Nevin Manimala

Nano Lett. 2023 Aug 10. doi: 10.1021/acs.nanolett.3c02176. Online ahead of print.

ABSTRACT

The use of DNA triplex association is advantageous for the reconfiguration of dynamic DNA nanostructures through pH alteration and can provide environmental control for both structural changes and molecular signaling. The combination of pH-induced triplex-forming oligonucleotide (TFOs) binding with toehold-mediated strand displacement has recently garnered significant attention in the field of structural DNA nanotechnology. While most previous studies use single-stranded DNA to displace or replace TFOs within the triplex, here we demonstrate that pH alteration allows a DNA duplex, with a toehold assistance, to displace TFOs from the components of another DNA duplex. We examined the dependence of this process on toehold length and show that the pH changes allow for cyclic oscillations between two molecular formations. We implemented the duplex/triplex design onto the surface of 2D DNA origami in the form outlining binary digits 0 or 1 and verified the oscillatory conformational changes between the two formations with atomic force microscopy.

PMID:37561947 | DOI:10.1021/acs.nanolett.3c02176

J Am Acad Orthop Surg. 2023 Aug 8. doi: 10.5435/JAAOS-D-23-00123. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to compare the clinical outcome of minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) versus standard revision diskectomy for recurrent lumbar disk herniation (RLDH).

BACKGROUND: RLDH is the most common cause of redo surgery after a microdiscectomy. Commonly, in patients without evidence of spinal instability, many surgeons would simply redo microdiscectomy, while others proceed to a redo microdiscectomy with arthrodesis. According to the literature, there is no evidence of what the best management of an RLDH would be.

METHODS: This study involved 90 patients who underwent lumbar microdiscectomy in the past and were now experiencing a new lumbar disk herniation for the first time. The patients were divided into two groups, each with 45 patients: group A received standard revision microdiscectomy, whereas group B received revision microdiscectomy with MIS TLIF.The Japanese Orthopaedic Association score, operating time, blood loss, duration of hospital stay, costs, and complications were all prospectively recorded in a database and examined. Back and leg discomfort were measured using the visual analog scale.

RESULTS: The mean total postoperative Japanese Orthopaedic Association score across the groups exhibited no statistically significant difference, nor did the preoperative clinical and epidemiological data. Although postoperative leg pain was comparable in both groups, postoperative lower back pain in group A was much worse than that in group B. Additional revision surgery was necessary for six individuals in group A. Group A had higher rates of dural rupture and postoperative neurological impairment. Group A experienced much less intraoperative blood loss, longer operation times, and postoperative hospital stays.

CONCLUSION: In patients with RLDH, revision microdiscectomy is effective. In comparison with conventional microdiscectomy, MIS TLIF reduces intraoperative risk of dural rupture or neural injury, postoperative incidence of mechanical instability or recurrence, and postoperative lower back pain.

STUDY DESIGN: Prospective, randomized, multicenter, comparative study.

PMID:37561938 | DOI:10.5435/JAAOS-D-23-00123

J Nurs Educ. 2023 Aug;62(8):454-460. doi: 10.3928/01484834-20230612-04. Epub 2023 Aug 1.

ABSTRACT

BACKGROUND: Nurse educators are called to develop innovative teaching strategies to build clinical competency. Expert modeling videos (EMVs) promote clinical competency by demonstrating exemplar nursing care.

METHODS: A quasiexperimental research study was conducted using a prebriefing intervention of a nursing process video for demonstration (experimental) and discussion (control) groups of nursing students. Simulation competency was measured using the Creighton Competency Evaluation Instrument (CCEI).

RESULTS: Students in the experimental group demonstrated a statistically significant improvement in simulation competency (p = .001) and performed significantly better in the CCEI domains of communication (p = .009) and patient safety (p = .002).

CONCLUSION: The use of EMVs in simulation prebriefing is an innovative teaching strategy to prepare undergraduate nursing students with the knowledge and skills required to enter the simulated environment. Through watching an exemplar demonstration of desired behaviors, students significantly improved their simulation performance and demonstrated clinically competent care of an acutely ill simulated patient. [J Nurs Educ. 2023;62(8):454-460.].

PMID:37561901 | DOI:10.3928/01484834-20230612-04

J Nurs Educ. 2023 Aug;62(8):443-449. doi: 10.3928/01484834-20230612-02. Epub 2023 Aug 1.

ABSTRACT

BACKGROUND: Nursing students experience higher rates of mental health issues than other college students. This study examined the effect of a mindfulness meditation intervention on nursing students’ levels of self-reported depression, stress, and anxiety.

METHOD: This randomized, experimental study implemented an online mindfulness meditation intervention for an experimental group of nursing students and provided nursing news modules for a control group of nursing students. Participants in experimental and control groups completed the Depression, Anxiety, and Stress Scale online before and after completing 4 weeks of audio modules.

RESULTS: Results showed a statistically significant decrease in reported scores for depression, stress, and anxiety in the experimental group.

CONCLUSION: This study demonstrated the potential benefits of implementing an online mindfulness meditation intervention to support and improve mental health for nursing students. [J Nurs Educ. 2023;62(8):443-449.].

PMID:37561896 | DOI:10.3928/01484834-20230612-02

Science. 2023 Aug 11;381(6658):eabq5693. doi: 10.1126/science.abq5693. Epub 2023 Aug 11.

ABSTRACT

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

PMID:37561875 | DOI:10.1126/science.abq5693

Endocr Regul. 2023 Aug 10;57(1):144-151. doi: 10.2478/enr-2023-0018. Print 2023 Jan 1.

ABSTRACT

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆_T3M=12.8%; ∆_T6M=11.5%; ∆_T12M=11.1%), and a decrease in time above range (∆_T3M=13.6%; ∆T6M=11.9%; ∆_T12M=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆_T6M=2 kg; ∆_T12M=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m². One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.

PMID:37561831 | DOI:10.2478/enr-2023-0018

J Orthop Sports Phys Ther. 2023 Aug 10:1-29. doi: 10.2519/jospt.2023.11982. Online ahead of print.

ABSTRACT

OBJECTIVE: Identify factors that elite sport clinicians, coaches, and athletes perceive are associated with low back pain (LBP) recovery. DESIGN: Concept mapping methodology. METHOD: Participants brainstormed, sorted (thematically) and rated (“5-point Likert scales”: importance and feasibility) statements in response to the prompt: What factors are associated with the recovery of an elite athlete from low back pain? Data cleaning, analysis (multidimensional scaling, hierarchical cluster analysis and descriptive statistics) and visual representation (cluster map and go-zone graph) were conducted following concept mapping guidelines. RESULTS: Participants (brainstorming, n=56; sorting, n=34 and rating, n=33) comprised 75% clinicians, 15% coaches and 10% athletes and represented 13 countries and 17 sports. 82 unique and relevant statements were brainstormed. Sorting resulted in six LBP recovery-related themes: 1) coach and clinician relationships, 2) inter-disciplinary team factors, 3) athlete psychological factors, 4) athlete rehabilitation journey, 5) athlete non-modifiable risk factors and 6) athlete physical factors. Participants rated important recovery factors as: athlete empowerment and psychology, coach-athlete and athlete-clinician relationships, care team communication, return to sport planning, and identifying red flags. CONCLUSIONS: Factors perceived as important to LBP recovery in elite athletes align with the biopsychosocial model of community LBP management. Clinicians should consider that an athlete’s psychology, relationships, care team communication and rehabilitation plan may be as important to their LBP recovery as the formulation of a diagnosis, or the medications, or exercises prescribed.

PMID:37561822 | DOI:10.2519/jospt.2023.11982

PLoS Comput Biol. 2023 Aug 10;19(8):e1011389. doi: 10.1371/journal.pcbi.1011389. Online ahead of print.

ABSTRACT

All but the simplest phenotypes are believed to result from interactions between two or more genes forming complex networks of gene regulation. Sleep is a complex trait known to depend on the system of feedback loops of the circadian clock, and on many other genes; however, the main components regulating the phenotype and how they interact remain an unsolved puzzle. Genomic and transcriptomic data may well provide part of the answer, but a full account requires a suitable quantitative framework. Here we conducted an artificial selection experiment for sleep duration with RNA-seq data acquired each generation. The phenotypic results are robust across replicates and previous experiments, and the transcription data provides a high-resolution, time-course data set for the evolution of sleep-related gene expression. In addition to a Hierarchical Generalized Linear Model analysis of differential expression that accounts for experimental replicates we develop a flexible Gaussian Process model that estimates interactions between genes. 145 gene pairs are found to have interactions that are different from controls. Our method appears to be not only more specific than standard correlation metrics but also more sensitive, finding correlations not significant by other methods. Statistical predictions were compared to experimental data from public databases on gene interactions. Mutations of candidate genes implicated by our results affected night sleep, and gene expression profiles largely met predicted gene-gene interactions.

PMID:37561813 | DOI:10.1371/journal.pcbi.1011389

PLoS Comput Biol. 2023 Aug 10;19(8):e1011368. doi: 10.1371/journal.pcbi.1011368. Online ahead of print.

ABSTRACT

This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, “all pairs,” is designed to retain long distance network connections while the other, “sequential” methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

PMID:37561812 | DOI:10.1371/journal.pcbi.1011368

PLoS One. 2023 Aug 10;18(8):e0287966. doi: 10.1371/journal.pone.0287966. eCollection 2023.

ABSTRACT

INTRODUCTION: Tuberculosis (TB), a curable and preventable infectious disease, becomes difficult to treat if resistance against most effective and tolerable first line anti-TB drugs is developed. The objective of the present study was to evaluate the treatment outcomes and predictors of poor outcomes among drug-resistant tuberculosis (DR-TB) patients treated at a programmatic management unit of drug resistant tuberculosis (PMDT) unit, Punjab, Pakistan.

METHODS: This prospective observational study was conducted at a a PMDT unit in Multan, Punjab, Pakistan. A total of 271 eligible culture positive DR-TB patients enrolled for treatment at the study site between January 2016 and May 2017 were followed till their treatment outcomes were recorded. World Health Organization’s (WHO) defined criteria was used for categorizing treatment outcomes. The outcomes of cured and treatment completed were collectively placed as successful outcomes, while death, lost to follow-up (LTFU) and treatment failure were grouped as unsuccessful outcomes. Multivariable binary logistic regression analysis was employed for getting predictors of unsuccessful treatment outcomes. A p-value <0.05 was considered statistically significant.

RESULTS: Of the 271 DR-TB patients analysed, nearly half (51.3%) were males. The patient’s (Mean ± SD) age was 36.75 ± 15.69 years. A total of 69% patients achieved successful outcomes with 185 (68.2%) patients being cured and 2 (0.7%) completed therapy. Of the remaining 84 patients with unsuccessful outcomes, 48 (17.7%) died, 2 (0.7%) were declared treatment failure, 34 (12.5%) were loss to follow up. After adjusting for confounders, patients’ age > 50 years (OR 2.149 (1.005-4.592) with p-value 0.048 and baseline lung cavitation (OR 7.798 (3.82-15.919) with p-value <0.001 were significantly associated with unsuccessful treatment outcomes.

CONCLUSIONS: The treatment success rate (69%) in the current study participants was below the target set by WHO (>75%). Paying special attention and timely intervention in patients with high risk of unsuccessful treatment outcomes may help in improving treatment outcomes at the study site.

PMID:37561810 | DOI:10.1371/journal.pone.0287966