SUMO1 and Defective Spermatozoa Correlate with Endogenous Hydrogen Peroxide and Live Birth Outcome in Intrauterine Insemination Cycles for Unexplained Infertility.

This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment.

Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

Background and purpose: This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Materials and methods: Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs. ≥ 5 mm) and different adjuvant treatments (RT vs. CCRT). Results: Median follow-up time, age, and invasion depth were 88.5 months, 57 years, and 14 mm, respectively. More patients undergoing adjuvant CCRT had surgical margins < 5 mm (47.6% vs. 21.5%, p < 0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins ≥ 5 mm, worse LRRFS trends were observed in patients with surgical margins < 5 mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p = 0.06). Conclusion: Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins < 5 mm.

Analysis of Immune-Cell Distribution of Bone Marrow in Patients with Myelodysplastic Syndrome.

Myelodysplastic syndrome (MDS) immunity plays an important role in the proliferation and apoptosis of aberrant cells. Immune dysregulation has been studied in various prognostic subgroups. This study analyzed 60 patients with MDS via multidimensional flow cytometry to evaluate the expression of aberrant markers, such as CD7 and cytoplasmic CD3 on lymphocytes. The Revised International Prognostic Scoring System (IPSS-R) scores were used to classify the patients into risk groups. The results showed a significant downregulation of CyCD3- T cells in low-intermediate versus high-risk patients (p = 0.013). This study is the first to show that a significant decrease in cyCD3- T cells in patients with a lower IPSS-R score may indicate microenvironmental changes conducive to transformation in MDS.

Association of Peripheral Arterial Occlusive Disease and Deep Venous Thrombosis with Risk of Consequent Sepsis Event: A Retrospective Population-Based Cohort Study.

Peripheral artery occlusive disease (PAOD) and deep vein thrombosis (DVT) can cause a variety of acute and chronic vascular complications and put patients at risk of subsequent sepsis. This study aimed to determine whether DVT compared with PAOD patients would increase the risk of sepsis. This study recruited 43,535 patients newly diagnosed as having PAOD and 6932 patients who were newly diagnosed as having DVT from a population of 2 million patients from the Longitudinal Health Insurance Database. Propensity score matching (PSM) between the PAOD and DVT groups was performed for age, sex, comorbidities, and prior antibiotic administration. A total of 4383 patients with PAOD and 4383 patients with DVT were analyzed for risk of sepsis. The incidence density of sepsis per 1000 person years for patients with PAOD was 25.75 (95% CI = 23.90 to 27.74) and 35.61 (95% CI = 33.29 to 38.09) for patients with DVT. After age, sex, associated comorbidities, and antibiotic administration were adjusted for, the risk of sepsis for the DVT group was 1.46-fold (95% CI = 1.32-1.62) higher than that for the PAOD group. In conclusion, patients with DVT were associated with a higher risk of subsequent sepsis than patients with PAOD. Aging was another risk factor.

Repurposing gestrinone for tumor suppressor through P21 reduction regulated by JNK in gynecological cancer.

Endometriosis has been shown to increase the risk of gynecological cancers. However, the effect of gestrinone, a clinical endometriosis drug, on gynecological cancers remains unclear. This study aimed to understand the effect of gestrinone on gynecological cancers. A retrospective study was conducted using the Longitudinal Health Insurance Database 2000 of the Taiwan National Health Insurance Research Database (NHIRD) to observe the risk of gynecological cancers. Medication records from the Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital CSMUH and cancer records from the Taiwan Cancer Registry were collected to analyze the correlation between gestrinone use and gynecological cancers. Subsequently, human cell lines were used to investigate the effect of gestrinone on gynecological cancers. A total of 8330 endometriosis patients were enrolled, and analyses revealed that endometriosis patients had a higher risk of developing ovarian and endometrial cancer. However, the rate of cervical cancer was not statistically different (P = 0.249). Analyses of both the NHIRD and CSMUH databases revealed that gestrinone may reduce the risk of gynecological cancer. Cellular experiments verified the anticancer effects of gestrinone, which effectively and specifically inhibited the growth of HeLa cervical cancer cells, decreased P21 expression via JNK phosphorylation, and induced apoptosis. Combining the results of clinical database analysis and cell experiments, our findings prove that gestrinone has the potential to protect against cancer through regulation of the JNK-P21 axis. Repurposing the anticancer efficacy of gestrinone may be a strategy for targeted therapy in the future.

