Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

The prevalence of overt, occult, and no-demonstrated stress urinary incontinence and their clinical and urodynamic findings in women with advanced-stage cystoceles.

OBJECTIVES: To elucidate the prevalence of overt, occult and no demonstrated (ND) stress urinary incontinence (SUI) in women with advanced-stage cystoceles. STUDY DESIGN: Between November 2011 and January 2017, all women with ≥stage 2 cystoceles were retrospectively enrolled. Overt SUI was diagnosed before the prolapse reduction test, and occult SUI was diagnosed when urine leakage was noted after a reduction test with vaginal gauze. Otherwise, a diagnosis of ND-SUI was made. MAIN OUTCOME MEASURES: The prevalence, clinical and urodynamic findings of overt SUI, occult SUI, and ND-SUI. RESULTS: In 480 enrolled women, 62% had overt SUI, 17% had occult SUI, and 21% had ND-SUI. The occult SUI group had the most advanced prolapse. The pad weight results after prolapse reduction (37.3 ± 44.3 vs. 13.4 ± 21.9, p < 0.05), the bladder capacity (243 ± 54 vs. 273 ± 48, p < 0.001), and questionnaires regarding life quality were significantly different between the overt SUI and the occult SUI groups. Bladder oversensitivity (BO) was the most common urodynamic diagnosis (389/480, 81%), especially in overt SUI, while urodynamic stress incontinence (56/480, 12%) and detrusor overactivity (60/480, 13%) were uncommon. The cutoff value of stage 3 uterine prolapse was the strongest predictor for predicting occult SUI (sensitivity = 30.3%, specificity = 78.5%; area = 0.60, 95% CI: 0.52-0.68). CONCLUSIONS: SUI occurs in a ratio of 3:1:1 among cases with overt, occult, and no demonstrable symptoms. BO is the most common urodynamic diagnosis. Pad test with prolapse reduction remains an important tool, especially for coexistent stage 3 uterine prolapse.

Prevalence and predictors of nocturnal polyuria in females with overactive bladder syndrome.

PURPOSE: To describe the prevalence and predictors of nocturnal polyuria (NP) in women with overactive bladder syndrome (OAB). METHODS: Between July 2009 and January 2018, women with OAB were enrolled. NP was defined when the nocturnal polyuria index (NPI) (nighttime voided volume over 24-h voided volume) was > 33% (NPI33) in women ≥ 65 years-old and > 20% (NPI20) in women < 65 years old. Repeated analysis was also performed for NP defined by the NPI33 definition at all ages. RESULTS: A total of 1071 women with OAB were analyzed. The overall prevalence of NP was 30% (319/1071), with the highest prevalence in women in the perimenopausal period (46-50 years old), while NP was diagnosed by age-dependent NPI. The overall prevalence of NP was 12% (128/1071), with an increasing trend with increasing age, while NP was diagnosed by the NPI33 definition only. Daytime frequency and nocturia episodes were both predictors for NP in both definitions. Receiver operating characteristic curve analysis revealed that more than 5 nocturia episodes noted in the 3-day bladder diary were an optimal cutoff value to predict nocturnal polyuria [(sensitivity = 85.6%, specificity = 61.0%; area = 0.80, 95% CI 0.77-0.82) and (sensitivity = 88.3%, specificity = 65.9%; area = 0.83, 95% CI 0.80-0.85), respectively, in the two definitions]. CONCLUSIONS: NP is common in women with OAB, especially in women with more than 5 nocturia episodes in their 3-day bladder diaries, and adjuvant therapy for better treatment efficacy is needed.

Laparoendoscopic two-site myomectomy (LETS-M) using conventional laparoscopic instruments and the glove-port technique.

