ABSTRACT
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.
Subject(s)
Kidney Calculi , Lithotripsy , RNA, Long Noncoding , Acute Kidney Injury/etiology , Acute Kidney Injury/urine , Biomarkers/urine , Humans , Kidney/injuries , Kidney/surgery , Kidney Calculi/etiology , Kidney Calculi/therapy , Kidney Calculi/urine , Lithotripsy/adverse effects , NLR Family, Pyrin Domain-Containing 3 Protein/urine , RNA, Long Noncoding/urine , RNA, Messenger/urineABSTRACT
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.
Subject(s)
Antipsychotic Agents/administration & dosage , Off-Label Use , Olanzapine/administration & dosage , Psychomotor Agitation/drug therapy , Antipsychotic Agents/therapeutic use , Humans , Injections, Intravenous , Male , Olanzapine/therapeutic use , Treatment Outcome , United StatesABSTRACT
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.
Subject(s)
Dementia/economics , Dementia/therapy , Hospitalization/economics , Palliative Care/economics , Referral and Consultation/economics , Aged , Aged, 80 and over , Female , Humans , Male , Retrospective StudiesABSTRACT
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.
Subject(s)
Intensive Care Units , Palliative Care , Referral and Consultation , Respiration, Artificial , Terminal Care , Aged , Cost Control , Drug Costs , Female , Humans , Length of Stay/statistics & numerical data , Male , Retrospective Studies , Time Factors , Withholding TreatmentABSTRACT
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.
ABSTRACT
Development of cancer cell resistance, low accumulation of therapeutic drug in the lungs, and severe adverse treatment side effects represent main obstacles to efficient chemotherapy of lung cancer. To overcome these difficulties, we propose inhalation local delivery of anticancer drugs in combination with suppressors of pump and nonpump cellular resistance. To test this approach, nanoscale-based delivery systems containing doxorubicin as a cell death inducer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2 mRNA as a suppressor of nonpump resistance, were developed and examined on an orthotopic murine model of human lung carcinoma. The experimental results show high antitumor activity and low adverse side effects of proposed complex inhalatory treatment that cannot be achieved by individual components applied separately. The present work potentially contributes to the treatment of lung cancer by describing a unique combinatorial local inhalation delivery of drugs and suppressors of pump and nonpump cellular resistance.
Subject(s)
Doxorubicin/therapeutic use , Drug Resistance, Neoplasm , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Oligonucleotides/pharmacology , Administration, Inhalation , Animals , Cell Line, Tumor , Cell Survival/drug effects , Disease Models, Animal , Down-Regulation/drug effects , Doxorubicin/administration & dosage , Drug Delivery Systems , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/genetics , Mice , Mice, Nude , Multidrug Resistance-Associated Proteins/genetics , Oligonucleotides/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2ABSTRACT
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.
Subject(s)
Chronic Pain/drug therapy , Aged , Analgesics, Opioid/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Female , Humans , Male , Pain MeasurementABSTRACT
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.
Subject(s)
Gout , Hyperuricemia , Humans , Hyperuricemia/complications , Hyperuricemia/drug therapy , Losartan/adverse effects , Gout/drug therapy , Antihypertensive Agents/adverse effectsABSTRACT
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.
Subject(s)
Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Epigenesis, Genetic , Phytochemicals/pharmacology , Phytochemicals/therapeutic useABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Cognitive Training , Memory, Short-Term , Child , Female , Humans , Male , Attention Deficit Disorder with Hyperactivity/psychology , Cognitive Training/methods , Feasibility Studies , Feedback , Mathematics , Parents , Patient Compliance , Sample Size , Saudi Arabia , Treatment OutcomeABSTRACT
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.
Subject(s)
Geriatrics , Polypharmacy , Referral and Consultation , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Quality of Life , Retrospective StudiesABSTRACT
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.
Subject(s)
Cataract , Iris Diseases , Adrenergic alpha-1 Receptor Antagonists/adverse effects , Cataract/chemically induced , Humans , Intraoperative Complications/chemically induced , Iris , Iris Diseases/chemically induced , Iris Diseases/diagnosis , Iris Diseases/prevention & control , Sulfonamides/adverse effects , Tamsulosin/adverse effectsABSTRACT
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.
ABSTRACT
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).
Subject(s)
Endothelin-1/metabolism , MicroRNAs/blood , Non-alcoholic Fatty Liver Disease/blood , RNA, Long Noncoding/blood , Biomarkers/blood , Endothelin-1/genetics , Female , Humans , Male , MicroRNAs/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/genetics , RNA, Long Noncoding/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
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.
Subject(s)
Adipose Tissue/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Insulin Resistance , Insulin/blood , Myofibrils/drug effects , Quercetin/analogs & derivatives , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/enzymology , Diabetes Mellitus, Type 2/pathology , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Myofibrils/metabolism , Myofibrils/pathology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Quercetin/pharmacology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Rats, Wistar , Receptor, IGF Type 1/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
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.
ABSTRACT
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.
Subject(s)
Acute Coronary Syndrome/diagnosis , Biomarkers/blood , Gene Expression Regulation , Lysophospholipase , Acute Coronary Syndrome/blood , Humans , MicroRNAs/blood , RNA, Long Noncoding/blood , RNA, Messenger/bloodABSTRACT
OBJECTIVES: Determine the influence of warnings from the Food and Drug Administration (FDA) regarding antipsychotic use for the management of dementia-related psychosis on clinical practice. DESIGN/SETTINGS/PARTICIPANTS: A survey of health care professionals specializing in geriatrics was conducted with the use of a Web-based software program. The questions focused on practitioners' familiarity with recent FDA warnings, perceptions of their validity, and changes in antipsychotic use patterns. Sixty-five geriatric practitioners belonging to major national geriatric organizations completed the survey. INTERVENTION: Responses were reviewed once the survey was closed, six weeks after Web posting. MAIN OUTCOME MEASURE(S): Changes in prescribing practices for the management of dementia-related psychosis in light of the antipsychotic FDA warnings. RESULTS: The majority of participants responded that they were "very familiar" with the FDA warnings. The results indicated that 68% of participants reported using antipsychotic medications in elderly patients with known cerebral/cardiovascular diseases. Forty-nine percent of participants reported that they changed the way they managed elderly patients with dementia-related psychosis based on this notification. The most commonly reported barriers for not taking into consideration the FDA warnings were: no alternative treatment available, lack of guidance, lack of evidence, and poor availability of data. The majority of participants reported the use of atypical antipsychotics more frequently than the typical antipsychotics. CONCLUSIONS: Despite FDA warnings, antipsychotics are still being used for the management of dementia-related psychosis; management of behaviors associated with dementia either through drug therapy or nonpharmacologic interventions remains a challenge.
Subject(s)
Antipsychotic Agents/therapeutic use , Drug Labeling , Practice Patterns, Physicians'/statistics & numerical data , Psychotic Disorders/drug therapy , Aged , Antipsychotic Agents/adverse effects , Dementia/drug therapy , Health Care Surveys , Humans , United States , United States Food and Drug AdministrationABSTRACT
PURPOSE: To enhance the efficacy of cancer treatment, we propose a complex approach: simultaneous delivery to the tumor of a chemotherapeutic agent and a suppressor of hypoxia-inducible factor 1 alpha (HIF1A). EXPERIMENTAL DESIGN: The novel complex liposomal drug delivery system was developed and evaluated in vitro and in vivo on nude mice bearing xenografts of multidrug-resistant human ovarian carcinoma. The proposed novel complex drug delivery system consists of liposomes as a nanocarrier, a traditional anticancer drug (doxorubicin) as a cell death inducer, and antisense oligonucleotides targeted to HIF1A mRNA as a suppressor of cellular resistance and angiogenesis. RESULTS: The system effectively delivers active ingredients into tumor cells, multiplies the cell death signal initiated by doxorubicin, and inhibits cellular defensive mechanisms and angiogenesis by down-regulating BCL2, HSP90, and vascular endothelial growth factor proteins. This, in turn, activates caspases, promotes apoptosis, necrosis, and tumor shrinkage. The proposed novel complex multipronged approach enhances the efficiency of chemotherapy. CONCLUSIONS: The proposed combination therapy prevents the development of resistance in cancer cells, and thus, increases the efficacy of chemotherapy to an extent that cannot be achieved by individual components applied separately. It could form the foundation for a novel type of cancer therapy based on simultaneous delivery of an anticancer drug and a suppressor of HIF1A.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drug Delivery Systems/methods , Hypoxia-Inducible Factor 1, alpha Subunit/drug effects , Oligonucleotides, Antisense/administration & dosage , Ovarian Neoplasms/drug therapy , Animals , Blotting, Western , Cell Line, Tumor , Doxorubicin/administration & dosage , Drug Resistance, Neoplasm , Female , Humans , Mice , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Nanoparticles , Reverse Transcriptase Polymerase Chain Reaction , Xenograft Model Antitumor AssaysABSTRACT
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.