Synthesis and Characterization of ZnO Nanoparticles from Extracts of \u3cem\u3eAllium sativum\u3c/em\u3e and \u3cem\u3eHydrastis canadensis\u3c/em\u3e

Zinc oxide nanoparticles (ZnO NPs) have become one of the most popular metal oxide nanoparticles for their uses in biomedical applications due to their antibacterial properties. ZnO NPs, when capped with natural products from plant extracts with known antibacterial properties, are hypothesized to cause bacterial stasis and have enhanced bactericidal performance. This project focuses on synthesizing and characterizing natural product capped ZnO NPs and determining how the incorporation of natural products alters the physicochemical properties of ZnO. The ZnO NPs were synthesized using zinc nitrate hexahydrate and aqueous extracts from Allium sativum and Hydrastis canadensis, prepared by alkali precipitation from an aqueous solution at 65°C. These NPs were characterized by TGA-MS, FTIR, XRD, UV-Vis spectroscopy, and SEM. The photocatalytic degradation of malachite green dye by capped ZnO NPs was investigated from an aqueous solution under UVA irradiation, to assess how the incorporation of the plant extract modifies ZnO chemical reactivity. A phytochemical test panel was conducted on the plant extracts of Allium sativum and Hydrastis canadensis using standard biochemical protocols. The research was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant P20GM103408

Relationship of tissue dimensions and three captive bolt placements on cadaver heads from mature swine (Sus scrofa domesticus) > 200 kg body weight

Three penetrating captive bolt (PCB) placements were tested on cadaver heads from swine with estimated body weight (BW) >200 kg (sows = 232.9 ± 4.1 kg; boars = 229.3 ± 2.6 kg). The objectives were to determine tissue depth, cross-sectional brain area, visible brain damage (BD), regions of BD, and bolt-brain contact; and determine relationships between external head dimensions and tissue depth at each placement. A Jarvis PAS – Type P 0.25R PCB with a Long Stunning Rod Nosepiece Assembly and 3.5 gr power loads was used at the following placements on heads from 111 sows and 46 boars after storage at 2-4° C for approximately 62 h before treatment: FRONTAL (F) – 3.5 cm superior to the optic orbits at midline, TEMPORAL (T) – at the depression posterior to the lateral canthus of the eye within the plane between the lateral canthus and the base of the ear, or BEHIND EAR (BE) – directly caudal to the pinna of the ear on the same plane as the eyes and targeting the middle of the opposite eye. For sows, the bolt path was in the plane of the brain for 42/42 (100%, 95% CI: 91.6-100.0%) F heads, 39/40 (97.5%, 95% CI: 86.8-99.9%) T heads, and 34/39 (87.5%, 95% CI: 72.6-95.7%) BE heads; for the heads that could reliably be assessed for BD damage was detected in 25/26 (96.2%, 95% CI: 80.4-99.9%) F heads, 24/35 (68.6%, 95% CI: 50.7-83.2%) T heads, and 5/40 (12.5%, 95% CI: 4.2-26.8%) BE heads. For boars, the bolt path was in the plane of the brain for 17/17 (100.0%, 95% CI: 80.5-100.0%) F heads, 18/18 (100.0%, 95% CI: 81.5-100.0%) T heads, and 14/14 (100.0%, 95% CI: 76.8-100.0%) BE heads; damage was detected in 11/12 (91.7%, 95% CI: 61.5-99.8%) F heads, 2/15 (13.3%, 95% CI: 1.7-40.5%) T heads, and 7/14 (50.0%, 95% CI: 23.0-77.0%) BE heads. Tissue depth was reported as mean ± standard error followed by 95% one-sided upper reference limit (URL). For sows, total tissue thickness was different (P 200 kg BW, F placement may be more effective than T or BE due to less soft tissue thickness, which may reduce concussive force. The brain was within the plane of bolt travel for 100% of F heads with brain damage for 96.2% and 91.7% of F sow and boar heads, respectively.This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Animal Science following peer review. The version of record: Anderson, Karly N., Kaysie J. Allen, Angela Baysinger, Madonna Benjamin, Jennifer Berger, James R. Claus, Brian J. Greco et al. "Relationship of tissue dimensions and three captive bolt placements on cadaver heads from mature swine (Sus scrofa domesticus)> 200 kg body weight." 99, no. 12 Journal of Animal Science (2021) is available online at DOI: 10.1093/jas/skab327. Copyright The Author(s) 2021. Posted with permission

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act

BACKGROUNDKidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population.METHODSUsing a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure.RESULTSHOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001).CONCLUSIONSListing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act

Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P  < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P  < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P  < 0.001). Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV

ctDNA monitoring using patient-specific sequencing and integration of variant reads.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4 + T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion