Category: Nevin Manimala

Iran J Med Sci. 2023 Jan;48(1):57-69. doi: 10.30476/IJMS.2022.92284.2352.

ABSTRACT

BACKGROUND: Despite growing evidence, there is still uncertainty about potentially modifiable risk factors for neonatal early-onset sepsis (EOS). This study aimed to identify potential clinical risk factors for EOS based on a literature review and expert opinions.

METHODS: A literature search was conducted in PubMed (MEDLINE), Cochrane, Embase, and Scopus databases. Articles in English, published up to May 2021, on clinical risk factors for neonatal EOS were included. Initially, a questionnaire on risk factors for EOS was developed and validated. The fuzzy Delphi method (FDM) was used to formulate the final version of the questionnaire. The validity of the risk factors was assessed using the Chi square test. P<0.05 was considered statistically significant.

RESULTS: In the review phase, 30 risk factors were approved by two neonatologists and included in the FDM phase. In total, 25 risk factors met the consensus criteria and entered the validation phase. During the observational study, 114 neonates (31 with and 83 without EOS) were evaluated for two months. The results of the Chi square test showed that cesarean section was not a significant risk factor for EOS (P=0.862). The need for mechanical ventilation and feed intolerance was observed in about 70% of neonates with EOS, and therefore considered significant risk factors for EOS (P<0.001). Finally, 26 potential clinical risk factors were determined.

CONCLUSION: Neonatal-related risk factors for EOS were birth weight, one-min Apgar score, and prematurity. Maternal-related risk factors were gestational age and urinary tract infection. Delivery-related risk factors were premature rupture of membranes, chorioamnionitis, and intrapartum fever.

PMID:36688195 | PMC:PMC9843461 | DOI:10.30476/IJMS.2022.92284.2352

Iran J Med Sci. 2023 Jan;48(1):70-76. doi: 10.30476/IJMS.2022.91192.2241.

ABSTRACT

BACKGROUND: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN.

METHODS: A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher’s exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant.

RESULTS: CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07).

CONCLUSION: Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

PMID:36688194 | PMC:PMC9843459 | DOI:10.30476/IJMS.2022.91192.2241

Iran J Med Sci. 2023 Jan;48(1):35-42. doi: 10.30476/IJMS.2022.92656.2395.

ABSTRACT

BACKGROUND: Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease.

METHODS: This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The t test was used for the statistical analysis, with a significance level of P<0.05.

RESULTS: The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes.

CONCLUSION: Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway.

PMID:36688193 | PMC:PMC9843455 | DOI:10.30476/IJMS.2022.92656.2395

Iran J Med Sci. 2023 Jan;48(1):26-34. doi: 10.30476/IJMS.2022.91669.2282.

ABSTRACT

BACKGROUND: Non-Hodgkin lymphoma (NHL) is the eleventh leading cause of cancer-related death in the world. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. Up to winter 2021-2022, the death toll caused by the coronavirus disease 2019 (COVID-19) has exceeded 5.6 million worldwide. Possible molecular mechanisms involved in the systemic inflammation, and cytokine storm in COVID-19 patients are still not fully understood. MicroRNA-155 (miR-155) plays a role in the post-transcriptional gene regulation of hematopoiesis, oncogenesis, and inflammation. The present study aimed to evaluate the expression of miR-155 in patients with DLBCL and/or COVID-19.

METHODS: A cross-sectional study was conducted from July to December 2020 in Tehran (Iran) to evaluate the expression of miR-155 in adult patients diagnosed with DLBCL and/or COVID-19. The real-time polymerase chain reaction technique was used to evaluate the expression of miR-155 in the sera of 92 adults who were either healthy or suffering from DLBCL and/or COVID-19. Relative quantification of gene expression was calculated in terms of cycle threshold (Ct) value. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant.

RESULTS: The expression of miR-155 was not associated with the sex or age of the participants. In comparison with healthy individuals (-ΔCt -1.92±0.25), the expression of miR-155 increased in patients with COVID-19 (1.95±0.14), DLBCL (2.25±0.16), or both (4.33±0.65).

CONCLUSION: The expression of miR-155 increased in patients with DLBCL and/or COVID-19.

PMID:36688191 | PMC:PMC9843467 | DOI:10.30476/IJMS.2022.91669.2282

Front Aging Neurosci. 2023 Jan 6;14:1073258. doi: 10.3389/fnagi.2022.1073258. eCollection 2022.

ABSTRACT

INTRODUCTION: Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult FMR1 premutation carriers (55-200 CGGs). Clinical symptoms in FXTAS patients usually begin with an action tremor. After that, different findings including ataxia, and more variably, loss of sensation in the distal lower extremities and autonomic dysfunction, may occur, and gradually progress. Cognitive deficits are also observed, and include memory problems and executive function deficits, with a gradual progression to dementia in some individuals. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the central nervous system. Changes in AQP4 activity and expression have been implicated in several central nervous system disorders. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with brain-water homeostasis, and neurodegeneration disease. To date, this association has not been studied in FXTAS.

METHODS: To investigate the association of AQP4 SNPs with the risk of presenting FXTAS, a total of seven common AQP4 SNPs were selected and genotyped in 95 FMR1 premutation carriers with FXTAS and in 65 FMR1 premutation carriers without FXTAS.

RESULTS: The frequency of AQP4-haplotype was compared between groups, denoting 26 heterozygous individuals and 5 homozygotes as carriers of the minor allele in the FXTAS group and 25 heterozygous and 2 homozygotes in the no-FXTAS group. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of FXTAS.

DISCUSSION: Although AQP4 has been implicated in a wide range of brain disorders, its involvement in FXTAS remains unclear. The identification of novel genetic markers predisposing to FXTAS or modulating disease progression is critical for future research involving predictors and treatments.

PMID:36688175 | PMC:PMC9853890 | DOI:10.3389/fnagi.2022.1073258

Front Aging Neurosci. 2023 Jan 6;14:1109485. doi: 10.3389/fnagi.2022.1109485. eCollection 2022.

ABSTRACT

OBJECTIVES: The abnormal functional connectivity (FC) pattern of default mode network (DMN) may be key markers for early identification of various cognitive disorders. However, the whole-brain FC changes of DMN in delayed neurocognitive recovery (DNR) are still unclear. Our study was aimed at exploring the whole-brain FC patterns of all regions in DMN and the potential features as biomarkers for the prediction of DNR using machine-learning algorithms.

METHODS: Resting-state functional magnetic resonance imaging (fMRI) was conducted before surgery on 74 patients undergoing non-cardiac surgery. Seed-based whole-brain FC with 18 core regions located in the DMN was performed, and FC features that were statistically different between the DNR and non-DNR patients after false discovery correction were extracted. Afterward, based on the extracted FC features, machine-learning algorithms such as support vector machine, logistic regression, decision tree, and random forest were established to recognize DNR. The machine learning experiment procedure mainly included three following steps: feature standardization, parameter adjustment, and performance comparison. Finally, independent testing was conducted to validate the established prediction model. The algorithm performance was evaluated by a permutation test.

RESULTS: We found significantly decreased DMN connectivity with the brain regions involved in visual processing in DNR patients than in non-DNR patients. The best result was obtained from the random forest algorithm based on the 20 decision trees (estimators). The random forest model achieved the accuracy, sensitivity, and specificity of 84.0, 63.1, and 89.5%, respectively. The area under the receiver operating characteristic curve of the classifier reached 86.4%. The feature that contributed the most to the random forest model was the FC between the left retrosplenial cortex/posterior cingulate cortex and left precuneus.

CONCLUSION: The decreased FC of DMN with regions involved in visual processing might be effective markers for the prediction of DNR and could provide new insights into the neural mechanisms of DNR.

CLINICAL TRIAL REGISTRATION: : Chinese Clinical Trial Registry, ChiCTR-DCD-15006096.

PMID:36688167 | PMC:PMC9853194 | DOI:10.3389/fnagi.2022.1109485

Front Aging Neurosci. 2023 Jan 5;14:939155. doi: 10.3389/fnagi.2022.939155. eCollection 2022.

ABSTRACT

BACKGROUND: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH).

METHODS: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation.

RESULTS: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = -0.569, p < 0.001), cerebral cortex (r = -0.563, p < 0.001), and hippocampi (r = -0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = -0.403, p = 0.016), executive functions (r = -0.402, p = 0.017), memory (r = -0.463, p = 0.005), and processing speed (r = -0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = -0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes.

CONCLUSION: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease.

PMID:36688160 | PMC:PMC9849573 | DOI:10.3389/fnagi.2022.939155

Front Med Technol. 2023 Jan 4;4:1007708. doi: 10.3389/fmedt.2022.1007708. eCollection 2022.

ABSTRACT

INTRODUCTION: Artificial intelligence and data-driven predictive modeling have become increasingly common tools integrated in clinical practice, heralding a new chapter of medicine in the digital era. While these techniques are poised to affect nearly all aspects of medicine, medical education as an institution has languished behind; this has raised concerns that the current training infrastructure is not adequately preparing future physicians for this changing clinical landscape. Our institution attempted to ameliorate this by implementing a novel artificial intelligence in radiology curriculum, “AI-RADS,” in two different educational formats: a 7-month lecture series and a one-day workshop intensive.

METHODS: The curriculum was structured around foundational algorithms within artificial intelligence. As most residents have little computer science training, algorithms were initially presented as a series of simple observations around a relatable problem (e.g., fraud detection, movie recommendations, etc.). These observations were later re-framed to illustrate how a machine could apply the underlying concepts to perform clinically relevant tasks in the practice of radiology. Secondary lessons in basic computing, such as data representation/abstraction, were integrated as well. The lessons were ordered such that these algorithms were logical extensions of each other. The 7-month curriculum consisted of seven lectures paired with seven journal clubs, resulting in an AI-focused session every two weeks. The workshop consisted of six hours of content modified for the condensed format, with a final integrative activity.

RESULTS: Both formats of the AI-RADS curriculum were well received by learners, with the 7-month version and workshop garnering 9.8/10 and 4.3/5 ratings, respectively, for overall satisfaction. In both, there were increases in perceived understanding of artificial intelligence. In the 7-lecture course, 6/7 lectures achieved statistically significant (P < 0.02) differences, with the final lecture approaching significance (P = 0.07). In the one-day workshop, there was a significant increase in perceived understanding (P = 0.03).

CONCLUSION: As artificial intelligence becomes further enmeshed in clinical practice, it will become critical for physicians to have a basic understanding of how these tools work. Our AI-RADS curriculum demonstrates that it is successful in increasing learner perceived understanding in both an extended and condensed format.

PMID:36688145 | PMC:PMC9845918 | DOI:10.3389/fmedt.2022.1007708

Front Med Technol. 2023 Jan 4;4:1055189. doi: 10.3389/fmedt.2022.1055189. eCollection 2022.

ABSTRACT

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is an often performed procedure in spine neurosurgery. These are often performed using an operating microscope (OM) for better illumination and visualization. But its use is limited to the surgeon and the assistant. There is difficulty in maneuvering long surgical instruments due to the limited space available. Exoscope (EX) has been used as an alternative to microscopes and endoscopes. We used an EX in patients undergoing ACDF for cervical spondylotic myelopathy.

METHODS: A prospective comparative trial was conducted to test the safety and usability of a low-cost EX compared to a conventional surgical binocular OM in ACDF. Twenty-six patients with degenerative cervical myelopathy symptoms were operated by ACDF assisted by the EX and OM between December 2021 and June 2022. The authors collected and compared data on operative time, intraoperative hemorrhage, hospital admission, and complications in the two groups.

RESULTS: There were no statistically significant differences between the two groups in mean operative time, hospital stay, or postoperative complications. The average intraoperative blood loss was significantly more in the OM group. There were no surgical complications related to the use of the EX or OM. The comfort level, preoperative setup and intraoperative adjustment of position and angle of the EX were rated higher than the OM group. The image quality, depth perception, and illumination were rated as inferior to that of the OM. The low-cost EX was rated to be superior to that of the OM with regard to education and training purposes.

CONCLUSION: Our study showed that the low-cost EX appears to be a safe and effective alternative for OM-assisted ACDF with great comfort and ergonomics and serves as an essential tool for education and training purposes. However, some limitations of our EX included slightly inferior image quality and illumination when compared with the OM.

PMID:36688142 | PMC:PMC9846206 | DOI:10.3389/fmedt.2022.1055189

JAAD Int. 2022 Nov 13;10:68-74. doi: 10.1016/j.jdin.2022.11.002. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory skin disease commonly onset during infancy.

OBJECTIVE: We examine the association between pre-and postnatal antibiotic exposure and the development of AD.

METHODS: A retrospective, observational study analyzed 4106 infants at the University of Florida from June 2011 to April 2017.

RESULTS: Antibiotic exposure during the first year of life was associated with a lower risk of AD. The association was strongest for exposure during the first month of life. There were no significant differences in the rates of AD in infants with or without exposure to antibiotics in months 2 through 12, when examined by month. Antibiotic exposure during week 2 of life was associated with lower risk of AD, with weeks 1, 3, and 4 demonstrating a similar trend.

LIMITATIONS: Retrospective data collection from a single center, use of electronic medical record, patient compliance with prescribed medication, and variable follow-up.

CONCLUSIONS: Early life exposures, such as antibiotics, may lead to long-term changes in immunity. Murine models of atopic dermatitis demonstrate a “critical window” for the development of immune tolerance to cutaneous microbes. Our findings suggest that there may also be a “critical window” for immune tolerance in human infants, influenced by antibiotic exposure.

PMID:36688099 | PMC:PMC9850168 | DOI:10.1016/j.jdin.2022.11.002