Association between GnRH Receptor Polymorphisms and Luteinizing Hormone Levels for Low Ovarian Reserve Infertile Women.

The choice of ovarian stimulation protocols in assisted reproduction technology (ART) cycles for low ovarian reserve patients is challenging. Our previous report indicated that the gonadotrophin-releasing (GnRH) agonist (GnRHa) protocol is better than the GnRH antagonist (GnRHant) protocol for young age poor responders. Here, we recruited 269 patients with anti-Müllerian hormone (AMH) < 1.2 ng/mL undergoing their first ART cycles for this nested case-control study. We investigated the genetic variants of the relevant genes, including follicular stimulating hormone receptor (FSHR; rs6166), AMH (rs10407022), GnRH (rs6185), and GnRH receptor (GnRHR; rs3756159) in patients <35 years (n = 86) and patients ≥35 years of age (n = 183). Only the genotype of GnRHR (rs3756159) is distributed differently in young (CC 39.5%, CT/TT 60.5%) versus advanced (CC 24.0%, CT/TT 76.0%) age groups (recessive model, p = 0.0091). Furthermore, the baseline luteinizing hormone (LH) levels (3.60 (2.45 to 5.40) vs. 4.40 (2.91 to 6.48)) are different between CC and CT/TT genotype of GnRHR (rs3756159). In conclusion, the genetic variants of GnRHR (rs3756159) could modulate the release of LH in the pituitary gland and might then affect the outcome of ovarian stimulation by GnRHant or GnRHa protocols for patients with low AMH levels.

Correlation of skin carotenoid levels with embryo development and pregnancy result of in vitro fertilization cycles for couples with unexplained infertility.

Oxidative stress-related DNA damage is a significant pathology for male subfertility and unexplained infertility (UI). Antioxidant supplement by food or nutrition may benefit sperm function of UI couples. However, the role of antioxidant status on fertilization outcome and embryo development for UI couples is not clear. A total of 63 semen samples from UI couples undergoing in vitro fertilization (IVF) treatment (26 pregnant cycles and 37 nonpregnant cycles) were recruited for this prospective observational study. The reactive oxygen species (ROS) levels of sperm cells are detected by a chemiluminescence assay. Total antioxidant capacity (TAC) of seminal plasma is evaluated according to an antioxidant assay kit. The skin carotenoid status in the male partners of UI couples is measured by resonance Raman spectroscopy to determine the antioxidant potential from dietary supplement. The skin carotenoid status (23,115 ± 6,831 vs. 19,432 ± 5,242 Raman intensity, p = .0329 by Mann-Whitney U test) and day 3 good embryo rates (49.6 ± 27.1% vs. 26.8 ± 23.1%, p = .002 by Mann-Whitney U test) are higher in pregnant cycles compared to those in nonpregnant cycles. The local antioxidant capacity (seminal TAC) is closely correlated with fertilization rates (r = .35, p = .005). In contrast, skin carotenoid status is intimately associated with good embryo rates in IVF cycles (r = .34, p = .007). In conclusion, the skin carotenoid status of male partners of UI couples may benefit embryo development and the subsequent pregnancy outcome of IVF treatment. Further investigation about the effect and mechanism of nutritional supplement on embryo development in IVF cycles for UI couples is deserved.

Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer.

The presence of an activating mutation of the Wnt/ß-catenin signaling pathway is found in ~90% of colorectal cancer (CRC) cases. Death domain-associated protein (DAXX), a nuclear protein, interacts with ß-catenin in CRC cells. We investigated DAXX expression in 106 matched sample pairs of CRC and adjacent normal tissue by Western blotting. This study evaluated DAXX expression and its clinical implications in CRC. The results revealed that DAXX expression was significantly lower in the patients with the positive serum carcinoembryonic antigen (CEA) screening results compared to the patients with negative CEA screening levels (p < 0.001). It has been reported that CD24 is a Wnt target in CRC cells. Here, we further revealed that DAXX expression was significantly correlated with CD24 expression (rho = 0.360, p < 0.001) in 106 patients. Consistent with this, in the CEA-positive subgroup, of which the carcinomas expressed DAXX at low levels, they were significantly correlated with CD24 expression (rho = 0.461, p < 0.005). Therefore, reduced DAXX expression is associated with reduced CD24 expression in CRC. Notably, in the Hct116 cells, DAXX knockdown using short-hairpin RNA against DAXX (shDAXX) not only caused significant cell proliferation, but also promoted metastasis. The DAXX-knockdown cells also demonstrated significantly decreased CD24 expression, however the intracellular localization of CD24 did not change. Thus, DAXX might be considered as a potential regulator of CD24 or ß-catenin expression, which might be correlated with proliferative and metastatic potential of CRC.

