Nevin Manimala

J Crit Care. 2022 May 4;70:154052. doi: 10.1016/j.jcrc.2022.154052. Online ahead of print.

ABSTRACT

PURPOSE: Emerging evidence suggests that minimizing mean perfusion pressure (MPP) deficit during vasopressor therapy for shock can potentially reduce adverse kidney-related outcomes in ICU. We assessed feasibility and preliminary efficacy of individualizing MPP targets based on patients’ own pre-illness basal-MPP among vasopressor-treated patients with shock.

MATERIAL AND METHODS: In this prospective before-and-after trial, 31 patients during the ‘before’/observational phase and 31 patients during the ‘after’/intervention phase were enrolled at two tertiary-level Australian ICUs. Feasibility endpoint was time-weighted average MPP-deficit during vasopressor therapy. Preliminary efficacy outcomes were new significant AKI, major adverse kidney events within 14 days (MAKE-14), and 90-day mortality.

RESULTS: Patients in the after group had lower MPP-deficit (median 18%, [interquartile range [IQR]: 11-23] vs. 4%, [IQR: 2-9], p < 0.001) and lower incidence of new significant AKI (8/31 [26%] vs. 1/31 [3%], p = 0.01) than the before group. The between-group differences in MAKE-14 (9/31 [29%] vs. 4/31 [13%], p = 0.12) and 90-day mortality (6/31 [19%] vs. 2/31 [6%], p = 0.13) were not statistically significant.

CONCLUSIONS: An individualized blood pressure target strategy during vasopressor therapy in ICU was feasible and appeared to be efficacious in this preliminary study. Testing this strategy in a larger randomized controlled trial is warranted.

STUDY REGISTRATION: ACTRN12617001459314.

PMID:35525132 | DOI:10.1016/j.jcrc.2022.154052

Eur J Radiol. 2022 Apr 30;152:110337. doi: 10.1016/j.ejrad.2022.110337. Online ahead of print.

ABSTRACT

PURPOSE: To compare the diagnostic performance of a deep learning (DL) model with that of musculoskeletal physicians and radiologists for detecting bone marrow edema on dual-energy CT (DECT).

METHOD: This retrospective study included adult patients underwent hip DECT and MRI within 1 month between April 2018 and December 2020. A total of 8709 DECT images were divided into training/validation (85%, 7412 augmented images) and test (15%, 1297 images) sets. The images were labeled as present/absent bone marrow edema, with MRI as reference standard. We developed and trained a DL model to detect bone marrow edema from DECT images. Thereafter, DL model, two orthopedic surgeons, and three radiologists evaluated the presence of bone marrow edema on every test image. The diagnostic performance of the DL model and readers was compared. Inter-reader agreement was calculated using Fleiss-kappa statistics.

RESULTS: A total of 73 patients (mean age, 59 ± 12 years; 38 female) were included. The DL model had a significantly higher area under the curve (AUC, 0.84 vs. 0.61-0.70, p < 0.001) and sensitivity (79% vs. 29-66%) without loss of specificity (90% vs. 74-93%) than the non- or less-experienced readers and similar to the trained reader (AUC, 0.83, p = 0.402; sensitivity, 71%; specificity, 94%). Additionally, AUCs were strongly dependent on the reader’s DECT experience. Inter-reader agreement was fair (κ = 0.303).

CONCLUSION: The DL model showed better diagnostic performance than less-experienced physicians in detecting bone marrow edema on DECT and comparable performance to a trained radiologist.

PMID:35525130 | DOI:10.1016/j.ejrad.2022.110337

Psychoneuroendocrinology. 2022 Apr 14;142:105767. doi: 10.1016/j.psyneuen.2022.105767. Online ahead of print.

ABSTRACT

Prior work demonstrates that an additive serotonergic multilocus genetic profile score (MGPS) predicts amplified risk for depression following significant life stress, and that it interacts with elevations in the cortisol awakening response to predict depression. The serotonin system and HPA-axis have bidirectional influence, but whether this MGPS predicts acute cortisol reactivity, which might then serve as a mechanism for depression, is unknown. Our prior work suggests that depression risk factors predict blunted cortisol reactivity to explicit negative evaluative lab-based stress. Thus, we hypothesized that a 4-variant serotonergic MGPS (three SNPs from the original 5-variant version plus 5HTTLPR) would predict blunted cortisol reactivity to explicit negative evaluative stress versus a control. In Sample 1, growth curve modeling showed that the MGPS predicted heightened cortisol reactivity (p = 0.0001) in an explicitly negative evaluative Trier Social Stress Test variant (TSST) versus a control condition among non-depressed emerging adults (N = 152; 57% female). In Sample 2, 125 males completed the Socially Evaluative Cold Pressor Test (SECPT), an ambiguously negative evaluative manipulation; findings displayed a similar pattern but did not reach statistical significance (ps.075-.091). A participant-level meta-analysis of the two samples demonstrated a significant effect of negative evaluation severity, such that the MGPS effect size on reactivity increased linearly from control to SECPT to an explicitly negative evaluative TSST. Findings indicate that this MGPS contributes to sensitivity to social threat and that cortisol dysregulation in the context of social stress may be one mechanism by which this MGPS contributes to depression.

PMID:35525123 | DOI:10.1016/j.psyneuen.2022.105767

Prev Vet Med. 2022 Apr 30;204:105662. doi: 10.1016/j.prevetmed.2022.105662. Online ahead of print.

ABSTRACT

Countries have implemented control programmes (CPs) for cattle diseases such as bovine viral diarrhoea virus (BVDV) that are tailored to each country-specific situation. Practical methods are needed to assess the output of these CPs in terms of the confidence of freedom from infection that is achieved. As part of the STOC free project, a Bayesian Hidden Markov model was developed, called STOC free model, to estimate the probability of infection at herd-level. In the current study, the STOC free model was applied to BVDV field data in four study regions, from CPs based on ear notch samples. The aim of this study was to estimate the probability of herd-level freedom from BVDV in regions that are not (yet) free. We additionally evaluated the sensitivity of the parameter estimates and predicted probabilities of freedom to the prior distributions for the different model parameters. First, default priors were used in the model to enable comparison of model outputs between study regions. Thereafter, country-specific priors based on expert opinion or historical data were used in the model, to study the influence of the priors on the results and to obtain country-specific estimates. The STOC free model calculates a posterior value for the model parameters (e.g. herd-level test sensitivity and specificity, probability of introduction of infection) and a predicted probability of infection. The probability of freedom from infection was computed as one minus the probability of infection. For dairy herds that were considered free from infection within their own CP, the predicted probabilities of freedom were very high for all study regions ranging from 0.98 to 1.00, regardless of the use of default or country-specific priors. The priors did have more influence on two of the model parameters, herd-level sensitivity and the probability of remaining infected, due to the low prevalence and incidence of BVDV in the study regions. The advantage of STOC free model compared to scenario tree modelling, the reference method, is that actual data from the CP can be used and estimates are easily updated when new data becomes available.

PMID:35525066 | DOI:10.1016/j.prevetmed.2022.105662

J Environ Manage. 2022 May 4;315:115152. doi: 10.1016/j.jenvman.2022.115152. Online ahead of print.

ABSTRACT

This study reports on a meta-analysis covering the impact of design and operating factors on published MFC performance data to inform MFC research and implementations. Factors of substrate composition, operating phase, electrode material, configuration, and pre-treatments employed were considered. The meta-analysis results indicate that dual-chamber MFCs overall achieve 18% higher COD removal and 73% higher coulombic efficiencies over that of single-chamber MFCs. MFCs using a solid operating phase achieved ˃38% higher coulombic efficiencies than those using a liquid operating phase. Statistical analyses comparing brush vs flat surface anodes revealed that brush anodes can achieve 130% higher power density than flat surface anodes. The use of a platinum catalyst was found to improve power density, as opposed to catalyst-free cathodes. However, coulombic efficiency is less likely to be influenced by the catalyst used and more likely to be dependent on the inclusion of a membrane separator. The meta-analysis results indicate that even in the presence of expensive catalysts like platinum, membrane separators are of prime importance to maintain a stable MFC operation on a long-term basis and achieve high coulombic efficiency in an MFC. Results presented in this paper outline the impact of MFC design choices on performance and can be used to guide future MFC research. These findings can be beneficial for municipalities as it provides a pathway for future MFC design and optimization by analyzing critical associations between MFC response parameters and multiple varying factors.

PMID:35525044 | DOI:10.1016/j.jenvman.2022.115152

Am J Health Syst Pharm. 2022 May 7:zxac129. doi: 10.1093/ajhp/zxac129. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: This review of chronic heart failure with preserved ejection fraction (HFpEF), including new and emerging evidence for treatment of patients with this condition, is intended to offer data supporting the use of specific agents for this patient population.

SUMMARY: Chronic heart failure is a major health concern affecting millions of Americans annually and remains a significant burden on the healthcare system. Heart failure is divided into categories based on left ventricular ejection fraction (LVEF). Current treatments for heart failure with reduced ejection fraction, defined by an LVEF of less than 40%, involve a variety of agents with established morbidity and mortality benefits. This is in stark contrast to directed treatments for patients with HFpEF, defined by an LVEF of greater than 50%. Treatments for this form of heart failure have been elusive until recently, when studies were published with sacubitril/valsartan and empagliflozin. Results of the PARAGON-HF trial suggested benefit from sacubitril/valsartan in patients with an ejection fraction between 45% and 57%, leading to its approval in 2021 as the first medication indicated for treatment of patients with a preserved ejection fraction. Months later, the results of the EMPEROR-Preserved trial demonstrated a statistically significant benefit in the composite outcome of heart failure hospitalizations and cardiovascular death in patients with HFpEF taking empagliflozin. This medication has yet to gain approval for HFpEF; however, these data along with ongoing and future trials will likely impact standard treatment for these patients.

CONCLUSION: The PARAGON-HF and EMPEROR-Preserved trials will serve as the foundation for a new era in the treatment of HFpEF.

PMID:35524990 | DOI:10.1093/ajhp/zxac129

Am J Vet Res. 2022 May 8;83(6):ajvr.21.09.0152. doi: 10.2460/ajvr.21.09.0152.

ABSTRACT

OBJECTIVE: To determine the in vitro effects of the proteasome inhibitor bortezomib in feline injection site sarcoma (FISS) cell lines.

SAMPLE: In vitro cultures of the FISS cell lines Ela-1, Hamilton, and Kaiser.

PROCEDURES: Cells were treated with increasing doses of bortezomib or vehicle alone (dimethyl sulfoxide) and evaluated for cell viability via an adenosine triphosphate concentration assay, proteasome activity via a commercially available proteasome assay, accumulation of ubiquitinated proteins via Western blot, and apoptosis via flow cytometry.

RESULTS: All 3 cell lines were sensitive to bortezomib with a 50% inhibitory concentration after 48 hours of treatment at 17.46 nM (95% CI, 15.47 to 19.72 nM) for Ela-1, 19.48 nM (95% CI, 16.52 to 23.00 nM) for Hamilton, and 21.38 nM (95% CI, 19.24 to 23.78 nM) for Kaiser. In the Ela-1 cell line, 20 nM bortezomib inhibited 20S proteasome activity by 90.9% compared with the vehicle-only control. In the Kaiser cell line, 20 nM bortezomib decreased 20S proteasome activity by 70%, compared with the untreated vehicle-only control. Last, treatment with bortezomib (25 and 40 nM) resulted in statistically significant decreases in viable cells accompanied by a statistically significant increase in apoptotic cells.

