Substrate selectivity and unique sequence signatures in SWEET/semiSWEET homologs of four taxonomic groups: Sequence analysis and phylogenetic studies.

The recently discovered SWEET (Sugar Will Eventually be Exported Transporter) proteins are involved in the selective transport of monosaccharides and disaccharides. The prokaryotic counterparts, semiSWEETs, form dimers with each monomer forming a triple-helix transmembrane bundle (THB). The longer eukaryotic SWEETs have seven transmembrane helices with two THBs and a linker helix. Structures of semiSWEETs/SWEETs have been determined experimentally. Experimental studies revealed the role of plant SWEETs in vital physiological processes and identified residues responsible for substrate selectivity. However, SWEETs/semiSWEETs from metazoans and bacteria are not characterized. In this study, we used structure-based sequence alignment and compared more than 2000 SWEET/semiSWEETs from four different taxonomic groups. Conservation of residue/chemical property was examined at all positions. Properties of clades/subclades of phylogenetic trees from each taxonomic group were analyzed. Conservation pattern of known residues in the selectivity-filter was used to predict the substrate preference of plant SWEETs and some clusters of metazoans and bacteria. Some residues at the gating and substrate-binding regions, pore-facing positions and at the helix-helix interface are conserved across all taxonomic groups. Conservation of polar/charged residues at specific pore-facing positions, helix-helix interface and in loops seems to be unique for plant SWEETs. Overall, the number of conserved residues is less in metazoan SWEETs. Plant and metazoan SWEETs exhibit high conservation of four and three proline residues respectively in "proline tetrad." Further experimental studies can validate the predicted substrate selectivity and significance of conserved polar/charged/aromatic residues at structurally and functionally important positions of SWEETs/semiSWEETs in plants, metazoans and bacteria.

Mannose-specific plant and microbial lectins as antiviral agents: A review.

Lectins are non-immunological carbohydrate-binding proteins classified on the basis of their structure, origin, and sugar specificity. The binding specificity of such proteins with the surface glycan moiety determines their activity and clinical applications. Thus, lectins hold great potential as diagnostic and drug discovery agents and as novel biopharmaceutical products. In recent years, significant advancements have been made in understanding plant and microbial lectins as therapeutic agents against various viral diseases. Among them, mannose-specific lectins have being proven as promising antiviral agents against a variety of viruses, such as HIV, Influenza, Herpes, Ebola, Hepatitis, Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and most recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The binding of mannose-binding lectins (MBLs) from plants and microbes to high-mannose containing N-glycans (which may be simple or complex) of glycoproteins found on the surface of viruses has been found to be highly specific and mainly responsible for their antiviral activity. MBLs target various steps in the viral life cycle, including viral attachment, entry and replication. The present review discusses the brief classification and structure of lectins along with antiviral activity of various mannose-specific lectins from plants and microbial sources and their diagnostic and therapeutic applications against viral diseases.

RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials.

OBJECTIVE: To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy. METHODS: Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment. RESULTS: Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%). CONCLUSIONS: The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

Robotic Vaginal Hernia Repair for Recurrent Vaginal Prolapse Status Post-Radical Cystectomy with an Indiana Pouch.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse following a radical cystectomy is challenging to treat and recurrence of prolapse after primary repair is common owing to compromised pelvic floor support and tissue quality. Vaginal prolapse repairs are often preferred because of concern for patients' complex intraabdominal pathological conditions. However, for those with recurrent prolapse following colpocleisis, limited definitive treatment options exist. METHODS: This surgical video presents a 64-year-old G4P4 with a history of radical cystectomy with an Indiana Pouch for invasive urothelial carcinoma who presented with recurrent stage IV vaginal prolapse two years following colpocleisis. Owing to thin vaginal tissue, a sacrocolpopexy with vaginal mesh could not be performed, thus, the patient underwent robotic-assisted vaginal hernia repair with a polypropylene-reinforced ovine tissue matrix attached to Cooper's ligament and the levator ani muscles. RESULTS: The surgery was free from complications and her postoperative Pelvic Organ Prolapse Quantification examination revealed a leading vaginal tissue remnant at the level of the hymen. The patient reported overall improved health and quality of life following surgery and recovery on postoperative validated questionnaires. CONCLUSIONS: Vaginal and pelvic floor hernia repair with a polypropylene-reinforced tissue matrix is a feasible definitive surgical treatment for patients with prior radical cystectomy in whom colpocleisis has failed.

Proximity of percutaneous tibial nerve stimulation needle insertion to surrounding anatomic structures: a cadaveric study.

BACKGROUND: Percutaneous tibial nerve stimulation is a third-line treatment for overactive bladder and urgency urinary incontinence. During the procedure, a needle is inserted cephalad to the medial malleolus and posterior to the tibia. In recent years, permanent implants and leads have been developed for insertion into the medial ankle via a small incision. There are many important structures present in the medial compartment of the ankle, including the great saphenous vein, saphenous nerve, tibial nerve, posterior tibial vessels, and tendons of the posterior compartment leg muscles. OBJECTIVE: The primary objective of this study was to identify the proximity of the percutaneous tibial nerve stimulation needle placed per Food and Drug Administration-approved device instructions to nearby important anatomic structures. The secondary objectives were to identify the proximity of the tibial nerve to the needle site, identify clinically relevant ankle anatomic structures, and confirm the tibial nerve and posterior tibial vasculature by histologic analysis. STUDY DESIGN: Detailed medial ankle dissections were performed bilaterally on 10 female lightly embalmed anatomic donors (cadavers) obtained from the Willed Body Program at the University of Louisville. A pin was inserted at the percutaneous tibial nerve stimulation needle site, and the medial ankle was minimally dissected so the surrounding anatomic structures were visible but not disrupted. The shortest distance from the pin to the selected structures of the medial ankle region was measured. On completion of each dissection and set of measurements, tissue was harvested for histologic examination. The distances between the pin and each structure were assessed using means and standard deviations. A paired t test was used to assess the difference in the locations between the left and right ankles. Statistical analysis was performed on left-sided, right-sided, and combined measurements. An 80% prediction interval was found to represent the expected range of values for the measurement of a new cadaver or patient, and the 95% confidence interval of the mean was computed to characterize the average distance across all cadavers or patients. RESULTS: The medial ankle of 10 adult female lightly embalmed cadavers were examined bilaterally. Dissections were completed from October 2021 to July 2022. Of note, 80% prediction intervals for the tibial nerve, the posterior tibial artery or vein, and the flexor digitorum longus tendon had a lower range of 0.0 mm from the pin and extending to 12.1, 9.5, and 13.9 mm, respectively. Moreover, 2 of the structures were found to be asymmetrical between the right and left ankles. The great saphenous vein was further from the pin on the left (20.5 mm [standard deviation of 6.4 mm] on the left vs 18.1 mm [standard deviation of 5.3 mm] on the right; P=.04). The calcaneal (Achilles) tendon was further from the pin on the right side (13.2 mm [standard deviation of 6.8 mm] vs 7.9 mm [standard deviation of 6.7 mm]; P=.04). Tibial neurovascular structures were confirmed with microscopic analysis. CONCLUSION: The anatomic structures within the medial ankle lie unexpectedly close to the percutaneous tibial nerve stimulation needle site as noted per Food and Drug Administration-approved device instructions. There is a possibility that some medial ankle structures are not symmetrical. It is crucial that practitioners understand medial ankle anatomy when performing percutaneous tibial nerve stimulation or permanent device insertion.

Evaluation of gastrointestinal tract injury within 1 year of surgery for pelvic organ prolapse.

