Category: Nevin Manimala

Eur J Med Res. 2024 Nov 24;29(1):559. doi: 10.1186/s40001-024-02164-0.

ABSTRACT

OBJECTIVES: In adult hypertensive patients, blood pressure variability is considered a risk factor for heart failure. The relationship between pulse pressure variability and the risk of heart failure remains unclear. This study aims to explore the impact of pulse pressure variability (PPV) on heart failure through a secondary analysis of the SPRINT randomized controlled trial.

METHODS: The data were derived from the SPRINT (Systolic Blood Pressure Intervention Trial) study. The trial recruited participants 50 years or older, with SBP ≥ 130 mm Hg and at least one additional CVD risk factor. We calculated pulse pressure based on the systolic and diastolic blood pressure obtained during follow-up, and used the coefficient of variation to represent pulse pressure variability (PPV) for statistical analysis. We considered the incidence of acute decompensated heart failure as the outcome measure. We employed multivariable Cox regression analysis to examine the relationship between PPV and the risk of heart failure occurrence. Additionally, we used a restricted cubic spline model to analyze the dose-response relationship between PPV and the risk of heart failure occurrence.

RESULTS: In this study, a total of 9429 participants were included. During a median follow-up time of 3.87 years, 188 new cases of heart failure were observed. The mean age of the study population was 67.9 ± 9.4 years and 3382 participants (35.5%) were females. The average PPCV was 13.85 ± 5.37%. The results from the multivariable Cox regression analysis indicated that the risk of heart failure increased by 3% for every 1% increase in PPCV (HR = 1.030 [95% CI 1.016-1.044]; P < 0.001).

CONCLUSIONS: The study found that PPV is an independent risk factor for the occurrence of heart failure. This underscores the importance of maintaining long-term stability in pulse pressure, in preventing the development of heart failure.

PMID:39582008 | DOI:10.1186/s40001-024-02164-0

Microb Cell Fact. 2024 Nov 25;23(1):318. doi: 10.1186/s12934-024-02587-8.

ABSTRACT

BACKGROUND: To discover effective drugs for treating Influenza (a disease with high annual mortality), large amounts of recombinant neuraminidase (NA) with suitable catalytic activity are needed. However, the functional activity of the full-length form of this enzyme in the bacterial host (as producing cells with a low cost) in a soluble form is limited. Thus, in the present study, a truncated form of the neuraminidase (derived from California H1N1 influenza strain) was designed, then biosynthesized in Escherichia coli BL21 (DE3), Shuffle T7, and SILEX systems. E. coli BL21 (DE3) was selected as a best host for statistical optimization. Using central composite design methodology, neuraminidase expression level was measured at 20 different runs considering most effective factors including; concentration of isopropyl-β-D-thiogalactopyranoside (IPTG), temperature, and induction time.

RESULT: The recombinant neuraminidase was purified using Ni-affinity chromatography in soluble form. The neuraminidase expression was confirmed by western blot technique with a molecular mass of 48 kDa. The optimum expression condition was at temperature (30°C), induction time (3 h), and concentration of IPTG (0.6 mM) resulting in maximum neuraminidase expression (7.6 µg/mL) with P < 0.05. The analysis of variance with the significant value of R² (0.97) indicated that the quadratic model utilized for this prediction was highly significant (p < 0.0001). Applying the optimized condition led to a ~ 2.2-fold increase in NA expression level (from 3.4 to 7.6 µg/ml). The kinetic parameters were also confirmed by fluorescent signals (by 2′-(4-Methylumbelliferyl)-α-D-N acetyl neuraminic acid substrate) with specific activity; ~3.5 IU/mg and Km: 86.49 ± 0.1 µ, close to the Vibrio Cholera neuraminidase with specific activity; 4 IU/mg. The neuraminidase inhibition test confirmed the inhibition of the neuraminidase activity by the drug inhibitor (Oseltamivir) compared to the control sample.

CONCLUSION: The high quality and proper functional activity of the truncated neuraminidase described in this research show that E. coli can be a suitable host for a wide range of applications with less cost and risk compared to eukaryotic expression systems.

PMID:39582000 | DOI:10.1186/s12934-024-02587-8

BMC Oral Health. 2024 Nov 24;24(1):1432. doi: 10.1186/s12903-024-05190-w.

ABSTRACT

OBJECTIVES: This study aimed to investigate the association between sleep disorders and the prevalence of taste dysfunction and the mediation effect of oral microbe in adults over 40 years.

MATERIALS AND METHODS: Cross-sectional data were utilized from the National Health and Nutrition Examination Survey (2011-2014). Regression models were employed, adjusting for demographic variables and covariates. Subgroup analyses were conducted based on age, sex, ethnicity, and education level. Multiplicative interactions were assessed through likelihood ratio tests. Additionally, the impact of sleep disturbance on the alpha diversity of the oral microbiome was examined using the rank-sum test (significance threshold: p < 0.05). Mediation analysis based on oral microbiota was conducted.

