Nevin Manimala

J Chem Theory Comput. 2021 Mar 17. doi: 10.1021/acs.jctc.0c01151. Online ahead of print.

ABSTRACT

A variety of enhanced statistical and numerical methods are now routinely used to extract important thermodynamic and kinetic information from the vast amount of complex, high-dimensional data obtained from molecular simulations. For the characterization of kinetic properties, Markov state models, in which the long-time statistical dynamics of a system is approximated by a Markov chain on a discrete partition of configuration space, have seen widespread use in recent years. However, obtaining kinetic properties for molecular systems with high energy barriers remains challenging as often enhanced sampling techniques are required with biased simulations to observe the relevant rare events. Particularly, the calculation of diffusion coefficients remains elusive from biased molecular simulation data. Here, we propose a novel method that can calculate multidimensional position-dependent diffusion coefficients equally from either biased or unbiased simulations using the same formalism. Our method builds on Markov state model analysis and the Kramers-Moyal expansion. We demonstrate the validity of our formalism using one- and two-dimensional analytic potentials and also apply it to data from explicit solvent molecular dynamics simulations, including the water-mediated conformations of alanine dipeptide and umbrella sampling simulations of drug transport across a lipid bilayer. Importantly, the developed algorithm presents significant improvement compared to standard methods when the transport of solute across three-dimensional heterogeneous porous media is studied, for example, the prediction of membrane permeation of drug molecules.

PMID:33728916 | DOI:10.1021/acs.jctc.0c01151

Health Rep. 2021 Mar 17;32(3):3-16. doi: 10.25318/82-003-x202100300001-eng.

ABSTRACT

BACKGROUND: Prescription medications are used throughout the life course, including among children and youth. Prescribing practices may be influenced by emerging medical conditions, the availability of new medications, changing clinical practices, and evolving knowledge of the safety and effectiveness of medications. The Canadian Health Measures Survey (CHMS) provides national-level information to help monitor the use of prescribed medications in the population.

DATA AND METHODS: Based on data from the CHMS (2012 to 2017), this article describes prescription medication use in the past month among those aged 3 to 19 years. Information on up to 45 prescription medications was recorded and classified according to Health Canada’s Anatomical Therapeutic Chemical classification. Frequencies and bivariate analyses examined medication use by sociodemographic and health-related factors. The most common medication classes were identified for each age group.

RESULTS: An estimated 23% of Canadian children and youth (1.5 million) had used at least one prescription medication in the past month and 9% had used two or more prescription medications.Prescription medication use was more common among those who reported lower levels of general and mental health, as well as among those with asthma (51%), a mood disorder (71%), attention deficit disorder (60%) or a learning disability (43%). Medications for the respiratory and nervous systems were among those most commonly prescribed. Of youth aged 14 years or older, 4% had misused prescription medications for non-medicinal purposes, for the experience, for the feeling they cause or to get high.

DISCUSSION: Prescription medication use among children and youth is common in Canada. It is associated with lower levels of self-reported health and the presence of chronic conditions. The estimates provide a benchmark to help monitor prescription drug use in Canada.

PMID:33728887 | DOI:10.25318/82-003-x202100300001-eng

Monaldi Arch Chest Dis. 2021 Mar 16. doi: 10.4081/monaldi.2021.1758. Online ahead of print.

ABSTRACT

Coronavirus disease (COVID-19) may predispose patients to pulmonary embolism (PE), despite standard thromboprophylaxis. Our retrospective study aimed to report the prevalence of PE in patients with COVID-19 and severe respiratory failure (SRF) treated with intermediate- to full-dose enoxaparin. We analyzed data from patients with COVID-19 pneumonia and SRF admitted to our Respiratory Intensive Care Unit (RICU) from February 27 to April 20, 2020. All patients received at least intermediate-dose enoxaparin (40 mg twice daily). Computed tomography pulmonary angiography (CTPA) was used to detect PE. Ninety-two patients with COVID-19 pneumonia and SRF were admitted to our RICU. Twenty-two patients underwent CTPA (24 %), 11 of whom had PEs (12%). We hypothesize that the enoxaparin treatment may be responsible for the lower prevalence of PE as compared to previous reports of similar patients, even if our report had several limitations, mainly the small sample size.

PMID:33728885 | DOI:10.4081/monaldi.2021.1758

NPJ Digit Med. 2021 Mar 16;4(1):51. doi: 10.1038/s41746-021-00420-9.

ABSTRACT

The true risk of a COVID-19 resurgence as states reopen businesses is unknown. In this paper, we used anonymized cell-phone data to quantify the potential risk of COVID-19 transmission in business establishments by building a Business Risk Index that measures transmission risk over time. The index was built using two metrics, visits per square foot and the average duration of visits, to account for both density of visits and length of time visitors linger in the business. We analyzed trends in traffic patterns to 1,272,260 businesses across eight states from January 2020 to June 2020. We found that potentially risky traffic behaviors at businesses decreased by 30% by April. Since the end of April, the risk index has been increasing as states reopen. There are some notable differences in trends across states and industries. Finally, we showed that the time series of the average Business Risk Index is useful for forecasting future COVID-19 cases at the county-level (P < 0.001). We found that an increase in a county’s average Business Risk Index is associated with an increase in positive COVID-19 cases in 1 week (IRR: 1.16, 95% CI: (1.1-1.26)). Our risk index provides a way for policymakers and hospital decision-makers to monitor the potential risk of COVID-19 transmission from businesses based on the frequency and density of visits to businesses. This can serve as an important metric as states monitor and evaluate their reopening strategies.

PMID:33727636 | DOI:10.1038/s41746-021-00420-9

Sci Rep. 2021 Mar 16;11(1):6084. doi: 10.1038/s41598-021-85692-7.

