Category: Nevin Manimala

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

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

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

Psychometrika. 2022 May 7. doi: 10.1007/s11336-022-09863-9. Online ahead of print.

ABSTRACT

Latent variable models have been playing a central role in psychometrics and related fields. In many modern applications, the inference based on latent variable models involves one or several of the following features: (1) the presence of many latent variables, (2) the observed and latent variables being continuous, discrete, or a combination of both, (3) constraints on parameters, and (4) penalties on parameters to impose model parsimony. The estimation often involves maximizing an objective function based on a marginal likelihood/pseudo-likelihood, possibly with constraints and/or penalties on parameters. Solving this optimization problem is highly non-trivial, due to the complexities brought by the features mentioned above. Although several efficient algorithms have been proposed, there lacks a unified computational framework that takes all these features into account. In this paper, we fill the gap. Specifically, we provide a unified formulation for the optimization problem and then propose a quasi-Newton stochastic proximal algorithm. Theoretical properties of the proposed algorithms are established. The computational efficiency and robustness are shown by simulation studies under various settings for latent variable model estimation.

PMID:35524934 | DOI:10.1007/s11336-022-09863-9

Oral Radiol. 2022 May 7. doi: 10.1007/s11282-022-00615-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To introduce a new classification, aiming to correspond TMJ disc configuration with diagnosis, meanwhile reduce difficulty and subjectivity in TMJ MRI evaluation and training of TMD diagnosis for dental students.

METHODS: 90 patients sought for TMD treatment were enrolled in the study, whose MRIs were used to establish the new classification. A total of 180 discs were evaluated using MRI for position (normal, DDWR or DDWoR) and classified by morphology according to previous (Murakami’s classification) and new classification respectively. 60 discs were selected and judged by two groups (2 TMJ specialists and 30 dental students) to assess the reliability and validity of the new classification. Questionnaires were acquired for all observers to assess the attitude toward two classification systems. Descriptive statistics, Spearman’s rank correlation coefficient, and intraclass correlation coefficient were performed. P < 0.05 was considered statistically significant.

RESULTS: In the new classification, Class 1 disc was significantly correlated with DDWR and Class 3 disc was significantly correlated with DDWoR. Interobserver reliability/consistency for observers between TMJ specialists was 0.867 when Murakami’s classification was applied and 0.948 when the new classification was applied. Interobserver ICC value for dental students was 0.656 when using Murakami’s classification, and 0.831 when using the new classification. The difference in attitude toward different classification systems was statistically significant.

CONCLUSION: A new classification of TMJ disc configuration is presented. The correlation between disc morphology and position revealed helps diagnosis and management. The new classification improves TMJ MRI interpreting accuracy and provides a better learning and using experience.

PMID:35524903 | DOI:10.1007/s11282-022-00615-0

Obes Surg. 2022 May 7. doi: 10.1007/s11695-022-06091-z. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is a risk factor for chronic kidney disease and albuminuria. Despite the well-documented obesity association with diabetes mellitus and hypertension, its predisposition to albuminuria is not related to these comorbidities, and, in some times, its occurrence is independent of DM or hypertension.

PURPOSE OF THE STUDY: The present study aimed to evaluate bariatric surgery effect on albuminuria in patients with severe obesity with no DM or hypertension.

MATERIALS AND METHODS: The study consisted of 137 patients with extreme obesity and albuminuria scheduled for bariatric surgery and did not have diabetes or hypertension. They underwent an assessment for 24-h urinary albumin at baseline (T0) and 6 months postoperatively (T2).

RESULTS: Albuminuria remission occurred in 83% of patients; there was a statistically highly significant difference between the baseline and the 6-month postoperative in the 24-h urinary albumin assessment. Weight loss and BMI at T2 were independent predictors of albuminuria remission.

CONCLUSION: The current work emphasizes the importance and promising role of bariatric surgery as an effective weight reduction management method in improving albuminuria, an early sign of chronic kidney disease, and a potential risk factor for cardiovascular disease.

PMID:35524905 | DOI:10.1007/s11695-022-06091-z

EJNMMI Res. 2022 May 7;12(1):28. doi: 10.1186/s13550-022-00900-3.

ABSTRACT

BACKGROUND: Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [¹⁸F]FDG PET/CT in a subgroup of patients.

METHODS: SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [¹⁸F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUV_max) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUV_max values were related to the tumour type (TC versus AC) for both SSTR and [¹⁸F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUV_max values were compared to the pathological status (N⁺ versus N^–) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed.

RESULTS: A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [¹⁸F]FDG PET/CT was available in 46 patients. Analysis of the SUV_max values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUV_max 18.4 vs 3.8; p = 0.003) and significantly higher [¹⁸F]FDG uptake in AC compared to TC (median SUV_max 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [¹⁸F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[¹⁸F]FDG SUV_max values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [¹⁸F]FDG PET/CT (difference 0.17; 95% confidence interval – 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed.

CONCLUSION: Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [¹⁸F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.

PMID:35524900 | DOI:10.1186/s13550-022-00900-3

J Patient Rep Outcomes. 2022 May 7;6(1):44. doi: 10.1186/s41687-022-00452-z.

ABSTRACT

BACKGROUND: Chronic pain management multi/interdisciplinary programs attempt to address all elements of the biopsychosocial model. The primary objective of this retrospective study (based on practice-based audit) was to determine the effectiveness of a patient-centered, comprehensive and intense interdisciplinary pain management program in a publicly funded community-based pain clinic in the Greater Toronto Area.

METHOD: This retrospective longitudinal study was conducted on 218 carefully selected sequential chronic pain patients, with 158 completing a 3-4-month interdisciplinary program between January 2016 and December 2018. Data collected upon exit, at 6 months and 12 months post-discharge included demographic information, pain characteristics, emotional/functional status obtained by validated instruments and global impression of change (GIC). Additionally, social health outcomes (return to work or school) were retrieved through retrospective chart review. Means of pre-and post-program variables were compared to assess changes of each patient’s “journey”.

RESULTS: Physical and mental/ emotional health outcomes at exit, 6 months and 12 months post-discharge, showed initial and sustained, statistically and clinically significant improvement from pre-treatment levels, with GIC (much/very much improved) reported as 77%, 58% and 76%, respectively. Additionally, a substantial positive change in social health outcomes was noted particularly in patients on disability (29%), part time workers gaining full time employment (55%), and students (71%) who improved their level of schooling.

CONCLUSION: The study showed that careful patient selection in a community-based publicly funded interdisciplinary pain management program can produce significant improvement in pain, physical, mental/emotional health and social function, with sustained long-term outcomes.

PMID:35524863 | DOI:10.1186/s41687-022-00452-z

Environ Sci Pollut Res Int. 2022 May 7. doi: 10.1007/s11356-022-20435-3. Online ahead of print.

ABSTRACT

The digital economy, which gradually emerged with a new generation of information technologies, has become an unavoidable reality for manufacturing firms in conducting green innovation activities. In this context, using matched panel data at the province and manufacturing firm levels in China during the period 2011-2019 as the sample, this article examines the nonlinear impact of the digital economy on firm green innovation, and further identifies the moderation mechanism of government quality and the heterogeneity of its effects. The two-way fixed-effects model reveals that there is not a simple linear association between the digital economy and firm green innovation as traditionally perceived, but rather an inverted U-shaped relationship that first promotes and then inhibits, which remains robust after applying endogenous and robustness tests. And most provinces have not yet crossed the inflection point; thus, the digital economy overall positively impacts green innovation. Further analysis shows that government quality positively moderates the relationship between the digital economy and firm green innovation, statistically reflecting that the turning point shifts upwards to the right under a higher-quality government. It is worth noting that, when heterogeneity in firm ownership, scale, and region is considered, the inverted U-shaped curve still exists, but the level of the digital economy at the inflection point differs, and the digital economy plays a greater role in promoting green innovation for state-owned, large-scale, or midwestern firms. This research has significant policy implications as it establishes an inverse U-shaped relationship between the digital economy and firm green innovation and indicates that while a firm’s green patent output increases with the development of digitalization, it begins to decrease after a limit.

PMID:35524847 | DOI:10.1007/s11356-022-20435-3