PURPOSE: To evaluate the perioperative outcome of laparoendoscopic two-site myomectomy (LETS-M). METHODS: The medical records of 204 women receiving LETS-M in a tertiary referral center, including 183 surgeries performed by the experienced surgeon and 21 surgeries performed by 3 well-supervised trainees were retrospectively reviewed. RESULTS: The age of the participants was 39.3 ± 6.4 years. The mean diameter of the largest myoma and the mean number of myomas were 8.5 ± 2.2 cm and 1.7 ± 1.1, respectively. Thirty-one (15%) operations removed more than 2 myomas larger than 5 cm in diameter. The mean weight of the myomas was 281.1 ± 183.1 g. The operation time was 97.6 ± 40.2 min, and the intraoperative blood loss was 99.3 ± 115.2 mL. There were 3 (1%) cases of excessive blood loss (more than 500 mL) and 2 (1%) of postoperative hematoma. The only significant difference between the experienced surgeon and trainees was the operation time (92.3 ± 32.2 min vs. 141.2 ± 54 min, p < .001), while the myoma number, myoma diameter, myoma weight, and intraoperative blood loss were not significantly different. The operation time did not differ among different myoma locations. In multivariate analysis, virginity, myoma number, more than 2 large myomas, and myoma size were independent variables for longer operation times. No patient experienced any major complications. CONCLUSION: LETS-M using conventional laparoscopic equipment is a minimally invasive surgical method that is safe, effective, and easy to learn for managing uterine myoma. It is useful to achieve a favorable perioperative outcome with acceptable operation time.

Clinical outcome and urodynamic changes of tailored transvaginal mesh surgery for pelvic organ prolapse: A mid-term 40 Months follow-up.

PURPOSE: To evaluate the changes in clinical outcome and urodynamic parameters after tailored anterior transvaginal mesh (ATVM) surgeries in a mid-term follow-up. METHODS: Between November 2011 and December 2015, women with ≥stage II pelvic organ prolapse (POP) who underwent ATVM surgeries were retrospectively reviewed. The data-reviewing timeframe was until December 2021. Clinical and urodynamic diagnoses regarding urinary symptoms were evaluated before and after the operation. RESULTS: A total of 160 women were included. Stress urinary incontinence decreased significantly after the operation (99% (159/160) vs. 43% (68/160), p < 0.01), as well as the pad weight (20.5 ± 2.7 vs. 9.4 ± 2.0, p < 0.001) and diagnosis of urodynamic stress incontinence (83% (132/160) vs. 51% (82/160), p < 0.01). Overactive bladder syndrome increased significantly after the operation (18% (29/160) vs. 28% (45/160), p = 0.03), even though the objective parameters, such as first and strong desire to void, bladder oversensitivity, and detrusor overactivity, were all improved after the operation. The pad weight was mostly improved significantly within the first postoperative 2 years. Eighteen (11%) women had global recurrent POP, and only one (0.6%) woman had true recurrence of cystocele. Twenty-four (15%) women had mesh extrusion, and two-thirds of them could be managed in an office setting. CONCLUSION: In women with advanced cystocele, the ATVM surgery provides a favorable anatomic reduction outcome with an acceptable mesh extrusion rate. The ATVM provides an anti-incontinence effect, both in subjective symptoms and objective parameters, but this effect might decline after postoperative 2 years.

On-Line Coupling of Simultaneous Distillation-Extraction Using the Likens-Nickerson Apparatus with Gas Chromatography.

Simultaneous distillation-extraction (SDE) using the Likens-Nickerson apparatus is a convenient technique used to isolate volatile organic compounds (VOCs) from complex liquid matrices. The technique combines steam distillation with solvent extraction. While analytical extractions are normally followed by off-line separation/detection, it is advantageous to couple extractions on-line with separation and detection systems that are employed in the same analytical workflow. Here, we have coupled the Likens-Nickerson apparatus on-line with a gas chromatograph hyphenated with a mass spectrometer. For that purpose, we have devised an automated liquid transfer setup comprising a peristaltic pump, control unit, customized transfer vial with a drain port, and an autosampler arm to deliver liquid extract aliquots at defined time points. The on-line SDE-GC/MS system enables one to record real-time extraction profiles. These profiles reveal extraction kinetics of various VOCs present in the extracted samples. The data sets were fitted with the first order kinetic equation to obtain numeric values characterizing the extraction process (rate constants ranging from 0.21 to 0.01 min-1 for the ethyl esters from C6 to C19). A comparison of on-line and off-line results reveals that the on-line system is more dependable, while the off-line analysis leads to artifacts. To demonstrate the operation of the on-line SDE-GC/MS system, we performed analyses of selected real samples (beer). The real-time data sets revealed extraction kinetics for VOCs present in these samples. The devised extraction-analysis system allows the analysts to make an evidence-based decision on the extraction time for different groups of analytes in order to maximize extraction yield and minimize analyte losses.

Predictors of an improvement in the severity of concomitant urodynamic stress incontinence after transvaginal mesh surgery for pelvic organ prolapse.