Site-Directed Alkylation Detected by In-Gel Fluorescence (SDAF) to Determine the Topology Map and Probe the Solvent Accessibility of Membrane Proteins.

The topology of helix-bundle membrane proteins provides low-resolution structural information with regard to the number and orientation of membrane-spanning helices, as well as the sidedness of intra/extra-cellular domains. In the past decades, several strategies have been developed to experimentally determine the topology of membrane proteins. However, generally, these methods are labour-intensive, time-consuming and difficult to implement for quantitative analysis. Here, we report a novel approach, site-directed alkylation detected by in-gel fluorescence (SDAF), which monitors the fluorescent band shift caused by alkylation of the EGFP-fused target membrane protein bearing one single introduced cysteine. In-gel fluorescence provides a unique readout of target membrane proteins with EGFP fusion from non-purified samples, revealing a distinct 5 kDa shift on SDS-PAGE gel due to conjugation with mPEG-MAL-5K. Using the structurally characterised bile acid transporter ASBTNM as an example, we demonstrate that SDAF generates a topology map consistent with the crystal structure. The efficiency of mPEG-MAL-5K modification at each introduced cysteine can easily be quantified and analysed, providing a useful tool for probing the solvent accessibility at a specific position of the target membrane protein.

High Glucose Concentrations Negatively Regulate the IGF1R/Src/ERK Axis through the MicroRNA-9 in Colorectal Cancer.

Studies have revealed that people with hyperglycemia have a high risk of colorectal cancer (CRC). Hyperglycemia may be responsible for supplying energy to CRC cells. However, the potential molecular mechanism for this association remains unclear. Furthermore, microRNA-9 (miR-9) has a tumor-suppressive function in CRC. Aberrant reduced expression of miR-9 is involved in the development and progression of malignancy caused by a high glucose (HG) concentration. In this study, we used an HG concentration to activate miR-9 downregulation in CRC cells. Our results indicated that miR-9 decreased the insulin-like growth factor-1 receptor (IGF1R)/Src signaling pathway and downstream cyclin B1 and N-cadherin but upregulated E-cadherin. The HG concentration not only promoted cell proliferation, increased the G1 population, and modulated epithelial-to-mesenchymal transition (EMT) protein expression and morphology but also promoted the cell migration and invasion ability of SW480 (low metastatic potential) and SW620 (high metastatic potential) cells. In addition, low glucose concentrations could reverse the effect of the HG concentration in SW480 and SW620 cells. In conclusion, our results provide new evidence for multiple signaling pathways being regulated through hyperglycemia in CRC. We propose that blood sugar control may serve as a potential strategy for the clinical management of CRC.

Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus among nasal carriage strains isolated from emergency department patients and healthcare workers in central Taiwan.

BACKGROUND AND OBJECTIVE: Screening and identification of methicillin-resistant Staphylococcus aureus (MRSA) carriage are helpful for controlling MRSA dissemination in hospitals. The aim of our study was to determine the prevalence of nasal carriages and diversity of MRSA among patients and healthcare workers (HCWs) at two regional hospitals in Taiwan. METHODS: Nasal swabs were obtained prospectively from 204 patients visiting the emergency department (ED) and 326 HCWs in two regional hospitals in Changhua, Taiwan, between February 2015 and June 2015. All the MRSA isolates were further molecularly characterized. RESULTS: Of the 204 participating patients, the nasal carriage rates of S. aureus and MRSA were 22.1% and 7.8%, respectively. For HCWs, the S. aureus and MRSA carriage rates were 26.1% and 6.1%, respectively. There was no statistically significant difference in MRSA carriage rate between patients and HCWs (P = 0.447). Patients receiving hemodialysis were significantly associated with MRSA colonization (P = 0.012). The leading three sequence types (ST) were ST59 (16, 44.4%), ST45 (11, 30.6%), and ST239 (3, 8.3%) for all 36 MRSA isolates. ST59/SCCmec IV/t437/PVL-negative and ST45/SCCmec V/t1081/PVL-negative were the predominant clones among HCWs (30%) and participating patients (19%), respectively. CONCLUSION: Overall, a substantial proportion of patients visiting the ED and HCWs harbored CA-MRSA, mostly ST59 strains, in their nares. It is noteworthy that MRSA ST45 strains supplanted ST239 as the second leading nasal MRSA colonization strain in our study.

