Nevin Manimala

Bioinformation. 2021 May 31;17(5):599-607. doi: 10.6026/97320630017599. eCollection 2020.

ABSTRACT

The prevalence of self-medication (SM) has increased in health professionals due to awareness of disease and symptoms. Incorrect use of medication caused harmful effects. To assess the knowledge, attitude and practice of health professionals, this survey was conducted. A cross-sectional study was carried out among health professionals of different specialities. Knowledge, attitude and practice-based questions were asked through an electronically distributed questionnaire. Data were statistically tested using the Chi-square test with SPSS. Most of the health professionals were aware with the term of self-medication; however the knowledge about related questions was not satisfactory. Almost half of the participants practiced self-medication. The prevalence of self-medication among participants was high. They need to be trained and educate about the incorrect use of self-medication.

PMID:35095234 | PMC:PMC8770411 | DOI:10.6026/97320630017599

Dev Psychopathol. 2021 Dec;33(5):1665-1684. doi: 10.1017/s0954579421000651. Epub 2021 Dec 7.

ABSTRACT

The National Institute of Mental Health Research Domain Criteria’s (RDoC) has prompted a paradigm shift from categorical psychiatric disorders to considering multiple levels of vulnerability for probabilistic risk of disorder. However, the lack of neurodevelopmentally-based tools for clinical decision-making has limited RDoC’s real-world impact. Integration with developmental psychopathology principles and statistical methods actualize the clinical implementation of RDoC to inform neurodevelopmental risk. In this conceptual paper, we introduce the probabilistic mental health risk calculator as an innovation for such translation and lay out a research agenda for generating an RDoC- and developmentally-informed paradigm that could be applied to predict a range of developmental psychopathologies from early childhood to young adulthood. We discuss methods that weigh the incremental utility for prediction based on intensity and burden of assessment, the addition of developmental change patterns, considerations for assessing outcomes, and integrative data approaches. Throughout, we illustrate the risk calculator approach with different neurodevelopmental pathways and phenotypes. Finally, we discuss real-world implementation of these methods for improving early identification and prevention of developmental psychopathology. We propose that mental health risk calculators can build a needed bridge between RDoC’s multiple units of analysis and developmental science.

PMID:35095215 | PMC:PMC8794223 | DOI:10.1017/s0954579421000651

J Cachexia Sarcopenia Muscle. 2022 Jan 30. doi: 10.1002/jcsm.12916. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related loss in skeletal muscle mass, quality, and strength, known as sarcopenia, is a well-known phenomenon of aging and is determined clinically using methods such as dual-energy X-ray absorptiometry (DXA). However, these clinical methods to measure sarcopenia are not practical for population-based studies, and a five-question screening tool known as SARC-F has been validated to screen for sarcopenia.

METHODS: We investigated the relationship between appendicular skeletal lean mass/height² (ALM/HT² ) (kg/m² ) assessed by DXA and SARC-F in a subset of 1538 (778 men and 760 women) participants in the Multiethnic Cohort (MEC) Study after adjustment for race/ethnicity, age, and body mass index (BMI) at the time of DXA measurement. We then investigated the association between SARC-F and mortality among 71 283 (41 757 women and 29 526 men) participants in the MEC, who responded to the five SARC-F questions on a mailed questionnaire as part of the MEC follow-up in 2012-2016.

RESULTS: In women, SARC-F score was significantly inversely associated with ALM/HT² after adjusting for race/ethnicity, and age and BMI at DXA (r = -0.167, P < 0.001); the result was similar in men although it did not reach statistical significance (r = -0.056, P = 0.12). Among the 71 000+ MEC participants, SARC-F score ≥ 4, as an indicator of sarcopenia, was higher in women (20.9%) than in men (11.2%) (P < 0.0001) and increased steadily with increasing age (6.3% in <70 vs. 41.3% in 90+ years old) (P < 0.0001). SARC-F score ≥ 4 was highest among Latinos (30.8% in women and 16.1% in men) and lowest in Native Hawaiian women (15.6%) and Japanese American men (8.9%). During an average of 6.8 years of follow-up, compared with men with SARC-F score of 0-1 (indicator of no sarcopenia), men with SARC-F 2-3 (indicator of pre-sarcopenia) and SARC-F ≥ 4 had significantly increased risk of all-cause mortality [hazard ratio (HR) = 1.00, 1.77, 3.73, P < 0.001], cardiovascular disease (CVD) mortality (HR = 1.00, 1.85, 3.98, P < 0.001), and cancer mortality (HR = 1.00, 1.46, 1.96, P < 0.001) after covariate adjustment. Comparable risk association patterns with SARC-F scores were observed in women (all-cause mortality: HR = 1.00, 1.47, 3.10, P < 0.001; CVD mortality: HR = 1.00, 1.59, 3.54, P < 0.001; cancer mortality: HR = 1.00, 1.30, 1.77, P < 0.001). These significant risk patterns between SARC-F and all-cause mortality were found across all sex-race/ethnic groups considered (12 in total).

CONCLUSIONS: An indicator of sarcopenia, determined using SARC-F, showed internal validity against DXA and displayed racial/ethnic and sex differences in distribution. SARC-F was associated with all-cause mortality as well as cause-specific mortality.

PMID:35098697 | DOI:10.1002/jcsm.12916

Biotechnol J. 2022 Jan 31:e2100427. doi: 10.1002/biot.202100427. Online ahead of print.

ABSTRACT

BACKGROUND: Tuberculosis (TB) and its evolving drug resistance have exerted severe threats on the global health, hence it is still essential to develop novel anti-TB antibiotics. Ilamycin-E1/E2 is a pair of cycloheptapeptide enantiomers obtained from a marine Streptomyces atratus SCSIO ZH16-ΔilaR mutant, and have presented significant anti-TB activities as promising drug lead compounds, but their clinical development has been hampered by low fermentation titers.

MAIN METHODS AND MAJOR RESULTS: By applying the statistical Plackett-Burman design (PBD) model, bacterial peptone was first screened out as the only significant but negative factor to affect the ilamycin-E1/E2 production. Subsequent single factor optimization in shaking flasks revealed that the replacement of bacterial peptone with malt extract could not only eliminate the accumulation of porphyrin-type competitive byproducts, but also improve the titer of ilamycin-E1/E2 from original 13.6±0.8 to 142.7±5.7 mg/L, about 10.5-fold increase. Next, a pH coordinated feeding strategy was adopted in 30L fermentor and obtained 169.8±2.5 mg/L ilamycin-E1/E2, but further scaled-up production in 300L fermentor only gave a titer of 131.5±7.5 mg/L due to the unsynchronization of feeding response and pH change. Consequently, a continuous pulse feeding strategy was utilized in 300L fermentor to solve the above problem and finally achieved 415.7±29.2 mg/L ilamycin-E1/E2, representing a 30.5-fold improvement.

IMPLICATION: Our work has provided a solid basis to acquire sufficient ilamycin-E1/E2 lead compounds and then support their potential anti-TB drug development. This article is protected by copyright. All rights reserved.

PMID:35098690 | DOI:10.1002/biot.202100427

Orthop Surg. 2022 Jan 30. doi: 10.1111/os.13217. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis.

METHODS: The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X-ray and three-dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis.

RESULTS: The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X-ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively.

CONCLUSION: The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique.

PMID:35098677 | DOI:10.1111/os.13217

Emerg Med Australas. 2022 Jan 30. doi: 10.1111/1742-6723.13928. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to determine, in those who present to the ED with low back pain (LBP): (i) the prevalence of four key diagnostic categories, (ii) trends in lumbar imaging from 2015 to 2019 and (iii) the effect of a new model of care on lumbar imaging in the ED.

METHODS: We conducted a retrospective analysis of routinely collected medical data of four tertiary hospitals in Sydney, Australia. We analysed ED presentations for LBP between January 2012 and October 2019. Outcomes were the prevalence of four key diagnostic categories of LBP and use of lumbar imaging. We examined trends in lumbar imaging over time and used interrupted time series analysis to determine the impact of model of care implementation on imaging use.

RESULTS: There were 31 168 presentations for LBP of which 64.5% were non-specific LBP, 27.2% were problems beyond the spine, 5.3% were LBP with neurological signs and 2.3% were serious spinal conditions. 28.9% received lumbar imaging; use did not change substantially between 2012 and 2019. Patients diagnosed with serious spinal conditions were more likely to receive imaging (59%) than those diagnosed with non-specific LBP (29%). Implementation of a state-wide model of care in November 2016 did not appear to influence imaging use.

CONCLUSION: Most presentations to the ED for LBP are for non-specific LBP. Around 2% will have specific spinal pathology. Use of imaging in those diagnosed with non-specific LBP remains high and was unaffected by implementation of a state-wide model of care.

PMID:35098665 | DOI:10.1111/1742-6723.13928

Asia Pac J Clin Oncol. 2022 Jan 30. doi: 10.1111/ajco.13748. Online ahead of print.

ABSTRACT

As an important transcription factor that is widely expressed in most tissues of the human body, Myc-associated zinc finger protein (MAZ) has been reported highly expressed in many malignant tumors and thought to be a promising therapeutic target for cancer treatment. In this review, we aim to offer a comprehensive understanding of MAZ regulation in malignant tumors. The carboxy terminal of MAZ protein contains six C2H2 zinc fingers, and its regulation of transcription is based on the interaction between the GC-rich DNA binding sites of target genes and its carboxy-terminal zinc finger motifs. MAZ protein has been found to activate or inhibit the transcriptional initiation process of many target genes, as well as play an important role in the transcriptional termination process of some target genes, so MAZ poses dual regulatory functions in the initiation and termination process of gene transcription. Through the transcriptional regulation of c-myc and Ras gene family, MAZ poses an important role in the occurrence and development of breast cancer, pancreatic cancer, prostate cancer, glioblastoma, neuroblastoma, and other malignant tumors. Our review shows a vital role of MAZ in many malignant tumors and provides novel insight for cancer diagnosis and treatment.

