The Impact of Heat on an Emergency Department in Italy: Attributable Visits among Children,Adults, and the Elderly during the Warm Season

Introduction

Recent studies suggest that heat is associated with an increase in the number of ambulance calls and emergency department visits. We investigated the association between heat and daily number of emergency department visits at the University Hospital of Verona during the warm seasons 2011–2012 and we assessed the magnitude of the impact in terms of attributable events, focusing on the role of age and triage codification.

Materials and methods

We used a Poisson model to analyse the association between daily number of visits and daily mean apparent temperature, accounting for air pollution level and seasonality. The analyses were stratified by age group and were performed both on the total number of emergency department visits and on the subsample of high-priority visits. Impact estimates were obtained only for this subsample, using a Monte Carlo approach to account for sampling variability. Number of attributable events and attributable community rate were calculated.

Results

We found a positive and immediate association between event occurrence and mean apparent temperatures exceeding a threshold located around 28–29°C. The estimated percent change in the total number of visits per 1°C increase of exposure above the threshold was equal to 3.75 (90% CI: 3.01; 4.49). Focusing only on high-priority visits, the estimated percent change was larger and the greatest effect was among children. We estimated that apparent temperatures above the threshold were responsible for 1177 high-priority visits during the study period. Due to the record high temperatures observed in 2012 in Italy and in Europe, the impact in 2012 was much larger than in 2011, and consisted in 34 high-priority visits every 10000 children, 30 every 10000 people aged 15–64, and 38 every 10000 people aged 65 and over.

Discussion

Our results indicate that heat affects not only the elderly, but also children and non-elderly adults, stressing the need for developing public health preparedness plans for the entire community.     

Mutations in DOCK7 in Individuals with Epileptic Encephalopathy and Cortical Blindness

Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs^∗48] and c.3709C>T [p.Arg1237^∗]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328^∗] and c.6232G>T [p.Glu2078^∗]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic interneurons in the developing cortex. All together, these observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes.     

Mutations in QARS,Encoding Glutaminyl-tRNA Synthetase,Cause Progressive Microcephaly,Cerebral-Cerebellar Atrophy,and Intractable Seizures

Progressive microcephaly is a heterogeneous condition with causes including mutations in genes encoding regulators of neuronal survival. Here, we report the identification of mutations in QARS (encoding glutaminyl-tRNA synthetase [QARS]) as the causative variants in two unrelated families affected by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres. Whole-exome sequencing of individuals from each family independently identified compound-heterozygous mutations in QARS as the only candidate causative variants. QARS was highly expressed in the developing fetal human cerebral cortex in many cell types. The four QARS mutations altered highly conserved amino acids, and the aminoacylation activity of QARS was significantly impaired in mutant cell lines. Variants p.Gly45Val and p.Tyr57His were located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, and recombinant QARS proteins bearing either substitution showed an over 10-fold reduction in aminoacylation activity. Conversely, variants p.Arg403Trp and p.Arg515Trp, each occurring in a different family, were located in the catalytic core and completely disrupted QARS aminoacylation activity in vitro. Furthermore, p.Arg403Trp and p.Arg515Trp rendered QARS less soluble, and p.Arg403Trp disrupted QARS-RARS (arginyl-tRNA synthetase 1) interaction. In zebrafish, homozygous qars loss of function caused decreased brain and eye size and extensive cell death in the brain. Our results highlight the importance of QARS during brain development and that epilepsy due to impairment of QARS activity is unusually severe in comparison to other aminoacyl-tRNA synthetase disorders.     

The causes and scope of political egalitarianism during the Last Glacial: a multi-disciplinary perspective

This paper reviews and synthesizes emerging multi-disciplinary evidence toward understanding the development of social and political organization in the Last Glacial. Evidence for the prevalence and scope of political egalitarianism is reviewed and the biological, social, and environmental influences on this mode of human organization are further explored. Viewing social and political organization in the Last Glacial in a much wider, multi-disciplinary context provides the footing for coherent theory building and hypothesis testing by which to further explore human political systems. We aim to overcome the claim that our ancestors’ form of social organization is untestable, as well as counter a degree of exaggeration regarding possibilities for sedentism, population densities, and hierarchical structures prior to the Holocene with crucial advances from disparate disciplines.     