OBJECTIVE: To identify the incidence and risk factors of gastrointestinal injury (GITI) related to pelvic organ prolapse (POP) surgery. METHODS: Women who underwent POP surgery between 2000 and 2020 were identified in the Premier Healthcare Database. The primary outcome was GITI, defined as small or large bowel injury or repair, and fistula or fistula repair. Differences between patients with and without GITI were evaluated, and a multivariable regression was performed to determine independent predictors of GITI. RESULTS: We identified 563,661 index POP surgeries in female patients aged 18 years and older. Of these, 4582 (0.8%) had a bowel injury code within 1 year of index POP surgery. Patients who experienced GITI were more likely to be younger (49.9 ± 12.8 vs 50.9 ± 13.7), and receive surgery with a surgeon who performed less than 12 surgeries per year (48% vs 42%). Most GITI was diagnosed in the same month (73.4%) and same hospital encounter (54%) as index POP surgery. After adjusting for confounders, lysis of adhesions (aOR = 2.03, 95% CI: 1.48-2.72) and perioperative hematoma/hemorrhage (aOR = 2.87, 95%C I: 1.70-4.59) were strongly associated with GITI, while having surgery with a surgeon performing > 50 POP surgeries per year (aOR = 0.66, 95%C I: 0.59-0.75 and concomitant obliterative procedures (aOR = 0.48, 95% CI: 0.34-0.65) were associated with a lower probability of GITI. CONCLUSIONS: The rate of GITI after POP surgery is less than 1%, and injuries are commonly diagnosed and treated in the same month as index surgery. High-volume surgeons and obliterative procedures may be protective against GITI.

General anesthesia versus regional anesthesia in patients undergoing obliterative vaginal procedures for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to compare outcomes in patients receiving general versus regional anesthesia when undergoing obliterative vaginal surgery for pelvic organ prolapse. METHODS: Obliterative vaginal procedures performed from 2010 to 2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes. Surgeries were categorized into general anesthesia (GA) or regional anesthesia (RA). Rates of reoperation, readmission, operative time, and length of stay were determined. A composite adverse outcome was calculated including any of the following: nonserious or serious adverse events, 30-day readmission, or reoperation. Propensity score-weighted analysis of perioperative outcomes was performed. RESULTS: The cohort included 6,951 patients, of whom 6,537 (94%) underwent obliterative vaginal surgery under GA and 414 (6%) received RA. When comparing outcomes under the propensity score-weighted analysis, operative times were shorter (median 96 vs 104 min, p<0.01) in the RA group versus GA. There were no significant differences between composite adverse outcomes (10% vs 12%, p=0.06), or readmission (5% vs 5%, p=0.83) and reoperation rates (1% vs 2%, p=0.12) between the RA and GA groups. Length of stay was shorter in patients receiving GA than in those receiving RA, especially when undergoing concomitant hysterectomy (67% discharged within 1 day in GA vs 45% in RA, p<0.01). CONCLUSIONS: Composite adverse outcomes, reoperation rates, and readmission rates were similar in patients who received RA for obliterative vaginal procedures compared with GA. Operative times were shorter in patients receiving RA than in those receiving GA, and length of stay was shorter in patients receiving GA than in those receiving RA.

Video Playback as an Educational Tool for Improving Resident Laparoscopic Performance: A Randomized Controlled Trial.

