Headavila3068

To report a case of a testosterone deficient man desiring maintenance of spermatogenesis converting from clomiphene citrate (CC) to Natesto, who had a decrease in gonadotropins and semen parameter values after making this medication change. The data on men maintaining gonadotropins and semen parameter values after converting from CC to Natesto is also reported.

A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed.

A 32-year-old testosterone deficient man desiring to maintain future fertility potential who had a poor symptomatic response to CC despite an adequate serum testosterone response was converted to Natesto 11 mg twice daily. His gonadotropins diminished as did his semen parameter values but with dose titration of Natesto to 11 mg in the morning and 5.5 mg in the evening he had normalization of gonadotropins and a rise in semen parameter values back towards his values on CC witmatic response to treatment.

To evaluate pain improvement and recurrent stress incontinence (SUI) following painful synthetic midurethral sling (MUS) removal.

We conducted a retrospective review of patients who underwent synthetic MUS removal at our institution from 2009-2016 for the indication of pain. We recorded sling type (transobturator vs. retropubic), complete vs. partial removal, and presenting symptoms. Postoperative pain improvement was categorized as resolved (pain resolved, requiring no further therapy), improved (pain less bothersome, may require further therapy), or unresolved (no/minimal improvement, requiring further management). Recurrent incontinence and further reconstructive procedures were assessed.

87 patients (49 complete and 38 partial removal) with pain as the primary indication for removal were included. Median age at intervention was 54 years with median follow-up of 8 months. Overall, pain improved or resolved in 78.1% of cases. Complete removal was associated with significantly greater percentage of paival in both retropubic and transobturator slings. Rates of recurrent SUI and reintervention for SUI were not related to the extent of sling removal.

To report our initial experience with the extra-tunical grafting (ETG) procedure. This procedure was recently introduced by UCSF investigators as a tunica-sparing technique for management of penile concavity deformities.

We retrospectively reviewed records of patients who underwent ETG at our tertiary-care referral center between 2017-2020. A collagen graft made from bovine pericardium (Lyoplant®) was placed overlying the defect without violating the tunica albuginea or mobilizing the neurovascular bundle. The stretched penile length (SPL) and circumference at the location of deformity were measured intra-operatively. Patient reported outcomes were evaluated by an anonymous ten-question online survey.

Nineteen men underwent ETG with a median follow-up of 59 (IQR 24 - 708) days. ETG was performed via either a window (15/19, 78%) or a de-gloving (4/19, 21%) incision with concomitant penile plication performed in 16/19 (84%) patients. Penile circumference increased by an average of 1.4 cm + 0.5 (p = 0.03) at the location of deformity, while pre- and post-operative SPL were similar (14.0 + 1.4 vs. 14.0 + 1.3 cm, p = 0.95). Overall patient satisfaction was reported by 13/15 (86%) patients. Twelve out of 15 (80%) patients reported concavity deformity to be "improved", with 73% reporting "much better". Among 8 patients with follow up greater than six months, graft palpability was reported in 4/8 (50%) patients but was not bothersome.

The ETG procedure appears to be safe and effective for the treatment of penile concavity deformities. Patient outcomes and satisfaction are favorable at intermediate follow up.

The ETG procedure appears to be safe and effective for the treatment of penile concavity deformities. Patient outcomes and satisfaction are favorable at intermediate follow up.

To retrospectively evaluate enhanced recovery after surgery (ERAS) protocol administration, hospital length of stay, 30-day readmission, and complication rates among cystectomy and/or urinary diversion patients with benign or malignant indication.

Data was extracted retrospectively for cystectomy and/or urinary diversion performed at our institution from June 2016 to May 2019. Descriptive statistics, Chi squared, Wilcoxon rank-sum, binary logistic regression, and linear regression functions in R 4.0.4 (R Foundation), R Package "Tidverse" V1.3.0.9, and RStudio V1.44.1106 (RStudio, PBC) were used to analyze data.

