Distributed storage healthcare - the basis of a planet-wide public health care network.
As health providers move towards higher levels of information technology (IT) integration, they become increasingly dependent on the availability of the electronic health record (EHR). Current solutions of individually managed storage by each healthcare provider focus on efforts to ensure data security, availability and redundancy. Such models, however, scale poorly to a future of a planet-wide public health-care network (PWPHN). Our aim was to review the research literature on distributed storage systems and propose methods that may aid the implementation of a PWPHN. A systematic review was carried out of the research dealing with distributed storage systems and EHR. A literature search was conducted on five electronic databases: Pubmed/Medline, Cinalh, EMBASE, Web of Science (ISI) and Google Scholar and then expanded to include non-authoritative sources. The English National Health Service Spine represents the most established country-wide PHN but is limited in deployment and remains underused. Other, literature identified and established distributed EHR attempts are more limited in scope. We discuss the currently available distributed file storage solutions and propose a schema of how one of these technologies can be used to deploy a distributed storage of EHR with benefits in terms of enhanced fault tolerance and global availability within the PWPHN. We conclude that a PWPHN distributed health care record storage system is technically feasible over current Internet infrastructure. Nonetheless, the socioeconomic viability of PWPHN implementations remains to be determined.


Pattern development in palleal buds of botryllid ascidians: Relation between parent and its buds in their body axes.
In order to determine how the zooid pattern (normal or reversed bilateral asymmetry) is transmitted through asexual reproduction in botryllid ascidians, the axial relationship between a zooid and its palleal buds was observed in Symplegmo reptans, Metandrocarpa uedai, Polyandrocarpa misakiensis, and P. stolonifera. The bud axes developed in harmony with the parent axes, with both normal and reversed body patterns, so that (1) when buds are given off from the right (left) side of the parent, their distal side becomes the right (left) in the future zooids (coincidence of the anteroposterior axis), (2) the free surface of the developing buds, like the parent, becomes dorsal (the coincidence of dorsoventral axis), and (3) the heart (gut loop), which is an organ representing the bilateral asymmetry, arises on the distal side of the developing buds, when the buds are derived from the side where the parent heart (gut loop) was situated (coincidence of the transverse axis). This shows that the bud develops as if it knew the position on the parent lateral wall from which it has arisen, a phenomenon referred to as the parental lateral effect.


Bandgap-controlled hollow polyaniline nanostructures synthesized by Mn-dependent nano-confined polymerization.
Herein, we report a de novo synthesis approach to produce bandgap-controlled polyaniline (PAni) nanostructure via Mn-mediated oxidative polymerization at the catalytic nanoreactor. To achieve systemic nanoconfined polymerization, manganese oxide (MnOx) nanoparticles coated with silica were used as the sacrificial nanotemplate. Interestingly, the catalytic nanoreactor simultaneously allowed the nanoconfined oxidative polymerization and controlling of the bandgap. MnOx could be reduced by the addition of aniline monomers and consecutive redox reaction at the nanoreactor. Furthermore, core cavity was generated, and ionized Mn could control the bandgap by coordination at the nanostructures.


An anisotropic biphasic theory of tissue-equivalent mechanics: the interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance.
We present a general mathematical theory for the mechanical interplay in tissue-equivalents (cell-populated collagen gels): Cell traction leads to compaction of the fibrillar collagen network, which for certain conditions such as a mechanical constraint or inhomogeneous cell distribution, can result in inhomogeneous compaction and consequently fibril alignment, leading to cell contact guidance, which affects the subsequent compaction. The theory accounts for the intrinsically biphasic nature of collagen gel, which is comprised of collagen network and interstitial solution. The theory also accounts for fibril alignment due to inhomogeneous network deformation, that is, anisotropic strain, and for cell alignment in response to fibril alignment. Cell alignment results in anisotropic migration and traction, as modeled by a cell orientation tensor that is a function of a fiber orientation tensor, which is defined by the network deformation tensor. Models for a variety of tissue-equivalents are shown to predict qualitatively the alignment that arises due to inhomogeneous compaction driven by cell traction.


Early-onset breast cancer--histopathological and prognostic considerations.
Young age at diagnosis is claimed to be a prognostic factor in the natural history of breast cancer. Of 2879 patients aged < 70 years treated for primary operable breast cancer (< 5 cm diameter) at Nottingham City Hospital between 1973 and 1993, 120 were less than 35 years of age at diagnosis. Histopathological and prognostic variables were compared between patients aged < 35, 35-50 and 51-70 years. A significant reduction in metastasis disease-free survival and actuarial survival was seen in breast cancer patients aged < 35 years compared with the two older age groups. Patients aged < 35 years at diagnosis presented more frequently with high-grade cancers and vascular invasion. No differences were seen for tumour size or lymph node stage. The Nottingham Prognostic Index (NPI) was used to stratify cancers in each age group. Because of the tendency to high grade, a greater percentage of patients aged < 35 years fell into the poor-prognosis group. Within each prognostic group, no difference in actuarial survival was seen between age groups. The association of young age at diagnosis with a worse prognosis in this series is explained by a higher proportion of poorly differentiated cancers; age itself had no influence on the prognosis of the individual.


Safety and Effectiveness of Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.
Recent clinical trials have shown that while bivalirudin exhibits similar efficacy with heparin, it offers several advantages over heparin, such as a better safety profile. We aimed to evaluate the efficacy and safety of bivalirudin use during Percutaneous Coronary Intervention (PCI) in the treatment of angina and acute coronary syndrome (ACS). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, EMBASE, and Science Direct from January 1980 to January 2016. Randomized controlled trials (RCTs) comparing bivalirudin to heparin during the course of PCI in patients with angina or ACS were included. Outcome measures included all-cause mortality, myocardial infarction, revascularisation, stent thrombosis, stroke, and major bleeding. The selection, quality assessment, and data extraction of the included trials were done independently by four authors, and disagreements were resolved by consensus. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated. A total of 12 RCTs involving 44,088 subjects were included. Bivalirudin appeared to be non-superior compared to heparin in reducing all-cause mortality, myocardial infarction, revascularisation, and stroke. Bivalirudin appeared to be related to a higher risk of stent thrombosis when compared to heparin plus provisional use of a glycoprotein IIb/IIIa inhibitor (GPI) at day 30 (RR 1.94 [1.16, 3.24] p < 0.01). Overall, bivalirudin-based regimens present a lesser risk of major bleeding (RR 0.56 [0.44-0.71] p < 0.001), and Thrombolysis In Myocardial Infarction (TIMI) major bleeding (RR 0.56 [0.43-0.73]) compared with heparin-based regimens either with provisional or routine use of a GPI. However, the magnitude of TIMI major bleeding effect varied greatly (p < 0.001), depending on whether a GPI was provisionally used (RR 0.42 [0.34-0.52] p < 0.001) or routinely used (RR 0.60 [0.43 -0.83] p < 0.001), in the heparin arm. This meta-analysis demonstrated that bivalirudin is associated with a lower risk of major bleeding, but a higher risk of stent thrombosis compared to heparin.


