Lasers in Gynecology.

The first published reports on the use of laser for cervical pathology date back to 1973. Technical advancements in flexible and rigid laser fibers revolutionized video laser laparoscopy in the 1990s. Fractionated lasers have been used to treat vulvovaginal symptoms associated with genitourinary syndrome of menopause, lichen sclerosus, and urinary incontinence. Review of available data suggests that fractionated lasers can improve both subjective and objective signs of vaginal atrophy and lichen sclerosus, but the evidence is weak because most of the trials are underpowered, are at risk for bias, and lack long-term follow-up. There is no strong evidence to support fractionated laser therapy for urinary incontinence or low-level laser therapy for chronic pelvic pain. Although short-term, single-arm trials suggest benefit of fractionated laser therapy for genitourinary syndrome of menopause, lichen sclerosus, and urinary incontinence, additional adequately powered, prospective, randomized, and longer-term comparative trials are needed before lasers can be recommended for these specific conditions. The purpose of this Clinical Expert Series is to review basic laser biophysics and the mechanism of action for modern fractionated lasers as relevant to the gynecologist. We also summarize safety and effectiveness data for lasers used for some of the most commonly studied gynecologic conditions: the vulvovaginal atrophy component of genitourinary syndrome of menopause, lichen sclerosus, and urinary incontinence.

Assessment of patient satisfaction with home vs office indwelling catheter removal placed for urinary retention after female pelvic floor surgery: a randomized controlled trial.

BACKGROUND: Postoperative urinary retention is burdensome for patients. We seek to improve patient satisfaction with the voiding trial process. OBJECTIVE: This study aimed to assess patient satisfaction with location of indwelling catheter removal placed for urinary retention after urogynecologic surgery. STUDY DESIGN: All adult women who were diagnosed with urinary retention requiring postoperative indwelling catheter insertion after undergoing surgery for urinary incontinence and/or pelvic organ prolapse were eligible for this randomized controlled study. They were randomly assigned to catheter removal at home or in the office. Those who were randomized to home removal were taught how to remove the catheter before discharge, and were discharged home with written instructions, a voiding hat, and 10-mL syringe. All patients had their catheter removed 2 to 4 days after discharge. Those patients who were allocated to home removal were contacted in the afternoon by the office nurse. Subjects who graded their force of urine stream 5, on a scale of 0 to 10, were considered to have safely passed their voiding trial. For patients randomized to the office removal group, the voiding trial consisted of retrograde filling the bladder to maximum they could tolerate up to 300 mL. Urinating >50% of instilled volume was considered successful. Those who were unsuccessful in either group had catheter reinsertion or self-catheterization training in the office. The primary study outcome was patient satisfaction, measured based on patients' response to a question, "How satisfied were you with the overall removal process of the catheter?" A visual analogue scale was created to assess patient satisfaction and 4 secondary outcomes. A sample size of 40 participants per group were needed to detect a 10 mm difference in satisfaction between groups on the visual analogue scale. This calculation provided 80% power and an alpha of 0.05. The final number accounted for 10% loss to follow up. We compared the baseline characteristics, including urodynamic parameters, relevant perioperative indices, and patient satisfaction between the groups. RESULTS: Of the 78 women enrolled in the study, 38 (48.7%) removed their catheter at home and 40 (51.3%) had an office visit for catheter removal. Median and interquartile range for age, vaginal parity, and body mass index were 60 (49-72) years, 2 (2-3), and 28 (24-32) kg/m2, respectively, in the overall sample. Groups did not differ significantly in age, vaginal parity, body mass index, previous surgical history, or type of concomitant procedures. Patient satisfaction was comparable between the groups, with a median score (interquartile range) of 95 (87-100) in the home catheter removal group and 95 (80-98) in the office catheter removal group (P=.52). Voiding trial pass rate was similar between women who underwent home (83.8%) vs office (72.5%) catheter removal (P=.23). No participants in either group had to emergently come into the office or hospital due to inadequate voiding afterwards. Within 30 days post operatively, a lower proportion of women in the home catheter removal group (8.3%) had urinary tract infection, compared to patients in the office catheter removal group (26.3%) (P=.04). CONCLUSION: In women with urinary retention after urogynecologic surgery, there is no difference in satisfaction concerning the location of indwelling catheter removal when comparing home and office.

