Maternal cardiovascular potential and kinetic energy indices in pre-eclamptic and small-for-gestational-age pregnancies

Objective Non-invasive assessment of maternal cardiovascular potential and kinetic energy can be used to derive potential-to-kinetic-energy ratio (PKR) and Smith–Madigan inotropic index (SMII), which reflect the balance between blood pressure and blood flow. The aim of this study was to evaluate PKR and SMII in pregnancies complicated by hypertensive disorders of pregnancy (HDP) and/or small-for-gestational-age (SGA) birth. Methods This was a prospective study that enrolled women with a singleton pregnancy between 5 and 41 weeks' gestation. Women who developed HDP and/or SGA underwent cardiovascular profiling from 20 weeks. To establish reference ranges for PKR and SMII, women without any pre-existing medical problems at the time of booking who did not develop HDP, SGA or other complications during pregnancy were also recruited for cardiovascular profiling. Measurements of cardiovascular parameters were obtained using a non-imaging ultrasound cardiac output monitor. Results A total of 688 women completed the study, including 626 controls, 21 cases with HDP, 19 cases with SGA and 22 cases with HDP and SGA. PKR was significantly elevated in pregnancies with placental dysfunction compared with controls (HDP only, 29.81 ± 9.5; HDP and SGA, 44.33 ± 24.27; SGA only, 31.05 ± 13.14; vs controls, 22.30 ± 7.93; all P < 0.05). SMII values were significantly lower only in cases affected by SGA alone when compared with controls (1.47 ± 0.23 W/m2 vs 1.75 ± 0.40 W/m2; P < 0.005). These differences remained statistically significant when the analysis was undertaken using multiples of the median values corrected for gestational age. Conclusions The findings of this study suggest that point-of-care non-invasive cardiovascular profiling using PKR and SMII may help distinguish between pregnancies affected by specific placental disorders and those exhibiting healthy cardiovascular adaptation to pregnancy. Women with HDP and/or SGA appear to have distinctive PKR and SMII profiles that reflect low kinetic energy in pregnancies with SGA and high potential energy in pregnancies affected by HDP. Finally, non-invasive assessment of potential and kinetic cardiovascular energy demonstrates physiological high-flow and low-resistance adaptation in uncomplicated pregnancies

Ionize Hard: Interstellar PO+ Detection

We report the first detection of the phosphorus monoxide ion (PO+) in the interstellar medium. Our unbiased and very sensitive spectral survey toward the G+0.693–0.027 molecular cloud covers four different rotational transitions of this molecule, two of which (J = 1–0 and J = 2–1) appear free of contamination from other species. The fit performed, assuming local thermodynamic equilibrium conditions, yields a column density of N=(6.0 \ub1 0.7) 7 1011\ua0cm−2. The resulting molecular abundance with respect to molecular hydrogen is 4.5 7 10–12. The column density of PO+ normalized by the cosmic abundance of P is larger than those of NO+ and SO+, normalized by N and S, by factors of 3.6 and 2.3, respectively. The N(PO+)/N(PO) ratio is 0.12 \ub1 0.03, more than one order of magnitude higher than that of N(SO+)/N(SO) and N(NO+)/N(NO). These results indicate that P is more efficiently ionized than N and S in the ISM. We have performed new chemical models that confirm that the PO+ abundance is strongly enhanced in shocked regions with high values of cosmic-ray ionization rates (10–15 − 10–14 s−1), as occurring in the G+0.693–0.027 molecular cloud. The shocks sputter the interstellar icy grain mantles, releasing into the gas phase most of their P content, mainly in the form of PH3, which is converted into atomic P, and then ionized efficiently by cosmic rays, forming P+. Further reactions with O2 and OH produces PO+. The cosmic-ray ionization of PO might also contribute significantly, which would explain the high N(PO+)/N(PO) ratio observed. The relatively high gas-phase abundance of PO+ with respect to other P-bearing species stresses the relevance of this species in the interstellar chemistry of P

Triggering Mechanisms of Tsunamis in the Gulf of Cadiz and the Alboran Sea: An Overview

The Gulf of Cadiz and the Alboran Sea are characterized by tectonic activity due to oblique convergence at the boundary between the Eurasian and Nubian plates. This activity has favoured a variety of tsunamigenic sources: basically, seismogenic faults and submarine landslides. The main tsunamigenic faults in the Gulf of Cadiz would comprise the thrust systems of Gorringe Ridge, Marquês de Pombal, São Vicente Canyon, and Horseshoe faults with a high susceptibility; meanwhile in the Alboran Sea would be the thrust system of the northern Alboran Ridge with high susceptibility, and the thrust systems of north Xauen and Adra margin, the transpressive segment of Al Idrissi fault, and the Yusuf-Habibas and Averroes faults, with moderate to high susceptibility. The areas with the greatest potential to generate tsunamigenic submarine landslides are in the Gulf of Cadiz, the São Vicente Canyon, Hirondelle Seamount, and Gorringe Ridge; and in the Alboran Sea are the southern and northern flanks of Alboran Ridge. Both sources are likely to generate destructive tsunamis in the Gulf of Cadiz, given its history of bigger earthquakes (>7 Mw) and larger landslides. To fully assess tsunamigenic sources, further work needs to be performed. In the case of seismogenic faults, research focuses on geometry, offsets, timing, paleoearthquakes, and recurrence, and in landslides on early post-failure evolution, age, events, and recurrence. In situ measurements, paleotsunami records, and long-term monitoring, in addition to major modelling developments, will be also necessary.Versión del edito

Hypertension in the very old; prevalence, awareness, treatment and control: a cross-sectional population-based study in a Spanish municipality

<p>Abstract</p> <p>Background</p> <p>Information on hypertension in the very elderly is sparse. Until recently evidence of benefits from pharmacological treatment was inconclusive. We estimated the prevalence of hypertension in subjects aged 80 or more, the proportion of awareness, treatment and control. Explanatory variables associated with good control were also studied.</p> <p>Methods</p> <p>Cross sectional, population-based study, conducted in Martorell, an urban Spanish municipality, in 2005. By simple random sampling from the census, 323 subjects aged 80 or more were included. Patients were visited at home or in the geriatric institution and after giving informed consent, the study variables were collected. These included: supine and standing blood pressure and information about diagnosis and treatment of hypertension. The estimation and 95% confidence interval were obtained and a logistic regression model was used to study explanatory variables associated with blood pressure below 140/90 mm Hg.</p> <p>Results</p> <p>The prevalence of hypertension was 72.8% (95%CI: 69.5 – 76.6%) and 93% of the patients were aware of this condition, of whom 96.3% (95%CI: 93.65 – 97.9%) had been prescribed pharmacological treatment and 30.7% (95%CI: 25.8 – 36.1%) had blood pressure below 140/90 mm Hg. Some of the patients (43%) had one antihypertensive drug and 39.5% had two in combination. Explanatory variables associated with blood pressure below 140/90 mm Hg included prescription of a diuretic, OR: 0.31 (95%CI: 0.14 – 0.66), and history of ischemic heart disease, OR: 0.21 (95%CI: 0.1 – 0.47).</p> <p>Conclusion</p> <p>The prevalence of hypertension in population aged 80 or more was over 70%. Most patients were aware of this condition and they had antihypertensive medication prescribed. Approximately one third of treated patients had blood pressure below 140/90 mm Hg. Patients with heart disease and with diuretics had more frequently blood pressure below this value.</p

Genome Sequence of Brucella abortus Vaccine Strain S19 Compared to Virulent Strains Yields Candidate Virulence Genes

The Brucella abortus strain S19, a spontaneously attenuated strain, has been used as a vaccine strain in vaccination of cattle against brucellosis for six decades. Despite many studies, the physiological and molecular mechanisms causing the attenuation are not known. We have applied pyrosequencing technology together with conventional sequencing to rapidly and comprehensively determine the complete genome sequence of the attenuated Brucella abortus vaccine strain S19. The main goal of this study is to identify candidate virulence genes by systematic comparative analysis of the attenuated strain with the published genome sequences of two virulent and closely related strains of B. abortus, 9–941 and 2308. The two S19 chromosomes are 2,122,487 and 1,161,449 bp in length. A total of 3062 genes were identified and annotated. Pairwise and reciprocal genome comparisons resulted in a total of 263 genes that were non-identical between the S19 genome and any of the two virulent strains. Amongst these, 45 genes were consistently different between the attenuated strain and the two virulent strains but were identical amongst the virulent strains, which included only two of the 236 genes that have been implicated as virulence factors in literature. The functional analyses of the differences have revealed a total of 24 genes that may be associated with the loss of virulence in S19. Of particular relevance are four genes with more than 60bp consistent difference in S19 compared to both the virulent strains, which, in the virulent strains, encode an outer membrane protein and three proteins involved in erythritol uptake or metabolism

Cancer Screening by Systemic Administration of a Gene Delivery Vector Encoding Tumor-Selective Secretable Biomarker Expression

Cancer biomarkers facilitate screening and early detection but are known for only a few cancer types. We demonstrated the principle of inducing tumors to secrete a serum biomarker using a systemically administered gene delivery vector that targets tumors for selective expression of an engineered cassette. We exploited tumor-selective replication of a conditionally replicative Herpes simplex virus (HSV) combined with a replication-dependent late viral promoter to achieve tumor-selective biomarker expression as an example gene delivery vector. Virus replication, cytotoxicity and biomarker production were low in quiescent normal human foreskin keratinocytes and high in cancer cells in vitro. Following intravenous injection of virus >90% of tumor-bearing mice exhibited higher levels of biomarker than non-tumor-bearing mice and upon necropsy, we detected virus exclusively in tumors. Our strategy of forcing tumors to secrete a serum biomarker could be useful for cancer screening in high-risk patients, and possibly for monitoring response to therapy. In addition, because oncolytic vectors for tumor specific gene delivery are cytotoxic, they may supplement our screening strategy as a “theragnostic” agent. The cancer screening approach presented in this work introduces a paradigm shift in the utility of gene delivery which we foresee being improved by alternative vectors targeting gene delivery and expression to tumors. Refining this approach will usher a new era for clinical cancer screening that may be implemented in the developed and undeveloped world

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization