Tag: nevin manimala

J Med Chem. 2021 Jul 19. doi: 10.1021/acs.jmedchem.1c00890. Online ahead of print.

ABSTRACT

Selective cyclooxygenase (COX)-2 inhibitors have been extensively studied for colorectal cancer (CRC) chemoprevention. Celecoxib has been reported to reduce the incidence of colorectal adenomas and CRC but is also associated with an increased risk of cardiovascular events. Here, we report a series of gut-restricted, selective COX-2 inhibitors characterized by high colonic exposure and minimized systemic exposure. By establishing acute ex vivo ¹⁸F-FDG uptake attenuation as an efficacy proxy, we identified a subset of analogues that demonstrated statistically significant in vivo dose-dependent inhibition of adenoma progression and survival extension in an APC^min/+ mouse model. However, in vitro-in vivo correlation analysis showed their chemoprotective effects were driven by residual systemic COX-2 inhibition, rationalizing their less than expected efficacies and highlighting the challenges associated with COX-2-mediated CRC disease chemoprevention.

PMID:34279934 | DOI:10.1021/acs.jmedchem.1c00890

Genet Test Mol Biomarkers. 2021 Jul;25(7):504-514. doi: 10.1089/gtmb.2020.0093.

ABSTRACT

Objective: This study was designed to analyze the expression of CSNK1D in hepatocellular carcinoma (HCC) and investigate the relationship between the expression of CSNK1D and the prognosis of HCC patients. Methods: The CSNK1D and alpha-fetoprotein (AFP) expression levels in patients with HCC and their corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) and sorted with a Perl program. CSNK1D and AFP expression differences in liver tissue and liver cancer were compared and analyzed, based on the online database human cancer metastasis database, the relationships between the expression levels of CSNK1D and AFP and the proliferation and metastases of HCC were explored. The immunohistochemical data obtained from the Human Protein Atlas Database further verified the differences in the expression levels of CSNK1D and AFP in liver tissues and liver cancer tissues. Through Kaplan-Meier survival analysis, the effects of CSNK1D and AFP expression levels on the prognosis of patients with HCC were investigated, and the influences of and patients’ gender, age and grades of cancer cells, tumor size, the status of lymph node metastasis, distant metastasis, and tumor stage on the expression of CSNK1D were analyzed with R language. The influence of differential expressions of CSNK1D on survival time was compared and the prognostic factors influencing the survival of HCC patients were statistically explored by univariate analysis and multivariate analysis. The potential influencing mechanism of CSNK1D on the prognosis of HCC patients was explored by Gene Set Enrichment Analysis (GSEA) enrichment. Results: The expression level of CSNK1D and AFP in cancer foci was significantly higher than that in normal tissues, However, in the same patient, the expression levels of AFP in paracarcinoma tissues and cancer tissues showed no significant difference. The expression level of CSNK1D in HCC with distant metastases was higher than that in those without metastasis, but the expression level of AFP in metastatic HCC was lower than that in those HCC without metastases. In immunohistochemical tests, CSNK1D was moderately positive in normal liver tissues, slightly positive in normal bile duct tissues, and highly positive in HCC. AFP was slightly positive in normal liver tissues and negative in HCC, but it was not detected in normal intrahepatic bile duct tissue. Survival analysis results suggested that the higher expression level of CSNK1D corresponded to the shorter survival period, whereas the expression level of AFP showed no significant influence on survival time. The expression level of CSNK1D was not correlated with gender, age, the status of lymph node metastasis status, or distant metastasis of patients. The main factors influencing the expression level of CSNK1D included tumor size, cancer cell grade, and tumor stage. The expression levels of CSNK1D in T2 and T3 were higher than that in T1. The expression levels of CSNK1D in G3 and G4 were higher than that in G1. The expression levels of CSNK1D in Stage II and Stage III were higher than that in Stage I. Univariate analysis suggested that tumor size, cell grade, distant metastasis, clinical stage, and CSNK1D expression level were the prognostic factors influencing the survival of patients. Multivariate analysis suggested that CSNK1D expression level was an independent factor influencing the prognosis of HCC patients. GSEA enrichment analysis indicated that CSNK1D mainly affected the prognosis of HCC patients through cell cycle, WNT signaling pathway, amino acid degradation metabolism, and other pathways. Conclusion: CSNK1D is an independent influencing factor for the prognosis of HCC patients and has the potential to be developed as a potential therapeutic target for HCC, and better than AFP in predicting the prognosis of HCC.