STUDY OBJECTIVE: In this single-masked randomized controlled study, we evaluate whether watching video recordings of oneself performing Fundamentals of Laparoscopic Skills (FLS) exercises results in an improvement on the 30-point Global Operative Assessment of Laparoscopic Skills (GOALS) assessment among Obstetrics and Gynecology (Ob/Gyn) residents. DESIGN: Twenty-three Ob/Gyn residents in the 2020-2021 academic year completed the FLS exercises while being timed, video recorded, and receiving real-time feedback from an Ob/Gyn faculty member. Baseline GOALS assessment was completed by participants and faculty. After the intervention, all participants then repeated the FLS exercises while being timed and were again scored using the GOALS assessment. Each participant completed the study in a single session. In addition, all participants completed a pre- and post-test survey. SETTING: University of Louisville Laparoscopic Skills Labortaory. PARTICIPANTS: University of Louisville Ob/Gyn residents in the 2020-2021 academic year. INTERVENTION: Twelve participants were randomized to the intervention and were allowed to watch their video recording in addition to receiving verbal feedback whereas the remaining 11 received verbal feedback only. MEASUREMENTS AND MAIN RESULTS: There were significant improvements in faculty (p <.01) and self-reported GOALS scores (p <.01) when comparing both the intervention and control group with baseline scores. The intervention group improved by 3.2 points more than that of the control group based on masked faculty evaluation (95% confidence interval, 1.4-5.0 points; p <.01). The difference was not significant in resident self-scores. Overall time improved for all participants (15:54 ± 0.21 minutes before and 13:13 ± 0.14 minutes after), but this difference was not significant between the 2 groups. Higher postgraduate year (PGY) residents reported significantly more comfort performing laparoscopic tasks, earned higher GOALS score (faculty and self-scores), and completed the first set of exercises in less time. A significant interaction between PGY and intervention was detected with improvement in GOALS score most strongly associated with PGY4 residents (p <.01). CONCLUSION: Although all learners objectively benefit from watching recordings of themselves performing surgical tasks, advanced learners may benefit the most when video recordings are used as an educational tool.

Interactions of urbanisation, climate variability, and infectious disease dynamics: insights from the Coimbatore district of Tamil Nadu.

Climate change and shifts in land use/land cover (LULC) are critical factors affecting the environmental, societal, and health landscapes, notably influencing the spread of infectious diseases. This study delves into the intricate relationships between climate change, LULC alterations, and the prevalence of vector-borne and waterborne diseases in Coimbatore district, Tamil Nadu, India, between 1985 and 2015. The research utilised Landsat-4, Landsat-5, and Landsat-8 data to generate LULC maps, applying the maximum likelihood algorithm to highlight significant transitions over the years. This study revealed that built-up areas have increased by 67%, primarily at the expense of agricultural land, which was reduced by 51%. Temperature and rainfall data were obtained from APHRODITE Water Resources, and with a statistical analysis of the time series data revealed an annual average temperature increase of 1.8 °C and a minor but statistically significant rainfall increase during the study period. Disease data was obtained from multiple national health programmes, revealing an increasing trend in dengue and diarrhoeal diseases over the study period. In particular, dengue cases surged, correlating strongly with the increase in built-up areas and temperature. This research is instrumental for policy decisions in public health, urban planning, and climate change mitigation. Amidst limited research on the interconnections among infectious diseases, climate change, and LULC changes in India, our study serves as a significant precursor for future management strategies in Coimbatore and analogous regions.

Robotic sacrohysteropexy: an instructional video for uterovaginal prolapse repair in patients with desired uterine preservation.

INTRODUCTION: Minimally invasive sacrohysteropexy is a feasible and safe option for the treatment of uterovaginal prolapse in patients with prior sacrorectopexy. This video demonstrates an approach to robotic sacrohysteropexy while also adapting for a patient's prior sacrorectopexy. Sacrohysteropexy has been shown to be a viable option in women undergoing pelvic reconstructive surgery for the repair of uterovaginal prolapse. METHODS: This video demonstrates key steps in performing a robotic sacrohysteropexy without compromising the integrity of the patient's prior sacrorectopexy. First, incision and dissection of the anterior and posterior peritoneum overlying the cervical stroma is carried out. Tunnels are made through the avascular plane of the broad ligament lateral to the uterine vessels, so as not to compromise uterine blood supply. The anterior and posterior arms of the mesh are attached with interrupted sutures to the cervical stroma. The presacral space is entered and dissected such that the anterior longitudinal ligament is exposed. Care is taken not to disrupt the sutures from the prior sacrorectopexy as the sacral arm of the mesh is secured with two interrupted stitches. CONCLUSION: At completion of the procedure the patient had a well-supported apical compartment.

When prolapse cannot be reduced: incarcerated procidentia due to pelvic mass.

