Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps

Estudio comparativo del efecto antiinflamatorio del plantago major “llantén” y del diclofenaco

We have determined the 50 Lethal dose of the Metanolic extract of Plantago major "Llanten" given by intraperitoneal route. We have found that 50LD was 4000 mg/Kg. Of animal weigtht, using 36 mice divided in six groups with 6 animal s each one. 40 rats divided in four groups of ten animals each one received on the back 2 mI of carragenin 1 % to the air pouch. After 30 minutes, the extract and diclofenac were administered. Six hours afterwards the animal s were killed. The exudate obtained was used to find the leucocyte count in the Coulter Counter. The rest of the material was centrifuged to determine the concentracion of proteins with de Gornall colorimetric method using the Biuret reactive and a model of protein lof 70 g/L. We found the anti-inflammatory properties of the methanolic extract, administered by the intraperitoneal route 400 mg/Kg. and 800mg/Kg and with diclofenac using the standardized technique of Edwards (CYTED) from the granuloma of .. PoucheSe determinó la Dosis Letal 50(DL50) del extracto metanólico del Plantago major "Llantén" administrado por vía intraperitoneal, hallándose como resultado una DL50 equivalente a 4,000 mg/Kg de peso de animal utilizándose para ello 36 ratones divididos en 6 grupos de 6 animales cada uno. Se utilizarón 40 ratas albinas divididas en 4 grupos de 10 animales cada uno, a las cuales se les infiltró en el lomo 2ml de carragenina al 1% a las bolsas de aire. Después de 30' de haber colocado la carragenina se administró los extractos y el diclofenaco. A las seis horas fueron sacrificados los animales. Del exudado obtenido se utilizó una parte para el recuento de Leucocitos en el Coulter Counter, el resto se centrifugó para determinar la concentración de proteínas totales por el método colorimétrico de Gornall utilizando el reactivo de Biuret y un patrón de proteína de 70 g/L. Se evidenció las propiedades antiinflamatorias significativas del extracto metanólico, administrado por vía intraperitoneal, a la dosis de 400 mg/Kg y 800 mg/Kg de peso frente al diclofenaco, utilizando la técnica estandarizada de Edwars (CYTED), del Granuloma de Pouche

Molecular and Clinical Analyses of Greig Cephalopolysyndactyly and Pallister-Hall Syndromes: Robust Phenotype Prediction from the Type and Position of GLI3 Mutations

Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations (among 60 probands); when these were combined with previously published mutations, two genotype-phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/nonsense and splicing mutations. Second, among the frameshift/nonsense mutations, there was a clear genotype-phenotype correlation. Mutations in the first third of the gene (from open reading frame [ORF] nucleotides [nt] 1–1997) caused GCPS, and mutations in the second third of the gene (from ORF nt 1998–3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3′ third of the gene (after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease