Ethanol and caffeine age-dependently alter brain and retinal neurochemical levels without affecting morphology of juvenile and adult zebrafish (Danio rerio).

Adolescent alcohol exposure in humans is predictive of adult development of alcoholism. In rodents, caffeine pre-exposure enhances adult responsiveness to ethanol via a pathway targeted by both compounds. Embryonic exposure to either compound adversely affects development, and both compounds can alter zebrafish behaviors. Here, we evaluate whether co-exposure to caffeine and/or alcohol in adolescence exerts neurochemical changes in retina and brain. Zebrafish (Danio rerio) were given daily 20 min treatments to ethanol (1.5% v/v), caffeine (25-100 mg/L), or caffeine + ethanol for 1 week during mid-late adolescence (53-92 days post fertilization (dpf)) or early adulthood (93-142 dpf). Immediately after exposure, anatomical measurements were taken, including weight, heart rate, pigment density, length, girth, gill width, inner and outer eye distance. Brain and retinal tissue were subsequently collected either (1) immediately, (2) after a short interval (2-4d) following exposure, or (3) after a longer interval that included an acute 1.5% ethanol challenge. Chronic ethanol and/or caffeine exposure did not alter anatomical parameters. However, retinal and brain levels of tyrosine hydroxylase were elevated in fish sacrificed after the long interval following exposure. Protein levels of glutamic acid decarboxylase were also increased, with the highest levels observed in 70-79 dpf fish exposed to caffeine. The influence of ethanol and caffeine exposure on neurochemistry demonstrates specificity of their effects during postembryonic development. Using the zebrafish model to assess neurochemistry relevant to reward and anxiety may inform understanding of the mechanisms that reinforce co-addiction to alcohol and stimulants.

Rapid Emergence and Epidemiologic Characteristics of the SARS-CoV-2 B.1.526 Variant - New York City, New York, January 1-April 5, 2021.

Recent studies have documented the emergence and rapid growth of B.1.526, a novel variant of interest (VOI) of SARS-CoV-2, the virus that causes COVID-19, in the New York City (NYC) area after its identification in NYC in November 2020 (1-3). Two predominant subclades within the B.1.526 lineage have been identified, one containing the E484K mutation in the receptor-binding domain (1,2), which attenuates in vitro neutralization by multiple SARS-CoV-2 antibodies and is present in variants of concern (VOCs) first identified in South Africa (B.1.351) (4) and Brazil (P.1).* The NYC Department of Health and Mental Hygiene (DOHMH) analyzed laboratory and epidemiologic data to characterize cases of B.1.526 infection, including illness severity, transmission to close contacts, rates of possible reinfection, and laboratory-diagnosed breakthrough infections among vaccinated persons. Preliminary data suggest that the B.1.526 variant does not lead to more severe disease and is not associated with increased risk for infection after vaccination (breakthrough infection) or reinfection. Because relatively few specimens were sequenced over the study period, the statistical power might have been insufficient to detect modest differences in rates of uncommon outcomes such as breakthrough infection or reinfection. Collection of timely viral genomic data for a larger proportion of citywide cases and rapid integration with population-based surveillance data would enable improved understanding of the impact of emerging SARS-CoV-2 variants and specific mutations to help guide public health intervention efforts.

Electronic Dose Monitoring Identifies a High-Risk Subpopulation in the Treatment of Drug-resistant Tuberculosis and Human Immunodeficiency Virus.

BACKGROUND: In generalized drug-resistant tuberculosis (DR-TB) human immunodeficiency virus (HIV) epidemics, identifying subpopulations at high risk for treatment failure and loss to care is critically important to improve treatment outcomes and prevent amplification of drug resistance. We hypothesized that an electronic dose-monitoring (EDM) device could empirically identify adherence-challenged patients and that a mixed-methods approach would characterize treatment challenges. METHODS: A prospective study of patients with DR-TB HIV on antiretroviral therapy (ART) initiating bedaquiline-containing regimens in KwaZulu-Natal, South Africa. Separate EDM devices measured adherence for bedaquiline and ART. Patients with low adherence (<85%) to both bedaquiline and ART were identified as high risk for poor outcomes. Baseline survey, study visit notes, and focus group discussions characterized treatment challenges. RESULTS: From December 2016-February 2018, 32 of 198 (16%) enrolled patients with DR-TB HIV were identified as dual-adherence challenged. In a multivariate model including baseline characteristics, only receiving a disability grant was significantly associated with dual nonadherence at 6 months. Mixed-methods identified treatment barriers including alcohol abuse, family conflicts, and mental health issues. Compared with adherent patients, dual-adherence-challenged patients struggled to prioritize treatment and lacked support, and dual-adherence-challenged patients experienced higher rates of detectable HIV viral load and mortality than more adherent patients. CONCLUSIONS: EDM empirically identified a subpopulation of patients with DR-TB HIV with dual-adherence challenges early in treatment. Mixed-methods revealed intense psychosocial, behavioral, and structural barriers to care in this subpopulation. Our data support developing differential, patient-centered, adherence support interventions focused on psychosocial and structural challenges for subpopulations of at-risk DR-TB HIV patients.

COVID-19 Outbreak - New York City, February 29-June 1, 2020.

New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.

Evaluation and Comparison of Contemporary Energy-Based Surgical Vessel Sealing Devices.

INTRODUCTION: We evaluated and compared five currently available energy-based vessel sealing devices to assess typical surgical metrics. METHODS: We tested Caiman 5 (C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure (LS), and Enseal G2 (ES) on small (2-5 mm), medium (5.1-7 mm), and large (7.1-9 mm) vessels obtained from 15 Yorkshire pigs. Vessels were randomly sealed and transected. We recorded sealing and transection time, charring and carbonization, thermal spread, and bursting pressure (BP). Specimens were sent for histopathologic evaluation of seal quality and thermal spread. RESULTS: A total of 246 vessels were evaluated: 125 were arteries and 121 were veins. There was no difference in BPs for small size arteries. For medium arteries, C5 provided the highest BP (proximal and distal jaw), followed by HA7, ES, LS, and HA [1740, 1600, 1165, 1165, 981, and 571 mm Hg, respectively, HA250 mm Hg.

Assessing the Effect of an Intensive 2-Week Surgical Training and Innovation Program for High-School Students.

OBJECTIVE: The summer surgery program (SSP) was founded in 2012 as an educational program for students at the critical juncture between high school and college to engender interest in medicine, science, and innovation. This program has a distinct emphasis on innovation and problem solving based on real-life operative challenges identified by students during surgical observation in the operating room. The effect of the SSP regarding postsecondary education and career goals was evaluated by participants using a follow-up questionnaire. DESIGN: Retrospective cohort study using web-based survey administered to students at least 1 year after participation in the SSP. Associations between demographics and survey responses were made using Fisher's exact test and a Bonferonni correction was used to account for multiple comparisons. PARTICIPANTS: Between July 2012 and August 2015, 119 students enrolled in the SSP. We sent a web-based questionnaire link to all participants who completed the program. The questionnaire contained 80 questions assessing the participant's interest in studying medicine or science in college, knowledge of health care, and their appreciation and understanding of innovation. SETTING: UC Irvine Medical Center, Orange, CA; Institutional tertiary care center. RESULTS: In total, 77 (64.7%) of 119 students who matriculated in the SSP completed the follow-up survey; the mean number of years after the program was 2.09 years. Nearly all students reported the program increased their interest in studying medicine or science in college (97.4%), led them to a better understanding of their own career goals (93.5%) and made them more confident in their ability to succeed in a career in health care (88.3%). The majority indicated the program led them to better understand the training and schooling required of doctors and surgeons (94.8%), and led them to better appreciate the roles of different medical specialties (96.1%). Overall 96% of students reported that the program led them to better understand the importance of innovation and 86% of the respondents noted they better understood the process of innovation. Participants in the SSP were confident they would be able to become a health professional (p < 0.0001). Of note, there was no drop off in the ratings for the program when comparing classes that were 1, 2, 3, or 4 years after their SSP experience. CONCLUSIONS: The follow-up survey revealed that the 2 week SSP had a markedly, long lasting positive effect on participants in areas of academic, career, and innovation-related variables.

Development and evaluation of a retroperitoneal dialysis porcine model.

OBJECTIVES: We attempted to create a surgical model to evaluate the retroperitoneal space for the ability to transfer solutes through the retroperitoneal membrane. Our dual objectives were to develop a technique to assess the feasibility of retroperitoneal dialysis (RPD) in a porcine model. METHODS: We incorporated two 35-kg Yorkshire pigs for this pilot study. In the first animal, we clamped renal vessels laparoscopically. In the second animal, we embolized renal arteries. In both animals, we dilated the retroperitoneal space bilaterally and deployed dialysis catheters. We measured serum creatinine (Cr), urea, and electrolytes at baseline 6 hours before the dialysis and every 4 hours after. RESULTS: We successfully created retroperitoneal spaces bilaterally and deployed dialysis catheters in both animals. In the first animal, dialysate and plasma Cr ratio (D/P) on the left and right side were 0.43 and 0.3, respectively. Cr clearance by 40 minutes of dialysis treatment was 6.3 mL/min. The ratio of dialysate glucose at 4 hours dwell time to dialysate glucose at 0 dwell time (D/D0) for left/rights sides were 0.02 and 0.02, respectively. kt/Vurea was 0.43. In the second animal, D/P Cr for left/right sides were 0.34 and 0.33, respectively. kt/Vurea was 0.17. We euthanized the pigs due to fluid collection in the peritoneal space and rapid increase of serum Cr, urea, and electrolytes. CONCLUSIONS: We demonstrated the feasibility of creation of a functionally anephric porcine model with successful development of retroperitoneal spaces using balloon inflation. Notwithstanding minimal clearance and limited diffusion capacity in this experiment, additional studies are needed to examine potential use of retroperitoneal space for peritoneal dialysis.

Comparison of Flow Characteristics of Novel Three-Dimensional Printed Ureteral Stents Versus Standard Ureteral Stents in a Porcine Model.

PURPOSE: We compared the flow characteristics of novel three-dimensional (3D) printed ureteral stents with four conventional double-pigtail stents in an ex vivo porcine model. MATERIALS AND METHODS: In six ex vivo porcine urinary systems with kidneys and ureters intact, we deployed a 5F occlusion catheter in an interpolar calix. We tested each system with antegrade irrigation with a 0.9% saline bag placed 35 cm above the renal pelvis. We evaluated four standard stents (6F Universa® Soft, 7F Percuflex,™ 7/10F Applied Endopyelotomy, 8.5F Filiform Double Pigtail) and compared them with a 9F 3D printed prototype stent. For each stent, we measured the total, extraluminal, and intraluminal flow rates. RESULTS: The mean total flow rates for 3D printed stents were significantly higher than the 6F, 7F, and 7/10F stents (P<0.05). No significant difference was seen in the total flow rate for the 3D printed stent and the 8.5F stent. The mean extraluminal flow rates for the 3D stents were similar to those of 7F stents, but significantly lower than 6F stents (P<0.001) and 8.5F stents (P<0.05) and higher than 7/10F stents (P<0.001). The mean intraluminal flow rates for the 3D printed stents were significantly higher than the 6F, 7F, 7/10F, and 8.5F stents (P<0.05). CONCLUSIONS: In this pilot study, 3D printed stents manifested a mean total flow rate comparable to the flow rates of contemporary stents. Continued advances in technology and material may permit functionally feasible 3D printed ureteral stents.

Evaluation of Ignition and Burn Risk Associated with Contemporary Fiberoptic and Distal Sensor Endoscopic Technology.

PURPOSE: To evaluate the ignition and burn risk associated with contemporary fiberoptic and distal sensor endoscopic technologies. MATERIALS AND METHODS: We used new and used SCB Xenon 300 light sources to illuminate a 4.8 mm fiberoptic cable, 10 mm laparoscope, 5 mm laparoscope, rigid cystoscope, semirigid ureteroscope, flexible cystoscope, flexible fiberoptic ureteroscope, distal sensor cystoscope, and a distal sensor ureteroscope (Karl Storz, Inc., Tuttlingen, Germany). We measured peak temperatures at the distal end of each device. We then evaluated each device on a flat and folded surgical drape to establish ignition risk. Finally, we evaluated the effects of all devices on human cadaver skin covered by surgical drape. RESULTS: Peak temperatures recorded for each device ranged from 26.9°C (flexible fiberoptic ureteroscope) to 194.5°C (fiberoptic cable). Drape ignition was noted when the fiberoptic cable was placed against a fold of drape. Contact with the fiberoptic cable, 10 mm laparoscope, 5 mm laparoscope, and distal sensor cystoscope resulted in cadaver skin damage. Cadaver skin damage occurred despite little or no visible change to the surgical drape. Rigid and flexible fiberoptic cystoscopes and flexible fiberoptic ureteroscopes had no effect on surgical drapes or cadaver skin. CONCLUSIONS: Fiberoptic light cables and some endoscopic devices have the potential to cause thermal injury and drape ignition. Thermal injury may occur without visible damage to drapes. Surgeons should remain vigilant regarding the risks associated with these devices and take necessary safety precautions to prevent patient injury.