Citations

A validated reverse-phase ultra-performance liquid chromatography (UPLC) method has been developed for the precise determination of impurities in Clidinium Bromide (CDB) and Chlordiazepoxide Hydrochloride (CDH) Capsules. This study focuses on the separation of impurities, namely Benzylic acid (BZY) related to Clidinium, Chlordiazepoxide Related Compound A (CDRC-A), and Chlordiazepoxide Related Compound C (CDRC-C). The Water’s H-Class UPLC system, equipped with a PDA Detector, was employed with a 15µL loop size, operating at a detection wavelength of 215 nm in gradient mode with a flow rate of 0.3 mL/min, resulting in a total run time of 55 min. The chromatographic separation utilized a Waters Acquity UPLC BEH C18 column (150 mm × 2.1 mm i.d., 1.7 µm particle size) at a column temperature of 55°C. The method demonstrated robustness and accuracy with retention times for CDB (4.4), BZY (5.2), CDRC-A (8.5), CDH (12.1), and CDRC-C (33.8). The % Accuracy at 100% for CDB is 98.2, BZY is 0.0765, CDRC-A is 0.1350, CDH is 98.2 and CDRC-C is 101.0 respectively. LOQ values for CDB is 0.0756, BZY is 0.0765, CDRC-A is 0.1464, CDH is 0.0749 and CDRC-C is 0.1932. Linear responses were observed for all impurities, including CDB and CDH. This validated UPLC method is deemed more appropriate to regular QC analysis as well as Stability study analysis of CDB and CDH Capsules formulations.

Abstract Introduction: Cognitive decline and sleep concerns are significant health issues among older adults. Nonpharmacological treatments to address these concerns are needed, particularly for older adults who are more likely to be prescribed multiple medications and experience adverse effects of additional drugs. The aim of the current qualitative study was to understand and document the experiences of older adults with subjective memory decline participating in prolonged nightly fasting (PNF) intervention. Methods: This single-group pilot study was conducted as a fully remote, 8-week, pre/postintervention. Postintervention, 16 participants (≥65 years) participated in semistructured qualitative exit interviews about their experiences with the PNF intervention. Interviews lasted approximately 20–30 minutes, were conducted by trained study staff, and then analyzed by the team to understand relevant themes. Results: Two major themes that emerged from the data were engagement with and perceived effects of the PNF intervention. Within these two themes, nine subthemes emerged: accountability; use of days off; feasibility; intervention tools; behavioral strategies; timing/routine; awareness; self-efficacy; and perceived health-related outcomes. Overall, interviews suggested strong engagement with the PNF intervention as well as a number of positive perceived effects of the intervention. Conclusions: These findings contribute to a broad field of intermittent fasting by exploring and understanding the direct experiences of older adults participating in PNF. Some participants identified challenges of participation, yet this qualitative approach can guide future PNF implementation with older adults. Notably, responses support the quantitative data suggesting that PNF is a feasible and acceptable intervention for older adults.

Introduction: Urethral strictures affect about 1% of men over 65 in the United States and significantly impact quality of life. 1 Most strictures (92.2%) occur anteriorly. 2 Urethroplasty, the gold standard treatment, is traditionally open but can be performed endoscopically with comparable results. This prospective study describes a technique for transmeatal urethral surgery with buccal graft urethroplasty for anterior urethral strictures. Methods: A 21 French direct vision internal urethrotomy (DVIU) cystoscope is used to inspect the stricture and make an incision along its ventral aspect. After the stricture is measured, a graft of buccal mucosa is harvested. For graft deployment, we utilize a 26 French Wolf Offset Nephroscope™ and a rigid injeTAK® cystoscopy needle. At the distal aspect of the urethrotomy, the needle is passed through the urethra and out the perineum. A pair of the sutures is placed on either side of the urethrotomy and held externally at the meatus. The graft is oriented with the lamina propria facing the spongiosum. The previously placed sutures are then passed from lamina propria to mucosa at the distal aspect of the graft. The sutures are tied, creating a knot on the mucosal side. The external sutures are then pulled, and the graft retracts into the urethra. The JNW Urtract™ and Securestrap® are then used for graft fixation. Graft Deployment: At the distal aspect of the urethrotomy, the injeTAK® needle is passed through the urethra and out of the perineum. A pair of the sutures is then placed on either side of the urethrotomy. These are held in place at the meatus to maintain proper laterality and avoid twisting. The graft is oriented into position, with the anti-mucosa facing the exposed spongiosum and the mucosa facing the lumen. The previously placed sutures are then passed from anti-mucosa to mucosa using a free Mayo needle at the distal aspect of the graft. The suture pairs are tied, creating a knot on the mucosal side. The external sutures are then pulled, and the graft retracts into the urethra. Cystoscopy is performed to ensure the graft is covering the urethrotomy. Graft Fixation: The JNW Urtract was then introduced with the Securestrap® (a Vicryl tacking suture). While a finger externally compresses the perineum toward the tip of the Securestrap®, the ventral midline portion of the graft is secured. A 22 French Foley catheter is then placed over a wire. Results: Out of 20 total patients, 13 are eligible for their 4-month follow-up. Of those who have completed follow-up, 86% had urethral patency on cystoscopy. The average duration of foley catheterization was 2.4 weeks. The average operative time was 100.8 minutes, and the average estimated blood loss was 37.5 cc. Conclusion: Transmeatal urethral surgery is a safe and effective repair option for management of anterior urethral stricture disease. The authors have no disclosures or commercial associations that might create a conflict of interest. Authors have received and archived patient consent for video recording/publication in advance of video recording of the procedure. Data and video obtained during the treatment of patients at Mayo Clinic in Rochester, Minnesota. Authors have received and archived patient consent for video recording/publication in advance of video recording of the procedure. No conflicts of interest or obligations resulted from data collection. Runtime of video: 8 mins 52 secs.