BACKGROUND/PURPOSE: Factors affecting the anti-incontinence efficacy of a tailored anterior transvaginal mesh (ATVM) surgery are undetermined. Thus, our aim was to investigate predictors for anti-incontinence efficacy of this ATVM surgery. METHODS: Medical records of women with pelvic organ prolapse and concomitant evident or occult urodynamic stress incontinence, who underwent the ATVM surgery but without concomitant anti-incontinence surgery, were reviewed. RESULTS: A total of 134 women were reviewed, including those who underwent ATVM only (n = 45), ATVM and posterior transvaginal mesh surgery (n = 88), and ATVM with total vaginal hysterectomy (n = 1). Multivariable analysis revealed that stage of cystocele (coefficient = 56.4), functional profile length (cm, coefficient = 61.1) and the score of general health perceptions in the King's Health Questionnaire (coefficient = -3.3) were independent predictors of the percentage change in pad weight from baseline. Seven (5.2%) women were found to have recurrent or persistent stress urinary incontinence, and 6 of the above 7 women underwent transobturator mid-urethral sling procedure. Free of further anti-incontinence surgery probabilities were 94.7% and 89.2% at 3 and 6 years after surgery, respectively. Functional profile length (hazard ratio = 2.61) was also identified as a predictor for further anti-incontinence surgery. CONCLUSION: Lesser degree of cystocele, shorter functional profile length and poorer general health perceptions were predictors of greater anti-incontinence effect after the tailored ATVM surgery. Besides, longer functional profile length was also a predictor for further anti-incontinence surgery after the ATVM surgery.

Prevalence of detrusor underactivity and bladder outlet obstruction in women with cystocele and changes in voiding function after cystocele repair.

PURPOSE: To evaluate the prevalence of detrusor underactivity (DU) and bladder outlet obstruction (BOO) in women with high-grade cystocele and the impacts of cystocele repair. METHODS: Between November 2010 and September 2018, women with ≥stage II cystocele were included. DU (detrusor pressure at maximum flow rate (PdetQmax) < 20 cmH2O, maximum flow rate (Qmax) < 15 mL/s, and bladder voiding efficiency < 90%) and BOO (PdetQmax ≥ 40 cmH2O and Qmax < 12 mL/s) were diagnosed by urodynamic study (UDS). Women who underwent cystocele repair were further analyzed with preoperative and postoperative comparisons. RESULTS: A total of 623 women were included. Forty-four (7%) and 17 (3%) women were diagnosed with DU and BOO, respectively. Among the 314 operatively treated women, a significant increase in DU (7% vs. 15%, p = 0.0007), especially in those with stage III cystocele, and a slightly decreased rate of BOO were noted postoperatively. UDS revealed that the postvoid residual volume, functional profile length, maximum urethral closure pressure (MUCP), and pressure transmission ratio at the MUCP decreased significantly, as did the pad weight. Nearly all lower urinary tract symptoms (LUTS) improved significantly, except nocturnal enuresis. Among bladder diary parameters, nocturia episodes, daytime frequency, urgency episodes, and incontinence episodes decreased significantly after the operation. CONCLUSION: The prevalence rates of DU and BOO in women with high-grade cystocele were 7% and 3%, respectively. After cystocele repair, the rate of DU increased. Most LUTS improved subjectively on questionnaires and objectively on UDS and bladder diary parameters after operation.

Comparison of the vault prolapse rate after vaginal hysterectomy with or without residual uterine ligament ligations: A retrospective cohort study.

PURPOSE: To evaluate the post-hysterectomy vault prolapse (PHVP) rates performed using different methods of vaginal total hysterectomy (VTH). METHODS: A total of 251 women who underwent VTH with/without concomitant surgeries between January 1986 and December 2001 in a tertiary center. Thirty-eight women were excluded due to not only a vaginal approach. Of the remaining 213 women, 129 and 84 underwent VTH via the Tsuzi method with residual uterine ligament ligations (ligations group) and traditional VTH (without ligations group), respectively. The χ2 and Mann-Whitney U tests were applied appropriately. The cumulative percentages of women without PHVP were calculated over time and compared using Kaplan-Meier curves and log-rank tests. A p value of less than 0.05 was considered statistically significant. RESULTS: Compared to the without ligations group, women in the ligations group had longer operation time (115.9 ± 37.1 vs. 103.3 ± 41.4 min, p = 0.002) and more blood loss (217.4 ± 137.8 vs. 148.2 ± 149.0 mL, p < 0.001). When focusing on women with uterine prolapse, only operation time and grade of uterine prolapse were different between the groups (117.3 ± 24.8 vs. 107.9 ± 40.5 min, p = 0.025, and 21% vs. 41%, p = 0.018, respectively). The rate of PHVP was significantly lower in the ligation group than in the without ligations group (0 vs. 5, p = 0.005). CONCLUSION: VTH via the Tsuzi method with residual uterine ligament ligations resulted in fewer cases of PHVP than occurred in traditional VTH. If native tissue repair is planned in pelvic reconstruction surgery, VTH with residual uterine ligament ligations should be considered.

