2D-cadmium MOF and gismondine-like zinc coordination network based on the N-(2-tetrazolethyl)-4′-glycine linker

We have designed and synthesized two new metal-organic-frameworks (MOFs) using the novel N-(2-tetrazolethyl)-4′-glycine spacer (TeGly)2−. These materials exhibit intense photoluminescence.This work was supported by the MEC of Spain (Project CTQ2011-24478) and the Junta de Andalucía (FQM-1484). D. F.-J. thanks the Royal Society for a University Research Fellowship.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5NJ00011

Frequency of sequence mutations and variants for the BRCA1 and BRCA2 genes in a sample of Colombian women with suspected hereditary breast cancer syndrome: case series

Objetivo: describir variantes de secuencia en los genes BRCA1 y BRCA2 en una muestra de pacien­tes colombianas con historia personal o familiar de cáncer de mama sugestiva de riesgo genético. Materiales y métodos: serie de casos compuesta por 67 pacientes que fueron remitidas para estu­dio genético por sospecha de síndrome de cáncer de mama y ovario hereditario (HBOC). De los 67 casos, 42 (62,7%) cumplieron con los criterios de indicación médica de la National Comprehensive Cancer Network (NCCN) del 2013, y en ellos se realizó secuenciación completa de los genes BRCA1 y BRCA2. Se determinó la frecuencia de mutación, variantes de secuencia y significancia clínica de las variantes halladas con base en Breast Cancer Informa-tion Core (BIC). Resultados: se identificaron mutaciones para el gen BRCA1 en seis pacientes (14,3%), no se docu­mentó mutación para el gen BRCA2, además se detectaron 43 variantes genéticas en 27 pacientes (64,2% de 42 casos). De estas, 21 (48,8%) fueron identificadas en el gen BRCA1 y 22 (51,2%) en el gen BRCA2.Dentro de estas variantes, se identi­ficaron 5 mutaciones patogénicas solo en el gen BRCA1, de las cuales solo una había sido reportada previamente en Colombia. Conclusiones: este estudio identifica variantes genéticas patogénicas en el gen BRCA1no descritas en estudios previos en la población colombiana y otras conocidas en diferentes poblaciones; permi­tiendo de esta forma ampliar el conocimiento sobre las variantes en población colombiana de los genes BRCA1 y BRCA2. Sin embargo, se requieren más es­tudios con suficiente poder y calidad metodológica para poder estimar la frecuencia de mutaciones y de variantes de secuencia para estos genes en mujeres colombianas con sospecha de síndrome de cáncer de mama u ovario hereditario.Objective: To describe sequence variants in the BRCA1 and BRCA2 genes in a sample of Colombian patients with a personal or family histor y of breast cancer suggestive of genetic risk. Materials and methods: Case series consisting of 67 patients referred for genetic testing because of suspected hereditar y breast and ovarian cancer syndrome (HBOC). Of the 67 cases, 42 (62.7%) met the medical indication criteria of the 2013 National Comprehensive Cancer Network (NCCN) and they were subjected to the entire sequencing of the BRCA1 and BRCA2 genes. A determination was made of the frequency of sequence mutation, variants, and of the clinical significance of the variants found based on the Breast Cancer Information Core (BIC). Results: Mutations were identified for the BRCA 1 gene in six patients (14.3%), no mutation was documented for the BRCA 2 gene, and 43 genetic variants were found in 27 patients (64.2% of 42 cases). Of these, 21 (48.8%) were identified in the BRCA1 gene and 22 (51.2%) in the BRCA 2 gene. Among these variants, 5 pathogenic mutations were found only in the BRCA1 gene and, of those, only 1 had been reported previously in Colombia.Conclusions: This study identifies pathogenic genetic variants in the BRCA1 gene not described previously in the Colombian population, as well as others known in different populations. Therefore, it helps expand knowledge regarding the variants of the BRCA1 and BRCA2 genes in the Colom­bian population. However, additional studies are required with sufficient power and methodologi­cal quality to estimate the frequency of sequence mutations and variants for the BRCA1 and BRCA2 genes in Colombian women suspected of having the hereditar y breast or ovarian cancer syndrome

A Ribosomal Misincorporation of Lys for Arg in Human Triosephosphate Isomerase Expressed in Escherichia coli Gives Rise to Two Protein Populations

We previously observed that human homodimeric triosephosphate isomerase (HsTIM) expressed in Escherichia coli and purified to apparent homogeneity exhibits two significantly different thermal transitions. A detailed exploration of the phenomenon showed that the preparations contain two proteins; one has the expected theoretical mass, while the mass of the other is 28 Da lower. The two proteins were separated by size exclusion chromatography in 3 M urea. Both proteins correspond to HsTIM as shown by Tandem Mass Spectrometry (LC/ESI-MS/MS). The two proteins were present in nearly equimolar amounts under certain growth conditions. They were catalytically active, but differed in molecular mass, thermostability, susceptibility to urea and proteinase K. An analysis of the nucleotides in the human TIM gene revealed the presence of six codons that are not commonly used in E. coli. We examined if they were related to the formation of the two proteins. We found that expression of the enzyme in a strain that contains extra copies of genes that encode for tRNAs that frequently limit translation of heterologous proteins (Arg, Ile, Leu), as well as silent mutations of two consecutive rare Arg codons (positions 98 and 99), led to the exclusive production of the more stable protein. Further analysis by LC/ESI-MS/MS showed that the 28 Da mass difference is due to the substitution of a Lys for an Arg residue at position 99. Overall, our work shows that two proteins with different biochemical and biophysical properties that coexist in the same cell environment are translated from the same nucleotide sequence frame

