Malaria: looking for selection signatures in the human PKLR gene region

The genetic component of susceptibility to malaria is both complex and multigenic and the better‐known protective polymorphisms are those involving erythrocyte‐specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase‐encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub‐Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase‐deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.     

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single‐nucleotide polymorphism‐detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc.     

Clinical review: Continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest

There has been a dramatic change in hospital care of cardiac arrest survivors in recent years, including the use of target temperature management (hypothermia). Clinical signs of recovery or deterioration, which previously could be observed, are now concealed by sedation, analgesia, and muscle paralysis. Seizures are common after cardiac arrest, but few centers can offer high-quality electroencephalography (EEG) monitoring around the clock. This is due primarily to its complexity and lack of resources but also to uncertainty regarding the clinical value of monitoring EEG and of treating post-ischemic electrographic seizures. Thanks to technical advances in recent years, EEG monitoring has become more available. Large amounts of EEG data can be linked within a hospital or between neighboring hospitals for expert opinion. Continuous EEG (cEEG) monitoring provides dynamic information and can be used to assess the evolution of EEG patterns and to detect seizures. cEEG can be made more simple by reducing the number of electrodes and by adding trend analysis to the original EEG curves. In our version of simplified cEEG, we combine a reduced montage, displaying two channels of the original EEG, with amplitude-integrated EEG trend curves (aEEG). This is a convenient method to monitor cerebral function in comatose patients after cardiac arrest but has yet to be validated against the gold standard, a multichannel cEEG. We recently proposed a simplified system for interpreting EEG rhythms after cardiac arrest, defining four major EEG patterns. In this topical review, we will discuss cEEG to monitor brain function after cardiac arrest in general and how a simplified cEEG, with a reduced number of electrodes and trend analysis, may facilitate and improve care.     

Correlation between human papillomavirus infection and histopathological diagnosis of women in Northeast Brazil

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN-1), cervical intraepithelial neoplasia type 2 (CIN-2), cervical intraepithelial neoplasia type 3 (CIN-3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction–restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV-16, HPV-18, and HPV-31. HPV-16, HPV-31, HPV-35, and HPV-18 were the most common types in CIN-1 with a single infection. HPV-16 and HPV-18 were the most often found in CIN-2 with a single infection. HPV-16, HPV-18, and HPV-31 were the most detected in CIN-3 with a single infection. HPV-16 and HPV-31 were the most frequent in cancer with a single infection. Multiple infection with HPV-16 shows a 2.7 times greater risk of CIN-3 (P = .04). Multiple infections for HPV with HPV-16 and excluding the HPV18/31 types, were associated with CIN-3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.     

Benign liver neoplasms

A variety of benign focal liver lesions are easily characterized with currently available imaging techniques and contrast agents. The most common benign liver lesions, such as hemangioma, bile duct cyst, and FNH, reveal characteristic cross-sectional imaging features that allow an accurate diagnosis. For atypical variants and more uncommon lesions, including HCA, angiomyelioma, infantile hemagioendothelioma, and mesenchymal hamartoma, integration of clinical data can often help in the interpretation of imaging studies. Finally, for the remaining lesions, such as hepatic adenomatosis, the imaging findings may not be specific enough to negate the need for a tissue biopsy.     

White blood cell count is associated with carotid and femoral atherosclerosis

ObjectiveRelationship of high sensitivity C-reactive protein (hsCRP) with Metabolic Syndrome (MetS) is well documented in many populations, but comprehensive data is lacking in Indian population. Thus, we set out to investigate the association of hsCRP levels with MetS and its features and the effect of obesity and insulin resistance on this association in urban Indians.MethodsThis is a cross-sectional study that included 9517 subjects comprising 4066 subjects with MetS. MetS was defined according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria for Asians.ResultsMedian levels of hsCRP were considerably higher in individuals with MetS with higher levels in women compared to men. Among the features of MetS, waist circumference was most strongly correlated with hsCRP levels (r = 0.28) and contributed maximally (β = 0.025 mg/l ln hsCRP, P = 7.4 × 10^?147). Subjects with high risk hsCRP levels (>3 mg/l) were at high risk of MetS (OR (95% CI) = 1.65(1.41–1.92), P = 1.7 × 10^?10). Risk of MetS increased in a dose dependent manner from low risk to high risk hsCRP category with increase in BMI and HOMA-IR.ConclusionsOur findings suggest that hsCRP predicts the risk of MetS, independent of obesity and insulin resistance, and therefore, can be a valuable tool to aid the identification of individuals at risk of MetS. The study provides a lead for future investigation for effects of hsCRP, obesity, and insulin resistance on MetS in this population.     

Formation of extra digits in the interdigital spaces of the chick leg bud is not preceded by changes in the expression of the Msx and Hoxd genes

By in situ hybridization we studied the expression patterns of Msx and Hoxd genes during the late development of the chick leg autopodium (foot) and compared them to patterns during the experimental development of interdigital extra digits. Extra digits are induced in the third interdigital space after various experimental manipulations, such as transient isolation of the interdigit, or removal of the interdigital marginal ectoderm and mesoderm. Msx1 and Msx2 are normally expressed in the interdigital tissue programmed to die. Our experiment changes the fate of the interdigital tissue from cell death to chondrogenesis and provides a good model for studying Msx involvement in defining areas of programmed cell death. Among the proposed roles for Hoxd genes is their involvement in the specification of digit identity early in development. The induction of extra digits allows us to examine whether this new morphogenetic commitment of the interdigital tissue involves changes in the domains of expression of Hoxd genes. Our results show that extra digits develop without a previous modification of the normal pattern of expression of Msx or Hoxd genes. This observation does not support the correlation between the expression of Msx genes and programmed cell death and suggests a role for these genes in maintaining the interdigital tissue in an undifferentiated state. Our results show that an increased number of digits can be formed without modifications in the pattern of expression of the 5-located Hoxd genes and suggest the existence of latent or residual digit organization mechanisms past the time when digits are normally determined, independent of Hoxd gene expression.