Tag: nevin manimala

Physiol Rep. 2021 Oct;9(19):e15043. doi: 10.14814/phy2.15043.

ABSTRACT

The Scn5a gene encodes the major pore-forming Na_v 1.5 (α) subunit, of the voltage-gated Na⁺ channel in cardiomyocytes. The key role of Na_v 1.5 in action potential initiation and propagation in both atria and ventricles predisposes organisms lacking Scn5a or carrying Scn5a mutations to cardiac arrhythmogenesis. Loss-of-function Na_v 1.5 genetic abnormalities account for many cases of the human arrhythmic disorder Brugada syndrome (BrS) and related conduction disorders. A murine model with a heterozygous Scn5a deletion recapitulates many electrophysiological phenotypes of BrS. This study examines the relationships between its Scn5a^+/- genotype, resulting transcriptional changes, and the consequent phenotypic presentations of BrS. Of 62 selected protein-coding genes related to cardiomyocyte electrophysiological or homeostatic function, concentrations of mRNA transcribed from 15 differed significantly from wild type (WT). Despite halving apparent ventricular Scn5a transcription heterozygous deletion did not significantly downregulate its atrial expression, raising possibilities of atria-specific feedback mechanisms. Most of the remaining 14 genes whose expression differed significantly between WT and Scn5a^+/- animals involved Ca²⁺ homeostasis specifically in atrial tissue, with no overlap with any ventricular changes. All statistically significant changes in expression were upregulations in the atria and downregulations in the ventricles. This investigation demonstrates the value of future experiments exploring for and clarifying links between transcriptional control of Scn5a and of genes whose protein products coordinate Ca²⁺ regulation and examining their possible roles in BrS.

PMID:34617689 | DOI:10.14814/phy2.15043

Singapore Med J. 2021 Oct 7. doi: 10.11622/smedj.2021130. Online ahead of print.

ABSTRACT

INTRODUCTION: The use of peri-articular (PA) tranexamic acid (TXA) and its efficacy in comparison with intra-articular (IA) tranexamic acid has not been well explored in literature. This retrospective cohort study aims to compare the effects of IA and PA TXA with analgesic components in reducing blood loss and improving immediate post-operative pain relief and functional outcomes in unilateral primary total knee replacement (TKA) patients.

METHODS: 63 patients who underwent a unilateral primary total knee replacement procedure were divided into 2 groups: 42 patients in the IA TXA delivery group, 21 patients in the PA TXA group. 1g of TXA was utilized for all patients. All patients had pericapsular infiltration consisting of 0.5ml of Adrenaline, 0.4ml of Morphine, 1g of Vancomycin, 1ml of Ketorolac and 15ml of Ropivacaine. Outcomes for blood loss, and surrogate markers for immediate functional recovery were measured.

RESULTS: 54.0% of the patients were female, 46.0% male. The mean drop in post-operative Hb levels in the PA and IA group was 2.0g/dL and 1.6 g/dL respectively, and statistically insignificant (p=0.10). The mean HCT drop in the PA and IA group was 6.1% and 5.3% respectively and statistically insignificant (p=0.58). The POD 1 and discharge day flexion angles, POD 1 and POD 2 VAS scores, gait distance on discharge, and length of hospitalization stay were largely similar in both groups.

CONCLUSION: Our study shows that both IA and PA TXA with analgesic components are equally efficient in reducing blood loss and improving immediate postoperative pain relief and functional outcomes.

PMID:34617694 | DOI:10.11622/smedj.2021130

Ann Clin Transl Neurol. 2021 Oct 7. doi: 10.1002/acn3.51457. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relationship between the topography of amyloid-β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia.

METHODS: We evaluated 154 individuals who were assessed with amyloid-β PET with [¹⁸ F]AZD4694, tau-PET with [¹⁸ F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid-β PET with [¹⁸ F]Florbetapir, tau-PET with [¹⁸ F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel-wise linear regressions between amyloid-PET, tau-PET, and their interaction with cognitive function, correcting for age, sex, and years of education.

RESULTS: In both cohorts, we observed that tau-PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR-SoB) scores independently of local amyloid-PET uptake (FWE corrected at p < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau-PET and clinical function were dependent on local amyloid-PET (FWE corrected at p < 0.001).

INTERPRETATION: In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid-β, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid-β and tau pathologies such as the posterior cingulate and medial frontal cortices, tau’s relationship with cognitive dysfunction was dependent on local amyloid-β concentrations. Our results provide evidence that amyloid-β in Alzheimer’s disease influences cognition by potentiating the deleterious effects of tau pathology.

PMID:34617688 | DOI:10.1002/acn3.51457

Pharmacol Res Perspect. 2021 Oct;9(5):e00844. doi: 10.1002/prp2.844.

