Children at risk of domestic accidents when are locked up at home: the other side of COVID-19 outbreak lockdown

Background We proposed to analyze thoroughly the impact of the COVID-19 lockdown (CL) in changes of profiles and in trend of the domestic accidents (DAs) in children. Methods This was a single experience, cross-sectional study conducted at the emergency department (ED) of III trauma center. We enrolled children under 18 years admitted to ED with a diagnosis of DAs comparing the CL period from 10(th) March 2020 to 4(th) May 2020 with the same period of the previous year,10(th) March 2019 to 4(th) May 2019. Results In CL period, the cumulative incidence of ED visits for DAs increased from 86.88 to 272.13 per 1,000 children and the cumulative incidence of hospitalizations for DAs increased from 409.72 to 534.48 per 1,000 children. We reported in CL a decrease in the severity of ED presentation assessed by proxy measures: the level of priority ED visits reduced by 67% in CL period (OR: 0.33; 95%CI 0.22-0.48; p < 0.001); the likelihood of delayed time of presentation to ED increased by 65% in case of domestic injuries occurring in CL period (OR: 1.65; 95% CI: 1.17-2.34; p = 0.004); the odds of transfer from other hospital decreased by 78% in CL (OR: 0.15-0.33; p < 0.001). Children were more at risk of poisoning (OR:3.35-106.11; p = 0.001), of body foreign ingestion (OR: 1.83-14.39; p = 0.002) and less at risk of animal bite trauma (OR:0.05-0.35; p < 0.001). Conclusion Although the need to stay home has made a decisive breakthrough on the spread of COVID-19, the experience from this study underlines how this preventive measure has also had a downside in term of increased cumulative incidence of ED visits and of hospitalizations for DA

One Year of Lung Ultrasound in Children with SARS-CoV-2 Admitted to a Tertiary Referral Children's Hospital: A Retrospective Study during 2020-2021

During the COVID-19 pandemic, the lung ultrasound (LU) turned out to be a pivotal tool to study the lung involvement in the adult population, but the same was not well evaluated in children. We detected the LU patterns through an integrated approach with clinical-laboratory features in children hospitalized for COVID-19 in relation to the temporal trend of the Italian epidemic. We conducted a retrospective study which took place at a pediatric tertiary hospital from 15 March 2020 to 15 March 2021. We compared the characteristics of the initial phase of the first COVID-19 year-in the spring and summer (15 March-30 September 2020)-and those of the second phase-in the autumn and winter (1 October 2020-15 March 2021). Twenty-eight patients were studied both in the first and in the second phase of the first COVID-19 year. The disease severity score (DSS) was significantly greater in the second phase (p = 0.015). In the second phase of the first COVID-19 year, we detected a more significant occurrence of the following LU features than in the first phase: the irregular pleural line (85.71% vs. 60.71%; p = 0.035), the B-lines (89.29% vs. 60%; p = 0.003) and the several but non-coalescent B-lines (89.29% vs. 60%; p = 0.003). The LU score correlated significantly with the DSS, with a moderate relationship (r = 0.51, p < 0.001). The combined clinical, laboratory and ultrasound approaches might be essential in the evaluation of pulmonary involvement in children affected by COVID-19 during different periods of the pandemic

S100P is a molecular determinant of E-cadherin function in gastric cancer

Background: E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods: A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results: S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad- tumours, despite not being significantly associated with overall survival on its own. Conclusions: We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies.This work was financed by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Internacionalização (POCI), Programa Operacional Regional do Norte (Norte 2020) and by National Funds through the Portuguese Foundation for Science and Technology (FCT), under the projects PTDC/BIMONC/0171/2012, PTDC/BIM-ONC/0281/2014, NORTE-01-0145-FEDER-000029, PTDC/MED-GEN/30356/2017, PTDC/BTM-SAL/30383/2017; doctoral grant SFRH/BD/114687/2016-AMM; post-doctoral grant SFRH/BPD/87705/2012-JF. We acknowledge the IFCT Program for funding JP and SV

