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Introduction: International criteria are used for the diagnosis of multiple sclerosis (MS) and Isolated Clinical Syndrome (ACS), and Neuromyelitis Optica (NMO). PEVs are not included in any of them. We intend to analyse the sensitivity and specificity of visual evoked potentials in the initial diagnosis of MS, ACS, and NMO. Patients and methods: Descriptive, observational, retrospective study of patients treated for a first episode of RR-EM, NMO, or ACS. VEPs are performed during the study of the first episode, with and without ocular symptoms, between October 2012 and March 2019. Results: 142 patients with suspected demyelinating disease, 100 with disease. Of them, 61 women (61%), mean age: 38.82 years ± SD 4.6. Of the total, 83 with RREM, 6 NMO, 11 ACS. Of the 6 patients with NMO, 1 (16.66%) had altered VEPs; of 11 with ACS, 2 (18.18%) with altered VEP; Of the 83 patients with RR-MS, 45 patients (54.21%) had altered VEP. The sensitivity and specificity of visual evoked potentials in MS was 92.86% and 84.74%, respectively. In NMO, the sensitivity was 16.66%, and the specificity was 93.34%. In ACS, the sensitivity was 18.18%, and the specificity was 96.94%. Conclusion: The sensitivity of VEP in our series is slightly higher than other series published in optic neuritis in RR-MS, being very low in patients with NMO and ACS. However, the very high specificity of the test in these variants can help its diagnosis. These data should be corroborated in larger series. Resumen: Introducción: Para el diagnóstico de esclerosis múltiple (EM) y síndrome Clínico Aislado (SCA) y Neuromielitis óptica (NMO) se utilizan los criterios internacionales. En ninguno de ellos no se incluyen los PEV. Nos proponemos analizar la sensibilidad y especificidad de los potenciales evocados visuales en el diagnóstico inicial de EM, SCA y NMO. Pacientes y métodos: Estudio descriptivo, observacional, retrospectivo, de pacientes atendidos por primer brote de EM-RR, NMO ó SCA. Se realizan los PEV durante el estudio del primer episodio, con y sin clínica ocular, entre Octubre 2012 y Marzo 2019. Resultados: 142 pacientes con sospecha de enfermedad desmielinizante, 100 con enfermedad. De ellos, 61 mujeres (61%), media de edad: 38,82 años +/-DE 4.6. Del total, 83 con EM-RR, 6 NMO, 11 SCA. De los 6 pacientes con NMO, 1 (16,66%) tenía los PEV alterados; de 11 con SCA, 2 (18,18%) con PEV alterados; de los 83 pacientes con EM-RR, 45 pacientes (54,21%) con PEV alterados. La sensibilidad y especificidad de los potenciales evocados visuales en EM fue de 92,86% y 84,74% respectivamente. En NMO la sensibilidad fue de 16,66%, y especificidad de 93,34%. En SCA, la sensibilidad fue de 18,18%, y especificidad de 96,94%. Conclusion: La sensibilidad de los PEV en nuestra serie es discretamente superior a otras series publicadas en neuritis óptica en EM-RR, siendo muy baja en pacientes con NMO y SCA. Sin embargo, la altísima especificidad del test en estas variantes puede ayudar a su diagnóstico. Estos datos deberían ser corroborados en series más amplias.

Public spaces are considered areas that promote users’ physical and mental health. The role of these people in public spaces makes it necessary to evaluate such areas. In this study, 12 urban parks on the island of Tenerife were evaluated, combining the assessment of a trained observer and the perception of users, to analyse and categorise the environmental quality of the parks. The findings of this study conclude that users are good evaluators of public spaces; that the Public Space Characteristics Observation Questionnaire (PSCOQ) tool allows the classification of public spaces and that physical order is capable of predicting the environmental quality and the restorative capacity of spaces, as perceived by users. The PSCOQ observation tool makes it possible to detect the strengths and weaknesses of public spaces so they can be improved and adapted to the needs of users.

Background: To understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area. Methods: As part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16–64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR. Results: 32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 − 29%, HPV11 − 18%, HPV16 − 23%, and HPV18 − 17%; seroprevalence was high in the youngest age-group (16–19: 26–37%). HPV seropositivity was associated with having ≥ 3 lifetime sexual partners (OR=2.5, 95% CI=1.7–3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2–2.6). Conclusions: The high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16.

