Category: Nevin Manimala

Am J Public Health. 2023 Feb 9:e1-e8. doi: 10.2105/AJPH.2022.307197. Online ahead of print.

ABSTRACT

Data System. Federal health surveys, like the National Health Interview Survey (NHIS), represent important surveillance mechanisms for collecting timely, representative data that can be used to monitor the health and health care of the US population. Data Collection/Processing. Conducted by the National Center for Health Statistics (NCHS), NHIS uses an address-based, complex clustered sample of housing units, yielding data representative of the civilian noninstitutionalized US population. Survey redesigns that reduce survey length and eliminate proxy reporting may reduce respondent burden and increase participation. Such were goals in 2019, when NCHS implemented a redesigned NHIS questionnaire that also focused on topics most relevant and appropriate for surveillance of child and adult health. Data Analysis/Dissemination. Public-use microdata files and selected health estimates and detailed documentation are released online annually. Public Health Implications. Declining response rates may lead to biased estimates and weaken users’ ability to make valid conclusions from the data, hindering public health efforts. The 2019 NHIS questionnaire redesign was associated with improvements in the survey’s response rate, declines in respondent burden, and increases in data quality and survey relevancy. (Am J Public Health. Published online ahead of print February 9, 2023:e1-e8. https://doi.org/10.2105/AJPH.2022.307197).

PMID:36758202 | DOI:10.2105/AJPH.2022.307197

Can Urol Assoc J. 2023 Feb 2. doi: 10.5489/cuaj.8085. Online ahead of print.

ABSTRACT

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is a challenging procedure that urology trainees should be familiar with during residency. Simulators, such as the PERC Mentor, allows the development of this competency in a safer, stress-free environment. There are two primary fluoroscopic methods of gaining percutaneous renal access: the triangulation method and the bull’s eye method. Our goal was to assess which method is easier to teach novices by using the PERC Mentor simulator. A secondary goal is to assess differences in subjective and objective outcomes.

METHODS: Fifteen simulator and procedure-naive medical trainees were randomized into two groups using a crossover, randomized study design. Participants were provided with written, video, in-person demonstrations and hands-on practice for each technique. They then performed each method and were assessed objectively using the PERC Mentor performance data report and subjectively using the PCNL global rating scale (GRS) scoring system. Statistical analysis was performed using Student’s T-test and non-parametric Wilcoxon signed rank test.

RESULTS: There was no statistical difference in the outcomes and complication rates between the two methods. The bull’s eye method of obtaining percutaneous access was associated with a significant decrease in operative time (91 seconds vs. 128 seconds, p=0.03) and fluoroscopy time (87 seconds vs, 123 seconds, p=0.03) compared to the triangulation method.

CONCLUSIONS: Teaching of both techniques was equally well-acquired by students. Both techniques had similar outcomes; however, the bull’s eye method was associated with less operative and fluoroscopy time when compared to the triangulation method among novices.

PMID:36758181 | DOI:10.5489/cuaj.8085

J Am Soc Nephrol. 2023 Feb 9. doi: 10.1681/ASN.0000000000000087. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical practice lacks strategies to treat acute kidney injury (AKI). Interestingly, preconditioning by hypoxia (HP) and caloric restriction (CR) is highly protective in rodent AKI models. However, the underlying molecular mechanisms of this process are unknown.

METHODS: CRISPR generated kynureninase (KYNU) knockout mice and comparative transcriptome, proteome, and metabolite analyses of murine kidneys (C57Bl6N wild type and KYNU-deficient) pre- and post-ischemia-reperfusion injury, in the context of CR or ad libitum diet, performed. Additionally, acetyl-lysin enrichment and mass spectrometry were used to assess protein acetylation..

RESULTS: We identified KYNU as a downstream target of CR and show that KYNU strongly contributes to the protective effect of CR. The KYNU-dependent de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway is necessary for CR-associated maintenance of NAD+ levels. This finding is associated with reduced protein acetylation in CR-treated animals, specifically affecting enzymes in energy metabolism. Importantly, the impact of CR on de novo NAD+ biosynthesis pathway metabolites can be recapitulated in humans.

