Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe — recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency

Wstęp: Wyniki badań z ostatnich lat dokumentują wiele korzyści wynikających z działania witaminy D na organizm człowieka na wszystkichetapach jego życia. Większość badań epidemiologicznych sugeruje, że niedobór witaminy D jest powszechny wśród mieszkańców EuropyŚrodkowej. Naturalną konsekwencją tej sytuacji jest konieczność ciągłego uświadamiania społeczeństwu oraz środowisku medycznemu,jaką rolę odgrywa witamina D w rozwoju i funkcjonowaniu organizmu ludzkiego.Metody: Na podstawie przeglądu danych literaturowych Polski Zespół Wielodyscyplinarny opracował tezy dotyczące zasad suplementacjiwitaminą D, które przesłano do członków Komitetu Naukowego konferencji „Witamina D — minimum, maksimum, optimum”,19–20 Październik, 2012, Warszawa. W trakcie powyższej konferencji z udziałem 550 delegatów oraz Ekspertów różnych dziedzin medycynyomówiono i przedyskutowano propozycje wytycznych suplementacji witaminą D populacji Europy Środkowej.Wyniki: W efekcie przeprowadzonych dyskusji Zespół Ekspertów opracował wytyczne suplementacji witaminą D dla wszystkich grupwiekowych populacji Europy Środkowej. Określono również kryteria diagnostyczne charakteryzujące stan zaopatrzenia organizmu w witaminę D: deficyt witaminy D ustalono jako stężenie 25(OH)D < 20 ng/mL (< 50 nmol/L)], suboptymalne zaopatrzenie jako stężenie25(OH)D wynoszące 20–30 ng/mL (50–75 nmol/L), a stężenie 30–50 ng/mL (75–125 nmol/L) uznano za docelowe dla zapewnienia efektuplejotropowego witaminy D.Wnioski: Poprawa obecnego stanu zaopatrzenia witaminy D w grupach dzieci, młodzieży, osób aktywnych zawodowo i seniorówpowinna zostać włączona do priorytetów polityki zdrowotnej społeczeństw Europy Środkowej.Introduction: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium–phosphate metabolismas well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activityappear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest thatVitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conferencefocused on overcoming Vitamin D deficiency.Methods: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses onrecommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to ScientificCommittee members of the ‘Vitamin D — minimum, maximum, optimum’ conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting ‘Vitamin D — minimum, maximum, optimum’ was held on October 19–20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists’ votingwere reviewed and discussed during eight plenary sessions and two workshops.Results: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges ofserum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20–30 ng/mL(50–75 nmol/L)], and target concentration for optimal Vitamin D effects [30–50 ng/mL (75–125 nmol/L)]. General practical guidelines regardingsupplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, childrenand adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed.Conclusions: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementationguidance and population strategies for Vitamin D in Central Europe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Introduction to Surface Avatar: the First Heterogeneous Robotic Team to be Commanded with Scalable Autonomy from the ISS

Robotics is vital to the continued development toward Lunar and Martian exploration, in-situ resource utilization, and surface infrastructure construction. Large-scale extra-terrestrial missions will require teams of robots with different, complementary capabilities, together with a powerful, intuitive user interface for effective commanding. We introduce Surface Avatar, the newest ISS-to-Earth telerobotic experiment series, to be conducted in 2022-2024. Spearheaded by DLR, together with ESA, Surface Avatar builds on expertise on commanding robots with different levels of autonomy from our past telerobotic experiments: Kontur-2, Haptics, Interact, SUPVIS Justin, and Analog-1. A team of four heterogeneous robots in a multi-site analog environment at DLR are at the command of a crew member on the ISS. The team has a humanoid robot for dexterous object handling, construction and maintenance; a rover for long traverses and sample acquisition; a quadrupedal robot for scouting and exploring difficult terrains; and a lander with robotic arm for component delivery and sample stowage. The crew's command terminal is multimodal, with an intuitive graphical user interface, 3-DOF joystick, and 7-DOF input device with force-feedback. The autonomy of any robot can be scaled up and down depending on the task and the astronaut's preference: acting as an avatar of the crew in haptically-coupled telepresence, or receiving task-level commands like an intelligent co-worker. Through crew performing collaborative tasks in exploration and construction scenarios, we hope to gain insight into how to optimally command robots in a future space mission. This paper presents findings from the first preliminary session in June 2022, and discusses the way forward in the planned experiment sessions

Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain

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Soft tissue response to different abutment materials: A controlled and randomized human study using an experimental model.

OBJECTIVES Aim of this study was to compare the soft-tissue response to implant abutments made of titanium, zirconia, zirconia veneered with feldspar ceramics and PEEK by various clinical, histological, microbiological and molecular biological markers in an experimental model. MATERIALS AND METHODS 40 experimental one-piece healing abutments of four different materials were mounted on bone-level implants in 20 volunteering patients (split-mouth design). After a three months period of open healing, clinical parameters at the abutments were assessed and adjacent mucosa was sampled for inflammatory cytokine mRNA-concentrations and histological analysis by a novel method. In addition, PISF-samples were obtained for the analysis of periodonto-pathogenic bacteria counts and active MMP-8 levels. Marginal bone level change was measured by intra oral radiographs. RESULTS Abutments of the different materials did not exhibit significant differences regarding clinical parameters, pathogenic bacteria counts or pro-inflammatory cytokine concentrations. Likewise, no significant differences were detected regarding soft tissue morphology or bone level change. Compared to titanium abutments, significantly less mononuclear inflammatory cells were detected in the mucosa at abutments made of zirconia veneered with feldspar ceramics. CONCLUSIONS All examined abutment materials exhibited a similar soft tissue response compared to titanium and histological data did not reveal early signs of elevated inflammation caused by PEEK- and feldspar-veneered zirconia abutments. Due to the short observation period and the small sample size, a final conclusion on the long term suitability of those abutment materials cannot be drawn. However, based on the presented data, we consider further studies on that subject as appropriate

Urinary iodine concentrations in mothers and their term newborns in country with sufficient iodine supply

The main aim of the study was to evaluate maternal and newborn urinary iodine concentrations according to the usage of iodine supplementation during pregnancy.The main aim of the study was to evaluate maternal and newborn urinary iodine concentrations according to the usage of iodine supplementation during pregnancy