Tag: pubmed

J Ultrasound Med. 2021 Apr 23. doi: 10.1002/jum.15728. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the performance of a two-step strategy compared with the International Ovarian Tumor Analysis (IOTA) – Assessment of Different NEoplasias in the adneXa (ADNEX) model for preoperative classification of adnexal masses.

METHODS: An ambispective diagnostic accuracy study based on ultrasound data collected at one university hospital between 2012 and 2018. Two ultrasonographers classified the adnexal masses using IOTA Simple Rules (first step). Not classifiable masses were evaluated using the IOTA ADNEX model (second step). Also, all masses were classified using the IOTA ADNEX model. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and receiver operating characteristic (ROC) curve were estimated. A P value of <.05 was used to determine statistical significance.

RESULTS: The study included 548 patients and 606 masses. Patients’ median age was 41 years with an interquartile range between 32 and 51 years. In the first step, 89 (14%) masses were not classifiable. In the second step, 55 (61.8%) masses were classified as malignant. Furthermore, for the totality of 606 masses, the IOTA ADNEX model estimated the probability that 126 (20.8%) masses were malignant. The two-step strategy had a sensitivity, specificity, PPV, NPV, LR+, LR-, and ROC curve of 86.8%, 91.01%, 51.9%, 98.4%, 9.7, 0.1, and 0.889, respectively; compared to IOTA ADNEX model that had values of 91.8%, 87.16%, 44.4%, 99%, 7.1, 0.09, and 0.895, respectively.

CONCLUSION: The two-step strategy shows a similar diagnostic performance when compared to the IOTA ADNEX model. The IOTA ADNEX model involves only one step and can be more practical, and thus would be recommended to use.

PMID:33890698 | DOI:10.1002/jum.15728

Int J Pharm Pract. 2021 Apr 23:riab013. doi: 10.1093/ijpp/riab013. Online ahead of print.

ABSTRACT

OBJECTIVES: Pharmacy professionals are required to take all necessary steps to protect commonly misused drugs such as opioids at their pharmacies to minimize the risk of diversion. The aim of this study is to assess Canadian pharmacy professionals’ knowledge and compliance with federal and provincial regulations using the computer-based educational platform Pharmacy5in5.

METHODS: A Narcotic Inventory module was created and reviewed by experts representing provincial and federal regulators. Descriptive statistics were used to analyze users’ performance in quizzes. Binomial regression and logistic regression models were used to investigate the effect of demographic factors on users’ performance. P-values less than 0.05 were considered statistically significant.

KEY FINDINGS: The analysis included data collected over a period of three months. A total of 792 users accessed the Narcotic Inventory module on the Pharmacy5in5 website between July 2019 and November 2019. Most of the users were licenced pharmacists (64%), female (72%), received their training in Canada (68%), and were practising in Ontario (80%). Users performed best on the quiz addressing the steps for reconciliation of inventory (93%), and worst on the quiz reviewing how to prepare for a Health Canada visit (66%).

CONCLUSIONS: Overall, pharmacy professionals showed adequate knowledge of the CDSA and provincial/territorial regulations regarding opioids inventory management. Conversely, the study highlighted poor compliance with the reporting of losses and theft of controlled substances by pharmacy professionals. Innovative approaches are needed to influence pharmacy professionals’ behaviours to improve their compliance with best practices concerning inventory management to reduce drug diversion.

PMID:33890668 | DOI:10.1093/ijpp/riab013

Int J Pharm Pract. 2021 Apr 23:riab019. doi: 10.1093/ijpp/riab019. Online ahead of print.

ABSTRACT

BACKGROUND: Sub-Saharan Africa, a region faced with a double challenge of infectious and non-communicable diseases requires strengthening of hospital pharmacy practice to improve treatment outcomes and patient safety.

OBJECTIVES: The objectives of this study were to assess the current state of pharmacy practice in hospitals in Namibia and to identify opportunities for expanding pharmacists’ role in addressing public health challenges and improving medicines use outcomes.

METHODS: A survey utilized FIP’s self-assessment tool to evaluate current hospital pharmacy practice in Namibia against best practices articulated in the Basel Statements. The study was conducted among hospital pharmacists across Namibia. Quantitative and qualitative data were analysed using descriptive statistics and thematic analysis.

