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Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as "stem cell," "alopecia," "hair loss," "Androgenetic alopecia," "male-pattern hair loss," "female-pattern hair loss," "regenerative hair growth," "cell therapy," "mesenchymal stem cells," "MSC-derived extracellular vesicles," "MSC-derived exosomes," and "platelet-rich plasma" and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.
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Background: Inclusion of ethnic/racial minorities in clinical trials is essential to fully assess therapeutic efficacy. It is well-known that populations respond dissimilarly to interventions. Our objective is to analyze the inclusion of minority men in clinical trials for erectile dysfunction (ED). Methods: We searched ClinicalTrials.gov for the disease keyword: "Erectile Dysfunction" and used "Prostate Cancer" for comparison. Completed trials which reported demographic data were included for analysis. Literature was reviewed to determine the prevalence of ED and prostate cancer (PC) among Hispanic, Black, White, and Asian men. The proportion of individuals of each group that participated in trials is divided by the proportion of each group in the disease population to calculate the "Participation to Prevalence Ratio" (PPR). PPRs between 0.8 and 1.2 indicates adequate representation, <0.8 is under-representation and >1.2 is over-representation. Results: A total of 312 trials were assessed: 289 for prostate cancer and 23 for ED. Hispanic men comprised 11.8% of ED trial participants and 4.6% of prostate cancer trial participants, yet represented 18% of ED patients and 7.3% of PC patients. Black/African-American (AA) men accounted for 10.2% of ED trial participants and 9.4% of PC trial participants, but comprise 16% of ED patients, and 16.3% of PC patients. Hispanic and AA men are under-represented in trials for ED and Prostate Cancer (Hispanic ED PPR = 0.66; Hispanic PC PPR = 0.63; AA ED PPR = 0.64; AA PC PPR = 0.58). Conclusion: Our analysis shows that both Hispanic and AA men are underrepresented in both ED and PC clinical trials.
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Phenylketonuria (PKU) is a rare genetic condition caused by inborn error(s) in the gene for the enzyme phenylalanine hydroxylase. Resulting loss of phenylalanine (Phe) metabolism requires strict dietary therapy and/or medication to prevent toxic accumulation of Phe. Novel investigational therapies, including gene therapies that aim to address underlying causes of PKU, are now entering clinical trials. However, perceptions of this technology in the PKU community have not been assessed. We conducted a qualitative survey recruiting adult patients, caregivers, and patient advocates from the US and 3 EU countries to assess the impact of living with PKU and the perceptions of gene therapy. Telephone interviews were conducted for up to 60 min following a standardized discussion guide. Interviewers classified each participant by their level of knowledge regarding gene therapy as either: low (little or no prior awareness); moderate (awareness of gene therapy as a concept in PKU); or high (working knowledge of gene therapy, e.g., vectors). In total, 33 participants were recruited (patients, n = 24; caregivers, n = 5; advocates, n = 4). The patient sample was well balanced among age groups, sex, and US/EU geographies. The participants' experiences and burden of living with PKU were largely negative, characterized by frustrations with current management consistent with prior reports. Most participants (n = 18/33) were identified as displaying moderate gene-therapy knowledge, 10/33 as displaying high knowledge, and 5/33 as displaying low knowledge. Both positive and negative perceptions were observed; positive perceptions were often linked to "hope" that gene therapy may represent a cure, whereas negative perceptions were linked to the "uncertainty" of outcomes. High knowledge of gene therapy appeared to trend with negative perceptions; 7/10 participants from this group reported high levels of concern over gene therapy. In contrast, participants who displayed low knowledge reported low (n = 3/5) or moderate (n = 2/5) concern, with predominantly positive perceptions. These data highlight the need for education around the theoretical risk:benefit profile of gene therapy. Despite current unknowns around gene therapy, our study demonstrates the important role of healthcare providers as educators who can use available data to provide balanced information to patients and caregivers.
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Oxidative damage to lens epithelial cells plays an important role in the development of age-related cataract, and the health of the lens has important implications for overall ocular health. As a result, there is a need for effective therapeutic agents that prevent oxidative damage to the lens. Thiol antioxidants such as tiopronin or N-(2-mercaptopropionyl)glycine (MPG), N-acetylcysteine amide (NACA), N-acetylcysteine (NAC), and exogenous glutathione (GSH) may be promising candidates for this purpose, but their ability to protect lens epithelial cells is not well understood. The effectiveness of these compounds was compared by exposing human lens epithelial cells (HLE B-3) to the chemical oxidant tert-butyl hydroperoxide (tBHP) and treating the cells with each of the antioxidant compounds. MTT cell viability, apoptosis, reactive oxygen species (ROS), and levels of intracellular GSH, the most important antioxidant in the lens, were measured after treatment. All four compounds provided some degree of protection against tBHP-induced oxidative stress and cytotoxicity. Cells treated with NACA exhibited the highest viability after exposure to tBHP, as well as decreased ROS and increased intracellular GSH. Exogenous GSH also preserved viability and increased intracellular GSH levels. MPG scavenged significant amounts of ROS, and NAC increased intracellular GSH levels. Our results suggest that both scavenging ROS and increasing GSH may be necessary for effective protection of lens epithelial cells. Further, the compounds tested may be useful for the development of therapeutic strategies that aim to prevent oxidative damage to the lens.
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The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.
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Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms.
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BACKGROUND: Hepatitis B virus (HBV) infection is an important etiology for chronic hepatitis globally, and especially so in China. HBV infection can lead to the development of cirrhosis through the pathological process of liver fibrosis. The effective suppression of HBV replication with NAs or interferon-alpha can histologically regress the fibrotic pathological process, but there remain patients who have achieved anti-viral responses and normalization of serum liver tests, but not liver fibrosis regression. This subset of patients typically presents with advanced liver fibrosis at baseline. Therefore, it is reasonable to administer the anti-fibrotic agents, coupled with antivirals for patients with advanced liver fibrosis due to HBV, in order to improve the fibrotic regression of the patients. Fuzheng Huayu (FZHY) tablet is a botanical product with evidence demonstrating its efficacy against mild to moderate liver fibrosis. The current clinical trial evaluates the efficacy and safety of the combination therapy of traditional Chinese medicine (TCM) (FZHY and herbal granule) and entecavir for HBV compensated cirrhosis. We will enroll HBV patients who presented with a good viral response after 2 years of entecavir treatment but had advanced liver fibrosis (≥Ishak F5). METHODS: This is a single-arm clinical trial, conducted in 20 centers in mainland China over a period of 60 weeks, including 48 weeks of treatment observation and 12 weeks of follow-up. The main inclusion criteria include HBsAg positive more than 6 months, 2 years administration of entecavir, HBV DNA less than 20 IU/ml, liver fibrotic stage ≥ F5, and Child-Pugh scoring <7 (Stage A). The sample size is estimated to be about 190, considering a 20% drop-out and 60% of patient's compliance for the second liver biopsy so a total of 350 participants will be enrolled. All eligible participants are divided into 3 subgroups according to the TCM clinic pattern. And all patients will take 1 Entecavir tablet (0.5 mg) per day, 4 FZHY tablets (1.6 g) three times a day, and specific TCM granule three times a day, which is decided by TCM clinical patterns (CPs) differentiation. The patients were treated for 48 weeks, and follow-up visits at 12, 24, 36, 48 weeks and 60 weeks. The patients will receive the second liver biopsy at the end of 48 weeks, with a 12 weeks follow-up after that.The primary endpoint is the proportion of subjects with a 1-point improvement of liver fibrosis stage using the Ishak score from baseline to week 48 in the study, according to consensus readings evaluated by a panel of hepato-pathologists. The secondary endpoints are the brightness-mode ultrasonic, fibrotic biomarkers. The adverse events (AEs) will be recorded for 60 weeks, and the safety of the combination therapy will be evaluated. Meanwhile, the efficacy in the 3 sub-groups will be stratified and analyzed. DISCUSSION: The study has been designed to test the therapeutic effects and safety of the combination therapy of FZHY and herbal granule with entecavir on persistent advanced stage fibrosis/cirrhosis following 2 years entecavir treatment, and to explore an effective integrative therapy on HBV cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02241616. Registered on September 16, 2014.
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BACKGROUND/OBJECTIVES: Although much has been learnt regarding pregnancy after liver transplantation, data from India are scant. Hence, we evaluated the maternal and fetal outcomes of pregnancies after liver transplantation at our center. METHODS: We conducted a retrospective review of all patients who underwent liver transplantation and later conceived at our center between 2006 and 2019. RESULTS: Of the 750 liver transplantations performed at our center, 129 were female and 62 of them were in the childbearing age group (15-44 years). A total of seven conceptions occurred in seven patients during the study period. All the pregnancies occurred spontaneously. The median age of the patients at the time of liver transplantation and conception was 25 years (range, 24-33 years) and 29 years (range, 26-36 years), respectively. The median interval between transplantation and conception was 40 months (range, 7-48 months). All patients were on tacrolimus monotherapy. None of the patients had rejection during pregnancy despite a low median tacrolimus trough level of 2.7 ng/mL. Live birth (five cesarean and one normal) occurred in six of seven pregnancies at a median gestation age of 37.5 weeks. Mean birth weight was 3055.8 g (range, 2470-3635 g). Antenatal rubella infection and grade III intrauterine growth restriction resulting in still birth at 29 weeks occurred in one patient. The median postnatal follow-up was 25 months (range, 2-81 months). All babies and mothers were healthy. CONCLUSIONS: Pregnancy after liver transplantation has a favorable outcome with a multidisciplinary team approach. There is a physiological reduction of tacrolimus trough levels during pregnancy for which dose augmentation is not usually required.
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BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis. METHODS: This targeted literature review sought first to identify the humanistic burden of disease from the perspective of patients with diagnosed NASH-cirrhosis and, secondly, to identify generic or disease-specific patient-reported outcome measures (PROMs) used to assess the impact of NASH-cirrhosis. Searches were conducted in bibliographical databases, grey or unpublished literature, liver disease websites, support group websites and online blogs. A quality assessment of specific PROMs was conducted. RESULTS: Patients with NASH-cirrhosis are reported to suffer from lower HRQoL than patients with non-cirrhotic NASH and the general population with respect to physical health/functioning, emotional health and worry, and mental health. Thirteen PROMs were identified, of which 4 were liver-disease specific: CLDQ, CLDQ-NAFLD, LDQoL and LDSI. The most commonly used measures do not comply with current industry or regulatory standards for PROMs and/or are not validated for use in a cirrhotic NASH population. CONCLUSIONS: Patients with NASH-cirrhosis have lower HRQoL and poorer physical health than patients with non-cirrhotic NASH. However, the literature lacked detail of the everyday impact on patients' lives. Currently, a number of PROMs are available to measure the impact of the disease in patients with chronic liver conditions. The lack of studies that include qualitative insights in this population mandates further exploration and research. LAY SUMMARY: It is not well understood how having non-alcoholic fatty liver disease (NAFLD)-related cirrhosis affects a person's everyday wellbeing and quality of life. Some research has been done with patients who have early stages of liver disease but not people with cirrhosis. We found that patients with NAFLD-related cirrhosis tended to have poorer health than patients without cirrhosis. But there was not very much information from patients themselves and there were no tools or questionnaires just for this group of patients.
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As part of the United States Pharmacopeia's ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140â¯mg to â¼1000â¯mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)."
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BACKGROUND: Endoscopic intervention is often the first line of therapy for GI nonvariceal bleeding. Although some of the devices and techniques used for this purpose have been well studied, others are relatively new, with few available outcomes data. METHODS: In this document, we review devices and techniques for endoscopic treatment of nonvariceal GI bleeding, the evidence regarding their efficacy and safety, and financial considerations for their use. RESULTS: Devices used for endoscopic hemostasis in the GI tract can be classified into injection devices (needles), thermal devices (multipolar/bipolar probes, hemostatic forceps, heater probe, argon plasma coagulation, radiofrequency ablation, and cryotherapy), mechanical devices (clips, suturing devices, banding devices, stents), and topical devices (hemostatic sprays). CONCLUSIONS: Endoscopic evaluation and treatment remains a cornerstone in the management of nonvariceal upper- and lower-GI bleeding. A variety of devices is available for hemostasis of bleeding lesions in the GI tract. Other than injection therapy, which should not be used as monotherapy, there are few compelling data that strongly favor any one device over another. For endoscopists, the choice of a hemostatic device should depend on the type and location of the bleeding lesion, the availability of equipment and expertise, and the cost of the device.
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Advancements in in silico techniques of lead molecule selection have resulted in the failure of around 70% of new chemical entities (NCEs). Some of these molecules are getting rejected at final developmental stage resulting in wastage of money and resources. Unfavourable physicochemical properties affect ADME profile of any efficacious and potent molecule, which may ultimately lead to killing of NCE at final stage. Numerous techniques are being explored including nanocrystals for solubility enhancement purposes. Nanocrystals are the most successful and the ones which had a shorter gap between invention and subsequent commercialization of the first marketed product. Several nanocrystal-based products are commercially available and there is a paradigm shift in using approach from simply being solubility enhancement technique to more novel and specific applications. Some other aspects in relation to parenteral nanosuspensions are concentrations of surfactant to be used, scalability and in vivo fate. At present, there exists a wide gap due to poor understanding of these critical factors, which we have tried to address in this review. This review will focus on parenteral nanosuspensions, covering varied aspects especially stabilizers used, GRAS (Generally Recognized as Safe) status of stabilizers, scalability challenges, issues of physical and chemical stability, solidification techniques to combat stability problems and in vivo fate.
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Ciguatera Fish Poisoning (CFP) is a tropical disease caused by the consumption of fish contaminated with ciguatoxins (CTXs). Currently, the only feasible prevention methods for CFP are to avoid the consumption of fish of certain species from some regions, avoid larger fish of certain species, or avoid all fish caught from specific regions. Here, we quantified levels of P-CTX-1B in Spanish Mackerel (Scomberomorus commerson), which is the main fish species that causes CFP in New South Wales and Queensland, Australia, using LC-MS detection against a toxin standard. We found detectable P-CTX-1B in both flesh and liver tissues in fish from New South Wales (n = 71, 1.4% prevalence rate, with a confidence interval of 1%-4%, and 7% prevalence, 1%-12%, in flesh and liver, respectively). In the small sample of fish from Queensland, there was a 46% prevalence (19-73%, n = 13). Toxin levels found were 0.13 µg kg-1 to <0.1 µg kg-1 in flesh, and 1.39 µg kg-1 to <0.4 µg kg-1 in liver, indicating that liver tissue had a significantly higher concentration (â¼5 fold) of P-CTX-1B. No apparent relationship was observed between the length or weight of S. commerson and the detection of P-CTX-1B in this study. Footnote.
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The data presented in this article supports the rat brain sample preparation procedure previous to its injection into the liquid chromatography-tandem mass spectrometry (LC-MS/MS) system to monitor levels of adrenaline, noradrenaline, glutamic acid, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, and 3-methoxy-4-hydroxyphenylglycol. In addition, we describe the method validation assays (such as calibration curve, lower limit of quantification, precision and accuracy intra- and inter-day, selectivity, extraction recovery and matrix effect, stability, and carry-over effect) according to the United States Food and Drug Administration and European Medicine Agency to measure in one step different neurotransmitters and their metabolites. The data supplied in this article is related to the research study entitled: "Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression" (Wojnicz et al. 2016) [1].
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Microalgae are increasingly being utilized as food ingredients for a variety of applications, including as sources of protein, egg and dairy substitutes, and cooking oils. The dietary safety of a new structuring fat produced using a heterotrophic fermentation process by a strain of Prototheca moriformis was evaluated in a 13-week dietary toxicity study and compared with kokum fat, a structuring fat of similar composition used in the food industry and derived from Garcinia indica seeds. The algal structuring fat was evaluated for its genotoxic potential using both in vitro and in vivo assays. No treatment-related adverse events occurred in rats consuming algal structuring fat or kokum fat in the 13-week study; no treatment-related effects were reported for body weight, food consumption, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology. While statistically significant effects occurred in some parameters, none were dose-related or considered adverse. Overall, the NOAELs for the algal structuring fat and the kokum fat were 100 000 ppm, the highest concentrations tested. The algal structuring fat was not mutagenic in the bacterial reverse mutation assay in the Salmonella typhimurium or Escherichia coli strains tested and was not clastogenic in the in vivo mouse bone marrow chromosome aberration assay.
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Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines.
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Adyuvantes Inmunológicos/toxicidad , Vacunas/toxicidad , Animales , Humanos , Vacunas contra Papillomavirus/inmunología , Vigilancia de Productos Comercializados , Medición de Riesgo , SeguridadRESUMEN
Here, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471) and the in vitro chromosomal aberration test (OECD test guideline No. 473) under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU) was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low.
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INTRODUCTION: Since the introduction of the first retropubic tension-free synthetic sling to treat stress urinary incontinence (SUI), newer approaches, different techniques and new devices have been created. Transobturator and single-incision sling (SIS) techniquespara-were developed with the goal of diminishing the rate of complications andspeeding the recovery phase. METHODS: For this review we searched Medline for relevant papers, with an emphasis on meta-analysis and randomised controlled trials (RCTs). Specially selected reports were identified to address both 'index patients' (defined as those with genuine SUI and no previous anti-incontinence procedure or other genitourinary sign or symptom that might affect her SUI) and, briefly, non-index patients. Two authors independently reviewed papers for eligibility. RESULTS: Level 1 evidence from a Cochrane review and two meta-analyses indicated that subjective outcomes with the mid-urethral sling (MUS) were similar to those from colposuspension. However, the MUS was better than colposuspension when assessing objective outcomes (Level 1). MUS are equally effective as autologous pubovaginal slings (Level1). Two meta-analyses suggest that retropubic MUS (RMUS) might be better than transobturator MUS when assessing objective outcomes. Five more recent RCTs with longer term outcomes showed high success rates and only one reported a significant advantage for the RMUS in women with intrinsic sphincteric deficiency. One meta-analysis addressing the SIS showed inferior outcomes to the MUS (Level 1). New and improved SIS techniques have been used, but long-term outcomes are limited and results are still controversial when compared to the MUS. CONCLUSION: MUS are still the standard to treat the index patient as previously stated by the American and European Associations of Urology. Currently data are lacking to define which sling and what approach works best. Complications are significantly different between sling types and are dependent on technique.