Association of progesterone production with serum anti-Müllerian hormone levels in assisted reproductive technology cycles with corifollitropin alfa.

The use of corifollitropin alfa (CA) in assisted reproductive technology (ART) cycles is dependent on the antral follicle count and body weight of patients. The present study investigated the safety and efficacy of using 100µg of CA in predicted excessive responders based on serum anti-Mullerian hormone (AMH) level. The results of 381 ART cycles stimulated by CA versus daily recombinant follicle-stimulation hormone (rFSH) in patients with low (<1.0 ng/mL; n = 38 vs. n = 90), moderate (1.0-3.36 ng/mL; n = 38 vs. n = 95), and high (> 3.36 ng/mL; n = 48 vs. n = 72) serum AMH levels, were analyzed. Pregnancy and live birth rates did not significantly differ between CA and daily rFSH groups. In the patients with high AMH levels, serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) injection were significantly lower in the CA group than in the rFSH group (0.93 ± 0.55 vs. 1.16 ± 0.64 ng/mL). Furthermore, serum P4 levels on the day of hCG injection were negatively correlated with baseline AMH levels in the CA group, but not in the rFSH group, in the patients with high AMH levels. In conclusion, the use of 100 µg of CA in patients with high AMH levels is safe and effective and is associated with a lower P4 level on the day of hCG injection compared with the use of daily rFSH.

GnRH agonist long protocol versus GnRH antagonist protocol for various aged patients with diminished ovarian reserve: A retrospective study.

This retrospective analysis compared the efficiency of the gonadotropin- releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the GnRH agonist long (GnRH-a) protocol for patients with diminished ovarian reserve (DOR). A total of 1,233 patients with DOR (anti-Mullerian hormone <1.1 ng/mL) were recruited for this retrospective case-control study. They were divided into two groups according to female age. Younger patients were assigned to POSEIDON group3 (PG3: age ≤35 years); older patients were assigned to POSEIDON group 4 (PG4: age >35 years). All patients with DOR underwent controlled ovarian stimulation and fresh embryo transfer (ET) on day 3. We recruited 283 GnRH-a and 54 GnRH-ant cycles for PG3, and 663 GnRH-a and 233 GnRH-ant cycles for PG4. In PG3, the GnRH-a protocol was associated with a lower ET cancellation rate (30/283 = 10.2% vs. 12/54 = 22.2%, p = 0.018) and a higher live birth rate (7/54 = 13.0% vs. 78/283 = 27.6%, p = 0.024) than the GnRH-ant protocol for the initiated cycles. Furthermore, the GnRH-a protocol was correlated with a higher implantation rate than the GnRH-ant protocol for ET cycles (146/577 = 25.3% vs. 11/103 = 10.7%, P = 0.027). No differences in the ET cancellation rate, live birth rate and implantation rate between GnRH-a and GnRH-ant groups were observed among PG4 patients. In conclusion, the GnRH-a protocol was more effective than the GnRH-ant protocol for young patients with DOR. The low ET cancellation rate and high implantation rate may be related to embryo quality or endometrial receptivity, which warrant further investigation.

Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex.

Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex. These and other associated changes in DNA conformation allow the formation of a minor groove pocket for tight binding of the second echinomycin molecule. We also show that echinomycin displays enhanced cytotoxicity against mismatch repair-deficient cell lines, raising the possibility of repurposing the drug for detection and treatment of mismatch repair-deficient cancers.

Correlation of serum anti-Mullerian hormone to follicular follicle stimulating hormone and implantation potential of the ensuing embryos.

