Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites

Background information The pathology causing stages of the human malaria parasite Plasmodium falciparum reside within red blood cells that are devoid of any regulated transport system. The parasite, therefore, is entirely responsible for mediating vesicular transport within itself and in the infected erythrocyte cytoplasm, and it does so in part via its family of 11 Rab GTPases. Putative functions have been ascribed to Plasmodium Rabs due to their homology with Rabs of yeast, particularly with Saccharomyces that has an equivalent number of rab/ypt genes and where analyses of Ypt function is well characterized. Results Rabs are important regulators of vesicular traffic due to their capacity to recruit specific effectors. In order to identify P. falciparum Rab (PfRab) effectors, we first built a Ypt-interactome by exploiting genetic and physical binding data available at the Saccharomyces genome database (SGD). We then constructed a PfRab-interactome using putative parasite Rab-effectors identified by homology to Ypt-effectors. We demonstrate its potential by wet-bench testing three predictions; that casein kinase-1 (PfCK1) is a specific Rab5B interacting protein and that the catalytic subunit of cAMP-dependent protein kinase A (PfPKA-C) is a PfRab5A and PfRab7 effector. Conclusions The establishment of a shared set of physical Ypt/PfRab-effector proteins sheds light on a core set Plasmodium Rab-interactants shared with yeast. The PfRab-interactome should benefit vesicular trafficking studies in malaria parasites. The recruitment of PfCK1 to PfRab5B+ and PfPKA-C to PfRab5A+ and PfRab7+ vesicles, respectively, suggests that PfRab-recruited kinases potentially play a role in early and late endosome function in malaria parasites

Hyper parathyroidisim jaw tumor syndrome: a rare condition of incongruous features

Background: Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome is a rare genetic disorder bearing both a germline and a somatic CDC73 mutation (formerly known as HRPT2), which has been mapped to chromosome 1q25-q31. The association of jaw ossifying fibroma with primary hyperparathyroidisim (PHPT) is typical of HPT-JT. It may also include cystic and neoplastic renal abnormalities and uterine tumors.Case Details: Here, we report a case of HPT-JT with an initial presentation of declination in reproductive fitness. Extensive literature search and thorough investigation helped us parturitate the underlying syndrome, thereby predictively improving the prognosis.Conclusion: The features of HPT-JT are clinically difficult to ascertain because the parathyroid disease, ossifying fibroma in the jaw and other abnormalities, often occurs asynchronously and may be diagnosed and treated separately.Keywords: Hyperparathyroidism, HPT-JT, Ossifying fibroma, Syndrom

Clinical, ultrasonographic and CT markers for botulinum toxin injections into the piriformis muscle

Pla general de la platja de la Barceloneta. Hi destaca l'escultura Peix

Low-Cost Transceiver Architectures for 60 GHz Ultra Wideband WLANs

Millimeter-wave multiport transceiver architectures dedicated to 60 GHz UWB short-range communications are proposed in this paper. Multi-port circuits based on 90° hybrid couplers are intensively used for phased antenna array, millimeter-wave modulation and down-conversion, as a low-cost alternative to the conventional architecture. This allows complete integration of circuits including antennas, in planar technology, on the same substrate, improving the overall transceiver performances

A high-powered replication study finds no effect of starting or stopping hormonal contraceptive use on relationship quality

A number of recent studies have implicated that incongruent use of hormonal contraceptives (HCs) negatively affects various aspects of women’s romantic relationships. It has been suggested that women with incongruent HC use (a discrepancy in HC use status between when they first met their current partner and the time of study participation) report less sexual satisfaction and higher jealousy scores compared to women with congruent HC use. A similar effect has also been hypothesized for general relationship satisfaction, and recent findings suggest that the association between HC incongruency and general relationship satisfaction is moderated by women’s perceived facial attractiveness of male partners. Using a large convenience sample (N = 948) of Finnish women, we attempted to replicate previously reported findings but found no support for the HC congruency hypothesis, despite excellent statistical power (≥98.7%) to detect previously reported effect sizes. Instead, after dividing our sample into four groups based on HC congruency/incongruency, we found that the largest differences in jealousy, sexual satisfaction, and relationship satisfaction scores tended to be found between women who were consistent HC users and consistent non-users (i.e., between women with different kinds of congruent HC use). We also detected a significant main effect of current HC use on jealousy. We conclude that, as the effect size of the HC incongruency effect reported in previous studies was small, unequal distributions of current HC users within congruent and incongruent HC user groups may give rise to spurious HC incongruency effects in studies using small samples

The Characteristics of Postoperative Mediastinitis During the Changing Phases of Cardiac Surgery

Background. Mediastinitis is a serious complication of open heart surgery associated with high mortality, considerable health care costs, and prolonged hospital stay. We examined characteristics and incidence of mediastinitis during 29 years when indications and patient material have been in a process of change. Methods. This was a retrospective population-based study comprising all mediastinitis patients more than 16 years of age after open heart surgery between 1990 and 2018 from a population of 1.7 million. Patient records of 50 mediastinitis patients from 2004 to 2014 were reviewed and compared with 120 patients from 1990 to 1999. Results. Annual mediastinitis rate varied 0% to 1.5% with a decreasing trend-from a level exceeding 1.2% to approximately 0.3%-over the study period. In 2004 to 2014 patients with mediastinitis were older, more often smokers, and more often had diabetes mellitus and renal insufficiency than in 1990 to 1999. No difference in length of hospital treatment, antibiotic prophylaxis or treatment, intensive care unit treatment, or mortality was observed between 1990 to 1999 and 2004 to 2014. Coronary artery bypass graft surgery became less common and valve replacement and hybrid operations more common among operations leading to mediastinitis. Staphylococcus aureus increased (from 25% to 56%, p = .005) whereas coagulase-negative staphylococci (46% to 23%, P < .001) and gramnegative bacteria (18% to 12%, P = .033) decreased as causative agents. Surgery for mediastinitis remained similar except introduction of vacuum-assisted closure treatment. Conclusions. The rate of mediastinitis decreased during these 29 years. No difference in 30-day mortality in mediastinitis was seen: 0.9% in 1990 to 1999 and 2% in 2004 to 2014. (C) 2021 by The Society of Thoracic SurgeonsPeer reviewe

A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya : comparison between Rotarix and RotaTeq vaccines

Background Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Methods Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. Results The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Conclusion Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability

Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides

All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express alpha(3)beta(1) integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to alpha(3)beta(1) integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.Peer reviewe