Tag: nevin manimala

Reprod Sci. 2021 Apr 14. doi: 10.1007/s43032-021-00576-5. Online ahead of print.

ABSTRACT

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.

PMID:33852137 | DOI:10.1007/s43032-021-00576-5

J Racial Ethn Health Disparities. 2021 Apr 14. doi: 10.1007/s40615-021-01037-0. Online ahead of print.

ABSTRACT

BACKGROUND: Understanding concerns for receiving COVID-19 vaccines is key to ensuring appropriately tailored health communications to increase vaccine uptake. However, limited data exists about vaccine concerns among Asian Americans and Pacific Islanders (AAPI).

METHODS: Data from the COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS), a cross-sectional, national survey for AAPI adults in the U.S. were used (N=1,646). Descriptive statistics were used to assess sample characteristics including proportions of AAPI with various COVID-19 vaccine concerns, categorized as none, side-effects only, unsafe only, and multiple reasons, and differences in vaccine concerns by socio-demographics. Ordinary multivariable logistic regression analyses were conducted to evaluate associations between a characteristic and having any vaccine concerns.

RESULTS: Overall, 76% of the respondents reported having at ≥1 concerns about the vaccine. The most common concern was side effects (65%). Vietnamese Americans reported less concerns (vs. Chinese Americans). Those who were 30-39 and 40-49 years old (vs. <30), females (vs. males), and experienced mild negative impacts from COVID-19 on family income/employment (vs. no change) reported more concerns about the vaccine. Those who had less vaccine concerns were those who reported higher (vs. low) health status, ≥60 years old (vs. <30), and separated/divorced/widowed (vs. single).

DISCUSSION: AAPI is a diverse population and this study revealed differences in vaccine concerns across AAPI groups. Findings revealed potential targets for patient education needs. Effective strategies to address various vaccine concerns across subgroups of AAPI will be crucial to ensure equity in vaccination uptake.

PMID:33852148 | DOI:10.1007/s40615-021-01037-0

Obes Surg. 2021 Apr 14. doi: 10.1007/s11695-021-05360-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Obesity increases the risk of pelvic floor disorders in individuals with obesity, including faecal incontinence. Faecal incontinence (FI) is a condition with important clinical and psychosocial consequences. Though it is associated with obesity, the effect of bariatric surgery on the prevalence and severity of FI is not well reported.

OBJECTIVE: To assess the effect of bariatric surgery on the prevalence and severity of FI in adult patients with obesity.

METHODS: This systematic review was conducted in accordance with the PRISMA statement. Two independent reviewers performed a literature search in MEDLINE, PubMed, Cochrane and Embase from 1 January 1980 to 12 January 2019. We included published English-language randomized control trials and observational studies assessing pre- and post-bariatric surgery prevalence or severity of FI. Random-effects models with DerSimonian and Laird’s variance estimator were used for meta-analysis.

RESULTS: Thirteen studies were included, eight assessing prevalence (678 patients) and 11 assessing severity of FI (992 patients). There was no significant difference in prevalence post-operatively overall, though it trended towards a reduction [pooled OR=0.55; =0.075]. There was a significant reduction of FI prevalence in women post-bariatric surgery [95% CI 0.22 to 0.94, p=0.034]. There was a statistically significant reduction in FI prevalence following Roux-en-Y gastric bypass and one anastomosis gastric bypass [0.46, 95% CI 0.26 to 0.81; p=0.007]. There was no significant reduction of incontinence episodes post-operatively [pooled mean difference =-0.17, 95% CI -0.90 to 0.56; p=0.65]. Quality of life (QOL) was not significantly improved post-bariatric surgery [mean differences for the following facets of QOL: behaviour -0.35, 95% CI -0.94 to 0.24; depression 0.04, 95% CI -0.12 to 0.2; lifestyle -0.33, 95% CI -0.98 to 0.33; p values of 0.25, 0.61 and 0.33, respectively].

DISCUSSION: There was a significant reduction in FI prevalence in women and those who underwent Roux-en-Y or one anastomosis gastric bypass. Our results for FI prevalence overall, FI severity and impact on quality of life were not statistically significant. Larger studies are needed in this under-researched area to determine the true effect of bariatric surgery on FI.

PMID:33852150 | DOI:10.1007/s11695-021-05360-7

Breast Cancer Res Treat. 2021 Apr 14. doi: 10.1007/s10549-021-06200-z. Online ahead of print.

ABSTRACT

PURPOSE: Herein, our purpose was to calculate the 5-year and lifetime risk of breast cancer and to assess new breast cancer potential contributors among Egyptian women utilizing the modified Gail model, while presenting a global comparison of risk assessment.

METHODS: This study included 7009 women from both urban and rural areas scattered across 40% of the Egyptian provinces. The 5-year risk categories were defined as low risk (≤ 1.66%) or high risk (> 1.66%), whereas the lifetime risk categories were defined as low risk (≤ 20%) or high risk (> 20%). Pearson’s Chi-squared test was performed to determine the association between participants’ characteristics and distinct risk categories. Binary logistic regression was carried out for correlation analysis.

RESULTS: The mean estimated risk for developing invasive breast cancer over 5 years was 0.86 (± 0.67), whereas the mean lifetime breast cancer risk score was 11.26 (± 5.7). Accordingly, only 614 (8.75%) and 470 (6.7%) women were categorized as individuals with high risk of breast cancer incidence in 5-year and lifetime, respectively. Only 192 participants (2.7%) conferred both high 5-year and high lifetime risk scores. Marital status, method of feeding, physical activity behavior, contraceptive use, menopause and number of children were found to have a statistically significant association with both 5-year and lifetime breast cancer risk categories.

CONCLUSION: We revealed that modified Gail model had a well-fitting and discrimination accuracy in Egyptian women when compared with other countries.

PMID:33852122 | DOI:10.1007/s10549-021-06200-z

Behav Res Methods. 2021 Apr 14. doi: 10.3758/s13428-021-01579-5. Online ahead of print.

ABSTRACT

Ongoing goal-directed movements can be rapidly adjusted following new environmental information, e.g., when chasing pray or foraging. This makes movement trajectories in go-before-you-know decision-making a suitable behavioral readout of the ongoing decision process. Yet, existing methods of movement analysis are often based on statistically comparing two groups of trial-averaged trajectories and are not easily applied to three-dimensional data, preventing them from being applicable to natural free behavior. We developed and tested the cone method to estimate the point of overt commitment (POC) along a single two- or three-dimensional trajectory, i.e., the position where the movement is adjusted towards a newly selected spatial target. In Experiment 1, we established a “ground truth” data set in which the cone method successfully identified the experimentally constrained POCs across a wide range of all but the shallowest adjustment angles. In Experiment 2, we demonstrate the power of the method in a typical decision-making task with expected decision time differences known from previous findings. The POCs identified by cone method matched these expected effects. In both experiments, we compared the cone method’s single trial performance with a trial-averaging method and obtained comparable results. We discuss the advantages of the single-trajectory cone method over trial-averaging methods and possible applications beyond the examples presented in this study. The cone method provides a distinct addition to existing tools used to study decisions during ongoing movement behavior, which we consider particularly promising towards studies of non-repetitive free behavior.

PMID:33852130 | DOI:10.3758/s13428-021-01579-5

Eur J Drug Metab Pharmacokinet. 2021 Apr 14. doi: 10.1007/s13318-021-00671-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Population pharmacokinetic analysis explored the pharmacokinetics of sunitinib and its primary active metabolite, SU012662, in children and evaluated the sunitinib dose(s) that produce comparable plasma exposures to adults receiving the approved daily dose.

METHODS: Data were from 65 children with gastrointestinal stromal tumors (GIST) or solid tumors. Pharmacokinetic models of sunitinib and SU012662 were developed using a systematic multi-step approach employing nonlinear mixed-effects modeling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Final models were validated using visual predictive check and statistical techniques.

RESULTS: The final dataset comprised 439 sunitinib and 417 SU012662 post-baseline plasma observations. Base models were characterized by two-compartment models with first-order absorption and lag time. Body surface area (BSA) was the only covariate that affected (P < 0.001) pharmacokinetic parameters for sunitinib and SU012662 and was incorporated into the final models. Bootstrap results indicated that the final models represented the final dataset adequately. Based on the final models, a sunitinib dose of ~ 20mg/m²/day in children with GIST aged 6-17 years would be expected to lead to similar total plasma exposures of sunitinib and SU012661 as a dose of 50 mg/day in an adult with GIST on schedule 4/2.

CONCLUSIONS: In children with GIST or solid tumors receiving sunitinib, population pharmacokinetic analysis identified BSA as the only covariate that affected pharmacokinetic parameters and predicted a dose of ~ 20 mg/m²/day as achieving equivalent exposure to 50 mg/day in adults with GIST on schedule 4/2.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers (date registered): NCT01396148 (July 2011); NCT01462695 (October 2011); NCT00387920 (October 2006).

PMID:33852135 | DOI:10.1007/s13318-021-00671-7

Clin Oral Investig. 2021 Apr 14. doi: 10.1007/s00784-021-03880-1. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the effects of epidermal growth factor (EGF)-coated titanium (Ti) discs on the adhesion and metabolism of keratinocytes and gingival fibroblasts exposed to nitrogen-containing bisphosphonates.

MATERIALS AND METHODS: Keratinocytes and fibroblasts were seeded (1 × 10⁵ cells/disc) on Ti discs coated with EGF (100 nM). After 24 h, cells were exposed or not to sodium alendronate (SA) or zoledronic acid (ZA) at different concentrations (0 = control, 0.5, 1, or 5 μM) for 48 h. Cell adhesion to the substrates was evaluated by fluorescence microscopy. Cell viability (alamarBlue, n = 6) and synthesis of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and keratinocytes growth factor (KGF) (ELISA, n = 6) were assessed. Data were statistically analyzed by one-way ANOVA and Tukey tests (α = 0.05).

RESULTS: Higher cell adhesion rate was observed when keratinocytes and fibroblasts were seeded onto EGF-coated discs in comparison to uncoated discs. ZA treatment hindered the adhesion of both cell lines on the Ti discs as well as reduced the viability and synthesis of VEGF, KGF and MMP-2 by cells (p < 0.05). SA treatment did not affect cell viability, but interfered negatively on the adhesion and synthesis of EGF and KGF by the cells (p < 0.05). EGF-coated surface increased cell viability and synthesis of growth factors as well as downregulated the synthesis of MMP-2 in comparison to control (p < 0.05).

CONCLUSION: EGF applied on Ti surface improves the biological responses of oral mucosa cells exposed to SA and ZA.

CLINICAL RELEVANCE: EGF-coating on titanium may be a suitable strategy to improve oral mucosa cellular events related to biological sealing, especially for patients under bisphosphonate therapy.

PMID:33852064 | DOI:10.1007/s00784-021-03880-1

Eur J Nutr. 2021 Apr 14. doi: 10.1007/s00394-021-02556-6. Online ahead of print.

ABSTRACT

PURPOSE: The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017.

METHODS: China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber.

RESULTS: In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017.

CONCLUSIONS: China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

PMID:33852070 | DOI:10.1007/s00394-021-02556-6

Breast Cancer Res Treat. 2021 Apr 14. doi: 10.1007/s10549-021-06221-8. Online ahead of print.

ABSTRACT

PURPOSE: To compare efficacy and safety of capecitabine and lapatinib with or without IMC-A12 (cituxumumab) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.

PATIENTS AND METHODS: Following an initial safety run-in cohort, patients were randomized 1:2 to Arm A (capecitabine and lapatinib) or to Arm B (capecitabine, lapatinib, and cituxumumab). Given the frequency of non-hematologic grade ≥ 3 adverse events in those receiving the three-drug combination in the safety cohort, lapatinib and capecitabine doses were reduced in Arm B only. The primary objective was to determine if the addition of cituxumumab to capecitabine and lapatinib improved progression-free survival (PFS) compared with capecitabine and lapatinib. Secondary objectives included a comparison between arms of other clinical endpoints, safety, change in overall quality of life (QOL) and self-assessed fatigue, rash, diarrhea, and hand-foot syndrome.

RESULTS: From July 2008 to March 2012, 68 patients (out of 142 planned) were enrolled and 63 were evaluable, including 8 for the safety run-in and 55 for the randomized cohort. Study enrollment was stopped early due to slow accrual. The addition of cituxumumab to capecitabine and lapatinib did not improve PFS (HR 0.93, 95% CI: 0.52-1.64). Furthermore, no difference in objective response rate or overall survival (OS) was observed. No difference between arms was observed in grade ≥ 3 adverse events, overall QOL change from baseline after 4 cycles of treatment.

CONCLUSION: The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC.

CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00684983.

PMID:33852121 | DOI:10.1007/s10549-021-06221-8

Eur J Nucl Med Mol Imaging. 2021 Apr 14. doi: 10.1007/s00259-021-05354-8. Online ahead of print.

ABSTRACT

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [¹⁸F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy.

METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [¹⁸F]DCFPyL tracer and a diagnostic CT. The detection rates of [¹⁸F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported.

RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [¹⁸F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [¹⁸F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [¹⁸F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [¹⁸F]DCFPyL administration.

CONCLUSIONS: [¹⁸F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [¹⁸F]DCFPyL PET/CT scan.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

PMID:33852051 | DOI:10.1007/s00259-021-05354-8