RESULTS: The analysis included 4869 participants. After adjusting for adjusting for demographic variables and covariates, individuals with sleep disorders exhibited a 36% increased risk of taste dysfunctions compared to those without sleep disorders (OR: 1.36, 95% CI: 1.00-1.84, p = 0.05). Interaction analyses indicated no significant differences between sleep disorders and taste dysfunctions concerning sex, educational level, and age across various models (Crude Model, Model 1, Model 2, and Model 3; p for interaction > 0.05). Furthermore, compared with the non-sleep disorder group, patients with sleep disorders demonstrated decreased numbers of OTUs, Shannon-Wiener indices, and Faith’s phylogenetic diversity indices in the oral microbiota (p < 0.05). However, the mediation analysis failed to reveal an indirect effect of oral microbiome on taste dysfunction (p > 0.05.) CONCLUSION: Sleep disorders independently correlate with a higher risk of taste dysfunctions, potentially associated with alterations in oral flora.

PMID:39581997 | DOI:10.1186/s12903-024-05190-w

Ren Fail. 2024 Dec;46(2):2427178. doi: 10.1080/0886022X.2024.2427178. Epub 2024 Nov 24.

ABSTRACT

BACKGROUND: The relationships of serum neurofilament light chain (NfL) levels with chronic kidney disease (CKD) and renal function indicators remain controversial, and comprehensive studies with large sample sizes are lacking.

METHODS: In total, 2,051 participants aged 20 to 75 years were identified from the National Health and Nutrition Examination Survey (2013-2014 cycle). Logistic regression models were used to assess the associations between serum NfL levels and CKD, whereas multivariate linear models were used to investigate the relationships between serum NfL levels and two kidney function indicators, namely, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Adjustments were made to account for potential confounding variables in the analysis. Subgroup analyses stratified by age and sex were conducted. When sNfL is incorporated into the model as continuous variables, a log transformation is applied.

RESULTS: The present study included a cohort of 2,051 individuals ranging in age from 20 to 75 years. After covariate adjustment, multivariable logistic regression revealed a significant association between high serum NfL levels and an increased prevalence of CKD (OR 1.60; 95% CI 1.40-1.82; p < 0.0001), which remained significant when analyzed by quartiles (p for trend <0.0001). There was a statistically significant inverse correlation between the serum NfL level and the eGFR (β=-6.34; 95% CI -8.32 to -4.37; p < 0.0001), as well as a positive correlation between the serum NfL level and the UACR (β = 84.67; 95% CI 19.52-149.83; p < 0.0001). Furthermore, when stratified by age, there were significant interactions of serum NfL levels with CKD, the eGFR, and the UACR (p for interaction = 0.008, 0.016, and 0.020, respectively).

CONCLUSION: Serum NfL levels are positively associated with the prevalence of CKD and the UACR but negatively correlated with the eGFR, particularly in older patients.

PMID:39581996 | DOI:10.1080/0886022X.2024.2427178

J Headache Pain. 2024 Nov 25;25(1):204. doi: 10.1186/s10194-024-01919-8.

ABSTRACT

OBJECTIVE: To delineate the structural connectome alterations in patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs).

BACKGROUND: The pathogenesis of migraine chronification remains elusive, with structural brain network changes potentially playing a key role. However, there is a paucity of research employing graph theory analysis to explore changes in the whole brain structural networks in patients with CM and EM.

METHODS: The individual structural brain connectome of 60 patients with CM, 34 patients with EM, and 39 healthy control participants were constructed by using deterministic diffusion-tensor tractography. Graph metrics including global efficiency, characteristic path length, local efficiency, clustering coefficient, and small-world parameters were evaluated to describe the topologic organization of the white matter structural networks. Additionally, nodal clustering coefficient and efficiency were considered to assess the regional characteristics of the brain connectome. A graph-based statistic was used to assess brain network properties across the groups.

RESULTS: Graph theory analysis revealed significant disruptions in the structural brain networks of CM patients, characterized by reduced global efficiency, local efficiency, and increased characteristic path length compared to HCs. Additionally, CM patients exhibited significantly lower local efficiency than EM patients. Notably, the CM group demonstrated marked reductions in local clustering coefficient and nodal local efficiency in the frontal and temporal regions compared with the healthy control group and EM group. Nodal local efficiency can effectively distinguish CM from EM and HCs. Moreover, the disrupted topologic efficiency was significantly associated with attack frequency and MIDAS score in patients with migraine after Bonferroni correction.

CONCLUSION: Decreased structural connectivity in the frontal and temporal regions may serve as a neuroimaging marker for migraine chronification and disease progression, providing valuable insights into the pathophysiology of chronic migraine.

PMID:39581995 | DOI:10.1186/s10194-024-01919-8

BMC Anesthesiol. 2024 Nov 25;24(1):424. doi: 10.1186/s12871-024-02817-x.

ABSTRACT

BACKGROUND: Delirium is one of the most common neurological complications after cardiac surgery. The purpose of our study was to assess the relationship between perioperative blood pressure variability (BPV) and postoperative delirium (POD) in the patients undergoing cardiac surgery.

METHODS: Adult patients received cardiac surgery and stayed in Cardiovascular Intensive Care Unit (ICU) for more than 24 h after surgery during the study period between June 2019 and December 2022 were included in this study. Baseline characteristics, perioperative hemodynamic variables and postoperative laboratory results of the cardiac patients were collected and analyzed. Perioperative BPV was quantified by calculating the standard deviation (SD) and average real variability (ARV) of blood pressure. Assessment of delirium was based on the mental status of the patients and CAM-positive. The relationship between perioperative BPV and POD was analyzed by LASSO and logistic regression using R (R package, 4.3.2).

RESULTS: The incidence of POD was 15.0% (324/2164) in the patients receiving cardiac surgery, and the average day for POD occurred at day 3 after surgery. Patients with POD had statistically lower levels of intraoperative mean blood pressure (P = 0.015) and blood pressure ARV (P < 0.001) as well as mean blood pressure at 24 h postoperatively (P = 0.003) when compared to those without. Whereas, ARV for systolic blood pressure (8.64 vs. 7.91 mmHg, P < 0.001), diastolic blood pressure (4.00 vs. 3.77 mmHg, P = 0.014) and mean blood pressure (5.23 vs. 4.94 mmHg, P = 0.001) at 24 h postoperatively was significantly higher in the patients with POD than those without. LASSO regression and further logistic regression revealed that intraoperative blood pressure ARV (OR:0.92, P < 0.001), mean central venous pressure (OR:1.05, P = 0.048) and ARV of systolic blood pressure (OR:1.17, P = 0.002) at 24 h postoperatively were independent risk factors for POD.

CONCLUSIONS: Perioperative ARV, especially postoperative high ARV exposure, was associated with POD in the patients receiving cardiac surgery. Maintaining a relatively stable blood pressure after cardiac surgery might be beneficial to avoid POD in those patients.

PMID:39581994 | DOI:10.1186/s12871-024-02817-x

Confl Health. 2024 Nov 24;18(1):71. doi: 10.1186/s13031-024-00623-3.

ABSTRACT

BACKGROUND: IOM piloted the use of Ag RDTs for COVID-19 in Iraq, in collaboration with FIND, the Global Alliance for Diagnostics, to facilitate access to testing and understand barriers and opportunities for testing in a displacement context. The purpose was to (i) evaluate the performance metrics of the Sure Status COVID-19 Antigen Card Test in this population; (ii) compare Ag RDT results across high- and low-probability cases, vaccination status, and symptom severity; and (iii) report participant perspectives on Ag RDT use for COVID-19 and other diseases.

METHODS: Secondary analysis was conducted using de-identified cross-sectional data collected from November 2022-March 2023 in four IDP camps in the Kurdistan region of Iraq. Data was collected during the recording, reporting, and monitoring processes of the pilot project using Ag RDTs for COVID-19 among displaced populations. Descriptive statistics and bivariate analyses were conducted in Stata (version 17).

RESULTS: 9,346 Sure Status Ag RDTs were performed from November 2022-March 2023. Observed performance metrics were as follows: sensitivity = 72.73% (95% CI: 69.56-75.80%); specificity = 99.74% (95% CI: 99.39-100%), PPV = 92.31% (95% CI: 92.31-94.15%), and NPV = 98.85% (95% CI: 98.11-99.58%). Ag RDT uptake was higher among women and symptomatic individuals, and preference for Ag RDTs was especially strong among illiterate respondents. The overall positivity of Ag RDTs and PCR results in this population remained lower than national averages. Concerningly, 23.39% of respondents declined an Ag RDT because they did not believe in COVID-19.

CONCLUSIONS: This pilot program was among the first to explore Ag RDT use in Iraqi Kurdistan. Over 99% of respondents reported satisfaction with their experience, and over 90% wanted to see Ag RDTs available for other diseases. Findings can inform implementation of RDTs and screening protocols for other infectious diseases, and patient perspectives on Ag RDTs for testing and screening of COVID-19 among displaced populations can inform health programming within Iraq and globally.

PMID:39581993 | DOI:10.1186/s13031-024-00623-3

Crit Care. 2024 Nov 24;28(1):383. doi: 10.1186/s13054-024-05167-9.

ABSTRACT

BACKGROUND: Despite the clinical importance of sepsis-associated acute kidney injury (SA-AKI), little is known about its epidemiology. We aimed to investigate the incidence and outcomes of SA-AKI, as well as the risk factors for mortality among patients with severe SA-AKI in critically ill patients.

METHODS: This secondary multicenter, observational, prospective cohort analysis of sepsis in South Korea evaluated patients aged ≥ 19 years admitted to intensive care units with a diagnosis of sepsis. The primary outcome was the incidence of SA-AKI, defined using the new consensus definition of the Acute Disease Quality Initiative 28 Workgroup. Secondary outcomes were in-hospital mortality and risk factors for in-hospital mortality.

RESULTS: Between September 2019 and December 2022, 5100 patients were admitted to intensive care units with a diagnosis of sepsis, and 3177 (62.3%) developed SA-AKI. A total of 613 (19.3%), 721 (22.7%), and 1843 (58.0%) patients had stage 1, 2, and 3 SA-AKI, respectively. Severe SA-AKI (stages 2 and 3 combined) was associated with an increased risk of in-hospital mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle was associated with a decreased risk of in-hospital mortality in severe SA-AKI (adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.79; P < 0.001).

CONCLUSIONS: Of the patients admitted to the intensive care unit for sepsis, 62.3% developed SA-AKI. Severe SA-AKI was associated with an increased risk of mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle can potentially improve outcomes in these patients.

PMID:39581988 | DOI:10.1186/s13054-024-05167-9

BMC Med Ethics. 2024 Nov 25;25(1):137. doi: 10.1186/s12910-024-01138-5.

ABSTRACT

BACKGROUND: In 2021, a survey was conducted among doctors and nurses at Landspítali Iceland University Hospital (LIUH) regarding their views on medical assistance in dying (MAID) and the underlying arguments, the inclusion criteria and modality of implementation. Surveys on identically defined study groups in 1995 and 2010 were used for comparison.

METHODS: The survey was sent to 357 doctors and 516 nurses working at LIUH. It included seven questions and several subquestions. Participants’ answers were compared by profession, age group, and specialisation status. Descriptive and inferential statistics were used.

RESULTS: A total of 135 doctors (38% response rate) and 103 nurses (20% response rate) answered the survey, representing 27% of the study group. A total of 145 (61%) participants were positive about MAID, with the most common argument being patient autonomy. The 95% margin of error for this view was ± 6.2%. Compared to 19% in 2010, support for MAID had tripled in 2021 (p < 0.05). Approximately 18% of participants did not support MAID of any kind, mostly due to arguments regarding preserving life or inconsistencies with the role of health care professionals. Finally, 19% of participants were uncertain of their views towards MAID, mostly due to the high level of complexity of the matter.

CONCLUSION: Compared to previous surveys, a large increase in positive attitudes towards MAID was observed among this study population. The results revealed the reasons for participants’ attitudes; weighing patients’ dignity/autonomy against professionals’ duty to “not to kill”/palliate and showing some differences between professions.

PMID:39581987 | DOI:10.1186/s12910-024-01138-5

BMC Bioinformatics. 2024 Nov 23;25(1):363. doi: 10.1186/s12859-024-05982-5.

ABSTRACT

BACKGROUND: Over the last decade the drop in short-read sequencing costs has allowed experimental techniques utilizing sequencing to address specific biological questions to proliferate, oftentimes outpacing standardized or effective analysis approaches for the data generated. There are growing amounts of bacterial 3′-end sequencing data, yet there is currently no commonly accepted analysis methodology for this datatype. Most data analysis approaches are somewhat ad hoc and, despite the presence of substantial signal within annotated genes, focus on genomic regions outside the annotated genes (e.g. 3′ or 5′ UTRs). Furthermore, the lack of consistent systematic analysis approaches, as well as the absence of genome-wide ground truth data, make it impossible to compare conclusions generated by different labs, using different organisms.

RESULTS: We present PIPETS, (Poisson Identification of PEaks from Term-Seq data), an R package available on Bioconductor that provides a novel analysis method for 3′-end sequencing data. PIPETS is a statistically informed, gene-annotation agnostic methodology. Across two different datasets from two different organisms, PIPETS identified significant 3′-end termination signal across a wider range of annotated genomic contexts than existing analysis approaches, suggesting that existing approaches may miss biologically relevant signal. Furthermore, assessment of the previously called 3′-end positions not captured by PIPETS showed that they were uniformly very low coverage.

CONCLUSIONS: PIPETS provides a broadly applicable platform to explore and analyze 3′-end sequencing data sets from across different organisms. It requires only the 3′-end sequencing data, and is broadly accessible to non-expert users.

PMID:39580611 | DOI:10.1186/s12859-024-05982-5