Category: Nevin Manimala

Pain Med. 2022 Jun 16:pnac094. doi: 10.1093/pm/pnac094. Online ahead of print.

ABSTRACT

OBJECTIVES: Recurrent, severely painful episodes, known as vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD) and the primary reason for hospitalization. Opioids have been the gold standard for VOC treatment without significant improvement pain outcomes. To aid analgesia and combat opioid related adverse effects (ORAEs), some SCD clinicians have trialed infusions of sub-anesthetic ketamine along with opioids to treat VOCs. In this retrospective analysis, we compared adult SCD patients who received early versus late adjunctive sub-anesthetic ketamine infusions for VOCs.

METHODS: We identified adult SCD patients (age 18-50 years) who presented to Duke University with a VOC and received sub-anesthetic ketamine infusions from July 2015 to June 2019. We assessed both daily opioid consumption (measured as oral morphine milligram equivalents (MME)) and self-reported 0-10 numeric pain ratings (NPR) at one, two, and three days after infusion initiation, as well as one day after discontinuation.

RESULTS: A total of 56 patients were identified with a median age of 30 years. Compared to late administration, early infusion of sub-anesthetic ketamine was associated with a 24.5% (p = 0.0003) and 25.9% (p = 0.0006) reduction, respectively, in median NPR at one day and two days after infusion initiation but did not persist at three days following initiation of the infusion. A statistically significant reduction in MME was not observed.

CONCLUSION: In a non-randomized study of sickle cell patients with VOCs, early sub-anesthetic ketamine infusion led to greater reduction in subjective pain intensity than late initiation of the infusion. Randomized studies should further explore whether early versus late ketamine infusion improves management of acute SCD pain.

PMID:35708641 | DOI:10.1093/pm/pnac094

Syst Biol. 2022 Jun 16:syac043. doi: 10.1093/sysbio/syac043. Online ahead of print.

ABSTRACT

Contamination of a genetic sample with DNA from one or more non-target species is a continuing concern of molecular phylogenetic studies, both Sanger sequencing studies and Next-Generation Sequencing (NGS) studies. We developed an automated pipeline for identifying and excluding likely cross-contaminated loci based on detection of bimodal distributions of patristic distances across gene trees. When the contamination occurs between samples within a dataset, comparisons between a contaminated sample and its contaminant taxon will yield bimodal distributions with one peak close to zero patristic distance. This new method does not rely on a priori knowledge of taxon relatedness nor does it determine the causes(s) of the contamination. Exclusion of putatively contaminated loci from a dataset generated for the insect family Cicadidae showed that these sequences were affecting some topological patterns and branch supports, although the effects were sometimes subtle, with some contamination-influenced relationships exhibiting strong bootstrap support. Long tip branches and outlier values for one anchored phylogenomic pipeline statistic (AvgNHomologs) were correlated with the presence of contamination. While the AHE markers used here, which target hemipteroid taxa, proved effective in resolving deep and shallow level Cicadidae relationships in aggregate, individual markers contained inadequate phylogenetic signal, in part probably due to short length. The cleaned dataset, consisting of 429 loci, from 90 genera representing 44 of 56 current Cicadidae tribes, supported three of the four sampled Cicadidae subfamilies in concatenated-matrix maximum likelihood (ML) and multispecies coalescent-based species tree analyses, with the fourth subfamily weakly supported in the ML trees. No well-supported patterns from previous family-level Sanger sequencing studies of Cicadidae phylogeny were contradicted. One taxon (Aragualna plenalinea) did not fall with its current subfamily in the genetic tree, and this genus and its tribe Aragualnini is reclassified to Tibicininae following morphological re-examination. Only subtle differences were observed in trees after removal of loci for which divergent base frequencies were detected. Greater success may be achieved by increased taxon sampling and developing a probe set targeting a more recent common ancestor and longer loci. Searches for contamination are an essential step in phylogenomic analyses of all kinds and our pipeline is an effective solution.

PMID:35708660 | DOI:10.1093/sysbio/syac043

Rheumatology (Oxford). 2022 Jun 16:keac311. doi: 10.1093/rheumatology/keac311. Online ahead of print.