Comparison of clinical outcomes between tailored transvaginal mesh surgery and native tissue repair for pelvic organ prolapse.

BACKGROUND/PURPOSE: The most suitable surgical technique for pelvic organ prolapse (POP) remains undetermined. The aim of this study was to compare clinical outcomes of the tailored transvaginal mesh (TVM) surgery and vaginal native tissue repair (NTR) surgery for POP. METHODS: Between November 2011 and August 2014, medical records of 339 women receiving POP surgeries were reviewed. RESULTS: Compared with the NTR group (n = 169), the use of TVM surgery (n = 170) was a predictor for longer operation time (coefficient = 25.2 min, P < 0.001) and larger blood loss (coefficient = 79.9 mL, P < 0.001) by multivariable analysis. However, a higher recurrence rate of cystoceles (log-rank test, P = 0.001) was found in the NTR group, compared with the TVM group; but not apical prolapse (P = 0.32) or rectocele (P = 0.45). Multivariable analysis revealed that the TVM surgery (hazard ratio = 0.24, 95% confidence interval = 0.09-0.64, P = 0.004) and old age (hazard ratio = 1.07, 95% confidence interval = 1.02-1.11, P = 0.005) were independent predictors for the recurrence of cystoceles. Based on the receiver operating characteristic curve (ROC) analysis, the cut-off age value was 64 years with an ROC area of 0.65. In women with intact uterus (n = 162), the recurrence rate of cystoceles was lower in the TVM group (log-rank test, P = 0.0001), compared with the NTR group. However, there was no between-group difference in the recurrence rate of cystoceles in women with prior or concomitant hysterectomy (n = 177, P = 0.17). CONCLUSION: In women with intact uterus, the TVM group has a lower recurrence rate of cystoceles than the NTR group. In addition, old age, especially more than 64 years old, is a risk factor for cystocele recurrence.

A Flexible 5-In-1 Microsensor for Internal Microscopic Diagnosis of Vanadium Redox Flow Battery Charging Process.

Multiple important physical parameters in the vanadium redox flow battery are difficult to measure accurately, and the multiple important physical parameters (e.g., temperature, flow, voltage, current, pressure, and electrolyte concentration) are correlated with each other; all of them have a critical influence on the performance and life of vanadium redox flow battery. In terms of the feed of fuel to vanadium redox flow battery, the pump conveys electrolytes from the outside to inside for reaction. As the performance of vanadium redox flow battery can be tested only by an external machine-after which, the speed of pump is adjusted to control the flow velocity of electrolyte-the optimum performance cannot be obtained. There is a demand for internal real-time microscopic diagnosis of vanadium redox flow batteries, and this study uses micro-electro-mechanical systems (MEMS) technology to develop a flexible five-in-one (temperature, flow, voltage, current, and pressure) microsensor, which is embedded in vanadium redox flow battery, for real-time sensing. Its advantages include: (1) Small size and the simultaneous measurement of five important physical quantities; (2) elastic measurement position and accurate embedding; and (3) high accuracy, sensitivity, and quick response time. The flexible five-in-one microsensor embedded in the vanadium redox flow battery can instantly monitor the changes in different physical quantities in the vanadium redox flow battery during charging; as such, optimum operating parameters can be found out so that performance and life can be enhancec.

Age-specific prevalence, clinical and urodynamic findings of detrusor underactivity and bladder outlet obstruction in female voiding dysfunction.

OBJECTIVE: Female voiding dysfunction with cystocele have been widely studied, but there are no data regarding women without cystoceles. The present study aimed to evaluate the prevalence of detrusor underactivity (DU) and bladder outlet obstruction (BOO) without cystoceles in a large sample size. METHODS: This was a retrospective cohort study. Between April 1996 and September 2018, 602 neurologically intact women with voiding dysfunction without cystoceles were enrolled. Detrusor pressure (DU) at the maximum flow rate (PdetQmax) <20 cmH2O, maximum flow rate (Qmax) <15 mL/s, and a bladder voiding efficiency <90% and BOO (PdetQmax ≥40 cmH2O and Qmax <12 mL/s) were diagnosed by urodynamic study. Otherwise, a non-DU/BOO diagnosis was made. The prevalence of DU and BOO was the primary outcome. The secondary outcomes were the analyses of the differences between these three groups in objective UDS parameters and subjective questionnaires and bladder diary parameters. RESULTS: This study included 100 (17%) women with DU, 60 (10%) with BOO, and 442 (73%) with a non-DU/BOO diagnosis. DU increased with age, but BOO decreased as age increased. The women in the DU group were older, had higher parity and pad weights, and lower PdetQmax, maximum urethral closure pressure, and functional profile length than the BOO group. The urodynamic findings did not correlate well to subjective questionnaire parameters. None of the symptoms revealed a significant difference between the groups. The retrospective design was the limitation of the study. CONCLUSION: The prevalence of DU increased with age in women with voiding dysfunction without advanced cystoceles. Conversely, BOO decreased with age. Prevalence intersected in the fourth decade. Diagnosis requires urodynamic evaluation, as subjective symptoms are inconclusive.

The Association Between Maternal Depressive Symptoms and Toddlers' Developmental and Behavioral Problems: A Population-Based Study.

This study aims to compare the developmental-behavioral profiles of 2-year-olds of mothers who experienced postpartum and/or current depression with profiles of toddlers of mothers without depression at either time using population-based Rhode Island data. Weighted data from Rhode Island Department of Health's Pregnancy Risk Assessment Monitoring System and Rhode Island's follow-up Toddlers Wellness Overview Survey distributed to mothers giving birth between 2006 and 2008 were analyzed. Compared with non-depressed mothers, those with any depression following childbirth reported more concerns with their toddlers' receptive language, social-emotional development, and their sleep and feeding behaviors. When adjusted for demographics, persistent depression remained associated with social-emotional (adjusted odds ratio [aOR] = 7.53, 2.78-20.34) and feeding concerns (aOR = 3.13, 1.36-7.22), and current depression was associated with social-emotional concerns (aOR = 2.52, 1.26-5.01). We conclude that pediatric providers should explore maternal mental health as a mediating and potentially modifiable factor beyond the postpartum period when toddlers present with developmental-behavioral challenges.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

Relationship between Q-Tip Test and Urethral Hypermobility on Perineal Ultrasound.

BACKGROUND: The aim of this study was to assess the correlation between the overall rest-stress distance measured by transperineal ultrasound (TPUS) and Q-tip test angle in women with urodynamic stress incontinence (USI), and determine a cut-off value of rest-stress distance for predicting urethral hypermobility (UH). METHODS: Women with USI scheduled for mid-urethral sling surgery were retrospectively recruited. UH was defined as a Q-tip angle more than or equal to 30 degrees. Ultrasonic measurement of the overall rest-stress distance was defined as the linear distance of bladder-neck position change from resting status to maximal strain. RESULTS: Among the 132 enrolled women, the Pearson correlation coefficient between the overall rest-stress distance in TPUS and Q-tip test angle was 0.9104 (95% CI, 0.8758-0.9357, p < 0.001). In receiver-operating-characteristic-curve analysis, a rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH (sensitivity = 76.47%, specificity = 93.3%; area = 0.937, 95% confidence interval: 0.881-0.972). CONCLUSIONS: The overall rest-stress distance in TPUS correlated well with the Q-tip test angle, indicating that it can be an alternative method for the assessment of USI. A rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH in women with USI.

Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents.

Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45µM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC(50) values of 2.2-3.0µM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase.

Impact of mirabegron versus solifenacin on autonomic function and arterial stiffness in female overactive bladder syndrome: a randomized controlled trial.

