Nevin Manimala

Allergy Asthma Clin Immunol. 2025 Aug 13;21(1):34. doi: 10.1186/s13223-025-00979-y.

ABSTRACT

In recent years, the use of monoclonal antibodies directed against interleukin-5 (anti-IL-5) and its receptor alpha (anti-IL-5R) has proven to be an effective therapeutic option for patients with severe asthma by reducing the number of eosinophils, which may promote disease remission. This study aimed to evaluate clinical improvement and remission in patients with severe asthma treated with anti-IL-5 and anti-IL-5R antibodies over a period of 12 months. A cohort study was conducted with 49 patients diagnosed with severe eosinophilic asthma and who did not respond to conventional treatment. During follow-up, medical control was performed every 3 months using spirometry, eosinophil counts, quality of life scales, and disease control. The results revealed an improvement in FEV1 after 3 months of treatment, with statistical significance at 12 months in patients treated with anti-IL-5 and at 9 months in those treated with anti-IL-5R. In addition, better perceptions of asthma control and quality of life were observed, with significant differences at 6 and 12 months. Correlations between spirometry and ACT, ACQ, and AQLQ reflect a progressive recovery of well-being and function. Finally, the remission rate was 41.1% with anti-IL-5 treatment and 47.3% with anti-IL-5R treatment after one year of follow-up. These findings support the efficacy of anti-IL-5 and anti-IL-5R treatment in improving severe asthma control and patients’ quality of life, suggesting their key role in disease remission.

PMID:40804423 | DOI:10.1186/s13223-025-00979-y

Eur J Med Res. 2025 Aug 14;30(1):749. doi: 10.1186/s40001-025-02951-3.

ABSTRACT

BACKGROUND: Epidural fibrosis (EF) is the major complication that develops in the operative region of the spinal vertebrae. This fibrous scar connects the connective tissue around the lateral nerve roots and epidural, resulting in severe pain post-spinal operation and impairment of the nerves’ function.

PURPOSE: This study was conducted to investigate the effect of using platelet-rich fibrin (PRF), chitosan, and their combination in reducing epidural fibrosis after laminectomy in rats.

METHODS: Ninety male Sprague Dawley rats weighing 255 ± 55 g were randomly assigned to five groups, each consisting of 15 rats: the normal group (control), the laminectomy group, the PRF group, the chitosan group, the combination group (PRF/chitosan), and the donor group. All rats, except the control group, had lumbar laminectomy surgeries between L3 and L5. Macroscopic analysis, histological evaluations, and mRNA analysis for TGFβ-1 and IL6 were compared statistically after a 30-day follow-up.

RESULTS: In comparison to the laminectomy group, the EF area was significantly decreased in the PRF, chitosan, and combination groups. Histological study, macroscopic inspection, and mRNA expression of TGFβ-1 (P < 0.0001) and IL6 (P < 0.0001) show that the use of PRF with chitosan topically in dura following laminectomy resulted in a decrease in scar tissue formation, inflammation, and EF post-laminectomy.

CONCLUSION: The combination of chitosan with PRF is a potential therapeutic approach for minimizing EF in rats after laminectomy.

PMID:40804422 | DOI:10.1186/s40001-025-02951-3

Addict Sci Clin Pract. 2025 Aug 13;20(1):67. doi: 10.1186/s13722-025-00593-8.

ABSTRACT

BACKGROUND: Amphetamine-type stimulant use and overdoses have increased sharply across the US in recent years, largely driven by methamphetamine. Increased access to treatments for amphetamine-type stimulant use disorder (AT-StUD), including in primary care settings, is needed to mitigate these problems, yet effective behavioral treatments are often inaccessible and there are no FDA-approved medications for AT-StUD. In the current study, we characterize how often patients with clinically documented AT-StUD in predominantly rural-serving Pacific Northwest primary care clinics received medications that have been conditionally recommended in practice guidelines for treatment of AT-StUD.

METHODS: Electronic health record data from 23 primary care clinics in the Pacific Northwest US were obtained through the Data QUEST network. Adult patients with clinically documented “other stimulant abuse” or “other stimulant dependence” diagnoses typically reflecting AT-StUD between 01/2017 and 12/2021 were included. Prescription records were used to identify orders for bupropion, mirtazapine, topiramate, naltrexone-bupropion combination, methylphenidate, dextroamphetamine, and modafinil. Statistical analyses quantified the percentage of patients with medication orders placed within one year after any documented AT-StUD diagnosis.

RESULTS: Patients (N = 963) were predominantly female (53.3%), White (81.7%), and non-Hispanic (70.5%). In total, 14.3% of patients received orders for a non-stimulant medication conditionally recommended in practice guidelines; 2.7% received orders for a stimulant medication. Consistent with clinical guidelines, medications were more often prescribed when patients had documented co-occurring disorders for which the medications could also be effective.

CONCLUSIONS: In this sample of rural-serving primary care clinics, approximately 1 in 7 primary care patients with AT-StUD received orders for medications with preliminary evidence of effectiveness. Efforts are needed to increase access to AT-StUD treatments within primary care. These efforts could include training health professionals to consider judicious use of pharmacotherapy consistent with clinical guidelines, increasing capacity for behavioral health services including contingency management, and continuing research on pharmacologic agents.

PMID:40804420 | DOI:10.1186/s13722-025-00593-8

Cardiovasc Diabetol. 2025 Aug 13;24(1):331. doi: 10.1186/s12933-025-02884-5.

ABSTRACT

BACKGROUND: Mitochondrial dysfunction plays a pivotal role in the onset and progression of diabetic cardiomyopathy (DCM). It is hypothesized that ultrastructural mitochondrial abnormalities, molecular dynamics imbalance, and bioenergetic impairments collectively contribute significantly to cardiac dysfunction. Consequently, investigating mitochondrial ultrastructural changes and metabolic disturbances is crucial for elucidating the mechanistic underpinnings of DCM.

OBJECTIVE: This study aims to comprehensively characterize alterations in mitochondrial ultrastructure and energy metabolism in DCM and examine the interplay between these two factors.

METHODS: High glucose-treated H9c2 cardiomyocytes and DCM model mice were analyzed via scanning electron microscopy (SEM) and 3D imaging. Three-dimensional morphometric parameters-such as Length3D, Thickness3D, Width3D, Area3D, Volume3D, Anisotropy, Flatness, and Elongation-were quantified to evaluate mitochondrial architecture. At the two-dimensional (2D) level, mitochondria-associated membrane (MAM) parameters were analyzed. Further, detailed statistical analysis was conducted on mitochondrial cristae, including cristae scores, count, width, gap size, and junction widths in myocardial tissues. Mitochondrial dynamics and autophagy-related protein expression (Mfn1, Mfn2, Opa1, p-Drp1(ser616), PINK1, Parkin1) in myocardial tissues were assessed by Western blot. Mitochondrial bioenergetics were measured by ATP content, membrane potential, mtDNA copy number, SOD levels, mitochondrial Ca²⁺ levels, and oxidative phosphorylation (OXPHOS) activity across Complexes I-V in myocardial tissue. Additionally, the oxygen consumption rate (OCR) of viable H9c2 cells was measured using the O2k system.