CONCLUSIONS: CR induces the de novo NAD+ synthesis pathway in the context of Ischemia-reperfusion injury and is essential for its full nephroprotective potential. Differential protein acetylation may be the molecular mechanism underlying the relationship of NAD+, CR, and nephroprotection.

PMID:36758124 | DOI:10.1681/ASN.0000000000000087

Percept Mot Skills. 2023 Feb 9:315125231156003. doi: 10.1177/00315125231156003. Online ahead of print.

ABSTRACT

The 6-Minute Step Test (6-MST) is a simple, inexpensive field test that is increasingly used to evaluate cardiorespiratory fitness. Whether sufficient performance is revealed by this test and the effect on it of motivational factors such as music is unknown. In this cross-sectional, randomized, and crossover research design, we aimed to analyze 6-MST performance and test outcomes in different music-related auditory conditions of non-musical/non-rhythmic [NM/NR], musical/non-rhythmic [M/NR], and musical/rhythmic [M/R]). We had 38 healthy young adults (M age = 21.21, SD = 1.21 years; 60% male) complete all tests, and we measured their number of steps taken, heart rate, blood pressure, respiratory rate, peripheral oxygen saturation, perceived dyspnea, and fatigue on the modified Borg scale. We recorded individually calculated submaximal values according to heart rate reached after three tests. The number of steps increased in the M/R condition relative to other conditions (p = 0.003), and the amount of change in perceived leg fatigue was also higher in the M/R condition (p < 0.017). Despite variable test performances in different auditory conditions, we found no statistically significant difference in cardiovascular fitness and symptoms (p > 0.05). We concluded that the 6-MST is a useful tool for assessing maximum cardiac tolerance, especially if administered while listening to rhythmic music.

PMID:36758117 | DOI:10.1177/00315125231156003

PLoS One. 2023 Feb 9;18(2):e0272596. doi: 10.1371/journal.pone.0272596. eCollection 2023.

ABSTRACT

OBJECTIVE: To determine the concordance and statistical precision in gait velocity in people with multiple sclerosis (pwMS), measured with FeetMe® (insoles with pressure and motion sensors) compared with GAITRite® (classic reference system of gait analysis) in the timed 25-Feet Walk test (T25WT).

METHODS: This observational, cross-sectional, prospective, single center study was conducted between September-2018 and April-2019 in pwMS aged 18-55 years, with Expanded Disability Status Scale (EDSS) 0-6.5 and relapse free ≥30 days at baseline. Primary endpoint was gait velocity. Secondary endpoints were ambulation time, cadence, and stride length assessment, while the correlation between gait variables and the clinical parameters of MS subjects was assessed as an exploratory endpoint.

RESULTS: A total of 207 MS subjects were enrolled, of whom, 205 were considered in primary analysis. Most subjects were women (66.8%) and had relapsing-remitting MS (RRMS) (82.9%), with overall mean (standard deviation [SD]) age of 41.5 (8.0) year and EDSS 3.1 (2.0). There was a statistically significant (p<0.0001) and strong agreement (intra-class correlation coefficient (ICC) >0.830) in gait velocity, ambulation time and cadence assessment between FeetMe® and GAITRite®.

CONCLUSIONS: Agreement between devices was strong (ICC≥0.800). FeetMe® is the first validated wearable medical device that allows gait monitoring in MS subjects, being potentially able to assess disease activity, progression, and treatment response.

PMID:36758111 | DOI:10.1371/journal.pone.0272596

PLoS Comput Biol. 2023 Feb 9;19(2):e1010886. doi: 10.1371/journal.pcbi.1010886. Online ahead of print.

