Category: Nevin Manimala

NPJ Breast Cancer. 2021 Jul 1;7(1):84. doi: 10.1038/s41523-021-00291-z.

ABSTRACT

While tumor infiltration by CD8⁺ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method ‘occupancy’) to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

PMID:34210991 | DOI:10.1038/s41523-021-00291-z

NPJ Genom Med. 2021 Jul 1;6(1):55. doi: 10.1038/s41525-021-00220-w.

ABSTRACT

Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.

PMID:34210994 | DOI:10.1038/s41525-021-00220-w

Sci Rep. 2021 Jul 1;11(1):13712. doi: 10.1038/s41598-021-92699-7.

ABSTRACT

We present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.

PMID:34211012 | DOI:10.1038/s41598-021-92699-7

NPJ Sci Learn. 2021 Jul 1;6(1):14. doi: 10.1038/s41539-021-00093-9.

ABSTRACT

Knowing when the brain learns is crucial for both the comprehension of memory formation and consolidation and for developing new training and neurorehabilitation strategies in healthy and patient populations. Recently, a rapid form of offline learning developing during short rest periods has been shown to account for most of procedural learning, leading to the hypothesis that the brain mainly learns during rest between practice periods. Nonetheless, procedural learning has several subcomponents not disentangled in previous studies investigating learning dynamics, such as acquiring the statistical regularities of the task, or else the high-order rules that regulate its organization. Here we analyzed 506 behavioral sessions of implicit visuomotor deterministic and probabilistic sequence learning tasks, allowing the distinction between general skill learning, statistical learning, and high-order rule learning. Our results show that the temporal dynamics of apparently simultaneous learning processes differ. While high-order rule learning is acquired offline, statistical learning is evidenced online. These findings open new avenues on the short-scale temporal dynamics of learning and memory consolidation and reveal a fundamental distinction between statistical and high-order rule learning, the former benefiting from online evidence accumulation and the latter requiring short rest periods for rapid consolidation.

PMID:34210989 | DOI:10.1038/s41539-021-00093-9

J Trauma Nurs. 2021 Jul-Aug 01;28(4):228-234. doi: 10.1097/JTN.0000000000000590.

ABSTRACT

BACKGROUND: Evidence suggests that the effect of 0.12% chlorhexidine (CHX) use for oral care on the development of ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT) is lacking. Evidence-based approaches to the prevention of VAP and VAT are of paramount importance for improving patients’ outcomes.

OBJECTIVES: This study aimed to (1) compare the effect of 0.12% CHX use for oral care on preventing VAP and VAT with the placebo group, as well as (2) compare its effect on oral health and prevention of oral microbial colonization with the placebo group.

METHODS: Prospective, single-blinded, randomized controlled trial performed in 2 intensive care units at a hospital. The sample comprised 57 mechanically ventilated adults randomly allocated to the 0.12% CHX group and the placebo group. Barnason’s oral assessment guide was used to evaluate the oral health of both groups before oral care during the first 24 hr of tracheal intubation (Day 0) and at Day 2 and Day 3. Oropharyngeal secretion, endotracheal tube aspirate, and nonbronchoscopic bronchoalveolar lavage samples were collected on Day 0 and Day 3.

RESULTS: The rate of VAT development was not statistically different between the groups (p = .318). However, a significant difference existed in the rate of VAP development (p = .043). The frequency of oropharyngeal colonization significantly decreased in the 0.12% CHX group compared with the placebo group at Day 3 (p = .001).

CONCLUSION: The use of 0.12% CHX for oral care could be effective for VAP prevention and reducing microbial colonization in mechanically ventilated patients.

PMID:34210941 | DOI:10.1097/JTN.0000000000000590

J Contemp Dent Pract. 2021 Mar 1;22(3):259-263.

ABSTRACT

AIM AND OBJECTIVE: The aim of this study was to compare the formation of dentinal cracks with nickel-titanium (NiTi) instruments working in continuous rotation and reciprocating motion.

MATERIALS AND METHODS: One hundred sixty extracted human mandibular first molars were selected for the study. The mesial roots were resected and mounted in resin blocks with simulated periodontal ligaments. Those teeth were randomly assigned to five groups (n = 32 teeth/group). The first one was treated with K-files and served as control group, and the remaining 128 teeth were divided into 4 groups depending on the root canal preparation technique. Group 2 samples were prepared by sequential ProTaper Universal (PTU), group 3 samples with rotary ProTaper Universal (RPTU), group 4 achieved by the One Shape (OS), and group 5 with the WaveOne (WO) primary files. Roots were then horizontally sectioned at 3, 6, and 9 mm from the apex, and the slices were then observed under a stereomicroscope at ×40 magnification to determine the presence of internal dentinal microcracks. The presence or absence of dentinal defaults was recorded and the statistical analysis was performed by Pearson Chi-square test. The significance level was set at p < 0.05. The study was made in the oral biology and biotechnology research laboratory of the faculty of medical dentistry of Rabat, Morocco.

RESULTS: No dentinal defect was seen with the stainless steel hand file (group 1). The manual PTU (group 2), the RPTU (group 3), the OS (group 4), and the WO (group 5) in reciprocating motion caused cracks in 15.6%, 12.4%, 21.9%, and 6.2% of samples, respectively. The highest percentage of dentinal defect was showed in group 4 but without significant difference with the other group (p > 0.05).

CONCLUSIONS: Dentinal cracks are produced indifferently of motion kinematics. Within the limits of this study and the current literature, such incidence is less with instruments working in reciprocating motion compared with those working in continuous rotation. Manual and rotary NiTi sequential systems showed fewer microcracks than the single file system working by continuous rotation motion.

PMID:34210925

J Contemp Dent Pract. 2021 Mar 1;22(3):278-283.

ABSTRACT

AIM: To compare the bond strength of addition silicone with different commonly used custom tray materials by means of different retentive methods (mechanical, chemical, and a combination of chemical and mechanical methods).

MATERIALS AND METHODS: Fabrications of 90 samples of different tray resin materials were done using an aluminum mold. They were divided into three main groups. Perforations, adhesive application, and a combination of both were done according to the grouping of samples. Polyvinyl siloxane material (medium body) was loaded over the samples. A universal testing machine with a crosshead speed of 5 mm/minute was used to determine the tensile bond strength of tray resin samples to medium body impression material. Based on these values, Student’s-test, group statistics, and ANOVA test were used for statistical analysis.

RESULTS: Visible light cure (VLC) resin showed the highest bond strength in chemicomechanical methods. This was followed by repair resin material. Tray resin material showed poor bond strength in all three retentive methods. The mechanical method was the least retentive in all three resin materials.

CLINICAL SIGNIFICANCE: VLC tray resin material can be used with chemical and mechanical retention in clinical situations to make predictably accurate elastomeric impressions.

CONCLUSION: It was concluded that VLC tray resin shows good bond strength with polyvinyl siloxane impression material when both mechanical perforations and adhesive applications were done.

PMID:34210929

J Contemp Dent Pract. 2021 Mar 1;22(3):316-323.

ABSTRACT

AIM: To assess the effectiveness of adjuvant analgesics/anesthetics in pain control after separator placement compared with no medication.

BACKGROUND: Separator placement to create space for cementing bands is the first clinical procedure done in orthodontics. Pain in this stage can negatively affect patient compliance and trust in the clinician. To date, there is no universally accepted regimen for pain control.

MATERIALS AND METHODS: Electronic databases of PubMed, Scopus, and Web of Science were searched. One hundred and thirty-two potentially relevant studies were found. A total of eight randomized clinical trials including 642 subjects were selected. Data were extracted into customized forms, and selected studies were assessed for risk of bias using the Joanna Briggs Institute.