ABSTRACT

OBJECTIVES: Lung vascular and parenchymal changes can be recently assessed quantitatively in thoracic computed tomography (CT) images using automated software tools. We investigated the vessel parameters of patients with Systemic Sclerosis (SSc), quantified by CT imaging, and correlated them with the interstitial lung disease (ILD) features.

METHODS: SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analyzed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio LTA. Vascular analysis (volumes, numbers, and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted.

RESULTS: 79 patients (52 women, 40 ILD, age 56.2 ± 14.2 years, total ILD extent 9.5 ± 10.7%, PVV/LV% 2.8%) were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-ILD patients presented with an increased number and volume of arterial vessels, in particular those between 2-4 mm of diameter, and with a higher density of arteries and veins of < 8 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment.

CONCLUSION: In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment and may represent a biomarker of SSc-ILD severity.

PMID:35708639 | DOI:10.1093/rheumatology/keac311

J Med Food. 2022 Jun;25(6):636-644. doi: 10.1089/jmf.2022.K.0007.

ABSTRACT

There is a lack of studies on the effects of Korean ginseng (Panax ginseng C.A. Meyer) on face or body temperature. Therefore, in this study, we evaluated the effects of a black ginseng extract, KGR-BG1, on head and face temperatures and compared them with those of red ginseng extract and a placebo. We assessed their safety and tolerability and examined changes in the serum levels of biomarkers associated with immune responses, as well as with glucose and lipid metabolism. A randomized, double-blind, placebo-controlled study was conducted with 180 participants. The participants were randomly assigned to the KGR-BG1, red ginseng extract, or placebo group. Each group received a 1500 mg oral dose of their respective substances containing 1000 mg of the active component or placebo twice daily for 6 weeks. After treatment, changes in the head, face, and body temperature were measured, and serum biomarkers were evaluated. A total of 172 participants completed the evaluation after 6 weeks of treatment. No significant differences were observed in the head, face, and body temperatures among the treatment groups. After 6 weeks of treatment, the serum levels of biomarkers associated with inflammation, glucose metabolism, and lipid metabolism were similar to the baseline levels in all treatment groups. KGR-BG1 was well-tolerated compared with red ginseng extract and placebo. KGR-BG1 did not significantly alter head, face, or body temperature, or serum biomarker levels, and it was well tolerated in healthy volunteers over 6 weeks of treatment. Study Registration: Registered at Clinical Research Information Service (CRIS; https://cris.nih.go.kr) as KCT0003126.

PMID:35708631 | DOI:10.1089/jmf.2022.K.0007

Phys Sportsmed. 2022 Jun 16. doi: 10.1080/00913847.2022.2090869. Online ahead of print.

ABSTRACT

OBJECTIVES: Certain occupations are associated with greater risk of triggering a sudden cardiac event because of high levels of physical exertion and extreme thermal environments in which they occur. The extent to which sports officials-particularly high school (HS) American football referees-experience these conditions is unknown. Forty-six male HS officials (72% White/Caucasian; age=48±12 y, body mass index=31.7±6.6 kg·m^-2) were studied to quantify the physiological strain and physical demands of officiating.

METHODS: Referee demographics (e.g., experience, habitual exercise), pre-game urine specific gravity (U_SG), thermal (peak core temperature [T_core]) and cardiovascular (average heart rate [HR]) strain, kinematic activity (e.g., total distance, speed, mechanical intensity), and environmental conditions were measured during 10 regular season varsity HS football games (≈2.5 h each) in the Southeastern United States (average wet bulb globe temperature and relative humidity: 18.9±6.0 °C and 78.2±12.1%). Analyses included descriptive statistics, bivariate correlations, and linear regression.

RESULTS: Referees covered 5.2±1.2 km per game, eliciting average HR and peak T_core of 71.5%±8.0% HR_max and 38.3±0.5 °C, respectively; 38% began games dehydrated (U_SG=1.026±0.004). Multiple regression analyses revealed that obesity (β=0.34), not participating in regular exercise (β=-0.36), and officiating at lower mechanical intensity (β=-0.33) predicted greater cardiovascular strain (all p≤0.03). White/Caucasian race/ethnicity (β=0.59), younger age (β=-0.46), and obesity (β=0.28) predicted greater thermal strain (all p≤0.01).

CONCLUSION: HS football referees experienced elevated levels of physiological strain while officiating, with individual factors modulating the magnitude of strain. Strategies aimed at reducing obesity, increasing exercise participation, and improving cardiovascular health should be emphasized to mitigate strain and prevent cardiac events.

PMID:35708121 | DOI:10.1080/00913847.2022.2090869

Haematologica. 2022 Jun 16. doi: 10.3324/haematol.2021.280027. Online ahead of print.

ABSTRACT

Achievement of complete remission (CR) signifies a crucial milestone in the therapy of acute myeloid leukemia (AML) while refractory disease is associated with dismal outcomes. Hence, accurately identifying patients at risk is essential to individually tailor treatment concepts to disease biology. We used nine machine learning (ML) models to predict CR and 2-year overall survival (OS) in a large multi-center cohort of 1383 AML patients who received intensive induction therapy using clinical, laboratory, cytogenetic and molecular genetic data and validated our results on an external multicenter cohort. Our ML models autonomously selected predictive features both including established markers of favorable or adverse risk as well as identifying markers of so-far controversial relevance. De novo AML, extramedullary AML, double-mutated (dm) CEBPA, mutations of CEBPA-bZIP, NPM1, FLT3-ITD, ASXL1, RUNX1, SF3B1, IKZF1, TP53, U2AF1, t(8;21), inv(16)/t(16;16), del(5)/del(5q), del(17)/del(17p), normal or complex karyotypes, age and hemoglobin at initial diagnosis were statistically significant markers predictive of CR, while t(8;21), del(5)/del(5q), inv(16)/t(16;16), del(17)/del(17p), dmCEBPA, CEBPA-bZIP, NPM1, FLT3-ITD, DNMT3A, SF3B1, U2AF1, TP53, age, white blood cell count, peripheral blast count, serum LDH and Hb at initial diagnosis as well as extramedullary manifestations were predictive for 2-year OS. For prediction of CR and 2-year OS, AUROCs ranged between 0.77 – 0.86 and 0.63 and 0.74, respectively in our test set and 0.71 – 0.80 and 0.65 – 0.75 in the external validation cohort. We demonstrate the feasibility of ML for risk stratification in AML as a model disease for hematologic neoplasms using a scalable and reusable ML framework. Our study illustrates the clinical applicability of ML as a decision support system in hematology.

PMID:35708137 | DOI:10.3324/haematol.2021.280027

J Magn Reson Imaging. 2022 Jun 16. doi: 10.1002/jmri.28293. Online ahead of print.

NO ABSTRACT

PMID:35708113 | DOI:10.1002/jmri.28293

Nutr Diet. 2022 Jun 16. doi: 10.1111/1747-0080.12741. Online ahead of print.

ABSTRACT

AIM: Australian children consume 35% of energy from discretionary food and beverages which increases their risk of non-communicable diseases like type 2 diabetes. Despite this concerning statistic, broad analysis of the profile of discretionary food intake has not been fully undertaken. This study asks: what is the discretionary food and beverage intake profile, contribution to nutrient intakes, and associations with demographic and health characteristics?

METHODS: Cross-sectional data from the 2011-12 National Nutrition and Physical Activity Survey (n = 2812, 2-18 years) were used to profile discretionary food consumption. Dietary intake was assessed by 24-h recall. General linear models tested the difference in respondent characteristics by age group, sex, and quartiles of discretionary food energy contribution.

RESULTS: Ninety-nine percent of respondents consumed discretionary foods, 74% exceeded the maximum discretionary food recommended serves. Among 10 eating occasions available to select: snack, dinner, lunch and morning tea appeared to contribute 76% of discretionary food energy, with snack and dinner contributing 24% each. Age and frequency of discretionary food consumption were positively associated with energy intake from discretionary foods (p < 0.001); while sex, socio-economic status, physical activity and body composition had no association. High discretionary food consumers chose specific discretionary food items in a large quantity (1.0-3.5-serves/discretionary food) compared to low discretionary food consumers (0.4-1.4-serves/discretionary food).