INTRODUCTION AND HYPOTHESIS: Our objective is to demonstrate a surgical approach to the treatment of incarcerated procidentia with obstructed ureters due to a pelvic mass. METHODS: A 61-year-old woman presented with constipation, vaginal swelling, and difficulty voiding. On examination she had complete procidentia, which could not be reduced with gentle pressure. On imaging the prolapse appeared to contain a large pelvic mass measuring 11.5 cm in its greatest diameter, with features consistent with a mature teratoma. She was also noted to have bilateral ureteral obstruction and prominent hydronephrosis. After unsuccessful prolapse reduction under anesthesia, Bovie electrocautery was used to perform a posterior colpotomy. The obstructing mass was dissected away from the uterus and its connecting pedicle transected. The prolapse could then be reduced and a robotic hysterectomy performed. RESULTS: Pathology showed multiple pelvic masses including an 8-cm necrotic cystic nodule most consistent with uterine fibroids and a 4.5-cm mature cystic teratoma with associated seromucinous cystadenoma of the left ovary. Bilateral nephrostomy tubes were placed postoperatively. CONCLUSION: Incarcerated procidentia is an uncommon occurrence, which in rare cases may be due to a pelvic mass. Surgical management may be required with colpotomy for removal of the pelvic mass in order to reduce the prolapse and resolve the case.

Good to excellent Quality of Life in patients suffering from severe obesity post bariatric surgery - A single-center retrospective study report using BAROS Questionnaire.

CONTEXT: Despite the positive outcomes reported in terms of weight loss and resolution of co-morbidities, the impact of bariatric surgery on patient-reported outcomes of quality of life (QoL) still remains scarce, particularly in the Indian population. The present study was conducted to evaluate the efficacy of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) procedures in patients with severe obesity over a period of 2 years in terms of weight loss, resolution of comorbidities, safety and changes in QoL using the Bariatric analysis and reporting outcome system (BAROS). SUBJECTS AND METHODS: The data of 100 patients who underwent RYGB and LSG between March 2014 and December 2017 were analyzed. The study endpoints such as QoL, major and minor complication rates, co-morbidity resolutions and the percentage of excess weight loss (%EWL) were measured using the Moorehead-Ardelt BAROS questionnaire II. RESULTS: At a follow-up point of 2 years, patients achieved a mean %EWL of 79.2 (±28.9) % and the mean postoperative body mass index decreased to 31.7 (±6.22) kg/m2. No major complications were reported to have occurred. Excellent global BAROS outcome was obtained in 20% of patients, very good in 47%, good in 29%, fair 2% and failure in 2% patients 24 months post-surgery. The mean BAROS score was 5.8 ± 1.73, and a 'good' to 'excellent' QoL outcome was observed in 96% of patients. CONCLUSION: RYGB and LSG are safe and effective bariatric procedures. These procedures provided substantial results in good to excellent health-related QoL, weight loss and medical conditions.

Proper assembly of a self-retaining, vaginal Magrina-Bookwalter retractor and demonstration of its use during a vaginal hysterectomy.

INTRODUCTION/AIM OF THE VIDEO: Vaginal surgery often presents challenges of access. To gain adequate visualization of relevant structures, surgical assistants often assume awkward positioning with inadequate stability of handheld retractors. Additionally, the lead surgeon is typically the only member of the surgical team who can adequately visualize the procedure being performed. To that end, devices have been manufactured with aims of optimizing both visualization and workspace while reducing the need of handheld retractors during vaginal surgery. This video presents one of those retractors: a reusable, self-retaining, vaginal Magrina-Bookwalter, with details to help achieve the optimal visualization and workspace with its use. METHODS: A narrated video provides a brief history, components and proper assembly of the retractor with stepwise application of components demonstrated during a vaginal hysterectomy. CONCLUSION: The self-retaining, vaginal Magrina-Bookwalter retractor is a helpful tool to optimize the visualization and workspace while reducing the need for handheld retractors during vaginal procedures deeper into the pelvis.

Mimivirus encodes a multifunctional primase with DNA/RNA polymerase, terminal transferase and translesion synthesis activities.

