Nevin Manimala

Infect Dis Clin Microbiol. 2024 Dec 19;6(4):258-267. doi: 10.36519/idcm.2024.367. eCollection 2024 Dec.

ABSTRACT

OBJECTIVE: Cytokines and chemokines are clinically relevant for severity prediction and treatment of COVID-19 caused by SARS-CoV-2. We aimed to demonstrate the potential cytokines for severity prediction in the five days after symptom onset and describe the importance of serum cytokine levels for patients with different disease severity.

MATERIALS AND METHODS: Hospitalized COVID-19 patients and healthy control participants were recruited, and serial sera were collected from COVID-19 patients. Thirteen cytokines, including interleukin (IL) 1β, interferon (IFN) α2, IFN- γ, tumor necrosis factor (TNF) α, monocyte chemoattractant protein (MCP-1/CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33, were studied by bead-based multiplex assay by flow cytometry. Data regarding routine laboratory test results (leucocyte count, neutrophil count, lymphocyte count, platelet count, hemoglobin, liver transaminases, C-reactive protein [CRP], procalcitonin, and creatinine) were collected.

RESULTS: We demonstrated that COVID-19 patients had elevated serum levels of IFN-α2, TNF-α, MCP-1/CCL2, IL-6, IL-8, IL-18, IL-33 compared to healthy participants. Elevated levels of CRP and decreased lymphocyte count were observed in the critical disease group. Longitudinal analysis revealed a statistically significant increase in IL-6, IL-18, and MCP-1 serum levels of critical patients compared to healthy controls.

CONCLUSION: MCP-1, IL-6, and IL-18 were found to be the best predictors of critical COVID-19 disease, and MCP-1 has the highest level of predictive performance.

PMID:39744658 | PMC:PMC11687237 | DOI:10.36519/idcm.2024.367

Curr J Neurol. 2024 Apr 3;23(2):89-95. doi: 10.18502/cjn.v23i2.16837.

ABSTRACT

Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder that is diagnosed using clinical signs and symptoms and confirmed via nerve conduction studies (NCSs). While NCS is a semi-invasive procedure, magnetic resonance imaging (MRI) is a non-invasive diagnostic tool that detects macroscopic nerve abnormalities and evaluates a patient’s surgical or medication treatment options. This study assessed magnetic resonance neurography (MRN)’s diagnostic and grading value by comparing it to electrodiagnostic studies in patients with CTS and healthy individuals. Methods: This was a cross-sectional study on 27 wrists with CTS and 27 healthy wrists. After history taking and physical examination, we employed an NCS to confirm and determine the severity of CTS, then MRN and diffusion tensor imaging (DTI) were used to calculate apparent diffusion coefficient (ADC), fractional anisotropy (FA), and cross-sectional area (CSA). Results: 18 patients with CTS (27 median nerves) and 15 healthy controls (27 median nerves) were evaluated. The mean FA in the CTS group was significantly lower (0.38 ± 0.05 vs. 0.45 ± 0.06, P < 0.001). The mean CSA and ADC were higher in patients with CTS but not statistically significant. FA’s diagnostic cut-off was 0.42, with a sensitivity of 70.4% and a specificity of 63%. Conclusion: MRN with DTI can be an effective and non-invasive diagnostic technique for the detection of CTS. The FA measure demonstrated adequate sensitivity and specificity for differentiating patients with CTS from healthy individuals.

PMID:39744656 | PMC:PMC11685557 | DOI:10.18502/cjn.v23i2.16837

Curr J Neurol. 2024 Apr 3;23(2):124-130. doi: 10.18502/cjn.v23i2.16841.

