Ssn3, also known as Cdk8, is a member of the four protein Cdk8 submodule within the multi-subunit Mediator complex involved in the co-regulation of transcription. In Candida albicans, the loss of ...Ssn3 kinase activity affects multiple phenotypes including cellular morphology, metabolism, nutrient acquisition, immune cell interactions, and drug resistance. In these studies, we generated a strain in which Ssn3 was replaced with a functional variant of Ssn3 that can be rapidly and selectively inhibited by the ATP analog 3-MB-PP1. Consistent with ssn3 null mutant and kinase dead phenotypes, inhibition of Ssn3 kinase activity promoted hypha formation. Furthermore, the increased expression of hypha-specific genes was the strongest transcriptional signal upon inhibition of Ssn3 in transcriptomics analyses. Rapid inactivation of Ssn3 was used for phosphoproteomic studies performed to identify Ssn3 kinase substrates associated with filamentation potential. Both previously validated and novel Ssn3 targets were identified. Protein phosphorylation sites that were reduced specifically upon Ssn3 inhibition included two sites in Flo8 which is a transcription factor known to positively regulate C. albicans morphology. Mutation of the two Flo8 phosphosites (threonine 589 and serine 620) was sufficient to increase Flo8-HA levels and Flo8 dependent transcriptional and morphological changes, suggesting that Ssn3 kinase activity negatively regulates Flo8.Under embedded conditions, when ssn3Δ/Δ and efg1Δ/Δ mutants were hyperfilamentous, FLO8 was essential for hypha formation. Previous work has also shown that loss of Ssn3 activity leads to increased alkalinization of medium with amino acids. Here, we show that the ssn3Δ/Δ medium alkalinization phenotype, which is dependent on STP2, a transcription factor involved in amino acid utilization, also requires FLO8 and EFG1. Together, these data show that Ssn3 activity can modulate Flo8 and its direct and indirect interactions in different ways, and underscores the potential importance of considering Ssn3 function in the control of transcription factor activities.
Delayed orgasm and anorgasmia Jenkins, Lawrence C; Mulhall, John P
Fertility and sterility,
11/2015, Letnik:
104, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed ...orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy.
Abstract Context and objective To present a summary of the 2nd International Consultation on Bladder Cancer recommendations on the screening, diagnosis, and markers of bladder cancer using an ...evidence-based strategy. Evidence acquisition A detailed Medline analysis was performed for original articles addressing bladder cancer with regard to screening, diagnosis, markers, and pathology. Proceedings from the last 5 yr of major conferences were also searched. Evidence synthesis The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analyzed. Conclusions Cystoscopy alone is the most cost-effective method to detect recurrence of bladder cancer. White-light cystoscopy is the gold standard for evaluation of the lower urinary tract; however, technology like fluorescence-aided cystoscopy and narrow-band imaging can aid in improving evaluations. Urine cytology is useful for the diagnosis of high-grade tumor recurrence. Molecular medicine holds the promise that clinical outcomes will be improved by directing therapy toward the mechanisms and targets associated with the growth of an individual patient's tumor. The challenge remains to optimize measurement of these targets, evaluate the impact of such targets for therapeutic drug development, and translate molecular markers into the improved clinical management of bladder cancer patients. Physicians and researchers eventually will have a robust set of molecular markers to guide prevention, diagnosis, and treatment decisions for bladder cancer.
Despite physicians frequently caring for patients with sexual health issues, only 50% of United States medical schools require formal education in sexual medicine, and there are currently no ...guidelines pertaining to this with research which found that medical trainees are ill-equipped to provide sexual healthcare.
This study aims to identify areas to improve sexual health training in order to increase physician confidence and competence in evaluating and training patients with sexual health problems.
A prospective survey was sent via REDCap to medical students (n = 190, 68.6%), residents (n = 75, 27.1%), and fellows (n = 11, 3.9%) via a known listserv. Participants (N = 276, ∼15% response rate) were asked to provide demographic information, whether they received sexual health training during medical school and rate their confidence in addressing patients' sexual health concerns.
Medical students and residents currently do not receive sufficient education on sexual health and medicine, particularly in fields outside of OB-GYN and Urology, leaving them underqualified and less confident than needed for adequate patient care.
65.6% of trainees reported receiving formal sexual health education, while 13.9% received informal education, and 20.6% received no education during medical school. Although trainees desire to understand a patients' sexual health (P < .001), only residents in a relevant field (Urology, OB-GYN) felt confident in their ability to assist patients with a sexual health issue (P = .013). All other trainees lacked confidence in attending to sexual health concerns (P < .001), regardless of training level (P > .1).
More efforts should be made to integrate sexual health education into medical school curriculum.
The strength of this study includes specific evaluation of medical student and resident confidence level with 15 individual sexual health topics. The limitations include that the demographic was regionally confined to the Midwest of the United States and women were more strongly represented among medical students.
Due to the lack of standardized education, medical trainees (except for Urology and OB-GYN residents) feel unprepared to treat patients with sexual health issues, and medical schools should make sexual health education mandatory. Beebe S, Payne N, Posid T, et al. The Lack of Sexual Health Education in Medical Training Leaves Students and Residents Feeling Unprepared. J Sex Med 2021;18:1998-2004.