Formation and characterization of an all-ferrous Rieske cluster and stabilization of the [2Fe-2S]0 core by protonation.
The all-ferrous Rieske cluster, [2Fe-2S](0), has been produced in solution and characterized by protein-film voltammetry and UV-visible, EPR, and Mössbauer spectroscopies. The [2Fe-2S](0) cluster, in the overexpressed soluble domain of the Rieske protein from the bovine cytochrome bc(1) complex, is formed at -0.73 V at pH 7. Therefore, at pH 7, the [2Fe-2S](1+/0) couple is 1.0 V below the [2Fe-2S](2+/1+) couple. The two cluster-bound ferrous irons are both high spin (S = 2), and they are coupled antiferromagnetically (-J > or = 30 cm(-1), H =-2JS1.S2) to give a diamagnetic (S = 0) ground state. The ability of the Rieske cluster to exist in three oxidation states (2+, 1+, and 0) without an accompanying coupled reaction, such as a conformational change or protonation, is highly unusual. However, uncoupled reduction to the [2Fe-2S](0) state occurs at pH > 9.8 only, and at high pH the intact cluster persists in solution for <1 min. At pH < 9.8, the all-ferrous cluster is stabilized significantly by protonation. A combination of experimental data and calculations based on density functional theory suggests strongly that the proton binds to one of the cluster mu(2)-sulfides, consistent with observations that reduced [3Fe-4S] clusters are protonated also. The implications for our understanding of coupled reactions at iron-sulfur clusters and of the factors that determine the relative stabilities of their different oxidation states are discussed.


Influence of bidisperse self-assembled monolayer structure on the slip boundary condition of thin polymer films.
Alkylsilane self-assembled monolayers (SAMs) are often used as model substrates for their ease of preparation and hydrophobic properties. We have observed that these atomically smooth monolayers also provide a slip boundary condition for dewetting films composed of unentangled polymers. This slip length, an indirect measure of the friction between a given liquid and different solids, is switchable and can be increased [R. Fetzer et al., Phys. Rev. Lett. 95, 127801 (2005); O. Bäumchen et al., J. Phys.: Condens. Matter 24, 325102 (2012)] if the alkyl chain length is changed from 18 to 12 backbone carbons, for example. Typically, this change in boundary condition is affected in a quantized way, using one or the other alkyl chain length, thus obtaining one or the other slip length. Here, we present results in which this SAM structure is changed in a continuous way. We prepare bidisperse mixed SAMs of alkyl silanes, with the composition as a control parameter. We find that all the mixed SAMs investigated show an enhanced slip boundary condition as compared to the single-component SAMs. The slip boundary condition is accessed using optical and atomic force microscopy, and we describe these observations in the context of X-ray reflectivity measurements. The slip length, varying over nearly two orders of magnitude, of identical polymer melts on chemically similar SAMs is found to correlate with the density of exposed alkyl chains. Our results demonstrate the importance of a well characterized solid/liquid pair, down to the angstrom level, when discussing the friction between a liquid and a solid.


Does the Margin Matter in Esophageal Cancer.
The prognostic impact of circumferential resection margin (CRM) involvement in resected esophageal cancer (EC) is controversial discussed. The College of American Pathologists (CAP) and the Royal College of Pathologists (RCP) provide 2 different definitions of CRM involvement. The aim of this systematic review was to evaluate the clinical significance of CRM involvement on patients' survival following esophagectomy due to EC. PubMed, Science Direct, and Google scholar were searched for studies analyzing the clinical impact of CRM in EC. A total of 28 studies analyzed the prognostic effect of a positive CRM in EC. A wide range of CRM involvement (8.6-83.1%) was reported. Both available meta-analyses found a significant association between a positive CRM and patients' survival irrespective of RCP (OR 2.52 [95% CI 1.96-3.25; p < 0.001]) or CAP (OR 4.02 [95% CI 2.25-7.20; p < 0.001]) criteria. The influence of neoadjuvant therapy on the CRM remains unclear. Key Messages: CRM involvement is a useful parameter for EC patients' prognosis. The application of CAP criteria should be preferred since patients with a poor prognosis can be identified more sufficiently. Neoadjuvant therapy and en bloc transthoracic esophagectomy show favorable results for achievement of negative CRM.


Easing Medical Device Regulatory Oversight: The FDA and Testing Amidst the COVID-19 Pandemic.
The FDA already subjects most medical devices to much less stringent approval requirements than drugs and biologics, and attempts to speed up rollout during the COVID crisis have been problematic. Agency decisions, including to allow antibody test marketing without emergency use authorization or review, and the back-and-forth guidance on laboratory-developed tests, have met harsh criticism and unreliable results. Though the long-term results of these decisions are unclear, the FDA's credibility, reliability, and commitment to safety are threatened by even further lessening medical device regulatory oversight during the coronavirus pandemic. The relaxed and fix-it-later approach to many of the FDA's public health emergency decisions regarding medical devices reflect the ongoing criticisms of medical device regulation in general, specifically the 510(k) process and laboratory developed test regulation, offering a point of reflection towards reform. Adaptive legislation and a risk-based and evidentiary approach to premarket and postmarket review can begin to address these issues both generally and in an emergency context.


The psychiatric vulnerability gene CACNA1C and its sex-specific relationship with personality traits, resilience factors and depressive symptoms in the general population.
Genome-wide association studies have reported an association between the A-allele of rs1006737 within CACNA1C and affective disorders and schizophrenia. The aim of the present study was to investigate the relationship between rs1006737 and established and potential endophenotypes for these disorders in a population-based cohort of 3793 subjects, using an analytical method designed to assess a previously reported sex-specific effect of CACNA1C. The investigated endophenotypes included personality traits and resilience factors. At 10-year follow-up, subjects were screened for depressive symptoms. All subjects were genotyped for rs1006737. The direction of the effect and mode of inheritance of rs1006737 differed between the sexes. In men, the A-allele was associated with higher emotional lability and lower resilience, that is, lower sense of coherence (P=0.021), lower perceived social support (P=0.018), lower dispositional optimism (P=0.032) and more depressive symptoms at follow-up (P=0.007). In women, the A-allele was associated with lower emotional lability and stronger resilience, that is, higher sense of coherence (P=0.00028), higher perceived social support (P=0.010), lower neuroticism (P=0.022) and fewer depressive symptoms at follow-up (P=0.035). After conservative Bonferroni correction for 32 tests, results only remained significant for sense of coherence in women (P=0.009). These results suggest that CACNA1C is involved in the genetic architecture of endophenotypes for affective disorders and schizophrenia, and that it shows a distinct sex-specific effect. Comprehensive phenotype characterization in case-control samples and the general population, as well as an adequate modeling of sex-specific genetic effects, may be warranted to elucidate the pathogenetic mechanisms conferred by robustly identified susceptibility genes.


[Susceptibility of clinical strains of gram-negative rods to selected beta-lactam antibiotics].
The aim of the study was to determine the activity of four beta-lactam antibiotics against nosocomial strains of gram-negative bacilli. Two antibiotics combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical strains were isolated from patients hospitalized in the following wards: surgery and intensive care unit of State Clinical Hospital No 1 in Warsaw. The strains were identified in the automatic ATB system using ID 32 E and ID 32 GN strips. The susceptibility of isolates to antibacterial agents was determined in the automatic ATB system using ATB G- and ATB PSE strips. The susceptibility of the strains to imipenem, meropenem, timentin and tazocin was tested by disc-diffusion method. 157 strains of gram-negative bacilli were cultured. 100 strains were isolated from patients hospitalized in surgical ward and 57 strains from patients hospitalized in ICU. Nonfermenting rods dominated among isolated strains-91. The results obtained indicate that multiresistant gram-negative rods causing serious therapeutic problems are often isolated from clinical specimens. The contribution of nonfermenting rods, especially Pseudomonas spp. and Acinetobacter spp. to the etiology of infections in hospitalized patients has increased. Infections caused by these strains are difficult to cure. Tazocin and carbapenems (imipenem and meropenem) are highly active in vitro against the examined strains of gram-negative bacilli.


Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity.
Increasing evidence point to the role of the adipose tissue on the insulin resistance associated with reduced fetal growth. Since adiponectin, exclusively produced by the adipose tissue, exerts an important insulin-sensitizing activity, it appears critical to investigate the effect of being born small for gestational age (SGA) on adiponectin production in adulthood and its relationship with insulin sensitivity. Serum adiponectin concentrations were measured in 486 young adults born SGA, precisely selected on birth data, who were compared to 573 age-matched subjects born appropriate for gestational age (AGA). The relationship between serum adiponectin levels and insulin-resistance indices measured under OGTT were tested and compared between the two groups. The SGA group demonstrated significantly reduced serum adiponectin levels than controls (12.6 +/- 6.9 vs 13.2 +/- 6.4 microg/ml, P = 0.02) and the difference remained significant when the key regulatory factors were taken into account (P = 0.008). In the AGA group, fasting I/G taken as an insulin-resistance index negatively correlated with serum adiponectin concentrations (P = 0.02), while the relationship followed a U-shape with increased fasting I/G ratio despite high concentrations of serum adiponectin in the SGA group (P = 0.12). Subjects born SGA demonstrated significantly reduced serum adiponectin levels, which were not related to insulin-resistance indices in comparison to what observed in age-matched subjects born AGA. Although this defect in adiponectin production and in its insulin-sensitizing action remains to be elucidated at the molecular level, it strengthens the critical contribution of the adipose tissue in the metabolic complications associated with reduced fetal growth.


Practices, attitudes and knowledge of midwives and nurses regarding gestational diabetes and pregnancy-induced hypertension.
Midwives (M) and obstetric nurses (ON) play a critical role in providing healthcare for pregnant patients at all stages of pregnancy, and ongoing training and education are essential to ensure the best outcomes. This longitudinal quantitative research study aimed to assess the impact of an educational program on the knowledge, attitudes, and practices of 125 midwives and obstetric nurses regarding care for patients with gestational diabetes and pregnancy-induced hypertension. The original questionnaire consisted of 56 items grouped into 3 subscales assessing knowledge (15 items), attitudes (18 items), and practices (23 items). The questionnaire was administered at three distinct intervals during the educational program: pre-test, post-test, and follow-up at three months. The data were analyzed using ANOVA and Pearson correlation coefficients to determine the significance of the differences between the 3 moments of the administration of the questionnaire. There was a significant increase in the level of knowledge, attitudes, and practices of midwives and obstetric nurses following the training module, which was sustained at 3 months after completion compared to pre-training. The comparative analysis of the total scores for every 3 sets of items revealed the positive impact of the educational program on the level of knowledge, attitudes, and practices of midwives and obstetric nurses.


Hybrid quantum systems with high-T[Formula: see text] superconducting resonators.
Superconducting microwave resonators are crucial elements of microwave circuits, offering a wide range of potential applications in modern science and technology. While conventional low-T[Formula: see text] superconductors are mainly employed, high-T[Formula: see text] cuprates could offer enhanced temperature and magnetic field operating ranges. Here, we report the realization of [Formula: see text] superconducting coplanar waveguide resonators, and demonstrate a continuous evolution from a lossy undercoupled regime, to a lossless overcoupled regime by adjusting the device geometry, in good agreement with circuit model theory. A high-quality factor resonator was then used to perform electron spin resonance measurements on a molecular spin ensemble across a temperature range spanning two decades. We observe spin-cavity hybridization indicating coherent coupling between the microwave field and the spins in a highly cooperative regime. The temperature dependence of the Rabi splitting and the spin relaxation time point toward an antiferromagnetic coupling of the spins below 2 K. Our findings indicate that high-Tc superconducting resonators hold great promise for the development of functional circuits. Additionally, they suggest novel approaches for achieving hybrid quantum systems based on high-T[Formula: see text] superconductors and for conducting electron spin resonance measurements over a wide range of magnetic fields and temperatures.


Left upper lobectomy can be a risk factor for thrombosis in the pulmonary vein stump.
Thrombosis in the left upper pulmonary vein stump after left upper lobectomy is a very rare but important complication because it occurs in the systemic circulation system. We previously made the first ever report on the frequency and risk factors of thrombosis in the pulmonary vein stump after lobectomy. In this study, we conducted an investigation in a different hospital to determine whether this was a common complication. From 2008 to 2012, 151 patients who underwent lobectomy and following enhanced CT within 2 years after the operation were studied. Postoperative contrast-enhanced CT imaging was retrospectively checked. We found thrombosis in the pulmonary vein stump in 5 of the 151 patients (3.3%). All 5 patients underwent left upper lobectomy (17.9% of the patients who underwent left upper lobectomy). These 5 patients did not have infarction of any vital organ. The thrombus was disappeared several months later on contrast-enhanced CT in 3 patients and followed in 2 patients. On univariate analysis, there was a significant difference only in the operative procedure (p<0.001). Thrombosis in the pulmonary vein stump occurred with high frequency in patients who underwent left upper lobectomy. Because the frequency of thrombosis in this study was the same as in our previous report, this might be a common complication.


Combined therapy for stage III-IV head and neck cancer: preliminary results.
As part of a combined modality treatment program using chemotherapy, surgery, and/or radiotherapy, 25 patients with previously untreated stage III or IV head and neck cancer received initial combination chemotherapy. Pathologically confirmed complete remission was noted in nine patients (36%). The overall objective major response rate (with all patients included in analysis) was 68%. The chemotherapy regimen included bleomycin, cisplatin, vinblastine, methotrexate, and 5-fluorouracil. A novel concept of drug scheduling was used, based on chemotherapy-induced improvement in RBC deformability. The underlying concept is that improved RBC deformability results in improved capillary blood flow and thereby, increased drug delivery to tumor cells. Treatment resulted in moderate hematologic and renal toxicity with no treatment-related deaths. This exceptionally high, pathologically confirmed complete response rate will hopefully provide a mechanism by which combined modality therapy can adequately be tested for its ability to prolong survival of patients with advanced head and neck cancer.


Cervix Stromal Cells and the Progesterone Receptor A Isoform Mediate Effects of Progesterone for Prepartum Remodeling.
The prepartum transition from a soft to ripening cervix is an inflammatory process that occurs well before birth when systemic progesterone is near peak concentration. This 2-part study first determined that stromal fibroblasts but not macrophages in the cervix have progesterone receptors (PRs). Neither the number of PR cells in cervix sections nor the relative abundance or ratio of nuclear PR isoforms (PR-A/PR-B) were diminished in mice between day 15 of pregnancy and term. Second in mice lacking PR-B ( Pgrtm20mc), the number of cells that expressed the PR-A isoform were maintained during this period of prepartum cervix remodeling. Thus, progesterone effects to sustain pregnancy, as well as soften and ripen the cervix, are mediated by a stable stromal cell population that expresses PR-A and, through interactions with resident macrophages, are likely to mediate inflammatory ripening processes in preparation for birth.


Management of Discharge Instructions for Children With Medical Complexity: A Systematic Review.
Children with medical complexity (CMC) are at risk for adverse outcomes after discharge. Difficulties with comprehension of and adherence to discharge instructions contribute to these errors. Comprehensive reviews of patient-, caregiver-, provider-, and system-level characteristics and interventions associated with discharge instruction comprehension and adherence for CMC are lacking. To systematically review the literature related to factors associated with comprehension of and adherence to discharge instructions for CMC. PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, Web of Science (database initiation until March 2023), and OAIster (gray literature) were searched. Original studies examining caregiver comprehension of and adherence to discharge instructions for CMC (Patient Medical Complexity Algorithm) were evaluated. Two authors independently screened titles/abstracts and reviewed full-text articles. Two authors extracted data related to study characteristics, methodology, subjects, and results. Fifty-one studies were included. More than half were qualitative or mixed methods studies. Few interventional studies examined objective outcomes. More than half of studies examined instructions for equipment (eg, tracheostomies). Common issues related to access, care coordination, and stress/anxiety. Facilitators included accounting for family context and using health literacy-informed strategies. No randomized trials met inclusion criteria. Several groups (eg, oncologic diagnoses, NICU patients) were not examined in this review. Multiple factors affect comprehension of and adherence to discharge instructions for CMC. Several areas (eg, appointments, feeding tubes) were understudied. Future work should focus on design of interventions to optimize transitions.


Mechanochemical and thermal formation of 1H-benzotriazole coordination polymers and complexes of 3d-transition metals with intriguing dielectric properties.
Liquid-assisted grinding (LAG) reactions have been successfully applied to achieve a series of complexes and coordination polymers based on divalent 3d-transition metal chlorides (TM chlorides) and the aromatic ligand 1H-benzotriazole (BtzH). The obtained substances were investigated via single crystal X-ray, powder X-ray determination and simultaneous DTA/TG analysis as model compounds for structural and chemical influences on their dielectric properties. Depending on the synthesis method, different constitutions and structures are observed. Two polymorphous forms of the 1D polymer [MnCl2(BtzH)2] (1 and 2) as well as the complexes [ZnCl2(BtzH)2]·BtzH (3) and [CoCl2(BtzH)2]·BtzH (4) have been obtained as phase-pure bulk substances via the mechanochemical LAG route, and even single crystals are available. For comparison, thermal reactions were also carried out and have led to the formation of the neutral complexes: [CoCl2(BtzH)2] (5) and [CoCl2(BtzH)4]·4BtzH (6), [ZnCl2(BtzH)2] (7) and the anionic complex BtzH2[CoCl3BtzH] (8). In addition, thermal treatment of 3 yields the benzotriazolium salt {(BtzH)2H}Cl (9). The transition metal compounds were additionally analysed regarding their dielectric properties by frequency-dependent as well as temperature-dependent permittivity investigations. It is intriguing that compounds 1 and 3 show remarkably low dielectric constants and loss factors up to 50 °C highlighting them as potential "low-k materials".


[Visual evoked potential from dura in rats].
Visual evoked potentials (VEPs) were recorded from 8 different points (from points A and B near the bregma to points G and H near the occipital bone) of the dura under parietal bone in rats. The study was performed with 68 adult male Slc: Wistar/ST rats weighing 259.9-298.0g. VEPs recorded from the dura had a large negative component with a peak around 45 msec (N1), a large positive component with a peak around 75 msec and a large negative component with a peak around 120 msec (N2). Points A and B were not suitable for recording of the VEPs because some rats showed no N2 peak. The amplitude of peaks N1 to P at point E, upper the left optic layer of the superior colliculus, was higher than those from other points. Point E was the best position for recording of the VEP from dura in Slc: Wistar/ST rats.


Activation of the PGI(2)/IP system contributes to the development of circulatory failure in a rat model of endotoxic shock.
Prostacyclin levels are increased in septic patients and several animal models of septic shock, and selective inhibition of cyclooxygenase-2 improved cardiovascular dysfunction in rats treated with lipopolysaccharide (LPS). Here, we examine the specific role of prostacyclin and of the receptor for prostacyclin (IP) in the development of LPS-induced circulatory failure. Intravenous injection of LPS (10 mg/kg) into male Sprague-Dawley rats caused a strong increase in plasma prostacyclin levels, which was paralleled by a decrease in blood pressure and an increase in heart rate. Moreover, LPS injection increased the mRNA expression of the IP receptor in the heart, aorta, lung, liver, adrenal glands, and kidneys. Cotreatment with the IP antagonist CAY-10441 (1, 10, 30, and 100 mg/kg) dose-dependently moderated the LPS-induced changes in mean arterial blood pressure, heart rate, cardiac output, and systemic vascular resistance. The development of cardiovascular failure was ameliorated by CAY-10441 in spite of the typical LPS-induced increases in plasma levels of cytokines and NO. In vitro, cytokines dose- and time-dependently induced IP expression in rat vascular smooth muscle cells. Incubation of cells with the stable IP agonist iloprost in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-mehylxanthine resulted in higher cAMP levels in cytokine-treated cells compared with untreated cells. Taken together, our data demonstrate a prominent role of the prostacyclin/IP system in the development of LPS-induced cardiovascular failure.


Intratracheal antitumor necrosis factor-α antibody attenuates lung tissue damage following cardiopulmonary bypass.
The aim of this study is to investigate the protective effect and underlying mechanism of antitumor necrosis factor-α antibody (TNF-α Ab) on lung tissue injury after cardiopulmonary bypass (CPB). Twenty-eight healthy New Zealand white rabbits were randomly divided into four groups. Group I received only an open chest operation. Groups II-IV all received CPB. Furthermore, groups III and IV received post-CPB endotracheal intubation with phosphate buffered saline or TNF-α Ab (2400 pg/kg), respectively. Perioperative blood neutrophil count, TNF-α level, and malondialdehyde (MDA) levels were determined in both the right and left atriums. Lung water content, TNF-α messenger RNA, protein, apoptosis in situ, and pathomorphological changes were also measured. The results show that TNF-α Ab can significantly inhibit leukocyte accumulation, reduce secretion of TNF-α and MDA, decrease lung tissue apoptosis, and attenuate post-CPB pathomorphological changes. TNF-α Ab administration, however, cannot suppress the expression of TNF-α, suggesting that the protective effects of TNF-α Ab originate from inhibiting the numerous biological functions of TNF-α. Intratracheal TNF-α Ab administration demonstrates a notable protective effect against lung injury after CPB.


Toxic epidermal necrolysis due to lamotrigine in a pediatric patient.
A 12-year-male child developed toxic epidermal necrolysis (TEN) probably due to lamotrigine. The patient was on antiepileptic therapy (sodium valproate and clonazepam) since 6-7 months, and lamotrigine was added in the regimen 1-2 months back. A serious cutaneous reaction is more likely to occur during the first 2 months of starting lamotrigine. The use of lamotrigine as an add-on to valproate may have precipitated the reaction. Other drugs were ruled out based on the incubation period of TEN. Drug interactions should be kept in mind with multiple antiepileptic therapies. The patient died because of the severity of reactions and delay in starting the treatment with steroids. One must be vigilant in early detection of the reaction.


Highly Stereoselective Synthesis of Tetrasubstituted Acyclic All-Carbon Olefins via Enol Tosylation and Suzuki-Miyaura Coupling.
A highly stereocontrolled synthesis of tetrasubstituted acyclic all-carbon olefins has been developed via a stereoselective enolization and tosylate formation, followed by a palladium-catalyzed Suzuki-Miyaura cross-coupling of the tosylates and pinacol boronic esters in the presence of a Pd(OAc)2/RuPhos catalytic system. Both the enol tosylation and Suzuki-Miyaura coupling reactions tolerate an array of electronically and sterically diverse substituents and generate high yield and stereoselectivity of the olefin products. Judicious choice of substrate and coupling partner provides access to either the E- or Z-olefin with excellent yield and stereochemical fidelity. Olefin isomerization was observed during the Suzuki-Miyaura coupling. However, under the optimized cross-coupling reaction conditions, the isomerization was suppressed to <5% in most cases. Mechanistic probes indicate that the olefin isomerization occurs via an intermediate, possibly a zwitterionic palladium carbenoid species.


Phosphodiesterase 8a supports HIV-1 replication in macrophages at the level of reverse transcription.
HIV-1 infected macrophages play a key role in HIV-1 infection. Even during anti-retroviral treatment, macrophages keep producing virus due to suboptimal tissue penetration and reduced efficacy of antiretrovirals. It is therefore of major importance to understand which host factors are involved in HIV-1 replication in macrophages. Previously, we have shown that genetic polymorphisms in phosphodiesterase 8a (PDE8A) are strongly associated with HIV-1 replication in these cells. Here we analyzed the mechanism and regulation of PDE8A in HIV-1 replication in macrophages. PDE8A mRNA expression strongly increases upon differentiation of monocytes into macrophages, which corresponds to the increased susceptibility of mature macrophages to HIV-1. In parallel, expression of microRNA miR-145-5p, predicted to target PDE8A mRNA, strongly decreased. The interaction of miR-145-5p with the 3' UTR of PDE8A mRNA could be experimentally validated, suggesting that indeed miR-145-5p can regulate PDE8A expression levels. Knockdown of PDE8A in macrophages resulted in a decrease in total HIV-1 replication and proviral DNA levels. These observations confirm that PDE8A regulates HIV-1 replication in macrophages and that this effect is mediated through early steps in the viral replication cycle. PDE8A is highly expressed in macrophages, and its expression is regulated by miR-145-5p. Our findings strongly suggest that PDE8A supports HIV-1 replication in macrophages and that this effect is mediated at the level of reverse transcription.


Synthesis of Functional Particles by Condensation and Polymerization of Monomer Droplets in Silicone Oils.
We studied the synthesis of poly(4-vinylpyridine) and poly(2-hydroxyethyl methacrylate) polymer particles in silicone oil using a sequential vapor phase polymerization method in which monomer droplets were first condensed onto a layer of silicone oil and subsequently polymerized via a free radical mechanism. The viscosity of the silicone oil was systematically varied. At lower viscosities, a heterogeneous particle size distribution was produced where small particles were formed by engulfment of the monomer droplets at the liquid surface and large particles were formed by coalescence of the monomer droplets inside the liquid layer. Coalescence could be inhibited by increasing the viscosity of the silicone oil leading to a decreased average radius and a narrower size distribution of the polymer particles. The advantages of our method for the fabrication of polymer particles are that it does not require surfactants or organic solvents.


Use of microaxial flow pumps in adolescents.
The Impella 5.5 has been successfully used in the adult population; however, safety and efficacy data in patients aged less than 18 years are limited. Six pediatric patients, aged 13 to 16 years and weighing 45 to 113 kg, underwent axillary artery graft placement and attempted placement of the Impella 5.5 device at our institution between August 2020 and March 2023. Indications for implantation were heart failure secondary to myocarditis (2), rejection of prior orthotopic heart transplant, idiopathic dilated cardiomyopathy (2), and heart failure after transposition of the great arteries repair. Placement was unsuccessful in a 13.8-year-old female patient due to prohibitively acute angulation of the right subclavian artery, and venoarterial extracorporeal membrane oxygenation cannulation was performed via the axillary graft. In 5 patients with successful Impella 5.5 placement, median duration of support was 13.5 days (range, 7-42 days). One experienced cardiac arrest secondary to coagulation-associated device failure, requiring temporary HeartMate3 implantation. Four patients were bridged to transplant; 3 patients received a transplant directly from Impella 5.5, and 1 patient received a transplant after HeartMate3. The final patient received the HeartMate3 on Impella day 42 and is awaiting transplant. Although exact size cutoffs and anatomy are still being determined, our experience provides a framework for use of the Impella 5.5 in adolescents.


VARIATIONAL DENOISING OF DIFFUSION WEIGHTED MRI.
In this paper, we present a novel variational formulation for restoring high angular resolution diffusion imaging (HARDI) data. The restoration formulation involves smoothing signal measurements over the spherical domain and across the 3D image lattice. The regularization across the lattice is achieved using a total variation (TV) norm based scheme, while the finite element method (FEM) was employed to smooth the data on the sphere at each lattice point using first and second order smoothness constraints. Examples are presented to show the performance of the HARDI data restoration scheme and its effect on fiber direction computation on synthetic data, as well as on real data sets collected from excised rat brain and spinal cord.


The role of fluoroalcohols as counter anions for ion-pairing reversed-phase liquid chromatography/high-resolution electrospray ionization mass spectrometry analysis of oligonucleotides.
Hexafluoroisopropanol (HFIP) has been widely used as a counter anion in the mobile phase for ion-pairing reversed-phase liquid chromatography/mass spectrometry (IP-RP-LC/MS) analysis of oligonucleotides. However, researchers are still searching for improvements to counter anions for LC/MS analysis of oligonucleotides. This study aimed to find alternatives to HFIP for analyzing oligonucleotides. The study was performed using an Agilent 1290 ultra-high-performance liquid chromatography (UHPLC) system coupled to an Agilent 6540 mass spectrometer by using an oligonucleotide BEH C18 column (100 × 2.1 mm, 1.7 μm). Buffer systems containing ion-pairing reagents (triethylamine, tripropylamine, hexylamine, dimethylbutylamine, diisopropylethylamine, N,N-dimethylcyclohexylamine, and octylamine) and fluoroalcohols (HFIP and hexafluoro-2-methyl-2-propanol (HFTP)) were compared chromatographically and mass spectrometrically. Results showed that HFTP has better desalting ability than HFIP, but both HFIP and HFTP have comparable effects on the separation of oligonucleotides sized from 10mer to 40mer for most of ion-pairing reagents, with the exception of triethylamine and N,N-dimethylcyclohexylamine, where HFIP performed better than HFTP. The choice of fluoroalcohols in IP-RP-LC/MS analysis of oligonucleotides depends on the type of ion-pairing reagents used in the mobile phase. As a guideline, we would recommend to use either HA-HFIP or HA-HFTP for small oligonucleotides, but TPA-HFTP for large oligonucleotides for IP-RP-LC/MS analysis of synthetic oligonucleotides.


Cyberbullying among Adolescents: Psychometric Properties of the CYB-AGS Cyber-Aggressor Scale.
The present study aims to analyze the psychometric properties of the revised version of the Adolescent Cyber-Aggressor scale (CYB-AGS). This scale is composed of 18 items that measure direct and indirect cyberbullying. A cross-sectional study was conducted using two independent samples of adolescents. The first sample included 1318 adolescents (52.6% girls) from 12 to 16 years old (M = 13.89, SD = 1.32). The second sample included 1188 adolescents (48.5% boys) from 12 to 16 years old (M = 14.19, SD = 1.80). First, to study the psychometric properties of the CYB-AGS, exploratory factor analysis was performed on Sample 1. Results indicated a two-factor structure: direct cyber-aggression and indirect cyber-aggression. Second, to verify the structure of the CYB-AGS, we selected Sample 2 to conduct confirmatory factor analysis and test the scale's convergent validity with theoretically-related measures. Results confirmed the reliability and validity of the two-dimensional model. Moreover, measurement invariance was established. Finally, regarding convergent validity, positive correlations were obtained between cyberbullying and aggressive behaviors in school, anger expression, negative attitudes towards school, and transgression of norms. Furthermore, negative correlations were found between cyberbullying and attitudes towards institutional authority.


Experimental gastroesophageal reflux in the Australian brush-tailed possum.
It has been suggested that the lower esophageal sphincter (LES) plays an important role in preventing gastroesophageal reflux. This study was designed to determine if abolition of the LES alone is sufficient to induce gastroesophageal reflux and esophagitis. Studies were performed in the Australian brush-tailed possum (Trichosurus vulpecula) which has a lower esophagus resembling that of man. Esophageal manometry, esophagoscopy, and contrast radiography of the lower esophagus and stomach were performed before and after surgery in a group of animals undergoing cardioplasty and in a group of sham operated control animals. In the animals undergoing cardioplasty, LES pressure fell from a preoperative level of 12.6 +/- 1.3 mm Hg to 0 mm Hg. This was followed by the development of gastroesophageal reflux and esophagitis. Sham operation did not alter LES pressure or result in either gastroesophageal reflux or esophagitis. In 4 of 5 animals undergoing cardioplasty, LES activity returned after 10 weeks, and this time gastroesophageal reflux ceased and esophagitis healed. It is concluded that abolition of the LES alone can induce gastroesophageal reflux and esophagitis.


Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins.
Diverse subtypes of voltage-gated sodium channels (VGSCs) have been found throughout tissues of the brain, muscles and the heart. Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch (BmK) act as sodium channel-specific modulators and have therefore been widely used to study VGSCs. α-type neurotoxins, named BmK I, BmK αIV and BmK abT, bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs. In contrast, β-type neurotoxins, named BmK AS, BmK AS-1, BmK IT and BmK IT2, occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels. Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs, however, indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simple α-type and β-type neurotoxin distinction. Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region- and/or species-specific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs. In this review, we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3- or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.


Bioactive Compounds from the Aerial Parts of Evolvulus linarioides.
Three new caryophyllane-type sesquiterpenoids, linariophyllenes A-C (1-3), two new hamamelitol derivatives, linaritols A (4) and B (5), two new chromones, linariosides A (6) and B (7), and three known chromones, cnidimol C (8), monnieriside A (9), and undulatoside A (10), were identified from the aerial parts of Evolvulus linarioides. The structures of these compounds were elucidated by NMR, MS, and IR data. The absolute configurations of compounds 1-5 and 7 were established via electronic circular dichroism data. The anti-inflammatory potential of compounds 1-5 and 7-10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and proinflammatory cytokine IL-1β by stimulated J774 macrophages. Compounds tested at noncytotoxic concentrations inhibited NO production by macrophages, exhibiting IC50 values between 17.8 and 66.2 μM, and inhibited IL-1β production by stimulated macrophages by 72.7-96.2%.


Cheap and long-life reusable polymer for asymmetric organozinc catalysis based on camphor-derived hydroxyamides.
Polystyrene grafted with a chiral zinc-complexing camphor-derived N,N-disubstituted hydroxyamide is proposed as a new type of functional polymer of high reusability for the development of sustainable organozinc-catalyzed asymmetric reactions. The main goal of this new functional polymer is the ease of the hydroxyamide-moiety preparation (cheap chiral ligand obtained straightforwardly from an enantiopure starting material coming from the chiral pool), as well as its chemical robustness when compared with other related zinc-complexing functional groups. The latter allows the polymer to be active after multiple applications, without significant loss of its catalytic activity. This fact is exemplified by the design and preparation of a polymer functionalized with a bis(hydroxyamide) proved previously as active in the homogeneous enantioselective addition of diethylzinc to aldehydes. The result is a cheap functional polymer with a very high reusability (the enantioselectivity and chemical yield are maintained practically constant after 20 applications). Additionally, a methodology for the multicycle use of these functional polymers is presented.


[Fallacies in arterial blood gas interpretation].
The arterial blood gas analysis (ABGA) is a valuable diagnostic tool in daily clinical practice. It yields information about oxygenation, ventilation and acid-base status. ABGAs should always be interpreted within a clinical context. If a result is absolutely not compatible with a clinical situation, the probe should be repeated or prompt further differential diagnoses. A probe should be free of air bubbles and be rapidly proceeded in the laboratory. Body temperature and fraction of inspired oxygen are mandatory prerequisites for adequate interpretation. With CO-oximetry, not only oxygenated hemoglobin but also carboxihemoglobin and met-hemoglobin content can be measured in the case of a suspected intoxication. For the assessment of ventilation, PaCO2 must be interpreted in the context of PaO2, as already a "normal value" of PaCO2 may indicate severe ventilator failure in a patient with hypoxemia. A normal pH does not exclude acid-base disorders, PaCO2 and bicarbonate must also be taken into account. When FIO2 is changed, steady state conditions must be awaited before a next control especially in the case of ventilation-perfusion mismatch, e. g. in COPD, pneumonia, pulmonary embolism. In a hypoxic state, immediate application of oxygen is warranted, in hypercapnia, ventilation should be increased. In acid-base disorders, treatment of the underlying disease is most often conducive.


Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain.
Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 ± 0.55 vs 1.64 ± 0.22; parietal, 2.50 ± 0.52 vs 1.74 ± 0.22; posterior cingulate, 2.84 ± 0.59 vs 1.73 ± 0.22; and WM in the centrum semiovale, 2.21 ± 0.53 vs 2.42 ± 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.


Fetal Programming of Renal Dysfunction and High Blood Pressure by Chronodisruption.
Adverse prenatal conditions are known to impose significant trade-offs impinging on health and disease balance during adult life. Among several deleterious factors associated with complicated pregnancy, alteration of the gestational photoperiod remains largely unknown. Previously, we reported that prenatal manipulation of the photoperiod has adverse effects on the mother, fetus, and adult offspring; including cardiac hypertrophy. Here, we investigated whether chronic photoperiod shifting (CPS) during gestation may program adult renal function and blood pressure regulation. To this end, pregnant rats were subjected to CPS throughout pregnancy to evaluate the renal effects on the fetus and adult offspring. In the kidney at 18 days of gestation, both clock and clock-controlled gene expression did not display a daily pattern, although there were recurrent weaves of transcriptional activity along the 24 h in the control group. Using DNA microarray, significant differential expression was found for 1,703 transcripts in CPS relative to control fetal kidney (835 up-regulated and 868 down-regulated). Functional genomics assessment revealed alteration of diverse gene networks in the CPS fetal kidney, including regulation of transcription, aldosterone-regulated Na+ reabsorption and connective tissue differentiation. In adult offspring at 90 days of age, circulating proinflammatory cytokines IL-1β and IL-6 were increased under CPS conditions. In these individuals, CPS did not modify kidney clock gene expression but had effects on different genes with specific functions in the nephron. Next, we evaluated several renal markers and the response of blood pressure to 4%NaCl in the diet for 4 weeks (i.e., at 150 days of age). CPS animals displayed elevated systolic blood pressure in basal conditions that remained elevated in response to 4%NaCl, relative to control conditions. At this age, CPS modified the expression of Nhe3, Ncc, Atp1a1, Nr3c1 (glucocorticoid receptor), and Nr3c2 (mineralocorticoid receptor); while Nkcc, Col3A1, and Opn were modified in the CPS 4%+NaCl group. Furthermore, CPS decreased protein expression of Kallikrein and COX-2, both involved in sodium handling. In conclusion, gestational chronodisruption programs kidney dysfunction at different levels, conceivably underlying the prehypertensive phenotype observed in the adult CPS offspring.


