Nevin Manimala

Respiration. 2022 Jan 3:1-12. doi: 10.1159/000520884. Online ahead of print.

ABSTRACT

BACKGROUND: Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial.

OBJECTIVES: This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients.

METHODS: A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14-30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores.

RESULTS: Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40-0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28-0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78-2.84]). The risk of and time to the next exacerbation was similar for both groups.

CONCLUSION: Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.

PMID:34979502 | DOI:10.1159/000520884

Curr Res Transl Med. 2021 Dec 31;70(2):103330. doi: 10.1016/j.retram.2021.103330. Online ahead of print.

ABSTRACT

PURPOSE: MALT lymphoma is thought to have a genetic component. Genetic studies in the greek population are rare and genetic determinants remain to be established. The current study aimed to seek correlations between genetic polymorphisms and risk of MALT lymphoma in the Greek population.

PATIENTS AND METHODS: 83 MALT lymphoma patients and 60 age-matched healthy outpatients were recruited. SNPs in TNFa, LTA and CTLA-4 genes and IL1RN-VNTR and GSTT1 and GSTTM1 null polymorphisms were genotyped using published PCR/PCR-RFLP methods, while two novel PCR-RFLP methods were developed for IL-22 rs7314777 and TCF19 rs7750641 SNPs. Part of the results was validated by DNA-sequencing. Statistical analysis was performed using SPSS and the SNPstats bioinformatic tool.

RESULTS: The mean age of the patients and controls were 55.9 and 56.2 years respectively. The majority of patients (63) suffered gastric marzinal zone lymphoma (GMZL) and 71.1% were stage I at diagnosis. A statistically significant association was noted for the CTLA-4 49A/ G G variant (OR:2.56,p: 0.006) and the TCF19 rs7750641 SNP T variant (OR: 3.86, p:0.023).

CONCLUSIONS: Our study confirmed a role for CTLA-4 49A/G and TCF19 rs7750641 SNPs in the Greek population. Additional studies could help confirm these associations and possibly link them to prognosis or response to treatment parameters.

PMID:34979486 | DOI:10.1016/j.retram.2021.103330

Gait Posture. 2021 Dec 30;92:435-441. doi: 10.1016/j.gaitpost.2021.12.017. Online ahead of print.

ABSTRACT

BACKGROUND: The use of insoles, which is increasingly widespread, can promote changes in biomechanics during running.

RESEARCH QUESTION: Can the use of insoles with various patterns of infracapital support influence factors related to the dynamic stability of the lower limbs during running on a treadmill in recreational runners?

METHODS: This is controlled single-blind repeated measures. Static baropodometric data were collected, as well as kinematic data for the lower limbs and electromyographic data for the gluteus maximus and gluteus medius muscles, for twelve recreational runners on a treadmill using four models of insoles (neutral and with forefoot elements – infracapital bar).

RESULTS: Neutral insoles were able to reduce laterolateral displacement, increase the displacement of the mass to the posterior, and increase the lateral rotation of the left knee and medial rotation of the right hip. Insoles with a 2 mm total infracapital bar were able to move the mass to the posterior, increase laterolateral displacement and activate the gluteus medius. Insoles with a 2 mm medial infracapital bar were able to increase the displacement of the mass to the posterior, increase the adduction of left hip and the medial rotation of right hip, and activate the gluteus medius. Insoles with a 4 mm medial infracapital element were able to move the body mass to the posterior and to the left, increase laterolateral displacement, increase the adduction of left hip, the medial rotation of right hip and the abduction of right knee.

SIGNIFICANCE: The insoles evaluated in the present study were able to modify biomechanical variables of recreational runners related to dynamic stability during running on a treadmill and static baropodometric variables.

PMID:34979430 | DOI:10.1016/j.gaitpost.2021.12.017

Am J Emerg Med. 2021 Dec 28;53:54-58. doi: 10.1016/j.ajem.2021.12.056. Online ahead of print.

ABSTRACT

INTRODUCTION: Space travel is expected to grow in the near future, which could lead to a higher burden of sudden cardiac arrest (SCA) in astronauts. Current methods to perform cardiopulmonary resuscitation in microgravity perform below earth-based standards in terms of depth achieved and the ability to sustain chest compressions (CC). We hypothesised that an automated chest compression device (ACCD) delivers high-quality CC during simulated micro- and hypergravity conditions.

METHODS: Data on CC depth, rate, release and position utilising an ACCD were collected continuously during a parabolic flight with alternating conditions of normogravity (1 G), hypergravity (1.8 G) and microgravity (0 G), performed on a training manikin fixed in place. Kruskal-Wallis and Mann-Withney U test were used for comparison purpose.

RESULTS: Mechanical CC was performed continuously during the flight; no missed compressions or pauses were recorded. Mean depth of CC showed minimal but statistically significant variations in compression depth during the different phases of the parabolic flight (microgravity 49.9 ± 0.7, normogravity 49.9 ± 0.5 and hypergravity 50.1 ± 0.6 mm, p < 0.001).

CONCLUSION: The use of an ACCD allows continuous delivery of high-quality CC in micro- and hypergravity as experienced in parabolic flight. The decision to bring extra load for a high impact and low likelihood event should be based on specifics of its crew’s mission and health status, and the establishment of standard operating procedures.

PMID:34979409 | DOI:10.1016/j.ajem.2021.12.056

Comput Biol Med. 2021 Dec 30;141:105163. doi: 10.1016/j.compbiomed.2021.105163. Online ahead of print.

ABSTRACT

The spike protein of SARS-CoV-2 and the host ACE2 receptor plays a vital role in the entry to the cell. Among which the hotspot residue 501 is continuously subjected to positive selection pressure and induces unusual virulence. Keeping in view the importance of the hot spot residue 501, we predicted the potentially emerging structural variants of 501 residue. We analyzed the binding pattern of wild type and mutants (Spike RBD) to the ACE2 receptor by deciphering variations in the amino acids’ interaction networks by graph kernels along with evolutionary, network metrics, and energetic information. Our analysis revealed that N501I, N501T, and N501V increase the binding affinity and alter the intra and inter-residue bonding networks. The N501T has shown strong positive selection and fitness in other animals. Docking results and repeated simulations (three times) confirmed the structural stability and tighter binding of these three variants, correlated with the previous results following the global stability trend. Consequently, we reported three variants N501I, N501T, and N501V could worsen the situation further if they emerged. The relations between the viral fitness and binding affinity is a complicated game thus the emergence of high affinity mutations in the SARS-CoV-2 RBD brings up the question of whether or not positive selection favours these mutations or not?

PMID:34979405 | DOI:10.1016/j.compbiomed.2021.105163

J Pediatr Nurs. 2021 Dec 31;63:46-51. doi: 10.1016/j.pedn.2021.12.018. Online ahead of print.

ABSTRACT

PURPOSE: Evidence-based practice (EBP) within healthcare leads to improved patient outcomes, high-quality care, job satisfaction, reduced turnover, professional autonomy, and validates nursing practice. Although a plethora of research focuses on implementing EBP, there has been little attention on assessing organizational readiness for integration. The primary aims of this study were to explore nursing beliefs and attitudes about EBP and explore the culture and readiness among pediatric nurses for system-wide integration of EBP.

DESIGN AND METHODS: This study was a quantitative, cross-sectional survey-based study conducted at a large pediatric health system.

RESULTS: Overall pediatric nurses had a mean score of 61.78 ± 9.32 on the EBPB (n = 396). Results of the EBPB Scale and OCRSIEP showed no statistical difference between nursing roles EBPB scores; however, nursing leaders had higher scores than any other nursing role. The OCRSIEP had a mean score of 84.98 ± 19.53 (n = 388).

CONCLUSIONS: Findings suggest that pediatric nurses believe that EBP results in the best clinical care for patients and can improve clinical care, but they lack the skills and time necessary to engage in the process. This study found that increasing awareness of EBP resources and developing EBP competencies may assist pediatric nurse leaders with EBP integration into daily practice.

PRACTICE IMPLICATIONS: Increasing visibility and competencies of EBP may positively impact organizational readiness by increasing confidence needed to remove identified barriers and engrain EBP in the organization’s culture.

PMID:34979382 | DOI:10.1016/j.pedn.2021.12.018

J Mol Graph Model. 2021 Dec 28;112:108119. doi: 10.1016/j.jmgm.2021.108119. Online ahead of print.

ABSTRACT

G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Their abundance and role in nearly all physiological systems make GPCR the largest protein family targeted for development of pharmaceuticals. Ligand discovery aimed at identification of chemical tools and drug leads is aided by molecular docking simulations that allow critical analysis of the potential interactions between small molecules and proteins in resulting complexes. However, blind assessments of ligand pose quality and affinity prediction have thus far not provided broadly generalizable performance expectations for docking into experimentally-characterized GPCR targets. Likewise, the relative importance of receptor activation state and ligand function differences have also not been systematically assessed. This study compares performance when docking ligands of varied function into varied GPCR activation states in the absence of extensive resampling of the input GPCR structure, and only limited sidechain flexibility after ligand placement. Simulations were performed using 37 experimental structures of 11 Class A GPCR crystallized in multiple activation states (giving rise to 37 self-docking and 68 cross docking simulations). Our results show that one specific subset of cross-docking simulations gave results of similar quality to self-docking. Median ligand RMSD values for top-scored poses were 1.2 Å and 2.0 Å for self-docking and State_Match/Function_Match cross-docking, respectively. The distributions of ligand RMSD values were not statistically different for these two conditions, according to a Kolmogorov-Smirnov test. Therefore, docking performance against GPCR targets can be estimated in advance based on docking target structure activation states, with higher accuracy expected when docking agonists into active state structures and inverse agonists or antagonists into inactive state structures. Receptor conformational sampling in advance of docking or receptor conformational adjustment after docking are more likely to produce substantial improvements for other pairings of receptor activation state and ligand function.

PMID:34979368 | DOI:10.1016/j.jmgm.2021.108119

Parkinsonism Relat Disord. 2021 Dec 23;95:28-34. doi: 10.1016/j.parkreldis.2021.12.014. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite substantial clinical and pathophysiological differences, the characteristics of tremor in Parkinson’s disease (PD) and essential tremor (ET) patients bear certain similarities. The presented study delineates tremor-related structural networks in these two disorders.

METHODS: 42 non-advanced PD patients (18 tremor-dominant, 24 without substantial tremor), 17 ET, and 45 healthy controls underwent high-angular resolution diffusion-weighted imaging acquisition to reconstruct their structural motor connectomes as a proxy of the anatomical interconnections between motor network regions, implementing state-of-the-art globally optimised probabilistic tractography.

RESULTS: When compared to healthy controls, ET patients exhibited higher structural connectivity in the cerebello-thalamo-cortical network. Interestingly, the comparison of tremor-dominant PD patients and PD patients without tremor yielded very similar results – higher structural connectivity in tremor-dominant PD sharing multiple nodes with the tremor network detected in ET, despite the generally lower structural connectivity between basal ganglia and frontal cortex in the whole PD group when compared to healthy controls.

CONCLUSION: The higher structural connectivity of the cerebello-thalamo-cortical network seems to be the dominant tremor driver in both PD and ET. While it appears to be the only tremor-related network in ET, its combination with large scale hypoconnectivity in the frontal cortico-subcortical network in PD may explain different clinical features of tremor in these two disorders.

PMID:34979362 | DOI:10.1016/j.parkreldis.2021.12.014

Oper Dent. 2022 Jan 3. doi: 10.2341/20-270-L. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to investigate the effects of hydrothermal treatment on four types of monolithic, translucent, yttria-stabilized, tetragonal zirconia polycrystals (Y-TZPs).

METHODS AND MATERIALS: Two commercially available Y-TZP brands-SuperfectZir High Translucency (Aidite Technology Co, China) and Katana HT (Kuraray Noritake Dental, Japan) were assessed. For each brand of Y-TZP, materials of four coloring types, including noncolored (NC), colored by staining (CS), precolored (PC), and multilayered (ML) specimens were investigated after hydrothermal aging in an autoclave at 134°C/0.2 MPa for 0 (control group), 5, 10, and 20 hours. The tetragonal-to-monoclinic phase transformation, surface roughness, flexural strength, and structural reliability (Weibull analysis) were measured and statistically analyzed (α=0.05). The subsurface microstructure was analyzed with scanning electron microscopy.

RESULTS: The group ML exhibited the lowest flexural strength and Weibull characteristic strength among the four coloring types (p<0.05). Slight increases in the monoclinic phase volume, flexural strength, and Weibull characteristic strength were observed after hydrothermal aging (pall<0.05). Regardless of coloring type, no significant effects of aging on the Weibull modulus or surface roughness were found for the tested materials. Compared with the Katana HT cross-sections, the SuperfectZir High Translucency cross-sections exhibited a similar but thicker transformation zone.

CONCLUSIONS: The coloring procedure and material type were found to affect the mechanical properties and aging resistance of translucent monolithic Y-TZP ceramics. Regardless of the aging time, the surface roughness of the tested Y-TZP ceramics remained unchanged.

PMID:34979031 | DOI:10.2341/20-270-L

Oper Dent. 2022 Jan 3. doi: 10.2341/20-236-C. Online ahead of print.

ABSTRACT

This study aimed to evaluate the effect of the bleaching gel application site on chromatic changes and postoperative sensitivity in teeth. Thirty patients were selected and allocated to three groups (n=10 per group), according to the location of the gel: GI, cervical application; GII, incisal application; and GIII, total facial. The amount and time of application of the 35% hydrogen peroxide (H2O2) gel were standardized. Color changes were analyzed by ΔE and Wid (bleaching index), using the values obtained in the readings conducted on a digital spectrophotometer in the cervical (CRs) and incisal regions (IRs) of the teeth. Spontaneous sensitivity was assessed using the questionnaire, and the stimulated sensitivity caused by the thermosensory analysis (TSA). The analysis occurred in five stages: baseline, after the first, second, and third whitening sessions (S), and 14 days after the end of the whitening, using the linear regression statistical model with mixed effects and post-test by orthogonal contrasts (p<0.05). Although the IR was momentarily favored, at the end of the treatment, the restriction of the application site provided results similar to those obtained when the gel was applied over the entire facial surface. Regarding sensitivity, only the GI showed spontaneous sensitivity. In the TSA, GIII had less influence on the threshold of the thermal sensation. It was concluded that the chromatic alteration does not depend on the gel application site. Spontaneous sensitivity is greater when the gel is concentrated in the cervical region (CR), and the teeth remain sensitized by thermal stimuli even after 14 days.

PMID:34979026 | DOI:10.2341/20-236-C