To develop and evaluate a mobile phone-based skills assessment tool that measures procedural competency of urology residents learning to perform a common, non-robotic urology procedure as a means of ...tracking current skillset and improvement over time.
The assessment tool was a Qualtrics survey accessed via a smartphone link that breaks down a vasectomy into 6 critical steps. Level of competency was measured on a scale of '1-novice' to '5-expert.' Nine residents from Post graduate year (PGY)-1 to PGY-5 were evaluated by one instructor after completing a vasectomy (86 single-side cases recorded over a 6-month period). We compared individual trainees to each other, analyzed performance (improvement) over time, and evaluated competency against cohort and program averages.
As an example, a single resident ('Resident 2,' N = 11 cases) was compared to cohort (PGY, M = 7.5/resident) and program (all residents, M = 7.4/resident). Results indicate similar skillfulness across Step 1 (puncturing and isolation of vas and hand positioning; P > 0.1), but marginally lower competency on Step 2 (opening of vasal sheath to expose/isolate vas; vs. cohort: P = 0.076, vs. residents: P = 0.082). Significantly lower competency on Steps 3-6 (all P < 0.04) suggests targeted teaching could improve cautery technique, fascial interposition, hemostasis, and positioning of stumps.
Our mobile-based skills assessment is a low cost, novel, and efficient assessment that would support current Accreditation Council for Graduate Medical Education (ACGME) goals to increase competency-based residency training. This tool is easily created and accessed, provides real-time feedback to learners, and can be used for individual and group assessment at a single timepoint or longitudinally.
After a focused telehealth visit, patients can now access phosphodiesterase-5 inhibitor (PDE5 inhibitor) prescriptions through online direct-to-consumer (DTC) healthcare companies. This study seeks ...to quantify the cost of DTC PDE5 inhibitor treatment compared to a traditional physician visit and local pharmacy prescription. Two DTC companies, two compounding pharmacies with national reach, three online Canadian pharmacies, and sixteen American pharmacy chains were queried for prices of 90-day regimens of common PDE5 inhibitors. Prices for chains were determined using their publicly available price on GoodRx
with coupon. Cost of physician visit was determined using 2020 Center for Medicare and Medicaid Services reimbursement for a level 3 new patient visit. For sildenafil 20 mg, a physician visit and local prescription cost a low of $125.45 compared to $144.35 for compounding, $169.34 for Canadian, and $195.00 for DTC. For sildenafil 100 mg, a physician visit and local prescription cost a low of $137.16 compared to $289.35 for compounding, $200.36 for Canadian, and $900.00 for DTC. For tadalafil 5 mg, a physician visit and local prescription cost a low of $125.80 compared to $169.35 for compounding, $195.34 for Canadian, and $720.00 for DTC. For tadalafil 20 mg, a physician visit and local prescription cost a low of $161.00 compared to $289.35 for compounding, $229.00 for Canadian, and $2880.00 for DTC. Thus, local pharmacies, in conjunction with online coupons, consistently provide a markedly less-expensive option for fulfillment of PDE5 inhibitor prescriptions than online DTC services.
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is often fatal. To determine predictors of risk for death, we conducted a retrospective cohort study. We examined 699 episodes of MRSA ...bacteremia involving 603 patients admitted to an academic medical center in New York City during 2002-2007. Data came from chart reviews, hospital databases, and recultured frozen MRSA specimens. Among the 699 episodes, 55 were caused by vancomycin-intermediate resistant S. aureus strains, 55 by heteroresistant vancomycin-intermediate S. aureus strains, and 589 by non-vancomycin-resistant strains; 190 (31.5%) patients died. We used regression risk analysis to quantify the association between clinical correlates and death. We found that older age, residence in a nursing home, severe bacteremia, and organ impairment were independently associated with increased risk for death; consultation with an infectious disease specialist was associated with lower risk for death; and MRSA strain types were not associated with risk for death.
A single-use flexible cystoscope with integrated grasper (
; Coloplast, Denmark) has recently become commercially available. The objective of our study is to compare the costs of stent removal in an ...outpatient clinical environment between the single-use
system (Coloplast) to our existing approach using a reusable cystoscope and stent grasper.
The number of stent removal procedures at our tertiary center was recorded as a proportion of all cystoscopic procedures performed between February 2016 and February 2017. Elements in the micro-cost assessment included original purchasing price of an Olympus digital reusable cystoscope, repair fee (based on a 1-year contract), sterilization equipment and accessory costs, reprocessing costs of the cystoscope, and labor costs. The costs were estimated on a per-use basis and compared to the purchasing price of
.
A total of 1775 cystoscopic procedures were performed, and the reusable cystoscope was used for stent removal in 871 (49%) cases. The per-use cost for stent removal procedures using the reusable cystoscope was estimated to be $161.85. The single per-use purchasing price for the
device is $200. Based on the current volume, the break-even point was calculated to be 704 stent pulls. After 704 stent pulls, the cost benefit favors the reusable cystoscope.
Based on this micro-cost analysis, per-use costs appear to favor the reusable cystoscope for stent removal. It appears that centers with high volumes of stent pulls may find the reusable cystoscope and stent grasper more cost beneficial than the single-use system.
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