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.

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 ).

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).

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.

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.

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.

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.

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.

Adapting Index/Partner Services for the Treatment of Chlamydia Among Young African American Men in a Community Screening Program.

BACKGROUND: Screening for asymptomatic Chlamydia trachomatis (Ct) among men has not been recommended because feasibility and efficacy are unknown. Check It is a seek-test-treat community-based Ct screening program for African American men who have sex with women and who are 15 to 24 years of age. This is an evaluation of adaptations made to the program aimed at improving index/partner notification and treatment rates. METHODS: The original Check It intervention included free testing and treatment, contact tracing performed by a third party, expedited index therapy, and expedited partner therapy via pharmacy pickup. The intervention was adapted after a series of in-depth interviews eliciting information to refine the program. Changes included continuity of testing, notification, and treatment by the same staff; expanded hours; and patient-delivered partner therapy with a medication mail-delivery option. Rates of index male and partner treatment were compared using log-binomial models and generalized estimating equations. RESULTS: Men in the adapted intervention (n = 85) were more likely than men in the original intervention (n = 99) to be contacted (relative risk [RR], 1.14; 95% confidence interval [CI], 1.02-1.27), make a treatment plan (RR, 1.14; 95% CI, 1.01-1.27), and complete treatment (RR, 1.45; 95% CI, 1.20-1.75). Female sexual partners were significantly more likely to complete treatment in postadaptation (n = 153) compared with preadaptation (n = 161; RR, 3.02; 95% CI, 1.81-5.05). CONCLUSIONS: Compared with third-party notification and expedited index therapy/expedited partner therapy available by pharmacy pickup only, patient-delivered partner therapy with mail-delivery option, staff available at nontraditional hours, and staff continuity across testing, notification, and treatment significantly improved index and partner treatment completion.

The role of contraception in preventing HIV-positive births: global estimates and projections.

BACKGROUND: Meeting the contraceptive needs of women living with HIV (WLHIV) has primary health benefits for women, in addition to being a key element to prevent mother-to-child HIV transmission. This analysis will estimate the current number of infant HIV infections prevented by contraception in the era of increased HIV treatment coverage and; 2) model the additional HIV benefits of preventing unintended births to WLHIV. METHODS: Secondary data analysis was conducted using publicly available data from the United Nations Programme on HIV/AIDS (UNAIDS) and Population Division, Demographic Health Surveys, and peer-review literature. National data from 70 countries, that had a UNAIDS estimate for the number of WLHIV nationally, were combined into country-level models. Models estimated the current number of infant HIV infections averted by contraception annually and potentially averted if unintended births to WLHIV were prevented. Estimates take into account pregnancy and live birth rates, contraceptive coverage, contraceptive method mix and failure rates, and HIV treatment coverage during pregnancy to prevent mother to child transmission. RESULTS: Contraception use among WLHIV prevents an estimated 43,559 new infant HIV infections annually across 70 countries. Countries with the largest number of infant infections averted by contraception included South Africa (9441), Nigeria (4195), Kenya (3508), Zimbabwe (2586), and India (2145). Preventing unintended births to WLHIV could avert an additional 43,768 new infant infections per year, with the greatest potential gains to be made in South Africa (12,036), Nigeria (2770), Uganda (2552), and the Democratic Republic of the Congo (2324). CONCLUSIONS: Contraception continues to play an integral role in global HIV prevention efforts in the era of increasing HIV treatment coverage, especially in sub-Saharan Africa. Broad contraceptive availability, increased contraceptive voluntarism and method mix are key components to preventing unintended births and ending new infant HIV infections worldwide.

Excitation-Wavelength-Dependent Photoinduced Electron Transfer in a π-Conjugated Diblock Oligomer.