Background: Oncogenic HPV infection is associated to anogenital cancer. We estimate the prevalence and correlates of anogenital HPV infection among a population-based sample of women aged 16–64 years living in the metropolitan area of Puerto Rico. Methods: 564 women completed face-to-face and computer assisted interviews and self-collected anal and cervical specimens. HPV DNA testing used MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for sample amplification. Positive specimens were typed by dot-blot hybridization. Results: Weighted prevalence of cervical, anal, and cervical/anal co-infection was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%), correspondingly. Having ≥3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5–3.5) and last year anal intercourse (OR: 1.6; 95% CI: 1.1–2.5) increased the odds of anogenital HPV infection. Cervical infection was independently associated to anal infection (OR: 3.0; 95% CI: 2.0–4.6). Conclusions: Similar to others, our results confirm the burden of anogenital HPV infection in women and its relationship with sexual behavior. As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease. Keywords: Anogenital HPV infection, Women, Hispanics, Puerto Rico

In vitro and in vivo experiments were designed to evaluate the effectiveness of laboratory-made di-d-fructose dianhydride (DFA)-enriched caramels. The DFA-enriched caramels were obtained from d-fructose (FC), d-fructose and sucrose (FSC), or d-fructose and β-cyclodextrin (FCDC). In the in vitro experiment, raftilose and all caramels increased (P

Summary: Background: Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. Methods: This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Findings: Among 2212 participants, we identified five classes, including four classes with “Low” (565 participants, 26%), “Normal” (651 participants, 29%), “High” (569 participants, 26%), or “Very High” (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, “High Fatigue/Sleep/Pain and Low Anxiety/Depression” (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the “High” class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of “High Fatigue/Sleep/Pain and Low Anxiety/Depression” class participants were similar to the “High” severity class. Interpretation: Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life. Funding: National Institute of Nursing Research (F31NR019007), Canadian Institutes of Health Research, Arthritis Society Canada, the Lady Davis Institute for Medical Research, the Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland.

Babesia bovis is a hemoprotozoan parasite of cattle that has a complex life cycle within vertebrate and invertebrate hosts. In the mammalian host, B. bovis undergoes asexual reproduction while in the tick midgut, gametes are induced, fuse, and form zygotes. The zygote infects tick gut epithelial cells and transform into kinetes that are released into the hemolymph and invade other tick tissues such as the ovaries, resulting in transovarial transmission to tick offspring. To compare gene regulation between different B. bovis life stages, we collected parasites infecting bovine erythrocytes and tick hemolymph. Total RNA samples were isolated, and multiplexed libraries sequenced using paired-end 100 cycle reads of a HiSeq 2500. The data was normalized using the TMM method and analysed for significant differential expression using the generalized linear model likelihood ratio test (GLM LRT) in edgeR. To validate our datasets, ten genes were selected using NormFinder. Genes that had no significant fold change between the blood and tick stages in the RNA-Seq datasets were tested by quantitative PCR to determine their suitability as “housekeeping” genes. The normalized RNA-Seq data revealed genes upregulated during infection of the mammalian host or tick vector and six upregulated genes were validated by quantitative PCR. These datasets can help identify useful targets for controlling bovine babesiosis.

Babesia bovis, Babesia bigemina and Theileria equi are worldwide tick-borne hemoprotozoan that cause diseases characterized by fever, anemia, weight loss and abortion. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the host for life, and becoming a reservoir for tick transmission. The live-attenuated vaccines for B. bovis and B. bigemina are not available for worldwide use due to legal restrictions and other concerns such as potential erythrocyte antigen and pathogen contamination, and a vaccine for T. equi is not available. The use of chemotherapeutics is essential to treat and control these diseases, but several studies have shown the development of drug-resistance by these parasites, and safe and effective alternative drugs are needed. Tulathromycin, a macrolide antibiotic, has proven to be effective against a vast range of bacteria and Plasmodium yoelli, a Babesia and Theileria related intra-erythrocytic apicomplexan. Draxxin® (tulathromycin) is currently licensed to treat infections that cause respiratory diseases in cattle in several countries. In this study, the activity of Draxxin® was tested in vitro on cultured B. bovis, B. bigemina and T. equi. Addition of the drug to in vitro cultures resulted in cessation of parasite replication of the three species tested, B. bovis, B. bigemina and T. equi, with estimated IC50 of 16.7 ± 0.6 nM; 6.2 ± 0.2 nM and 2.4 ± 0.1 nM, respectively, at 72 h. Furthermore, neither parasites nor parasite DNA were detectable in cultures treated with IC100, suggesting Draxxin® is a highly effective anti-Babesia/Theileria drug. Importantly, the IC50 calculated for Draxxin® for the Babesia/Theileria parasites tested is lower that the IC50 calculated for some drugs currently in use to control these parasites. Collectively, the data strongly support in vivo testing of Draxxin® for the treatment of bovine babesiosis and equine piroplasmosis. Keywords: Draxxin®, Tulathromycin, Babesia bovis, Babesia bigemina, Theileria equi, In vitro inhibition growth

Background: People who inject drugs (PWID) have been a marginalized and a stigmatized population since the beginning of the AIDS epidemic and have not experienced the same life-changing benefits of antiretroviral therapy as others. Tele-Harm Reduction (THR) is a telehealth-enhanced, harm reduction intervention, delivered within a trusted SSP venue. It aims to facilitate initiation of care and achieve rapid HIV viral suppression among PWID living with HIV., Methods: In this mixed-methods study, we employed the Practical, Robust, Implementation and Sustainability Model (PRISM) implementation science framework to identify multilevel barriers and facilitators to implementing the THR intervention. Focus groups (n = 2, 16 participants), stakeholder interviews (n = 7) and in-depth interviews were conducted with PWID living with HIV (n = 25). In addition, to assess feasibility and acceptability, we pilot tested the THR intervention and reported viral suppression at 6 months., Results: Focus groups and stakeholder interviews revealed system and organizational level barriers to implementation including requirements for identification and in person visits, waiting times, stigma, case management inexperience, multiple electronic health records, and billing. A potential facilitator was using telehealth for case management and initial provider visit. In the in depth interviews conducted with PWID living with HIV, participants expressed that the SSP creates a convenient, comfortable, confidential environment for delivering multiple, non-stigmatizing PWID-specific services. 35 PWID living with HIV were enrolled in the pilot study, 35 initiated antiretroviral therapy, and 25 (78.1%) were virally suppressed at six months., Conclusion: Rooted in harm reduction, the THR intervention shows promise in being an acceptable and feasible intervention that may facilitate engagement in HIV care and viral suppression among PWID., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Concerning the letter by Moriguchi et al., we describe our experience with a case of encephalopathy with and atypical damage on magnetic resonance imaging (MRI) in a patient with severe infection due to the SARS-CoV2 virus. A 56-year-old woman, without previous pathologies, developed cough, fever, and respiratory failure for five days, after returning from a 6-day trip to Venice. Chest radiography shows a large bilateral interstitial infiltrate. In the first 24 hours, she was admitted to the Intensive Care Unit (ICU) for severe respiratory failure and positive protein chain reaction-PCR in nasal exudate. She needed intubation for ten days. In the first 48 hours outside the ICU, she developed an acute confusional syndrome (hyperactive delirium). Neurological examination showed temporal-spatial disorientation and incoherent fluent speech. An electroencephalogram (EEG) showed generalized hypovoltaic activity. Cranial magnetic resonance imaging showed a bilateral and symmetrical increase in the supratentorial white matter's signal intensity, with a discrete thickening of both temporal lobes, with a slight increase in signal intensity and a sequence of normal diffusion. The lumbar puncture showed no changes (glucose 71 mg/dL, protein 30 mg/dL, 1 leukocyte). Within 72 hours of starting symptoms, she was neurologically asymptomatic. Our final diagnosis was an inflammatory encephalopathy related to a SARS-CoV2 infection., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Study Objective: To compare the cost-effectiveness of ultrasound (US)-guided aspiration and ethanol sclerotherapy versus laparoscopic surgery for benign-appearing ovarian endometrioma., Design: Prospective, cohort pilot study., Setting: Multiple centers, Spain., Patients: Forty patients with suspected ovarian endometrioma identified by US, with a maximum diameter of 35 to 100 mm, of whom 33 met inclusion criteria., Interventions: The study group (n = 17) underwent US-guided aspiration plus sclerotherapy with ethanol, and the control group (n = 14) underwent laparoscopic cystectomy., Measurements and Main Results: Recurrence, complications, and direct costs were compared. One of 17 sclerotherapy patients recurred (5.9%) compared with 4 of 14 laparoscopic surgery patients (28.6%) (odds ratio 0.18, 0.01-1.53). No serious adverse effects (Clavien-Dindo ≥ III) were observed in the sclerotherapy group; 1 patient in the surgery group had a Clavien-Dindo IIIb complication. Median hospital direct costs were significantly lower in the sclerotherapy group than those in the surgery group-266 euros versus 2189 euros., Conclusion: Ethanol sclerotherapy seems to be cost-effective for endometrioma and also appears to reduce complications. In this pilot study, recurrence was not higher than with conventional surgery., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: This study presents the largest clinical experience of percutaneously placed axillary intra-aortic balloon pump (IABP) in patients with advanced heart failure., Background: Transfemoral placement of IABP limits mobility and recuperation in patients who need prolonged support. We had previously reported a novel percutaneous method of IABP placement in the axillary artery and now present our expanded experience with this technique., Methods: We performed a retrospective chart review of patients with advanced heart failure with percutaneous axillary IABP placement from November 2007 to June 2018 at Houston Methodist Hospital. We defined successful cardiac replacement therapy as heart transplant or left ventricular assist device implantation. We compared patients who had successful cardiac replacement with those who died and those who needed unplanned escalation of mechanical circulatory support., Results: Of the 195 patients identified, 133 (68%) underwent successful cardiac replacement (120 transplants and 13 left ventricular assist device) as planned. End-organ function improved on IABP support in patients bridged to next therapy. There were 16 patients that died while on IABP support and 18 needed escalation of support. Higher right atrial/wedge ratio, higher right atrial pressure, smaller left ventricular end diastolic dimension, and ischemic cardiomyopathy were associated with death on the IABP in multivariate analysis. Post-transplant and post left ventricular assist device survival for those bridged successfully was 87% and 62%, respectively. Although bedside repositioning was frequent, 37% needed replacement for malfunction. Vascular complications occurred in a minority., Conclusions: Percutaneous axillary approach for IABP placement is a feasible strategy for prolonged mechanical circulatory support in patients with advanced heart failure., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objective: To identify risk factors associated with postoperative urinary retention in patients undergoing outpatient minimally invasive hysterectomy., Design: A retrospective cohort study., Setting: An academic medical center., Patients: All patients undergoing outpatient minimally invasive hysterectomy between January 2013 and July 2018 were considered for inclusion in the study., Interventions: Outpatient laparoscopic, vaginal, or robotically assisted laparoscopic hysterectomy., Measurements and Main Results: Four hundred forty-four patients met the inclusion criteria. Postoperative urinary retention occurred in 94 patients, and 347 patients successfully passed their voiding trial in the postanesthesia care unit for a pass rate of 79%. Demographic characteristics were similar, except patients who experienced postoperative urinary retention were less likely to be menopausal (23.4% vs 34.7%, p = .038). Those with urinary retention received more perioperative opioids (morphine milligram equivalent of 14.4 mg vs11.2 mg, p = .012), had longer operative times (122.9 ± 55.6 vs 95.7 ± 42.3 minutes, p < .01), and experienced more blood loss (105.3 ± 134.4 vs 78.5 ± 86.8 mL, p = .025). The rate of urinary tract infections was similar. Logistic regression analysis showed that the route of hysterectomy and age were not associated with an increased risk for urinary retention, whereas a longer operative time and higher doses of