Nevin Manimala

Environ Sci Pollut Res Int. 2021 Mar 18. doi: 10.1007/s11356-021-13124-0. Online ahead of print.

ABSTRACT

The effects of meteorological factors on health outcomes have gained popularity due to climate change, resulting in a general rise in temperature and abnormal climatic extremes. Instead of the conventional cross-sectional analysis that focuses on the association between a predictor and the single dependent variable, the distributed lag non-linear model (DLNM) has been widely adopted to examine the effect of multiple lag environmental factors health outcome. We propose several novel strategies to model mortality with the effects of distributed lag temperature measures and the delayed effect of mortality. Several attempts are derived by various statistical concepts, such as summation, autoregressive, principal component analysis, baseline adjustment, and modeling the offset in the DLNM. Five strategies are evaluated by simulation studies based on permutation techniques. The longitudinal climate and daily mortality data in Taipei, Taiwan, from 2012 to 2016 were implemented to generate the null distribution. According to simulation results, only one strategy, named MV_DLNM, could yield valid type I errors, while the other four strategies demonstrated much more inflated type I errors. With a real-life application, the MV_DLNM that incorporates both the current and lag mortalities revealed a more significant association than the conventional model that only fits the current mortality. The results suggest that, in public health or environmental research, not only the exposure may post a delayed effect but also the outcome of interest could provide the lag association signals. The joint modeling of the lag exposure and the delayed outcome enhances the power to discover such a complex association structure. The new approach MV_DLNM models lag outcomes within 10 days and lag exposures up to 1 month and provide valid results.

PMID:33735414 | DOI:10.1007/s11356-021-13124-0

Arch Dermatol Res. 2021 Mar 18. doi: 10.1007/s00403-021-02213-2. Online ahead of print.

ABSTRACT

Cutaneous squamous cell carcinoma (SCC) causes approximately 1,000,000 cases and 9000 deaths each year in the United States. While individual tumor sequencing studies have discovered driver mutations in SCC, there has yet to be a review and subsequent analysis synthesizing current studies. To conduct a comprehensive synthesis and analysis of SCC sequencing studies with individual patient-level data, a comprehensive literature search was performed. Statistical analyses were performed to identify trends. Studies meeting inclusion criteria included a total of 279 patients (189 localized SCCs, 90 metastatic SCCs). Several mutations were correlated with demographic characteristics (TP53, MLL4, BRCA2, COL4A1). TP53, TERT, SPEN, MLL3, and NOTCH2 mutations were significantly more likely to be found in metastatic versus localized SCCs even after the Bonferroni correction for multiple comparisons. Silent mutations were found more in localized SCCs than metastatic SCCs, and nonsense mutations were found more in metastatic SCCs than localized SCCs (p = 0.0003 and p = 0.04, respectively). Additional mutations were identified that have not yet been explored in SCC including AHNAK2, LRP1B, TRIO, MDN1, COL4A2, SVIL, VPS13C, DST, DMD, and DYSF. Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.

PMID:33735396 | DOI:10.1007/s00403-021-02213-2

J Clin Endocrinol Metab. 2021 Mar 18:dgab181. doi: 10.1210/clinem/dgab181. Online ahead of print.

ABSTRACT

CONTEXT: Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk.

OBJECTIVE: Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared to hypogonadal men without T2D.

DESIGN, METHOD AND PARTICIPANTS: Single arm, open-label clinical (NCT01378299) trial involving 105 men (40-74 years old), with average morning testosterone<300ng/dl. Subjects were injected intramuscularly with testosterone cypionate (200mg) every 2 weeks for 18 months. Testosterone and estradiol assessed by liquid-chromatography/mass-spectroscopy; serum C-telopeptide (CTX), osteocalcin and sclerostin by ELISA; A1C by high performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography.

RESULTS: Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared to non-T2D men (p<0.01). T2D men increased lumbar spine aBMD (p<0.05), total area at 38% tibia (p<0.01) and periosteal and endosteal circumferences at the same site (p<0.01 for both). T2D men had reduced tibial vBMD (p<0.01), but with preserved bone mineral content (p=0.01). Changes in A1c or body composition were similar between the 2 groups.

CONCLUSIONS: Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their non-diabetic counterparts.

PMID:33735389 | DOI:10.1210/clinem/dgab181

Pain Med. 2021 Mar 18;22(3):533-547. doi: 10.1093/pm/pnaa440.

ABSTRACT

OBJECTIVE: Define and contrast acute pain trajectories vs. the aggregate pain measurements, summarize appropriate linear and nonlinear statistical analyses for pain trajectories at the patient level, and present methods to classify individual pain trajectories. Clinical applications of acute pain trajectories are also discussed.

SETTING: In 2016, an expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM) established an initiative to create a pain taxonomy, named the ACTTION-APS-AAPM Pain Taxonomy (AAAPT), for the multidimensional classification of acute pain. The AAAPT panel commissioned the present report to provide further details on analysis of the individual acute pain trajectory as an important component of comprehensive pain assessment.

METHODS: Linear mixed models and nonlinear models (e.g., regression splines and polynomial models) can be applied to analyze the acute pain trajectory. Alternatively, methods for classifying individual pain trajectories (e.g., using the 50% confidence interval of the random slope approach or using latent class analyses) can be applied in the clinical context to identify different trajectories of resolving pain (e.g., rapid reduction or slow reduction) or persisting pain. Each approach has advantages and disadvantages that may guide selection. Assessment of the acute pain trajectory may guide treatment and tailoring to anticipated symptom recovery. The acute pain trajectory can also serve as a treatment outcome measure, informing further management.

CONCLUSIONS: Application of trajectory approaches to acute pain assessments enables more comprehensive measurement of acute pain, which forms the cornerstone of accurate classification and treatment of pain.

PMID:33735384 | DOI:10.1093/pm/pnaa440

Am J Hypertens. 2021 Mar 18:hpab051. doi: 10.1093/ajh/hpab051. Online ahead of print.

ABSTRACT

BACKGROUND: This study sought to assess the relationship between stage 1 hypertension and subclinical coronary atherosclerosis.

METHODS: A total of 4666 individuals with available coronary computed tomography angiography (CCTA) results from a health checkup were enrolled. The classification of hypertension was adapted from the American College of Cardiology/American Heart Association (ACC/AHA) 2017 guideline. The presence of coronary plaques and its characteristics, coronary artery calcium (CAC) score, and significant stenosis defined as luminal narrowing >50% were assessed.

RESULTS: The mean age was 52.6±7.3 years, and 3311 (71.0%) were men. There was a linear relationship between blood pressure (BP), both systolic BP (SBP) and diastolic BP (DBP), and the presence of coronary plaque. Patients were classified into four groups according to the BP category: normal BP (SBP<120 mm Hg and DBP <80 mm Hg; n=2395; 51.3%), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg; n=467; 10.0%), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg; n=1139; 24.4%), and stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg; n=665; 14.2%). Compared to the normal BP group after multivariate adjustment, the stage 1 hypertension group was significantly associated with the presence of atherosclerotic plaque (adjusted odds ratio [95% confidential interval], 1.37 [1.17-1.62]; P<0.001), especially in non-calcified and mixed plaques. The relationship between stage 1 hypertension and stenosis >50% was not statistically significant. Isolated diastolic and isolated systolic stage 1 hypertensions were significantly related to the presence of coronary plaque. The elevated BP group was not associated with any positive CCTA findings.

CONCLUSIONS: Stage 1 hypertension was independently associated with subclinical coronary atherosclerosis.

PMID:33735371 | DOI:10.1093/ajh/hpab051

Mol Omics. 2021 Mar 18. doi: 10.1039/d0mo00150c. Online ahead of print.

ABSTRACT

Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.

PMID:33735360 | DOI:10.1039/d0mo00150c

PLoS One. 2021 Mar 18;16(3):e0248679. doi: 10.1371/journal.pone.0248679. eCollection 2021.

ABSTRACT

BACKGROUND: Mobile health (mHealth) technologies are innovative solutions for delivering instructions to patients preparing for colonoscopy.

OBJECTIVE: To systematically review the literature evaluating the effectiveness of mHealth technologies supporting colonoscopy preparation on patient and clinical outcomes.

METHODS: MEDLINE, EMBASE, CINAHL and CENTRAL were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of mHealth technologies for colonoscopy preparation on patient and clinical outcomes. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality using the Cochrane Risk-of-Bias tool. Data were pooled using random effects models and when heterogeneity, assessed using I2, was statistically significant, a qualitative synthesis of the data was performed. Publication bias was assessed using a funnel plot.

RESULTS: Ten RCTs (3,383 participants) met inclusion criteria. MHealth interventions included smartphone apps, SMS text messages, videos, camera apps, and a social media app. Outcomes were bowel cleanliness quality, user satisfaction, colonoscopy quality indicators (cecal intubation time, withdrawal time, adenoma detection rate), adherence to diet, and cancellation/no-show rates. MHealth interventions were associated with better bowel cleanliness scores on the Boston Bowel Preparation Scale [standardized mean difference (SMD) 0.57, 95%CI 0.37-0.77, I2 = 60%, p = 0.08] and the Ottawa Bowel Preparation Scale [SMD -0.39, 95%CI -0.59-0.19, I2 = 45%, p = 0.16], but they were not associated with rates of willingness to repeat the colonoscopy using the same regimen [odds ratio (OR) 1.88, 95%CI 0.85-4.15, I2 = 48%, p = 0.12] or cancellations/no-shows [OR 0.96, 95%CI 0.68-1.35, I2 = 0%]. Most studies showed that adequate bowel preparation, user satisfaction and adherence to diet were better in the intervention groups compared to the control groups, while inconsistent findings were observed for the colonoscopy quality indicators. All trials were at high risk of bias for lack of participant blinding. Visual inspection of a funnel plot revealed publication bias.

