Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank.

BACKGROUND: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. METHODS: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. RESULTS: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores). CONCLUSION: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Comparison of Contralateral Acceleromyography and Electromyography for Posttetanic Count Measurement.

BACKGROUND: Electromyography has advantages over mechanomyography and acceleromyography. Previously, agreement of the train-of-four counts between acceleromyography and electromyography was found to be fair. The objective of this study was to assess the agreement of posttetanic count including agreement of neuromuscular blockade status (intense block, posttetanic count equal to 0; or deep block, posttetanic count 1 or greater and train-of-four count equal to 0) between acceleromyography and electromyography. METHODS: Thirty-six patients, aged 20 to 65 yr, participated in this study. A dose of 0.6 mg/kg rocuronium, with additional dose of 0.3 mg/kg if required, was administered to the patients. The train-of-four and posttetanic counts were monitored in the contralateral arm using electromyography at the first dorsal interosseus or adductor pollicis, and acceleromyography at the adductor pollicis. Posttetanic count measurements were performed at 6-min intervals; the responses were recorded until the train-of-four count reached 1. The authors evaluated the agreement of degree of neuromuscular blockade (intense or deep block) and that of posttetanic count between acceleromyography and electromyography. RESULTS: The authors analyzed 226 pairs of measurements. The percentage agreement indicating the same neuromuscular blockade status (intense or deep block) between acceleromyography and electromyography was 73%. Cohen's kappa coefficient value was 0.26. After excluding data with acceleromyography-posttetanic counts greater than 15, a total of 184 pairs of posttetanic counts were used to evaluate the agreement between the two monitoring methods. For acceleromyography-posttetanic count, 42 (23%) pairs had the same electromyography-posttetanic count, and 93 (50%) pairs had more than the electromyography-posttetanic count. The mean posttetanic count on electromyography was 38% (95% CI, 20 to 51%) lower than that on acceleromyography (P = 0.0002). CONCLUSIONS: Acceleromyography frequently counted more twitches than electromyography in posttetanic count monitoring. Acceleromyography- and electromyography-posttetanic counts cannot be used interchangeably to assess the degree of neuromuscular blockade.

Lymphohematopoietic cancer mortality among Korean semiconductor manufacturing workers.

BACKGROUND: We aimed to examine the lymphohematopoietic cancer mortality in a cohort of workers at a semiconductor manufacturing company in South Korea according to their jobs. METHODS: A retrospective cohort was constructed using the personnel records of semiconductor manufacturing workers who were employed in a semiconductor company in South Korea in 1998-2012. Data on their vital status and causes of death were obtained from the National Statistical Office of South Korea. The standardized mortality ratios (SMRs) of lymphohematopoietic cancer were calculated. RESULTS: A total of 288 deaths were reported, of which 22 were caused by lymphohematopoietic cancer, among 65,782 workers in 878,325 person-years. The SMRs for lymphohematopoietic cancer were 0.78 (95% confidence interval [CI] = 0.39-1.40; the number of observed cases [Obs] = 11) among male workers and 1.71 (95% CI = 0.85-3.06; Obs = 11) among female workers. Among female operators, excess deaths due to lymphohematopoietic cancer (SMR = 2.59, 95% CI = 1.24-4.76) and leukemia (SMR = 2.92, 95% CI = 1.26-5.76) were observed. However, they were not observed among office workers, facility managers, utility managers, or process managers. CONCLUSION: Female operators involved in the semiconductor wafer fabrication process had higher risk of mortality from lymphohematopoietic cancer.

Reliability of submaximal stimulation for the train-of-four test using acceleromyography and electromyography with individualized stimulation currents.

PURPOSE: The supramaximal stimulation (SMS) of the TOF test causes uncomfortable sensations in patients. We aimed to determine whether the submaximal stimulation would be reliable in TOF tests with reduced painful sensation. METHODS: The accelomyography (AMG) and electromyography (EMG) monitor was applied at each arm and general anesthesia was induced and maintained by total intravenous anesthesia. At extubation, we conducted TOF test three times at each of four different currents: SMS, 70% SMS, 50% SMS, and 30% SMS. The same procedure was performed in the postanesthesia care unit (PACU) only with EMG, and the pain scores on the numerical rating scale (NRS) during the tests were recorded. RESULTS: A total of 36 patients were enrolled. At extubation, TOF ratios with SMS in AMG and EMG were 112.0 ± 13.1% and 93.7 ± 8.9%, respectively. There were no significant differences in TOF ratios between the SMS and lower stimulation intensities. However, 30% and 50% SMS showed significantly higher rates of the unmeasurable results of tests in the PACU. In terms of the stimulation pain, NRS showed a downward pattern as the current decreased and was significantly lower at 50% and 30% SMS than the NRS at SMS. CONCLUSION: The TOF test with submaximal stimulation is still reliable and can reduce stimulation pain. Considering the importance of the TOF results in determining extubation, the authors suggest the minimal current for the TOF test as 70% SMS.

Optimal cutoff values for anthropometric indices of obesity as discriminators of metabolic abnormalities in Korea: results from a Health Examinees study.

BACKGROUND: Obesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cutoff values for obesity indices to discriminate the presence of metabolic abnormalities as a primary risk factor for cardiovascular diseases in a Health Examinees study (HEXA). METHODS: The current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index, waist to hip ratio, waist to height ratio, waist circumference, and conicity index. RESULTS: The AUC of metabolic abnormalities was the highest for waist-to-height ratio (AUC [95% CIs], 0.677 [0.672-0.683] among men; 0.691 [0.687-0.694] among women), and the lowest for the C index (0.616 [0.611-0.622] among men; 0.645 [0.641-0.649] among women) among both men and women. The optimal cutoff values were 24.3 kg/m2 for the body mass index, 0.887 for the waist-to-hip ratio, 0.499 for the waist-to-height ratio, 84.4 cm for waist circumference and 1.20 m3/2/kg1/2 for the conicity index among men, and 23.4 kg/m2 for the body mass index, 0.832 for the waist-to-hip ratio, 0.496 for the waist-to-height ratio, 77.0 cm for the waist circumference and 1.18 m3/2/kg1/2 for the conicity index among women. CONCLUSION: The waist-to-height ratio is the best index to discriminate metabolic abnormalities among middle-aged Koreans. The optimal cutoff of obesity indices is lower than the international guidelines for obesity. It would be appropriate to use the indices for abdominal obesity rather than general obesity and to consider a lower level of body mass index and waist circumference than the current guidelines to determine obesity-related health problems in Koreans.

Cut-off points between pain intensities of the postoperative pain using receiver operating characteristic (ROC) curves.

BACKGROUND: Pain assessment and management are important in postoperative circumstances as overdosing of opioids can induce respiratory depression and critical consequences. We aimed this study to check the reliability of commonly used pain scales in a postoperative setting among Korean adults. We also intended to determine cut-off points of pain scores between mild and moderate pain and between moderate and severe pain by which can help to decide to use pain medication. METHODS: A total of 180 adult patients undergoing elective non-cardiac surgery were included. Postoperative pain intensity was rated with a visual analog scale (VAS), numeric rating scale (NRS), faces pain scale revised (FPS-R), and verbal rating scale (VRS). The VRS rated pain according to four grades: none, mild, moderate, and severe. Pain assessments were performed twice: when the patients were alert enough to communicate after arrival at the postoperative care unit (PACU) and 30 min after arrival at the PACU. The levels of agreement among the scores were evaluated using intraclass correlation coefficients (ICCs). The cut-off points were determined by receiver operating characteristic curves. RESULTS: The ICCs among the VAS, NRS, and FPS-R were consistently high (0.839-0.945). The pain categories were as follow: mild ≦ 5.3 / moderate 5.4 ~ 7.1 /severe ≧ 7.2 in VAS, mild ≦ 5 / moderate 6 ~ 7 / severe ≧ 8 in NRS, mild ≦ 4 / moderate 6 / severe 8 and 10 in FPS-R. The cut-off points for analgesics request were VAS ≧ 5.5, NRS ≧ 6, FPS-R ≧ 6, and VRS ≧ 2 (moderate or severe pain). CONCLUSIONS: During the immediate postoperative period, VAS, NRS, and FPS-R were well correlated. The boundary between mild and moderate pain was around five on 10-point scales, and it corresponded to the cut-off point of analgesic request. Healthcare providers should consider VRS and other patient-specific signs to avoid undertreatment of pain or overdosing of pain medication.

