP expenditures. The proportion of targets assigned to partners which do not specialize in key populations increased from FY 2018 to 2019. CONCLUSIONS: Current key population policies have not resulted in a tight connection between targets and expenditures. This includes assigning a large proportion of key populations programming to partners who do not specialize in key populations, which may weaken the performance management role of the targets. These results signal that a new approach to key populations programming is needed.

Human Immunodeficiency Virus and Hepatitis C Linkage-to-Care Initiative for New Orleans Residents Experiencing Homelessness During the COVID-19 Pandemic.

BACKGROUND: People experiencing homelessness are disproportionately infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). In response to COVID-19, cities nationwide temporarily housed people experiencing homelessness in unused hotels. One such initiative in New Orleans also enacted a screening, counseling, and linkage-to-care model for HIV and HCV treatment for this temporarily housed population between May and July 2020. METHODS: A nonconcurrent cohort study was performed assessing follow up in the treatment of HIV and HCV for this population. Outcome data were collected on seropositive patients' electronic medical record to assess patient progression through the treatment cascade. RESULTS: Of 102 unhoused residents, 25 (24.5%) tested HCV seropositive. Of the HCV positive 21/25 (84%) were connected to the associated clinic for follow up care and 10 (40%) obtained HCV treatment medication. Furthermore, all 3 patients who tested seropositive for HIV either started or re-initiated antiviral treatment. The greatest barrier to providing medication for the HCV seropositive patients, once care was initiated, was loss-to-follow-up. CONCLUSIONS: Targeting homeless persons living in temporary residences for HCV and HIV screening can be effective at promoting access to care for those infected due to this population's high HCV seropositivity especially significant if the patient has a history of intravenous drug use or is older than 40 years. However, continued outreach strategies are needed to assist patients in retention of care.