The study aims to elucidate the impact of mirabegron versus solifenacin on autonomic function and peripheral arterial conditions in women with overactive bladder syndrome (OAB). All consecutive women with OAB were randomized to receive 12 weeks of mirabegron 25 mg or solifenacin 5 mg once per day. Heart rate variability, cardio-ankle vascular index, ankle-brachial pressure index, blood pressure, and heart rate were compared between the two groups. There were 87 women (mirabegron, n = 43; and solifenacin, n = 44) who completed 12-week treatment and underwent heart rate variability examination. Systolic blood pressure (median: - 4.5 to - 5.5 mmHg) and diastolic blood pressure (median: - 0.5 to - 3.5 mmHg) decreased after solifenacin treatment, and heart rate (median: + 2 bpm) increased after mirabegron treatment, despite of no between-group difference. In addition, posttreatment heart rate variability, cardio-ankle vascular index, and ankle-brachial pressure index did not differ compared with baseline; and there were no between-group differences. In conclusion, solifenacin might decrease blood pressure, and mirabegron might increase heart rate. Nonetheless, there were no significant impacts of 12-week mirabegron versus solifenacin treatment on autonomic function and arterial stiffness.

Changes in sexual function and vaginal topography using transperineal ultrasound after vaginal laser treatment for women with stress urinary incontinence.

We aim to assess the changes in sexual function and vaginal topography using 3-D transperineal ultrasound in stress-incontinent women treated with Er:YAG vaginal laser. Two hundred and twenty women with stress urinary incontinence (SUI) treated with Er:YAG laser were recruited. Assessment before and 6 months after the treatment included vaginal topography using 3-D transperineal ultrasound and sexual function using female sexual function index questionnaire (FSFI). A total of 50 women with complete data showed that the symptomatic improvement was noted in 37 (74%) women. After Er:YAG vaginal laser treatment, significantly decreased width and cross-sectional area in proximal, middle, and distal vagina were found in women with SUI. Nearly all of the domains of FSFI improved significantly after the vaginal laser treatment, except sexual desire. In conclusion, 3-D transperineal ultrasound can be used to conduct vaginal topography. After Er:YAG vaginal laser treatment, the anatomical changes of vaginal shrinkage and the improvement of female sexual function were both noted. The favorable outcome of sexual function partly related to the tightening of vagina, as evidenced by the measurements of the 3-D transperineal ultrasound.

A Lung Cancer Screening Education Program Impacts both Referral Rates and Provider and Medical Assistant Knowledge at Two Federally Qualified Health Centers.

BACKGROUND: Federally Qualified Health Centers (FQHCs) serve minority and low-socioeconomic populations and provide care to high-risk smokers. These centers frequently experience barriers, including low provider and medical assistant (MA) knowledge around lung cancer screening (LCS). Subsequent low LCS referral rates by providers at FQHCs limit utilization of LCS in eligible, high-risk, underserved patients. METHODS: Providers and MAs from two FQHCs participated in a LCS educational session. A pre-educational survey was administered at the start of the session and a post-educational survey at the end. The intervention included a presentation with education around non-small cell lung cancer, LCS, tobacco cessation, and shared-decision making. Both surveys were used to evaluate changes in provider and MA ability to determine eligible patients for LCS. The Pearson's Chi-squared test with Yates' continuity correction was used to measure the impact. RESULTS: A total of 29 providers and 28 MAs enrolled in the study from two FQHCs. There was an improvement, P < .009 and P < .015 respectively, in provider and MA confidence in identifying patients for LCS. Additionally, one year prior to the program, 9 low-dose computed tomography (LDCTs) were ordered at one of the FQHCs and 0 at the other. After the program, over 100 LDCTs were ordered at each FQHC. CONCLUSIONS: A targeted LCS educational program improves provider and MAs' ability to identify eligible LCS patients and is associated with an increase in the number of patients referred to LDCT at FQHCs.

Antitumor agents 283. Further elaboration of desmosdumotin C analogs as potent antitumor agents: activation of spindle assembly checkpoint as possible mode of action.

In our ongoing study of the desmosdumotin C (1) series, twelve new analogues, 21-32, mainly with structural modifications in ring-A, were prepared and evaluated for in vitro antiproliferative activity against several human tumor cell lines. Among them, the 4'-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant antiproliferative activity against multiple human tumor cell lines with ED(50) values of 1.1-2.8 µM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural compound 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an isobutyl ether showed selective antiproliferative activity against lung cancer A549 cells (ED(50) 1.7 µM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase.