A translational framework to DELIVER nanomedicines to the clinic.

Nanomedicines have created a paradigm shift in healthcare. Yet fundamental barriers still exist that prevent or delay the clinical translation of nanomedicines. Critical hurdles inhibiting clinical success include poor understanding of nanomedicines' physicochemical properties, limited exposure in the cell or tissue of interest, poor reproducibility of preclinical outcomes in clinical trials, and biocompatibility concerns.

Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence.

Background: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC.

Materials And Methods: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease.

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial.

Background: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia.

Methods: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial.

Synthesis of novel sugar derived aziridines, as starting materials giving access to sugar amino acid derivatives.

D-Erythrosyl aziridines were obtained from D-erythrosyl triazoles either by photolysis or through diazirine intermediates. These were found to undergo rich, high yielding chemistry by reaction with protic acids (HCl, BiI/HO and trifluoroacetic acid) leading to two types of furanoid sugar α-amino acids, and polyhydroxylprolines. Based on experimental evidence, reaction mechanisms have been proposed for the syntheses.

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.

(3S,4R)-3,4-Dihydroxy-N-alkyl-l-homoprolines: synthesis and computational mechanistic studies.

This is the first synthetic report of (3S,4R)-dihydroxy-N-alkyl-l-homoprolines described so far. 2,4-O-Benzylidene-d-erythrose was obtained from d-glucose with an improved yield, and then transformed into the title (3S,4R)-dihydroxy-N-alkyl-l-homoprolines, in a two-step strategy, with excellent overall yields. Hydrogenolysis of the benzyl group led to the NH congener.

Characterizing the Potential of the Non-Conventional Yeast UTAD17 in Winemaking.

Non- yeasts have received increased attention by researchers and winemakers, due to their particular contributions to the characteristics of wine. In this group, is one of the less studied species. In the present study, a native strain, UTAD17 isolated from the Douro wine region was characterized for relevant oenological traits.

Diversity and Functionality of Culturable Endophytic Bacterial Communities in Chickpea Plants.

The aims of this study were to isolate, identify and characterize culturable endophytic bacteria from chickpea ( L.) roots grown in different soils. In addition, the effects of rhizobial inoculation, soil and stress on the functionality of those culturable endophytic bacterial communities were also investigated.

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.

Total facial selectivity of a D-erythrosyl aromatic imine in [4π + 2π] cycloadditions; synthesis of 2-alkylpolyol 1,2,3,4-tetrahydroquinolines.

Different electron-rich dienophiles were combined with the imine obtained from 2,4-O-benzylidene-d-erythrose and p-anisidine furnishing enantiomerically pure tetrahydroquinolines, by inverse electron-demand [4π + 2π] cycloaddition. The imine was also reacted with 2-substituted electron-rich 1,3-butadienes giving the diastereomeric pure product, resulting from the normal electron demand cycloaddition. The facial selectivity of both processes is proposed on the basis of a 1,4-relationship between the hydroxyl group and the nitrogen atom in the chiral N-(p-methoxyphenyl)imine derivative.

Five-Year Outcome in Stroke Patients Submitted to Thrombolysis.

Background And Purpose: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT).

Methods: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit.

The role of pain catastrophizing in the provision of rescue analgesia by health care providers following major joint arthroplasty.

Background: After surgery, patient reports or health care professional evaluations of heightened acute pain intensity should lead to extra analgesia provision, which is designated by rescue analgesia (RA). Whether RA is administered or not, it is not directly dependent on the patient but rather on clinical decisions, which should be based on pain management guidelines. There is a general lack of studies focusing on pain-related decision-making regarding RA provision.

Differential predictors of acute post-surgical pain intensity after abdominal hysterectomy and major joint arthroplasty.

Background: Psychological factors have a significant role in post-surgical pain, and their study can inform pain management.

Purpose: The aims of this study are to identify psychological predictors of post-surgical pain following abdominal hysterectomy (AH) and major joint arthroplasty (MJA) and to investigate differential predictors by type of surgery.

Method: One hundred forty-two women undergoing AH and 110 patients undergoing MJA were assessed 24 h before (T1) and 48 h after (T2) surgery.

Synthesis and evaluation of α-, β-glucosidase inhibition of 1-N-carboxamide-1-azafagomines and 5-epi-1-azafagomines.

1-N-Carboxamide 1-azafagomines and 5-epi-1-azafagomines were obtained from 1-azafagomine and 5-epi-1-azafagomine. The hydroxyl groups and the N-2 pyridazine position were protected prior to reaction with different isocyanates to form ureas. Protective groups were removed leading to the target compounds in 18-23% global yields.

Advances in the synthesis of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: Leads for the synthesis of active α-glycosidase inhibitors.

A new expeditious preparation of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine has been devised. Stoodley's diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione was merged with Bols's protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time.