Extragastric manifestations of Helicobacter pylori infection

The possible role of Helicobacter pylori as a trigger for some extragastric diseases has been largely investigated in the last year. There are, in fact, several studies concerning cardiovascular diseases, neurological disorders, diabetes mellitus, ear and eyes diseases, immunological and hematological disorders, liver and bile tract diseases, gynecological and respiratory tract pathologies. Among them, idiopathic sideropenic anemia and idiopathic thrombocytopenic purpura still remain the extragastric diseases showing the most convincing results. Concerning ischemic heart disease, there are new interesting data playing in favor of the association, even though there are still some open issues to be clarified. For the other diseases, more studies are needed to clarify the reality of the proposed association.     

Study of mRNA Expression by Real Time PCR of Cpkk1, Cpkk2 and Cpkk3, three MEKs of Cryphonectria parasitica,in Virus‐free and Virus‐infected Isogenic Isolates

Cpkk1 and Cpkk2 are two previously characterized Mitogen‐activated protein kinase kinases (MEK) from Cryphonectria parasitica. For the characterization of the third MEK, primers designed to a conserved region of the known fungal MEK sequences were used in a PCR reaction to amplify genomic DNA from C. parasitica. The sequence of the resulting amplicon was compared to known sequences in the database using a Blast search. Results of the sequence comparison indicated that the initial fragment obtained encoded for a new MEK from C. parasitica, that had highest homology to Pbs2 from Saccharomyces cerevisiae. By inverse PCR we obtained a genomic fragment spanning the entire coding sequence of this MEK, which was named Cpkk3. The cDNA of Cpkk3 was obtained by compiling the sequences of RT‐PCR products resulting from the amplification of purified mRNA. TaqMan^® Probes were designed to analyse the expression of Cpkk1, Cpkk2 and Cpkk3 mRNA through RT‐Real Time PCR. This protocol allowed the expression of Cpkk3 to be successfully compared to the expression of Cpkk1 and Cpkk2, two previously cloned C. parasitica MEKs. No variation in expression was associated with the presence of a virus after 2 days of growth in standard conditions whereas an increase in the expression level of all the three MEKs was shown after 4 days of growth.     

Rapid sexual maturity and short life span in the blue-legged frog and the rainbow frog from the arid Isalo Massif, southern-central Madagascar

Longevity and age at sexual maturity were estimated in two anurans from the arid Isalo Massif (southern-central Madagascar), the blue-legged frog (Mantella expectata) and the rainbow frog (Scaphiophryne gottlebei). Phalanges from 69 individuals of M. expectata and 38 individuals of S. gottlebei were analyzed, using the skeletochronological method, in samples collected during two periods: January-February and November-December 2004. The male gonads of both species were also analyzed in order to better correlate reproductive activity with phenology. The phalangeal diaphysis in adults of both species was composed of two concentric bone layers: an innermost endosteal bone, which was less developed or sometimes lacking in S. gottlebei, and an outermost and broader layer of periosteal bone. Lines of arrested growth (LAGs) were observed in both species, although their recognition was more problematic and their distinctiveness much less evident in S. gottlebei. The results presented here indicate that M. expectata and S. gottlebei have a short life span and attain sexual maturity within the first active season after metamorphosis. Maximum longevity was 3 years in M. expectata and 2 years in S. gottlebei. In S. gottlebei the adult body size is likely attained during the same season in which metamorphosis occurs, but then breeding occurs only after the first latency period. Thus, mature individuals have only one LAG, corresponding to 1 year. The low number of individuals with two LAGs suggests that most animals die before the second latency period.     

Recognition of Smac-mimetic compounds by the BIR domain of cIAP1

Inhibitor of apoptosis proteins (IAPs) are negative regulators of apoptosis. As IAPs are overexpressed in many tumors, where they confer chemoresistance, small molecules inactivating IAPs have been proposed as anticancer agents. Accordingly, a number of IAP-binding pro-apoptotic compounds that mimic the sequence corresponding to the N-terminal tetrapeptide of Smac/DIABLO, the natural endogenous IAPs inhibitor, have been developed. Here, we report the crystal structures of the BIR3 domain of cIAP1 in complex with Smac037, a Smac-mimetic known to bind potently to the XIAP-BIR3 domain and to induce degradation of cIAP1, and in complex with the novel Smac-mimetic compound Smac066. Thermal stability and fluorescence polarization assays show the stabilizing effect and the high affinity of both Smac037 and Smac066 for cIAP1- and cIAP2-BIR3 domains.