Synthesis of Telechelic and Three‐Arm Polytetrahydrofuran‐block‐amylose

Telechelic amine terminated polytetrahydrofuran (PTHF) is prepared via cationic ring opening polymerization (CROP) of THF, initiated by trifluoromethanesulphonic anhydride (triflic anhydride). Hexamethylene tetramine (HMTA) is used as a terminating agent. The resulting HMTA terminated PTHF is hydrolyzed to result in an amine terminated PTHF. Reductive amination is carried out by reacting the PTHF with maltoheptaose resulting in maltoheptaose‐b‐PTHF‐b‐maltoheptaose. The product is prepared as a primer for the enzymatic polymerization to synthesize amylose‐b‐PTHF‐b‐amylose. In addition, a three‐arm PTHF is prepared via CROP of THF. The initiator is synthesized in situ by the reaction of triflic anhydride and triethanol amine. The resulting amine terminated three‐arm PTHF is reacted with maltoheptaose to synthesize a three‐arm PTHF‐b‐maltoheptaose which can be used for the enzymatic synthesis of three‐arm PTHF‐b‐amylose. Characterization of the products is difficult due to the amphiphilic behavior of both telechelic amylose‐b‐PTHF‐b‐amylose and three‐arm PTHF‐b‐amylose. Therefore, the analysis of the products is mainly based on attenuated total reflectance Fourier transform infrared spectroscopy.

     

Abdominal infections in patients with acute leukaemia: a prospective study applying ultrasonography and microbiology

A prospective study of 62 chemotherapy-induced neutropenic episodes in patients with acute leukaemia was conducted to determine the incidence and causes of abdominal infections, and to assess the diagnostic value of the combined use of ultrasonography (US) and microbiology. Each patient underwent US of liver, gallbladder and complete bowel before chemotherapy, on days 2-4 after the end of chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined with a standardized clinical examination and a broad spectrum of microbiological investigations. From January to August 2001, 243 US examinations were performed. The overall incidence of abdominal infectious diseases was 17.7% (11 out of 62, 95% confidence interval (CI): 9-29%). Four patients (6.5%) developed neutropenic enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm in these four patients ranged from 5.8 to 23.6 mm and was detected only in one patient with mucositis. In three other patients (4.8%) Clostridium difficile, and in one patient (1.6%) Campylobacter jejuni, caused enterocolitis without BWT. Cholecystitis was diagnosed in three patients (4.8%) and hepatic candidiasis was strongly suspected in one patient. Abdominal infections caused by gastroenteritis viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT is not a feature of chemotherapy-induced mucositis and should therefore be considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas, Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a very low incidence; and (iii) abdominal infections may be underestimated when US is not used in every patient with abdominal pain.     

Type 2N von Willebrand disease

Type 2N von Willebrand disease (VWD) refers to patients with a factor VIII (FVIII) deficiency caused by a markedly decreased affinity of von Willebrand factor (VWF) for FVIII. It is inherited as an autosomal recessive trait but is clinically similar to mild hemophilia. The differential biologic diagnosis, which is of major importance for providing relevant genetic counseling and optimal treatment, is based on the measurement of plasma VWF capacity to bind FVIII. Molecular biology techniques have allowed the identification of 20 missense mutations in the VWF gene that cause type 2N VWD. All of them induce changes in amino acid residues located in the N-terminal part of mature VWF, which contains the FVIII binding site. Their identification may provide a genetic diagnosis. Theoretically, patients with type 2N VWD should be treated with products containing VWF that is able to stabilize their endogenous normal FVIII.     

Orodispersible films as a personalized dosage form for nursing home residents,an exploratory study

International Journal of Clinical Pharmacy - Background A frequent problem in ageing patients, and thus in nursing home residents, is dysphagia, affecting the ability to swallow solid dosage forms....     

ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients

ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction.     

Growing up in foster families or institutions: Attachment representation and psychological adjustment of young adults

ABSTRACT

Background: Attachment Theory has become one of the leading theories in human development. Nonetheless, empirical studies focusing on how attachment unfolds during adolescence are still scarce particularly in Spain, due to the lack of adequate measures. Objective: This study aims to validate the Important People Interview (IPI) in a shorter questionnaire version (Important People- Questionnaire; IP-Q); to analyse the changes in different affiliative bonds to multiple figures -family, peers, romantic partners – over the course of adolescence; and to identify boys’ and girls’ hierarchical ordering of their specific attachment bonds. Method: 1025 Spanish adolescents, aged 12–17 years old completed the IP-Q. Results: The results showed that the IP-Q has convergent and divergent validity. Moreover, this measure indicated that peers overtake some family members in proximity-seeking and support-seeking, but not in the overall hierarchical ordering of the attachment bond during adolescence. Conclusions: The bond with the romantic partner increases in terms of scoring on the affiliative subscales as adolescence progresses. There are significant gender differences among the hierarchy patterns of attachment for boys and girls. Developmental changes in adolescent attachment are discussed.