A randomized double-blind comparison of the double-space technique versus the single-space technique in combined spinal-epidural anesthesia for cesarean section.

BACKGROUND: Combined spinal-epidural anesthesia (CSEA) can be performed with either a single-space technique or a double-space technique for cesarean section. We performed a double-blind randomized controlled study to compare the effect of the double-space technique with that of the single-space technique on sensory block level and side effects. METHODS: Parturients undergoing elective cesarean section under regional anesthesia were randomized to receive CSEA with either the double-space technique (double group, n = 20) or the single-space technique (single group, n = 20). In the double group, an epidural catheter was inserted at the L1-2 interspace, and dural puncture was performed at the L3-4 interspace. In the single group, the procedure was performed at the L3-4 interspace using the needle-through-needle technique. RESULTS: There were no differences in time to readiness or intraoperative level of sensory block between the two groups. The postoperative sensory level was maintained at a higher level in the double group than in the single group (1 h postoperatively, P = 0.029; 6 h postoperatively, P = 0.016). There was no difference between the two groups in terms of side effects. The parturient satisfaction scores 48 h postoperatively were significantly different between groups (9.5 in the double group vs. 8 in the single group, P = 0.004). CONCLUSIONS: We conclude that there were no differences in intraoperative variables between the double-space technique and the single-space technique for CSEA. However, double-space CSEA for cesarean section may be beneficial for controlling postoperative pain and improving parturient satisfaction. TRIAL REGISTRATION: The study was retrospectively registered at https://cris.nih.go.kr under the trial ID KCT0002514. Date of registration: October 27, 2017.

Factors Affecting Maternal and Fetal Outcomes of Non-Obstetric Surgery and Anesthesia during Pregnancy: a Retrospective Review of Data at a Single Tertiary University Hospital.

BACKGROUND: Anesthesia during pregnancy for non-obstetric surgery is generally known to have a negative impact on maternal and fetal outcomes. We assessed the risk of adverse outcomes in fetuses and mothers associated with non-obstetric surgery. METHODS: This retrospective study analyzed clinical data on pregnant women who received non-obstetric surgeries at a tertiary university hospital. We reviewed maternity admissions using hospital administrative data during the last 16 years. The outcome assessment included the presence of preterm labor, premature birth, abortion, or stillbirth and the data of newborns. Statistical analyses were performed using the t-test, χ² test, and multiple logistic regression was used for risk analysis. RESULTS: The incidence of non-obstetric surgery during pregnancy was 0.96%. Gestational age at or above 20 weeks increased the risk of all adverse events 4.5 fold when it was compared to gestational age less than 20 weeks, although the events were only preterm labor or premature birth and no fetal loss. All fetal loss cases occurred in patients at less than 20 weeks of pregnancy. The risk of adverse outcome increased by 2% for every 1 minute increase in anesthesia time. Babies of the mothers who had the adverse outcome event showed lower birth weight and higher neonatal intensive care unit admission rate than those of babies of the mothers without any adverse event after the surgery. CONCLUSION: Physicians should acknowledge and prepare for common possible adverse events at the stage of pregnancy after non-obstetric surgery, and effort to shorten the duration of surgery and anesthesia is needed.