CONCLUSIONS: Nearly all Australian children and adolescents consumed discretionary food daily. No demographic or anthropometric characteristics beyond increasing age were associated with higher discretionary food. Targeted public health policy and community interventions are required to focus on addressing the largest contributors to discretionary food intake in terms of equivalent serve sizes, popularity, and eating occasion.

PMID:35708110 | DOI:10.1111/1747-0080.12741

J Biomater Appl. 2022 Jun 16:8853282221108839. doi: 10.1177/08853282221108839. Online ahead of print.

ABSTRACT

Percutaneous devices-indwelling catheters-related infections are serious clinical incidents. It is accordingly necessary to develop anti-infective coating materials suitable for the devices for long-term effectiveness. In our research group, highly dispersible and crystalline hydroxyapatite (HAp) nanoparticles doped with metallic or halogen ions possessing antibacterial activities have been developed. In this study, antibacterial, dispersible, and crystalline zinc (Zn)-doped hydroxyapatite [Zn(15)-HAp] nanoparticles substituted with 13.5% Zn content [Zn/(Zn + Ca) × 100] were prepared by a wet chemical method using an anti-sintering agent through calcination. Antibacterial activities of Zn(15)-HAp nanoparticles were evaluated using Escherichia coli (E. coli) and Staphylococcus aureus. The survival rates of the bacteria on Zn(15)-HAp nanoparticles were significantly lower than that on normal HAp (nHAp) coated surfaces, while no influences were observed on proliferation of L929 cells. Even after soaking Zn(15)-HAp nanoparticles in PBS for 2 weeks, the antibacterial activities against E. coli were maintained at a similar level to a 20 min soaking. The bacterial death was related to not only ion-exchange phenomenon between Zn and magnesium ions but also accumulation of reactive oxygen species (ROS) in the cells. Allergic-like reactions-anaphylactoid reactions-might not readily occur with Zn(15)-HAp nanoparticles because the amounts of histamine released from HMC-1 cells co-cultured with nanoparticles were not significantly different to that of nHAp, but were statistically much lower than that of chlorhexidine.

PMID:35708097 | DOI:10.1177/08853282221108839

J Am Geriatr Soc. 2022 Jun 16. doi: 10.1111/jgs.17926. Online ahead of print.

ABSTRACT

INTRODUCTION: Growing evidence suggests that impairment in rest-activity rhythms may be a risk factor for cognitive decline and impairment in the aging population. However, previous studies included only a limited set of rest-activity metrics and produced mixed findings. We studied a comprehensive set of parametric and nonparametric characteristics of rest-activity rhythms in relation to mild cognitive impairment (MCI) and probable dementia in a cohort of older women.

METHODS: The prospective analysis included 763 women enrolled in two ancillary studies of the Women’s Health Initiative (WHI): the WHI Memory Study-Epidemiology of Cognitive Health Outcomes and Objective Physical Activity and Cardiovascular Health studies. The association between accelerometry-based rest-activity parameters and centrally adjudicated MCI and probable dementia were determined using Cox regression models adjusted for sociodemographic characteristics, lifestyle factors, and comorbidities.

RESULTS: Overall, the results support a prospective association between weakened rest-activity rhythms (e.g., reduced amplitude and overall rhythmicity) and adverse cognitive outcomes. Specifically, reduced overall rhythmicity (pseudo F statistic), lower amplitude and activity level (amplitude/relative amplitude, mesor, and activity level during active periods of the day [M10]), and later activity timing (acrophase and midpoint of M10) were associated with a higher risk for MCI and probable dementia. Women with lower amplitude and mesor also exhibited faster cognitive decline over follow-up.

CONCLUSION: Weakened rest-activity rhythms may be predictive markers for cognitive decline, MCI, and dementia among older women.

PMID:35708069 | DOI:10.1111/jgs.17926