Surgically Managed Gastrointestinal Stromal Tumors: A Comparative and Prognostic Analysis

BACKGROUND: Tyrosine kinase inhibitors have been shown to have marked clinical efficacy in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). We performed a comparative and prognostic analysis of our experience with surgically managed GIST to determine factors associated with adverse oncologic outcomes. METHODS: Oncologic outcomes of 191 patients with primary GIST surgically managed between 1978 and 2004 at a single institution were reviewed. Prognostic factors were analyzed by Cox analysis (hazard ratio [HR] and 95% confidence interval [95% CI]) and included age, sex, disease presentation (asymptomatic vs. symptomatic), tumor site (stomach, small bowel, colorectal), disease extent (localized vs. metastatic) and risk levels (high, intermediate, low, very-low) assigned on the basis of size and number of mitoses according to current National Institutes of Health recommendations. Primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: A total of 186 patients (97%) had c-kit-positive GIST. There were 54% high, 22% intermediate, 18% low, and 8% very low risk GIST originating from the stomach (54%), small bowel (36%), and colon and rectum (10%). Median patient age was 65 (range, 13-91) years, and 108 subjects (57%) were male. Seventy-two percent of patients had symptomatic local disease, and 21% patients had synchronous metastases. Most (95%) underwent R0 resections of their primary tumor. Among 146 patients (76%) with localized disease at presentation undergoing R0 resection, the 5-year DFS was 65%. High-risk GIST (HR 12, 95% CI, 5-32, P < .0001), symptomatic presentation (HR 2.5, 95% CI, 1.1-6, P = .04), and GIST in the small bowel (HR 2.8, 95% CI, 1-5, P = .003) were independently associated with decreased DFS. After a median follow-up of 63 months among survivors, the 5-year DSS was 68%. High-risk disease (HR 14.3, 95% CI, 5-41, P < .0001), symptomatic presentation (HR 3.1, 95% CI, 1.2-7.9, P = .02), and GIST in the small bowel (2.6,3 95% CI, 1-5, P = .006) were independently associated with decreased DSS. CONCLUSIONS: High-risk GIST are associated with increased disease recurrence and decreased survival despite complete surgical resection. These patients should receive adjuvant therapy in the form of tyrosine kinase inhibitors.     

Evidence-Based Recommendations for the Assessment and Management of Sleep Disorders in Older Persons

Sleep-related disorders are most prevalent in the older adult population. A high prevalence of medical and psychosocial comorbidities and the frequent use of multiple medications, rather than aging per se, are major reasons for this. A major concern, often underappreciated and underaddressed by clinicians, is the strong bidirectional relationship between sleep disorders and serious medical problems in older adults. Hypertension, depression, cardiovascular disease, and cerebrovascular disease are examples of diseases that are more likely to develop in individuals with sleep disorders. Conversely, individuals with any of these diseases are at a higher risk of developing sleep disorders. The goals of this article are to help guide clinicians in their general understanding of sleep problems in older persons, examine specific sleep disorders that occur in older persons, and suggest evidence- and expert-based recommendations for the assessment and treatment of sleep disorders in older persons. No such recommendations are available to help clinicians in their daily patient care practices. The four sections in the beginning of the article are titled, Background and Significance, General Review of Sleep, Recommendations Development, and General Approach to Detecting Sleep Disorders in an Ambulatory Setting. These are followed by overviews of specific sleep disorders: Insomnia, Sleep Apnea, Restless Legs Syndrome, Circadian Rhythm Sleep Disorders, Parasomnias, Hypersomnias, and Sleep Disorders in Long-Term Care Settings. Evidence- and expert-based recommendations, developed by a group of sleep and clinical experts, are presented after each sleep disorder.     

An Experimental Investigation of Static Properties of Bio-Oils and SAE40 Oil in Journal Bearing Applications

Considerable research has been conducted in the past decade and a half regarding the bio-lubricants potential to replace mineral-based lubricants as mainstream lubricants such as engine oil, hydraulic oil, compressor oil, and metalworking oil. This study studied several bio-lubricants (rapeseed oil, palm olein, and soybean oil) and a mineral-based lubricant, SAE40. The bio-lubricants have better physiochemical, tribological characteristics and environmental friendly nature, and are promising to replace mineral-based lubricants. In this study, a journal bearing test rig (JBTR) was developed in order to investigate the effect of journal speed on the temperature of oil film with time. Additionally, the load-carrying capacity of bio-oils was tested against the mineral-based lubricant SAE40 by adding a load on the journal. For all three speeds, i.e., 1000, 1500, and 2000 rpm, the bio-lubricants recorded minimum temperature. At 1000 rpm, rapeseed oil recorded a 9.2% lower temperature than SAE40. Similarly, at 2000 rpm, rapeseed oil recorded a minimum temperature that was 2.5% lower than SAE40; in comparison, at 1500 rpm, palm olein recorded a minimum temperature that was 1.8% less than SAE40. Overall, the results of this study revealed that bio-oils recorded a lower temperature rise than mineral oil. These results are very encouraging for further research in this area.     

Development of Therapeutic and Prophylactic Zinc Compositions for Use against COVID-19: A Glimpse of the Trends,Inventions, and Patents

Zinc is an essential nutrient for human health; it is involved in the catalytic, structural, and regulatory functions of the human cellular system. Different compositions of zinc, as well as its pharmaceutically acceptable salts, are available on the market. Recent studies have demonstrated the role of zinc in combating COVID-19. It has been determined that zinc prevents the entry of SARS-CoV-2 into cells by lowering the expression of ACE-2 receptors and inhibiting the RNA-dependent RNA polymerase of SARS-CoV-2. Zinc also prevents the cytokine storm that takes place after the entry of SARS-CoV-2 into the cell, via its anti-inflammatory activity. The authors believe that no study has yet been published that has reviewed the trends, inventions, and patent literature of zinc compositions to treat/prevent COVID-19. Accordingly, this review has been written in order to fill this gap in the literature. The information about the clinical studies and the published patents/patent applications was retrieved from different databases. This review covers patent literature on zinc compositions up to 31 January 2022. Many important patents/patent applications for zinc-based compositions filed by innovative universities and industries were identified. The patent literature revealed zinc compositions in combination with zinc ionophores, antioxidants, antivirals, antibiotics, hydroxychloroquine, heparin, ivermectin, and copper. Most of these studies were supported by clinical trials. The patent literature supports the potential of zinc and its pharmaceutical compositions as possible treatments for COVID-19. The authors believe that countless zinc-based compositions are still unexplored, and there is an immense opportunity to evaluate a considerable number of the zinc-based compositions for use against COVID-19.     

Synthesis of Novel Pyrimidin‐4‐One Bearing Piperazine Ring‐Based Amides as Glycogen Synthase Kinase‐3β Inhibitors with Antidepressant Activity

Novel pyrimidin‐4‐one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase‐3β (GSK‐3β) inhibitors. Among all the synthesized compounds, compound 5 (3‐methyl‐6‐phenyl‐2‐(piperazin‐1‐yl)‐3,4‐dihydropyrimidin‐4‐one) exhibited the most potent inhibitory activity against GSK‐3β with IC₅₀ value of 74 nm . The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val‐135 to the active site of GSK‐3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK‐3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK‐3β with antidepressant activity.     

Self-reported differences between oral health attitudes of pre-clinical and clinical students at a dental teaching institute in Saudi Arabia

ObjectiveTo compare the attitudes of preclinical and clinical dental students toward their own oral health using the Hiroshima University-Dental Behavioral Inventory (HU-DBI).MethodsThe English-language version of the 20-item HU-DBI was distributed to all preclinical and clinical students at the College of Dentistry, University of Dammam, Kingdom of Saudi Arabia. Dichotomized (agree/disagree) responses to 12 HU-DBI items were used in this study, with a maximum possible score of 12. Responses to the remaining eight statements reflected general oral health attitudes and were excluded from the analysis. Data were analyzed statistically.ResultsThe overall response rate was 72.2% (preclinical, 72.5%; clinical, 72%). The mean HU-DBI score was significantly higher among clinical than among preclinical dental students (7 vs. 5.8; P < 0.05). Higher proportions of preclinical than clinical students did not worry about visiting the dentist but postponed dental visits until they experienced toothache. Furthermore, more preclinical than clinical students reported that their gums bled upon brushing, used a child-sized toothbrush, had observed white, sticky deposits on their teeth, and used strong strokes for toothbrushing. More clinical than preclinical students reported that they did not feel that the condition of their teeth was worsening despite brushing, worried about the color of their teeth, brushed each of their teeth carefully, and checked their teeth in the mirror after brushing.ConclusionsDental health awareness programs should be implemented and information about positive oral health attitudes should be provided to the students at an initial stage of dental training.     

Biomonitoring of DNA damage in individuals exposed to brick kiln pollution from Peshawar,Khyber Pakhtunkhwa,Pakistan

Different kinds of harmful raw materials are used in brick kilns for baking bricks, thus exerting negative effects on the health of brick kiln workers and nearby residents. The comet assay technique monitors DNA damage in lymphocytes of brick kiln workers. Blood samples were collected from 150 participants to conduct comet assay. The results indicated a highly significant increase (p < .0001) in DNA damage in brick kiln workers (171.9 ± 62.1) as compared with the control group (101.9 ± 48.3). Duration of occupational exposure had positive correlation (r = .823, p < .05) with DNA damage. Age and tobacco use had significant effects on total comet score (TCS) of exposed group as compared to control group (p < .05). In summary, these findings indicate greater genotoxicity in brick kiln workers.