Spiropyrimidinetrione DNA Gyrase Inhibitors with Potent and Selective Antituberculosis Activity.

New antibiotics with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new spiropyrimidinetriones (SPTs), DNA gyrase inhibitors having activity against drug-resistant Mycobacterium tuberculosis (Mtb), the causative agent of TB. While the clinical candidate zoliflodacin has progressed to phase 3 trials for the treatment of gonorrhea, compounds herein demonstrated higher inhibitory potency against Mtb DNA gyrase (e.g., compound 42 with IC50 = 2.0) and lower Mtb minimum inhibitor concentrations (0.49 µM for 42). Notably, 42 and analogues showed selective Mtb activity relative to representative Gram-positive and Gram-negative bacteria. DNA gyrase inhibition was shown to involve stabilization of double-cleaved DNA, while on-target activity was supported by hypersensitivity against a gyrA hypomorph. Finally, a docking model for SPTs with Mtb DNA gyrase was developed, and a structural hypothesis was built for structure-activity relationship expansion.

Use of complementary medicines and lifestyle approaches by people living with dementia: Exploring experiences, motivations and attitudes.

BACKGROUND: Lack of effective treatments for chronic conditions is associated with high rates of complementary medicine (CM) use. However, little is known about CM use for dementia. AIMS AND OBJECTIVES: The aim of this study was to explore the experiences, motivations, and attitudes towards CM use by people living with dementia in an Australian setting. DESIGN: This study had a qualitative research design; quantitative demographic information was also collected. METHODS: In-depth interviews were conducted with people living with dementia and their caregivers (N = 18). A thematic (inductive) analysis approach was taken to interpret data. RESULTS: Three in four participants used CM for dementia, spending ~AUD$100/month (USD$70/month). Within three overarching themes, a range of sub-themes was identified: (1) CM knowledge and use: people living with dementia and caregivers understanding of CM, types of CM used, and CM usage patterns; (2) Self-determined reasons for use/non-use: maintain or improve quality of life, hope, management of dementia symptoms, level of awareness, willingness and evidence, perceptions on efficacy and safety of CM, experiences of conventional medicine, and holistic approach to wellness; (3) External determinants of use: information on CM, relationship influences on CM use, and experiences with General Practitioners (GPs) and CM. CONCLUSION: Findings highlight that CM use is widespread and positively viewed by people living with dementia and their caregivers. Decisions regarding CM use were based on personal opinions. Findings have important implications for conversations with health professionals regarding CM use by people living with dementia to improve communication, health literacy, and reduce the risk of adverse effects through polypharmacy. IMPLICATIONS FOR PRACTICE: This study showed that CM is a valued approach for dementia management by people living with dementia, their families, and healthcare providers. Future international research is required to evaluate the efficacy and safety of these approaches and promote accurate advice in nursing care.

Structure-activity relationship analyses of fusidic acid derivatives highlight crucial role of the C-21 carboxylic acid moiety to its anti-mycobacterial activity.

Fusidic acid (FA) is a potent congener of the fusidane triterpenoid class of antibiotics. Structure-activity relationship (SAR) studies suggest the chemical structure of FA is optimal for its antibacterial activity. SAR studies from our group within the context of a drug repositioning approach in tuberculosis (TB) suggest that, as with its antibacterial activity, the C-21 carboxylic acid group is indispensable for its anti-mycobacterial activity. Further studies have led to the identification of 16-deacetoxy-16ß-ethoxyfusidic acid (58), an analog which exhibited comparable activity to FA with an in vitro MIC99 value of 0.8 µM. Preliminary SAR studies around the FA scaffold suggested that the hydrophobic side chain at C-20, like the C-11 OH group, was required for activity. The C-3 OH group, however, can be functionalized to obtain more potent compounds.

Antimalarial Pyrido[1,2- a]benzimidazole Derivatives with Mannich Base Side Chains: Synthesis, Pharmacological Evaluation, and Reactive Metabolite Trapping Studies.

