Nevin Manimala

ACS Appl Bio Mater. 2024 May 3. doi: 10.1021/acsabm.4c00241. Online ahead of print.

ABSTRACT

Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.

PMID:38701399 | DOI:10.1021/acsabm.4c00241

Int J Neurosci. 2024 May 3:1-10. doi: 10.1080/00207454.2024.2352023. Online ahead of print.

ABSTRACT

Objective: To explore the improvement effect of probiotics combined with dietary fiber on constipation in patients with schizophrenia.Methods: To compare the improvement scores of constipation, constipation symptoms, quality of life, neurotrophic factors-related indicators, and clinical efficacy between the two groups.Results: There was no statistically significant difference in Cleveland Constipation Scoring System (CCS) scores in the control group before and after treatment (P > 0.05), while the CCS scores in the observation group decreased significantly after treatment (P < 0.05); Patient Assessment of Constipation Symptoms scores significantly decreased in the observation group compared to the control group (P < 0.05), with no significant difference in Patient Assessment of Constipation Quality of Life scores between the two groups pre- and post-treatment; Neuron-specific enolase levels decreased significantly in both groups post-treatment, while brain-derived neurotrophic factor, neuregulin-1, and nerve growth factor levels increased significantly, with a more pronounced rise in the observation group (P < 0.05). Additionally, the total effective rate of clinical treatment in the observation group was higher than that in the control group (P < 0.05).Conclusion: Probiotics combined with dietary fiber can improve constipation symptoms in patients with schizophrenia accompanied by constipation, effectively maintain the balance of intestinal microbiota, and improve the quality of life of patients. Additionally, levels of neurotrophic factors associated with bowel function and neurological health increased significantly, with a higher total effective rate of clinical treatment observed in the probiotics and dietary fiber group. These findings suggest the potential efficacy of probiotics and dietary fiber in managing constipation in this patient population.

PMID:38701375 | DOI:10.1080/00207454.2024.2352023

Blood Adv. 2024 May 3:bloodadvances.2023011458. doi: 10.1182/bloodadvances.2023011458. Online ahead of print.

ABSTRACT

Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with Chronic Lymphocytic leukemia. But whether vitamin D supplement affects the clinical course of CLL patients, remains an open question. In the current study, we aimed to retrospectively explore the clinical benefit of Vitamin D supplement, or one of its analogues, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch and wait approach. Among the 3,474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analogue, for a minimum of 6 months. We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age<=65) and was associated with a longer TFS for all ages (p-value=0.004). Among non-vitamin D users, the median TFS was found to be 84 months, while among vitamin D supplement users the median TFS extended to 169 months. In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch and wait active surveillance is significantly associated with a longer treatment free survival (in any age) and a longer time to first treatment among young patients (age<=65). A prospective clinical trial is needed to validate results.

PMID:38701347 | DOI:10.1182/bloodadvances.2023011458

Medicine (Baltimore). 2024 May 3;103(18):e37991. doi: 10.1097/MD.0000000000037991.

ABSTRACT

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

PMID:38701321 | DOI:10.1097/MD.0000000000037991

Medicine (Baltimore). 2024 May 3;103(18):e38009. doi: 10.1097/MD.0000000000038009.

ABSTRACT

Subdural hematoma is defined as blood collection in the subdural space between the dura mater and arachnoid. Subdural hematoma is a condition that neurosurgeons frequently encounter and has acute, subacute and chronic forms. The incidence in adults is reported to be 1.72-20.60/100.000 people annually. Our study aimed to evaluate the quality, reliability and readability of the answers to questions asked to ChatGPT, Bard, and perplexity about “Subdural Hematoma.” In this observational and cross-sectional study, we asked ChatGPT, Bard, and perplexity to provide the 100 most frequently asked questions about “Subdural Hematoma” separately. Responses from both chatbots were analyzed separately for readability, quality, reliability and adequacy. When the median readability scores of ChatGPT, Bard, and perplexity answers were compared with the sixth-grade reading level, a statistically significant difference was observed in all formulas (P < .001). All 3 chatbot responses were found to be difficult to read. Bard responses were more readable than ChatGPT’s (P < .001) and perplexity’s (P < .001) responses for all scores evaluated. Although there were differences between the results of the evaluated calculators, perplexity’s answers were determined to be more readable than ChatGPT’s answers (P < .05). Bard answers were determined to have the best GQS scores (P < .001). Perplexity responses had the best Journal of American Medical Association and modified DISCERN scores (P < .001). ChatGPT, Bard, and perplexity’s current capabilities are inadequate in terms of quality and readability of “Subdural Hematoma” related text content. The readability standard for patient education materials as determined by the American Medical Association, National Institutes of Health, and the United States Department of Health and Human Services is at or below grade 6. The readability levels of the responses of artificial intelligence applications such as ChatGPT, Bard, and perplexity are significantly higher than the recommended 6th grade level.

PMID:38701313 | DOI:10.1097/MD.0000000000038009

Medicine (Baltimore). 2024 May 3;103(18):e38046. doi: 10.1097/MD.0000000000038046.

ABSTRACT

BACKGROUND: Postcholecystectomy diarrhea (PCD) is among the most distressing and well-known clinical complications of cholecystectomy. Despite various available treatment options, clinical outcomes are greatly limited by unclear pathophysiological mechanisms. Chinese herbal medicine (CHM) is widely used as a complementary and alternative therapy for the treatment of functional diarrhea. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of CHM for the treatment of PCD.

METHODS: Electronic database searches were conducted using the Cochrane Library, PubMed, Web of Science, Embase, Wanfang Data, China National Knowledge Infrastructure, and the Chinese Scientific Journal Database. All RCTs on CHMs for managing patients with PCD were included. The meta-analysis was performed using RevMan 5.4 software.

RESULTS: The present meta-analysis included 14 RCTs published between 2009 and 2021 in China. The primary findings indicated that CHM had a higher total efficacy and cure rate as a monotherapy for PCD (P < .00001). Two trials reported the scores of the main symptoms with statistically significant differences in stool nature (P < .00001), defecation frequency (P = .002), and abdominal pain and bloating (P < .00001). In addition, CHM reduced CD3+ and CD4+ levels more effectively in terms of T lymphocyte subset determination (P < .00001). The main symptoms of PCD in traditional Chinese medicine (TCM) are splenic deficiency and liver stagnation. All treatments were used to strengthen the spleen and (or) soothing the liver.

CONCLUSION: CHM had a favorable effect on PCD. No adverse events were observed. Larger, high-quality RCTs are warranted to draw definitive conclusions and standardize treatment protocols.

PMID:38701312 | DOI:10.1097/MD.0000000000038046

Medicine (Baltimore). 2024 May 3;103(18):e38026. doi: 10.1097/MD.0000000000038026.

ABSTRACT

As point-of-care ultrasound (POCUS) is increasingly being used in clinical settings, ultrasound education is expanding into student curricula. We aimed to determine the status and awareness of POCUS education in Korean medical schools using a nationwide cross-sectional survey. In October 2021, a survey questionnaire consisting of 20 questions was distributed via e-mail to professors in the emergency medicine (EM) departments of Korean medical schools. The questionnaire encompassed 19 multiple-choice questions covering demographics, current education, perceptions, and barriers, and the final question was an open-ended inquiry seeking suggestions for POCUS education. All EM departments of the 40 medical schools responded, of which only 13 (33%) reported providing POCUS education. The implementation of POCUS education primarily occurred in the third and fourth years, with less than 4 hours of dedicated training time. Five schools offered a hands-on education. Among schools offering ultrasound education, POCUS training for trauma cases is the most common. Eight schools had designated professors responsible for POCUS education and only 2 possessed educational ultrasound devices. Of the respondents, 64% expressed the belief that POCUS education for medical students is necessary, whereas 36%, including those with neutral opinions, did not anticipate its importance. The identified barriers to POCUS education included faculty shortages (83%), infrastructure limitations (76%), training time constraints (74%), and a limited awareness of POCUS (29%). POCUS education in Korean medical schools was limited to a minority of EM departments (33%). To successfully implement POCUS education in medical curricula, it is crucial to clarify learning objectives, enhance faculty recognition, and improve the infrastructure. These findings provide valuable insights for advancing ultrasound training in medical schools to ensure the provision of high-quality POCUS education for future healthcare professionals.

PMID:38701308 | DOI:10.1097/MD.0000000000038026

Medicine (Baltimore). 2024 May 3;103(18):e38063. doi: 10.1097/MD.0000000000038063.

ABSTRACT

In this research, we aimed to investigate the predictive value of the systemic immune inflammation index and prognostic nutritional index on mortality among patients with an endoprosthesis after a hip fracture. In this retrospective, cross-sectional study, a total of 915 patient files applied to our hospital between 2020 and 2023 with an endoprosthesis after a hip fracture were subjected to the study. The patients were divided into 2 groups: alive (n = 396; 43.3%) and deceased (n = 519; 56.7%). The eosinophil-to-lymphocyte ratio, hemoglobin-to-red cell distribution width ratio (HRR), mean platelet volume-to-platelet ratio (MPVPR), neutrophil-to-lymphocyte ratio, monocyte/lymphocyte ratio, platelet-to-lymphocyte ratio, MPV-to-lymphocyte ratio, monocyte-to-eosinophil ratio (MER), neutrophile-to-monocyte ratio, systemic inflammation index (SII), and prognostic nutritional index (PNI) parameters of the patients were evaluated. The mortality rate was higher among male patients, with a statistically significant difference (P < .05). The follow-up duration, albumin, HGB, eosinophil, lymphocyte, eosinophil %, eosinophil-to-lymphocyte ratio, HRR, and PNI means were significantly higher in the living group (P < .05). Age, MPV, MPVPR, neutrophil-to-lymphocyte ratio, monocyte/lymphocyte ratio, platelet-to-lymphocyte ratio, MPV-to-lymphocyte ratio, MER, and systemic inflammation index were significantly higher in the deceased group (P < .05). The predictive value of gender (B = -0.362; P < .01), age (B = 0.036; P < .01), HRR (B = -1.100; P < .01), MPVPR (B = 8.209; P < .01), MER (B = 0.006; P < .01), and PNI (B = -0.078; P < .01) were statistically significant at the multivariate level. The time of death was significantly predicted by gender (B = 0.10; P < .05), age (B = -0.02; P < 0 = 1), HRR (B = 0.61; P < .01), MPVPR (r = -4.16; P < .01), MER (B = -0.01; P < .05), and PNI (B = 0.03; P < .01). The predictive value of PNI for the 30-day mortality rate was statistically significant (AUC: 0.643; P < .01). For a PNI cutoff value of 34.475, sensitivity was 69.7%, and specificity was 51.1%. The PNI has predictive value both in estimating overall mortality and in predicting the 30-day mortality rates among patients undergoing endoprosthesis after a hip fracture.