RESULTS: 3D reconstruction revealed key myocardial ultrastructures-including T-tubules, sarcoplasmic reticulum (SR), intercalated discs, and mitochondria-and demonstrated significant differences in mitochondrial morphology and 3D morphometric parameters across subpopulations. Under high glucose (HG) conditions, in vitro analysis showed a reduction in mitochondrial Length3D and Anisotropy in H9c2 cells, accompanied by increases in Thickness3D, Width3D, Flatness, and Elongation. HG exposure also led to an increase in the length of MAM contact sites and the MAM-to-mitochondria perimeter ratio. In vivo, the DCM group exhibited decreased 2D morphometric parameters (length, width, area, perimeter, and shape AP), as well as reductions in 3D measurements (Thickness3D, Width3D, and Volume3D) compared to controls. No significant differences were observed in Length3D, Area3D, Anisotropy, Flatness, and Elongation between groups. 3D surface analysis revealed rough mitochondrial surfaces in the DCM group, while controls displayed smooth surfaces. Control mitochondria exhibited well-aligned, well-defined cristae, whereas DCM mitochondria showed cristae dissolution, disorganized arrangements, and vacuolization within the cristae. The DCM group also had increased cristae junction width and spacing. Additionally, megamitochondria were observed in DCM samples. The DCM group showed a significant increase in MAM contact site length and MAM-to-mitochondria perimeter ratio in myocardial tissue. Molecular analysis revealed decreased expression of fusion proteins (Mfn1, Opa1) and increased levels of p-Drp1(ser616), alongside elevated autophagy markers (PINK1, Parkin1). Bioenergetic dysfunction was evident through decreased ATP production, mitochondrial membrane potential collapse (ΔΨm), reduced mtDNA copy number, decreased SOD levels, impaired activities of complexes I/III/IV/V, and diminished basal/maximal respiration, ATP-linked respiration, and spare respiratory capacity. Conversely, mitochondrial Ca²⁺ levels were elevated in the DCM group, along with increased proton leakage in H9c2 cells.

CONCLUSIONS: This study establishes a comprehensive framework linking “3D morphology-molecular regulation-metabolic dysfunction,” highlighting the synergistic interplay between mitochondrial ultrastructural remodeling and bioenergetic failure as key drivers of DCM progression. These findings provide valuable insights into DCM pathogenesis and suggest potential therapeutic targets.

PMID:40804395 | DOI:10.1186/s12933-025-02884-5

BMC Health Serv Res. 2025 Aug 13;25(1):1077. doi: 10.1186/s12913-025-13310-7.

ABSTRACT

BACKGROUND: The moral courage of nurses is crucial for complex decision-making, patient safety, and communication. However, the direct relationship between nurses’ moral courage and patient safety, particularly during the COVID-19 pandemic, remains unconfirmed. This study aims to investigate this relationship in both COVID-19 and non-COVID-19 departments.

METHODS: A cross-sectional analytical design was employed, with a sample of 300 nurses from five public hospitals in northwestern (…) affiliated with the University of Medical Sciences. Data were collected between 2021 and 2022 using the validated (…) version of the Hospital Survey on Patient Safety Culture and the Sekerka Moral Courage Scale. Descriptive and inferential statistical analyses were conducted.

RESULTS: The safety climate scores were 23.7% in the COVID-19 ward and 25.8% in the non-COVID-19 ward, with no significant difference between the two sectors. Moral courage scores were 50.4% in the COVID-19 wards and 44.9% in the non-COVID-19 wards, showing no significant difference. A strong relationship between moral courage and safety climate was observed in both wards. Regression analysis indicated a Cohen’s f² effect size of 1.77 for moral courage, suggesting a significant impact on patient safety culture.

CONCLUSIONS: This study found no significant differences in moral courage or patient safety culture between COVID-19 and non-COVID-19 departments. However, moral courage can predict improvements in patient safety, even in complex situations like the COVID-19 crisis. To enhance patient safety, it may be necessary to strengthen nurses’ moral courage through experiential training, supportive environments, and leadership workshops emphasizing empathy and ethical decision-making. Additionally, integrating these educational components into nursing education is important. By enhancing these skills in nursing education, we may improve patient safety and better prepare them to tackle future challenges and crises effectively.

PMID:40804383 | DOI:10.1186/s12913-025-13310-7

BMC Nephrol. 2025 Aug 13;26(1):457. doi: 10.1186/s12882-025-04393-9.

ABSTRACT

BACKGROUND: To assess satisfaction and perspectives of adult hemodialysis (HD) patients on different vascular access (VA) types (AVF, AVG, CVC) by synthesizing quantitative studies using validated questionnaires, focusing on overall satisfaction, physical symptoms, social functioning, and complications.

METHODS: We systematically searched Medline, Web of Science, and Scopus for studies assessing adult HD patients’ perspectives on VA using structured questionnaires. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random-effects model across three pairwise comparisons: AVF vs. CVC, AVF vs. AVG, and CVC vs. AVG.

RESULTS: Of 1,253 records, 11 studies (n = 2910) met inclusion criteria. AVF patients had higher overall satisfaction compared to those with CVCs (MD: 7.06%, 95% CI: 2.98-11.14). Compared to AVG, AVF patients had higher overall satisfaction, though not statistically significant (MD: 5.12%, 95% CI: – 0.42 to 10.66; p = 0.069). Dissatisfaction with physical symptoms was significantly higher in AVF patients than in those with CVCs (MD: 8.76%, 95% CI: 4.19 to 13.34). Compared to CVC, AVF patients reported significantly lower dissatisfaction in both social functioning (MD: – 9.48%, 95% CI: – 15.98 to – 2.98) and dialysis-related complications (MD: – 10.08%, 95% CI: -12.66 to -7.50).

CONCLUSIONS: AVFs are associated with higher overall patient satisfaction compared to other VA types. While AVF patients experience more physical discomfort, this is outweighed by significantly greater satisfaction in areas such as social functioning and dialysis-related complications. These findings emphasize the importance of considering patient-reported outcomes when evaluating VA options in HD care.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40804373 | DOI:10.1186/s12882-025-04393-9

BMC Infect Dis. 2025 Aug 13;25(1):1012. doi: 10.1186/s12879-025-11430-3.

ABSTRACT

BACKGROUND: Tuberculosis (TB) is a top infectious disease killer worldwide. The susceptibility to infectious diseases, including tuberculosis, has been linked to several cytokine gene polymorphisms.

METHOD: A case-control study was conducted at Abu Anja Chest Hospital, Omdurman, Khartoum state, using PCR-RFLP in 200 Sudanese patients with pulmonary tuberculosis and 200 healthy controls between February 2018 and February 2021. Data analysis was done using the IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp).

RESULT: The mutant and heterozygous genotypes of IL-12+16974 A/C polymorphism were associated with an almost four-fold [P-value <0.001 OR= 3.703(2.243- 6.115), 95% CI] increased risk of TB in the Sudanese population. No statistically significant differences were found in the genotype and allele frequencies of the IFN-γ+874T/A gene between patients and controls.

CONCLUSION: These findings suggest, for the first time in Sudan, the significant risk of TB in people carrying the mutant and heterozygous genotypes of IL-12+16974 A/C genes.

PMID:40804362 | DOI:10.1186/s12879-025-11430-3

BMC Neurol. 2025 Aug 13;25(1):340. doi: 10.1186/s12883-025-04361-8.

ABSTRACT

BACKGROUND: Stroke is a sudden focal neurological deficit caused by vascular damage to the central nervous system. Globally, stroke is a leading cause of death and disability, with a particularly significant burden in low- and middle-income countries. In Iran, the incidence of acute stroke is increasing, and the age of onset is lower compared to developed countries. This study examines factors causing pre-hospital delays in acute stroke patients at Shahid Rajaei Hospital, Tonekabon, North of Iran (2022-2023). Timely intervention is critical for improving outcomes, as delays significantly affect treatment effectiveness. This study aims to identify the primary causes of pre-hospital delays in acute stroke patients and provide actionable insights to enhance timely intervention strategies, ultimately improving patient outcomes.

METHODS: A retrospective descriptive-analytical study was conducted on 150 acute stroke patients using census sampling. Data included demographics, symptoms, and time intervals from onset to hospital arrival. Analysis was performed with SPSS using chi-square, T-tests, and ANOVA.

RESULTS: Of the 150 patients, 81.3% arrived over 4.5 hours after symptom onset, missing the thrombolytic treatment window. Statistical analysis revealed significant associations between some demographic and clinical factors: shorter distances to the hospital and faster arrival (p = 0.037), presence of a witness (p = 0.041), and stroke onset during the daytime (p = 0.002) were linked to reduced delays. Marital status also influenced arrival times significantly (p = 0.007). Other delay factors included unawareness of stroke symptoms (46%), being alone (14.7%), and symptoms occurring during sleep (8.6%).

CONCLUSIONS: The study highlights the need for public education on stroke symptoms and improved emergency systems to reduce delays. Addressing these gaps can enhance patient outcomes, especially in areas with limited awareness and resources.

PMID:40804361 | DOI:10.1186/s12883-025-04361-8

Sci Rep. 2025 Aug 13;15(1):29629. doi: 10.1038/s41598-025-14804-4.

ABSTRACT

Extreme events in turbulent flows are rare, fast excursions from typical behavior that can significantly impact systems performance and reliability. Predicting such events is challenging due to their intermittent nature and rare occurrence, which limits the effectiveness of data-intensive methods. This paper, therefore, introduces a novel data-driven approach for on-the-fly early-stage prediction of extreme events in time signals. The method identifies the most energetic time-only POD mode of an ensemble of time segments leading to extreme events in a signal. High similarity between incoming signals and the computed mode serves as an indicator of an approaching extreme event. A support vector machine is employed to classify the signals as preceding an extreme event or not. This approach is fully data-driven and requires minimal training data, making it particularly suitable for significantly rare events. The method is applied to predict extreme dissipation events in a wall-bounded shear flow at different Reynolds numbers and wall distances, demonstrating robust performance across a range of intermittency levels. Even with limited training data, leading to an imperfect representation of the extreme event statistics, the method provides predictions at lead times that match and usually exceed the timeframe for which the Hankel-DMD method remains accurate. This opens up the possibility of using the conditional POD method to flag incoming extreme events so that potentially unreliable forecasts from signal prediction methods, such as Hankel-DMD, can be discarded or their forecasting horizon shortened.

PMID:40804352 | DOI:10.1038/s41598-025-14804-4

Sci Rep. 2025 Aug 13;15(1):29657. doi: 10.1038/s41598-025-14688-4.

ABSTRACT

Norovirus is a highly contagious virus and the leading cause of acute gastroenteritis worldwide. The World Health Organization (WHO) estimates that approximately 685 million cases of norovirus infection occur each year, with around 200 million affecting children under the age of five. The impact of this virus is substantial, contributing to roughly 200,000 deaths annually-about 50,000 of which are among young children-mostly in low-income countries. In addition to the human toll, norovirus imposes a significant economic burden, with global costs reaching approximately $60 billion each year due to healthcare expenses and lost productivity. In this paper, we present a fractional-order mathematical analysis of the norovirus epidemic model, focusing on its transmission dynamics, incorporating memory effects. The total population, denoted as N(t), is categorized into four compartments: susceptible, exposed, infected, and recovered. We analytically derive the equilibrium points and the basic reproduction number of the model. Furthermore, we discuss the properties of positivity, boundedness, uniqueness, and existence to ensure the model’s validity. The non-linear model is linearized around its equilibrium points, and local stability is analyzed using the eigenvalues of the Jacobian matrix. In addition, global stability is examined using the Lyapunov function and LaSalle’s invariance principle. To validate the theoretical findings, a numerical scheme based on the GL-Non-Standard Finite Difference (NSFD) method is developed, which serves to verify the theoretical analysis of the norovirus epidemic model.

PMID:40804347 | DOI:10.1038/s41598-025-14688-4