Control of photoinduced electron transfer through selective excitation of a π-conjugated diblock oligomeric system featuring tetrathiophene (T4) and tetra(phenylene ethynylene) (PE4) donor blocks capped with a naphthalene diimide (NDI) acceptor (T4PE4NDI) is demonstrated. Each π-conjugated oligomeric segment has its own discrete ionization potential, electron affinity, and optical band gap which provides an absorption profile that has specific wavelengths that offer selective excitation of the PE4 and T4 blocks. Therefore, T4PE4NDI can be selectively excited to form a charge-separated state via ultrafast photoinduced electron transfer from the PE4 segment to NDI when excited at 370 nm, but it does not produce a charge-separated state when excited at 420 nm (T4). Picosecond transient absorption techniques were performed to probe the excited-state dynamics, revealing ultrafast charge separation (∼4 ps) occurring from the PE4 segment to NDI when excited at 370 nm, followed by delocalization of the hole over the T4 segment. On the contrary, electron transfer is suppressed with excitation at longer wavelengths (≥420 nm), where the spectrum is dominated by the T4 unit. The rate of electron transfer and charge recombination was investigated versus the length of the PE bridge unit in oligomers featuring zero and two PE units (T4NDI and T4PE2NDI). The rate of charge recombination decreases from 1.2 × 1011 to 1.0 × 109 s-1 with increasing bridge length between the T4 and NDI components (T4NDI to T4PE4NDI). Furthermore, wavelength-dependent photoinduced electron transfer was not observed in either T4NDI or T4PE2NDI due to an insufficient PEn bridge length. This work demonstrates the ability to use optical wavelength to control photoinduced electron transfer in a fully π-conjugated oligomer.

Fluorescent Charge-Transfer Excited States in Acceptor Derivatized Thiophene Oligomers.

A family of thiophene oligomers with lengths of 3, 4, 5, 6, and 8 units were synthesized and end-capped with a strongly coupled naphthalimide acceptor (TnNIF) which produces an emissive intramolecular charge-transfer state. A thorough photophysical study was performed on the oligomers including UV-vis absorption, fluorescence, and picosecond transient absorption spectroscopy to investigate the effect of thiophene oligomer length/donor strength and solvent polarity on the intramolecular charge-transfer properties. In hexane, the TnNIF compounds behave in a manner similar to that of oligothiophenes as fluorescence from a local singlet excited state and intersystem crossing to the triplet state dominates the excited-state dynamics. Interestingly, the excited-state dynamics become much more complicated with increasing solvent polarity, from ether to acetone, where emission from a charge-transfer state (δ+TnNIF-δ) and quenching from a charge-separated state (•+TnNIF-•) become competitive. A mechanism is proposed that consists of a four-state diagram including a locally excited singlet state (1TnNIF), a triplet state (3TnNIF), an emissive charge-transfer state, and a nonemissive charge-separated state. The population of each of these states is highly dependent on both the thiophene oligomer length and solvent polarity which results in a mixture of excited states.

Free Energy Dependence of Photoinduced Electron Transfer in Octathiophene-Diimide Dyads.

Donor-acceptor dyads consisting of octathiophene (T8) paired with three (di)imide acceptors (naphthalene diimide (NDI), benzene diimide (BDI), and naphthalimide (NI)) were synthesized and probed for their photoinduced forward electron transfer (ET) and charge recombination kinetics by using ultrafast transient absorption (TA) spectroscopy. The three acceptors have different electron affinities, leading to variation in the energy of the charge-separated state and the driving force (ΔG) for forward ET and charge recombination. Analysis of the TA spectra and kinetics allows assignment of rates for forward ET and charge recombination for each of the oligomers. Electrochemistry and photoluminescence spectroscopy are used to determine the ΔG values for the ET processes. For two of the oligomers (T8NDI and T8BDI), the rates for forward ET and charge recombination are very rapid (k > 3 × 1010 s-1). By contrast, for the third oligomer (T8NI), the rates for both processes are considerably slower (k < 5 × 109 s-1). Analysis of the rate/free energy correlation for the series of oligomers reveals generally good agreement with the Marcus semiclassical theory. In all of the oligomers, the ET reactions are nonadiabatic, in part, due to weak coupling caused by out-of-plane twisting of the phenylene spacer that lies between the T8 segment and the (di)imide acceptors. The rapid ET dynamics for T8NDI and T8BDI are explained as arising due to the processes occurring near the barrierless region (-ΔG ≈ λ) or slightly into the Marcus inverted region (-ΔG > λ). The slower dynamics for T8NI are explained as arising because the forward ET is weakly exothermic, whereas charge recombination is deep into the inverted region. This study is the first to produce experimental results that match a full Marcus bell-shaped curve with ET rates in the normal, barrrierless, and inverted regions in dyads based on a π-conjugated oligomer donor.