CLINICAL RELEVANCE: Treatment options for FISS, especially nonresectable FISS, are currently very limited. These results support further investigation of bortezomib either alone or in combination with other treatments in such cases.

PMID:35524959 | DOI:10.2460/ajvr.21.09.0152

Am J Vet Res. 2022 May 11;83(6):ajvr.21.12.0203. doi: 10.2460/ajvr.21.12.0203.

ABSTRACT

OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 670/0.75 and 6% HES 130/0.4 dilution of canine whole blood on coagulation using dynamic viscoelastic coagulometry (DVC).

ANIMALS: 56 healthy adult dogs.

PROCEDURES: 2 blood samples were obtained from each dog and randomized to 1 of 7 groups-undiluted or 2 dilutions (1:3 or 1:10) of 3 different fluids: saline (0.9% NaCl) solution, 6% HES 670/0.75, or 6% HES 130/0.4. Dilutions were calculated to simulate approximately a 10- or 30-mL/kg body weight IV bolus of each fluid. DVC was performed on each sample. Coagulation parameters compared between groups included clot rate (CR), platelet function (PF), and activated clotting time.

RESULTS: Dilution with saline solution did not significantly affect coagulation, while dilution with HES 670/0.75 and HES 130/0.4 caused a dose-dependent significant decrease in CR (1:3 HES 670/0.75, P = 0.007; 1:10 HES 670/0.75, P = 0.002; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0003) and PF (1:3 HES 670/0.75, P < 0.0001; 1:10 HES 670/0.75, P < 0.0001; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0015).

CLINICAL RELEVANCE: Dilution of canine blood with HES 670/0.75 and HES 130/0.4, at clinically relevant doses (10 and 30 mL/kg), led to significant hypocoagulability beyond dilutional effect. This was, in part, due to impaired PF, which was significantly greater with HES 670/0.75. Further research using DVC to assess the effects of HES on coagulation in dogs, ideally with clinical conditions warranting HES administration, is needed.

PMID:35524956 | DOI:10.2460/ajvr.21.12.0203

Mutagenesis. 2022 May 7:geac011. doi: 10.1093/mutage/geac011. Online ahead of print.

ABSTRACT

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

PMID:35524945 | DOI:10.1093/mutage/geac011

Genome Biol Evol. 2022 May 7:evac067. doi: 10.1093/gbe/evac067. Online ahead of print.

ABSTRACT

The Balearic shearwater (Puffinus mauretanicus) is the most threatened seabird in Europe and member of the most speciose group of pelagic seabirds, the order Procellariiformes, which exhibit extreme adaptations to a pelagic lifestyle. The fossil record suggests that human colonization of the Balearic Islands resulted in a sharp decrease of the Balearic shearwater population size. Currently, populations continue to be decimated mainly due to predation by introduced mammals and bycatch in longline fisheries, and some studies predict their extinction by 2070. Here, we generated the first high-quality reference genome for the species, with a completeness amongst the highest across available avian species, using a combination of short and long reads. We used this reference genome to study critical aspects relevant to the conservation status of the Balearic shearwater and to gain insights into the adaptation to a pelagic lifestyle of the order Procellariiformes. We detected relatively high levels of genome-wide heterozygosity in the Balearic shearwater despite its reduced population size. However, the reconstruction of its historical demography uncovered an abrupt population decline potentially linked to a reduction of the neritic zone during the Penultimate Glacial Period (∼194-135 kya). Comparative genomics analyses uncover a set of candidate genes that may have played an important role into the adaptation to a pelagic lifestyle of Procellariiformes, including those for the enhancement of fishing capabilities, night vision and the development of natriuresis. The reference genome obtained will be the keystone for future developments of genetic tools in conservation efforts for this Critically Endangered species.

PMID:35524941 | DOI:10.1093/gbe/evac067