Effects of Intraoperative Ventilation Strategy on Perioperative Atelectasis Assessed by Lung Ultrasonography in Patients Undergoing Open Abdominal Surgery: a Prospective Randomized Controlled Study.

BACKGROUND: Protective mechanical ventilation using low tidal volume has been introduced to surgical patients to reduce the incidence of postoperative pulmonary complications. We investigated the effects of protective ventilation (PV) techniques on anesthesia-induced atelectasis identified via lung ultrasonography in patients undergoing abdominal surgery. METHODS: A total of 42 adult patients who were scheduled for open abdominal surgery with an expected duration > 2 hours were included in the study. Patients were randomized to receive either conventional ventilation (CV; tidal volume of 9-10 mL/kg predicted body weight [PBW] with no positive end-expiratory pressure [PEEP]) or PV (tidal volume of 6-8 mL/kg PBW and 5 cmH2O PEEP) via pressure-controlled ventilation with volume guaranteed. Lung ultrasonography was performed at four predefined time points to assess perioperative atelectasis by dividing each hemithorax into six quadrants based on a modified lung ultrasound (LUS) scoring system. RESULTS: The tidal volume delivered to patients was 9.65 ± 1.65 mL/kg PBW in the CV group and 6.31 ± 0.62 mL/kg PBW in the PV group. Ventilation using low tidal volume led to similar LUS scores in all lung areas and at all time points compared to ventilation using high tidal volume. There was no significant difference between the groups in the number of patients requiring recruitment maneuvers at the end of surgery. CONCLUSION: Ventilation with low tidal volume combined with 5 cmH2O PEEP did not cause further loss of aeration compared to ventilation with high tidal volume. Low tidal volume ventilation can be used in patients without lung injury based on lung assessment by bedside lung ultrasonography. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003746.

Evaluation of gene-environment interactions for colorectal cancer susceptibility loci using case-only and case-control designs.

BACKGROUND: Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs. METHODS: Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk. RESULTS: The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10- 3, pcase-control = 1.5 × 10- 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02-2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62-0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10- 3, pcase-control = 1.6 × 10- 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97-10.80). CONCLUSION: Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.

Environmental contributions to gastrointestinal and liver cancer in the Asia-Pacific region.

In the Asia-Pacific region, gastric, colorectal, and hepatocellular (liver) cancer show substantial regional variation in incidence consistent with the presence of important environmental factors. For gastric cancer, global incidence is concentrated in Asia with substantially higher rates in East Asia than in South-East Asia and Australia. The differences in incidence rates for gastric cancer in the Asia-Pacific region may be due, in part, to differences in the prevalence of Helicobacter pylori infection and the prevalence of H. pylori virulence factors. Smoking is also correlated with gastric cancer risk and is responsible for the highest population attributable fraction among men in East Asia. Colorectal cancer has increased rapidly in incidence to become the third most common digestive cancer in Asia. According to cohort studies in Asia, smoking, alcohol use, obesity, and physical inactivity increase the risk of colorectal cancer. Unlike West Asia, East Asia and Australia have high incidence rates for colorectal cancer that correlates to a high Human Development Index and a high prevalence of alcohol consumption and obesity. Liver cancer is the second most common digestive cancer in Asia. The high incidence of liver cancer in East Asia and South-East Asia is concordant with the high prevalence of hepatitis B virus and hepatitis C virus infection. Other important risk factors include alcohol use, smoking, and diabetes. The identification of the earlier and other environmental factors (currently under investigation) is central to the development and implementation of effective cancer control programs for the region.

Ultrasound-guided bilateral rectus sheath block reduces early postoperative pain after laparoscopic gynecologic surgery: a randomized study.

PURPOSE: Rectus sheath block (RSB) is an anterior abdominal wall block that reduces postoperative pain associated with midline incisions. This study aims to investigate the effect of ultrasound-guided bilateral RSB (US-BRSB) on postoperative pain and analgesic consumption in patients undergoing laparoscopic gynecologic surgery. METHODS: Sixty patients who underwent laparoscopic gynecologic surgery were allocated to RSB (n = 30) or control (n = 30) group. A bilateral US-BRSB procedure (30 ml of 0.25% ropivacaine) was performed after induction of general anesthesia in the RSB group. The control group proceeded the surgery without sham block. All patients received fentanyl-based intravenous patient-controlled analgesia and rescue analgesics upon demand. Pain was scored by a blinded observer using a verbal numerical rating scale (VNRS) at rest while coughing at 0, 1, 6, 12, 24, and 48 h after postanesthesia care unit (PACU) admission. The primary outcome was the total number of rescue analgesics used in the 48-h postoperative period. RESULTS: At 0 h, VNRS were lower in the RSB group than in the control, both at rest (median VNRS 4.5 vs. 5, p = 0.02) and while coughing (median VNRS 6 vs. 7, p = 0.004). At 6 h, VNRS scores were lower in the RSB group than in the control while coughing (median VNRS 3 vs. 5, p = 0.01). Fentanyl use as rescue analgesics in the PACU was significantly lower in the RSB group than in the control (27.7 ± 32.1 vs. 53.3 ± 33.7 µg, respectively; p = 0.004). At 48 h postoperatively, the total number of rescue analgesics administered were significantly fewer in the RSB group than in the control (2.5 ± 2.5 vs. 3.9 ± 2.6, respectively; p = 0.04). CONCLUSION: US-BRSB reduces the immediate postoperative pain and opioid consumption during the early postoperative period. CLINICALTRIALS. GOV IDENTIFIER: NCT02476799, https://clinicaltrials.gov/ct2/show/NCT02476799 .

Association between body size, weight change and depression: systematic review and meta-analysis.

BackgroundThe association between body size, weight change and depression has not been systematically summarised, especially for individuals who are underweight.AimsTo conduct a systematic review and a meta-analysis to examine the association between indices of body size, weight change and depression.MethodA total of 183 studies were selected. Fully adjusted hazard ratios (HRs) or odds ratios (ORs) were extracted. A total of 76 studies contributed to data synthesis with a random-effect model, and subgroup analyses were conducted to evaluate the effect of potential moderators.ResultsIn cohort studies, underweight at baseline increased the risk of subsequent depression (OR = 1.16, 95% CI 1.08-1.24). Overweight (BMI 25-29.9 kg/m2) showed no statistically significant relationship with depression overall; however, the subgroup analyses found different results according to gender (men: OR = 0.84, 95% CI 0.72-0.97, women: OR = 1.16, 95% CI 1.07-1.25). In cross-sectional designs, obesity with BMI >40 kg/m2 showed a greater pooled odds ratio than obesity with BMI >30 kg/m2ConclusionsBoth underweight and obesity increase the risk of depression. The association between overweight and depression differs by gender.

Percutaneous Epidural Adhesiolysis with Epidural Steroid Injection: A Non-inferiority Test of Non-particulate Steroids Versus Particulate Steroids.

OBJECTIVES: To evaluate the efficacy of dexamethasone sodium phosphate (DSP), a non-particulate steroid, during percutaneous epidural adhesiolysis (PEA), as compared with triamcinolone acetate (TA). DESIGN: Retrospective observational study. SETTING: Interventional pain management clinic in a tertiary care center. SUBJECTS: Patients scheduled to receive PEA between March 2011 and January 2014. METHODS: 47 patients underwent the procedure with TA (TA group), and 26 patients underwent the procedure with DSP (DSP group). At the end of the procedure, 20 ml of 0.18% ropivacaine containing 3000 units of hyaluronidase and 80 mg of TA or 10 mg of DSP was injected. Success rates and means of percent decreases in terms of verbal numerical rating scale (VNRS) of pain and Oswestry Disability Index (ODI) at follow-up visits 3 and 6 months after PEA were compared. Non-inferiority test was used for statistical analysis. RESULTS: At 3 months, the success rate in VNRS of TA group and DSP group were 59.6% and 53.8%. The mean percent decreases of VNRS were 42.4% and 46.1% in TA group and DSP group, respectively. At this time point, non-inferiority was not demonstrated. In contrast at 6 months, the success rate in aspect of VNRS was 45.2% in TA group and 62.5% in DSP group. The mean of percent decreases in the VNRS was 34.9% in TA group and 52.8% in DSP group. The non-inferiority was met in two measurements. CONCLUSIONS: DSP presents non-inferiority to TA in terms of success rate and percentage decrease of the VNRS 6 months after PEA.

MiRGator v3.0: a microRNA portal for deep sequencing, expression profiling and mRNA targeting.

Biogenesis and molecular function are two key subjects in the field of microRNA (miRNA) research. Deep sequencing has become the principal technique in cataloging of miRNA repertoire and generating expression profiles in an unbiased manner. Here, we describe the miRGator v3.0 update (http://mirgator.kobic.re.kr) that compiled the deep sequencing miRNA data available in public and implemented several novel tools to facilitate exploration of massive data. The miR-seq browser supports users to examine short read alignment with the secondary structure and read count information available in concurrent windows. Features such as sequence editing, sorting, ordering, import and export of user data would be of great utility for studying iso-miRs, miRNA editing and modifications. miRNA-target relation is essential for understanding miRNA function. Coexpression analysis of miRNA and target mRNAs, based on miRNA-seq and RNA-seq data from the same sample, is visualized in the heat-map and network views where users can investigate the inverse correlation of gene expression and target relations, compiled from various databases of predicted and validated targets. By keeping datasets and analytic tools up-to-date, miRGator should continue to serve as an integrated resource for biogenesis and functional investigation of miRNAs.

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

BACKGROUND: Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. OBJECTIVE: The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. DESIGN: A randomised, double-blind controlled trial. SETTING: Single university tertiary care centre. PATIENTS: One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. INTERVENTIONS: Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. MAIN OUTCOME MEASURES: The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. RESULTS: Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. CONCLUSION: Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. TRIAL REGISTRATION: the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

gsGator: an integrated web platform for cross-species gene set analysis.

BACKGROUND: Gene set analysis (GSA) is useful in deducing biological significance of gene lists using a priori defined gene sets such as gene ontology (GO) or pathways. Phenotypic annotation is sparse for human genes, but is far more abundant for other model organisms such as mouse, fly, and worm. Often, GSA needs to be done highly interactively by combining or modifying gene lists or inspecting gene-gene interactions in a molecular network. DESCRIPTION: We developed gsGator, a web-based platform for functional interpretation of gene sets with useful features such as cross-species GSA, simultaneous analysis of multiple gene sets, and a fully integrated network viewer for visualizing both GSA results and molecular networks. An extensive set of gene annotation information is amassed including GO & pathways, genomic annotations, protein-protein interaction, transcription factor-target (TF-target), miRNA targeting, and phenotype information for various model organisms. By combining the functionalities of Set Creator, Set Operator and Network Navigator, user can perform highly flexible and interactive GSA by creating a new gene list by any combination of existing gene sets (intersection, union and difference) or expanding genes interactively along the molecular networks such as protein-protein interaction and TF-target. We also demonstrate the utility of our interactive and cross-species GSA implemented in gsGator by several usage examples for interpreting genome-wide association study (GWAS) results. gsGator is freely available at http://gsGator.ewha.ac.kr. CONCLUSIONS: Interactive and cross-species GSA in gsGator greatly extends the scope and utility of GSA, leading to novel insights via conserved functional gene modules across different species.

Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank.

Importance: Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome. Objectives: To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC. Design, Setting, and Participants: This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021. Exposures: The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained. Main Outcomes and Measures: Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses. Results: A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10-5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP). Conclusions and Relevance: In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.