High prevalence and diversity of HIV-1 non-B genetic forms due to immigration in southern Spain: A phylogeographic approach

Phylogenetic studies are a valuable tool to understand viral transmission patterns and the role of immigration in HIV-1 spread. We analyzed the spatio-temporal relationship of different HIV-1 non-B subtype variants over time using phylogenetic analysis techniques. We collected 693 pol (PR+RT) sequences that were sampled from 2005 to 2012 from naïve patients in different hospitals in southern Spain. We used REGA v3.0 to classify them into subtypes and recombinant forms, which were confirmed by phylogenetic analysis through maximum likelihood (ML) using RAxML. For the main HIV-1 non-B variants, publicly available, genetically similar sequences were sought using HIV-BLAST. The presence of HIV-1 lineages circulating in our study population was established using ML and Bayesian inference (BEAST v1.7.5) and transmission networks were identified. We detected 165 (23.4%) patients infected with HIV-1 non-B variants: 104 (63%) with recombinant viruses in pol: CRF02_AG (71, 43%), CRF14_BG (8, 4.8%), CRF06_cpx (5, 3%) and nine other recombinant forms (11, 6.7%) and unique recombinants (9, 5.5%). The rest (61, 37%) were infected with non-recombinant subtypes: A1 (30, 18.2%), C (7, [4.2%]), D (3, [1.8%]), F1 (9, 5.5%) and G (12, 7.3%). Most patients infected with HIV-1 non-B variants were men (63%, p < 0.001) aged over 35 (73.5%, p < 0.001), heterosexuals (92.2%, p < 0.001), from Africa (59.5%, p < 0.001) and living in the El Ejido area (62.4%, p<0.001). We found lineages of epidemiological relevance (mainly within Subtype A1), imported primarily through female sex workers from East Europe. We detected 11 transmission clusters of HIV-1 non-B Subtypes, which included patients born in Spain in half of them. We present the phylogenetic profiles of the HIV-1 non-B variants detected in southern Spain, and explore their putative geographical origins. Our data reveals a high HIV-1 genetic diversity likely due to the import of viral lineages that circulate in other countries. The highly immigrated El Ejido area acts as a gateway through which different subtypes are introduced into other regions, hence the importance of setting up epidemiological control measures to prevent future outbreaks

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

PREVALENCE OF DRUG RESISTANCE AND VIRULENCE FEATURES IN Salmonella spp. ISOLATED FROM FOODS ASSOCIATED OR NOT WITH SALMONELLOSIS IN BRAZIL

Salmonella is the most common etiological agent of cases and outbreaks of foodborne diarrheal illnesses. The emergence and spread of Salmonella spp., which has become multi-drug resistant and potentially more pathogenic, have increased the concern with this pathogen. In this study, 237 Salmonella spp., associated or not with foodborne salmonellosis in Brazil, belonging mainly to serotype Enteritidis, were tested for antimicrobial susceptibility and the presence of the virulence genes spvC, invA, sefA and pefA. Of the isolates, 46.8% were sensitive to all antimicrobials and 51.9% were resistant to at least one antimicrobial agent. Resistance to more than one antimicrobial agent was observed in 10.5% of the strains. The highest rates of resistance were observed for streptomycin (35.9%) and nalidixic acid (16.9%). No strain was resistant to cefoxitin, cephalothin, cefotaxime, amikacin, ciprofloxacin and imipenem. The invA gene was detected in all strains. Genes spvC and pefA were found in 48.1% and 44.3% of strains, respectively. The gene sefA was detected in 31.6% of the strains and only among S. Enteritidis. Resistance and virulence determinants were detected in Salmonella strains belonging to several serotypes. The high rates of antibiotic-resistance in strains isolated from poultry products demonstrate the potential risk associated with the consumption of these products and the need to ensure good food hygiene practices from farm to table to reduce the spread of pathogens relevant to public health

General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants

Background Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension. Methods We used data from studies carried out from 1990 to 2023 on BMI, WHtR and hypertension in people aged 20–64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR, and calculated Pearson’s correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both in relation to BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI). Findings The correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in south Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, Middle East and north Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and in Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of south Asia would need to be, on average, 2·79 kg/m² (95% CI 2·31–3·28) lower for women and 1·28 kg/m² (1·02–1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone. Interpretation BMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in south Asia, Latin America and the Caribbean, and the region of central Asia, Middle East and north Africa, have higher WHtR than in the other regions