RESULTS: Results showed the use of analgesics led to lower reported pain scores at almost all time intervals. NSAIDs resulted in a statistically significant reduction in pain compared to a control group.

CONCLUSION: According to the available literature, the use of analgesics is effective in controlling orthodontic pain due to separators. Acetaminophen and ibuprofen show a stable analgesic effect.

CLINICAL IMPLICATION: Acetaminophen 650 mg or ibuprofen 400 mg taken 1 hour prior to separator placement can reduce pain associated with the procedure.

PMID:34210935

J Contemp Dent Pract. 2021 Mar 1;22(3):237-241.

ABSTRACT

AIM AND OBJECTIVE: The present study aimed at evaluating the effectiveness of diverse remineralizing agents on artificial enamel lesion using confocal laser scanning microscope (CLSM).

MATERIALS AND METHODS: Totally 80 mandibular premolars which were single rooted were included. All teeth were suspended in a demineralizing solution to create artificial enamel lesions on the exposed enamel. The samples were separated randomly into four groups (20 each) depending on the application of the remineralizing agents as follows: group 1: control; group 2: calcium sucrose phosphate (CaSP); group 3: fluoride varnish; and group 4: casein phosphopeptides-amorphous calcium phosphate (CPP-ACP). The samples in individual group were treated with the corresponding remineralizing agent (except for the control group) two times a day for 14 days. The experimental and control groups were exposed to CLSM assessment to analyze the data of remineralization and demineralization.

RESULTS: The mean depth of remineralization of fluoride varnish group was slightly more compared to other groups. The highest mean depth of remineralization was found in the fluoride varnish group (122.26 ± 0.28) followed by CaSP (110.58 ± 1.34), CPP-ACP (107.08 ± 0.48), and control (157.78 ± 0.46) groups. The different comparisons among the remineralization material groups showed a statistically significant difference (p < 0.05) in almost all groups except group 2 vs group 4.

CONCLUSION: This study concluded that improved remineralization of artificial enamel lesion could be achieved with the fluoride varnish group when compared to the CaSP and CPP-ACP groups.

CLINICAL SIGNIFICANCE: Remineralization as a treatment technique has received a lot of consideration from clinicians. The process of remineralization and demineralization is considered an active process categorized by the movement of calcium and phosphate in and out of the enamel. Presently, the attention has changed toward increasing the resistance of the tooth by applying remineralizing agents topically, which has led to the notable fall in dental caries.

PMID:34210921

J Contemp Dent Pract. 2021 Mar 1;22(3):248-252.

ABSTRACT

AIM AND OBJECTIVE: This study is conducted to find the association of BMP2 (bone morphogenic protein 2) gene variant rs1005464 and rs15705 with skeletal class I crowding cases.

MATERIALS AND METHODS: Blood samples from 60 subjects who visited the Department of Orthodontics and Dentofacial Orthopaedics, D.A.P.M.R.V. Dental College, Bengaluru, were taken after written informed consent. These were divided into two groups: group A with 30 subjects having skeletal class I bases with crowding and group B with 30 subjects having skeletal class I bases without visible crowding or spacing (±2 mm). Around 2 mL of venous blood sample was procured from cases and controls after careful examination. All the samples were then subjected to polymerase chain reaction followed by DNA sequencing and capillary electrophoresis. BMP2 rs1005464 and rs15705 gene variants were assessed and Z-Test was used for statistical analysis.

RESULT: GG (p = 0.001) and CC (p = 0.0024) genotype of BMP2 gene variant rs1005464 and rs15705, respectively, are significantly associated with skeletal class I crowding cases.

CONCLUSION: This study concludes that BMP2 variants rs1005464 and rs15705 can be used as genetic markers for skeletal class I bases having crowding.

CLINICAL SIGNIFICANCE: Predisposing genetic markers BMP2 can be identified prior and this would help in predicting the probability of potential crowding in the future and this would help in early prevention and intervention of crowding.

PMID:34210923