perioperative opioid use were., Conclusion: In patients undergoing minimally invasive outpatient hysterectomy, a longer operative time and increased perioperative narcotic use increases the risk of postoperative urinary retention., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To review mortality rates in benign gynecologic minimally invasive laparoscopic and robotic surgery (MIS) and the rates associated with commonly performed MIS procedures., Data Sources: An electronic-based search was performed on PubMed, Embase, Scopus, Web of Science, and Cochrane Database for articles published in the last 10 years in English, French, German, Spanish, and Italian., Methods of Study Selection: All MIS articles in benign gynecology reporting operative mortality (within 30 days) were reviewed., Tabulation, Integration, and Results: The articles identified through the aforementioned search criteria were independently evaluated by the first 2 authors. The Newcastle-Ottawa scale for observational studies and Cochrane risk-of-bias assessment tool for randomized controlled trials were used to assess the risk of bias. Meta-analysis was applied to calculate pooled mortality rates using the inverse-variance method. Twenty-one articles (124 216 patients) were included. Operative mortality from any benign MIS (laparoscopy and robotics) procedure was 1:6456 (95% confidence interval [CI]: 1:3946-1:10 562). Studies were then grouped based on the surgical procedure. The mortality rate for hysterectomy (119 721 patients), sacrocolpopexy, and adnexal surgery and diagnostic laparoscopy was 1:6814 (95% CI: 1:4119-1:11 275), 1:1246 (95% CI: 1:36-1:44 700), and 1:2245 (95% CI: 1:45-1:113 372), respectively. Eighteen articles reported operative mortality for laparoscopic surgery and 4 for robotic surgery., Conclusion: Operative mortality in benign minimally invasive gynecologic surgery is low, and mortality for laparoscopic and robotic approaches appears to be similar., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To review early operative mortality (<30 days) for minimally invasive surgery (MIS), laparoscopic and robotic, in gynecologic oncology., Data Sources: An electronic-based search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Database in the last 10 years., Methods of Study Selection: All MIS studies in gynecologic oncology reporting operative mortality from any cause (within 30 days) were included. Studies were excluded if mortality was not reported for MIS or included benign gynecology., Tabulation, Integration, and Results: Meta-analysis was applied to calculate pooled mortality rates using the inverse-variance method. The relative risks and their corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. Sixty-five studies were included (39 183 patients) for an operative mortality of 1:381 (95% CI, 1:306-1:474). Studies were subselected and analyzed by procedures, malignancy, and surgical approach. Of 39 183 patients, 38 619 underwent any type of hysterectomy for a mortality of 1:379 (95% CI, 1:304-1:472). The mortality was 1:281 (95% CI, 1:169-1:469) for a laparoscopic approach and 1:476 (95% CI, 1:365-1:620) for a robotic approach. There were 3369 patients with early cervical cancer undergoing radical hysterectomy with a mortality of 1:2049 (95% CI, 1:356-1:11 832). There were 3501 patients with endometrial cancer undergoing hysterectomy with lymph node dissection with a mortality of 1:195 (95% CI, 1:109-1:349). There were 418 patients with ovarian cancer undergoing MIS procedures with a mortality of 1 in 685 (95% CI, 1:44-1:10971). Eleven studies with 4037 patients compared mortality of gynecologic oncology surgery of any type (laparoscopic [1:626] vs robotic [1:716] for a relative risk of 1.12 [95% CI, 0.35-3.49])., Conclusion: The overall operative mortality for minimally invasive surgery in gynecologic oncology is 1 in 381 (95% CI, 1:306-1:474). For patients with early cervical cancer, it is 1:2049 (95% CI, 1:356-1: 11832), for endometrial cancer with node dissection it is 1:195 (95% CI, 1:109-1:349), and for ovarian cancer it is 1 in 685 (95% CI, 1:44-1:10 971). There is no difference between the type of MIS approach for patients undergoing any type of gynecologic oncology surgery., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To describe a standardized technique for robotic complete excision of sacrocolpopexy mesh., Design: A step by step video demonstration of the technique., Setting: A tertiary care academic hospital., Patients: Three patients with persistent pain after sacrocolpopexy mesh insertion. Although exposure can usually be controlled with partial mesh removal, complete excision may be required for patients with persistent pain, exposure, or severe infection. Because of the inherent inflammation, fibrosis, and distortion of tissue planes with mesh augmentation, removal should be performed in a methodical fashion, preparing for possible visceral injury., Intervention: Robotic-assisted sacrocolpopexy mesh removal., Measurements and Main Results: This video (Video 1) presents a systematic, minimally invasive approach to sacrocolpopexy mesh removal, highlighting the technical and anatomic aspects that can facilitate the procedure. Retroperitoneal dissection along with identification of the anatomic landmarks, such as the sacral promontory, iliac vessels, right ureter, bladder, and rectum, are critical. Backfilling the bladder and the use of vaginal and rectal probes can also optimize difficult tissue planes. In each compartment, identifying the whole mesh before starting its removal may prevent leaving mesh fragments. The caudal to cranial and lateral to medial approach facilitates the extraction of the synthetic tissue. Removing the sacral mesh last allows the attachment to be used as a point of traction. Superior dissection of the mesh requires careful dissection and recognition of great vessels along with autonomic nervous structures such as the superior hypogastric plexus., Conclusion: Minimally invasive removal of sacrocolpopexy mesh can be standardized using this step by step approach., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To demonstrate our experience with hysteroscopic assistance in the laparoscopic repair of an isthmocele., Design: Surgical video article (Canadian Task Force classification III)., Setting: University hospital., Intervention: A 42-year-old woman with a history of previous caesarean section presented as an emergency with a large, seriously infected isthmocele. Once the infection was cured with antibiotics, sonography revealed a 23 × 14-mm isthmocele with 1.4-mm residual myometrium thickness. She reported postmenstrual spotting and dysmenorrhea of several years duration, as well as previous dyspareunia that had worsened after her cesarean section. Given her symptomatic isthmocele with thin residual myometrium and desire for childbearing, laparoscopic repair was offered. First, the bladder was dissected to expose the isthmus. Uterine arteries were dissected. Hysteroscopic guidance and transillumination revealed the edges of the defect. The isthmocele and fibrotic tissue were excised with cold scissors, minimizing cauterization. A hysterometer was placed in the uterine cavity to respect the cervical canal and posterior uterine wall, and the myometrium was then closed in 2 layers. The total surgical time was 120 minutes. The postoperative period was uneventful. At 2 months after surgery, sonography confirmed restoration, with a myometrium thickness of 8.3 mm. The patient was asymptomatic, except for dyspareunia. At 6 months after surgery, hysteroscopic examination was normal. We recommended that the patient avoid attempting pregnancy for 9 months., Conclusion: Hysteroscopic simultaneous assistance during laparoscopic isthmocele repair can be of great help in identifying the edges of the defect, especially in large cavities and in first cases, in which edges might not be clear otherwise. Resecting all of the fibrotic tissue while respecting healthy myometrium is essential. Excessive cauterization and ischemic suturing could prevent proper healing of the myometrium., (Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

The role of hyperphosphatemia in the pathogenesis of secondary hyperparathyroidism, cardiovascular disease, and progression of renal failure is widely known. Here we studied effects of dietary phosphate restriction on mortality and vascular calcification in uremic rats. Control and uremic rats were fed a high-phosphate diet and at 3 months a portion of rats of each group were killed. Serum phosphate and the calcium phosphate product increased in uremic rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were continued on diets containing high phosphate without and with sevelamer, or low phosphate, and after 3 more months they were killed. Serum phosphate was highest in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation than those of uremic rats on high phosphate. Importantly, kidneys from rats on low phosphate showed improvement over kidneys from high-phosphate rats at 3 months. Left ventricles from rats on low phosphate had less perivascular fibrosis and smaller cardiomyocyte size compared to rats on high phosphate. Thus, intensive phosphate restriction significantly reduces mortality in uremic rats with severe vascular calcification.

Malaria is a devastating mosquito-borne disease, which affects hundreds of millions of people each year. It is transmitted predominantly by Anopheles gambiae, whose females must be >10 days old to become infective. In this study, cuticular lipids from a laboratory strain of this mosquito species were analyzed using a mass spectrometry method to evaluate their utility for age, sex and mating status differentiation. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), in conjunction with an acenaphthene/silver nitrate matrix preparation, was shown to be 100% effective in classifying A. gambiae females into 1, 7-10, and 14 days of age. MALDI-MS analysis, supported by multivariate statistical methods, was also effective in detecting cuticular lipid differences between the sexes and between virgin and mated females. The technique requires further testing, but the obtained results suggest that MALDI-MS cuticular lipid spectra could be used for age grading of A. gambiae females with precision greater than with other available methods., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Antibodies capable of recognizing key molecular targets isolated e.g. by phage display technology have been used in the pursuit of new and improved therapies for prevalent human diseases. These approaches often take advantage of non-immunogenic antibody fragments to achieve specific toxin-, radioactivity- or effector-domain delivery. There is now a growing interest in using anti-idiotypic antibodies or other antigen mimics to induce potent immune responses against antigen structures in question. We have earlier reported on the functional rescue of antibodies that are active when fused to the phage, but inactive as soluble protein [Jensen, K.B., Larsen, M., Pedersen, J.S., Christensen, P.A., Alvarez-Vallina, L., Goletz, S., Clark, B.F. and Kristensen, P. (2002) Functional improvement of antibody fragments using a novel phage coat protein III fusion system. Biochem. Biophys. Res. Commun. 298, 566-73.]. The rescue was accomplished by maintaining the fusion between the antibody fragment and portions of the filamentous bacteriophage coat protein 3, as present in the original antibody-displaying phage. In the present study, we have applied this system in an attempt to improve immunogenicity of anti-idiotypic antibodies isolated by phage display. Here we demonstrate that by preserving linkage between phage antibody and the N-terminal domain of phage coat protein 3, we induce multimerization of the antibody fragments, and improve their immunogenicity. This immunization approach allows induction of anti-idiotypic antibodies in mice, and facilitates the use of antibodies that are non-functional as non-fused soluble protein.