CONCLUSIONS: MHealth technologies show promise as a way to improve bowel cleanliness, but trials to date were of low methodological quality. High-quality research is required to understand the effectiveness of mHealth technologies on colonoscopy outcomes.

PMID:33735320 | DOI:10.1371/journal.pone.0248679

J Phys Chem Lett. 2021 Mar 18:2997-3005. doi: 10.1021/acs.jpclett.1c00123. Online ahead of print.

ABSTRACT

Accurate description of finite-temperature vibrational dynamics is indispensable in the computation of two-dimensional electronic spectra. Such simulations are often based on the density matrix evolution, statistical averaging of initial vibrational states, or approximate classical or semiclassical limits. While many practical approaches exist, they are often of limited accuracy and difficult to interpret. Here, we use the concept of thermo-field dynamics to derive an exact finite-temperature expression that lends itself to an intuitive wavepacket-based interpretation. Furthermore, an efficient method for computing finite-temperature two-dimensional spectra is obtained by combining the exact thermo-field dynamics approach with the thawed Gaussian approximation for the wavepacket dynamics, which is exact for any displaced, distorted, and Duschinsky-rotated harmonic potential but also accounts partially for anharmonicity effects in general potentials. Using this new method, we directly relate a symmetry breaking of the two-dimensional signal to the deviation from the conventional Brownian oscillator picture.

PMID:33733773 | DOI:10.1021/acs.jpclett.1c00123

Environ Monit Assess. 2021 Mar 17;193(4):199. doi: 10.1007/s10661-021-08960-z.

ABSTRACT

Developing a predictive decision model for assessing the vulnerability of hidden groundwater reservoir formation to contamination risk via unavoidable anthropogenic activities is a key to managing water resources looming security crisis globally. This study explored multiple and robust methodologies including GIS, analytical hierarchy process (AHP)-based data mining, statistical and geophysical techniques for developing a novel “GODL” vulnerability method: a modified GOD model to ameliorate these challenges. The input for the modeling was based on the 65 located depth sounding geophysical data occupied in a schist belt environ, Southwestern Nigeria. From the geophysical data interpreted results, four factors, namely, groundwater hydraulic confinement (G), aquifer overlying strata (O), depth to water table (D), and longitudinal conductance (L), regarded as aquifer vulnerability causative factors (AVCFs) were derived. The GIS-based produced AVCFs’ themes were synthesized by employing the conventional GOD and the AHP-driven GODL algorithms. Based on these algorithms applied results, the GOD-based aquifer vulnerability prediction zone map and GODL-based aquifer vulnerability prediction zone (AVPZ) map were produced in GIS environment. The produced AVPZ maps were validated by applying the statistical model evaluation to the water chemistry correlation results. The validation result exhibits 70% prediction accuracy for the developed GODL model compared with 66% for the GOD model. The GODL model demonstrated better performance than the GOD model. The AVPZ maps produced in this study can be used for precise decision-making process in environmental planning and groundwater management.

PMID:33733712 | DOI:10.1007/s10661-021-08960-z

Int Urogynecol J. 2021 Mar 17. doi: 10.1007/s00192-021-04743-9. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Supervised pelvic floor muscle training (PFMT), weight loss and exercise are recommended for overweight/obese women with urinary incontinence (UI). This study aimed to implement and evaluate the feasibility, acceptability and effectiveness of a 12-week group exercise and healthy eating program (ATHENA) for overweight/obese women with UI.

METHODS: This study, using an implementation-effectiveness hybrid type 3 design, was conducted within a Women’s Health Physiotherapy outpatient service at an Australian tertiary public hospital. Intervention feasibility and acceptability were assessed through process evaluation of implementation, while clinical effectiveness was assessed via pre-/post-clinical and quality of life surveys. Process data were analyzed using descriptive statistics and effectiveness data were compared pre-/post-intervention using inferential statistics.

RESULTS: Of 156 eligible patients, 37 (24%) agreed to participate; 29 (78%) completed the ATHENA program. Median (IQR) age and body mass index were 53 (47-65) years and 30.8 (29.1-34.8) kg/m² respectively. ATHENA was feasible to implement, with all components delivered as intended and high participant satisfaction. Ninety-seven percent of participants reported improved UI symptoms (global rating of change) and significant improvements in overall pelvic floor dysfunction and quality of life utility scores (p = 0.001). While weight did not change, significant improvements were found in body-food choice congruence (intuitive eating scale-2; p < 0.01).

CONCLUSIONS: The ATHENA intervention was feasible, acceptable and clinically effective for overweight and obese women with urinary incontinence at a tertiary public hospital in Australia. Further research into longer term outcomes and the cost effectiveness of this group intervention is recommended.

TRIAL REGISTRATION: N/A. Ethics approval, HREC/2018/QGC/46582, date of registration 14/11/2018.

PMID:33733697 | DOI:10.1007/s00192-021-04743-9