Nevin Manimala

Ann Clin Biochem. 2023 Aug 4:45632231196052. doi: 10.1177/00045632231196052. Online ahead of print.

ABSTRACT

INTRODUCTION AND AIMS: Sodium can be measured with direct or indirect methods, abnormal plasma total protein concentration can impact on sodium measured by indirect ion-selective electrodes (ISE). Serum sodium is an important item to determine the Model for End Stage Liver Disease Sodium (MELD-Na) score, commonly used for liver graft allocation. Patients with cirrhosis usually have hypoproteinemia. The aim of this study was to determine if there was a significant difference between the MELD-Na scores calculated based on the results of two different serum sodium ISE: indirect and direct.

METHODS: This was a retrospective study, we included 166 patients that underwent liver transplant assessment, and that had paired (i.e. same date and time) direct and indirect sodium determinations. We calculated the MELD-Na scores with both sodium determinations, and we compared them.

RESULTS: There was a significant difference between MELD-Na scores, the mean difference was 0.4+1.3. If MELD-Na score had been determined by the sodium measured by the direct ISE, 69 patients (42%) would have stayed in the same place on the waiting list, 67 patients (40%) would have moved up, and 30 patients (18%) would have moved down.

CONCLUSIONS: There was a statistically significant difference between the MELD-Na scores calculated based on the two different sodium concentrations, which would theoretically result in changes in the order of the waiting list. This finding should prompt studies to assess if MELD-Na calculated based on direct methods has a better performance to predict clinically relevant outcomes.

PMID:37542376 | DOI:10.1177/00045632231196052

Biophys J. 2023 Aug 4:S0006-3495(23)00501-5. doi: 10.1016/j.bpj.2023.08.001. Online ahead of print.

ABSTRACT

Chromosomal dynamics plays a central role in a number of critical biological processes, such as transcriptional regulation, genetic recombination, and DNA replication. However, visualization of chromatin is generally limited to live imaging of a few fluorescently labeled chromosomal loci or high-resolution reconstruction of multiple loci from a single time frame. To aid in mapping the underlying chromosomal structure based on parsimonious experimental measurements, we present an exact analytical expression for the evolution of the polymer configuration based on a flexible-polymer model, and we propose an algorithm that tracks the polymer configuration from live images of chromatin marked with several fluorescent marks. Our theory identifies the resolution of microscopy needed to achieve high-accuracy tracking for a given spacing of markers, establishing the statistical confidence in the assignment of genome identity to the visualized marks. We then leverage experimental data of locus-tracking measurements to demonstrate the validity of our modeling approach and to establish a basis for the design of experiments with a desired resolution. Altogether, this work provides a computational approach founded on polymer physics that vastly improves the interpretation of in vivo measurements of biopolymer dynamics.

PMID:37542372 | DOI:10.1016/j.bpj.2023.08.001

J Diabetes Sci Technol. 2023 Aug 4:19322968231190413. doi: 10.1177/19322968231190413. Online ahead of print.

ABSTRACT

BACKGROUND: Significant complications of diabetes include pain and the loss of sensation in peripheral limbs. Pain management of diabetic symmetric peripheral neuropathy (DSPN) remains challenging. This study reports on utilizing pulsed electromagnetic field therapy (PEMF) to reduce pain and improve skin perfusion pressure (SPP) in subjects with DSPN.

METHODS: A randomized, sham-controlled, double-blind, clinical trial was conducted on subjects afflicted with foot pain associated with DSPN. Following informed consent, 182 subjects with diabetes and confirmed DSPN were entered into the trial for a period of 18 weeks. Subjects were randomized into active PEMF treatment or nonactive sham and instructed to treat to their feet for 30 minutes, twice daily and report daily pain scores. Some patients in the active arm experienced a transient low field strength notification (LFSN) due to improper pad placement during treatment. Skin perfusion pressure measurements were also collected at two and seven weeks to assess peripheral arterial disease effects via measurement of local microcirculatory flow and blood pressure.

RESULTS: Patients in the active arm who did not receive an LFSN experienced a clinically significant 30% reduction in pain from baseline compared to sham (P < .05). Though not statistically significant, SPP in the active group trended toward improvement compared to sham.

CONCLUSIONS: Pulsed electromagnetic field therapy appears effective as a nonpharmacological means for reduction of pain associated with diabetic peripheral neuropathy and holds promise for improvement of vascular physiology in microcirculatory dysfunction associated with diabetic peripheral arterial disease.

PMID:37542366 | DOI:10.1177/19322968231190413

Mol Pain. 2023 Aug 4:17448069231195975. doi: 10.1177/17448069231195975. Online ahead of print.

ABSTRACT

BACKGROUND: Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and mtDNA damage. People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses.

METHODS: The current study included PWH with (n=26), and without (n=29), chronic pain. Participants completed a single session that lasted approximately 180 minutes, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e. ND1 and ND6).

RESULTS: We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups.

CONCLUSION: PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.

PMID:37542365 | DOI:10.1177/17448069231195975

Med Teach. 2023 Aug 4:1-6. doi: 10.1080/0142159X.2023.2243023. Online ahead of print.

ABSTRACT

PURPOSE: This pilot study aimed to investigate the acceptability and efficacy of a patient storytelling intervention (live and recorded) on empathy levels of medical students.

MATERIALS AND METHODS: Medical students participated in a storytelling intervention that had three components: listening to live or recorded stories from women with abnormal uterine bleeding, reflective writing, and a debriefing session. Empathy scores of students pre- and post-intervention were measured using the Jefferson Scale of Empathy-student version (JSE-S). Students also completed a feedback survey. Descriptive and inferential statistics were used to analyse quantitative data and content analysis was used for text comments.

RESULTS: Both live and recorded storytelling interventions had positive effects on student’s empathy scores post intervention. Overall, students were satisfied with the intervention and reported that it improved their understanding of life experiences of women. Suggestions were made for an in-person storytelling session and interactive discussion after listening to each story.

CONCLUSION: A storytelling intervention has the potential to improve medical students’ empathy and understanding of lived experience of women with health conditions. This could be valuable when student-patient interactions are limited in healthcare settings, or to enable stories of small numbers of patient volunteers to reach students.

PMID:37542361 | DOI:10.1080/0142159X.2023.2243023

Chin Neurosurg J. 2023 Aug 4;9(1):22. doi: 10.1186/s41016-023-00337-0.

ABSTRACT

BACKGROUND: To compare the safety and efficacy of pipeline embolization device (PED) and Tubridge flow diverter (TFD) for unruptured posterior circulation aneurysms.

METHODS: Posterior aneurysm patients treated with PED or TFD between January, 2019, and December, 2021, were retrospectively reviewed. Patients’ demographics, aneurysm characteristics, treatment details, complications, and follow-up information were collected. The procedural-related complications and angiographic and clinical outcome were compared.

RESULTS: A total of 107 patients were involved; PED was applied for 55 patients and TFD for 52 patients. A total of 9 (8.4%) procedural-related complications occurred, including 4 (7.3%) in PED group and 5 (9.6%) in TFD group. During a mean of 10.3-month angiographic follow-up for 81 patients, complete occlusion was achieved in 35 (85.4%) patients in PED group and 30 (75.0%) in TFD group. The occlusion rate of PED group is slightly higher than that of TFD group. A mean of 25.0-month clinical follow-up for 107 patients showed that favorable clinical outcome was achieved in 53 (96.4%) patients in PED group and 50 (96.2%) patients in TFD group, respectively. No statistical difference was found in terms of procedural-related complications (p = 0.737), occlusion rate (p = 0.241), and favorable clinical outcome (0.954) between groups.

CONCLUSIONS: The current study found no difference in complication, occlusion, and clinical outcome between PED and TFD for unruptured PCAs.

PMID:37542351 | DOI:10.1186/s41016-023-00337-0

Microbiome. 2023 Aug 5;11(1):171. doi: 10.1186/s40168-023-01613-y.

ABSTRACT

BACKGROUND: Treating oral squamous cell carcinoma (OSCC) introduces new ecological environments in the oral cavity. This is expected to cause changes in the oral microbiome. The purpose of this study was to gain new information on the salivary microbiome of OSCC patients in order to improve the aftercare of OSCC patients. The aims of this study were to investigate possible changes in the salivary microbiome profiles of OSCC patients before and after cancer treatment and to compare these changes with the profiles of healthy controls.

PATIENTS AND METHODS: Paraffin-stimulated whole saliva samples were collected, and the salivary flow rate was measured from 99 OSCC patients prior to surgical resection of the tumor and other adjuvant therapy. After treatment, 28 OSCC patients were re-examined with a mean follow-up time of 48 months. In addition, 101 healthy controls were examined and sampled. After DNA extraction and purification, the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using Illumina MiSeq. The merged read pairs were denoised using UNOISE3, mapped to zero-radius operational taxonomic units (zOTUs), and the representative zOTU sequences were assigned a taxonomy using HOMD. Descriptive statistics were used to study the differences in the microbial profiles of OSCC patients before and after treatment and in comparison to healthy controls.

RESULTS: At baseline, the OSCC patients showed a higher relative abundance of zOTUs classified as Streptococcus anginosus, Abiotrophia defectiva, and Fusobacterium nucleatum. The microbial profiles differed significantly between OSCC patients and healthy controls (F = 5.9, p < 0.001). Alpha diversity of the salivary microbiome of OSCC patients was decreased at the follow-up, and the microbial profiles differed significantly from the pre-treatment (p < 0.001) and from that of healthy controls (p < 0.001).

CONCLUSIONS: OSCC patients’ salivary microbiome profile had a higher abundance of potentially pathogenic bacteria compared to healthy controls. Treatment of the OSCC caused a significant decrease in alpha diversity and increase in variability of the salivary microbiome, which was still evident after several years of follow-up. OSCC patients may benefit from preventive measures, such as the use of pre- or probiotics, salivary substitutes, or dietary counseling. Video Abstract.

PMID:37542310 | DOI:10.1186/s40168-023-01613-y

Orphanet J Rare Dis. 2023 Aug 4;18(1):231. doi: 10.1186/s13023-023-02848-6.

ABSTRACT

BACKGROUND: Pompe disease is a rare glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to glycogen deposition in multiple tissues. Infantile-onset Pompe disease (IOPD) patients present within the first year of life with profound hypotonia and hypertrophic cardiomyopathy. Treatment with enzyme replacement therapy (ERT) has significantly improved survival for this otherwise lethal disorder. This study aims to describe the clinical and molecular spectrum of Malaysian IOPD patients, and to analyze their long term treatment outcomes.

METHODS: Seventeen patients diagnosed with IOPD between 2000 and 2020 were included in this retrospective cohort study. Clinical and biochemical data were collated and analyzed using descriptive statistics. GAA enzyme levels were performed on dried blood spots. Molecular analysis of the GAA gene was performed by polymerase chain reaction and Sanger sequencing. Structural modelling was used to predict the effect of the novel mutations on enzyme structure.

RESULTS: Our cohort had a median age of presentation of 3 months and median age of diagnosis of 6 months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (76%). Fourteen different mutations in the GAA gene were identified, with three novel mutations, c.1552-14_1552-1del, exons 2-3 deletion and exons 6-10 deletion. The most common mutation identified was c.1935C > A p.(D645E), with an allele frequency of 33%. Sixteen patients received ERT at the median age of 7 months. Overall survival was 29%. Mean age of death was 17.5 months. Our longest surviving patient has atypical IOPD and is currently 20 years old.

CONCLUSIONS: This is the first study to analyze the genotype and phenotype of Malaysian IOPD patients, and has identified the c.1935C > A p.(D645E) as the most common mutation. The three novel mutations reported in this study expands the mutation spectrum for IOPD. Our low survival rate underscores the importance of early diagnosis and treatment in achieving better treatment outcomes.

PMID:37542277 | DOI:10.1186/s13023-023-02848-6

J Transl Med. 2023 Aug 4;21(1):527. doi: 10.1186/s12967-023-04357-3.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) and cancer are common age-related diseases, and epidemiological evidence suggests an inverse relationship between them. However, investigating the potential mechanism underlying their relationship remains insufficient.

METHODS: Based on genome-wide association summary statistics for 42,034 AD patients and 609,951 cancer patients from the GWAS Catalog using the two-sample Mendelian randomization (MR) method. Moreover, we utilized two-step MR to identify metabolites mediating between AD and cancer. Furthermore, we employed colocalization analysis to identify genes whose upregulation is a risk factor for AD and demonstrated the genes’ upregulation to be a favorable prognostic factor for cancer by analyzing transcriptomic data for 33 TCGA cancer types.

RESULTS: Two-sample MR analysis revealed a significant causal influence for increased AD risk on reduced cancer risk. Two-step MR analysis identified very low-density lipoprotein (VLDL) as a key mediator of the negative cause-effect relationship between AD and cancer. Colocalization analysis uncovered PVRIG upregulation to be a risk factor for AD. Transcriptomic analysis showed that PVRIG expression had significant negative correlations with stemness scores, and positive correlations with antitumor immune responses and overall survival in pan-cancer and multiple cancer types.

CONCLUSION: AD may result in lower cancer risk. VLDL is a significant intermediate variable linking AD with cancer. PVRIG abundance is a risk factor for AD but a protective factor for cancer. This study demonstrates a causal influence for AD on cancer and provides potential molecular connections between both diseases.

PMID:37542274 | DOI:10.1186/s12967-023-04357-3

BMC Public Health. 2023 Aug 5;23(1):1492. doi: 10.1186/s12889-023-16162-0.

ABSTRACT

OBJECTIVE: In this study, we investigated the impact of COVID-19 NPIs in South Africa to understand their effectiveness in the reduction of transmission of COVID-19 in the South African population. This study also investigated the COVID-19 testing, reporting, hospitalised cases, excess deaths and COVID-19 modelling in the first wave of the COVID-19 epidemic in South Africa.

METHODS: A semi-reactive stochastic COVID-19 model, the ARI COVID-19 SEIR model, was used to investigate the impact of NPIs in South Africa to understand their effectiveness in the reduction of COVID-19 transmission in the South African population. COVID-19 testing, reporting, hospitalised cases and excess deaths in the first COVID-19 epidemic wave in South Africa were investigated using regressional analysis and descriptive statistics.

FINDINGS: The general trend in population movement in South African locations shows that the COVID-19 NPIs (National Lockdown Alert Levels 5,4,3,2) were approximately 30% more effective in reducing population movement concerning each increase by 1 Alert Level. The translated reduction in the effective SARS-CoV-2 daily contact number (β) was 6.12% to 36.1% concerning increasing Alert Levels. Due to the implemented NPIs, the effective SARS-CoV-2 daily contact number in the first COVID-19 epidemic wave in South Africa was reduced by 58.1-71.1% while the peak was delayed by 84 days. The estimated COVID-19 reproductive number was between 1.98 to 0.40. During South Africa’s first COVID-19 epidemic wave, the mean COVID-19 admission status in South African hospitals was 58.5%, 95% CI [58.1-59.0] in the general ward, 13.4%, 95% CI [13.1-13.7] in the intensive care unit, 13.3%, 95% CI [12.6-14.0] on oxygen, 6.37%, 95% CI [6.23-6.51] in high care, 6.29%, 95% CI [6.02-6.55] on ventilator and 2.13%, 95% CI [1.87-2.43] in isolation ward respectively. The estimated mean South African COVID-19 patient discharge rate was 11.9 days per patient. While the estimated mean of the South African COVID-19 patient case fatality rate (CFR) in hospital and outside the hospital was 2.06%, 95% CI [1.86-2.25] (deaths per admitted patients) and 2.30%, 95% CI [1.12-3.83](deaths per severe and critical cases) respectively. The relatively high coefficient of variance in COVID-19 model outputs observed in this study shows the uncertainty in the accuracy of the reviewed COVID-19 models in predicting the severity of COVID-19. However, the reviewed COVID-19 models were accurate in predicting the progression of the first COVID-19 epidemic wave in South Africa.

CONCLUSION: The results from this study show that the COVID-19 NPI policies implemented by the Government of South Africa played a significant role in the reduction of COVID-19 active, hospitalised cases and deaths in South Africa’s first COVID-19 epidemic wave. The results also show the use of COVID-19 modelling to understand the COVID-19 pandemic and the impact of regressor variables in an epidemic.

PMID:37542267 | DOI:10.1186/s12889-023-16162-0