PMID:34280005 | DOI:10.1089/gtmb.2020.0093

Neuro Endocrinol Lett. 2021 Jul 19;42(3):200-212. Online ahead of print.

ABSTRACT

BACKGROUND: Emotionally unstable personality disorder (EUPD) is a challenging condition with a prevalence of 20% in inpatient services. Psychotherapy is the preferred treatment; nevertheless, off-license medications are widely used.

OBJECTIVES: To identify socio-demographics, clinical and service-delivery characteristics of people with EUPD admitted to inpatient services between 1st January 2017 and 31st December 2018.

METHODS: A retrospective review using data from patients’ records. Individuals, age 18-65 were included. Statistical analysis was conducted by the Mann-Whitney-Wilcoxon test and Chi-squared test with Yates’s continuity correction.

RESULTS: Of 1646 inpatients, 201 (12.2%); had the diagnosis of EUPD; 133 (66.0%) women, 68 (44.0%). EUPD was significantly (P < .001) more prevalent in women (18.2%) than men (7.4%). EUPD patients were significantly (P < .001) younger (32.2 years) than patients without EUPD (46 years), and had significantly (P < .001) more admissions (1.74) than patients without EUPD (1.2 admission). 70.5% of patients had one and 17.0% two Axis-I psychiatric co-morbidities. Substance use was significantly (P < .001) more often in men (57.3%) than in women (28.5%). Significantly (P = 0.047) more women (68.4%) than men (53.0%) reported sexual abuse. 87.5% used polypharmacy. Antidepressants were significantly (P = 0.02) often prescribed to women (76.6%) than men (69.1%). Significantly (P = 0.02) more women (83.5%) than men (67.6%) were on antipsychotics. 57.2% of the patients were on anxiolytics, 40.0% on hypnotics and 25.8% on mood stabilisers.

CONCLUSION: EUPD is a complex condition with widespread comorbidity. The term EUPD, Borderline Personality Disorder is unsuitable, stigmatising and too simplistic to reflect the nature, gravity and psychopathology of this syndrome.

PMID:34279863

Anal Chem. 2021 Jul 19. doi: 10.1021/acs.analchem.1c00596. Online ahead of print.

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to ravage the world, with many hospitals overwhelmed by the large number of patients presenting during major outbreaks. A rapid triage for COVID-19 patient requiring hospitalization and intensive care is urgently needed. Age and comorbidities have been associated with a higher risk of severe COVID-19 but are not sufficient to triage patients. Here, we investigated the potential of attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy as a rapid blood test for classification of COVID-19 disease severity using a cohort of 160 COVID-19 patients. A simple plasma processing and ATR-FTIR data acquisition procedure was established using 75% ethanol for viral inactivation. Next, partial least-squares-discriminant analysis (PLS-DA) models were developed and tested using data from 130 and 30 patients, respectively. Addition of the ATR-FTIR spectra to the clinical parameters (age, sex, diabetes mellitus, and hypertension) increased the area under the ROC curve (C-statistics) for both the training and test data sets, from 69.3% (95% CI 59.8-78.9%) to 85.7% (78.6-92.8%) and 77.8% (61.3-94.4%) to 85.1% (71.3-98.8%), respectively. The independent test set achieved 69.2% specificity (42.4-87.3%) and 94.1% sensitivity (73.0-99.0%). Diabetes mellitus was the strongest predictor in the model, followed by FTIR regions 1020-1090 and 1588-1592 cm^-1. In summary, this study demonstrates the potential of ATR-FTIR spectroscopy as a rapid, low-cost COVID-19 severity triage tool to facilitate COVID-19 patient management during an outbreak.

PMID:34279898 | DOI:10.1021/acs.analchem.1c00596

Ophthalmol Ther. 2021 Jul 19. doi: 10.1007/s40123-021-00375-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the correlation between several ocular parameters (intraocular pressure [IOP], corneal biomechanical properties) and the visual field (VF) mean deviation (VF MD) in eyes with open-angle glaucoma (OAG).

METHODS: We conducted a cross-sectional, observational study in which we measured the IOP with Goldmann applanation tonometry, the central corneal thickness (CCT), and the corneal parameters obtained from the Ocular Response Analyzer® (ORA®) and the Corvis® ST non-contact tonometer, in newly diagnosed and treatment-naïve eyes with OAG, to investigate whether there was any correlation between these ocular parameters and the VF MD.

RESULTS: A total of 51 eyes were analyzed. A statistically significant correlation was found only between the VF MD and corneal hysteresis (CH) (P = 0.003, r² = 0.16) and CCT (P = 0.03, r² = 0.08).

CONCLUSIONS: These results demonstrate that CH and CCT are associated with the amount of VF damage in treatment-naïve OAG eyes.

PMID:34279846 | DOI:10.1007/s40123-021-00375-w

Neuro Endocrinol Lett. 2021 Jul 19;42(3):185-199. Online ahead of print.

ABSTRACT

OBJECTIVES: The effect of short-term psychodynamic psychotherapy in patients with neurotic spectrum disorders may be related with predictive factors such as the severity of the disorder, diagnosis, self-stigma level, personality characteristics, comorbidity with depression and personality disorder, dissociation, and traumatic childhood experience. This study focuses on finding factors related to the effect of short-term psychodynamic psychotherapy in patients with neurotic spectrum disorders.

METHOD: The study was conducted at the Psychotherapeutic ward of the Psychiatric Department in Regional Hospital Liberec from October 2015 to March 2019. The assessment method used at the beginning was the objective and subjective Clinical global impression (objCGI, subjCGI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Dissociative Experience Scale (DES), Liebowitz Social Anxiety Scale (LSAS), Internalized Stigma of Mental Illness (ISMI), Temperament and Character Inventory (TCI), Parental Bonding Style (PBI), Childhood Trauma Questionnaire (CTQ). The 6-week therapeutic program combines group dynamic psychotherapy (4 times a week for 1.5 hours), pharmacotherapy and other therapeutic activities. The primary criterium of therapeutic outcome was the change in objCGI severity, and the secondary criteria were changes in subjCGI, BAI and BDI-II.

RESULTS: A total of 96 hospitalized patients with neurotic spectrum disorder diagnosed according to ICD-10, confirmed with the MINI (MINI-International Neuropsychiatric Interview) were included in the study and filled out the questionnaires’ battery. There was a statistically significant decrease in the anxiety and depression symptoms and an overall decrease in the disorder’s severity during the treatment. At the beginning of the treatment, a higher self-stigma rate was associated with a smaller decrease in anxiety symptoms (BAI) and depression (BDI-II). However, self-stigma is not a factor associated with the change in primary outcome criteria (objCGI change). Initial assessment of objective severity of the disorder (objCGI) and personality factor Novelty Seeking predict the change in objCGI severity.

CONCLUSIONS: Self-stigma predicted the change in anxiety and depressive symptom but not the change of the disorder’s global severity in short-term psychodynamic psychotherapy of patients with a neurotic spectrum disorder.

PMID:34279862

Adv Radiat Oncol. 2021 Jun 4;6(5):100735. doi: 10.1016/j.adro.2021.100735. eCollection 2021 Sep-Oct.

ABSTRACT

PURPOSE: We aimed to evaluate the growth of women within the general radiation oncology (RO) workforce in comparison to the growth among other medical specialties. We also sought to create a predictive model for gender diversity to guide future recruitment efforts.

METHODS AND MATERIALS: We identified 16 medical specialties, including RO, for analyses. We used data from the Association of American Colleges and assessed female representation at 4 time points (2006, 2011, 2016, and 2020). Additionally, we determined characteristics of medical specialties that were predictive of increased gender diversity. We performed univariate statistical analysis with linear regression to evaluate factors predictive of greater gender diversity among the medical specialties in our cohort.

RESULTS: The proportion of women within the represented specialties increased over time. Obstetrics/gynecology (14,750 [2006], 23,921 [2020]; 18.7% absolute growth) and dermatology (3568 [2006], 6329 [2020]; 15.1% absolute growth) experienced the highest absolute growth in female representation between 2006 and 2020. When assessing changes between various time points in RO, the absolute change in female physicians increased by 1.5% between 2006 and 2011, by 2.2% between 2011 and 2016, and by only 0.4% between 2016 and 2020, which was the lowest growth pattern relative to the other 15 specialties. Factors predictive of gender diversity among specialties were lower average step 1 scores (P = .0056), fewer years of training (P = .0078), fewer work hours (P = .046), the availability of a standard third year clerkship for a given specialty (P = .0061), and a high baseline number of female physicians within a specialty (P = .0078). Research activities (P = .099) and interest among matriculating medical students (P = .28) were not statistically significant.

CONCLUSIONS: The percentage of women in RO lags behind other medical specialties and has been notably low in the last few years. Interventions that incorporate novel initiatives proposed within this study may accelerate current recruitment milestones.

PMID:34278054 | PMC:PMC8267431 | DOI:10.1016/j.adro.2021.100735

Contemp Clin Trials Commun. 2021 Jun 29;23:100805. doi: 10.1016/j.conctc.2021.100805. eCollection 2021 Sep.

ABSTRACT

Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

PMID:34278043 | PMC:PMC8261539 | DOI:10.1016/j.conctc.2021.100805

Heliyon. 2021 Jul 1;7(7):e07424. doi: 10.1016/j.heliyon.2021.e07424. eCollection 2021 Jul.

ABSTRACT

BACKGROUND: At the heart in the development of any organization or nation is human resource. Over the years the world over, a sharp increase in too many numbers of qualified persons is being experienced yearly. This has impacted on recruitment and promotion costs to increase immensely, thereby affecting negatively manpower system costs. Dynamic Programming (DP) approach to optimal manpower recruitment and promotion policies for the two grade system has been proposed.

METHODS: Considering the fact that contemporary manpower systems are not limited to just two grades – a kind of “switch-approach” to manpower systems, we first establish the link between a manpower planning problem and a dynamic decision-making process. This linkage resulted to a multistage real-life decision-making problem whose solution demands that decisions be made sequentially at different levels and at different points in time and space. Dynamic Programming is a mathematical technique well appropriate for the optimization of multistage decision problems. This allows us to give a generalization to manpower systems by modifying the model to finite grades which came out to be more robust and actionable, a constrained deterministic Dynamic Programming (CDDP) found to function computationally as the very well-known Wagner-Whitin Model in inventory/production management. Five cost variables associated with manpower planning were identified and used as inputs to the modified deterministic DP model.

RESULTS/RELEVANCE: The data shows yearly recruitments and promotions totaling 507 and 266 staff respectively for a ten-period (year) planning horizon. Total manpower system cost (in ooo’s of Nigerian Naira) occasioned by yearly recruitments and promotions exercises for the period is 11334 (7092 for recruiting, 4100 for promoting, and 142 for overstaffing). Our DP model minimizes the manpower system cost to 9462 making a significant reduction of 1872. The optimal policy for the planning period calls for recruiting and promoting respectively 79 and 41 in period 1 only, 86 and 24 in period 2 for periods 2 and 3, 86 and 46 in period 4 for periods 4 and 5, 89 and 29 in period 6 only, 85 and 70 in period 7 for periods 7 and 8, and 82 and 56 in period 9 for periods 9 and 10.The study will contribute to the growing literature on applications of OR models to problems in manpower planning. The model outcomes would provide the basis for evaluating decision policies aimed at conducting recruitment promptly and to eliminate over-stagnated promotions.

CONCLUSION/FURTHER RESEARCH: We formulate decisions making in a finitely-graded manpower system as a multistage decision-making optimization problem which are best handled by dynamic programming. Five cost variables associated with manpower planning were identified and used as inputs to the modified deterministic DP model. Our model is resolute for minimizing manpower system costs occasioned by recruitments and promotions exercises in a wide range of multi-graded manpower systems instead of just two grades. The study’s limitations and scope for future research work are presented in the end.

PMID:34278026 | PMC:PMC8264120 | DOI:10.1016/j.heliyon.2021.e07424

Clin Transl Radiat Oncol. 2021 Jun 29;30:7-14. doi: 10.1016/j.ctro.2021.06.005. eCollection 2021 Sep.

ABSTRACT

BACKGROUND AND PURPOSE: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up.

MATERIALS AND METHODS: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified.

RESULTS: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, pre-salvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2).

CONCLUSION: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre- and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT.

PMID:34278009 | PMC:PMC8261471 | DOI:10.1016/j.ctro.2021.06.005