Serum anti-Mullerian hormone (AMH) is a predictor of the pregnancy outcome in assisted reproductive technology (ART) cycles, particularly for older women. This study attempts to elucidate the effect of serum AMH on follicular hormone profiles and implantation outcome of the ensuing embryos in ART cycles. A total of 412 patients undergoing ART cycles at a private infertility center were included and 780 follicular fluid samples were collected. Levels of follicular hormones, including FSH, LH, inhibin B, AMH, estradiol, progesterone, and androstenedione were measured. The implantation outcome of the ensuing embryos was traced as a main outcome measure. We demonstrated that the follicular levels of estradiol, progesterone, and androstenedione were considerably similar, but the overall implantation rates increased as the serum AMH increased. Logistic regression analysis revealed that the best predictor for embryo implantation was follicular FSH (>9.64mIU/mL, odds ratio [OR] 0.9). Furthermore, serum AMH (Spearman's rho=-0.352) and female age (rho=0.369) are correlated with follicular FSH levels in those follicles. In conclusion, the serum AMH might affect follicular hormone profiles by interaction with gonadotrophin rather than with steroidogenesis. The follicular FSH levels are correlated with the implantation potential of the ensuing embryos.

Aplastic anemia and risk of deep vein thrombosis and pulmonary embolism: A nationwide cohort study.

OBJECTIVES: Deep vein thrombosis (DVT) and pulmonary embolism (PE) constitute venous thromboembolism (VTE), which is not fully known in aplastic anemia (AA). Therefore, we investigated the incidence and risk of VTE in AA patients. METHODS: We conducted a nationwide cohort study to investigate the risk of DVT and PE in patients with AA. We identified patients with newly diagnosed AA as the AA cohort between 2000 and 2010 from the National Health Insurance Research Database (NHIRD). The initial admission date for AA diagnosis was set as the index date. For each patient with AA, 4 patients without a history of AA, frequency matched by sex, age (every 5-y span), and year of index date, were the non-AA cohort. All patients were followed from the index date to the date of DVT or PE diagnosis, withdrawal from the NHIRD, or the end of 2011. Cox models were used to evaluate the risk of developing DVT and PE in the AA cohort. RESULTS: We included 4001 and 15,998 patients in the AA and non-AA cohorts, respectively, and the overall incidence densities of VTE were significantly higher in the AA cohort than in the non-AA cohort (42.3 vs 10.2 per 10,000person-years). The AA cohort had a 2.56-fold higher risk of VTE (95% confidence interval [CI]=1.81-3.63) than did the non-AA cohort. CONCLUSION: This nationwide cohort study indicated that AA is associated with increased incidence and risk of VTE.

Effects of Synthetic Serum Supplementation in Sperm Preparation Media on Sperm Capacitation and Function Test Results.

Albumin supplementation of culture media induces sperm capacitation in assisted reproduction technique cycles. Synthetic serum supplementation is clinically used to replace albumin for preventing transmission of infectious agents. However, the effects of synthetic serum supplementation on sperm capacitation have rarely been investigated. Spermatozoa from 30 men with normal basic semen analysis results were collected, divided into five aliquots, and cultured in capacitating conditions in four combinations of two synthetic serum supplements, serum substitute supplement (SSS) and serum protein substitute (SPS), and two fertilization media, Quinns Advantage™ Fertilization (QF) and human tubular fluid (HTF) media. Reactive oxygen species (ROS) levels in spermatozoa were measured through chemiluminescence. Furthermore, acrosome reaction and western blotting for tyrosine phosphorylation were used to evaluate sperm capacitation. HTF+SSS had significantly higher ROS levels than QF+SPS did (11,725 ± 1,172 versus 6,278 ± 864 relative light units). In addition, the spermatozoa cultured in QF+SPS had lower motility, acrosome reaction rates, and tyrosine phosphorylation levels compared with those cultured in HTF+SSS. In conclusion, the effects of synthetic serum supplementation on sperm capacitation varied according to the combination of media. These differences may lead to variations in spermatozoon ROS levels, thus affecting sperm function test results.

Potentially Inappropriate Prescribing in Disabled Older Patients with Chronic Diseases: A Screening Tool of Older Persons' Potentially Inappropriate Prescriptions versus Beers 2012 Criteria.

OBJECTIVE: To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. SUBJECTS AND METHODS: One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. RESULTS: Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). CONCLUSION: This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications.

Impacts of microRNA gene polymorphisms on the susceptibility of environmental factors leading to carcinogenesis in oral cancer.

BACKGROUND: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60). CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.