Prevalence of non-communicable chronic diseases in rural India amongst peri- and post-menopausal women: Can artificial intelligence help in early identification?

AIMS: To identify peri- and post-menopausal women at risk of non-communicable diseases in rural India and to assess their prevalence amongst these groups via the use of artificial intelligence. SETTINGS AND DESIGN: An observational study conducted by the Indian Menopause Society in collaboration with the Government of Maharashtra. The study included rural women residents of three villages in the Latur district of Maharashtra, India. MATERIALS AND METHODS: Accredited social health activist workers identified 400 peri- and post-menopausal women aged 45-60 years. Specific symptoms able to predict the presence of a non-communicable disease were identified through the use of artificial intelligence. STATISTICAL ANALYSIS USED: Descriptive statistics and predictive network charts analysis. RESULTS: The mean age of 316 women included in the analysis was 50.4 years and the majority of them were illiterate (68 %). The prevalence of dyslipidaemia, osteopenia, diabetes mellitus, obesity and hypertension were 58 %, 50 %, 25 %, 25 %, and 20 % respectively. None of their symptoms or laboratory reports could be significantly correlated directly with any of these non-communicable diseases. Hence, we used a cluster of symptoms to suggest the presence of hypertension, diabetes mellitus, osteoporosis and hypothyroidism via predictive network analysis charts. CONCLUSIONS: Screening of at-risk women can be done using an artificial intelligence-based screening tool for early diagnosis, timely referral and treatment of non-communicable diseases with the support of community health workers.

Enhanced Efficacy of Carvedilol by Utilization of Solid Dispersion and Other Novel Strategies: A Review.

Carvedilol is classified as a second class drug of Biopharmaceutical classification system (BCS), and it is an excellent beta blocker and vasodilating agent. It is used in a diverse range of disease states. Despite having tremendous advantages, the drug cannot be used effectively and productively due to aquaphobicity and poor bioavailability. To overcome this limitation, numerous novel approaches and tactics have been introduced over the past few years, such as Selfmicro emulsifying drug delivery systems (SMEDDS), nanoparticles, solid dispersions and liposomal drug delivery. The present review aims to accentuate the role of solid dispersion in improving the dissolution profile and aqua solubility of carvedilol and also to emphasize other novel formulations of carvedilol proposed to prevail the limitations of carvedilol. Solid dispersion and other novel approaches were found to play a significant role in overcoming the drawbacks of carvedilol, among which solid dispersion is the most feasible and effective approach being used worldwide. Reduced particle size, more wettability, and large surface area are obtained by the implementation of solid dispersion technique, hence improving carvedilol solubility and bioavailability.

Role of poly(ADP-ribose) polymerase-1 in regulating human islet cell differentiation.

Poly(ADP-ribose) polymerase-1 (PARP1), a fundamental DNA repair enzyme, is known to regulate ß cell death, replication, and insulin secretion. PARP1 knockout (KO) mice are resistant to diabetes, while PARP1 overactivation contributes to ß cell death. Additionally, PARP1 inhibition (PARPi) improves diabetes complications in patients with type-2 diabetes. Despite these beneficial effects, the use of PARP1 modulating agents in diabetes treatment is largely neglected, primarily due to the poorly studied mechanistic action of PARP1 catalytic function in human ß cell development. In the present study, we evaluated PARP1 regulatory action in human ß cell differentiation using the human pancreatic progenitor cell line, PANC-1. We surveyed islet census and histology from PARP1 wild-type versus KO mice pancreas in a head-to-head comparison with PARP1 regulatory action for in-vitro ß cell differentiation following either PARP1 depletion or its pharmacological inhibition in PANC-1-differentiated islet cells. shRNA mediated PARP1 depleted (SiP) and shRNA control (U6) PANC-1 cells were differentiated into islet-like clusters using established protocols. We observed complete abrogation of new ß cell formation with absolute PARP1 depletion while its inhibition using the potent inhibitor, PJ34, promoted the endocrine ß cell differentiation and maturation. Immunohistochemistry and immunoblotting for key endocrine differentiation players along with ß cell maturation markers highlighted the potential regulatory action of PARP1 and augmented ß cell differentiation due to direct interaction of unmodified PARP1 protein elicited p38 MAPK phosphorylation and Neurogenin-3 (Ngn3) re-activation. In summary, our study suggests that PARP1 is required for the proper development and differentiation of human islets. Selective inhibition with PARPi can be an advantage in pushing more insulin-producing cells under pathological conditions and delivers a potential for pilot clinical testing for ß cell replacement cell therapies for diabetes.

XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

Does prior transurethral resection of prostate have a negative impact on the outcome of holmium laser enucleation of prostate? Results from a prospective comparative study.

Objectives: To prospectively evaluate safety and efficacy of holmium laser enucleation of prostate (HoLEP) for surgical treatment of recurrent symptoms due to prostatomegaly after prior transurethral resection of prostate (TURP). Materials and Methods: We prospectively evaluated 43 patients with a history of TURP who underwent HoLEP (study group). Patients in chronological order who underwent HoLEP without prior TURP were included in the control group. We hypothesized that prior TURP would increase technical difficulties, thereby leading to a reduction in procedure efficiency by 25%. Patients' demographic, intraoperative, and postoperative data were compared, and statistical analysis was performed. Results: Demographic data in both groups were comparable. The average interval between past TURP and HoLEP was 4.22 years. There was no difficulty in identifying the dissection plane in the study group and the difference in the procedure efficiency between the study and the control groups were statistically insignificant (0.75 ± 0.31 g/min-study group vs. 0.69 ± 0.36 g/min-control group; P = 0.665). The intraoperative parameters and postoperative outcomes were comparable in both groups. Conclusions: Prior TURP does not negatively impact the outcome of HoLEP in treating symptomatic recurrence for enlarged prostate after initial TURP.

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates.

The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhibitors and mass spectrometry. We uncover large dynamic ubiquitin signalling networks with substrates and sites preferentially regulated by DUBs or by the proteasome, highlighting the role of DUBs in degradation-independent ubiquitination. DUBs regulate substrates via at least 40,000 unique sites. Regulated networks of ubiquitin substrates are involved in autophagy, apoptosis, genome integrity, telomere integrity, cell cycle progression, mitochondrial function, vesicle transport, signal transduction, transcription, pre-mRNA splicing and many other cellular processes. Moreover, we show that ubiquitin conjugated to SUMO2/3 forms a strong proteasomal degradation signal. Interestingly, PARP1 is hyper-ubiquitinated in response to DUB inhibition, which increases its enzymatic activity. Our study uncovers key regulatory roles of DUBs and provides a resource of endogenous ubiquitination sites to aid the analysis of substrate specific ubiquitin signalling.

Bilateral same session flexible ureterorenoscopy for endoscopic management of bilateral renal calculi is noninferior to unilateral flexible ureterorenoscopy for management of multiple unilateral renal calculi: outcomes of a prospective comparative study.

PURPOSE: The aim of the study was to prospectively evaluate safety and efficacy of bilateral same session ureterorenoscopy (BSS-FURS) for management of bilateral renal calculi. METHODS: A prospective comparative study was designed to compare the results of BSS-FURS with unilateral flexible ureterorenoscopy (U-FURS) for management of renal calculi between June 2003 and May 2016. A sample size of 55 patients in each arm was calculated considering a 20% increase in the incidence of complications with BSS-FURS over 15% complication rate in U-FURS (alpha = 0.05; Beta = 0.90). Patient demographics, stone burden, total operative time, postoperative creatinine level, duration of hospital stay, perioperative complications and stone free rate (SFR) were compared in both the groups. The literature pertaining to BSS-FURS was reviewed. RESULTS: Although the study group patients had higher overall stone burden (18.60 ± 7.70 mm vs. 13.32 ± 6.43 mm) and significantly longer operative time (48.30 ± 16.71 min vs. 32.95 ± 13.05 min; p < 0.05) as compared to the control group, the length of hospital stay, SFR (67.85% vs. 78.5%; p = 0.436) and perioperative complications were comparable in both the groups. Most patients who developed postoperative fever from both groups had struvite stones. CONCLUSION: BSS-FURS is a safe and efficient procedure for the management of bilateral renal calculi in the hands of an experienced endourologist. It has comparable SFR and morbidity compared to U-FURS. Caution should be exercised in patients with struvite stones, as they are more likely to develop postoperative fever.

A Clinical Evaluation of Difference in Shades among Maxillary Central Incisor, Canine, and First Molar in a Young Age-group Using Digital Spectrophotometer: An In Vivo Study.

AIM: The aim of this study was to evaluate and compare the most common shades of maxillary central incisor, canine and first molar and to confirm the shade difference between maxillary central incisor and canine in a young population of 18-25 years. MATERIALS AND METHODS: The shade of the maxillary central incisor, canine, and first molar of 100 study participants in a young population between 18 and 25 years were measured by digital spectrophotometer (VITA Easyshade). The shade of each tooth was assessed thrice with a digital spectrophotometer at the center of the tooth. Statistical analysis was performed; Chi-squared test was applied to assess the difference in shades. RESULTS: For the age-group of 18-25 years, the most common shade of maxillary central incisor is A1 and for canine and first molar the most common shade is B3. A highly statistically significant difference (p < 0.001) was observed between teeth, suggesting a definitive shade difference between teeth. CONCLUSION: A definitive shade difference exists between the maxillary central incisor and the canine, with the canine being darker in shade than the central incisor. This result can be implied clinically while restoring maxillary anterior teeth to yield a better esthetic outcome. CLINICAL SIGNIFICANCE: This study reveals that there is a definitive shade difference between the Anterior teeth which should be considered while smile designing to replicate the natural appearance in a patient. Using a digital spectrometer makes the process of shade selection objective thereby eliminating any subjective variations.

A prospective evaluation of high- and low-power holmium laser settings for transurethral lithotripsy in the management of adults with large bladder calculi.

PURPOSE: To prospectively investigate the efficacy and safety of high-power (100 W) vs low-power (20 W) laser settings for transurethral laser lithotripsy in the management large vesical calculi (> 4 cm). METHODS: All patients with vesical calculi > 4 cm in the maximum dimension and scheduled for transurethral holmium laser lithotripsy were invited to participate in the study. Every alternate patient was treated with either the low- or high-power laser settings. We used a continuous irrigation resectoscope with laser bridge or a laser working element (Karl Storz) for laser lithotripsy of bladder stones. We compared the operative time, intra-operative/post-operative complications (up to 1 year), and stone-free rates between the treatment groups using IBM SPSS Statistics 24 software. Comparisons between treatment groups for continuous variables were assessed using the Welch test, while categorical variables were compared with either the Chi-square or Fisher's exact test. A p value < 0.05 was considered statistically significant. RESULTS: Twenty patients with ten in each cohort were recruited. Preoperative data and mean bladder stone size were comparable in both groups. The duration of surgery was significantly reduced from 70.80 ± 25.28 min in low-power cohort to 40.90 ± 15.01 min in the high-power group (p = 0.005). There were no significant intra-operative complications in either group. All patients were stone-free following the procedure. CONCLUSION: High-power laser setting of up to 100 W results in a significant reduction in duration of surgery without any increase in the complication rate for treatment of large bladder stones.

Poly(ADP-ribosyl)ation temporally confines SUMO-dependent ataxin-3 recruitment to control DNA double-strand break repair.

DNA damage-induced SUMOylation serves as a signal for two antagonizing proteins that both stimulate repair of DNA double-strand breaks (DSBs). Here, we demonstrate that the SUMO-dependent recruitment of the deubiquitylating enzyme ataxin-3 to DSBs, unlike recruitment of the ubiquitin ligase RNF4, additionally depends on poly [ADP-ribose] polymerase 1 (PARP1)-mediated poly(ADP-ribosyl)ation (PARylation). The co-dependence of ataxin-3 recruitment on PARylation and SUMOylation temporally confines ataxin-3 to DSBs immediately after occurrence of DNA damage. We propose that this mechanism ensures that ataxin-3 prevents the premature removal of DNA repair proteins only during the early phase of the DSB response and does not interfere with the subsequent timely displacement of DNA repair proteins by RNF4. Thus, our data show that PARylation differentially regulates SUMO-dependent recruitment of ataxin-3 and RNF4 to DSBs, explaining how both proteins can play a stimulatory role at DSBs despite their opposing activities.

Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3-7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

A randomized controlled trial comparing high and medium power settings for holmium laser enucleation of prostate.

PURPOSE: To report the results of a randomized controlled trial comparing outcomes between medium power (MP) and high power (HP) laser settings for HoLEPs. METHODS: The primary objective was to compare the enucleation efficiency (EE) of HP- HoLEP (80-100 W) with MP-HoLEP (50 - 60 W). The secondary objectives were to compare treatment efficacy and safety between both groups. To show a 25% difference in EE, a sample size of 45 individuals per treatment arm was required (alpha = 0.05; Beta = 0.80). Patients demographic and perioperative factors were analyzed, including EE, hemoglobin drop, duration of catheterization, and length of hospital stay. The surgical outcome was evaluated with AUA symptom score, maximum flow rate, postvoid residual urine, and complications to assess differences between MP and HP HoLEP at baseline, 3 months, 1, and 5 years. Quantitative outcomes were compared with independent sample t tests (2-tailed) and qualitative outcomes were compared with chi-square tests. RESULTS: Preoperative data with the exception of indication for surgery were comparable in both treatment arms. There was no statistically significant difference in enucleation efficiency between the HP-HoLEP and MP-HoLEP laser setting (0.97 ± 0.47 vs. 0.85 ± 0.47 gm/min, p = 0.209). MP laser settings did not increase perioperative or postoperative complications and resulted in durable outcome comparable with HP laser settings at 5-year follow-up. CONCLUSIONS: MP-HoLEP is safe and efficient and does not compromise the outcome for HoLEPs when compared with HP-HoLEP.

Holmium Laser Enucleation of Prostate Within 6 Weeks of Transrectal Ultrasound Guided Prostate Biopsy is Safe and Effective.

OBJECTIVE: To evaluate the safety and efficacy of performing Holmium laser enucleation of the prostate (HoLEP) for the treatment of bladder outlet obstruction secondary to an enlarged prostate within 6-weeks of a transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: We performed a retrospective review of patients who underwent a HoLEP at our institution, excluding any patients with a confounding urologic history and compared patients who underwent a TRUS-guided 6- or 12-core prostate biopsy, and then underwent a HoLEP within 6 weeks (study group) with all other patients (control group). Our primary outcomes were enucleation efficiency (EE) and perioperative complication rate. Our secondary outcomes included postoperative drop in hemoglobin, duration of catheterization, length of hospital stay, voiding metrics at 1 and 6 months and rate of incidental prostate cancer diagnosed on histopathological examination of prostate specimens after HoLEP. To test for differences between the study and control groups, we performed independent sample t-test (2-tailed) and chi-square tests for quantitative and qualitative variables, respectively. P values of < 0.05 were considered statistically significant. RESULTS: 552 patients met inclusion criteria and 84 patients underwent prostate biopsy within a period of 45 days prior to HoLEP. Enucleation efficiency was higher in the study group (P = 0.00). There was no significant difference between the 2 groups regarding perioperative complications, postoperative voiding outcomes, or rate of incidental prostate cancer detection. CONCLUSIONS: TRUS prostate biopsy performed within 6 weeks of HoLEP does not negatively impact operative difficulty or treatment outcome.

Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing.

WHAT IS KNOWN AND OBJECTIVE: Non-clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ-associated reduction in viral load from small studies in COVID-19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed. METHODS: Published studies and rapidly emerging data were reviewed to gather evidence on safety and efficacy of CQ and HCQ in patients with COVID-19 infection or as prophylaxis. The focus is on clinically relevant efficacy endpoints and their adverse effects on QT interval. RESULTS AND DISCUSSION: At the doses used, the two agents, given alone or with azithromycin (AZM), are not effective in COVID-19 infection. The choice of (typically subtherapeutic) dosing regimens, influenced partly by "QT-phobia," varied widely and seems anecdotal without any pharmacologically reliable supporting clinical evidence. A substantial proportion of patients receiving CQ/HCQ/AZM regimen developed QTc interval prolongation, many with absolute QTc interval exceeding the potential proarrhythmic threshold, but very few developed proarrhythmia. WHAT IS NEW AND CONCLUSION: The strategy to repurpose CQ/HCQ to combat COVID-19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT-related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID-19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally.

Methods to Study Intracellular Movement and Localization of the Nucleotide Excision Repair Proteins at the DNA Lesions in Mammalian Cells.

Nucleotide excision repair (NER) is the most versatile DNA repair pathway that removes a wide variety of DNA lesions caused by different types of physical and chemical agents, such as ultraviolet radiation (UV), environmental carcinogen benzo[a]pyrene and anti-cancer drug carboplatin. The mammalian NER utilizes more than 30 proteins, in a multi-step process that begins with the lesion recognition within seconds of DNA damage to completion of repair after few hours to several days. The core proteins and their biochemical reactions are known from in vitro DNA repair assays using purified proteins, but challenge was to understand the dynamics of their rapid recruitment and departure from the lesion site and their coordination with other proteins and post-translational modifications to execute the sequential steps of repair. Here, we provide a brief overview of various techniques developed by different groups over last 20 years to overcome these challenges. However, more work is needed for a comprehensive knowledge of all aspects of mammalian NER. With this aim, here we provide detailed protocols of three simple yet innovative methods developed by many teams that range from local UVC irradiation to in situ extraction and sub-cellular fractionation that will permit study of endogenous as well as exogenous NER proteins in any cellular model. These methods do not require unique reagents or specialized instruments, and will allow many more laboratories to explore this repair pathway in different models. These techniques would reveal intracellular movement of these proteins to the DNA lesion site, their interactions with other proteins during repair and the effect of post-translational modifications on their functions. We also describe how these methods led us to identify hitherto unexpected role of poly(ADP-ribose) polymerase-1 (PARP1) in NER. Collectively these three simple techniques can provide an initial assessment of the functions of known and unknown proteins in the core or auxiliary events associated with mammalian NER. The results from these techniques could serve as a solid foundation and a justification for more detailed studies in NER using specialized reagents and more sophisticated tools. They can also be suitably modified to study other cellular processes beyond DNA repair.

Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome.

The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.

Genotype-guided warfarin therapy: Still of only questionable value two decades on.

WHAT IS KNOWN AND OBJECTIVE: Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its clinical implementation. The objective of this critique is to re-evaluate key warfarin pharmacogenetic studies with a view to explaining why this may be so. METHODS: Major widely-cited warfarin pharmacogenetic studies as well as recent meta-analyses were identified and a critical analysis of these was undertaken to identify factors that may account for poor clinical implementation of pre-treatment genotyping. RESULTS AND DISCUSSION: Critical examination of major warfarin pharmacogenetic studies identified a number of methodological concerns such as marked variations in study designs with different variously-defined measures of outcome. Genotype testing involved only a limited number of CYP2C9/VKORC1 alleles. Claims of benefits of genotyping are based almost exclusively on INR-related parameters which are known to be highly time-labile and of limited value in predicting clinical risk or benefit. This is evidenced by lack of any significant effect of genotyping on rates of bleeding or thromboembolic events. Neither have the effects of potential phenoconversion or medication non-adherence in study populations been adequately investigated. Although the effect of ethnicity/race is now better characterised, studies lack the power to determine whether any benefits claimed are indication-sensitive. WHAT IS NEW AND CONCLUSION: Since 60% of inter-individual variability in warfarin dose/response is due to other factors (many of which are non-genetic), expectations of eliminating this variability simply by CYP2C9/VKORC1 genotyping are over-optimistic and efforts cost-ineffective. Real-world studies have not always corroborated trials-based claims of clinical benefit. It is time to consider redirecting scarce resources away from the study of warfarin pharmacogenetics to pharmacogenetic research of potentially greater clinical relevance.

Simultaneous Holmium Laser Enucleation of Prostate with Removal of the Permanent Prostatic Urethral Stent Using the High-Power Holmium Laser: Technique in Two Cases and Review of the Literature.

Background: Although the prostatic urethral stents are no longer used in the United States for treatment of prostatomegaly, urologists will encounter patients with complications of previously placed permanent prostatic stents. We report two cases of persistent bothersome lower urinary tract symptoms (LUTS) after prostatic stent placement treated with simultaneous holmium laser enucleation of prostate (HoLEP) with endoscopic removal of the prostatic urethral stent using high-power holmium laser. We also reviewed the literature regarding the removal of prostatic stents with holmium laser combined with surgical management of benign prostatic hyperplasia. Case Presentation: A 71-year-old man who presented with LUTS, recurrent gross hematuria, and urinary infection, which developed after placement of a prostatic stent 10 years prior for urinary retention secondary to prostatomegaly (80 g). He underwent combined HoLEP with endoscopic removal of the prostatic stent using 100 W holmium laser at a power setting of 2 J and 30 Hz. The surgical steps comprised fragmentation of the stent in situ by making incisions at 5, 7, and 12 o'clock positions followed by enucleation of the prostate. The stent was then separated from enucleated tissue in the urinary bladder. The remaining prostate adenoma was then morcellated and removed. The patient remained asymptomatic at 10-year follow-up. Another patient was 62-year-old man who developed recurrence of bothersome LUTS, 1 year after placement a prostatic stent for urinary retention. On investigation his prostate was 105 g and stent showed partial migration in the bladder with overlying calcification. HoLEP and stent removal was performed in a manner similar to the first patient. This patient also remained asymptomatic at a 1-year follow-up. Conclusion: Combined HoLEP with removal of a prostatic urethral stent using a high-power holmium laser is safe and effective with long-term durable outcome.

Synthesis of thiophene derivatives and their anti-microbial, antioxidant, anticorrosion and anticancer activity.

BACKGROUND: A new series of thiophene analogues was synthesized and checked for their in vitro antibacterial, antifungal, antioxidant, anticorrosion and anticancer activities. RESULTS: A series of ethyl-2-(substituted benzylideneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate derivatives were synthesized by using Gewald synthesis and their structures were confirmed by FTIR, MS and 1H-NMR. The synthesized compounds were further evaluated for their in vitro biological potentials i.e. antimicrobial activity against selected microbial species using tube dilution method, antiproliferative activity against human lung cancer cell line (A-549) by sulforhodamine B assay, antioxidant activity by using DPPH method and anticorrosion activity by gravimetric method. CONCLUSION: Antimicrobial screening results showed that compound S 1 was the most potent antibacterial agent against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi having MIC value 0.81 µM/ml and compound S 4 also displayed excellent antifungal activity against both Candida albicans and Aspergillus niger (MIC = 0.91 µM/ml) when compared with cefadroxil (antibacterial) and fluconazole (antifungal) as standard drug. The antioxidant screening results indicated that compound S 4 and S 6 exhibited excellent antioxidant activity with IC50 values 48.45 and 45.33 respectively when compared with the ascorbic acid as standard drug. Anticorrosion screening results indicated that compound S 7 showed more anticorrosion efficiency (97.90%) with low corrosion rate. Results of anticancer screening indicated that compound S 8 showed effective cytotoxic activity against human lung cancer cell line (A-549) at dose of 10-4 M when compared with adriamycin as standard.