ABSTRACT

Background: Stress has been known as a risk factor for the onset and modification of autoimmune disorders such as myasthenia gravis (MG). However, the patients can control their stress and improve their quality of life (QOL) using some factors such as psychological and social support. Psychological capital and social support play a key role in decreasing stress and improving QOL in the patients with MG. Therefore, the present study aimed to assess the mediator role of the psychological capital and social support in perceived stress and QOL of the patients with MG. Methods: In the present cross-sectional study, 203 patients with MG, including 138 women and 65 men, were selected from Iran Myasthenia Gravis Association and Shariati Hospital, Tehran City, Iran, using available sampling. The selected patients completed the Myasthenia Gravis Quality of Life questionnaire (MG-QOL), Luthans Psychological Capital Questionnaire (PCQ), Multidimensional Scale of Perceived Social Support (MSPSS), and Cohen Perceived Stress Scale (PSS-14). To assess the mediator role of the psychological capital and the perceived social support in the relationship with the perceived stress and QOL of the patients with MG, structural equation modeling (SEM) was used. Results: There was a significant negative relationship between the perceived stress and the variables of psychological capital (including hope, resilience, optimism, and self-efficacy), perceived social support dimensions (including support from important people, support from family, and support from friends), and QOL dimensions (including social activity and mental health) (P < 0.01). The results also showed that the perceived social support dimensions (including support from important people, support from family, and support from friends) and the variables of psychological capital (including hope, resilience, optimism, and self-efficacy) had a significant positive relationship with the QOL in patients with MG (P < 0.01). The indirect effect of perceived stress on the QOL through social support and psychological capital was 0.16 and 0.15, respectively, which was statistically significant (P < 0.05). Conclusion: The present study results show that a part of the shared variance between the conceptual circles of the perceived stress and QOL in patients with MG results from variability in the psychological capital and social support.

PMID:39744654 | PMC:PMC11685554 | DOI:10.18502/cjn.v23i2.16841

Obes Surg. 2025 Jan 2. doi: 10.1007/s11695-024-07652-0. Online ahead of print.

ABSTRACT

Metabolic and bariatric surgery (MBS) has been associated with weight reduction and obesity complications improvement. However, there is no clear evidence of the extent and consistency of the effects of this procedure on rheumatic diseases. This study aims to conduct a meta-analysis to address the impact of MBS on rheumatic diseases. We searched PubMed, Cochrane, and Embase for studies reporting the prevalence of rheumatic diseases, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the medication use after MBS. We conducted a random-effects meta-analysis using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). P-values < 0.05 were considered statistically significant. We included 28 studies comprising 43,421 patients, with 13,347 patients with rheumatic diseases. The prevalence of osteoarthritis (OA), rheumatoid arthritis, and psoriatic arthritis was significantly reduced after MBS (OR 0.20; 95% CI 0.12 to 0.33; P = 0.01). The WOMAC index for patients with OA had a statistically significant overall reduction after MBS at 6 months (MD – 20.60 points; 95% CI – 28.73 to – 12.47; P < 0.01) and at 12 months (MD – 15.88 points; 95% CI – 19.09 to – 12.66; P < 0.01). Medication use significantly decreased after MBS, both at the follow-up beyond 2 years (OR 0.49; 95% CI 0.35 to 0.69; P < 0.01) and up to 2 years (OR 0.32; 95% CI 0.15 to 0.69; P < 0.01). In this meta-analysis, we found a significant decrease in the prevalence of rheumatic diseases, improvements in the WOMAC index, and reduced medication use among patients undergoing MBS.

PMID:39743656 | DOI:10.1007/s11695-024-07652-0

Odontology. 2025 Jan 2. doi: 10.1007/s10266-024-01047-4. Online ahead of print.

ABSTRACT

This in vitro research assessed the influence of the instrument kinematics (rotary and reciprocating) and the apical preparation limit on the root canal disinfection and apical bacterial extrusion. After 21 days of Enterococcus faecalis biofilm formation in 72 mesial root canals of mandibular molars, the root canals were distributed into 2 groups (n = 36) according to the systems used for preparation: ProDesign S and Reciproc. The groups were redistributed according to the limit of apical preparation (n = 11): (a) 1 mm up to the apical foramen (TL-1); (b) at the apical foramen (TL = 0); (c) 1 mm beyond the apical foramen (TL + 1). After preparation, the remaining biofilm adhered to the dentin walls at the apical third was removed by sonication. The aliquots of bacterial suspension released, and the irrigating solution leaked through the apical foramen during preparation were plated for colony-forming units (CFUs) counting. Data were statistically assessed by the Kruskal-Wallis and Dunn tests (α = 5%). Both systems promoted decontamination of the apical third, regardless the limit of apical preparation (p > 0.05). A larger quantity of bacteria was extruded from the root canals prepared 1 mm beyond the apical foramen, regardless the instrumentation kinematics (p < 0.05). The apical third of the root canal was efficiently decontaminated after preparation, regardless the instrumentation kinematics and the apical limit. However, a larger quantity of bacterial extrusion was observed when preparation was performed beyond the anatomical root canal limits.

PMID:39743655 | DOI:10.1007/s10266-024-01047-4

Clin Oral Investig. 2025 Jan 2;29(1):39. doi: 10.1007/s00784-024-06124-0.

ABSTRACT

OBJECTIVES: The study aimed to assess the percent correct shade identification of four intraoral scanners (IOS) and a spectrophotometer, focusing on how reliably each device selects the correct tooth shade compared to a visual observer’s selection. The research question addresses how much clinicians can trust the device-selected shade without visual verification.

MATERIALS AND METHODS: Sixteen participants with natural, unrestored teeth were included. The teeth evaluated were tooth 21 (left maxillary central incisor), tooth 23 (left maxillary canine), and tooth 26 (first left maxillary molar). Tooth color was measured using four IOS devices and the Vita Easyshade V in three regions: incisal, middle, and cervical. The nearest 3D Master shade selected by each device was compared to the visual observer’s selection. The percent exact match, acceptable match (> 1.2, ≤ 2.7 ∆E_ab), and mismatch type A (< 2.7, ≤ 5.4 ∆E_ab) were calculated. Statistical analysis was performed using a chi-square test with a 95% confidence level.

RESULTS: The overall clinical pass rate was highest for Carestream (78.2%), followed by Easyshade (63.5%), Primescan (51.2%), Trios (39.5%), and Medit (31.3%). Carestream also recorded the highest rate of mismatch type A (47.7%). Significant differences between devices were observed for all categories (p < 0.05).

CONCLUSIONS: Carestream demonstrated the highest overall clinical pass rate, while Medit exhibited the lowest. The study highlights the variability between devices in shade matching performance.

CLINICAL RELEVANCE: This study highlights the importance of considering device performance when relying on IOS or spectrophotometers for shade selection without visual assessment, as the reliability can vary significantly across devices.

PMID:39743647 | DOI:10.1007/s00784-024-06124-0

J Mol Neurosci. 2025 Jan 2;75(1):4. doi: 10.1007/s12031-024-02241-3.

ABSTRACT

Acute ischemic stroke (AIS) is a severe disorder characterized by complex pathophysiological processes, which can lead to disability and death. This study aimed to determine necroptosis-associated genes in acute ischemic stroke (AIS) and to investigate their potential as diagnostic and therapeutic targets for AIS. Expression profiling data were acquired from the Gene Expression Omnibus database, and necroptosis-associated genes were retrieved from GeneCards. The differentially expressed genes (DEGs) and necroptosis-related genes were intersected to obtain the necroptosis-related DEGs (NRDEGs) in AIS. In AIS, a total of 76 genes associated with necroptosis (referred to as NRDEGs) were identified. Enrichment analysis of these genes revealed that they were primarily enriched in pathways known to induce necroptosis. Using weighted gene co-expression network analysis (WGCNA), five co-expression modules consisting of NRDEGs were identified, along with two modules that exhibited a strong correlation with AIS. Protein-protein interaction (PPI) analysis resulted in the identification of 20 hub genes. The Least absolute shrinkage and selection operator (LASSO) regression model demonstrated promising potential for diagnostic prediction. The receiver operating characteristic (ROC) curve validated the diagnostic model and selected nine characteristic genes that exhibited statistically significant differences (p < 0.05). By employing consensus clustering, distinct patterns of necroptosis were identified using these nine signature genes. The results were validated by quantitative PCR (qPCR) in venous blood from patients with AIS and healthy controls and HT22 cells, as well as external datasets. Furthermore, the analyzed ceRNA network included nine lncRNAs, six miRNAs, and three mRNAs. Overall, this study offers novel insights into the molecular mechanisms underlying NRDEGs in AIS. The findings provide valuable evidence and contribute to our understanding of the disease.