Methadone is a basic drug highly bound to alpha1-acid glycoprotein (AGP), a plasma protein that increases in several pathological situations. Our aims were to evaluate the processes (pharmacokinetics-PK and/or pharmacodynamics-PD) associated with changes of methadone analgesia under conditions of increased AGP, and whether these changes are dependent on binding, secondary to a pathology, or directly attributable to AGP. AGP levels, in rats, were increased by two different methods: (a) experimental inflammation with turpentine oil (TP), and (b) by directly infusing the protein (exo-AGP). Both had a corresponding control group. Tail-flick analgesia and PK were evaluated after methadone dose (0.35 mg/kg i.v.). Bicompartmental PK parameters as well as interanimal and assay variabilities were estimated using NONMEM. The relationship between Cp and analgesic effect (PD) was analyzed with WINNONLIN. AGP levels in both pretreated groups (TP and exo-AGP) were significantly increased, and the unbound fraction (fu) was decreased, compared to controls. All PK parameters were lower in the pretreated groups, but in exo-AGP the difference was maintained even when corrected by fu. Paradoxically, also in exo-AGP the analgesic effect was practically nonexistent, although the unbound Cp remained high, possibly associated to a change in the PD. AGP appears responsible for alterations in both PK and PD, beyond protein binding and inflammatory processes.

The effect of omeprazole on oral and intravenous (iv) RS-methadone pharmacokinetics and pharmacodynamics was studied in awake, freely moving rats, which were divided in four groups: oral RS-methadone (3 mg/kg) was given (a) to a control group (CO(oral)) (n = 65) and (b) to an omeprazole pretreated group (OP(oral)) (n = 77), and iv RS-methadone (0.35 mg/kg) was administered (c) to a control group (CO(iv)) (n = 86) and (d) to an omeprazole pretreated group (OP(iv)) (n = 86). Omeprazole (2 mg/kg) was given iv 2 h before RS-methadone. Plasma concentrations of RS-methadone (Cp) were determined by high-performance liquid chromatography and analgesic response by tail flick for 0-180 min (oral) and 0-120 min (iv). RS-Methadone rate of absorption (mean +/- SE) was faster in OP(oral) (k(01) = 0.31 +/- 0.04 min(-1)) than in CO(oral) (k(01) = 0.05 +/- 0.007 min(-1)), consequently plasma peak concentrations (C(max)) were greater (197.41 +/- 33.70 ng/mL versus 83.54 +/- 7.97 ng/mL) and the time to reach C(max) (t(max)) was shorter (11.23 +/- 1.32 min versus 39.18 +/- 1.74 min). Mean area under the Cp-time curve (AUC(0-infinity)) and hence bioavailability of oral RS-methadone were increased by omeprazole without significant changes in the elimination. Omeprazole did not affect the pharmacokinetics of iv RS-methadone. The changes of the analgesic effect of RS-methadone as a function of time were similar in all four groups. In the CO(oral) group, Cp and analgesic effect were defined by the E(max) model. The relationship between Cp and drug effect in the OP(oral) group showed a counterclockwise hysteresis (k(e0) of 0.018 +/- 0.006 min(-1)). For the iv groups (CO(iv) and OP(iv)), the Cp-analgesic effect relationship was described by an E(max) sigmoid model and omeprazole did not affect the pharmacodynamic parameters. It is concluded that omeprazole causes an increase in the bioavailability of oral RS-methadone without modifying the analgesic response but affecting the Cp-effect relationship., (Copyright 2002 Wiley-Liss Inc.)

The pharmacokinetics of lerisetron, a novel 5HT(3) antagonist, are studied together with its efficacy in inhibiting the serotonin (5-HT)-evoked transient bradycardia reflex (von Bezold-Jarisch reflex) in Sprague Dawley rats. [(14)C]Lerisetron (50, 100, and 200 microg/kg) was given to rats by intravenous (iv) injection and plasma levels of unchanged (UL) and total (unchanged + changed, TL) drug were measured by liquid chromatography with radioactivity monitoring and scintillation counting, respectively. Linearity of UL and TL pharmacokinetics over the dose range was established by noncompartmental analysis. Protein binding of lerisetron was measured in vitro by ultrafiltration. The unbound fraction was 14.4 +/- 1.4%. A nonlinear mixed effects ("population") bicompartmental pharmacokinetic analysis showed that volume of distribution and clearance (CL) were high for both forms of the drug, but CL was significantly smaller for TL [(mean +/- SEM) 0.014 +/- 0.03 L/min for UL versus 0.006 +/- 0.03 L/min for TL, p < 0.05)]. Large interindividual variabilities were observed for both forms. The response to lerisetron administration (inhibition of bradycardia) was evaluated at different doses (2, 3, 5, 6, and 10 microg/kg, iv) at times 2-180 min after dose administration and related to simulated concentrations. Inhibition was 100% 5 min after the 10-microg/kg dose and, 3 h later, it was still > 10%. Response to lerisetron was dose related in the range studied. Pharmacodynamic parameters were estimated by a sigmoid E(max) naive-pooled model. The parameters were also different between the two forms: EC(50) was 0.44 ng/mL (CV = 5.9%) for UL and 0.88 ng/mL (CV = 4.9%) for TL. We conclude that UL and TL pharmacokinetics were linear and that the differences in the kinetics and dynamics between the two forms suggest the presence of at least one metabolite., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To report for the first time a case series of vitreoretinal pathologic conditions after laser in situ keratomileusis (LASIK) and to determine its incidence., Design: Case series., Participants: Five refractive surgeons and 29,916 eyes that underwent surgical correction of ametropia (83.2% were myopic) ranging from -0.75 to -29.00 diopters (D; mean: -6.19 D) and from +1.00 to +6.00 D (mean: +3.23 D) participated in this retrospective study., Main Outcome Measures: Vitreoretinal complications after LASIK., Results: The clinical findings of 20 eyes (17 patients) with LASIK-related vitreoretinal pathologic conditions are presented. Fourteen eyes experienced rhegmatogenous retinal detachments (RDs). Two eyes experienced corneoscleral perforations with the surgical microkeratome when a corneal flap was being performed (one experienced a vitreous hemorrhage and the other later experienced an RD). In four eyes, retinal tears without RDs were found. In one eye, a juxtafoveal choroidal neovascular membrane (CNVM) developed. Retinal tears were treated with argon laser retinopexy or cryotherapy. Corneoscleral perforations were sutured, and the RD was managed with vitrectomy. The remaining RDs were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The CNVM was surgically removed. The incidence of vitreoretinal pathologic conditions determined in our study was 0.06%., Conclusions: Serious complications after LASIK are infrequent. Vitreoretinal pathologic conditions, if managed promptly, will still result in good vision. It is very important to inform patients that LASIK only corrects the refractive aspect of myopia. Complications of the myopic eye will persist.

The chemical synthesis and physical data of several new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are reported, which contain either a chloro- or an alkoxy-group as a substituent in the acid side-chain.

The chemical synthesis and physical data of several new esters of testosterone (17 beta-hydroxyandrost-4-en-3-one), which contain either a halogeno or an alkoxy substituent in the acid chain, are reported.

Some new derivatives of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are described in which the 17 beta-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated.

The synthesis of nine new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described, with the esterifying acids bearing an acetylenic or olefinic function in a chain of eight or nine carbon atoms, for evaluation as long-acting contraceptive agents.

Esters of levonorgestrel (13 beta-ethyl-17 beta-ethynyl-17 beta-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.