102 patients met selection criteria with 36 and 66 patients in the benign and malignant indication cohorts, respectively. Poly-D-lysine nmr Significant differences between cohorts included BMI, age, opioid exposure, and spinal anomalies. The malignant cohort had higher ERAS completion rates for preoperative and intraoperative protocols (41% and 53% versus 14% and 19%). The mean ERAS item administration for benign s and higher postoperative complication rates. Population-specific ERAS protocols targeted at increasing ERAS completion could reduce morbidity.Methicillin-resistant Staphylococcus aureus is one of the leading causes of community and nosocomial infections, which has created the urgent need for innovative anti-infective agents to control MRSA-associated infections. A conserved serine protease, caseinolytic peptidase P (ClpP) in Staphylococcus aureus is highly associated with pathogenicity and has been claimed to be a novel antimicrobial target. We aim to search suitable inhibitors of ClpP to attenuate the virulence of MRSA and combat their infections in vivo. Over 500 natural compounds were pre-screened via fluorescence resonance energy transfer using the Suc-LY-AMC substrate. The binding of myricetin to ClpP was determined and the mechanism of action was elucidated by thermal shift assay, surface plasmon resonance, and molecular dynamics simulations. The therapeutic effects of myricetin on S. aureus infection were further investigated using a S. aureus-induced pneumonia model. We revealed that myricetin could effectively block the activity of ClpP without disturbing the growth of the bacteria and the Gln-47 and Met-31 residues were necessary for myricetin binding to ClpP. Importantly, myricetin attenuated the pathogenicity of S. aureus in vivo, while improving the efficacy of the traditional antibiotic oxacillin against MRSA infection and protecting mice from fatal lung infections caused by MRSA. These findings indicate that myricetin has the potential to be applied in the pharmaceutical industry as a promising therapeutic agent.Chronic Environmental Enrichment (EE) has been shown to prevent the relapse to addictive behaviours, such as drug-taking and -seeking. Recently, acute EE was shown to reduce cue-induced sucrose-seeking, but its effects on contextual (Cx)-induced sucrose-seeking is still unknown. Here we report the effects of brief EE exposure on Cx-induced sucrose-seeking with and without prior Cx-memory reactivation. Adult male Sprague-Dawley rats were trained to sucrose self-administration associated to a specific conditioning Cx (CxA), followed by a 7-day extinction in a different Cx (CxB). Afterwards, rats were exposed for 22 h to EE, and 1 h later to either i) Cx-induced sucrose-seeking (1 h, renewal without Cx-memory reactivation), ii) or two different Cx-memory reactivations short (2-min) and long (15-min) CxA-retrieval session (Cx-Ret). In Cx-Ret experiments, CxA-induced sucrose-seeking test (1 h) was done after a subsequent 3-day extinction phase. The assessment of molecular markers of memory reactivation/reconsolidation, Zif-268 and rpS6P, was performed 2 h after Cx-Ret. Brief EE exposure enhanced Cx-induced sucrose-seeking without and with short but not long Cx-retrieval. Moreover, EE impaired discriminative responding at test prior to long, whereas improved it with or without short Cx-retrieval. Different changes in Zif-268 and rpS6P expression induced by short vs. long Cx-Ret were correlated to behavioural data, suggesting the occurrence of different memory processes affected by EE. Our data show that brief EE exposure may differently affect subsequent appetitive relapse depending on the modality of re-exposure to conditioned context. This finding suggests caution and further studies to understand the proper conditions for the use of EE against appetitive and addiction disorders.

Oral therapies targeting the integrin α4β7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4β7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC).

Invitro studies measured binding properties of PTG-100. Mouse studies measured biomarkers and drug concentrations in blood and tissues. The phase 1 study involved healthy volunteers. In phase 2a, patients with moderate to severe active UC were randomized to receive PTG-100 (150, 300, or 900 mg) or placebo once daily for 12-weeks.

PTG-100 potently and selectively blocks α4β7. Oral dosing of PTG-100 in mice showed high levels of target engagement and exposure in gut-associated lymphoid tissues. In healthy volunteers, PTG-100 showed dose-dependent increases in plasma exposure and blood target engagement. Although this phase 2a study initially did not meet the primary biological and clinical response and showed a dose response reflecting similar activities in preclinical models and healthy individuals. These data suggest that local gut activity of an oral α4β7 integrin antagonist, distinct from full target engagement in blood, are important for efficacy and the treatment of UC. (ClinicalTrials.gov, Number NCT02895100; EudraCT, Number 2016-003452-75).

The international consensus guidelines updated in 2017 recommended surgery to all main duct intraductal papillary mucinous neoplasms (MD-IPMNs) with the main pancreatic duct (MPD) of 10 mm or more and those with mural nodule regardless of its size. The aim of the present study is to identify predictors of malignancy in MD-IPMN among preoperative factors including sizes of MPD and mural nodule.

Twenty-six benign MD-IPMNs (7 resected and 19 nonresected MD-IPMNs) and 32 malignant MD-IPMNs (31 resected and 1 nonresected MD-IPMN) were enrolled. Magnetic resonance cholangiopancreatography (MRCP), computed tomography (CT), endoscopic ultrasonography (EUS), and cytology was performed using pancreatic juice collected by endoscopic retrograde pancrestography (ERP). Resected IPMNs were classified as benign or malignant by histological examination; nonresected MD-IPMNs by imaging, cytology, and observation. Cutoff values of candidate parameters were determined by receiver operating characteristic (ROC) curves. Univariate and multivariate analyses by regression model were performed.

Sizes of MPD and mural nodule and result of cytology differed significantly between benign and malignant groups. Cutoff values of MPD and mural nodule sizes were 15 mm and 10 mm with areas under the curve (AUC) of 0.66 and 0.86, respectively. Mural nodule of 10 mm or more (OR, 8.32; 95% CI, 1.13-61.2; P=0.038) and positive cytology (OR, 42.5; 95% CI, 4.10-439; P=0.002) were shown to be independent predictors of malignancy by multivariate analysis. When MD-IPMNs that had either of the predictors were diagnosed to be malignant, sensitivities, specificities, and overall accuracy for malignancy were 94%, 85%, and 90%, respectively.

Mural nodule of 10 mm or more and positive cytology were independent predictors of malignancy in MD-IPMN.

Mural nodule of 10 mm or more and positive cytology were independent predictors of malignancy in MD-IPMN.