Performance of alere determine HIV-1/2 Ag/Ab combo rapid test for acute HIV infection: A case report | Performance del test rapido Alere Determine HIV-1/2 Ag/Ab Combo nell?infezione acuta da HIV: Un caso clinic

We describe a case of symptomatic acute HIV infection in a young man where a fourth-generation rapid screening test combining HIV-specific antibody and p24 antigen was negative. In highly suspicious cases of acute HIV infection, plasma HIV RNA assays together with conventional, non-rapid screening tests should be used

Outcomes of three years of teamwork on critical limb ischemia in patients with diabetes and foot lesions

To evaluate the outcomes of a multidisciplinary team working on diabetic foot (DF) patients with critical limb ischemia (CLI) in a specialized center, the authors retrospectively traced all the patients admitted in their department in 3 consecutive years with a diagnosis of CLI. From January 2006 to December 2008, 245 consecutive DF patients with CLI according the TransAtlantic interSociety Consensus II criteria were included in the study. Treatment strategy was decided by a team of diabetologists, inteventional radiologists, and vascular surgeons. Technical and clinical success, mortality, and ulcer recurrence were evaluated at 6 months and at a mean follow-up of 19.5 +/- 13.4 months. Percutaneous transluminal angioplasty (PTA) was performed in 189 (77%) patients, whereas medical treatment, open surgical revascularization (OSR), and primary amputation were performed in 44 (18.3%), 11 (4.3%), and 1 (0.5%) patients, respectively. Revascularization was successful in 227/233 (97.4%) patients. At follow-up, the overall clinical success rate was 60.4%; it was significantly (P = .001) higher after revascularization (75.9%) compared with medical treatment (48.3%). During follow-up, surgical interventions in the foot were 1.5 +/- 0.4 in those treated with PTA, 1.6 +/- 0.5 in those treated with OSR, and 0.3 +/- 0.8 in those receiving medical therapy (P < .05 compared with the others). Ulcer recurrence occurred in 29 (11.8%) patients: 4 (1.6%) in PTA, 2 (0.8%) in OSR, and 23 (9.4%) in the medical therapy group (P < .05). Major amputation rate was 9.3%, being significantly (P = .04) lower after revascularization (5.2%) compared with medical therapy alone (13.8%). Cumulative mortality rate was 10.6%. In conclusion, this study confirms the positive role of a PTA-first approach for revascularizing the complex cases of DF with CLI in a teamwork management strategy

Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences

During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites

Pharmacological treatment in adult patients with CRPS-I: A systematic review and meta-analysis of randomised controlled trials

Objective. Several pharmacological treatments have been proposed for the treatment of complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse the efficacy of the various pharmacological approaches in adults with CRPS-I.Methods. We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30 June 2021 to identify placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, CSs, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or IVIGs for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment.Results. We included 20 placebo-controlled or active-controlled RCTs (including a total of 818 adults with CRPS-I) that used bisphosphonates (n = 7), ketamine (n = 2), CSs (n = 2), anti-epileptics (n = 1), NSAIDs/selective inhibitors of cyclooxygenase-2 (COXIBs) (n = 2), scavengers/magnesium sulphate (n = 5), or IVIGs (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. Treatment with bisphosphonates showed a significant reduction in the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: -23.8, 95% CI: -28.0 to -19.6; I-2 = 36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS for pain (random effects WMD: -8.27, 95% CI: -12.9 to -3.70; I-2 = 0%). Treatment with other agents did not reduce the values of the VAS/NRS assessments of pain.Conclusion. This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I

Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations

Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations

Nocardia infection over 5 years (2011-2015) in an Italian tertiary care hospital

This study was conducted reviewing clinical records of 14 patients affected by nocardiosis over 5 years in a tertiary care hospital. Nocardia abscessus was responsible for one third of infections, deviating significantly from the results reported by other epidemiological investigations and highlighting the key role of molecular identification tests. Indeed, a precise identification of species is crucial for the determination of antibiotic sensitivity patterns and, consequently, for the choice of antibiotic treatment. Noteworthy, 40% of isolates of N. abscessus (formerly N. asteroides complex) showed resistance to carbapenems, which are usually recommended for empirical therapy