PMID:35098656 | DOI:10.1111/ajco.13748

J Appl Clin Med Phys. 2022 Jan 30:e13544. doi: 10.1002/acm2.13544. Online ahead of print.

ABSTRACT

PURPOSE: The feasibility of transferring patients between unmatched machines for a limited number of treatment fractions was investigated for three-dimensional conformal radiation therapy (3DCRT) and volumetric modulated arc therapy (VMAT) treatments.

METHODS: Eighty patient-plans were evaluated on two unmatched linacs: Elekta Versa HD and Elekta Infinity. Plans were equally divided into pelvis 3DCRT, prostate VMAT, brain VMAT, and lung VMAT plans. While maintaining the number of monitor units (MUs), plans were recalculated on the machine not originally used for treatment. Relative differences in dose were calculated between machines for the target volume and organs at risk (OARs). Differences in mean dose were assessed with paired t-tests (p < 0.05). The number of interchangeable fractions allowable before surpassing a cumulative ±5% difference in dose was determined. Additionally, patient-specific quality assurance (PSQA) measurements using ArcCHECK for both machines were compared with distributions calculated on the machine originally used for treatment using gradient compensation (GC) with 2%/2-mm criteria.

RESULTS: Interchanging the two machines for pelvic 3DCRT and VMAT (prostate, brain, and lung) plans resulted in an average change in target mean dose of 0.9%, -0.5%, 0.6%, 0.5%, respectively. Based on the differences in dose to the prescription point when changing machines, statistically, nearly one-fourth of the prescribed fractions could be transferred between linacs for 3DCRT plans. While all of the prescribed fractions could typically be transferred among prostate VMAT plans, a rather large number of treatment fractions, 31% and 38%, could be transferred among brain and lung VMAT plans, respectively, without exceeding a ±5% change in the prescribed dose for two Elekta machines. Additionally, the OAR dosage was not affected within the given criterion with change of machine.

CONCLUSIONS: Despite small differences in calculated dose, transferring patients between two unmatched Elekta machines with similar multileaf collimator (MLC)-head for target coverage and minimum changes in OAR dose is possible for a limited number of fractions (≤3) to improve clinical flexibility and institutional throughput along with patient satisfaction. A similar study could be carried out for other machines for operational throughput.

PMID:35098654 | DOI:10.1002/acm2.13544

Phytochem Anal. 2022 Jan 30. doi: 10.1002/pca.3107. Online ahead of print.

ABSTRACT

INTRODUCTION: In this era of ‘omics’ technology in natural products studies, the complementary aspects of mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based techniques must be taken into consideration. The advantages of using both analytical platforms are reflected in a higher confidence of results especially when using replicated samples where correlation approaches can be used to statistically link results from MS to NMR.

OBJECTIVES: Demonstrate the use of Statistical Total Correlation (STOCSY) for linking results from MS and NMR data to reach higher confidence in compound identification.

METHODOLOGY: Essential oil samples of Melaleuca alternifolia and M. rhaphiophylla (Myrtaceae) were used as test objects. Aliquots of 10 samples were collected for GC-MS and NMR data acquisition [proton (¹ H)-NMR, and carbon-13 (¹³ C)-NMR as well as two-dimensional (2D) heteronuclear single quantum correlation (HSQC), heteronuclear multiple-bond correlation (HMBC), and HSQC-total correlated spectroscopy (TOCSY) NMR]. The processed data was imported to Matlab where STOCSY was applied.

RESULTS: STOCSY calculations led to the confirmation of the four main constituents of the sample-set. The identification of each was accomplished using; MS spectra, retention time comparison, ¹³ C-NMR data, and scalar correlations of the 2D NMR spectra.

CONCLUSION: This study provides a pipeline for high confidence in compound identification using a set of essential oils samples as test objects for demonstration.

PMID:35098600 | DOI:10.1002/pca.3107

Stat Med. 2022 Jan 31. doi: 10.1002/sim.9337. Online ahead of print.

ABSTRACT

In the era of immunotherapies and targeted therapies, the focus of early phase clinical trials has shifted from finding the maximum tolerated dose to identifying the optimal biological dose (OBD), which maximizes the toxicity-efficacy trade-off. One major impediment to using adaptive designs to find OBD is that efficacy or/and toxicity are often late-onset, hampering the designs’ real-time decision rules for treating new patients. To address this issue, we propose the model-assisted TITE-BOIN12 design to find OBD with late-onset toxicity and efficacy. As an extension of the BOIN12 design, the TITE-BOIN12 design also uses utility to quantify the toxicity-efficacy trade-off. We consider two approaches, Bayesian data augmentation and an approximated likelihood method, to enable real-time decision making when some patients’ toxicity and efficacy outcomes are pending. Extensive simulations show that, compared to some existing designs, TITE-BOIN12 significantly shortens the trial duration while having comparable or higher accuracy to identify OBD and a lower risk of overdosing patients. To facilitate the use of the TITE-BOIN12 design, we develop a user-friendly software freely available at http://www.trialdesign.org.

PMID:35098585 | DOI:10.1002/sim.9337