AbstractINTRODUCTIONTransgenic mice overexpressing familial Alzheimer's disease (AD) mutations (FAD) show non‐physiological traits, and their immunocompetent backgrounds limit their use in AD immunotherapy research. Preclinical models that reflect human immune responses in AD are needed.METHODSUsing CRISPR‐Cas9, we developed single (NA) and double (NAPS) knock‐in (KI) amyloid precursor protein (APP)KM670,671NL (Swedish) and presenilin 1 (PS 1)M146VFAD mutations on an immunodeficient NOG (NOD.Cg‐PrkdcscidIl2rgtm1Sug/JicTac) background. The models were confirmed by Sanger sequencing and evaluated for AD‐like pathology.RESULTSBoth NA and NAPS mice developed pathology without overexpression artifacts. Mutation‐induced upregulation of APP‐CTF‐β led to intraneuronal human amyloid beta (Aβ) (6E10) deposits and amyloid‐associated microgliosis as early as 3 months, which increased with age. The addition of the PS 1M146V mutation doubled the amyloid load. The models displayed broad neuronal loss, resulting in brain atrophy in older mice.DISCUSSIONThese models replicate intraneuronal amyloid pathology and, with human immune reconstitution potential, enable novel studies of human immune responses in AD.Highlights A novel Alzheimer's disease (AD) knock‐in (KI) mouse was developed and characterized on an immunodeficient NOG background. The model provides a platform for human immune studies and the evaluation of immunotherapies for AD. The KI mice demonstrate intraneuronal Aβ deposits and amyloid‐associated microglial reactions. KI mice demonstrate extensive neuronal loss. Human immune reconstitution enables studies of infectious AD co‐morbidities, such as the human immunodeficiency and herpes simplex viruses.

Abstract Aim Reversal of diverting loop ileostomy (DLI) traditionally occurs at ≥12 weeks after formation. Early closure has been performed in attempts to reduce DLI‐associated morbidity. Therefore, the aim of this study was to determine whether time to stoma reversal impacts postoperative morbidity. Method A retrospective review was conducted using institutional‐level American College of Surgeons National Surgical Quality Improvement Program data for adult patients who underwent DLI closure between January 2012 and December 2021 across a multistate health system. Time to DLI closure was stratified into three groups: ≤12, 12–24 or 24–36 weeks. Additional data were obtained from the electronic medical record. The primary outcome was major morbidity after DLI closure. Results A total of 482 patients underwent DLI closure. Eighty four patients underwent closure at ≤12 weeks (17.4%), 300 at 12–24 weeks (62.2%) and 98 at 24–36 weeks (20.3%). The most common diagnosis at DLI formation was cancer ( n = 211, 43.8%). Patients in the ≤12 weeks closure group more commonly had ulcerative colitis or diverticular disease and a lower American Society of Anesthesiologists class than patients with closure at 24–36 weeks ( p < 0.05). There were no significant differences in complication severity, overall major morbidity or its individual components amongst the time to DLI closure groups. There were no differences in anastomotic leaks or need for laparotomy. On multivariable analysis, immunosuppressive therapy and preoperative haematocrit <30% were significant risk factors for major morbidity after DLI closure. Conclusion Major morbidity did not differ by time to DLI closure group, indicating that closure at ≤12 weeks is safe in selected patients.

Abstract Quantitative computed tomography (CT) enables the measurement of biophysical processes characterized by morphology, composition, flow, and/or motion to aid in clinical diagnosis and intervention. Since its initial application for determining bone mineral density for skeletal fragility assessment, quantitative CT has continued to evolve alongside CT’s technological advancements. A key challenge facing quantitative CT is the lack of standardization pertinent to image acquisition, reconstruction, and image analysis. With the introduction of spectral CT involving dual-energy approaches and photon-counting detectors (PCD), we are now able to obtain detailed information regarding mass densities of endogenous and exogeneous materials. Furthermore, energy-resolved CT yields spectral image types (eg, virtual monoenergetic image) that are, in principle, independent of tube potential and patient size. This paves the way for workflow standardization and helps improve the consistency and reproducibility of CT-derived measurements. In this article, we review clinical applications of quantitative CT, discuss key challenges associated with quantitative CT and its adoption into routine practice, and outline the unique benefits ushered by new CT technologies such as PCD-CT towards improving quantitative imaging.