PMID:39743646 | DOI:10.1007/s12031-024-02241-3

Ultrasound Obstet Gynecol. 2025 Jan;65(1):71-77. doi: 10.1002/uog.29142.

ABSTRACT

OBJECTIVE: To compare the accuracy of four published reference standards for the umbilical artery pulsatility index (UA-PI) in predicting small-for-gestational age (SGA), adverse neonatal outcomes and obstetric complications in pregnancies at risk for fetal growth restriction.

METHODS: This was a secondary analysis of a prospective study of singleton pregnancies that underwent fetal growth assessment by ultrasound between 26 and 36 weeks’ gestation. Pregnancies with estimated fetal weight or abdominal circumference < 20^th percentile with UA-PI measurements available were included. We excluded fetuses with chromosomal anomaly or congenital malformation and those without delivery information. The predictive ability of UA-PI > 95^th percentile according to the reference standards of Acharya et al., the INTERGROWTH-21^st Project, the Fetal Medicine Foundation and Parra-Cordero et al. for SGA, a composite of adverse neonatal outcomes and a composite of obstetric complications was compared using the area under the receiver-operating-characteristics curve (AUC). Sensitivity, specificity and positive and negative predictive values were calculated.

RESULTS: Of the 1054 pregnancies that underwent fetal growth evaluation by ultrasound, 207 were included in our analysis. SGA, adverse neonatal outcomes and obstetric complications were diagnosed in 94 (45.4%), 50 (24.2%) and 69 (33.3%) cases, respectively. All reference standards had similar and statistically significant but poor predictive accuracy for SGA (AUC of 0.55 to 0.56), adverse neonatal outcomes (AUC of 0.57 to 0.60) and obstetric complications (AUC of 0.55 for all).

CONCLUSIONS: The reference standards for UA-PI evaluated herein have poor predictive ability for SGA, adverse neonatal outcomes and obstetric complications. At present, no particular UA-PI reference standard can be recommended over others. Larger trials are needed to answer this research question. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

PMID:39743627 | DOI:10.1002/uog.29142

Lasers Med Sci. 2025 Jan 2;40(1):4. doi: 10.1007/s10103-024-04216-7.

ABSTRACT

The broad spectrum of clinical manifestations caused by peripheral arterial disease [PAD] and the morphologic heterogeneity of associated atherosclerotic lesions present a considerable management challenge. Endovascular interventions are recognized an effective treatment for PAD. Within this revascularization strategy the role of atherectomy debulking modalities continue to evolve. Accordingly, the study herein assessed the efficacy and safety of a novel, solid state, Nd: YAG pulsed-wave [355 nm wavelength] laser atherectomy in the treatment of symptomatic infra-inguinal PAD. The EX-PAD-01 study, a prospective, single-arm, open label trial enrolled 50 patients (38 males, 12 females; mean age 64 years] with symptomatic peripheral arterial disease, who underwent percutaneous revascularization with a novel, solid state, pulsed-wave [355 nm wavelength] laser atherectomy followed with adjunct treatment. The Ankle-brachial index [ABI], Rutherford classification for chronic limb ischemia and the walking impairment questionnaire [WIQ] were used for assessment of the index clinical condition of the enrolled patients, for post procedure evaluation and during follow-up. Accordingly, the patients were followed for 12-months with repeated direct physician contact visits. Fifty-three atherosclerotic stenoses (51 femoropopliteal, 2 tibial) with a mean length of 7.4 cm. (ranged 1cm to 25cm) were treated. There were 79% occlusions, and 61% containing moderate-to-severe calcifications. The pre-procedure stenosis was 95.3 ± 10.3%, the Rutherford classification for chronic limb ischemia [CLI] was 2.90 ± 0.54 ranging between 2-4 and the WIQ 34.6 ± 8.62. Technical success was achieved in 52 of the 53 (98%) target lesions. Following laser debulking the baseline stenosis was reduced from 95.3 ± 10.3% to 61.3 ± 25.5% [ [p < 0.0001] and with adjunct balloon/stenting to final of 14.0 ± 14.0% [p < 0.0001]. Embolic protection devices were utilized in 6 [12%] patients. At 30-day post procedure evaluation the ABI increased from baseline of 0.57 ± 0.14 to 0.94 ± 0.14 [p < 0.0001] and no major adverse effects or device adverse effects were detected. At 6 months follow -up the ABI was 0.84 ± 0.20% (p < 0.0001 vs. initial) and at 1 year follow-up 0.79 ± 0.16 (P = 0.0001 vs. initial) without major adverse events. Out of 46 [92%] patients who reached the 12 months follow-up mark, 2 [4.3%] experienced clinically driven target lesion revascularization. Sustained clinical benefit for up to 12 months post procedure was demonstrated through documentation of statistically significant decrease of Rutherford CLI class as well as concomitant improvement in WIQ score and an increase of ABI value. The primary patency rate, as defined by peak systolic velocity ratio (PSVR) of < 2.5m/second was 95.7% (22 of 23) and 81.8% (18 of 22) at 6 months and 12 months, respectively. In an early European clinical experience with a series of 50 patients with symptomatic peripheral arterial disease, the novel Nd: YAG solid state, pulsed- wave 355nm cardiovascular laser atherectomy device provided effective and safe revascularization treatment. Follow-up at 6 and 12 months, respectively, substantiate the efficacy, safety profile and clinical merits of this novel laser. Thus, this device is useful in the management of select patients with symptomatic infra-inguinal atherosclerotic lesions.Clinical Trial Registration: Clinical trials.gov number: NTC02556255.

PMID:39743624 | DOI:10.1007/s10103-024-04216-7

Nature. 2025 Jan;637(8044):118-126. doi: 10.1038/s41586-024-08275-2. Epub 2025 Jan 1.

ABSTRACT

Many known and unknown historical events have remained below detection thresholds of genetic studies because subtle ancestry changes are challenging to reconstruct. Methods based on shared haplotypes^1,2 and rare variants^3,4 improve power but are not explicitly temporal and have not been possible to adopt in unbiased ancestry models. Here we develop Twigstats, an approach of time-stratified ancestry analysis that can improve statistical power by an order of magnitude by focusing on coalescences in recent times, while remaining unbiased by population-specific drift. We apply this framework to 1,556 available ancient whole genomes from Europe in the historical period. We are able to model individual-level ancestry using preceding genomes to provide high resolution. During the first half of the first millennium CE, we observe at least two different streams of Scandinavian-related ancestry expanding across western, central and eastern Europe. By contrast, during the second half of the first millennium CE, ancestry patterns suggest the regional disappearance or substantial admixture of these ancestries. In Scandinavia, we document a major ancestry influx by approximately 800 CE, when a large proportion of Viking Age individuals carried ancestry from groups related to central Europe not seen in individuals from the early Iron Age. Our findings suggest that time-stratified ancestry analysis can provide a higher-resolution lens for genetic history.

PMID:39743601 | DOI:10.1038/s41586-024-08275-2