PMID:38701306 | DOI:10.1097/MD.0000000000038063

Medicine (Baltimore). 2024 May 3;103(18):e37943. doi: 10.1097/MD.0000000000037943.

ABSTRACT

BACKGROUND: Lumbar disc herniation was regarded as an age-related degenerative disease. Nevertheless, emerging reports highlight a discernible shift, illustrating the prevalence of these conditions among younger individuals.

METHODS: This study introduces a novel deep learning methodology tailored for spinal canal segmentation and disease diagnosis, emphasizing image processing techniques that delve into essential image attributes such as gray levels, texture, and statistical structures to refine segmentation accuracy.

RESULTS: Analysis reveals a progressive increase in the size of vertebrae and intervertebral discs from the cervical to lumbar regions. Vertebrae, bearing weight and safeguarding the spinal cord and nerves, are interconnected by intervertebral discs, resilient structures that counteract spinal pressure. Experimental findings demonstrate a lack of pronounced anteroposterior bending during flexion and extension, maintaining displacement and rotation angles consistently approximating zero. This consistency maintains uniform anterior and posterior vertebrae heights, coupled with parallel intervertebral disc heights, aligning with theoretical expectations.

CONCLUSIONS: Accuracy assessment employs 2 methods: IoU and Dice, and the average accuracy of IoU is 88% and that of Dice is 96.4%. The proposed deep learning-based system showcases promising results in spinal canal segmentation, laying a foundation for precise stenosis diagnosis in computed tomography images. This contributes significantly to advancements in spinal pathology understanding and treatment.

PMID:38701305 | DOI:10.1097/MD.0000000000037943

Medicine (Baltimore). 2024 May 3;103(18):e37935. doi: 10.1097/MD.0000000000037935.

ABSTRACT

BACKGROUND: Inappropriate medication utilization among older adults is a pressing concern in the United States, owing to its high prevalence and the consequential detrimental impact it engenders. The adverse effects stemming from the inappropriate use of medication may be unequally borne by racial/ethnic minority populations, calling for greater efforts towards promoting equity in healthcare. The study objective was to assess the cost-effectiveness of Medication Therapy Management (MTM) services among Medicare beneficiaries and across racial/ethnic groups.

METHODS: Medicare administrative data from 2016 to 2017 linked to Area Health Resources Files were used to analyze Medicare fee-for-service patients aged 65 or above with continuous Parts A/B/D coverage. The intervention group included new MTM enrollees in 2017; the control group referred to patients who met the general MTM eligible criteria but did not enroll in 2016 or 2017. The 2 groups were matched using a propensity score method. Effectiveness was evaluated as the proportion of appropriate medication utilization based on performance measures developed by the Pharmacy Quality Alliance. Costs were computed as total healthcare costs from Medicare perspective. A multivariable net benefit regressions with a classic linear model and Bayesian analysis were utilized. Net benefit was calculated based on willingness-to-pay thresholds at various multiples of the gross domestic product in 2017. Three-way interaction terms among dummy variables for MTM enrollment, 2017, and racial/ethnic minority groups were incorporated in a difference-in-differences study design.

RESULTS: After adjusting for patient characteristics, the findings indicate that MTM receipt was associated with incremental net benefit among each race and ethnicity. For instance, the net benefit of MTM among the non-Hispanic White patients was $2498 (95% confidence interval = $1609, $3386) at a willingness-to-pay value of $59,908. The study found no significant difference in net benefits for MTM services between minority and White patients.

CONCLUSION: The study provides evidence that MTM is a cost-effective tool for managing medication utilization among the Medicare population. However, MTM may not be cost-effective in reducing racial/ethnic disparities in medication utilization in the short term. Further research is needed to understand the long-term cost-effectiveness of MTM on racial/ethnic disparities.

PMID:38701304 | DOI:10.1097/MD.0000000000037935