Drug Overdose, Loss of Consciousness, and Compartment Syndrome: A Life-Threatening Combination.

Acute extremity compartment syndrome is considered an orthopedic emergency that has serious consequences if a correct diagnosis is not made rapidly. Patients who lose consciousness due to a drug overdose are known to collapse onto their extremities. The limbs are compressed for hours, placing them at an increased risk for acute extremity compartment syndrome and its sequelae. Compartment syndrome due to a compression of a limb from loss of consciousness secondary to drug overdose, presents unique issues to health care providers. In the setting of overdose compartment syndrome, it is similar to the more common traumatic type of compartment syndrome with respect to the pathophysiology, diagnosis and treatment. However, it differs in relation to the muscles affected, physical assessment strategy, and accurately determining the amount of the time from onset of injury to the presentation of symptoms. The purpose of this article is to facilitate emergency department nurses' understanding of the complexities of overdose compartment syndrome, combined with the importance of early recognition of the condition. In addition, the authors review the pathophysiology, the traditional and innovative diagnostic techniques, and the current treatment options available for overdose compartment syndrome.

HIV-1 Tat and opioids act independently to limit antiretroviral brain concentrations and reduce blood-brain barrier integrity.

Poor antiretroviral penetration may contribute to human immunodeficiency virus (HIV) persistence within the brain and to neurocognitive deficits in opiate abusers. To investigate this problem, HIV-1 Tat protein and morphine effects on blood-brain barrier (BBB) permeability and drug brain penetration were explored using a conditional HIV-1 Tat transgenic mouse model. Tat and morphine effects on the leakage of fluorescently labeled dextrans (10-, 40-, and 70-kDa) into the brain were assessed. To evaluate effects on antiretroviral brain penetration, Tat+ and Tat- mice received three antiretroviral drugs (dolutegravir, abacavir, and lamivudine) with or without concurrent morphine exposure. Antiretroviral and morphine brain and plasma concentrations were determined by LC-MS/MS. Morphine exposure, and, to a lesser extent, Tat, significantly increased tracer leakage from the vasculature into the brain. Despite enhanced BBB breakdown evidenced by increased tracer leakiness, morphine exposure led to significantly lower abacavir concentrations within the striatum and significantly less dolutegravir within the hippocampus and striatum (normalized to plasma). P-glycoprotein, an efflux transporter for which these drugs are substrates, expression and function were significantly increased in the brains of morphine-exposed mice compared to mice not exposed to morphine. These findings were consistent with lower antiretroviral concentrations in brain tissues examined. Lamivudine concentrations were unaffected by Tat or morphine exposure. Collectively, our investigations indicate that Tat and morphine differentially alter BBB integrity. Morphine decreased brain concentrations of specific antiretroviral drugs, perhaps via increased expression of the drug efflux transporter, P-glycoprotein.

Impact of Medicaid Expansion on Access to Opioid Analgesic Medications and Medication-Assisted Treatment.

OBJECTIVES: To assess the impact of the expansion of Medicaid eligibility in the United States on the opioid epidemic, as measured through increased access to opioid analgesic medications and medication-assisted treatment. METHODS: Using Medicaid enrollment and reimbursement data from 2011 to 2016 in all states, we evaluated prescribing patterns of opioids and the 3 Food and Drug Administration-approved medications used in treating opioid use disorders by using 2 statistical models. We used difference-in-differences and interrupted time series models to measure prescribing rates before and after state expansions. RESULTS: Although opioid prescribing per Medicaid enrollee increased overall, we observed no statistical difference between expansion and nonexpansion states. By contrast, per-enrollee rates of buprenorphine and naltrexone prescribing increased more than 200% after states expanded eligibility, while increasing by less than 50% in states that did not expand. Methadone prescribing decreased in all states in this period, with larger decreases in expansion states. CONCLUSIONS: The Medicaid expansion enrolled a population no more likely to be prescribed opioids than the base Medicaid population while significantly increasing uptake of 2 drugs used in medication-assisted treatment.

Mapping the impact of the expanded Mexico City Policy for HIV/ family planning service integration in PEPFAR-supported countries: a risk index.

