Child outcomes after placement of a cervical pessary in women with a multiple pregnancy : A 4-year follow-up of the ProTWIN trial

Acknowledgements We like to thank the research nurses of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynecology for their help in finding contact details of the parents.Peer reviewedPublisher PD

Extraction of low molecular weight polyhydroxyalkanoates from mixed microbial cultures using bio-based solvents

(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) obtained from waste/wastewater using a mixed microbial culture (MMC) usually varies in its properties due to daily variation in the waste/wastewater composition applied as feedstock. In the current study, the average molecular weight (MW) of PHBV was purposely reduced from about 1 MDa to about 200 kDa by drying the PHBV-rich biomass at elevated temperature of 120 °C for 18 h to ease extraction and handling. Furthermore, conversion into value-added chemicals such as trans-crotonic acid (trans-CA) and trans-2-pentenoic acid (2-PA) by thermal decomposition (pyrolysis) benefits from the lower MW. For the extraction of low MW PHBV, the use of the bio-based solvents 2-methyltetrahydroxyfuran (2-MTHF) and dihydrolevoglucosenone (cyrene) was studied. The maximum extraction yield of 62 ± 3 % with purity of > 99 % was achieved with 2-MTHF at 80 °C for an hour with high biomass to solvent ratio of 5 % (g/mL). Cyrene-based extractions resulted in the highest yield of 57 ± 2 % with purity of > 99 % at 120 °C in 2 h with 5 % (g/mL) biomass to solvent ratio. The mass balance closure over the extraction process indicated that about 15 % and 10 % of polymer has remained in the residual biomass after extraction by 2-MTHF and cyrene, respectively. The performance of these new solvents to extract polymers with various average MW was compared to the benchmark extractions using chloroform and dimethyl carbonate (DMC). It was found that for the polymers with low average MW the extraction efficiency of the proposed solvents exceeds the benchmark solvents.ChemE/Advanced Soft Matte

Pessary for preterm birth prevention in twin pregnancy with short cervix : 3-year follow-up study

OBJECTIVE: We recently found in a randomized clinical trial (ProTWIN) that cervical pessary prevented preterm birth and improved neonatal outcome in women with a multiple pregnancy and a cervical length (CL) <38mm. In this follow-up study we evaluated long-term developmental outcomes in the offspring of these women at three years corrected age. METHODS: We conducted a follow-up study of the ProTWIN trial, a trial in which between 2009 and 2012 asymptomatic women with a multiple pregnancy had been randomized to pessary or no pessary. Our current follow-up and analysis was limited to mothers with a midtrimester CL< 38mm (78 and 55 mothers, 157 and 111 children in the pessary and control group, respectively). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. We compared death after randomization or neurodevelopmental disability (Bayley score of ≤ 85, 1SD below mean) rates between pessary and controls according to intention-to-treat principle and using multiple imputation for missing data. We compared mean Bayley-III scores in surviving children. A linear mixed effects model was used to adjust for correlation between children of one mother. RESULTS: In total 27 children had died (6 pessary vs 21 control group, 5% versus 26%, adjusted odds ratio (aOR) 0.14; [95% CI 0.04 to 0.50]). Bayley-III outcomes were collected for 173 out of 241 (72%) surviving children (114 (75%) pessary vs 59 (66%) control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) vs 23 (29%) in pessary and control group respectively; aOR 0.26 [95% CI 0.09 to 0.75]. We found neither statistical nor clinically relevant differences in cognitive, language and motor development among surviving children between both groups. Comparable results were found after multiple imputation. CONCLUSION: In women with a twin pregnancy and a CL < 38 mm, the use of cervical pessary strongly improved survival of the children without affecting neurodevelopmental disability at three years corrected age

Pessary for preterm birth prevention in twin pregnancy with short cervix : 3-year follow-up study

OBJECTIVE: We recently found in a randomized clinical trial (ProTWIN) that cervical pessary prevented preterm birth and improved neonatal outcome in women with a multiple pregnancy and a cervical length (CL) <38mm. In this follow-up study we evaluated long-term developmental outcomes in the offspring of these women at three years corrected age. METHODS: We conducted a follow-up study of the ProTWIN trial, a trial in which between 2009 and 2012 asymptomatic women with a multiple pregnancy had been randomized to pessary or no pessary. Our current follow-up and analysis was limited to mothers with a midtrimester CL< 38mm (78 and 55 mothers, 157 and 111 children in the pessary and control group, respectively). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. We compared death after randomization or neurodevelopmental disability (Bayley score of ≤ 85, 1SD below mean) rates between pessary and controls according to intention-to-treat principle and using multiple imputation for missing data. We compared mean Bayley-III scores in surviving children. A linear mixed effects model was used to adjust for correlation between children of one mother. RESULTS: In total 27 children had died (6 pessary vs 21 control group, 5% versus 26%, adjusted odds ratio (aOR) 0.14; [95% CI 0.04 to 0.50]). Bayley-III outcomes were collected for 173 out of 241 (72%) surviving children (114 (75%) pessary vs 59 (66%) control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) vs 23 (29%) in pessary and control group respectively; aOR 0.26 [95% CI 0.09 to 0.75]. We found neither statistical nor clinically relevant differences in cognitive, language and motor development among surviving children between both groups. Comparable results were found after multiple imputation. CONCLUSION: In women with a twin pregnancy and a CL < 38 mm, the use of cervical pessary strongly improved survival of the children without affecting neurodevelopmental disability at three years corrected age

Intermediate term survival following open versus robot-assisted radical cystectomy in the Netherlands:results of the Cystectomie SNAPSHOT study

There is insufficient knowledge on intermediate-term survival of non-metastatic muscle-invasive bladder cancer (MIBC) after open (ORC) versus robot-assisted (RARC) cystectomy, with or without neo-adjuvant chemotherapy (NAC). This retrospective study was performed in 19 Dutch hospitals between 2012 and 2015 to assess the five-year survival after both interventions and the influence of NAC. Out of 1,534 cT1-4N0-1-patients, 1,086 patients were treated with ORC and 389 with RARC. The 5-year survival rate after ORC was 51% (95% CI 47–53) versus 58% after RARC (95% CI 52–63), hazard ratio 1.00 (95% CI 0.84–1.20) after multivariable analysis. 226 of 965 cT2-4aN0 patients were treated with NAC. More patients had ypT0 after NAC than after no NAC (31% vs 15%; p?&lt; 0.01). The best five-year survival was in patients with ypT0 after NAC (89%; 95% CI 81–97). This study shows similar five-year survival of MIBC patients treated with ORC or RARC and shows that the best survival was after NAC

Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case–control matching study

Objectives: To assess survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) with or without neo-adjuvant chemotherapy (NAC) according to the pathological response at RC. Methods: 965 patients with MIBC (cT2-4aN0M0) who underwent RC with or without NAC were analyzed. Among the collected data were comorbidity, clinical and pathological tumor stage, tumor grade, nodal status (y)pN, and OS. Case–control matching of 412 patients was performed to compare oncological outcomes. Kaplan–Meier curves were created to estimate OS for patients who underwent RC with or without NAC, and for those with complete response (pCR), partial response (pPR), or residual or progressive disease (PD). Results: Patients with a pCR or pPR at RC, with or without NAC, had better OS than patients who had PD (both p values < 0.001). Moreover, the incidence of pCR was significantly higher in patients receiving NAC prior to RC than in patients undergoing RC only (31% versus 15%, respectively; p < 0.001). Case–control matching displayed better OS of patients who underwent RC with NAC, median survival not reached, than of those who underwent RC only, median 4.5 years (p = 0.023). Conclusions: This study showed that patients with MIBC who underwent NAC with RC had a significant better OS than those who underwent RC only. The proportion of patients with a pCR was higher in those who received NAC and RC than in those who were treated by RC only. The favorable OS rate in the NAC and RC cohort was probably attributed to the higher observed pCR rate

Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology

Solute carriers form one of three major superfamilies of membrane transporters in humans, and include uniporters, exchangers and symporters. Following several decades of molecular characterisation, multiple solute carriers that form obligatory heteromers with unrelated subunits are emerging as a distinctive principle of membrane transporter assembly. Here we comprehensively review experimentally established heteromeric solute carriers: SLC3-SLC7 amino acid exchangers, SLC16 monocarboxylate/H+ symporters and basigin/embigin, SLC4A1 (AE1) and glycophorin A exchanger, SLC51 heteromer Ost α-Ost β uniporter, and SLC6 heteromeric symporters. The review covers the history of the heteromer discovery, transporter physiology, structure, disease associations and pharmacology - all with a focus on the heteromeric assembly. The cellular locations, requirements for complex formation, and the functional role of dimerization are extensively detailed, including analysis of the first complete heteromer structures, the SLC7-SLC3 family transporters LAT1-4F2hc, b0,+AT-rBAT and the SLC6 family heteromer B0AT1-ACE2. We present a systematic analysis of the structural and functional aspects of heteromeric solute carriers and conclude with common principles of their functional roles and structural architecture