ABSTRACT

Epidemiological and clinical evidence indicates that humans infected with the 1918 pandemic H1N1 influenza virus and highly pathogenic avian H5N1 influenza viruses often displayed severe lung pathology. High viral load and extensive infiltration of macrophages are the hallmarks of highly pathogenic (HP) influenza viral infections. However, it remains unclear what biological mechanisms primarily determine the observed difference in the kinetics of viral load and macrophages between HP and low pathogenic (LP) viral infections, and how the mechanistic differences are associated with viral pathogenicity. In this study, we develop a mathematical model of viral dynamics that includes the dynamics of different macrophage populations and interferon. We fit the model to in vivo kinetic data of viral load and macrophage level from BALB/c mice infected with an HP or LP strain of H1N1/H5N1 virus using Bayesian inference. Our primary finding is that HP viruses have a higher viral infection rate, a lower interferon production rate and a lower macrophage recruitment rate compared to LP viruses, which are strongly associated with more severe tissue damage (quantified by a higher percentage of epithelial cell loss). We also quantify the relative contribution of macrophages to viral clearance and find that macrophages do not play a dominant role in the direct clearance of free viruses although their role in mediating immune responses such as interferon production is crucial. Our work provides new insight into the mechanisms that convey the observed difference in viral and macrophage kinetics between HP and LP infections and establishes an improved model-fitting framework to enhance the analysis of new data on viral pathogenicity.

PMID:36758109 | DOI:10.1371/journal.pcbi.1010886

PLoS Comput Biol. 2023 Feb 9;19(2):e1010462. doi: 10.1371/journal.pcbi.1010462. Online ahead of print.

ABSTRACT

Microbial specialised metabolism is full of valuable natural products that are applied clinically, agriculturally, and industrially. The genes that encode their biosynthesis are often physically clustered on the genome in biosynthetic gene clusters (BGCs). Many BGCs consist of multiple groups of co-evolving genes called sub-clusters that are responsible for the biosynthesis of a specific chemical moiety in a natural product. Sub-clusters therefore provide an important link between the structures of a natural product and its BGC, which can be leveraged for predicting natural product structures from sequence, as well as for linking chemical structures and metabolomics-derived mass features to BGCs. While some initial computational methodologies have been devised for sub-cluster detection, current approaches are not scalable, have only been run on small and outdated datasets, or produce an impractically large number of possible sub-clusters to mine through. Here, we constructed a scalable method for unsupervised sub-cluster detection, called iPRESTO, based on topic modelling and statistical analysis of co-occurrence patterns of enzyme-coding protein families. iPRESTO was used to mine sub-clusters across 150,000 prokaryotic BGCs from antiSMASH-DB. After annotating a fraction of the resulting sub-cluster families, we could predict a substructure for 16% of the antiSMASH-DB BGCs. Additionally, our method was able to confirm 83% of the experimentally characterised sub-clusters in MIBiG reference BGCs. Based on iPRESTO-detected sub-clusters, we could correctly identify the BGCs for xenorhabdin and salbostatin biosynthesis (which had not yet been annotated in BGC databases), as well as propose a candidate BGC for akashin biosynthesis. Additionally, we show for a collection of 145 actinobacteria how substructures can aid in linking BGCs to molecules by correlating iPRESTO-detected sub-clusters to MS/MS-derived Mass2Motifs substructure patterns. This work paves the way for deeper functional and structural annotation of microbial BGCs by improved linking of orphan molecules to their cognate gene clusters, thus facilitating accelerated natural product discovery.

PMID:36758069 | DOI:10.1371/journal.pcbi.1010462

PLoS One. 2023 Feb 9;18(2):e0280804. doi: 10.1371/journal.pone.0280804. eCollection 2023.

ABSTRACT

Support vector machine (SVM) is a new machine learning method developed from statistical learning theory. Since the objective function of the unconstrained SVM model is a non-smooth function, a lot of fast optimization algorithms can’t be used to find the solution. Firstly, to overcome the non-smooth property of this model, a new padé33 approximation smooth function is constructed by rational approximation method, and a new smooth support vector machine model (SSVM) is established based on the smooth function. Then, by analyzing the performance of the smooth function, we find that the smooth precision is significantly higher than existing smooth functions. Moreover, theoretical and rigorous mathematical analyses are given to prove the convergence of the new model. Finally, it is applied to the heart disease diagnosis. The results show that the Padé33-SSVM model has better classification capability than existing SSVMs.

PMID:36758063 | DOI:10.1371/journal.pone.0280804

PLoS One. 2023 Feb 9;18(2):e0281686. doi: 10.1371/journal.pone.0281686. eCollection 2023.

ABSTRACT

Although the global burden of ear, nose and throat (ENT) diseases is high, data relating to ENT disease epidemiology and diagnostic error in resource-limited settings remain scarce. We conducted a retrospective cross-sectional review of ENT patients’ clinical records at a resource-limited tertiary hospital. We determined the diagnostic accuracy and appropriateness of patient referrals for ENT specialist care using descriptive statistics. Cohens kappa coefficient (κ) was calculated to determine the diagnostic agreement between non-ENT clinicians and the ENT specialist, and logistic regression applied to establish the likelihood of patient misdiagnosis by non-ENT clinicians. Of the 1543 patients studied [age 0-87 years, mean age 25(21) years (mean(SD)], non-ENT clinicians misdiagnosed 67.4% and inappropriately referred 50.4%. Compared to those aged 0-5 years, patients aged 51-87 years were 1.77 (95%CI: 1.03-3.04) fold more likely to have a referral misdiagnosis for specialist care. Patients with ear (aOR: 1.63; 95% CI: 1.14-2.33) and those with sinonasal diseases (aOR: 1.80; 95% CI: 1.14-2.45) had greater likelihood of referral misdiagnosis than those with head and neck diseases. Agreement in diagnosis between the ENT specialist and non-ENT clinicians was poor (κ = 0.0001). More effective, accelerated training of clinicians may improve diagnostic accuracy in low-resource settings.

PMID:36758061 | DOI:10.1371/journal.pone.0281686

PLoS One. 2023 Feb 9;18(2):e0280944. doi: 10.1371/journal.pone.0280944. eCollection 2023.

ABSTRACT

Melioidosis is an infectious disease with high mortality rates in human, caused by the bacterium Burkholderia pseudomallei. As an intracellular pathogen, B. pseudomallei can escape from the phagosome and induce multinucleated giant cells (MNGCs) formation resulting in antibiotic resistance and immune evasion. A novel strategy to modulate host response against B. pseudomallei pathogenesis is required. In this study, an active metabolite of vitamin D3 (1α,25-dihydroxyvitamin D3 or 1α,25(OH)2D3) was selected to interrupt pathogenesis of B. pseudomallei in a human lung epithelium cell line, A549. The results demonstrated that pretreatment with 10-6 M 1α,25(OH)2D3 could reduce B. pseudomallei internalization to A549 cells at 4 h post infection (P < 0.05). Interestingly, the presence of 1α,25(OH)2D3 gradually reduced MNGC formation at 8, 10 and 12 h compared to that of the untreated cells (P < 0.05). Furthermore, pretreatment with 10-6 M 1α,25(OH)2D3 considerably increased hCAP-18/LL-37 mRNA expression (P < 0.001). Additionally, pro-inflammatory cytokines, including MIF, PAI-1, IL-18, CXCL1, CXCL12 and IL-8, were statistically decreased (P < 0.05) in 10-6 M 1α,25(OH)2D3-pretreated A549 cells by 12 h post-infection. Taken together, this study indicates that pretreatment with 10-6 M 1α,25(OH)2D3 has the potential to reduce the internalization of B. pseudomallei into host cells, decrease MNGC formation and modulate host response during B. pseudomallei infection by minimizing the excessive inflammatory response. Therefore, 1α,25(OH)2D3 supplement may provide an effective supportive treatment for melioidosis patients to combat B. pseudomallei infection and reduce inflammation in these patients.

PMID:36758060 | DOI:10.1371/journal.pone.0280944