The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis

Some studies suggest a relationship between semen quality and pregnancy rates of assisted reproduction technologies (ART). Others have questioned the utility of semen quality as proxy for fertility in couples attempting to conceive with or without assistance. We aimed to investigate the current body of evidence which correlates semen parameters and clinical pregnancy among couples utilizing ART (i.e. in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI]) through a systematic review and meta-analysis of cross-sectional and retrospective cohort studies. Pooled Odd Ratio (OR) for oligo-, astheno- and teratospermic compared to normospermic number of ART cycles were calculated among. Meta-regression and sub-group analysis were implemented to model the contribution of clinical/demographic and laboratory standards differences among the studies. Overall, 17 studies were analysed representing 17,348 cycles were analysed. Pooled OR for impaired sperm concentration, motility and morphology was 1 (95%Confidence Interval [CI]: 0.97-1.03), 0.88 (95%CI: 0.73-1.03) and 0.88 (95%CI: 0.75-1) respectively. Further analysis on sperm morphology showed no differences with regard of IVF versus ICSI (p = 0.14) nor a significant correlation with rising reference thresholds (Coeff: -0.02, p = 0.38). A temporal trend towards a null association between semen parameters and clinical pregnancy was observed over the 20-year observation period (Coeff: 0.01, p = 0.014). The current analysis found no association between semen quality (as measured by concentration, motility or morphology) and clinical pregnancy rates utilizing ART. Future investigations are necessary to explore the association between semen parameters and other ART outcomes (e.g. fertilization, implantation, birth and perinatal health)

Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

BACKGROUND: Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. OBJECTIVE: We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. METHODS: We conducted a case-control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,21-bis(4-chlorophenyl)-ethene (p p'-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. RESULTS: We found an increased risk of endometriosis for DL-PCB-118 (odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61-8.91), NDL-PCB-138 (OR = 3.78; 95% CI, 1.60-8.94), NDLPCB-153 (OR = 4.88; 95% CI, 2.01-11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41-8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25-14. 10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs1 and DL-PC13s given as total TEQs. CONCLUSIONS: The results of this study show that an association exists between increased PCB and p,p'-DDE serum concentrations and the risk of endometriosis

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patient

BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample

A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs

Kalirin: a novel genetic risk factor for ischemic stroke

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases

Variability in prescription drug expenditures explained by adjusted clinical groups (ACG) case-mix: A cross-sectional study of patient electronic records in primary care

<p>Abstract</p> <p>Background</p> <p>In view of rapidly increasing prescription costs, case-mix adjustment should be considered for effective control of costs. We have estimated the variability in pharmacy costs explained by ACG in centers using patient electronic records, profiled centers and physicians and analyzed the correlation between cost and quality of prescription.</p> <p>Methods</p> <p>We analyzed 65,630 patient records attending five primary care centers in Spain during 2005. Variables explored were age, gender, registered diagnosed episodes of care during 2005, total cost of prescriptions, physician and center. One ACG was assigned to each patient with ACG case-mix software version 7.1. In a two-part model, logistic regression was used to explain the incurrence of drug expenditure at the first stage and a linear mixed model that considered the multilevel structure of data modeled the cost, conditional upon incurring any expense. Risk and efficiency indexes in pharmacy cost adjusted for ACG were obtained for centers and physicians. Spearman rank correlation between physician expenditure, adjusted for ACG, and a prescription quality index was also obtained. Pediatric and adult data were analyzed separately.</p> <p>Results</p> <p>No prescription was recorded for 13% of adults and 39.6% of children. The proportion of variance of the incurrence of expenditure explained by ACGs was 0.29 in adults and 0.21 in children. For adults with prescriptions, the variance of cost explained by ACGs was 35.4%, by physician-center was 1.8% and age 10.5% (residual 52.3%). For children, ACGs explained 22.4% of cost and physician-center 10.9% (residual 66.7%). Center efficiency index for adults ranged 0.58 to 1.22 and for children 0.32 to 2.36.</p> <p>Spearman correlation between expenditure and prescription quality index was -0.36 in family physicians (p = 0.019, N = 41) and -0.52 in pediatricians (p = 0.08, N = 12).</p> <p>Conclusion</p> <p>In our setting, ACG is the variable studied that explains more variability in pharmacy cost in adults compared to physician and center. In children there is greater variability among physicians and centers not related to case-mix. In our sites, ACG is useful to profile physicians and centers using electronic records in real practical conditions. Physicians with lower pharmaceutical expenditure have higher scores for a prescription quality index.</p

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt