Category: Nevin Manimala

Braz J Cardiovasc Surg. 2022 Jul 26. doi: 10.21470/1678-9741-2021-0519. Online ahead of print.

ABSTRACT

INTRODUCTION: Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator fibers that were analyzed by scanning electron microscope (SEM) and to extensively study patients’ coagulation profiles, inflammatory markers, and functional blood tests.

METHODS: Twelve patients who had open heart surgery were randomly divided into two groups; the nonpulsatile flow (group NP, six patients) and pulsatile flow (group P, six patients) groups. Both superficial view and axial sections of the oxygenator fiber samples were examined under SEM to compare the thickness of absorbed blood proteins and amount of blood cells on the surface of oxygenators. Platelet count, coagulation profile, and inflammatory predictors were also studied from the blood samples.

RESULTS: Fibrinogen levels after cardiopulmonary bypass were significantly lower in group NP (group P, 2.57±2.78 g/L; group NP; 2.39±0.70 g/L, P=0.03). Inflammatory biomarkers such as C-reactive protein, interleukin (IL)-6, IL-12, apelin, S100β, and tumor necrosis factor alpha were comparable in both groups. Axial sections of the oxygenator fiber samples had a mean thickness of 45.2 µm and 46.5 µm in groups P and NP, respectively, and this difference is statistically significant (P=0.006). Superficial view of the fiber samples showed obviously lower platelet, leukocyte, and erythrocyte levels in group P.

CONCLUSION: Our study demonstrated that both cellular elements and protein adsorption on oxygenator fibers are lower in the group P than in the group NP. Pulsatile perfusion has better biocompatibility on extracorporeal circulation when analyzed by SEM technique.

PMID:35895987 | DOI:10.21470/1678-9741-2021-0519

Mol Pharm. 2022 Jul 27. doi: 10.1021/acs.molpharmaceut.2c00361. Online ahead of print.

ABSTRACT

An immunosuppressive tumor microenvironment and tumor heterogeneity have led to the resilience of metastatic castrate resistant prostate cancer (mCRPC) to current treatments. To address these challenges, we developed and evaluated a new drug paradigm, Radio-IMmunostimulant (RIMS), in a syngeneic model of murine prostate cancer. RIMS-1 was generated using a convergent synthesis employing solid phase peptide and solution chemistries. The prostate-specific membrane antigen (PSMA) inhibitory constant for ^natLu-RIMS-1 was determined, and radiolabeling with ¹⁷⁷Lu generated ¹⁷⁷Lu-RIMS-1. The TLR 7/8 agonist payload release from ^natLu-RIMS-1 was determined using a cathepsin B assay. The biodistribution of ¹⁷⁷Lu-RIMS-1 was evaluated in a bilateral xenograft model in NCru nude mice bearing PSMA(+) (PC3-PiP) and PSMA(-) (PC3-Flu) tumors at 2, 24, and 72 h. The therapeutic effect of ¹⁷⁷Lu-RIMS-1 was evaluated in C57BL/6J mice bearing RM1-PGLS (PSMA-positive, green fluorescent protein-positive, and luciferase-positive) tumors and compared to that of ¹⁷⁷Lu-PSMA-617 at the same total administered radioactivity of 57 MBq and molar activity of 5.18 MBq/nmol. ^natLu-RIMS-1 and vehicle were evaluated as the controls. Immuno-positron emission tomography (PET) using ⁸⁹Zr-DFO-anti-CD3 was used to visualize T-cell distribution during treatment. ¹⁷⁷Lu-RIMS-1 was quantitatively radiolabeled at >99% radiochemical purity and maintained a high affinity toward PSMA (K_i = 3.77 ± 0.5 nM). Cathepsin B efficiently released the entire immunostimulant payload in 17.6 h. ¹⁷⁷Lu-RIMS-1 displayed a sustained uptake in PSMA(+) tumor tissue up to 72 h (2.65 ± 1.03% ID/g) and was not statistically different (P = 0.1936) compared to ¹⁷⁷Lu-PSMA-617 (3.65 ± 0.59% ID/g). All animals treated with ¹⁷⁷Lu-RIMS-1 displayed tumor growth suppression and provided a median survival of 30 days (P = 0.0007) while ¹⁷⁷Lu-PSMA-617 provided a median survival of 15 days, which was not statistically significant (P = 0.3548) compared to the vehicle group (14 days). ImmunoPET analysis revealed 2-fold more tumor infiltrating T-cells in ¹⁷⁷Lu-RIMS-1-treated animals compared to ¹⁷⁷Lu-PSMA-617-treated animals; ¹⁷⁷Lu-RIMS-1 improves therapeutic outcomes in a syngeneic model of mouse prostate cancer and elicits greater T-cell infiltration to the tumor compared to ¹⁷⁷Lu-PSMA-617. These results support further investigation of the RIMS paradigm as the first example of a single molecular entity combining radiotherapy and immunostimulation.

PMID:35895995 | DOI:10.1021/acs.molpharmaceut.2c00361

Curr Opin Obstet Gynecol. 2022 Jul 16. doi: 10.1097/GCO.0000000000000807. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: High-quality research underpins the best healthcare practice. This article focuses on analyzing the current literature to promote research integrity across clinical trials.

RECENT FINDINGS: Recent admissions of questionable practices by researchers have undermined practitioner and public confidence. There is limited evidence specifically for ethical and professional standards in clinical trials to guide researchers and institutions to embed integrity into research practice.

SUMMARY: Unintentional errors and spin in research are not uncommon as training in design and conduct of clinical trials is not part of health education for medical and allied health professions. There is unfamiliarity with procedures, such as prospective registration, a priori documentation of statistical analysis plans, openness in data sharing, and so forth. This, combined with the academic culture of secrecy, has led to an environment where scientific suspicion, instead of trust, is the norm. Existing science integrity documents are devoid of specific recommendations about how to translate any guidance into clinical trial practice. There is a need for constructive, supportive and multidisciplinary approaches based on open dialogue and continuous training, targeting the research environment. Research integrity now needs to take centre stage to re-instill confidence in randomized trial evidence to inform clinical practice.

PMID:35895940 | DOI:10.1097/GCO.0000000000000807

J Environ Sci Health C Toxicol Carcinog. 2022;40(1):68-85. doi: 10.1080/26896583.2022.2050155.

ABSTRACT

In the present study, we have isolated endosulfan tolerant bacterial strains from the rhizosphere of plants growing in a pesticide-contaminated area. The tolerance capacities of these strains were tested up to 50,000 µg ml^-1 of endosulfan. It was found that out of nineteen, four strains (EAG-EC-12, EAG-EC-13, EAG-EC-14, and EAG-EC-15) were capable of surviving up to 50,000 µg ml^-1 endosulfan concentration in the media; thus, these four strains were selected for the characterization. Among four, two strains were identified as Serratia liquefaciens, while the other two strains were Bacillus sp. and Brevibacterium halotolerans. The result shows that growth of strain Serratia liquefaciens 1 and Serratia liquefaciens 2 in treated medium was statistically similar to that of control (cfu 6.8 × 10⁷) after 24 h, while strains Bacillus sp. and Brevibacterium halotolerans have shown growth significantly less than the control. The degradation potential of these strains was analyzed against 100 to 250 µg ml^-1 of endosulfan in a Minimal Broth Medium (MBM), and it was recorded that only 9, 2, 7, and 19% of endosulfan (100 µg ml^-1) remain after a 72 h incubation period of Bacillus sp., Serratia liquefaciens 1, Serratia liquefaciens 2, and Brevibacterium halotolerans, respectively. This endosulfan removal potential of studied strains was decreased with an increase in concentration of endosulfan.

PMID:35895931 | DOI:10.1080/26896583.2022.2050155

J Am Chem Soc. 2022 Jul 27. doi: 10.1021/jacs.2c04683. Online ahead of print.

ABSTRACT

Differences in entropies of competing transition states can direct kinetic selectivity. Understanding and modeling such entropy differences at the molecular level is complicated by the fact that entropy is statistical in nature; i.e., it depends on multiple vibrational states of transition structures, the existence of multiple dynamically accessible pathways past these transition structures, and contributions from multiple transition structures differing in conformation/configuration. The difficulties associated with modeling each of these contributors are discussed here, along with possible solutions, all with an eye toward the development of portable qualitative models of use to experimentalists aiming to design reactions that make use of entropy to control kinetic selectivity.

PMID:35895875 | DOI:10.1021/jacs.2c04683

Biometrics. 2022 Jul 27. doi: 10.1111/biom.13727. Online ahead of print.

ABSTRACT

High throughput spatial transcriptomics (HST) is a rapidly emerging class of experimental technologies that allow for profiling gene expression in tissue samples at or near single-cell resolution while retaining the spatial location of each sequencing unit within the tissue sample. Through analyzing HST data, we seek to identify sub-populations of cells within a tissue sample that may inform biological phenomena. Existing computational methods either ignore the spatial heterogeneity in gene expression profiles, fail to account for important statistical features such as skewness, or are heuristic-based network clustering methods that lack the inferential benefits of statistical modeling. To address this gap, we develop SPRUCE: a Bayesian spatial multivariate finite mixture model based on multivariate skew-normal distributions, which is capable of identifying distinct cellular sub-populations in HST data. We further implement a novel combination of Pólya-Gamma data augmentation and spatial random effects to infer spatially correlated mixture component membership probabilities without relying on approximate inference techniques. Via a simulation study, we demonstrate the detrimental inferential effects of ignoring skewness or spatial correlation in HST data. Using publicly available human brain HST data, SPRUCE outperforms existing methods in recovering expertly annotated brain layers. Finally, our application of SPRUCE to human breast cancer HST data indicates that SPRUCE can distinguish distinct cell populations within the tumor microenvironment. An R package spruce for fitting the proposed models is available through The Comprehensive R Archive Network (CRAN). This article is protected by copyright. All rights reserved.

PMID:35895854 | DOI:10.1111/biom.13727

Psychiatr Serv. 2022 Jul 27:appips202100718. doi: 10.1176/appi.ps.202100718. Online ahead of print.

ABSTRACT

OBJECTIVE: The study followed up with peer support specialists (PSSs) responding to an earlier survey to assess the pandemic’s continued employment and personal effects.

METHODS: A December 2020 online survey was conducted with respondents to a May 2020 survey. Items on employment status, work tasks, challenges, support, and benefits were included. Responses were analyzed with descriptive and inferential statistics.

RESULTS: A total of 496 PSSs completed both surveys. Unemployment remained at 7%. The proportion with full-time employment increased by December, but financial instability also increased. Tasks involving individual support and group facilitation, which had decreased significantly, rebounded somewhat by December, when nearly all PSSs (86%) reported having some new tasks. Job satisfaction remained stable and high. In both surveys, about 75% reported pandemic-related benefits. Symptoms and housing instability among clients increased.

CONCLUSIONS: Pandemic-related PSS unemployment was relatively stable, and work tasks evolved. Respondents reported increasing needs among clients, as well as pandemic-related work benefits.

PMID:35895840 | DOI:10.1176/appi.ps.202100718

Am J Vet Res. 2022 Jul 13;83(8):ajvr.21.10.0169. doi: 10.2460/ajvr.21.10.0169.

ABSTRACT

OBJECTIVE: To assess the efficacy of an equine-origin liquid amnion allograft (ELAA) derived from both amniotic fluid and amniotic membrane on the healing time of experimentally induced distal limb wounds in horses.

ANIMALS: 8 adult horses.

PROCEDURES: On day 0, horses were anesthetized and a 2.5 X 2.5-cm, full-thickness skin wound was created on the dorsal aspect of each metacarpus and bandaged. On day 9, wound margins were injected with ELAA (treatment) or 0.9% NaCl (control). Bandages were changed at specific intervals through day 91 and, on each occasion, wounds were photographed to allow calculation of wound area. Exuberant granulation tissue was resected, if present. Wounds were deemed healed when completely epithelialized. Mean wound area was compared between groups throughout the study period.

RESULTS: Only 1 wound (control) remained unhealed at day 91. No difference was found between the treatment and control groups in either wound area over time (P = 1.0) or time for wounds to reduce in size by 95% (P = .2) Exuberant granulation tissue required resection twice (1 control wound and 1 treatment wound).

CLINICAL RELEVANCE: In this model, a single treatment with ELAA administered locally by SC injection did not accelerate distal limb wound healing in horses. However, it is possible that naturally occurring, chronic, or nonhealing wounds would respond differently.

PMID:35895786 | DOI:10.2460/ajvr.21.10.0169

Am J Vet Res. 2022 Jul 25;83(9):ajvr.22.03.0054. doi: 10.2460/ajvr.22.03.0054.

ABSTRACT

OBJECTIVE: To compare metabolomic profiles of dogs eating grain-free (GF) versus grain-inclusive (GI) diets (1) for healthy dogs at baseline and (2) for dogs with subclinical cardiac abnormalities at 12 months after a diet change.

SAMPLE: Serum samples from 23 dogs eating GF diets and 79 dogs eating GI diets, of which 17 (8 eating a GF diet and 9 eating a GI diet) were reevaluated 12 months after a diet change.

PROCEDURES: Metabolomic profiles were developed by means of ultrahigh-performance liquid chromatography-tandem mass spectroscopy of serum samples. Baseline results for the GF group were compared with those for the GI group. Dogs from both groups with subclinical cardiac abnormalities were transitioned to a GI, pulse-free, intervention diet, and samples collected 12 months later were compared between diet groups. Statistical significance for biochemical group differences was defined as P < .05 with a false discovery rate (q) < .10.

RESULTS: Baseline differences in lipid metabolism and amino acid metabolism were found between the GF and GI diet groups. There were 46 metabolites that were higher and 82 metabolites that were lower in the GF group (n = 23), compared with the GI group (79). Comparison of the GF (n = 8) and GI (9) groups 12 months after the diet change showed only 6 metabolites that were higher and 11 metabolites that were lower in the GF group, compared with the GI group.

CLINICAL RELEVANCE: Metabolomic pathway differences between dogs eating GF versus GI diets highlight the important effect of diet in metabolomics analyses. The clinical importance of these differences and how they might relate to cardiac disease in dogs remains undetermined.

PMID:35895762 | DOI:10.2460/ajvr.22.03.0054

Am J Vet Res. 2022 Jul 18;83(9):ajvr.21.10.0171. doi: 10.2460/ajvr.21.10.0171.

ABSTRACT

OBJECTIVE: To compare the attenuation of the medial coronoid process (MCP) in dogs with and without arthroscopically confirmed evidence of medial coronoid disease (MCD).

ANIMALS: The database at our institution was searched for cases with thoracic limb lameness, diagnosed with MCD by arthroscopic examination that had CT as part of their investigation and compared with a control group of elbow joints from cadavers euthanized for reasons unrelated to MCD. A total of 84 elbow joints were included that met these criteria.

PROCEDURES: Following CT, a standardized measurement of the MCP was obtained from apex to base and the mean attenuation, SD, and total area were recorded. A comparative measurement was obtained from the proximal radial cortex at the level of the nutrient foramen. Elbow joint arthroscopy was carried out using standard portals, and the modified Outerbridge score was (MOS) used to score elbow joint cartilage. Descriptive and inferential statistics were carried out using MLwiN and R.

RESULTS: Attenuation of the MCP was reduced in dogs with MCD compared with those with no MCD (P < .002). No significant differences were observed in the attenuation between categories of severity (MOS). There was good inter- and intraobserver agreement between measurements (intraclass correlation coefficient = 0.89 and 0.95, respectively).

CLINICAL RELEVANCE: MCP attenuation is reduced in dogs with MCD compared with dogs with no evidence of MCD. This finding may be a useful tool for early detection of MCD, but there is no relationship with arthroscopic lesion severity.

PMID:35895761 | DOI:10.2460/ajvr.21.10.0171