Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) in Preventing Community-Acquired Pneumonia in Adults: A Population-Based Cohort Study.

Aim: The aim was to assess the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing CAP in adults.

Methods: This was a population-based cohort study, followed up over 5 years (2015-2019), that included 47,768 persons aged ≥18 years assigned to three primary care centres. Data were retrospectively obtained from electronic medical records and databases.

Frailty trends in Catalonia 2017-2021: An epidemiological study with 1.5 million people aged ≥65 years.

Objectives: Knowledge of frailty prevalence and incidence trends over time is essential for planning the necessary health and social resources. The objective of this study was to assess frailty prevalence, incidence, reversibility and mortality rates, and trends for the population aged ≥65 years in Catalonia over the period 2017-2021.

Study Design: Longitudinal epidemiological study.

Beyond a platform protein for the degradosome assembly: The Apoptosis-Inducing Factor as an efficient nuclease involved in chromatinolysis.

The Apoptosis-Inducing Factor (AIF) is a moonlighting flavoenzyme involved in the assembly of mitochondrial respiratory complexes in healthy cells, but also able to trigger DNA cleavage and parthanatos. Upon apoptotic-stimuli, AIF redistributes from the mitochondria to the nucleus, where upon association with other proteins such as endonuclease CypA and histone H2AX, it is proposed to organize a DNA-degradosome complex. In this work, we provide evidence for the molecular assembly of this complex as well as for the cooperative effects among its protein components to degrade genomic DNA into large fragments.

Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation.

The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleolar liquid-liquid phase separation usually serves the cell as a fast, smart mechanism to control the spatial localization and trafficking of nuclear proteins. Actually, the alternative reading frame (ARF), a tumor suppressor protein sequestered by nucleophosmin (NPM) in the nucleoli, is shifted out from NPM upon DNA damage.

Presenting Characteristics, Comorbidities, and Outcomes Among Patients With COVID-19 Hospitalized in Pakistan: Retrospective Observational Study.

Background: COVID-19 became a pandemic rapidly after its emergence in December 2019. It belongs to the coronavirus family of viruses, which have struck a few times before in history. Data based on previous research regarding etiology and epidemiology of other viruses from this family helped played a vital role in formulating prevention and precaution strategies during the initial stages of this pandemic.

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

Unsupervised bubble calorimetry analysis: Surface tension from isothermal titration calorimetry.

Hypothesis: The injection of air into the sample cell of an isothermal titration calorimeter containing a liquid provides a rich-in-information signal, with a periodic contribution arising from the creation, growing and release of bubbles. The identification and analysis of such contributions allow the accurate determination of the surface tension of the target liquid.

Experiments: Air is introduced at a constant rate into the sample cell of the calorimeter containing either a pure liquid or a solution.

Fluid interface calorimetry.

Hypothesis: Amphiphilic molecules spontaneously adsorb to fluid polar-nonpolar interfaces. The timescale of such adsorption depends on the molecular size and structure of the solute. This process should be accompanied by a power heat exchange that could be detected by commercial isothermal calorimeters.

W196 and the -Hairpin Motif Modulate the Redox Switch of Conformation and the Biomolecular Interaction Network of the Apoptosis-Inducing Factor.

The human apoptosis-inducing factor (hAIF) is a moonlight flavoprotein involved in mitochondrial respiratory complex assembly and caspase-independent programmed cell death. These functions might be modulated by its redox-linked structural transition that enables hAIF to act as a NAD(H/) redox sensor. Upon reduction with NADH, hAIF undergoes a conformational reorganization in two specific insertions-the flexible regulatory C-loop and the 190-202 -harpin-promoting protein dimerization and the stabilization of a long-life charge transfer complex (CTC) that modulates its monomer-dimer equilibrium and its protein interaction network in healthy mitochondria.

Proposed mechanism for regulation of H O -induced programmed cell death in plants by binding of cytochrome c to 14-3-3 proteins.

Programmed cell death (PCD) is crucial for development and homeostasis of all multicellular organisms. In human cells, the double role of extra-mitochondrial cytochrome c in triggering apoptosis and inhibiting survival pathways is well reported. In plants, however, the specific role of cytochrome c upon release from the mitochondria remains in part veiled yet death stimuli do trigger cytochrome c translocation as well.

Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan.

Background: Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3.

Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor.

Human riboflavin kinase (HsRFK) catalyzes vitamin B (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-β toxicity, and some malignant cancers progression. Its downregulation alters expression profiles of clock-controlled metabolic-genes and destroys flavins protection on stroke treatments, while its activity reduction links to protein-energy malnutrition and thyroid hormones decrease.

Tumor educated platelets, a promising source for early detection of hepatocellular carcinoma: Liquid biopsy an alternative approach to tissue biopsy.

Purpose: Liver cancer is considered to be the sixth deadliest cancer worldwide. Hepatocellular carcinoma (HCC) is known to be the most prevalent type of liver cancer. The number of deaths due to HCC reported per year is on a constant rise especially in lesser developed countries.

Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan.

This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment.

Spatial arrangement of LD motif-interacting residues on focal adhesion targeting domain of Focal Adhesion Kinase determine domain-motif interaction affinity and specificity.

Background: Leucine rich Aspartate motifs (LD motifs) are molecular recognition motifs on Paxillin that recognize LD-motif binding domains (LDBD) of a number of focal adhesion proteins in order to carry out downstream signaling and actin cytoskeleton remodeling. In this study, we identified structural features within LDBDs that influence their binding affinity with Paxillin LD motifs.

Methods: Various point mutants of focal adhesion targeting (FAT) domain of Focal Adhesion Kinase (FAK) were created by moving a key Lysine residue two and three helical turns in order to match the unique conformations as observed in LDBDs of two other focal adhesion proteins, Vinculin and CCM3.

MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2.

Background: MeCP2-a chromatin-binding protein associated with Rett syndrome-has two main isoforms, MeCP2-E1 and MeCP2-E2, differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, in addition to their different cellular localization and differential expression during brain development, suggest that they may also have non-overlapping molecular mechanisms. However, differential functions of MeCP2-E1 and E2 remain largely unexplored.

Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors.

Coordinated conformational transitions in oligomeric enzymatic complexes modulate function in response to substrates and play a crucial role in enzyme inhibition and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which has emerged as a drug target against multiple pathogenic bacteria. Activation of different ClpPs by inhibitors has been independently reported from drug development efforts, but no rationale for inhibitor-induced activation has been hitherto proposed.

Molecular crowding effects on the distribution of amphiphiles in biological media.

Biological systems are the result of the interactions established among their many distinct molecules and molecular assemblies. The high concentration of small molecules dissolved in the aqueous media alter the water properties with important consequences in the interactions established. In this work, the effects of high concentrations of the disaccharide trehalose on the solubility of a homologous series of fluorescent amphiphiles (NBD-Cn, n=4-16) and on their interaction with a lipid bilayer and a serum protein are quantitatively characterized.

AFFINImeter: A software to analyze molecular recognition processes from experimental data.

The comprehension of molecular recognition phenomena demands the understanding of the energetic and kinetic processes involved. General equations valid for the thermodynamic analysis of any observable that is assessed as a function of the concentration of the involved compounds are described, together with their implementation in the AFFINImeter software. Here, a maximum of three different molecular species that can interact with each other to form an enormous variety of supramolecular complexes are considered.

Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations.

A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy.

Redox- and Ligand Binding-Dependent Conformational Ensembles in the Human Apoptosis-Inducing Factor Regulate Its Pro-Life and Cell Death Functions.

The human apoptosis-inducing factor (hAIF) supports OXPHOS biogenesis and programmed cell death, with missense mutations producing neurodegenerative phenotypes. hAIF senses the redox environment of cellular compartments, stabilizing a charge transfer complex (CTC) dimer that modulates the protein interaction network. In this context, we aimed to evaluate the subcellular pH, CTC formation, and pathogenic mutations effects on hAIF stability, and a thermal denaturation high-throughput screening (HTS) assay to discover AIF binders.