ABSTRACT

This review aims to assess the benefits and adverse effects of sacubitril/valsartan in heart failure, with a focus on important patient outcomes. A systematic review was conducted of double-blind randomized controlled trials (RCTs) comparing sacubitril/valsartan versus a reference drug, in heart failure patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction, published in French or English. Searches were undertaken of Medline, Cochrane Central, and Embase. The primary outcomes were all-cause mortality and adverse events. From 2 082 articles analyzed, 5 were included. For all-cause mortality, the absolute numbers for HFrEF (2 RCTs, 4627 patients) were 16% on sacubitril/valsartan and 18% on enalapril, with a risk ratio (RR) of 0.85 [CI = 0.78, 0.93], and 13% vs 14% in with HFpEF (2 RCTs, 5097 patients), with no statistical difference. Under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the evidence for HFrEF patients was of moderate quality. For HFrEF patients, an increased risk of symptomatic hypotension and angioedema (low quality of evidence) was shown. There was no statistical difference for the risk of hyperkalemia or worsening renal function. There was a protective RR (0.50 [0.34, 0.75]) for worsening renal function for patients with HFpEF, with a high quality of evidence despite similar absolute numbers (1.4% vs. 2.8%). To keep in mind for shared decision-making, sacubitril/valsartan reduces all-cause mortality in HFrEF patients but for HFpEF further data are needed. Take into consideration the small number of studies to date to assess the risks.

PMID:34617669 | DOI:10.1002/prp2.844

Plant Genome. 2021 Oct 7:e20154. doi: 10.1002/tpg2.20154. Online ahead of print.

ABSTRACT

Grass pea (Lathyrus sativus L.) is an annual legume species, phylogenetically close to pea (Pisum sativum L.), that may be infected by Fusarium oxysporum f. sp. pisi (Fop), the causal agent of fusarium wilt in peas with vast worldwide yield losses. A range of responses varying from high resistance to susceptibility to this pathogen has been reported in grass pea germplasm. Nevertheless, the genetic basis of that diversity of responses is still unknown, hampering its breeding exploitation. To identify genomic regions controlling grass pea resistance to fusarium wilt, a genome-wide association study approach was applied on a grass pea worldwide collection of accessions inoculated with Fop race 2. Disease responses were scored in this collection that was also subjected to high-throughput based single nucleotide polymorphisms (SNP) screening through genotyping-by-sequencing. A total of 5,651 high-quality SNPs were considered for association mapping analysis, performed using mixed linear models accounting for population structure. Because of the absence of a fully assembled grass pea reference genome, SNP markers’ genomic positions were retrieved from the pea’s reference genome v1a. In total, 17 genomic regions were associated with three fusarium wilt response traits in grass pea, anticipating an oligogenic control. Seven of these regions were located on pea chromosomes 1, 6, and 7. The candidate genes underlying these regions were putatively involved in secondary and amino acid metabolism, RNA (regulation of transcription), transport, and development. This study revealed important fusarium wilt resistance favorable grass pea SNP alleles, allowing the development of molecular tools for precision disease resistance breeding.

PMID:34617677 | DOI:10.1002/tpg2.20154

Head Neck. 2021 Oct 7. doi: 10.1002/hed.26887. Online ahead of print.

ABSTRACT

BACKGROUND: We assessed long-term patient-reported dysphagia and xerostomia outcomes following definitive surgical management with transoral robotic surgery (TORS) in patients with oropharyngeal cancer (OPC) via a cross-sectional survey study.

METHODS: Patients with OPC managed with primary oropharyngeal surgery as definitive treatment at least 1 year ago between 2015 and 2019 were identified. The M. D. Anderson Dysphagia Inventory (MDADI) and Xerostomia Inventory (XI) scores were compared across treatment types (i.e., no adjuvant therapy [TORS-A] vs. adjuvant radiotherapy [TORS+RT] vs. adjuvant chemoradiotherapy [TORS+CT/RT]).

RESULTS: The sample had 62 patients (10 TORS-A, 30 TORS+RT, 22 TORS+CT/RT). TORS-A had clinically and statistically significantly better MDADI scores than TORS+RT (p = 0.03) and TORS+CT/RT (p = 0.02), but TORS+RT and TORS+CT/RT were not significantly different. TORS-A had clinically and statistically significantly less XI than TORS+RT (p < 0.01) and TORS+CT/RT (p < 0.01).

CONCLUSIONS: Patients with OPC who have undergone TORS+RT or TORS+CT/RT following surgery face clinically worse dysphagia and xerostomia outcomes relative to patients who undergo TORS-A.

PMID:34617643 | DOI:10.1002/hed.26887

Microsc Res Tech. 2021 Oct 6. doi: 10.1002/jemt.23953. Online ahead of print.

ABSTRACT

The purpose of this study was to examine the effect of different cleaning methods and resin cements on the shear bond strength (SBS) of contaminated zirconia. A total of 92 disc-shaped zirconia specimens were contaminated with different procedures. Then, the specimens were grouped according to cleaning methods and resin cements: no cleaning + Variolink Esthetic DC (CN_V ), no cleaning + Panavia V5 (CN_P ), sandblasted + Variolink Esthetic DC (SB_V ), sandblasted + Panavia V5 (SB_P ), Ivoclean + Variolink Esthetic DC (IC_V ), Ivoclean + Panavia V5 (IC_P ), Katana Cleaner + Variolink Esthetic DC (KC_V ), and Katana Cleaner + Panavia V5 (KC_P ). Following an aging protocol in a 37°C for 1 week, SBS analysis was performed with a universal test machine. For the surface topography and elemental analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS) were used. Significance was evaluated as p < .05 and p < .01. The highest SBS results were found in the SB_P group, showing a statistically significant difference from all other groups (p < .05). For the same cleaning method, Panavia V5 showed statistically significantly higher SBS values than Variolink Esthetic DC (p < .01), except the CN_P -CN_V (p = .880) and KC_P -KC_V (p = .082) groups. The most detected surface elements by EDS were Zr, O, C, and N, respectively. The contaminated zirconia surfaces must be cleaned for successful adhesion. The use of phosphate-containing adhesives in combination with sandblasting will increase the adhesion strength, and universal cleaning agents can be a good alternative to sandblasting.

PMID:34617647 | DOI:10.1002/jemt.23953

Aust Endod J. 2021 Oct 7. doi: 10.1111/aej.12580. Online ahead of print.

ABSTRACT

This research aimed to examine the impact of NaOCl and Irritrol solutions with/without autoclave sterilisation on the cyclic fatigue resistance of ProTaper, WaveOne Gold and Reciproc NiTi files. Seventy files in every group were separated into seven subgroups (n = 10) according to irrigation solutions and sterilisation procedures. The mean and standard deviations of the time to fracture was calculated for each group, and the data statistical analysis was performed (P ≤ 0.05). Significantly higher cyclic fatigue resistance was found in Reciproc files than the other types of files. The differences between the control and other subgroups were found to be statistically insignificant (P > 0.05), except for subgroups 5 and 7 (P ≤ 0.05). Immersing NiTi files in NaOCl or Irritrol with sterilisation for three times considerably reduced the cyclic fatigue resistance of these files. Reciproc files exhibited the highest cyclic fatigue resistance in comparison with ProTaper and WaveOne Gold files.

PMID:34617638 | DOI:10.1111/aej.12580

Aust Endod J. 2021 Oct 7. doi: 10.1111/aej.12575. Online ahead of print.

ABSTRACT

The purpose of this study was to evaluate the disinfection of dentinal tubules with diclofenac sodium (DS), N-acetylcysteine (NAC) and calcium hydroxide (CH). Contaminated dentinal blocks were divided into two control and seven experimental groups (n = 15): CH, DS, NAC, CH + 5% DS, 50% CH + 50% DS, CH + 5% NAC and 50% CH + 50% NAC. After seven days, dentine debris was obtained from two depths of 100 and 200 µm. The bacterial load was assessed by counting the number of colony-forming units (CFUs). Pure DS exhibited maximum antibacterial activity at both depths. At 200 µm, it showed statistically significant differences with all the other groups (P < 0.05). Mixing CH with either 5% or 50% of DS and NAC did not increase the antibacterial efficacy (P > 0.05). Pure DS was most effective in disinfecting dentinal tubules, and mixing CH with DS or NAC is not recommended.

PMID:34617640 | DOI:10.1111/aej.12575

Laryngoscope. 2021 Oct 7. doi: 10.1002/lary.29896. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze the clinical features and otologic manifestations of first branchial cleft anomalies (FBCAs) and the disparity between Work’s classification, and to explore the relationships between postoperative facial paralysis and features of FBCAs.

STUDY DESIGN: Retrospective clinical study.

METHODS: A retrospective analysis of 109 patients with FBCAs was conducted, including clinical characteristics and otologic features. Pearson chi-square tests and Fisher’s exact tests were used to compare disparity between Work’s classification, and the impact factors of postoperative facial paralysis among 86 patients who were explored in follow-up.

RESULTS: Patients with FBCAs presented with otologic symptoms, including cysts or fistula in the external auditory canal (EAC) and periauricular (43.2%), microtia (3.7%), EAC web (1.8%), otitis media (1.8%), and otorrhea (4.6%). Eighty-five cases (78.0%) were type I FBCAs and 24 (22.0%) were type II. Compared to type I FBCAs, type II (58.3%) was more likely to be located deep to the facial nerve (FN) and to have superficial parotidectomy on them (79.2%). This difference was statistically significant (P < .001). FBCAs deep to the FN had a higher incidence of postoperative facial paralysis (P < .05).

CONCLUSION: The majority of patients (55.0%) had otologic symptoms. The FBCAs of Work type II was commonly deep to the FN and superficial parotidectomy was frequently performed. Postoperative facial paralysis was associated with FBCAs located deep to the FN, but not with Work’s type.

LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

PMID:34617600 | DOI:10.1002/lary.29896