A novel series of pyrido[1,2- a]benzimidazoles bearing Mannich base side chains and their metabolites were synthesized and evaluated for in vitro antiplasmodium activity, microsomal metabolic stability, reactive metabolite (RM) formation, and in vivo antimalarial efficacy in a mouse model. Oral administration of one of the derivatives at 4 × 50 mg/kg reduced parasitemia by 95% in Plasmodium berghei-infected mice, with a mean survival period of 16 days post-treatment. The in vivo efficacy of these derivatives is likely a consequence of their active metabolites, two of which showed potent in vitro antiplasmodium activity against chloroquine-sensitive and multidrug-resistant Plasmodium falciparum ( P. falciparum) strains. Rapid metabolism was observed for all the analogues with <40% of parent compound remaining after 30 min of incubation in liver microsomes. RM trapping studies detected glutathione adducts only in derivatives bearing 4-aminophenol moiety, with fragmentation signatures showing that this conjugation occurred on the phenyl ring of the Mannich base side chain. As with amodiaquine (AQ), interchanging the positions of the 4-hydroxyl and Mannich base side group or substituting the 4-hydroxyl with fluorine appeared to block bioactivation of the AQ-like derivatives though at the expense of antiplasmodium activity, which was significantly lowered.

Assessment of quality of life in patients of urethral stricture on clean intermittent catheterization following direct vision internal urethrotomy.

CONTEXT: Clean intermittent catheterization (CIC) after direct vision internal urethrotomy (DVIU). AIMS: The aim is to assess the quality of life (QOL) in patients with urethral strictures on CIC following DVIU. SETTINGS AND DESIGN: Prospective study. MATERIALS AND METHODS: This prospective study was conducted between August 2013 and July 2015 in the Department of Urology at KGMU, Lucknow. We included patients above the age of 18 years with stricture urethra, who were on CIC following direct visual internal urethrotomy. Patients below the age of 18 years, noncompliance, concomitant neurogenic voiding dysfunction, multiple strictures, pan anterior strictures, and posterior stenosis were excluded from the study. A 16 French Foley catheter was used for CIC following DVIU. Patients were evaluated at follow-up visit at 3, 6, and 12 months. At each follow-up visits, patients were assessed using CIC-QOL questionnaire, maximum urine flow rate and complications related to CIC if any. STATISTICAL ANALYSIS USED: Unpaired t-test was used to compare continuous data, and Fisher's exact test was used to analyze categorical data. RESULTS: Among total 144 male patients evaluated, we included 97 patients, who underwent DVIU. Mean age of the study population was 37.7 ± 14.03 years. Most urethral strictures were idiopathic (64.02%) followed by postinflammatory (24.25%). A significant number of patients reported difficulty in performing CIC, which hampered daily activities. No major procedure related complications were reported. Patients who were compliant to CIC reported no stricture recurrence till 6 months follow-up. CONCLUSIONS: CIC following DVIU remains a reasonable adjunctive option. All the parameters of CIC-QOL questionnaire had improved on continuing CIC. Young men on CIC had greater impairment of QOL when compared to aged patients.

Identification of essential surgical competencies to be imparted in urological residency: A survey-based study.

INTRODUCTION: There are variations in surgical procedures included in urology residency curricula across various programs. We conducted a survey of practicing urologists to determine which procedures are considered essential to a core urology residency curriculum. MATERIALS AND METHODS: A web-based survey was conducted between October 2016 and February 2017 using SurveyMonkey. The questionnaire, comprising a set of 5-questions, was sent to the members of the Urological Society of India. Respondents were requested to grade 37 of the most common urological procedures (competencies) into three groups. Group A, were those that the respondent believed were vital for the trainee to learn (must know). Group B, were those that the respondent thought were essential to acquire (good to know). Group C procedures were labeled as desirable to know by respondents. RESULTS: A total of 485 (15.75%) responses were received out of 3018 members contacted. 67% respondents were working in the private-sector. Out of the 37 listed procedures, 20 procedures received a median weightage of 1 indicating vital clinical competency for urology curriculum, 15 were identified as "essential to know" while two procedures were identified as "desirable to know." CONCLUSIONS: Twenty surgical procedures were identified as'must-know' for a urology trainee. The choice of procedures was not affected by the region of the responder or his practice type, suggesting a wide consensus.

Prospective study to evaluate the clinical outcome of intralesional interferon-α2b in the management of Peyronie's disease.