ABSTRACT

Oestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E₂ levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E₂ levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E₂ levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

PMID:33727635 | DOI:10.1038/s41598-021-85692-7

Int J Obes (Lond). 2021 Mar 16. doi: 10.1038/s41366-021-00799-1. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Exercise may reduce the risk of breast cancer through adiposity changes, but the dose-response effects of exercise volume on adiposity markers are unknown in postmenopausal women. We aimed to compare the dose-response effects of prescribed aerobic exercise volume on adiposity outcomes.

PARTICIPANTS/METHODS: Data from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were pooled for this analysis (N = 720). These were 12-month randomized controlled trials, where participants were randomized to 225 min/week (mid-volume) of aerobic exercise versus usual inactive lifestyle (ALPHA), or 150 min/week (low-volume) versus 300 min/week (high-volume) (BETA). Fat mass and fat-free mass were measured using DXA and intra-abdominal and subcutaneous fat area were assessed with computed tomography.

RESULTS: After 12 months of aerobic exercise, increasing exercise volumes from no exercise/control to 300 min/week resulted in statistically significant reductions in BMI, weight, fat mass, fat percentage, intra-abdominal and subcutaneous fat area (P < 0.001). Compared with controls, fat mass loss was -1.13, -1.98 and -2.09 kg in the low-, mid- and high-volume groups, respectively. Similarly, weight loss was -1.47, -1.83, -2.21 kg in the low-, mid- and high-volume groups, respectively, compared to controls, and intra-abdominal fat area loss was -7.44, -15.56 and -8.76 cm² in the low-, mid- and high-volume groups, respectively, compared to controls. No evidence for a dose-response effect on fat-free mass was noted.

CONCLUSION: A dose-response effect of exercise volume on adiposity markers was noted, however, the differences in adiposity markers were smaller when comparing 225 min/week to 300 min/week of exercise. Given the strong positive associations between obesity and postmenopausal breast cancer risk, this study provides evidence on the importance of exercise volume as part of the exercise prescription to reduce adiposity and, ultimately, postmenopausal breast cancer risk.

PMID:33727632 | DOI:10.1038/s41366-021-00799-1

Sci Rep. 2021 Mar 16;11(1):5959. doi: 10.1038/s41598-021-85413-0.

ABSTRACT

More thermolabile drugs are becoming available, and in most cases, these medications are dispensed to ambulatory patients. However, there is no regulation once medications are dispensed to patients and little is known with regard to what happens during transport and home storage. Previous studies suggest that these drugs are improperly stored. The present study was designed to determine the storage conditions of thermolabile drugs once they are dispensed to the patient in the Hospital Pharmacy Department. This is a prospective observational study to assess the temperature profile of 7 thermolabile drugs once they are dispensed to ambulatory patients at a tertiary care hospital. A data logger was added to the medication packaging. Temperature was considered inappropriate if one of the following circumstances were met: any temperature record less than or equal to 0 °C or over 25 °C; temperatures between 0-2 or 8-25 °C for a continuous period over 30 min. The time series of temperature measurements obtained from each data logger were analyzed as statistically independent variables. The data shown did not undergo any statistical treatment and must be considered directly related to thermal measurements. One hundred and fourteen patients were included and 107 patients were available for the analysis. On the whole, a mean of 50.6 days (SD 18.3) were measured and the mean temperature was 6.88 °C (SD 2.93). Three data loggers (2.8%) maintained all the measurements between 2 and 8 °C with less than 3 continuous data (< 30 min) out of this range but no data over 25 °C or below or equal to 0 °C. 28 (26.2%) data loggers had at least one measurement below zero, 1 data logger had a measurement greater than 25 °C and 75 (70.1%) were between 0 and 2 °C and/or between 8 and 25 °C for more than 30 min. In conclusion, once dispensed to patients, most thermolabile drugs are improperly stored. Future studies should focus on clinical consequences and possible solutions.

PMID:33727627 | DOI:10.1038/s41598-021-85413-0

Sci Rep. 2021 Mar 17;11(1):6528. doi: 10.1038/s41598-021-85952-6.

NO ABSTRACT

PMID:33727608 | DOI:10.1038/s41598-021-85952-6

Sci Rep. 2021 Mar 16;11(1):5963. doi: 10.1038/s41598-021-85390-4.

ABSTRACT

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.

PMID:33727593 | DOI:10.1038/s41598-021-85390-4

Sci Rep. 2021 Mar 16;11(1):6071. doi: 10.1038/s41598-021-85207-4.

ABSTRACT

To meet the present and forecasted market demand, bacterial alkaline phosphatase (ALP) production must be increased through innovative and efficient production strategies. Using sugarcane molasses and biogenic apatite as low-cost and easily available raw materials, this work demonstrates the scalability of ALP production from a newfound Bacillus paralicheniformis strain APSO isolated from a black liquor sample. Mathematical experimental designs including sequential Plackett-Burman followed by rotatable central composite designs were employed to select and optimize the concentrations of the statistically significant media components, which were determined to be molasses, (NH₄)₂NO₃, and KCl. Batch cultivation in a 7-L stirred-tank bioreactor under uncontrolled pH conditions using the optimized medium resulted in a significant increase in both the volumetric and specific productivities of ALP; the alkaline phosphatase throughput 6650.9 U L^-1, and µ = 0.0943 h^-1; respectively, were obtained after 8 h that, ameliorated more than 20.96, 70.12 and 94 folds compared to basal media, PBD, and RCCD; respectively. However, neither the increased cell growth nor enhanced productivity of ALP was present under the pH-controlled batch cultivation. Overall, this work presents novel strategies for the statistical optimization and scaling up of bacterial ALP production using biogenic apatite.

PMID:33727590 | DOI:10.1038/s41598-021-85207-4