P53 expression correlates with low axillary tumor burden in breast cancer.

Background: The p53 mutation in breast cancer confers a worse prognosis and is usually associated with p53 overexpression (p53+) on immunohistochemistry. Previous studies have shown that p53+ tumors could be associated with low axillary tumor burden (ATB).

Objective: We aimed to evaluate the association between p53+ and ATB in a large series of breast cancers as an aid to personalizing axillary surgical treatment.

The impact of COVID-19 pandemic on the incidence of acute gastroenteritis outbreaks in Catalonia (Spain).

We carried out a retrospective study of acute gastroenteritis (AGE) outbreaks reported between 1 January 2015 and 31 December 2021 in Catalonia (Spain) to compare the incidence from 2015 to 2019 with that observed from 2020 to 2021. We observed a higher incidence rate of outbreaks during the prepandemic period (16.89 outbreaks/1,000,000 person-years) than during the pandemic period (6.

Relationship between Urinary Parameters and Double-J Stent Encrustation.

(1) Background: This study aimed to determine the relationship between metabolic urine conditions and the formation, severity, and composition of encrustations in ureteral stents. (2) Methods: Ninety stone-former patients requiring a double-J stent were prospectively enrolled. We collected 24 h metabolic urine samples and demographic data, including indwelling time and previous stone composition.

What Donation Features are Related to Complications in Donation after Circulatory Death Kidney Transplant? Analysis of Risk Factors for Complication after Circulatory Death Kidney Transplant.

Objective: Complications in donation after circulatory death (DCD) kidney transplants (KT) are barely described, while in some urological complications the cause is unknown. The aim of this study is to describe surgical and urological complications and analyze what donation features could be involved.

Methods: A prospective, single center study was performed from 2016 to 2019 including all KT from controlled cardiac death donors (cDCD).

Effect of Ischemia Times and Donor and Recipient Features on Maastricht Category III Kidney Transplant Outcomes.

Objective: Expansion of the donor pool has been enabled by the use of donation after circulatory death (DCD). The aim of this study is to identify what donation features are able to predict kidney transplant (KT) outcomes from DCD.

Materials And Methods: A prospective analysis of all DCD KT from June 2016 to November 2019 was conducted.

A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products.

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD).

Whole-Genome Analysis Surveillance of Influenza A Virus Resistance to Polymerase Complex Inhibitors in Eastern Spain from 2016 to 2019.

Molecular surveillance by whole-genome sequencing was used to monitor the susceptibility of circulating influenza A viruses to three polymerase complex inhibitors. A total of 12 resistance substitutions were found among 285 genomes analyzed, but none were associated with high levels of resistance. Natural resistance to these influenza A antivirals is currently uncommon.

Definitive diagnosis in suspected Middle East Respiratory Syndrome Coronavirus cases.

We evaluated the microbiological diagnosis in 14 patients with epidemiological and clinical suspicion of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) attended in a non-endemic area between June 2015 and January 2017. While no MERS-CoV was detected, other respiratory viruses were identified in 12 cases and Mycoplasma pneumoniae in 1 case.

Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis.

Human carbamoyl phosphate synthetase (CPS1), a 1500-residue multidomain enzyme, catalyzes the first step of ammonia detoxification to urea requiring N-acetyl-L-glutamate (NAG) as essential activator to prevent ammonia/amino acids depletion. Here we present the crystal structures of CPS1 in the absence and in the presence of NAG, clarifying the on/off-switching of the urea cycle by NAG. By binding at the C-terminal domain of CPS1, NAG triggers long-range conformational changes affecting the two distant phosphorylation domains.

Safety, tolerability, and immunogenicity of repeated doses of dermavir, a candidate therapeutic HIV vaccine, in HIV-infected patients receiving combination antiretroviral therapy: results of the ACTG 5176 trial.

Background: HIV-specific cellular immune responses are associated with control of viremia and delayed disease progression. An effective therapeutic vaccine could mimic these effects and reduce the need for continued antiretroviral therapy. DermaVir, a topically administered plasmid DNA-nanomedicine expressing HIV (CladeB) virus-like particles consisting of 15 antigens, induces predominantly central memory T-cell responses.

Molecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool.

The urea cycle disease carbamoyl-phosphate synthetase deficiency (CPS1D) has been associated with many mutations in the CPS1 gene [Häberle et al., 2011. Hum Mutat 32:579-589].

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

Background: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.

Methods And Findings: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF).

A randomized, placebo-controlled trial of abacavir intensification in HIV-1-infected adults with virologic suppression on a protease inhibitor-containing regimen.

Background And Objective: Maximizing the durability of viral suppression is a key goal of antiretroviral therapy. The objective of AIDS Clinical Trials Group Study 372A was to determine whether the intensification strategy of adding abacavir to an effective indinavir-dual nucleoside regimen would delay the time to virologic failure.

Methods: Zidovudine-experienced subjects (n=229) on therapy with indinavir + zidovudine + lamivudine with plasma HIV-1 RNA levels<500 copies/mL were randomized to abacavir 300 mg twice daily or placebo.

Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.

Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.

Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) plays a paramount role in liver ureagenesis since it catalyzes the first and rate-limiting step of the urea cycle, the major pathway for nitrogen disposal in humans. CPS1 deficiency (CPS1D) is an autosomal recessive inborn error which leads to hyperammonemia due to mutations in the CPS1 gene, or is caused secondarily by lack of its allosteric activator NAG. Proteolytic, immunological and structural data indicate that human CPS1 resembles Escherichia coli CPS in structure, and a 3D model of CPS1 has been presented for elucidating the pathogenic role of missense mutations.

Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis.

Carbamoyl-phosphate synthetase I (CPS1) deficiency (CPS1D), a recessively inherited urea cycle error due to CPS1 gene mutations, causes life-threatening hyperammonemia. The disease-causing potential of missense mutations in CPS1 deficiency can be ascertained with the recombinant CPS1 expression and purification system reported here, which uses baculovirus and insect cells. We study with this system the effects of nine clinical mutations and one polymorphism on CPS1 solubility, stability, activity, and kinetic parameters for NAG.

[Epidemiology of the meningococcal disease in Catalonia before and after vaccination against serogroup C].

Backgrounds: Meningococcal disease remains a serious public health problem worldwide. In Catalonia, after implementing the vaccination program, there has been a significant decrease in cases caused by meningococcus C.

Methods: Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine in Catalonia.

Pyrroline-5-carboxylate synthase and proline biosynthesis: from osmotolerance to rare metabolic disease.

Pyrroline-5-carboxylate synthase (P5CS) is a bifunctional enzyme that exhibits glutamate kinase (GK) and gamma-glutamyl phosphate reductase (GPR) activities. The enzyme is highly relevant in humans because it belongs to a combined route for the interconversion of glutamate, ornithine and proline. The deficiency of P5CS activity in humans is associated with a rare, inherited metabolic disease.

Expression and purification of recombinant human MCT-1 oncogene in insect cells.

MCT-1 protein is encoded by an oncogene highly expressed in lymphomas. It is implicated in the interaction with the cap complex of the mRNA, through an RNA binding domain, named PUA. Targeted suppression of this domain attenuates the malignant phenotype and hence MCT-1 is a potential target for therapeutic intervention.

Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase.

NAG (N-acetyl-L-glutamate), the essential allosteric activator of the first urea cycle enzyme, CPSI (carbamoyl phosphate synthetase I), is a key regulator of this crucial cycle for ammonia detoxification in animals (including humans). Automated cavity searching and flexible docking have allowed identification of the NAG site in the crystal structure of human CPSI C-terminal domain. The site, a pocket lined by invariant residues and located between the central beta-sheet and two alpha-helices, opens at the beta-sheet C-edge and is roofed by a three-residue lid.

Changes in the evolution of meningococcal disease, 2001-2008, Catalonia (Spain).

Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine. In <6 years, the incidence rate of serogroup C fell from 7.6 to 0.

A study of the Candida albicans cell wall proteome.

Considering the importance of proteins in the structure and function of the cell wall of Candida albicans, we analyzed the cell wall subproteome of this important human pathogen by LC coupled to MS (LC-MS) using different protein extraction procedures. The analyzed samples included material extracted by hydrogen fluoride-pyridine (HF-pyridine), and whole SDS-extracted cell walls. The use of this latter innovative procedure gave similar data as compared to the analysis of HF-pyridine extracted proteins.

Analysis of the proteins involved in the structure and synthesis of the cell wall of Ustilago maydis.

A study of the proteins involved in the synthesis and structure of the cell wall of Ustilago maydis was made by in silico analysis of the fungal genome, with reference to supporting experimental evidence. The composition of the cell wall of U. maydis shows similarities with the structural composition of the walls of Ascomycetes, but also shows important differential features.