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This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality.
The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets.
The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267–1.404), 1.219 (1.157–1.285) and 0.889 (0.840–0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = –0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively.
The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.
Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
This study aimed to analyse the results of chyle fistula testing using the SD LipidoCare system in patients who had undergone neck dissections performed in our hospital in 2019.
Sixty patients who underwent neck dissections from March 2019 to November 2019 were identified based on their medical records.
Post-operative chyle fistulas were observed in 3 of 60 patients (5 per cent). All patients who developed chyle fistulas had undergone left-sided neck dissections. Within 3 minutes, the SD LipidoCare test had produced triglyceride results of 49, 56 and 207 mg/dl in the three patients. The remaining 57 patients measured ‘low’ for triglycerides on the SD LipidoCare test system.
The SD LipidoCare test quickly and accurately diagnosed chyle fistulas in patients who had undergone neck dissections. All patients improved with conservative treatment following the early diagnosis of chyle fistulas.
ABSTRACT IMPACT: We compare the cost-effectiveness of treatments for early prostate cancer, and propose how to maximize the value of care within an increasingly cost-constrained healthcare climate. OBJECTIVES/GOALS: Each year 192,000 men in the United States are diagnosed with prostate cancer. With various treatment options available, there is a growing role for cost-effectiveness analyses which may help maximize the value of care to the patient. In this review we compare the cost-effectiveness of primary treatments for clinically localized prostate cancer. METHODS/STUDY POPULATION: In this systematic review we aim to compare the cost-effectiveness or cost-utility of primary treatment strategies for clinically localized prostate cancer. This review, which adheres to 2009 PRISMA guidelines, included studies of men with clinically localized prostate cancer comparing at least two treatment strategies using the incremental cost-effectiveness ratio (ICER). We included analyses only of the United States healthcare system with at least 10 years of follow-up. These studies were published from 2006 to 2019 and generally included men with low or low to intermediate risk prostate cancer. Most studies reported outcomes for men age 65-70. All studies were prospective simulated trials and used a Markov model to simulate patient outcomes. RESULTS/ANTICIPATED RESULTS: Ten articles were included in the analysis. All studies used a Markov model to simulate a randomized trial. Six studies primarily compared radiation modalities, and four compared observation with immediate treatment. There was substantial heterogeneity in treatment protocols and the patients being simulated. Sensitivity analyses showed these models to be influenced by utility values and length of follow-up. A meta-analysis was not possible as no studies reported the variance of the primary outcome. Heterogeneity in study design limited comparisons of treatments across studies. However, these models were sensitive to patient-specific clinical factors, including life expectancy and the utility during and after each treatment. DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies indicate collectively that the cost-effectiveness of prostate cancer treatment for similarly staged men may be heavily impacted by comorbidities and personal preferences. As the US moves towards value-based care, patient preferences may continue to drive the preferred treatment for newly diagnosed prostate cancer.
ABSTRACT IMPACT: Urine tumor DNA non-invasively detects minimal residual disease and infers tumor mutational burden in locally advanced bladder cancer prior to radical cystectomy, which may potentially enable the selection of patients for bladder-sparing treatment or facilitate personalized adjuvant immunotherapy. OBJECTIVES/GOALS: Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. The inability to assess minimal residual disease (MRD) non-invasively limits our ability to offer bladder-sparing treatment. We sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS/STUDY POPULATION: We applied uCAPP-Seq, a targeted sequencing method for detecting utDNA, to urine cell-free DNA samples acquired on the day of radical cystectomy from 42 patients with bladder cancer. utDNA variant-calling was performed non-invasively without prior tumor mutational knowledge. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. Tumor mutational burden (TMB) was inferred from the number of non-silent mutations detected in urine cell-free DNA by applying a linear relationship derived from TCGA whole exome sequencing of 409 MIBC tumors. RESULTS/ANTICIPATED RESULTS: utDNA levels were significantly higher in patients with residual disease detected in their surgical pathology compared to those who achieved a pathologic complete response (P = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD significantly predicted the absence of pathologic complete response with a sensitivity of 81% and specificity of 81%. Positive utDNA MRD also portended significantly worse progression-free survival (HR = 7.4; P = 0.03) compared to negative utDNA MRD. Furthermore, we applied a linear relationship (Pearson r = 0.84; P < 0.0001) to identify patients with high inferred TMB who may have been candidates for early immune checkpoint blockade. DISCUSSION/SIGNIFICANCE OF FINDINGS: utDNA MRD analysis prior to surgery correlated significantly with pathologic response and progression-free survival, which may help select patients for bladder-sparing treatment. utDNA can also non-invasively infer TMB, which could facilitate personalized adjuvant therapy for patients in the future.
Previous studies have reported the basic reproduction number (R0) of coronavirus disease from publicly reported data that lack information such as onset of symptoms, presence of importations or known super-spreading events. Using data from the Republic of Korea, we illustrated how estimates of R0 can be biased and provided improved estimates with more detailed data. We used COVID-19 contact trace system in Korea, which can provide symptom onset date and also serial intervals between contacted people. The total R0 was estimated as 2.10 (95% confidence interval (CI) 1.84–2.42). Also, early transmission of COVID-19 differed by regional or social behaviours of the population. Regions affected by a specific church cluster, which showed a rapid and silent transmission under non-official religious meetings, had a higher R0 of 2.40 (95% CI 2.08–2.77).
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Varicocele is the most common surgically correctable factor identified in infertile men. The negative impact of varicocele on testicular function, semen parameters and fertility potential have been well recognized for decades. Despite this, the role of varicocele repair in managing infertility remains controversial, especially since the advent of assisted reproductive technologies (ART). This chapter details the current status of varicocele in male infertility. We describe the anatomy, pathophysiology and diagnostics of varicocele and discuss the methods of repair. We then take a critical look at the efficacy and clinical utility of varicocele repair in infertile couples, with an emphasis on clinical benefits for couples undergoing ART.
Several cross-sectional studies, but no prospective studies, have reported an association between an abnormal lipid profile and posttraumatic stress disorder (PTSD). We hypothesized that an abnormal lipid profile might predict risk for developing PTSD. In this prospective study, we analyzed data from 237 antidepressant-naïve severely injured patients who participated in the Tachikawa Cohort of Motor Vehicle Accident Study. High-density lipoprotein cholesterol (HDL-C) levels at baseline were significantly lower in patients with PTSD than those without PTSD at 6 months after motor vehicle accident (MVA) and were inversely associated with risk for PTSD. In contrast, triglycerides (TG) at baseline were significantly higher in patients with PTSD than in those without PTSD at 6 months post-MVA and were positively associated with risk for PTSD. There was no clear association between low-density lipoprotein cholesterol or total cholesterol and risk for PTSD. In conclusion, low HDL-C and high TG may be risk factors for PTSD. Determining lipid profiles might help identify those at risk for PTSD after experiencing trauma.
: Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioral aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. in this study, we investigated the relationship between self-reported cognitive impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.
Twenty-one participants completed 3-Tesla magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.
The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency toward positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate.
These results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgment of alternative outcomes, and inhibitory control.
The acquisition and extinction of conditioned fear underlies the pathophysiology of anxiety disorders, including PTSD. Women have higher lifetime prevalence and greater risk of PTSD than men. Such sex differences may be attributed to a combination of genetic and hormonal factors. The catechol-O-methyltransferase (COMT) gene encodes an enzyme that metabolizes catechol compounds, including dopamine. The COMT Val158Met polymorphism affects the enzymatic activity of dopamine and has been associated with altered fear memory performance. Besides, when estrogen secretion is elevated, women show a greater extinction of conditioned fear than men. Here, we investigated the relationship between the COMT genotype and sex in the acquisition and extinction of conditioned fear. In a 3-day cued fear conditioning experiment, acquisition and extinction performance of 75 healthy men (21.8 years) and 45 healthy women in follicular phase (21.2 years) were examined. Visual cues and electric shocks were used as the conditioned stimulus and unconditioned stimulus, respectively. Subjects with Met/Met homozygotes showed less fear acquisition (p < .0001). Female Val carriers showed more extinction (p = .009) and less reconsolidation (p < .0001) than male Val carriers. Women with Val/Val homozygotes were less affected by a reinforcing stimulus than men with Val/Val homozygotes (p = .0001). These findings suggest a clear interaction between the COMT gene and sex in fear memory function, and that women have a greater tolerance for aversive experiences than men. Higher estrogen levels mediate increased dopaminagic activity, potentially optimizing the prefrontal function known to contribute to the fear-related symptomatology of PTSD.
Alterations in redox modulation are consistently reported in bipolar disorder (BD). MicroRNAs are targeted regulators of gene expression.
Objectives and aims
We aimed to examine if microRNAs that target redox modulators can discriminate between BD and healthy controls.
Data from brains of individuals with and without BD were obtained from Array Collection datasets. MicroRNAs targeting redox modulators were assessed for their ability to discriminate BD from the control group using machine-learning algorithms. Methylation of microRNAs, expression of their transcription factors and redox targets were assessed with ANCOVA with FDR correction. For validation, we acquired plasma samples belonging to 2 families of individuals with and without BD (n = 9). Plasma microRNAs were sequenced using the Ion Total RNA Sequencing Kit (Thermo Fisher Scientific), and microRNAs identified from the in silico analysis were examined in the validation dataset.
We identified 5 miRNAs (hsa-miR-299, hsa-miR-125a, hsa-miR-145, hsa-miR-30b, hsa-miR424) that were common in two of the four in silico datasets. Target genes glutathione peroxidase 4, ATP5A1, ATP5G1, NDUFS1, NDUFC2, and catalase were expressed at different levels between BD and the control group. Furthermore, our results showed that transcription factors CTCF and USF1 might control the expression of hsa-miR-145, while methylation differences were not found. Finally, hsa-miR-30b was significantly increased in the plasma of patients with BD compared to controls in the validation experiment.
Our study demonstrates that microRNAs may have an important role in the initiation of redox changes in BD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
To analyse how the auditory brainstem response changes in patients with sudden sensorineural hearing loss.
Data were collected via retrospective medical chart review.
Forty-three patients were included in this study. The mean latency of auditory brainstem response wave 1 was significantly longer for the affected side than for the unaffected side (p = 0.003). The mean latency of auditory brainstem response wave 1 was significantly shorter, and the mean amplitude of auditory brainstem response wave 1 was significantly larger, in the good response group compared to the poor response group. In forward conditional logistic regression analysis, auditory brainstem response wave 1 latency was an independent predictor of a good response (odds ratio = 34.37, 95 per cent confidence interval = 1.56–757.15, p = 0.025).
In patients with sudden sensorineural hearing loss, the latency of wave 1 of the auditory brainstem response was significantly increased and was related to prognosis.
We conducted active surveillance of acute respiratory viral infections (ARIs) among residents and healthcare personnel (HCP) at a long-term care facility during the 2015–2016 respiratory illness season. ARIs were observed among both HCP and patients, highlighting the importance of including HCP in surveillance programs.
This paper integrates seemingly disjoint studies on consumer behavior in micro and macroanalyses via an intertemporal two-stage budgeting procedure with durable goods and liquidity constraints. The model specifies an indirect utility function as a function of nondurable consumption, commodity (nondurables) prices, and durables stock, and derives the demand functions for nondurable goods. A demand function for durable goods is derived in an adjustment cost framework. The consumption growth equation accounts for relative price effects with precautionary saving, durables stock, and liquidity constraints. The stochastic discount factor is approximated by a time-varying linear function of nondurable consumption growth, commodity price growth, durables stock growth, and disposable income growth. The demand functions for six nondurable goods and services are jointly estimated with the Euler equations for bonds, stocks, and durable goods with allowance for liquidity constraints, using US data. Estimation provides new findings for intertemporal consumption and a multifactor consumption-based capital asset pricing model.
Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.
The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.