BACKGROUND: The previously-named Mexico City Policy (MCP) - which prohibited non U.S.-based non-governmental organizations (NGOs) from receiving U.S. family planning (FP) funding if they advocated, provided, counseled, or referred clients for abortions, even with non-U.S. funds - was reinstated and expanded in 2017. For the first time, the expanded MCP (EMCP) applies to HIV funding through the President's Emergency Plan for AIDS Relief (PEPFAR) in addition to FP funding. Previous, and more limited, iterations of the policy forced clinic closures and decreased contraceptive access, prompting the need to examine where and how the EMCP may impact FP/HIV service integration. METHODS: The likelihood of FP/HIV service de-integration under the EMCP was quantified using a composite risk index for 31 PEPFAR-funded countries. The index combines six standardized indicators from publically available sources organized into three sub-indexes: 1) The importance of PEPFAR for in-country service delivery of HIV and FP services; 2) The susceptibility of implementing partners to the EMCP; and 3) The integration of FP/HIV funds and programming through PEPFAR and USAID. RESULTS: Countries with the highest overall risk scores included Zambia (3.3) Cambodia (3.2), Uganda (3.1), South Africa (2.9), Haiti (2.8), Lesotho (2.8), Swaziland (2.1), and Burundi (1.5). Zambia's risk score is driven by sub-index 1, having a high proportion of country HIV expenditures provided by PEPFAR (86.3%). Cambodia and Uganda's scores are driven sub-index 3, with both countries reporting 100% of PEPFAR supported HIV delivery sites were providing integrated FP services in 2017. South Africa's risk score is driven by sub-index 2, where roughly 60% of PEPFAR funding is to non U.S.-based NGOs. Of the countries with the highest risk scores, Swaziland, Lesotho, and South Africa, are also in the top quartile of PEPFAR countries for HIV prevalence and unintended pregnancies among young women. CONCLUSION: This analysis highlights where and why the EMCP may have the greatest impact on FP/HIV service integration. The possible disruption of service integration in countries with generalized HIV epidemics highlights significant risks. Researchers, national governments, and non-U.S. funders can consider these risk factors to help target their responses to the EMCP and mitigate potential harms of the policy.

Photoinduced Electron Transfer in Naphthalene Diimide End-Capped Thiophene Oligomers.

A series of linear thiophene oligomers containing 4, 6, 8, 10, and 12 thienylene units were synthesized and end-capped with naphthalene diimide (NDI) acceptors with the objective to study the effect of oligomer length on the dynamics of photoinduced electron transfer and charge recombination. The synthetic work afforded a series of nonacceptor-substituted thiophene oligomers, Tn, and corresponding NDI end-capped series, TnNDI2 (where n is the number of thienylene repeat units). This paper reports a complete photophysical characterization study of the Tn and TnNDI2 series by using steady-state absorption, fluorescence, singlet oxygen sensitized emission, two-photon absorption, and nanosecond-microsecond transient absorption spectroscopy. The thermodynamics of photoinduced electron transfer and charge recombination in the TnNDI2 oligomers were determined by analysis of photophysical and electrochemical data. Excitation of the Tn oligomers gives rise to efficient fluorescence and intersystem crossing to a triplet excited state that is easily observed by nanosecond transient absorption spectroscopy. Bimolecular photoinduced electron transfer from the triplet states, 3Tn*, to N,N-dimethylviologen (MV2+) occurs, and by using microsecond transient absorption it is possible to assign the visible region absorption spectra for the one electron oxidized (polaron) states, Tn+•. The fluorescence of the TnNDI2 oligomers is quenched nearly quantitatively, and no long-lived transients are observed by nanosecond transient absorption. These findings suggest that rapid photoinduced electron transfer and charge recombination occurs, NDI-1(Tn)*-NDI → NDI-(Tn)+•-NDI-• → NDI-Tn-NDI. Preliminary femtosecond-picosecond transient absorption studies on T4NDI2 reveal that both forward electron transfer and charge recombination occur with k > 1011 s-1, consistent with both reactions being nearly activationless. Analysis with semiclassical electron transfer theory suggests that both reactions occur at near the optimum driving force where -ΔG ∼ λ.