Acanthamoeba polyphaga mimivirus is an amoeba-infecting giant virus with over 1000 genes including several involved in DNA replication and repair. Here, we report the biochemical characterization of gene product 577 (gp577), a hypothetical protein (product of L537 gene) encoded by mimivirus. Sequence analysis and phylogeny suggested gp577 to be a primase-polymerase (PrimPol)-the first PrimPol to be identified in a nucleocytoplasmic large DNA virus (NCLDV). Recombinant gp577 protein purified as a homodimer and exhibited de novo RNA as well as DNA synthesis on circular and linear single-stranded DNA templates. Further, gp577 extends a DNA/RNA primer annealed to a DNA or RNA template using deoxyribonucleoties (dNTPs) or ribonucleotides (NTPs) demonstrating its DNA/RNA polymerase and reverse transcriptase activity. We also show that gp577 possesses terminal transferase activity and is capable of extending ssDNA and dsDNA with NTPs and dNTPs. Mutation of the conserved primase motif residues of gp577 resulted in the loss of primase, polymerase, reverse transcriptase and terminal transferase activities. Additionally, we show that gp577 possesses translesion synthesis (TLS) activity. Mimiviral gp577 represents the first protein from an NCLDV endowed with primase, polymerase, reverse transcriptase, terminal transferase and TLS activities.

Comparative analyses of attitude, knowledge, and recollection of preoperative counseling regarding pelvic mesh among women with or without a mesh-related complication.

PURPOSE: Our objective was to compare the recollection of preoperative counseling regarding mesh for pelvic organ prolapse (POP) and/or stress urinary incontinence (SUI) among women with or without a mesh-related complication (MRC). We hypothesized that the patients who had MRC would better recollect counseling regarding complications associated with mesh. METHODS: We conducted a retrospective cohort study among women who had prior implantation of synthetic, non-absorbable mesh for POP and/or SUI at least 3 months prior who presented with or without a MRC. The primary outcome was the proportion of women who recalled being counseled preoperatively about the risk of mesh exposure. RESULTS: Ninety-six women were included in the final analysis (50 MRC; 46 no MRC). MRC women presented further in time from the index surgery [median 69 months [IQR 26-115] vs 12 months (IQR 6-64), p < 0.01]. After adjustment for time since surgery and age, MRC women were significantly less likely to recall being counseled about the possibility of any MRC [19/50 (38%) vs 32/44 (73%), aOR 0.29, 95% CI 0.11-0.79, p = 0.01]. They were also less likely to report they would undergo the same surgery again 5-point Likert scale [median 3 (IQR 1-4) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01], less satisfied with their mesh surgery [median 1 (IQR 1-3) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01] and recommended improved preoperative counseling [27/50 (54%) vs 6/46 (13%), p < 0.01]. CONCLUSION: Women who experienced MRC were less likely to recall being counseled about the possibility of MRC and report more unmet needs regarding perioperative counseling than women without MRC.

Breast cancer hypofractionated radiotherapy in 2-weeks with 2D technique: 5-year clinical outcomes of a phase 2 trial.

