Category: Nevin Manimala

PLoS Negl Trop Dis. 2022 Jan 3;16(1):e0010020. doi: 10.1371/journal.pntd.0010020. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients fromGauteng, South Africa.

METHODS: This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR.Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using EpiInfo.

RESULTS: MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria.Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample).Two of the four Middelburg virus positive cases,for which clinical information was available, had other comorbidities or infections at the time of infection.

CONCLUSION: Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.

PMID:34979534 | DOI:10.1371/journal.pntd.0010020

J Gerontol A Biol Sci Med Sci. 2022 Jan 3:glab386. doi: 10.1093/gerona/glab386. Online ahead of print.

ABSTRACT

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically-presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the two models. At the nexus of the three aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA.

PMID:34979545 | DOI:10.1093/gerona/glab386

ORL J Otorhinolaryngol Relat Spec. 2022 Jan 3:1-9. doi: 10.1159/000519575. Online ahead of print.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is characterized by an inflammatory reaction. High mobility group box 1 (HMGB1) protein and interleukin (IL)-33 are damage-associated molecular pattern molecules and have many characteristics similar to pro-inflammatory cytokines. However, the role of IL-33 and HMGB1 in AR remains unclear. The aim of this study is to explore the role of HMGB1 and IL-33 in AR.

METHODS: Twenty patients with AR (AR group) and 10 normal controls (normal group) were enrolled in this study. HMGB1 and IL-33 expression were analyzed by immunohistochemistry in epithelial cells of the inferior turbinate mucosa samples. Then, the human nasal mucosa epithelial cells (HNECs) were cultured in vitro, and the house dust mite allergen (Derp1) was used to stimulate the cells. Quantitative real-time PCR and ELISA assay were performed to detect HMGB1 and IL-33 expression in HNECs.

RESULTS: The expression of HMGB1 and IL-33 in the nasal mucosa was higher in the AR group than in the normal group, with a statistically significant difference (p < 0.05). In HNECs of AR, the expression of both HMGB1 and IL-33 in stimulated groups was higher than that in non-stimulated groups. The differences were statistically significant (p < 0.05). In addition, they increased gradually with the prolonging time and the concentration of the added Derp1.

CONCLUSIONS: The expression of HMGB1 and IL-33 were both increased in AR. HMGB1 and IL-33 may have a close relationship in AR.

PMID:34979505 | DOI:10.1159/000519575

Dermatology. 2022 Jan 3:1-9. doi: 10.1159/000520592. Online ahead of print.

ABSTRACT

BACKGROUND: Skin self-examination (SSE) is widely promoted for the detection of suspicious pigmented lesions. However, determining screening accuracy is essential to appraising the usefulness of SSE.

OBJECTIVES: The aim of this work was to pool estimates from studies of SSE diagnostic accuracy in the detection of suspicious pigmented lesions.

METHODS: This study was registered with PROSPERO (CRD42021246356) and conducted in accordance with PRISMA-DTA guidelines. A systematic search of Medline (PubMed) EMBASE, CINAHL, and The Cochrane Library was conducted to identify relevant studies. We included studies that examined the accuracy of SSE, either whole-body or site-specific, for detecting change in individual pigmented lesions or detecting an atypical naevus. A univariate random-effects model, based on logit-transformed data, was used to calculate a summary diagnostic odds ratio (DOR) as well as pooled sensitivity and specificity. Cochran’s Q test and the I2 statistic were calculated to assess heterogeneity. A proportional hazards model was used to calculate the area under the curve (AUC) and plot the summary receiver operator characteristic curve. We used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to grade study quality.

RESULTS: We identified 757 studies, of which 3 met inclusion criteria for quantitative synthesis. The pooled sensitivity and specificity based on 553 included participants was 59 and 82%, respectively. The summary DOR was 5.88 and the AUC was 0.71. There were some concerns regarding risk of bias in all 3 studies.

CONCLUSIONS: SSE can detect suspicious pigmented lesions with reasonable sensitivity and relatively high specificity, with the AUC suggesting acceptable discriminatory ability.

PMID:34979506 | DOI:10.1159/000520592

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

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

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

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

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

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