KEY FINDINGS: The study was conducted in 24 hospital pharmacies across Namibia, the majority of which were public facilities (67%). Overall, current hospital pharmacy practice activities are focused on medicine procurement, preparation and distribution. The main barriers to optimal hospital pharmacy services are associated with limited human resources and collaboration across healthcare providers, as well as policy gaps.

CONCLUSIONS: There is a strong desire among hospital pharmacists to expand their contributions to improving medicines outcomes and solving public health problems. Namibia’s pharmacy educational system is a strength and should be utilized to continue advancing hospital pharmacy practice and medicines use. Therapeutics committees are usually part of each hospital’s structure and can be very effective for hospital-based policy change. The opportunity exists to optimize pharmacists’ contributions by utilizing the local therapeutics committees in combination with the educational system to advance hospital pharmacy practice in Namibia.

PMID:33890674 | DOI:10.1093/ijpp/riab019

J Forensic Sci. 2021 Apr 23. doi: 10.1111/1556-4029.14710. Online ahead of print.

ABSTRACT

Fingermark ridge drift is a random modification of (aged) fingermark patterns at a ridge scale. This phenomenon was previously proven to alter key elements used for identifications, such as the appearance of minutiae. Little is currently reported on the underlying factors contributing to its occurrence. The present study was designed to investigate further the variables of a previous study by including a total of 768 fingermarks from a male and female, two substrates (glazed ceramic tile and plastic), two distinct color powder developers (carbon black and titanium dioxide), three indoor lighting conditions (direct natural light, shade, and darkness), and two secretion types (sebaceous- and eccrine-rich). Fingermarks were aged for 2-72 days, powdered, photographed, and drift detected by three independent observers. All aged fingermarks (672) were compared relative to fresh fingermarks (96), and ridge drift was observed in 42 of 672 (6%) fingermarks, while 168 (25%) were reported as indeterminate results. While ridge drift was detected in multiple fingermarks across all independent variables, statistical analysis using a multinomial logistics model showed that only powder type, secretion type, and the substrate indicated a significant correlation with increased incidences of this phenomenon. There was no significant correlation with the donor, time since deposition, or the environmental lighting conditions used. The highest incidence occurred when carbon black powder was used on a plastic substrate (>10%). The average observation of ridge drift is 6% of samples supporting that this phenomenon is not a rare event, particularly considering the conservative analysis approach implemented.

PMID:33890675 | DOI:10.1111/1556-4029.14710

Public Health Nurs. 2021 Apr 23. doi: 10.1111/phn.12913. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examines the knowledge levels pertaining to early childhood caries (ECC) among grassroot workers of rural India.

DESIGN: A questionnaire study assessing the awareness levels of various ECC aspects was carried out among 88 auxiliary nurse midwives (ANMs), 140 Anganwadi workers (AWWs), and 210 Accredited Social Health Activist (ASHA) workers in a district of Southern India. A 24-item pretested, structured, and close-ended, self-administered questionnaire was used to collect information on the knowledge of early childhood oral health-related factors. Descriptive statistics and multivariate ANOVA were used to summarize the results.

RESULTS: Overall, only 59% of ANMs, 49% of AWWs, and 47% of ASHA workers were found to have adequate knowledge about ECC.

CONCLUSION: The current study clearly highlighted the discrepancy in the awareness levels among grassroot health care workers. A deficit was found to exist in the knowledge of the tested health care workers regarding infant oral care and ECC transmissibility.

PMID:33890686 | DOI:10.1111/phn.12913

Lancet Digit Health. 2021 May;3(5):e280-e282. doi: 10.1016/S2589-7500(21)00054-6.

NO ABSTRACT

PMID:33890577 | DOI:10.1016/S2589-7500(21)00054-6

Hum Reprod. 2021 Apr 23:deab078. doi: 10.1093/humrep/deab078. Online ahead of print.

ABSTRACT

STUDY QUESTION: Do the epigenome-wide DNA methylation profiles of adolescents born from ART differ from the epigenome of naturally conceived counterparts?

SUMMARY ANSWER: No significant differences in the DNA methylation profiles of adolescents born from ART [IVF or ICSI] were observed when compared to their naturally conceived, similar aged counterparts.

WHAT IS KNOWN ALREADY: Short-term and longer-term studies have investigated the general health outcomes of children born from IVF treatment, albeit without common agreement as to the cause and underlying mechanisms of these adverse health findings. Growing evidence suggests that the reported adverse health outcomes in IVF-born offspring might have underlying epigenetic mechanisms.

STUDY DESIGN, SIZE, DURATION: The Growing Up Healthy Study (GUHS) is a prospective study that recruited 303 adolescents and young adults, conceived through ART, to compare various long-term health outcomes and DNA methylation profiles with similar aged counterparts from Generation 2 from the Raine Study. GUHS assessments were conducted between 2013 and 2017. The effect of ART on DNA methylation levels of 231 adolescents mean age 15.96 ± 1.59 years (52.8% male) was compared to 1188 naturally conceived counterparts, 17.25 ± 0.58 years (50.9% male) from the Raine Study.

PARTICIPANTS/MATERIALS, SETTING, METHODS: DNA methylation profiles from a subset of 231 adolescents (13-19.9 years) from the GUHS, generated using the Infinium Methylation Epic Bead Chip (EPIC) array were compared to 1188 profiles from the Raine Study previously measured using the Illumina 450K array. We conducted epigenome-wide association approach (EWAS) and tested for an association between the cohorts applying Firth’s bias reduced logistic regression against the outcome of ART versus naturally conceived offspring. Additionally, within the GUHS cohort, we investigated differences in methylation status in fresh versus frozen embryo transfers, cause of infertility as well as IVF versus ICSI conceived offspring. Following the EWAS analysis we investigated nominally significant probes using Gene Set Enrichment Analysis (GSEA) to identify enriched biological pathways. Finally, within GUHS we compared four estimates (Horvath, Hanuum, PhenoAge [Levine], and skin Horvath) of epigenetic age and their correlation with chronological age.

MAIN RESULTS AND THE ROLE OF CHANCE: Between the two cohorts, we did not identify any DNA methylation probes that reached a Bonferroni corrected P-value < 1.24E-0.7. When comparing IVF versus ICSI conceived adolescents within the GUHS cohort, after adjustment for participant age, sex, maternal smoking, multiple births, and batch effect, three methylation probes (cg15016734, cg26744878 and cg20233073) reached a Bonferroni correction of 6.31E-08. After correcting for cell count heterogeneity, two of the aforementioned probes remained significant and an additional two probes (cg 0331628 and cg 20235051) were identified. A general trend towards hypomethylation in the ICSI offspring was observed. All four measures of epigenetic age were highly correlated with chronological age and showed no evidence of accelerated epigenetic aging within their whole blood.

LIMITATIONS, REASONS FOR CAUTION: The small sample size coupled with the use of whole blood, where epigenetic differences may occur in other tissue. This was corrected by the utilized statistical method that accounts for imbalanced sample size between groups and adjusting for cell count heterogeneity. Only a small portion of the methylome was analysed and rare individual differences may be missed.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide further reassurance that the effects of the ART manipulations occurring during early embryogenesis, existing in the neonatal period are indeed of a transient nature and do not persist into adolescence. However, we have not excluded that alternative epigenetic mechanisms may be at play.

STUDY FUNDING/COMPETING INTEREST(S): This project was supported by NHMRC project Grant no. 1042269 and R.J.H. received funding support from Ferring Pharmaceuticals Pty Ltd. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from Merck Sharp & Dohme Corp.- Australia, Merck-Serono Australia Pty Ltd and Ferring Pharmaceuticals Pty Ltd. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia. The remaining authors have no conflicts of interest.

PMID:33890633 | DOI:10.1093/humrep/deab078

J Biomol Struct Dyn. 2021 Apr 23:1-20. doi: 10.1080/07391102.2021.1913231. Online ahead of print.

ABSTRACT

The dysregulation of cyclin-CDK6 interactions has been implicated in human breast cancer, providing a rationale for more therapeutic options. Recently, ATP-competitive inhibitors have been employed for managing breast cancer. These molecules, like most natural CDKs inhibitors, potently bind in the ATP-binding site of CDK6 to regulate trans-activation. Nonetheless, only a few numbers of these molecules are approved to mitigate breast cancer, thus, ensuring that the search for more selective inhibitors continues. In this study, we attempted to establish the selective predictive models for identifying potent CDK6 inhibitors against a human breast cancer cell-line using a dataset of fifty-two 1,3,4-thiadiazole derivatives. The significant eight descriptor hybrid QSAR models generated exhibited encouraging statistical attributes including R2> 0.70, Q²_LOO > 0.70, Q²_LMO > 0.60, Qfn2 > 0.6. Furthermore, the study designed new compounds based on the activity and structural basis for selectivity of compounds for CDK6. While demonstrating good potency and modest selectivity, the compound C16, which showed significantly high activity of 5.5607 µM and binding energy value of -9.0 Kcal/mol, was used as template for compounds design to generate 10 novel series of 1,3,4-thiadiazole analogues containing benzisoselenazolone scaffolds, with significant pharmacological activity and better selectivity for CDK6. By our rationale, four of the designed compounds (C16b, C16h, C16i, and C16j) with activity values of 6.2584 µM, 6.7812 µM, 6.4717 µM, and 6.2666 µM respectively, and binding affinities of -10.0 kcal/mol, -9.9 kcal/mol, -9.9 kcal/mol, and -9.9 kcal/mol respectively, may emerge as therapeutic options for breast cancer treatment after extensive in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

PMID:33890551 | DOI:10.1080/07391102.2021.1913231

Zygote. 2021 Apr 23:1-10. doi: 10.1017/S0967199420000933. Online ahead of print.

ABSTRACT

Dynamic changes in microRNAs in oocyte and cumulus cells before and after maturation may explain the spatiotemporal post-transcriptional gene regulation within bovine follicular cells during the oocyte maturation process. miR-20a has been previously shown to regulate proliferation and differentiation as well as progesterone levels in cultured bovine granulosa cells. In the present study, we aimed to demonstrate the function of miR-20a during the bovine oocyte maturation process. Maturation of cumulus-oocyte complexes (COCs) was performed at 39°C in an humidified atmosphere with 5% CO2 in air. The expression of miR-20a was investigated in the cumulus cells and oocytes at 22 h post culture. The functional role of miR-20a was examined by modulating the expression of miR-20a in COCs during in vitro maturation (IVM). We found that the miR-20a expression was increased in cumulus cells but decreased in oocytes after IVM. Overexpression of miR-20a increased the oocyte maturation rate. Even though not statistically significant, miR-20a overexpression during IVM increased progesterone levels in the spent medium. This was further supported by the expression of STAR and CYP11A1 genes in cumulus cells. The phenotypes observed due to overexpression of miR-20a were validated by BMP15 supplementation during IVM and subsequent transfection of BMP15-treated COCs using miR-20a mimic or BMPR2 siRNA. We found that miR-20a mimic or BMPR2 siRNA transfection rescued BMP15-reduced oocyte maturation and progesterone levels. We concluded that miR-20a regulates oocyte maturation by increasing cumulus cell progesterone synthesis by simultaneous suppression of BMPR2 expression.

PMID:33890561 | DOI:10.1017/S0967199420000933

Mayo Clin Proc. 2020 Oct 21:S0025-6196(20)31119-8. doi: 10.1016/j.mayocp.2020.08.051. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the presence of clinically actionable results and other genetic findings in an otherwise healthy population of adults seen in a medical practice setting and offered “predictive” genomic testing.

PATIENTS AND METHODS: In 2014, a predictive genomics clinic for generally healthy adults was launched through the Mayo Clinic Executive Health Program. Self-identified interested patients met with a genomic nurse and genetic counselor for pretest advice and education. Two genome sequencing platforms and one gene panel-based health screen were offered. Posttest genetic counseling was available for patients who elected testing. From March 1, 2014, through June 1, 2019, 1281 patients were seen and 301 (23.5%) chose testing. Uptake rates increased to 36.3% [70 of 193]) in 2019 from 11.8% [2 of 17] in 2014. Clinically actionable results and genetic findings were analyzed using descriptive statistics.

RESULTS: Clinically actionable results were detected in 11.6% of patients (35 of 301), and of those, 51.7% (15 of 29) with a cancer or cardiovascular result = did not have a personal or family history concerning for a hereditary disorder. The most common actionable results were in the BCHE, BRCA2, CHEK2, LDLR, MUTYH, and MYH7 genes. A carrier of at least one recessive condition was found in 53.8% of patients (162 of 301). At least one variant associated with multifactorial disease was found in 44.5% (134 of 301) (eg, 25 patients were heterozygous for the F5 factor V Leiden variant associated with thrombophilia risk).

CONCLUSION: Our predictive screening revealed that 11.6% of individuals will test positive for a clinically actionable, likely pathogenic/pathogenic variant. This finding suggests that wider knowledge and adoption of predictive genomic services could be beneficial in medical practice, although additional studies are needed.

PMID:33890576 | DOI:10.1016/j.mayocp.2020.08.051