Thermal stability analyses of human PERIOD-2 C-terminal domain using dynamic light scattering and circular dichroism.

At the molecular level, the circadian clock is regulated by a time delayed transcriptional-translational feedback loop in which the core proteins interact with each other rhythmically to drive daily biological rhythms. The C-terminal domain of a key clock protein PER2 (PER2c) plays a critically important role in the loop, not only for its interaction with the binding partner CRY proteins but also for the CRY/PER complex's translocation from the cytosol to the nucleus. Previous circular dichroism (CD) spectroscopic studies have shown that mouse PER2c (mPER2c) is less structured in solution by itself but folded into stable secondary structures upon interaction with mouse CRYs. To understand the stability and folding of human PER2c (hPER2c), we expressed and purified hPER2c. Three oligomerization forms of recombinant hPER2c were identified and thoroughly characterized through a combination of biochemical and biophysical techniques. Different to mPER2c, both thermal unfolding DLS and CD analyses suggested that all forms of hPER2c have very stable secondary structures in solution by themselves with melting temperatures higher than the physiological body temperature, indicating that hPER2c does not require CRY to fold. Furthermore, we examined the effects of EDTA, salt concentration, and a reducing agent on hPER2c folding and oligomerization. The ability of hPER2c forming oligomers reflects the potential role of hPER2c in the assembly of circadian rhythm core protein complexes.

Association Between Insurance Status and Access to Hospital Care in Emergency Department Disposition.

Importance: Studies of public hospitals have reported increasing incidence of emergency department (ED) transfers of uninsured patients for hospitalization, which is perceived to be associated with financial incentives. Objective: To examine the differences in risk-adjusted transfer and discharge rates by patient insurance status among hospitals capable of providing critical care. Design, Setting, and Participants: A cross-sectional analysis of the 2015 National Emergency Department Sample was conducted, including visits between January 2015 and December 2015. Adult ED visits throughout 2015 (n = 215 028) for the 3 common medical conditions of pneumonia, chronic obstructive pulmonary disease, and asthma, at hospitals with intensive care capabilities were included. Only hospitals with advanced critical care capabilities for pulmonary care were included. Main Outcomes and Measures: The primary outcomes were patient-level and hospital-level risk-adjusted ED discharges, ED transfers, and hospital admissions. Adjusted odds of discharge or transfer compared with admission among uninsured patients, Medicaid and Medicare beneficiaries, and privately insured patients are reported. Hospital ownership status was used for the secondary analysis. Results: Of the 30 542 691 ED visits to 953 hospitals included in the 2015 National Emergency Department Sample, 215 028 visits (0.7%) were for acute pulmonary diseases to 160 intensive care-capable hospitals. These visits were made by patients with a median (interquartile range [IQR]) age of 55 (40-71) years and who were predominantly female (124 931 [58.1%]). Substantial variation in unadjusted and risk-standardized ED discharge, ED transfer, and hospital admission rates was found across EDs. Compared with privately insured patients, uninsured patients were more likely to be discharged (odds ratio [OR], 1.66; 95% CI, 1.57-1.76) and transferred (adjusted OR [aOR], 2.41; 95% CI, 2.08-2.79). Medicaid beneficiaries had comparable odds of discharge (aOR, 1.00; 95% CI, 0.97-1.04) but higher odds of transfer (aOR, 1.19; 95% CI, 1.05-1.33). Conclusions and Relevance: After accounting for hospital critical care capability and patient case mix, the study found that uninsured patients and Medicaid beneficiaries with common medical conditions appeared to have higher odds of interhospital transfer.

Outcomes after observation stays among older adult Medicare beneficiaries in the USA: retrospective cohort study.

Objective To characterize rates and trends over time of emergency department treatment-and-discharge stays, repeat observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from observation stays.Design Retrospective cohort study.Setting 4750 hospitals in the USA.Participants Nationally representative sample of Medicare fee for service beneficiaries aged 65 or over discharged after 363 037 index observation stays, 2 540 000 index emergency department treatment-and-discharge stays, and 2 667 525 index inpatient stays from 2006-11.Main outcome measures Rates of emergency department treatment-and-discharge stays, observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from index observation stays. Rates were compared with corresponding outcomes within 30 days of discharge from both index emergency department treatment-and-discharge stays and index inpatient stays.Results Among 363 037 index observation stays resulting in discharge from 2006-11, 30 day rates of emergency department treatment-and-discharge stays were 8.4%, repeat observation stays were 2.9%, inpatient stays were 11.2%, any hospital revisit was 20.1%, and death was 1.8%. Of all revisits, 49.7% were for inpatient stays. Revisit rates for emergency department treatment-and-discharge stays, repeat observation stays, and any hospital revisit increased from 2006-11 (P<0.001 for trend), while 30 day rates of inpatient stays (P=0.054 for trend) and 30 day mortality (P=0.091 for trend) were both unchanged. Averaged over the study period, 30 day rates of any hospital revisit were similar after discharge from index emergency department treatment-and-discharge stays (19.9%) and index observation stays (20.1%), as was 30 day mortality (1.8% for both). Rates of any hospital revisit (21.8%) and death (5.2%) were highest after discharge from index inpatient stays.Conclusions Hospital revisits are common after discharge from observation stays, frequently result in inpatient hospitalizations, and have increased over time among Medicare beneficiaries. As revisit rates are similar after emergency department and observation stays, strategies shown to enhance emergency department transitional care may be reasonable starting points to improve post-observation outcomes.

Optimizing sgRNA structure to improve CRISPR-Cas9 knockout efficiency.

BACKGROUND: Single-guide RNA (sgRNA) is one of the two key components of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing system. The current commonly used sgRNA structure has a shortened duplex compared with the native bacterial CRISPR RNA (crRNA)-transactivating crRNA (tracrRNA) duplex and contains a continuous sequence of thymines, which is the pause signal for RNA polymerase III and thus could potentially reduce transcription efficiency. RESULTS: Here, we systematically investigate the effect of these two elements on knockout efficiency and showed that modifying the sgRNA structure by extending the duplex length and mutating the fourth thymine of the continuous sequence of thymines to cytosine or guanine significantly, and sometimes dramatically, improves knockout efficiency in cells. In addition, the optimized sgRNA structure also significantly increases the efficiency of more challenging genome-editing procedures, such as gene deletion, which is important for inducing a loss of function in non-coding genes. CONCLUSIONS: By a systematic investigation of sgRNA structure we find that extending the duplex by approximately 5 bp combined with mutating the continuous sequence of thymines at position 4 to cytosine or guanine significantly increases gene knockout efficiency in CRISPR-Cas9-based genome editing experiments.

Vigor of movements and the cost of time in decision making.

If we assume that the purpose of a movement is to acquire a rewarding state, the duration of the movement carries a cost because it delays acquisition of reward. For some people, passage of time carries a greater cost, as evidenced by how long they are willing to wait for a rewarding outcome. These steep discounters are considered impulsive. Is there a relationship between cost of time in decision making and cost of time in control of movements? Our theory predicts that people who are more impulsive should in general move faster than subjects who are less impulsive. To test our idea, we considered elementary voluntary movements: saccades of the eye. We found that in humans, saccadic vigor, assessed using velocity as a function of amplitude, was as much as 50% greater in one subject than another; that is, some people consistently moved their eyes with high vigor. We measured the cost of time in a decision-making task in which the same subjects were given a choice between smaller odds of success immediately and better odds if they waited. We measured how long they were willing to wait to obtain the better odds and how much they increased their wait period after they failed. We found that people that exhibited greater vigor in their movements tended to have a steep temporal discount function, as evidenced by their waiting patterns in the decision-making task. The cost of time may be shared between decision making and motor control.