BACKGROUND: To report clinical outcomes and late toxicities of a 2-week hypofractionated post-operative loco-regional radiotherapy in patients with breast cancer. MATERIALS AND METHODS: This trial was approved by the Institutional Ethics Committee and registered with gov, no. NCT02460744. Between June 2013 and October 2014, 50 patients with breast cancer, post mastectomy or breast conserving surgery (BCS) were included in this study, of whom 10 had BCS. Patients were planned on a 2-dimentional (2D) simulator with 2 tangential fields and an incident supraclavicular field. Radiotherapy dose was 34 Gy/10#/2 weeks and a sequential boost of 10 Gy/5#/1 wk in BCS patients. The primary endpoint was the rate of acute skin toxicities previously reported. Here, we report the secondary end points of late toxicities, cosmesis, local recurrence, disease-free survival (DFS) and overall survival (OS). Late skin toxicities were recorded according to the Radiotherapy and Oncology Group (RTOG) scoring criteria. Cosmetic outcomes were assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG breast cosmesis and the Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) scales for the breast and chest wall, respectively. Kaplan-Meier estimates of DFS and OS were calculated, and 5-year DFS and OS rates (with approximate 95% CIs) were estimated. RESULTS: Late grade ≥ 2 chest wall induration, hypopigmentation and subcutaneous fibrosis were seen in 3 (6%), 3 (6%) and 1 (2%) patients, respectively. Chest wall cosmesis was excellent/good in 34 (72%) and fair/bad in 13 (28%) patients. In BCS patients, grade 2 skin induration, subcutaneous fibrosis and edema was observed in 1 patient (11%) each. Cosmesis was excellent/good in 7 (78%) and fair/bad in 2 (22%) patients. Late grade ≥ 2 arm edema, pain and shoulder stiffness were reported by 1 (2%), 2 (4%) and 2 (4%) patients, respectively. No local recurrences were observed. Five patients developed distant metastases (10%). Seven patients died (14%). The 5-year DFS and OS rate was 90% (95% CI: 77-96%) and 88% (95% CI: 75-94%), respectively. CONCLUSION: Hypofractionated radiotherapy in 2 weeks in patients with breast cancer was associated with minimal late toxicity, good cosmetic outcome and excellent local control. This trial may be of relevance for developing countries where resources are limited.

Is the E. coli Homolog of the Formate/Nitrite Transporter Family an Anion Channel? A Computational Study.

Formate/nitrite transporters (FNTs) selectively transport monovalent anions and are found in prokaryotes and lower eukaryotes. They play a significant role in bacterial growth and act against the defense mechanism of infected hosts. Because FNTs do not occur in higher animals, they are attractive drug targets for many bacterial diseases. Phylogenetic analysis revealed that they can be classified into eight subgroups, two of which belong to the uncharacterized YfdC-α and YfdC-ß groups. Experimentally determined structures of FNTs belonging to different phylogenetic groups adopt the unique aquaporin-like hourglass helical fold. We considered the formate channel from Vibrio cholerae, the hydrosulphide channel from Clostridium difficile, and the uncharacterized channel from Escherichia coli (EcYfdC) to investigate the mechanism of transport and selectivity. Using equilibrium molecular dynamics and umbrella sampling studies, we determined temporal channel radius profiles, permeation events, and potential of mean force profiles of different substrates with the conserved central histidine residue in protonated or neutral form. Unlike the formate channel from V. cholerae and the hydrosulphide channel from C. difficile, molecular dynamics studies showed that the formate substrate was unable to enter the vestibule region of EcYfdC. Absence of a conserved basic residue and presence of acidic residues in the vestibule regions, conserved only in YfdC-α, were found to be responsible for high energy barriers for the anions to enter EcYfdC. Potential of mean force profiles generated for ammonia and ammonium ion revealed that EcYfdC can transport neutral solutes and could possibly be involved in the transport of cations analogous to the mechanism proposed for ammonium transporters. Although YfdC members belong to the FNT family, our studies strongly suggest that EcYfdC is not an anion channel. Absence or presence of specific charged residues at particular positions makes EcYfdC selective for neutral or possibly cationic substrates. Further experimental studies are needed to get a definitive answer to the question of the substrate selectivity of EcYfdC. This provides an example of membrane proteins from the same family transporting substrates of different chemical nature.

Development of a safety zone for rectus abdominis fascia graft harvest based on dissections of the ilioinguinal and iliohypogastric nerves.

