Machine-Learning-Based Identification of Key Feature RNA-Signature Linked to Diagnosis of Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the third prime cause of malignancy-related mortality worldwide. Early and accurate identification of HCC is crucial for good prognosis, efficacy of therapy, and survival rates of the patients. We aimed to develop a machine-learning model incorporating differentially expressed RNA signatures with laboratory parameters to construct an RNA signature-based diagnostic model for HCC. Methods: We have used five classifiers (KNN, RF, SVM, LGBM, and DNNs) to predict the liver disease (HCC). The classifiers were trained on 187 samples and then tested on 80 samples. The model included 22 features (age, sex, smoking, cirrhosis, non-cirrhosis, albumin, ALT, AST bilirubin (total and direct), INR, AFP, HBV Ag, HCV Abs, RQmiR-1298, RQmiR-1262, RQmiR-106b-3p, RQmRNARAB11A, and RQSTAT1, RQmRNAATG12, RQLnc-WRAP53, RQLncRNA- RP11-513I15.6). Results: LGBM achieved the highest accuracy of 98.75% in predicting HCC among all models surpassing Random Forest (96.25%), DNN (91.25%), SVC (88.75%), and KNN (87.50%). Conclusion: Our machine-learning model incorporating the expression data of RAB11A/STAT1/ATG12/miR-1262/miR-1298/miR-106b-3p/lncRNA-RP11-513I15.6/lncRNA-WRAP53 signature and clinical data represents a potential novel diagnostic model for HCC.

Phytochemicals in cervical cancer: an epigenetic overview.

Cervical cancer is the fourth most common female malignancy worldwide and a complex disease that typically starts with HPV infection. Various genetic and epigenetic alterations are implicated in its development. The current cervical cancer therapies have unsatisfactory outcomes due to their serious adverse effects, necessitating the need for safe, effective preventive and therapeutic modalities. Phytochemicals have been addressed in cervical cancer prevention and treatment, and further understanding the epigenetics of cervical cancer pathogenesis is critical to investigate new preventive and therapeutic modalities. Addressing the epigenetic mechanisms of potential phytochemicals will provide an overview of their use individually or in combination. The primary aim of this review is to highlight the epigenetic effects of the phytochemicals addressed in cervical cancer therapy.

Hyperuricemia and Gout: The Role of Losartan.

Losartan is the only angiotensin II receptor blocker that has shown to significantly lower uric acid levels. The addition of or switch to losartan as an antihypertensive agent for patients with gout is recommended by clinical guidelines because of its benefit as a uricosuric agent.

COGMED working memory training in children with Attention Deficit/Hyperactivity Disorder (ADHD): A feasibility study in Saudi Arabia.

Working memory training has been proven effective for improving cognitive functioning in patients with Attention Deficit/Hyperactivity Disorder (ADHD). However, the feasibility of this type of training for children in Saudi Arabia has not been previously explored. We investigated the feasibility of implementing Cogmed Working Memory Training (CWMT) in a sample of 29 Saudi children with ADHD. We found no significant demographic or clinical differences between compliant and noncompliant children. Although compliant children were initially better at following instructions and reported better improvements in working memory and math skills compared to those who did not complete the CWMT, all children who participated in the program showed improvements in performing the CWMT tasks. Most parents found the Cogmed training feasible for their children, were satisfied and keen to continue with the program, and felt the training helped them to address their problems. Most children did not encounter any difficulties in using the software, and many families were, therefore, likely to continue using the techniques from the program. We conclude that CWMT for children with ADHD is feasible in Saudi Arabia. Larger case-controlled studies are needed to thoroughly investigate the effects of CWMT compared to other interventions in Saudi children with ADHD.

Alpha Blocker-Associated Intraoperative Floppy Iris Syndrome.

Objective To evaluate the literature related to the use of alpha1-blockers and the risk of intraoperative floppy iris syndrome (IFIS), particularly in cataract surgery. IFIS is characterized by floppiness or billowing of the iris, iris prolapse, and progressive miosis, possibly leading to severe complications. It is thought to be associated with adrenergic alpha-1 receptor antagonists commonly used to treat lower urinary tract symptoms in patients with benign prostatic hyperplasia. Data Sources A literature search was conducted in Pubmed, EMBASE, and Web of Science through May 2021 with MeSH terms and keywords 'intraoperative floppy iris syndrome,' ' adrenergic alpha-1 receptor antagonists,' and 'cataract surgery.' Study Selection and Data Extraction Relevant articles were reviewed and included. In addition, reference lists from identified publications were reviewed to identify additional reports and studies of interest. Data Synthesis Numerous reports have linked IFIS to multiple risk factors including age, gender, hypertension, and the use of adrenergic alpha-1 receptor antagonists, most notably tamsulosin. Tamsulosin selectively blocks the adrenergic alpha-1 receptor in the iris dilator muscle, preventing mydriasis during cataract surgery. Other adrenergic alpha-1 receptor antagonists, including terazosin, doxazosin, alfuzosin, and sildosin, have also been linked to IFIS; however, their relationship to IFIS is not as well defined. Conclusion Patients should be educated regarding potential adverse effects and discuss this with their health care providers prior to cataract surgery. In addition, health care providers should be aware of the adverse effect and take steps to reduce the risk of surgical complications.

Predictive urinary RNA biomarkers of kidney injury after extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is considered one of the best choices for the treatment of various kinds of urinary tract calculi, although it might cause acute kidney injury. OBJECTIVE: To measure the urinary long non-coding RNA-messenger RNA (LncRNA-mRNA) panel before and after ESWL to evaluate post-ESWL renal injury in a reliable and non-invasive method. PATIENTS AND METHODS: The study included 60 patients with renal stones treated with ESWL and 30 healthy volunteers. Voided urine samples were obtained before, 2 h, and 1 day after ESWL. We measured the urinary level of LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) by real-time qPCR and compared the results with serum creatinine and eGFR. RESULTS: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were higher in patients with renal stones when compared with healthy volunteers. They showed a statistically significant increase in the level of LncRNA-mRNA panel in baseline and after ESWL treatment. CONCLUSION: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were significantly elevated following ESWL treatment, highlighting the usefulness of urinary biomarkers in identifying patients at higher risk of developing renal injury after ESWL treatment.

Circulatory Endothelin 1-Regulating RNAs Panel: Promising Biomarkers for Non-Invasive NAFLD/NASH Diagnosis and Stratification: Clinical and Molecular Pilot Study.

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4).

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study.

BACKGROUND: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. METHODS: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients' sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. RESULTS: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. CONCLUSION: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

A Review of Working Memory Training in the Management of Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Working memory deficits underlie many of the behavioural symptoms of ADHD. Alongside psychostimulant medications, strategies to improve working memory may play an important adjuvant role in the management of ADHD. In this study, we review the role of working memory deficits in ADHD, the evidence surrounding working memory training strategies in the management of the condition, and the factors affecting the success of these strategies in alleviating ADHD symptoms. More specifically, we review several non-pharmacological interventions that target working memory deficits in ADHD, with special emphasis on cognitive working memory training. We conclude that the development of evidence-based interventions such as computerised cognitive training (CCT) could provide an alternative or adjunct to the use of psychostimulants, especially in cases where side effects are a major issue.

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. METHOD: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. RESULTS: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. CONCLUSION: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

New insight into the role of isorhamnetin as a regulator of insulin signaling pathway in type 2 diabetes mellitus rat model: Molecular and computational approach.

We intended to examine the molecular mechanism of action of isorhamnetin (IHN) to regulate the pathway of insulin signaling. Molecular analysis, immunofluorescence, and histopathological examination were used to assess the anti-hyperglycemic and insulin resistance lowering effects of IHN in streptozotocin /high fat diet-induced type 2 diabetes using Wistar rats. At the microscopic level, treatment with IHN resulted in the restoration of myofibrils uniform arrangement and adipose tissue normal architecture. At the molecular level, treatment with IHN at three different doses showed a significant decrease in m-TOR, IGF1-R & LncRNA-RP11-773H22.4. expression and it up-regulated the expression of AKT2 mRNA, miR-1, and miR-3163 in both skeletal muscle and adipose tissue. At the protein level, IHN treated group showed a discrete spread with a moderate faint expression of m-TOR in skeletal muscles as well as adipose tissues. We concluded that IHN could be used in the in ameliorating insulin resistance associated with type 2 diabetes mellitus.

Pharmacy students' attitudes and perceptions toward pharmacogenomics education.

PURPOSE: To evaluate final-year pharmacy students' perceptions toward pharmacogenomics education, their attitudes on its clinical relevance, and their readiness to use such knowledge in practice. METHODS: A 19-question survey was developed and modified from prior studies and was pretested on a small group of pharmacogenomics faculty and pharmacy students. The final survey was administered to 978 final-year pharmacy students in 8 school/colleges of pharmacy in New York and New Jersey between January and May 2017. The survey targeted 3 main themes: perceptions toward pharmacogenomics education, attitudes toward the clinical relevance of this education, and the students' readiness to use knowledge of pharmacogenomics in practice. RESULTS: With a 35% response rate, the majority (81%) of the 339 student participants believed that pharmacogenomics was a useful clinical tool for pharmacists, yet only 40% felt that it had been a relevant part of their training. Almost half (46%) received only 1-3 lectures on pharmacogenomics and the majority were not ready to use it in practice. Survey results pointed toward practice-based trainings such as pharmacogenomics rotations as the most helpful in preparing students for practice. CONCLUSIONS: Final-year student pharmacists reported varying exposure to pharmacogenomics content in their pharmacy training and had positive attitudes toward the clinical relevance of the discipline, yet they expressed low confidence in their readiness to use this information in practice.

Intravenous Olanzapine for the Management of Agitation: Review of the Literature.

Objective: The purpose of this review is to summarize the current evidence of the off-label use of intravenous (IV) olanzapine and discuss its risks versus benefits for the management of agitation. Data Sources: A literature search was conducted to gather relevant data regarding IV use of olanzapine for the management of acute agitation. PubMed, EMBASE, MEDLINE, and IPA were searched using the keywords and MESH terms: olanzapine, intravenous, IV, off-label, and agitation. Study Selection and Data Extraction: All case reports, and retrospective and prospective studies evaluating the efficacy and safety of IV olanzapine administration for agitation from January 2004 to December 2018 were analyzed. Data Synthesis: Doses from 2.5 to 10 mg given as an IV bolus (maximum dose of 30 mg/d) have been administered. Rescue medications such as droperidol or parenteral benzodiazepines are sometimes coadministered to assist with achieving adequate sedation. Prospective studies demonstrate efficacy similar to droperidol in achieving adequate sedation within 10 minutes and similar time to onset of sedation. Rates of respiratory depression and airway obstruction are low and similar to that of comparative agents, including intramuscular olanzapine. Relevance to Patient Care and Clinical Practice: This review evaluated the off-label use of IV olanzapine to manage agitation based on case reports, and retrospective and prospective data. Conclusions: The use of IV olanzapine remains controversial in the absence of clear evidence evaluating safety and efficacy. Future studies are warranted comparing IV olanzapine with more commonly utilized and Food and Drug Administration-approved treatment modalities for acute agitation in the emergency department and other settings.

A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat.

This article informs the reader of the current information available on a novel therapeutic agent and new class of drug for the treatment of anemia. The data show promising results for alternative erythropoietin-stimulating agents and offers a time line of when Phase III data will be available. The information on this new drug and new drug class will change how nephrologists approach treating anemia within their patients.

The relationship between the timing of a palliative care consult and utilization outcomes for ventilator-assisted intensive care unit patients.

OBJECTIVE: Given the great number of chronic care patients facing the end of life and the challenges of critical care delivery, there has been emerging evidence supporting the benefit of palliative care in the intensive care unit (ICU). We studied the relationship between the timing of a palliative care consult (PCC) and two utilization outcomes - length of stay (LOS) and pharmacy costs - in ventilator-assisted ICU patients. METHOD: A retrospective chart review was conducted (N = 90). Summed pharmacy costs were compared using a paired t test before and after PCC. Spearman correlations were performed between days to PCC and ICU LOS, ventilator days, and days to death following ventilator discontinuation. RESULTS: Number of days from admission to PCC was correlated with total days on ventilator (ρ = 0.685, p < 0.0001) and total ICU LOS (ρ = 0.654, p < 0.0001). Number of days to PCC was correlated with pre-PCC total medication costs (ρ = 0.539, p < 0.0001). Median medication costs were significantly reduced after the PCC (p < 0.0001), from $230.96 to 30.62. Median medication costs decreased for all categories except for analgesics, antiemetics, and opioids. The number of patients receiving opioid infusion increased (37 vs. 90%) after PCC (p < 0.0001). SIGNIFICANCE OF RESULTS: Earlier timing for PCC in the ICU is associated with a lower LOS through quicker mechanical ventilation (MV) withdrawal, presenting a unique opportunity to both decrease costs and improve patient care.

Does a palliative care consult decrease the cost of caring for hospitalized patients with dementia?

OBJECTIVE: Advanced dementia (AD) is a terminal disease. Palliative care is increasingly becoming of critical importance for patients afflicted with AD. The primary objective of this study was to compare pharmacy cost before and after a palliative care consultation (PCC) in patients with end-stage dementia. A secondary objective was to investigate the cost of particular types of medication before and after a PCC. METHOD: This was a retrospective study of 60 hospitalized patients with end-stage dementia at a large academic tertiary care hospital from January 1, 2010 to October 1, 2011, in order to investigate pharmacy costs before and after a PCC. In addition to demographics, we carried out a comparison of the average daily pharmacy cost and comparison of the proportion of subjects taking each medication type (cardiac, analgesics, antibiotics, antipsychotics and antiemetics) before and after a PCC. RESULTS: There was a significant decrease in overall average daily pharmacy cost from before to after a PCC ($31.16 ± 24.71 vs. $20.83 ± 19.56; p < 0.003). There was also a significant difference in the proportion of subjects taking analgesics before and after PCC (55 vs. 73.3%; p < 0.009), with a significant average daily analgesic cost rise from pre- to post-PCC: $1.36 ± 5.07 (median = $0.05) versus. $2.35 ± 5.35 (median = $0.71), respectively, p < 0.011; average daily antiemetics cost showed a moderate increase from pre- to post-PCC: $0.08 ± 0.37 (median = $0) versus $0.23 ± 0.75 (median = $0), respectively, p < 0.047. SIGNIFICANCE OF RESULTS: Our findings indicate that PCC is associated with overall decreased medication cost in hospitalized AD patients. Additionally, receiving a PCC was related to greater use of pain medications in hospitalized dementia patients. Our study corroborates the benefits of palliative care team intervention in managing elderly hospitalized dementia patients.

Treating persistent pain in the elderly: how do we proceed?

OBJECTIVE: To describe a performance improvement initiative conducted in accordance with the American Geriatrics Society (AGS) guideline regarding pharmacological management of persistent pain in older adults. SETTINGS: Medical units of a tertiary care teaching hospital. PRACTICE DESCRIPTION: Elderly patients were included if treated for conditions associated with persistent pain. PRACTICE INNOVATION: Using three phases, the pharmacological management of persistent pain in older adults was evaluated before and after health care provider education on the AGS guideline recommendations. Educational seminars, in-service training, and handout materials focused on addressing specific shortfalls identified during the initial evaluation. MAIN OUTCOME MEASUREMENTS: Appropriate use of nonsteroidal anti-inflammatory agents (NSAIDs) and cyclooxygenase-2 selective inhibitors (coxibs), utilization of proper pain assessment tools, types of opioids used, and associated adverse effects. RESULTS: A total of 50 patients with comparable demographics were included in each phase. Following education, there was an improvement in the appropriate use of pain-assessment tools in cognitively impaired older adults. There was a trend toward improvement in the use of NSAIDs and coxibs, but there was no change in practice regarding the frequency of opioid use, combining long- and short-acting opioid preparations, or preventing opioid-induced constipation. CONCLUSION: Although findings from this study aided in recognizing areas for improvement in the management of persistent pain in older adults, further education of health care professionals is needed to ensure the safe and effective management of persistent pain.

Impact of geriatric consultation on the number of medications in hospitalized older patients.

OBJECTIVE: This study aims to determine the impact of the geriatric consultation on the number of medications in hospitalized older adults and the corresponding financial impact. DESIGN: Retrospective chart review of patients seen by geriatric consultants. SETTING: Tertiary-care teaching hospital. MAIN OUTCOME MEASURES: The number of medications prescribed before hospitalization, at time of consult, and at discharge, and the number and category of medications adjusted by the geriatrician. The monthly cost of the pharmaceutical interventions was computed based on the drugstore.com cost of acquisition of drugs. RESULTS: A cohort of 62 patients was reviewed with a mean age of 84.6 (± 7.3) years; 79% were women. The patients presented with an average of 5.6 (± 2.1) comorbidities of which hypertension, dementia, and musculoskeletal disorders were the most common. The most common reasons for geriatric consultations were neuropsychiatric, nutritional, and gait-related issues. The geriatric consultant identified 2.96 (± 1.5) additional diagnoses, of which debility, delirium, and pain were the most prevalent. The average number of medications on admission was 7.7 (± 3.7) and at discharge was 9.5 (± 2.12). The average number of medications adjusted by the geriatric consultant was 2.96 (± 2.12). The most common classes of adjusted medications were pain medications (22%), nutrition (13%), bowel regimens (8.5%), antipsychotics (8%), and osteoporosis (8%). The cost impact of the pharmaceutical intervention ranged between -$343 and $2,607, with an average increase of $102 (± 368). CONCLUSION: Geriatric consultations increased the total number of medications and the cost of medications used by elderly patients.

Neuroleptic-induced catatonia in two hospitalized patients.

PURPOSE: To report the cases of 2 hospitalized patients with chronic psychotic disorders who developed neuroleptic-induced catatonia (NIC), a catatonic-extrapyramidal syndrome occurring after administration of a D2-receptor antagonist, and delineate the importance of prompt recognition and treatment. METHODS: Two patients with chronic psychotic disorders were admitted to the hospital for unstable medical conditions at which time their maintenance antipsychotic therapy was discontinued. Following administration of intravenous haloperidol, both patients developed catatonic and extrapyramidal signs. Both patients developed catatonia, rigidity, hyperthermia, leukocytosis, and elevations in creatine kinase. In both cases, the patients met the criteria for catatonia as evidenced by motoric immobility, stupor, mutism, and negativism. The syndrome resolved within a few days of stopping haloperidol and initiation of lorazepam. CONCLUSION: Neuroleptic-induced catatonia is underrecognized and can lead to potentially severe complications, although early recognition and treatment may prevent progression and complications. Previous reports do not underscore the importance of prompt recognition and treatment.

The therapeutic use of vaptans for the treatment of dilutional hyponatremia.

Hyponatremia is a very common electrolyte abnormality. Dilutional hyponatremia is very difficult to treat effectively due to the complications of conventional treatment. Arginine-vasopressin (AVP) plays an integral role in circulatory and water homeostasis. AVP is a hormone released in response to increases in plasma tonicity or decreases in plasma volume in an attempt to maintain the plasma osmolality between 284 and 295 mOsm/L. AVP receptor antagonists or "vaptans" are a new class of drugs that allow for the safe and efficacious treatment of dilutional hyponatremia. Conivaptan, a mixed V1a/V2 receptor antagonist, and tolvaptan, a selective V2 receptor antagonist, are the only 2 vaptans approved by the US Food and Drug Administration.