CONTEXT: Interferon (IFN)-α2b in Peyronie's disease (PD). AIMS: This study aims to evaluate clinical efficacy of the IFN-α2b in both subjective and objective manner for the treatment of PD and compared with previously used intralesional verapamil in terms of cost-benefit analysis. SETTINGS AND DESIGN: Prospective study. MATERIALS AND METHODS: A prospective study conducted from January 2013 to July 2016 in the Department of Urology, Government Medical College, Kota, Rajasthan, India. We included patients with identifiable Peyronie's plaque with or without pain, curvature ranging between 30 and 90 degrees. We excluded patients with a calcified plaque and the ventral location of the plaque, any infective foci over the penis, erectile dysfunction due to other etiologies and patients who had received previous intralesional therapy. Patients were evaluated by clinical history, physical examination including plaque location, size, consistency, and penile curvature. Patients received intralesional IFN-α2b in a dose of 3 × 106 IU. Patients completed the visual analogue pain (VAS) score for pain, and International Index of Erectile Function-5 (IIEF-5) questionnaire at first visit as well as at follow-up of 1 month and 3 months. STATISTICAL ANALYSIS USED: Comparisons were performed using the paired Student's t-test and Chi-square tests as appropriate. Patient's objective and subjective clinical characteristics were described as a means (standard deviation). RESULTS: We included 86 patients in this study. Patients had a mean age of 48.6 years, mean plaque volume 256 mm3, and disease duration of 15.2 years. After 1 month of treatment, there was a significant change in plaque volume 256-60.8 mm3; P < 0.01) and penile curvature 34.8-24.6°; P < 0.01). The patients reported significant improvement in pain score VAS and IIEF-5. CONCLUSIONS: IFN-α2b, as minimal invasive (intralesional) options for the treatment of PD, demonstrated significant improvement in plaque volume, penile curvature with minimal complications. Patients subjectively reported significant improvement in pain on erection and sexual activities. IFN-α2b and verapamil had an almost similar clinical outcome, but verapamil at much lower cost.

Page kidney: A rare but surgically treatable cause of hypertension.

The Page kidney is a rare phenomenon. External renal parenchymal compression is the culprit. We report two cases of young males with flank pain, renal mass, and hypertension with history of blunt abdominal trauma. Initially, hypertension was controlled by angiotensin-converting enzyme (ACE) inhibitors but gradually became refractory to medical treatment. Laparoscopic nephrectomy was performed in both patients. We emphasize the Page kidney as a cause of hypertension in young patients, presenting with flank pain and renal mass with or without complications of hypertension. Management is aimed to control blood pressure by ACE inhibitors, aspiration of the hematoma, open hematoma evacuation, or nephrectomy.

Reversed isoniazids: Design, synthesis and evaluation against Mycobacterium tuberculosis.

Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculosis and a selected number of compounds were also tested ex vivo for intracellular activity as well as in the ethidium bromide (EB) assay for efflux pump inhibition efficacy. The potency of some compounds against various strains of M. tuberculosis (4a-c, 7 and 8; H37Rv-MIC99 ≤1.25 µM, R5401-MIC99 ≤2.5 µM, X_61-MIC99 ≤5 µM) demonstrated the potential of the reversed anti-TB agent strategy towards the development of novel anti-mycobacterial agents to address the rapidly growing issue of resistance. Further, macrophage activity with >90% inhibition by 1a-c and 3b (MIC90 ≤13.42 µM) and inhibition of EB efflux demonstrated by these compounds are encouraging.

A Prospective Study to Evaluate Sexual Dysfunction and Enlargement of Seminal Vesicles in Sexually Active Men Treated for Benign Prostatic Hyperplasia by Alpha-blockers.

OBJECTIVE: To evaluate sexual dysfunction and enlargement of seminal vesicles in sexually active men who were treated by α1-blockers for benign prostatic hyperplasia and its possible clinical application. MATERIALS AND METHODS: This is a prospective cohort study from January 2015 to December 2016. We enrolled sexually active men above the age of 40 years having moderate to severe lower urinary tract symptoms (LUTS). We excluded patients with a history of prostate surgery, suspicious digital rectal examination findings, a serum prostate-specific antigen of >4 ng/dL, and a history of medication with anticholinergic, cholinergic, and diuretic agents. Patients were divided into groups A, B, and C based on the prescription of silodosin 8 mg, tamsulosin 0.4 mg, or alfuzosin 10 mg orally once for LUTS and at 4 and 12 weeks. RESULTS: The mean age was 54.8 years (41-68 years). Twelve weeks of treatment with silodosin, tamsulosin, and alfuzosin resulted in a significant improvement in the total International Prostate Symptom Score and the quality of life score (P <.001). The baseline erectile function scores were 26.4, 27.6, and 28.1, and the baseline overall satisfaction (OS) (International Index of Erectile Function [IIEF]-OS) scores were 7.1, 8.3, and 8.6 among groups A, B, and C, respectively. After 12 weeks of α1-blockers, the IIEF-erectile function scores were 24.0, 24.7, and 26.2, and the IIEF-OS scores were 6.4, 7.8, and 7.9. All 3 groups demonstrated a statistically significant enlargement of seminal vesicles after 12 weeks' treatment, most significant in group A patients (7.65-14.11 cc, P <.001). CONCLUSION: Alpha-blockers as silodosin, tamsulosin, and alfuzosin are a safe and effective tool in benign prostatic hyperplasia for improving LUTS and the quality of life. Loss of seminal emission with alpha-blockers appears as the cause of seminal vesicle enlargement. The exact mechanism of these findings needs further clinical and experimental research.

What is the fate of insignificant residual fragment following percutaneous nephrolithotomy in pediatric patients with anomalous kidney? A comparison with normal kidney.

Pediatric population has increasing incidence of renal calculus and it is estimated to be around 50/10,000 population. The treatment of choice for large and complex stone in anomalous kidney is percutaneous nephrolithotomy (PCNL). The fate of insignificant residual fragment after PCNL in pediatric patients is not well documented. Here, we are reporting our long-term experience and follow-up of insignificant residual fragment in pediatric patients with anomalous kidney in comparison to normal kidney. Intuitional ethical approval was taken. A retrospective analysis of PCNL in pediatric (<18 years) anomalous kidney was performed from 2001 to 2013. The data of 52 pediatric patients with anomalous kidney (group B) have been compared to 251 normal kidneys (group A). The mean age of the patients was 7.83 + 3.45 (range 3-18) in group A and 8.21 ± 3.25 (range 5-18) in group B. The mean size of the insignificant residual fragment was 2.2 + 0.5 mm (1-4) in group A and 2.1 + 0.6 mm (range 1-4) in group B. Most of these residual fragments were single in number (72.55 vs. 67.30%, respectively). 54.98% children in group A and 67.30% in group B were symptomatic in the follow-up. Stone size was increased, stable and spontaneously passed in 49.8 vs. 71.15, 22.7 vs. 19.23 and 27.49 vs. 9.61% (p < 0.03), respectively, over mean follow-up of 50.34 months. Insignificant residual fragments in children are notorious for regrowth (49.8% in normal and 71.15% in anomalous kidney) in future. Most of the children will require symptomatic treatment (55.37 vs. 82.69%) or reintervention (39 vs. 46%) for insignificant residual fragment.

Evaluation of Impact of Voiding Posture on Uroflowmetry Parameters in Men.

PURPOSE: To evaluate the impact of voiding position on uroflowmetry parameters and to assess its potential clinical implications. MATERIALS AND METHODS: We conducted a prospective study from 2013 to 2015 and included men between 18 and 77 years old who were either healthy volunteers with an International Prostate Symptom Score (IPSS) ≤7 or men with benign prostate enlargement that were on alpha-blocker medication and had an IPSS <10. Participants underwent uroflowmetry and post-void residual urine (PVRU) measurements twice, once in a sitting position and once in a standing position. The participants were divided into 4 groups based on age (35 years or younger, 36 to 50 years, 51 to 60 years, and older than 60 years). RESULTS: A total of 740 men with a mean age of 40.35 years were evaluated. There was no significant difference in uroflowmetry parameters until the age of 50 years between the voiding positions. However, in those older than 50 years, PVRU volume was significantly lower in the sitting position than the standing position, whereas voiding time was significantly higher in the sitting position than the standing position. Other uroflowmetry parameters, including maximal and average urine flow rates, were non-significant. CONCLUSIONS: The voiding position plays an important role in the uroflowmetry parameters of elderly men. Voiding in the sitting position was found to be optimal for elderly men, whereas the role of the voiding position in healthy young men could not be determined. More research is needed to further study this issue.

Nephrolithisis in a newborn: a rare case and review of literature.

Nephrolithiasis, although a common entity in adults, is less common in children and rare in newborns. The evaluation and management strategies of renal stones in neonates are unclear. We report a rare scenario of renal calculus in a newborn aged 3 days presenting with decreased urine output, fever and crying during micturition. Patient was thoroughly investigated and managed conservatively. Further follow-up showed increase in stone size with recurrent urinary tract infections, hence shock wave lithotripsy was performed to successfully break and clear the stone fragments. Patient recovered well and was doing fine until last follow-up.

Does prostate size predict the urodynamic characteristics and clinical outcomes in benign prostate hyperplasia?

AIMS: Bladder outlet obstruction (BOO) in large and small prostates is managed in a similar manner despite considerably different pathophysiology, which can result in higher failure rates. We investigate the clinical and urodynamic features and study the outcome of patients with benign prostate hyperplasia (BPH) according to their prostate size. SUBJECTS AND METHODS: We prospectively analyzed 100 BPH patients undergoing urodynamic study between January 2015 and August 2016 and divided them into two groups according to their prostate size: small (≤30 mL) and large prostate (>30 mL) groups. We compared the groups regarding age, International Prostate Symptom Score, maximal flow rate (Qmax), postvoided residual, serum prostate-specific antigen (PSA), prostate volume measured by ultrasonography (USG), and urodynamic findings. STATISTICAL ANALYSIS USED: For testing the hypothesis, we used the Chi-square test, Student's t-test, and one-way analysis of variance when comparing between groups and conducted the logistic regression analysis for determining predictive factors of BOO. RESULTS: Although the total prostate volume significantly correlated with the PSA, patients with a small prostate had lower Qmax (5.27 ± 4.8 mL/s vs. 6.14 ± 6.66 mL/s; P = 0.74), higher incidence of abnormal baldder capacity (39.9% vs. 31.25%), lower voiding efficiency (39.3 ± 40.5% vs. 40.57 ± 32.11%), low compliance (44.4% vs. 31.3%), higher incidence of indeterminate detrusor contractions (38.9% vs. 37.5%), lower incidence of detrusor underactivity (33.3% vs. 28.1%), lower BOO index (40.9 ± 43.2 vs. 49.10 ± 44.48), lower bladder contractility index (77.8 ± 48.84 vs. 92.09 ± 52.79), and lower PdetQmax (51.44 ± 42.23 vs. 61.38 ± 42.01 cmH2O). Small prostates had higher failed voiding trials postsurgery. CONCLUSIONS: BOO patients with a small prostate showed poor urodynamic parameters and reported higher postoperative complications.

Emphysematous pyelonephritis: Changing trend of clinical spectrum, pathogenesis, management and outcome.

OBJECTIVE: To highlight changing trend of clinical spectrum, comparing management options and predictors of outcome of emphysematous pyelonephritis. MATERIAL AND METHODS: This study included patients who were diagnosed as emphysematous pyelonephritis between August, 2001 to July, 2015. We excluded other possible causes of gas in renal system. Baseline patient characteristics, clinical spectrum, serum and urinary biochemical parameters, radiological findings, management and outcomes were recorded. Patients were classified as "responders" and "non-responders". RESULTS: We studied a total of 74 patients and categorised them as responders (62 patients) and non-responders (12 patients). Women outnumbered men constituting 62.16% of the study population (M: F; 1: 1.6). Fever was the most common presenting symptom followed by flank pain. Diabetes mellitus (85.14%) was the most common comorbidity followed by urolithiasis (32.43%). Escherichia coli was the commonest organism grown in urine culture (79.73%). Non-responders had distinct laboratory findings relative to responders as low hemoglobin (7.8±2.1/11.2±3.2 g/dL; p=0.0007), thrombocytopenia (91.67% vs. 11.29%; p=0.0001), proteinuria >3 g/L (50% vs. 6.45%; p=0.0008) and positive blood culture (100% vs. 67.74%; p=0.0288). CONCLUSION: Advanced age, higher body mass index, renal impairment, thrombocytopenia, altered sensorium, shock at presentation can be used as scores for poor prognosis. Emphysematous pyelonephritis management requires multidisciplinary collaboration including hydration and electrolyte management, broad spectrum antibiotics, strict glycaemic control, effective urinary drainage and lastly it may require emergency nephrectomy as a salvage procedure.

Giant Hydronephrotic Kidney Masquerading as Urinoma: A Rare Presentation with Review of Literature.

Giant hydronephrosis (GH) is a condition in which pelvicalyceal system contains more than 1000 ml of urine. Common causes of GH are uretero-pelvic junction obstruction, renal calculus, abdominal trauma. We are reporting a case of 45 years' male, who presented with abdominal trauma and haematuria and was suspected a urinoma secondary to renal trauma. Examination revealed soft, cystic abdominal lump. Computed tomography of the abdomen revealed grossly hydronephrotic right kidney. The patient was managed by pyeloplasty after renal scan (estimated plasma renal flow- 91.92 ml/minute). Giant hydronephrotic kidney presenting with history of trauma may be confused with post traumatic urinoma.

Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and Correlation with Inhibition of ß-Hematin Formation.

The extensive use of praziquantel against schistosomiasis raises concerns about drug resistance. New therapeutic alternatives targeting critical pathways within the parasite are therefore urgently needed. Hemozoin formation in Schistosoma presents one such target. We assessed the in vitro antischistosomal activity of pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their ability to inhibit ß-hematin formation. We further evaluated the in vivo efficacy of representative compounds in experimental mice and conducted pharmacokinetic analysis on the most potent. At 10 µM, 48/57 compounds resulted in >70% mortality of newly transformed schistosomula, whereas 37 of these maintained >60% mortality of adult S. mansoni. No correlations were observed between ß-hematin inhibitory and antischistosomal activities against both larval and adult parasites, suggesting possible presence of other target(s) or a mode of inhibition of crystal formation that is not adequately modeled by the assay. The most active compound in vivo showed 58.7 and 61.3% total and female worm burden reduction, respectively. Pharmacokinetic analysis suggested solubility-limited absorption and high hepatic clearance as possible contributors to the modest efficacy despite good in vitro activity. The PBIs evaluated in this report thus merit further optimization to improve their efficacy and to elucidate their possible mode of action.

Outcomes of transurethral resection and holmium laser enucleation in more than 60 g of prostate: A prospective randomized study.

AIM: Transurethral resection of prostate (TURP) is considered a gold standard surgical procedure. The management of benign prostatic hyperplasia (BPH) has undergone tremendous change in recent years and shifted from open to minimal invasive procedure. With the advancement in technology and skills of surgeons, lasers have been used more liberally, particularly holmium laser. Holmium laser enucleation of prostate (HoLEP) is seen as close rival of TURP. The objective if this study is to observe long- and short-term outcomes of transurethral resection and holmium laser enucleation in the prostate of more than 60 g. MATERIALS AND METHODS: This prospective randomized study includes 164 patients. Inclusion criteria were age <75 years after failed or poor response to medical therapy, prostatic size >60 g, gross hematuria secondary to BPH, recurrent urinary tract infection, acute urinary retention, postvoid residual >150 ml, and Schafer Grade II or more. BPH associated with neurogenic bladder, stricture urethra, and carcinoma prostate were excluded from the study. Group 1 comprises patients who underwent TURP and Group 2 comprises who underwent HoLEP. Follow-up was done at 1, 3, 6, 12, and 24 months after the surgery. RESULTS: Data of 144 patients were analyzed. The mean age of patients in TURP and HoLEP group was 66.78 ± 7.81 and 67.70 ± 7.44 years, respectively (P = 0.47), mean prostatic volume was 74.5 ± 12.56 and 75.6 ± 12.84 g, respectively (P = 0.60), operative time was 73.10 ± 10.49 and 89.56 ± 13.81 min, respectively (P = 0.0001). Mean resected tissue was 44.80 ± 9.87 and 48.49 ± 10.87, respectively (P = 0.03). The sexual function did not changed significantly in postoperative follow-up. CONCLUSION: HoLEP is associated with less blood loss, lower transfusion rates, and a shorter hospital stay. The disadvantage of HoLEP is longer operative time and postoperative dysuria.

Rare association of congenital penile urethrocutaneous fistula with Y-type urethral duplication.

A 24-year-old man presented with symptoms of difficulty in passage of urine, mixed with gas and stool from penoscrotal junction since birth. He had a history of surgery (posterior sagittal anorectoplasty) for imperforate anus in first week of his life. On physical examination, external meatus was adequate with small 5×5 mm fistulous opening noted at penoscrotal junction with normal anal tone and opening. On evaluation with retrograde urethrography, voiding cystourethrogram, cystoscopy and barium enema, he was found to have penile urethrocutaneous fistula of 0.5×0.5 cm with Y-type incomplete urethral duplication. Urethroanal fistula (Y-type urethral duplication) was of small size (<5 mm), so closed primarily through perineal route with interposition of ischiorectal fat. Penile urethrocutaneous fistula (4 mm) too was closed primarily and covered with tunica vaginalis flap in single sitting. It has been 6 months since surgery and the patient is fully continent and voiding well with no urinary or faecal leak.

Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.