Unveiling Mechanobiology: A Compact Device for Uniaxial Mechanical Stimulation on Nanofiber Substrates and Its Impact on Cellular Behavior and Nanoparticle Distribution.

Biotechnology and its allied sectors, such as tissue culture, regenerative medicine, and personalized medicine, primarily rely upon extensive studies on cellular behavior and their molecular pathways for generating essential knowledge and innovative strategies for human survival. Most such studies are performed on flat, adherent, plastic-based surfaces and use nanofiber and hydrogel-like soft matrices from the past few decades. However, such static culture conditions cannot mimic the immediate cellular microenvironment, where they perceive or generate a myriad of different mechanical forces that substantially affect their downstream molecular pathways. Including such mechanical forces, still limited to specialized laboratories, using a few commercially available or noncommercial technologies are gathering increasing attention worldwide. However, large-scale consideration and adaptation by developing nations have yet to be achieved due to the lack of a cost-effective, reliable, and accessible solution. Moreover, investigations on cellular response upon uniaxial mechanical stretch cycles under more in vivo mimetic conditions are yet to be studied comprehensively. In order to tackle these obstacles, we have prepared a compact, 3D-printed device using a microcontroller, batteries, sensors, and a stepper motor assembly that operates wirelessly and provides cyclic mechanical attrition to any thin substrate. We have fabricated water-stable and stretchable nanofiber substrates with different fiber orientations by using the electrospinning technique to investigate the impact of mechanical stretch cycles on the morphology and orientation of C2C12 myoblast-like cells. Additionally, we have examined the uptake and distribution properties of BSA-epirubicin nanoparticles within cells under mechanical stimulation, which could act as fluorescently active drug-delivery agents for future therapeutic applications. Consequently, our research offers a comprehensive analysis of cellular behavior when cells are subjected to uniaxial stretching on various nanofiber mat architectures. Furthermore, we present a cost-effective alternative solution that addresses the long-standing requirement for a compact, user-friendly, and tunable device, enabling more insightful outcomes in mechanobiology.

Air-brush spray coated Ti3C2-MXene-graphene nanohybrid thin film based electrochemical biosensor for cancer biomarker detection.

Cancer is a significant health hazard worldwide and poses a greater threat to the quality of human life. Quantifying cancer biomarkers with high sensitivity has demonstrated considerable potential for compelling, quick, cost-effective, and minimally invasive early-stage cancer detection. In line with this, efforts have been made towards developing an f-graphene@Ti3C2-MXene nanohybrid thin-film-based electrochemical biosensing platform for efficient carcinoembryonic antigen (CEA) detection. The air-brush spray coating technique has been utilized for depositing the uniform thin films of amine functionalized graphene (f-graphene) and Ti3C2-MXene nanohybrid on ITO-coated glass substrate. The chemical bonding and morphological studies of the deposited nanohybrid thin films are characterized by advanced analytical tools, including XRD, XPS, and FESEM. The EDC-NHS chemistry is employed to immobilize the deposited thin films with monoclonal anti-CEA antibodies, followed by blocking the non-specific binding sites with BSA. The electrochemical response and optimization of biosensing parameters have been conducted using CV and DPV techniques. The optimized BSA/anti-CEA/f-graphene@Ti3C2-MXene immunoelectrode showed the ability to detect CEA biomarker from 0.01 pg mL-1 to 2000 ng mL-1 having a considerably lower detection limit of 0.30 pg mL-1.

Marginal Bone Level Measurements of Unsplinted Implants Used for Mandibular Overdentures: A Six-Month Randomized Prospective Clinical Study Comparing Early and Delayed Loading Protocols.

Background and purpose Implant-supported mandibular overdentures are a good alternative for patients having poor retention of mandibular conventional dentures. The aim of this prospective study was to evaluate and compare the results between early loading and delayed loading of mandibular overdentures on two unsplinted implants. Materials and methods  A total of 14 completely edentulous male patients in the age group of 50-60 years were selected for the study. Two 3.5×13 mm implants were placed in the mandibular interforaminal region. The patients were divided into two groups: (i) the test group in which the overdenture was connected after one week of surgery, and (ii) the control group, in which the overdenture was connected three months after surgery. Marginal bone levels were evaluated at baseline (during loading), three months, and six months post loading. Unpaired 't' test was used for the comparison of intergroup measurements.  Results No implants were lost. Marginal bone resorptions showed no statistically significant differences between the two groups over six months period after loading. Conclusion The results of this prospective clinical study suggested that there was no significant difference in the clinical and radiographic state of patients treated with implant-supported mandibular overdentures loaded either one week or three months after implant surgery.

Mandibular Advancement Device (MAD) for Obstructive Sleep Apnea in an Edentulous Patient.

Mandibular advancement devices have been efficiently used for the treatment of mild to moderate obstructive sleep apnea (OSA) by forward positioning of the tongue-mandible complex with a resultant increase in oropharyngeal volume. However, the literature on the treatment of edentulous patients is limited. This clinical report describes a clinical and laboratory method for the fabrication of a mandibular advancement device in a 75-year-old completely edentulous patient with mild OSA.

The microtubule end-binding proteins EB1 and Patronin modulate the spatiotemporal dynamics of myosin and pattern pulsed apical constriction.

Apical constriction powers amnioserosa contraction during Drosophila dorsal closure. The nucleation, movement and dispersal of apicomedial actomyosin complexes generates pulsed apical constrictions during early closure. Persistent apicomedial and circumapical actomyosin complexes drive unpulsed constrictions that follow. Here, we show that the microtubule end-binding proteins EB1 and Patronin pattern constriction dynamics and contraction kinetics by coordinating the balance of actomyosin forces in the apical plane. We find that microtubule growth from moving Patronin platforms governs the spatiotemporal dynamics of apicomedial myosin through the regulation of RhoGTPase signaling by transient EB1-RhoGEF2 interactions. We uncover the dynamic reorganization of a subset of short non-centrosomally nucleated apical microtubules that surround the coalescing apicomedial myosin complex, trail behind it as it moves and disperse as the complex dissolves. We demonstrate that apical microtubule reorganization is sensitive to Patronin levels. Microtubule depolymerization compromised apical myosin enrichment and altered constriction dynamics. Together, our findings uncover the importance of reorganization of an intact apical microtubule meshwork, by moving Patronin platforms and growing microtubule ends, in enabling the spatiotemporal modulation of actomyosin contractility and, through it, apical constriction.

Utility of trans-vaginal ultrasound in diagnosis and follow-up of non-pregnant sexually active females with lower ureteric calculi.

OBJECTIVE: To assess the utility of trans-vaginal ultrasonography in evaluation of non-pregnant sexually active female patients with lower ureteric calculi. METHODS: A prospective study was done from January 2015 to December 2017 including non-pregnant sexually active females with suspected ureteric calculus. Trans-abdominal ultrasound was initially done in all patients. In those patients in whom trans-abdominal ultrasound was inconclusive or there was indirect evidence of lower ureteric calculus in form of ureteral dilation but no calculus was evident, trans-vaginal ultrasound was done. The patients with ureteric calculi detected on trans-vaginal ultrasound and kept on conservative management were also followed up with trans-vaginal ultrasound. Non-contrast computed tomography was done in patients with inconclusive trans-vaginal ultrasound. RESULTS: As per the study protocol, 156 out of the total 468 patients evaluated by trans-abdominal ultrasound were eligible for trans-vaginal ultrasound. Trans-vaginal ultrasound was done in 149 patients, as seven patients did not give consent. Seventy-nine patients were detected with a lower ureteric calculus on trans-vaginal ultrasound and 27 patients had gynecologic or other cause for their symptoms. Forty-three patients had an inconclusive trans-vaginal ultrasound of which 36 underwent non-contrast computed tomography, among them only one patient had a lower ureteric calculus. Stone free status could be easily demonstrated on follow-up trans-vaginal ultrasound. CONCLUSION: Trans-vaginal ultrasound in addition to trans-abdominal ultrasound is a very useful tool in evaluation of sexually active females with suspected lower ureteric calculus.

Quick Sequential (Sepsis Related) Organ Failure Assessment: A high performance rapid prognostication tool in patients having acute pyelonephritis with upper urinary tract calculi.

Purpose: To analyze the utility of quick Sequential Organ Failure Assessment (qSOFA) in patients with uro-sepsis due to acute pyelonephritis (APN) with upper urinary tract calculi, we conducted this study. The role of qSOFA as a tool for rapid prognostication in patients with sepsis is emerging. But there has been a great debate on its utility. Literature regarding utility of qSOFA in uro-sepsis is scarce. Materials and Methods: Ours was a retrospective study including 162 consecutive patients who were admitted for APN with upper urinary tract calculi over a 3 and half years (total 42 months) period. We evaluated the accuracy of qSOFA in predicting inhospital mortality and intensive care unit (ICU) admissions and compared this with the predictive accuracy of systemic inflammatory response syndrome (SIRS). We used the Area Under Curve (AUC) of the Receiver Operator Characteristic curve to calculate it and also calculated the optimum cut off for qSOFA score. Results: The overall mortality and ICU admission rates were 7.4% and 12.9%, respectively. qSOFA had a higher predictive accuracy for in-hospital mortality (AUC, 0.981; 95% confidence interval [CI], 0.962-1.000) and ICU admissions (AUC, 0.977; 95% CI, 0.955-0.999) than SIRS. A qSOFA score of ≥2 was an optimum cut off for predicting prognosis. In a multivariate model qSOFA ≥2 was a highly significant predictor of in-hospital mortality and ICU admissions (p<0.001). Conclusions: qSOFA is a reliable and rapid bedside tool in patients with sepsis with accuracy more than SIRS in predicting inhospital mortality and ICU admissions.

Evaluation of resistive index of the prostate and bladder sonomorphologic parameters as replacements for urodynamics to predict bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: This study investigated whether the resistive index (RI) of prostate and bladder sonomorphologic parameters (total prostate volume [TPV], detrusor wall thickness [DWT], intraprostatic protrusion [IPP]) can be used instead of urodynamic studies (UDS) to predict bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). METHODS: Men aged ≥50 years with clinical BPH/LUTS were prospectively enrolled included. Basic evaluations, measurement of sonomorphologic parameters, and UDS were performed in accordance with the International Continence Society's Good Urodynamics Practices protocol. RESULTS: Data of 240 patients were divided into two groups based on the BOO index(BOOI). Group 1 consisted of patients negative for BOO (BOOI <40), whereas Group 2 consisted of patients positive for BOO (BOOI > 40). Patient age, International Prostate Symptom Score (IPSS), quality of life score and post-void residual volume were comparable between the two groups, whereas significant differences were evident in peak flow rate, TPV, DWT, RI, and IPP (P < 0.01 for all). Pearson correlation analysis revealed a significant correlation between BOOI and DWT (r = 0.198, P = 0.002), IPP (r = 0.450, P = 0.000), and RI (r = 0.334, P = 0.000). Multiple regression analysis revealed a significant correlation between BOOI and IPP (ß = 0.382, P = 0.000) and RI (ß = 0.226, P = 0.000). Receiver operating characteristic analysis showed that the area under curve was 0.785 for RI (95% confidence interval [CI] 0.703-0.867, P < 0.001) and 0.905 for IPP (95% CI 0.850-0.961, P < 0.001). At a cut-off value of 7.5 mm for IPP, the sensitivity was 86.9%, specificity was 83.3% and positive predictive value was 92.41%. CONCLUSION: IPP and RI may be the best non-invasive predictors for BOO in selected patients with LUTS/BPH.

Outcome of patients with failed pelvic fracture-associated urethral injury repair: A single centre 10-year experience.

OBJECTIVE: The management of recurrent posterior urethral strictures developing after pelvic fracture urethral injury (PFUI) is a challenging task. Despite availability of many surgical approaches, there is no consensus regarding the optimal approach. The objective of this study was to present our 10-year experience in the management of recurrent urethral strictures due to PFUI. MATERIAL AND METHODS: We did a retrospective single-institution review of patients who underwent surgical management for recurrent posterior urethral strictures from January 2006 to December 2016 using descriptive statistics. We included only those patients with PFUI who underwent some definitive surgical procedure for their previous failed repair(s). RESULTS: The final analysis included data of 50 male patients (10 adolescents and 40 adults). Mean age of the patients was 29.92±10.62 years. The average length of stricture was 3.02±1.47 cm. Progressive perineal urethroplasty (PPU) was done in 40 cases. Two patients with concomitant rectourethral fistula/false passage underwent transpubic urethroplasty (TPU). Three patients with complete bulbar necrosis were managed with single stage/staged preputial tube reconstruction. One patient underwent microsurgical urethroplasty using radial free forearm flap while in two patients each Mitrofanoff appendicovesicostomy and perineal urethrostomy was done. Majority of complications were minor (Clavien Grade 1 and 2). Overall success rate of PPU was 75%. Mean follow-up period was 29.46±10.68 months (range: 13-60 months). CONCLUSION: Most cases of recurrent posterior urethral strictures of <3 cm in length can be operated by PPU with reasonable success rates. Complex and long-segment (higher than 3 cm) strictures require use of ancillary procedures like TPU, substitution urethroplasty and Mitrofanoff appendicovescostomy.

Spectrum of urologic complications in obstetrics and gynecology: 13 years' experience from a tertiary referral center.

OBJECTIVE: To analyze the patterns of presentation and management for urologic complications of obstetrics and gynecology in the form of genitourinary fistulas at a tertiary referral center and highlight the social issues associated with them. MATERIAL AND METHODS: We conducted this retrospective study analyzing 311 patients with genitourinary fistulas after obstetric and gynecologic surgeries between January 2005 and January 2018. We recorded the patients' characteristics and area of residence and then analyzed the etiology, surgical management and success rates by grouping the patients into four types of genitourinary fistulas. The primary end point of success was patient being leak free. RESULTS: Majority of patients (90.4%) were from rural areas. The distribution of genitourinary fistulas in descending order was vesicovaginal (79.7%), ureterovaginal (11.8%), urethrovaginal (10.2%) and vesicouterine fistulas (2.6%). The mean time to presentation was 25.80±48.69 days with a wide range of 10 days to 360 months. The most common etiology was obstructed labour (58.5%) followed by abdominal hysterectomy (32.7%). For vesicovaginal fistulas the route to be used for repair depended on surgeon's preference and both transabdominal and transvaginal routes had almost equal success rates. The success rate of laparoscopic vesicovaginal fistula repair was 89.4% and all (100%) laparoscopic ureteroneocystostomies were successful. CONCLUSION: Genitourinary fistulas especially due to obstructed labour are still common in developing world showcasing the problem of inequitable distribution of healthcare. The surgical treatment approach depends on the surgeon's familiarity with the said procedure although versatility is required.

Inequalities in healthcare access: how a man with exstrophy in rural India coped.

We report a case of a 22-year-old man with adult exstrophy. The patient made a self-made urine collection device, which helped him to lead a normal life, carrying out his routine as well as occupational activities smoothly. This patient is a prime example of inequalities in healthcare distribution in low-income and middle-income countries. He was never taken to a proper medical centre to correct his condition nor was his mother ever given proper antenatal healthcare access. His background of being a poor person from rural India highlights the problems of inequalities in healthcare access.

Are there any predictive risk factors for failure of ureteric stent in patients with obstructive urolithiasis with sepsis?

Purpose: To compare patients with sepsis due to obstructive urolithiasis (Sep-OU) and underwent drainage by percutaneous nephrostomy (PCN) or a double-J (DJ)-ureteral stent and to identify predictive risk factors of DJ stent failure in these patients. Materials and Methods: We reviewed our records from January 2013 to July 2018 and identified 286 adult patients with Sep-OU out of which 36 had bilateral involvement, thus total 322 renal units were studied. Urologic residents in training carried out both ureteral stenting and PCN tube placement. Demographic data and stone characteristics were recorded along with Charlson comorbidity index. For predicting risk factors of DJ stent failure, those variables that had a p-value <0.1 in univariate analysis were combined in a multinomial regression analysis model. Results: The patients with PCN placement were significantly older than those with DJ stent placement (p=0.001) and also had significant number of units with multiple calculi (p=0.018). PCN was also placed more frequently in those patients with a upper ureteric calculi (p<0.05). On multinomial regression analysis multiple calculi (p=0.014; odds ratio [OR], 4.878; 95% confidence interval [CI], 1.377-17.276) and larger calculi size (p=0.040; OR, 0.974; 95% CI, 0.950-0.999) were the significant predictors of DJ stent failure. Conclusions: In patients with sepsis from obstructive urolithiasis due to larger and multiple calculi a PCN placement might be better suited although this data requires further prospective randomized studies to be extrapolated.

Giant vesicle calculi leading to spontaneous bladder rupture and acute renal failure: an unusual presentation.

Spontaneous rupture of the urinary bladder is extremely rare. We report a case of a 70-year-old man with spontaneous bladder rupture secondary to neglected giant vesicle calculi who presented as acute renal failure. The patient was stabilised with per-urethral catheterisation and extravesical drain placement. About 700 mL pus mixed with urine was drained through the per-urethral catheter and approximately 2000 mL of pus was drained through the extravesical drain. Cystolithotomy showed two large calculi which were removed.