Nevin Manimala

Int J Comput Assist Radiol Surg. 2022 Oct 22. doi: 10.1007/s11548-022-02776-z. Online ahead of print.

ABSTRACT

PURPOSE: To elucidate the role of atrial anatomical remodeling in atrial fibrillation (AF), we proposed an automatic method to extract and analyze morphological characteristics in left atrium (LA), left atrial appendage (LAA) and pulmonary veins (PVs) and constructed classifiers to evaluate the importance of identified features.

METHODS: The LA, LAA and PVs were segmented from contrast computed tomography images using either a commercial software or a self-adaptive algorithm proposed by us. From these segments, geometric and fractal features were calculated automatically. To reduce the model complexity, a feature selection procedure is adopted, with the important features identified via univariable analysis and ensemble feature selection. The effectiveness of this approach is well illustrated by the high accuracy of our models.

RESULTS: Morphological features, such as LAA ostium dimensions and LA volume and surface area, statistically distinguished ([Formula: see text]) AF patients or AF with LAA filling defects (AF(def+)) patients among all patients. On the test set, the best model to predict AF among all patients had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI, 0.8-1) and the best model to predict AF(def+) among all patients had an AUC of 0.92 (95% CI, 0.81-1).

CONCLUSION: This study automatically extracted and analyzed atrial morphology in AF and identified atrial anatomical remodeling that statistically distinguished AF or AF(def+). The importance of identified atrial morphological features in characterizing AF or AF(def+) was validated by corresponding classifiers. This work provides a good foundation for a complete computer-assisted diagnostic workflow of predicting the occurrence of AF or AF(def+).

PMID:36272019 | DOI:10.1007/s11548-022-02776-z

Clin Oral Investig. 2022 Oct 22. doi: 10.1007/s00784-022-04755-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the cleansing efficacy of an auto-cleaning device with nylon bristles (Y-brush®) to that of manual toothbrushing.

MATERIALS AND METHODS: Twenty probands refrained from oral hygiene for 3 days. Rustogi Modified Navy Plaque Index was assessed before and after (randomized) toothbrushing either with the auto-cleaning device for 5 s per jaw or with a manual toothbrush for a freely chosen time up to 4 min. The clinical investigation was repeated in a cross-over design. In a third trial period, the brushing time for auto-cleaning was increased to 15 s per jaw. The study was supplemented by plaster cast analyses.

RESULTS: Full-mouth plaque reduction was higher with manual toothbrushing than with auto-cleaning for 5 s per jaw (p < 0.001). There was no statistically significant difference on smooth tooth surfaces but on marginal and interdental sites. Increasing the brushing time of auto-cleaning to 15 s per jaw resulted in a comparable full-mouth plaque reduction as with manual toothbrushing (p = 0.177). In 95% of individuals, the device was too short not completely covering second molars. In 30.67% of teeth, the gingival margin was not covered by bristles.

CONCLUSIONS: Auto-cleaning devices with nylon bristles have a future potential to reach plaque reduction levels comparable to manual toothbrushing, although manufacturers must focus on improving an accurate fit.

CLINICAL RELEVANCE: Under the premise of an ameliorated fit, the auto-cleaning device might be recommendable for people with low brushing efficacy. Interdental sites remain a failure point if adjunct interdental cleaning is not viable.

PMID:36272010 | DOI:10.1007/s00784-022-04755-9

Eur Spine J. 2022 Oct 22. doi: 10.1007/s00586-022-07425-2. Online ahead of print.

ABSTRACT

PURPOSE: The Oswestry Disability Index (ODI) and the Neck Disability Index (NDI) scoring algorithms used by the Swedish spine register (Swespine) until April 2022 handled missing items somewhat differently than the original algorithms. The purpose of the current study was to evaluate possible differences in the ODI and NDI scores between the Swespine and the original scoring algorithms.

METHODS: Patients surgically treated for degenerative conditions of the lumbar or cervical spine between 2003-2019 (lumbar) and 2006-2019 (cervical) were identified in Swespine. Preoperative and 1-year postoperative ODI/NDI data were used to evaluate differences between the Swespine and the original ODI/NDI algorithms with adjustment for at most 1 or 2 missing items using mean imputation.

RESULTS: The preoperative as well as the 1-year postoperative ODI/NDI were approximately 1 unit out of 100 smaller for the Swespine algorithm, irrespective of adjustment model. The differences between preoperative and postoperative ODI/NDI scores were similar between the Swespine and the original scoring algorithms. There were occasional statistically significant differences between the preoperative-postoperative differences due to large sample sizes.

CONCLUSIONS: The Swespine algorithms, used until April 2022, underestimated the ODI and NDI by approximately 1 out of 100 units compared with the original algorithms. In addition, there were no statistically significant differences between the original algorithms when adjusting for at most 1 or 2 missing items. The algorithm has now been changed, also for historical data.

PMID:36271985 | DOI:10.1007/s00586-022-07425-2

Sci China Life Sci. 2022 Oct 20. doi: 10.1007/s11427-021-2179-8. Online ahead of print.

ABSTRACT

DNMT1 is a DNA methyltransferase that catalyzes and maintains methylation in CpG dinucleotides. It blocks the entrance of DNA into the catalytic pocket via the replication foci targeting sequence (RFTS) domain. Recent studies have shown that an H3-tail-conjugated two-mono-ubiquitin mark (H3Ub2) activates DNMT1 by binding to the RFTS domain. However, the activation mechanism of DNMT1 remains unclear. In this work, we combine various sampling methods of extensive simulations, including conventional molecular dynamics, Gaussian-accelerated molecular dynamics, and coarse-grained molecular dynamics, to elucidate the activation mechanism of DNMT1. Geometric and energy analyses show that binding of H3Ub2 to the RFTS domain of DNMT1 results in the bending of the α4-helix in the RFTS domain at approximately 30°-35°, and the RFTS domain rotates ∼20° anti-clockwise and moves ∼3 Å away from the target recognition domain (TRD). The hydrogen-bonding network at the RFTS-TRD interface is significantly disrupted, implying that the RFTS domain is dissociated from the catalytic core, which contributes to activating the auto-inhibited conformation of DNMT1. These results provide structural and dynamic evidence for the role of H3Ub2 in regulating the catalytic activity of DNMT1.

PMID:36271982 | DOI:10.1007/s11427-021-2179-8

Mol Biol Rep. 2022 Oct 22. doi: 10.1007/s11033-022-08017-5. Online ahead of print.

ABSTRACT

BACKGROUND: Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis.

METHODS AND RESULTS: Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated.

CONCLUSIONS: Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2.

PMID:36271980 | DOI:10.1007/s11033-022-08017-5

J Math Biol. 2022 Oct 22;85(5):58. doi: 10.1007/s00285-022-01827-y.

ABSTRACT

Atherosclerosis, one of the leading causes of death in USA and worldwide, begins with a lesion in the intima of the arterial wall, allowing LDL to penetrate into the intima where they are oxidized. The immune system considers these oxidized LDL as a dangerous substance and tasks the macrophages to attack them; incapacitated macrophages become foam cells and leads to the formation of a plaque. As the plaque continues to grow, it progressively restricts the blood flow, possibly triggering heart attack or stroke. Because the blood vessels tend to be circular, two-space dimensional cross section model is a good approximation, and the two-space dimensional models are studied in Friedman et al. (J Differ Equ 259(4):1227-1255, 2015) and Zhao and Hu (J Differ Equ 288:250-287, 2021). It is interesting to see whether a true three-space dimensional stationary solution can be developed. We shall establish a three-space dimensional stationary solution for the mathematical model of the initiation and development of atherosclerosis which involves LDL and HDL cholesterols, macrophages and foam cells. The model is a highly nonlinear and coupled system of PDEs with a free boundary, the interface between the plaque and the blood flow. We establish infinite branches of symmetry-breaking stationary solutions which bifurcate from the annular stationary solution in the longitude direction.

PMID:36271960 | DOI:10.1007/s00285-022-01827-y

J Exp Orthop. 2022 Oct 22;9(1):107. doi: 10.1186/s40634-022-00543-2.

ABSTRACT

PURPOSE: The anterolateral ligament (ALL) has been defined as a key stabilizer of internal tibial rotation at 35° or more of knee flexion, with a minimal primary or secondary stabilizing role in the AP direction. This study aimed to demonstrate that anatomical reconstruction of the ALL confers rotational stability equal to that of the uninjured knee.

HYPOTHESIS: anteroposterior (AP) and rotatory laxity will significantly vary after ALL tenotomy and ALL reconstruction with the author’s previously described technique.

METHODS: After ultrasound (US) ALL identification, different kinematic measurements were performed with an image-less Computer-Assisted Navigation System with dedicated software for Laxity Analysis in 5 knee specimens. Anteroposterior (AP) translations and varus/valgus (VV) and Internal-External (IE) rotations were evaluated by two trained orthopedic surgeons before ALL section, after ALL section, and after ALL anatomical reconstruction with doubled ipsilateral autologous gracilis tendon.

RESULTS: ALL resection significantly increased laxity in IE rotations with knee 90° flexed (IE90) and AP translation with tibia internally rotated and the knee 30° flexed (APlat) (p < 0.05). ALL reconstruction significantly reduced laxity in IE90 and APlat (p < 0.05) and reduced VV rotations at 30° of flexion (VV30) (p < 0.05). There were no statistically significant elongation differences between native ALL and reconstructed ALL (graft) during laxity tests. The inter-operator repeatability of the tests was excellent for each measurement.

CONCLUSIONS: ALL acted as an important internal tibial rotation restrain at 90° and a significant (secondary) AP stabilizer at 30° of knee flexion. The presented ALL reconstruction technique significantly restored the increase of knee laxity produced by the ALL section.

SCIENTIFIC LEVEL: Case-Controlled Laboratory Study, Level III.

PMID:36271953 | DOI:10.1186/s40634-022-00543-2

Eur J Appl Physiol. 2022 Oct 22. doi: 10.1007/s00421-022-05072-5. Online ahead of print.

ABSTRACT

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.

METHODS: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO₃) or ACE inhibitor (ACE_i: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention.

RESULTS: Forty-eight participants (n_ACEi = 23, n_PLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACE_i (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus.

CONCLUSION: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

PMID:36271942 | DOI:10.1007/s00421-022-05072-5

Ann Hematol. 2022 Oct 22. doi: 10.1007/s00277-022-05003-6. Online ahead of print.

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) show suboptimal responses to the vaccines against SARS-CoV-2; it has been shown though that a booster dose of the BNT162b2 vaccine may lead to a significant increase in the seroconversion rates of immunocompromised patients. We conducted a prospective, non-interventional study to evaluate the immunogenicity of a third dose of the BNT162b2 vaccine in adult patients with CLL. Sera were tested before the first, after the second, and before and after the third dose for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD). Thirty-nine patients with CLL were included in the study. The seroconversion rate increased from 28.2% before the third dose to 64.1% after the third dose and was higher in treatment-naïve patients (72.7% versus 47.1% in actively treated patients, p = 0.042). All but one patient achieving a seroconversion after the second dose retained after the third, while eight patients not achieving a seroconversion after the second dose (38.1%), did so after the third. Moreover, patients actively treated with venetoclax had a higher seroconversion rate than those treated with ibrutinib (87.5% versus 14.3%, p = 0.001). This study confirms the beneficial effect of a third dose of the BNT162b2 vaccine on the seroconversion rate in patients with CLL. Our results also strongly suggest that the use of venetoclax is correlated with higher immunogenicity/seroconversion rates than that of ibrutinib, a finding that has been reported by another study. A treatment strategy change during the pandemic favoring the use of venetoclax may be suggested based on our results, although these results should be validated in larger studies.

PMID:36271935 | DOI:10.1007/s00277-022-05003-6

Eur Arch Psychiatry Clin Neurosci. 2022 Oct 22. doi: 10.1007/s00406-022-01464-y. Online ahead of print.

ABSTRACT

Enhanced behavioral interventions are gaining increasing interest as innovative treatment strategies for major depressive disorder (MDD). In this study protocol, we propose to examine the synergistic effects of a self-administered home-treatment, encompassing transcranial direct current stimulation (tDCS) along with a video game based training of attentional control. The study is designed as a two-arm, double-blind, randomized and placebo-controlled multi-center trial (ClinicalTrials.gov: NCT04953208). At three study sites (Israel, Latvia, and Germany), 114 patients with a primary diagnosis of MDD undergo 6 weeks of intervention (30 × 30 min sessions). Patients assigned to the intervention group receive active tDCS (anode F3 and cathode F4; 2 mA intensity) and an action-like video game, while those assigned to the control group receive sham tDCS along with a control video game. An electrode-positioning algorithm is used to standardize tDCS electrode positioning. Participants perform their designated treatment at the clinical center (sessions 1-5) and continue treatment at home under remote supervision (sessions 6-30). The endpoints are feasibility (primary) and safety, treatment efficacy (secondary, i.e., change of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week six from baseline, clinical response and remission, measures of social, occupational, and psychological functioning, quality of life, and cognitive control (tertiary). Demonstrating the feasibility, safety, and efficacy of this novel combined intervention could expand the range of available treatments for MDD to neuromodulation enhanced interventions providing cost-effective, easily accessible, and low-risk treatment options.ClinicalTrials.gov: NCT04953208.

PMID:36271928 | DOI:10.1007/s00406-022-01464-y