Dialkyl carbonates: scale-up synthesis and application as green solvents for PVDF membranes preparation

Dialkyl carbonates (DACs) are well-known green solvents and reagents that have been extensively investigated as safe alternatives to chlorine-based compounds. In fact, they can replace alkyl halides and dimethyl sulfate in alkylation and carbonylation reactions as well as phosgene and its derivatives in alkoxycarbonylation ones. Recently we have developed a high yielding scale-up synthesis of non-commercially available or expensive DACs via transcarbonylation reactions of an alcohol with dimethyl carbonate (DMC) promoted by the nitrogen-based organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene TBD. Compared to previously published works, the proposed procedure has been customized for DACs large scale production (up to 100 mL of product obtained). Purification of these compounds has been achieved by fractional distillation and the exceeding reagents have been recovered and recycled. Selected DACs for this study include both symmetrical and unsymmetrical compounds, incorporating several alkyl, alkoxyalkyl, alkylamino and alkylthio functional groups. Chemical-physical properties of the new DACs have been also evaluated, as well as their water solubility. Furthermore, biodegradability and cytotoxicity tests have been carried out to investigate the effects of the different substituents on the greenness of these potential solvents and reagents. DACs application as green solvents for membrane preparation was next investigated, using non-solvent induced phase separation (NIPS) and vapor induced phase separation (VIPS) techniques, achieving both porous and plain membranes [4]. Morphology, additives effect, physical-chemical and mechanical proprieties as well as their performances in terms of water permeability and rejection were evaluated and compared to membranes obtained using commercially available cyclic carbonates (namely ethylene carbonate – EC and propylene carbonate – PC)

Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites

Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD

Abstract Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even observed a slight mean linear increase of 4.5 ml/m per year during childhood and adolescence for the overall cohort. Patients with two null PKHD1 variants had larger first documented haeTKV values than children with missense variants (median (IQR) haeTKV 793 (450–1098) ml/m in Null/null, 403 (260–538) ml/m in Null/mis, 230 (169–357) ml/m in Mis/mis). In the overall cohort, estimated glomerular filtration rate decreases with increasing haeTKV (median (IQR) haeTKV 210 (150–267) ml/m in CKD stage 1, 472 (266–880) ml/m in stage 5 without kidney replacement therapy). Strikingly, there is a clear correlation between haeTKV in the first eighteen months of life and kidney survival in childhood and adolescence with ten-year kidney survival rates ranging from 20% in patients of the highest to 94% in the lowest quartile. Early childhood haeTKV may become an easily obtainable prognostic marker of kidney disease in ARPKD, e.g. for the identification of patients for clinical studies

Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD)

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (� 3 months; VEBNE) and early (4�15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset � 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort. © 2020, The Author(s)

Continuing education Ultrasound-guided injections in the middle and lower cervical spine

Abstract Injection therapies play a major role in the treatment of cervical pain and are becoming integral parts of a multidisciplinary approach in treatment and rehabilitation of such patients. Pararadicular-and facet-joint injections in the cervical spine are preferentially performed under computed tomography (CT) or fluoroscopy-guidance. In this article we present an alternative, simple and easy to learn step by step US-guided technique for injection therapy in the cervical spine

Book of Abstracts ITM SEMINAR DAY 2021

Dialkyl carbonates (DACs) are well-known green solvents and reagents that are extensively investigated as safe alternatives to chlorine reagents. In fact, they can replace alkyl halides and dimethyl sulfate in alkylation and carbonylation reactions as well as phosgene and its derivatives in the alkoxycarbonylation ones [1,2]. In this talk, I will be presenting our latest results in the high yielding scale-up synthesis of non-commercially available or expensive DACs via transcarbonylation reactions of an alcohol with DMC promoted by the nitrogen-based organocatalyst, 1,5,7- triazabicyclo[4.4.0]dec-5-ene (TBD). Compared to previously published works [3,4], the proposed procedure has been customized for DACs large scale production (up to 100 mL of product obtained). Purification of these compounds has been achieved by fractional distillation and the exceeding reagents have been recovered and recycled. The selected DACs for this study include both symmetrical and unsymmetrical compounds, incorporating several alkyl, alkoxyalkyl, alkylamino and alkylthio functional groups. Chemical-physical properties of the new DACs have been also evaluated, as well as their water solubility. Furthermore, biodegradability and cytotoxicity tests have been carried out to investigate the effects of the different substituents on the greenness of these potential solvents and reagents. Finally, both commercially available cyclic carbonates (namely ethylene carbonate – EC and propylene carbonate – PC) and selected samples of the newly synthetized DACs, have been investigated as green solvents for membrane preparation, using nonsolvent induced phase separation (NIPS) and vapor induced inverse phase separation (VIPS) techniques, achieving both porous and plain membranes. Physical-chemical, morphology, mechanical proprieties and the performance in terms of water permeability and rejection of these new membranes have been also evaluated