BACKGROUND: As a result of the vaginal mesh controversy, surgeons are performing more nonmesh, autologous fascia pubovaginal slings to treat stress urinary incontinence in women. The rectus abdominis fascia is the most commonly harvested site for autologous pubovaginal slings, so it is crucial that surgeons are familiar with the relationship between this graft harvest site and the ilioinguinal and iliohypogastric nerves, which can be injured during this procedure. OBJECTIVE: The aims of this study were as follows: (1) to estimate the safest area between the bilateral courses of the ilioinguinal and iliohypogastric nerves in which a rectus abdominis fascia graft could be harvested with minimal risk of injury to these nerves and (2) to determine the location and dimensions of a graft harvest site that maximized graft length while remaining close to the pubic symphysis. STUDY DESIGN: The ilioinguinal and iliohypogastric nerves were dissected bilaterally in 12 unembalmed female anatomical donors. The distances of these nerves to a 10 × 2 cm rectus abdominis fascia graft site located 4 cm above the pubic symphysis were measured. Nerve courses inferior to the graft site were determined for each donor by linearly extrapolating measurement points; analysis was performed with and without extrapolation. Average nerve trajectories were estimated assuming a linear regression function to predict the horizontal measurement as a quadratic function of the vertical distance; 95% confidence bands were also estimated. An estimated safety zone was determined to be the region between all credible nerve bounds. RESULTS: The largest safety zone that was closest to the pubic symphysis was located at 5.4 cm superior to the pubic symphysis. At this location, the inferior border of the graft could measure 9.4 cm in length (4.7 cm bilaterally from the midline). Extrapolated nerve courses below the study graft site yielded a smaller safety zone located 2.7 cm superior to the pubic symphysis, allowing for the inferior border of the graft to be 4.8 cm (2.4 cm bilaterally from the midline). CONCLUSION: A rectus abdominis fascia graft harvested 5.4 cm superior to the pubic symphysis with the inferior border of the graft measuring 9.4 cm in length should minimize injury to the ilioinguinal and iliohypogastric nerves. These dimensions allow for the longest graft while remaining relatively close to the pubic symphysis. The closer a graft is harvested to the pubic symphysis, the smaller in length the graft must be to avoid injury to the ilioinguinal and iliohypogastric nerves.

Cadaveric surgical demonstration of middle to distal ureteral injury repairs in urologic and gynecologic surgeries.

INTRODUCTION AND HYPOTHESIS: Iatrogenic ureteral injuries can occur during any surgery but are more likely to occur during urologic and gynecologic procedures. The middle and distal ureter are especially at risk of injury during these surgeries. METHODS: The objective of this surgical educational video was to demonstrate how to repair middle to distal ureteral injuries with the following techniques: direct ureteroureterostomy, ureteroneocystotomy, vesico-psoas hitch, and Boari-Ockerblad bladder flap. RESULTS: A female cadaver was used to show how to surgically repair injuries to the middle and distal ureter. CONCLUSIONS: Middle to distal ureteral injuries occurring during urologic and gynecologic surgeries can be repaired by the techniques demonstrated in this video manuscript.

Citation classics: the 100 most cited articles in Urogynecology.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to utilize objective citation analyses to describe the 100 most cited articles in the field of Female Pelvic Medicine & Reconstructive Surgery (FPMRS) and to review their characteristics. METHODS: We searched the Thomas Reuters Web of Science database for the most cited articles within all journals classified as Obstetrics and Gynecology (Ob/Gyn), Urology (Uro), Colorectal Surgery (CRS), and vital General Medicine (GM) journals (New England Journal of Medicine; Journal of the American Medical Association; Lancet; The BMJ). We reviewed search results for FPMRS content and compiled a list of the top 100 most cited articles relevant to FPMRS. RESULTS: We screened 34,934 articles yielded by the initial search and compiled the 100 most cited articles relevant to FPMRS. Of these 100 titles, 40% (42 out of 105) were published in Ob/Gyn, 46.7% (49 out of 105) in Uro, 1.9% (2 out of 105) in CRS, and 11.4% (12 out of 105) in GM journals. The most cited FPMRS article was "The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society" (3,810 total and 242 citations per year). Over half the articles were observational in nature and the majority (58%) of them were related to urinary incontinence in women. CONCLUSIONS: Highly cited FPMRS articles come from a variety of journals, and nearly 50% of the 100 most cited FPMRS articles are from the urology literature. The most cited articles were largely observational rather than interventional studies and mostly related to female urinary incontinence.