[Amrinone (Wincoram)--a new positive inotropic and vasodilator agent].
The bipyridine derivative amrinone is a specific phosphodiesterase III blocking agent. In vitro and in vivo studies show a dose-dependent increase in myocardial contractility induced by amrinone. In patients with congestive heart failure, the inotropic and vasodilator effects of amrinone contribute to cardiac improvement. When amrinone is used, the increase in myocardial oxygen consumption due to increased contractility is offset by the reductions in preload and afterload. In hearts with very high wall tension, myocardial oxygen consumption may even decrease with amrinone. Amrinone therapy is not accompanied by significant increases in heart rate. Tachyphylaxis has not been observed. The elimination half-life ranges between 2.5 and 3.5 h. A large quantity of amrinone is excreted unchanged, and therefore in cases of renal impairment the possibility of cumulation exists. The main adverse reaction of amrinone is a reversible thrombocytopenia induced by a dose-dependent decrease in platelet survival time. Therefore, frequent platelet counts are necessary when amrinone is administered. Numerous studies in patients with chronic congestive heart failure confirmed the beneficial hemodynamic effects of amrinone. Experience in the treatment of acute perioperative heart failure with amrinone are still limited, but the present results are encouraging; an additive effect of amrinone to catecholamines seems especially promising in the therapy of severe postoperative low-cardia-output syndrome.


JC polyomavirus viremia and progressive multifocal leukoencephalopathy in human leukocyte antigen-sensitized kidney transplant recipients desensitized with intravenous immunoglobulin and rituximab.
Desensitization (DES) with intravenous immunoglobulin (IVIG) + rituximab is effective, safe, and increases the transplantation rate in human leukocyte antigen-sensitized patients. However, reports of progressive multifocal leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV) in autoimmune patients treated with rituximab is concerning. Here, we report on the JCPyV viremia and PML status in kidney transplant patients with/without DES (non-DES). In total 1195 and 699 DNA samples from plasma in 117 DES (78% lymphocyte-depleting [LyD] induction) and 100 non-DES patients (45% LyD), respectively, were submitted for JCPyV-polymerase chain reaction. Results were compared in both groups. No patients in either DES or non-DES developed PML or presented with any neurological symptoms. The JCPyV viremia rate was similar in DES and non-DES patients (3/117 vs. 9/100, P = 0.07). The JCPyV levels were low (median peak levels, 1025 copies/mL) and JCPyV viremia was observed only once during the study period in most patients. All 3 DES patients with JCPyV(+) received 1 dose rituximab and no DES patients with >1 dose rituximab showed JCPyV(+). All 3 JCPyV(+) DES patients received LyD induction, while only 2 of 9 JCPyV(+) non-DES patients did so, and the remaining 7 received non-LyD or no induction. JCPyV in leukocyte was mostly negative in DES and non-DES patients. Immunosuppression in patients with or without JCPyV(+) was similar. BK polyomavirus viremia was observed more commonly in patients with JCPyV(+) than in those without (P < 0.02). Patients with IVIG + rituximab DES followed by transplantation with LyD induction and additional rituximab rarely show JCPyV viremia and appear at low risk for PML.


Mammalian 3-oxosteroid delta4-delta5-isomerase. A membrane-bound enzyme. II. Activation by divalent cations.
Alkaline-earth ions (Mg2+, Ca2+ and Sr2+) have two specific effects on the kinetic parameters of the beef adrenal 3-oxosteroid delta4-delta5-isomerase activity in the microsomes and in the particles obtained after disrupting the membrane structure by action of 1 M MgCl2. On the microsomal enzyme, a 2-fold increase of V is observed with the three cations under study. The small difference in the effect of the three ions could be related to their hydration energy. It is suggested that the interaction of the ion with water is the determinant step of the activation mechanism and not the fixation of the ion on the enzyme or on some others possible binding sites in this system. With the enzyme in the proteolipidic particles, the use of EDTA as a chelating agent for the cations present in the enzymatic assay, allows the characterization of two effects: at low concentration of EDTA, an increase of Km is observed and at higher concentration (2 mM), V is decreased. A subsequent addition of Mg2+ leads to an activation in two steps: V is increased in the first step without change in Km, the second step consists of a decrease of Km without any change in V. A relation between the structural perturbations induced by the ions (Gallay, J., Vincent, M. and Alfsen, A. (1975) Biochim. Biophys. Acta 397, 489-500) and their kinetic effect on the enzymatic reaction is established.


Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis.
Articular cartilage is routinely subjected to mechanical forces and growth factors. Adipose-derived stem cells (ASCs) are multi-potent adult stem cells and capable of chondrogenesis. In the present study, we investigated the comparative and interactive effects of dynamic compression and insulin-like growth factor-I (IGF-I) on the chondrogenesis of rabbit ASCs in chitosan/gelatin scaffolds. Rabbit ASCs with or without a plasmid overexpressing of human IGF-1 were cultured in chitosan/gelatin scaffolds for 2 days, then subjected to cyclic compression with 5% strain and 1 Hz for 4 h per day for seven consecutive days. Dynamic compression induced chondrogenesis of rabbit ASCs by activating calcium signaling pathways and up-regulating the expression of Sox-9. Dynamic compression plus IGF-1 overexpression up-regulated expression of chondrocyte-specific extracellular matrix genes including type II collagen, Sox-9, and aggrecan with no effect on type X collagen expression. Furthermore, dynamic compression and IGF-1 expression promoted cellular proliferation and the deposition of proteoglycan and collagen. Intracellular calcium ion concentration and peak currents of Ca(2+) ion channels were consistent with chondrocytes. The tissue-engineered cartilage from this process had excellent mechanical properties. When applied together, the effects achieved by the two stimuli (dynamic compression and IGF-1) were greater than those achieved by either stimulus alone. Our results suggest that dynamic compression combined with IGF-1 overexpression might benefit articular cartilage tissue engineering in cartilage regeneration.


A mixed methods study of multiple health behaviors among individuals with stroke.
Individuals with stroke often have multiple cardiovascular risk factors that necessitate promoting engagement in multiple health behaviors. However, observational studies of individuals with stroke have typically focused on promoting a single health behavior. Thus, there is a poor understanding of linkages between healthy behaviors and the circumstances in which factors, such as stroke impairments, may influence a single or multiple health behaviors. We conducted a mixed methods convergent parallel study of 25 individuals with stroke to examine the relationships between stroke impairments and physical activity, sleep, and nutrition. Our goal was to gain further insight into possible strategies to promote multiple health behaviors among individuals with stroke. This study focused on physical activity, sleep, and nutrition because of their importance in achieving energy balance, maintaining a healthy weight, and reducing cardiovascular risks. Qualitative and quantitative data were collected concurrently, with the former being prioritized over the latter. Qualitative data was prioritized in order to develop a conceptual model of engagement in multiple health behaviors among individuals with stroke. Qualitative and quantitative data were analyzed independently and then were integrated during the inference stage to develop meta-inferences. The 25 individuals with stroke completed closed-ended questionnaires on healthy behaviors and physical function. They also participated in face-to-face focus groups and one-to-one phone interviews. We found statistically significant and moderate correlations between hand function and healthy eating habits (r = 0.45), sleep disturbances and limitations in activities of daily living (r = - 0.55), BMI and limitations in activities of daily living (r = - 0.49), physical activity and limitations in activities of daily living (r = 0.41), mobility impairments and BMI (r = - 0.41), sleep disturbances and physical activity (r = - 0.48), sleep disturbances and BMI (r = 0.48), and physical activity and BMI (r = - 0.45). We identified five qualitative themes: (1) Impairments: reduced autonomy, (2) Environmental forces: caregivers and information, (3) Re-evaluation: priorities and attributions, (4) Resiliency: finding motivation and solutions, and (5) Negative affectivity: stress and self-consciousness. Three meta-inferences and a conceptual model described circumstances in which factors could influence single or multiple health behaviors. This is the first mixed methods study of individuals with stroke to elaborate on relationships between multiple health behaviors, BMI, and physical function. A conceptual model illustrates addressing sleep disturbances, activity limitations, self-image, and emotions to promote multiple health behaviors. We discuss the relevance of the meta-inferences in designing multiple behavior change interventions for individuals with stroke.


Consumer-Brand Relationships under the Marketing 3.0 Paradigm: A Literature Review.
Consumer-brand relationships encompass several dimensions, most of which have attracted growing research attention during the last years. Building these relationships is especially important in the marketing 3.0 era, where it is suggested that customers will choose those brands that satisfy their deepest needs. With these ideas in mind, this article provides a review of two key concepts implied in such relationships: brand love and customer engagement. Although both conceptions focus on different stages of consumer-brand relationships, they actually cover different perspectives on the same process. Moreover, they come from diverse conceptual paradigms: whilst brand love comes from the psychology discipline, engagement derives from diverse areas of the marketing field (e.g., the service-dominant logic perspective). However, their further empirical developments have taken place in marketing. Besides, both terms appear to be applied to different empirical perspectives: brand love is usually linked to the Fast Moving Consumer Goods industry and customer engagement to services.


Cavernous hemangioma of the dura mater mimicking meningioma.
Cavernomas are benign lesions that most commonly occur intra-parenchymally, but occasionally they have been described as arising from the dura mater. Extra-axial cavernous angiomas (or hemangiomas) account for 0.4-2% of all intracranial vascular malformations, and they usually occur in the middle cranial fossa, associated with the cavernous sinus. Other possible localizations (e.g. tentorium, convexity, anterior cranial fossa, cerebellopontine angle, Meckel's cave, sella turcica and internal auditory meatus) are rare, and they account only for 0.2-0.5%. We report a case of a 30-year-old female presenting with a 2 years history of headache unresponsive to drug therapy. The magnetic resonance imaging showed a dural-based lesion in the left frontal region; the lesion size was: 1.5 cm × 3.5 cm. The appearance suggested a convexity meningioma. A left frontal craniotomy was performed, and the histopathological diagnosis deposed for a cavernous hemangioma of the dura mater. The follow-up at 1-year was good without any neurologic deficit. Dural-based cavernous hemangiomas of the convexity are uncommon lesions. Up to now, only 13 cases have been described in the literature. The authors have discussed clinical aspects, radiological features, surgical treatment, and operative findings.


Gallic esters of sucrose as efficient radical scavengers in lipid peroxidation.
Three tests of increasing complexity were used to assess the antioxidant activity of five synthetic gallic esters of sucrose bearing 3, 6, 7, or 8 galloyl units. In addition, two of these compounds had 1 or 2 hydrocarbon (C10-C12) acyl chains. Reaction with the DPPH radical led to the evaluation of the number of radicals trapped per galloyl unit n (3-4), as well as the apparent second-order rate constant for H atom donation k (1200-1500/M/s). These results indicated similar contribution and reactivity of all the galloyl units. Inhibition of the AAPH-initiated peroxidation of linoleic acid in a micellar medium confirmed the additive contribution of the galloyl units, whereas the presence of the hydrocarbon acyl chains had no influence. These results suggest an inhibition of initiation at high antioxidant levels and an underlying prooxidant effect of the galloyl radicals at low concentrations. Finally, LDL peroxidation was inhibited in proportion to the number of galloyl units, in agreement with the preceding tests.


Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent.
We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults. We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40-75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates. Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS. Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.


[Evaluation of the role of Campylobacter spp. in the occurrence of foodborne diseases and modern methods to detect the pathogen].
Infections caused by Campylobacter spp. are now considered to be one of the most important foodborne diseases worldwide, this organism is one of the most epidemiologically significant zoonotic pathogens. Among these pathogens Campylobacter jejuni have the greatest epidemiological importance, they are responsible for 90% of laboratory confirmed cases of food campylobacteriosis. The frequency of detection of campylobacters in the environmental and on many raw foods, of both plant and animal origin, in normal intestine biota of domestic and wild animal and birds, indicates the prevalence of these bacteria and the high risk of contamination of food and water. The main factors of transmission in sporadic campylobacteriosis are the poultry and poultry products (up to 70% of the total number of cases), water (8%), raw milk (5%). One of the risk factors for the spread of emergent pathogen is its ability to persist in aquatic ecosystems. Continuing changes in landscape and agricultural intensification can cause further enhance microbial contamination of freshwater bodies and groundwater, and the associated increase in the number of cases of waterborne campylobacteriosis. Intensification of agriculture, expanding the range of applied disinfectants and antiseptics, uncontrolled use of antibiotics in livestock often leads to the selection of the sustainable strains of Campylobacter spp., which have antibiotic resistance and multiple virulence determinants. This paper presents an overview of modern methods for the detection of Campylobacter spp., detailed culture and biochemical methods for the isolation of C. jejuni based on the use of selective culture media and diagnostic kits for the characterization of the phenotypic profiles of the strains. These methods are the starting point in selecting the most effective schemes of food control and surveillance. It is emphasized that the basis of microbiological analysis should be molecular methods based on real-time PCR, which allows to quantify present in foods of thermotolerant Campylobacter, including C. jejuni.


Dural entrance of the bridging vein into the transverse sinus provides a reliable measure for preoperative planning: an anatomic comparison between cadavers and neuroimages.
Understanding the anatomy of the transverse sinus and its associated bridging veins (BVs) is essential to approaching the posterior and middle incisural space. The venous phase of neuroimages has received increasing attention in preoperative planning. The aims of this study are to identify anatomic features of the dural entrance of the BVs into the transverse sinus on the cadaver and to correlate such features with those of digital subtraction angiography (DSA), computed tomographic venography (CTV), and magnetic resonance venography (MRV). A total of 30 adult cadavers and 76 patients were examined through anatomic dissection and DSA, CTV, and MRV, respectively. The number, diameter, and location of the BVs entering the sinus were measured, and comparisons were made between the cadavers and neuroimages. We found that the way BVs entered the transverse sinus varied but was identifiable in DSA, CTV, and MRV images. Compared with the cadavers, DSA, CTV, and MRV revealed less than 50% of the BV entering the sinus because the smaller BVs were not seen on the neuroimages. However, the distribution pattern of the dural entrance of the BVs into the transverse sinus was relatively consistent between cadavers and neuroimages. Unique anatomic features of the dural entrance of a BV into the transverse sinus in the cadaver correspond to those evident in neuroimages; thus, identification of the dural entrance of the BVs with neuroimaging modalities provides a reliable measure for preoperative planning.


Incidence of hip fracture in Romania and the development of a Romanian FRAX model.
A FRAX(®) model for Romania calibrated to the total Romanian population was released June 1, 2011. This article describes the data used to develop the Romanian FRAX model and illustrates its features compared to models for other countries. Age- and sex-stratified hip fracture incidence rates and mortality rates for 2010 were extracted from nationwide databases from the age of 40 years. For other major fractures, Romanian incidence rates were imputed, using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm, and clinically symptomatic vertebral fractures). Fracture incidence rates increased with increasing age: for hip fracture, incidence rates were higher among younger men than women but with a female preponderance from the age of 65 years. The 10-year probability of hip or major fracture was increased in patients with a clinical risk factor (CRF), lower BMI, female gender, higher age, and decreased BMD T score. Of the CRFs, a parental hip fracture accounted for the greatest increase in 10-year fracture probability. The Romanian FRAX tool is the first country-specific fracture prediction model. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Romanian FRAX tool a good candidate for implementation into clinical practice.


Effects of perindopril on glucose and lipid metabolism in patients with mild-to-moderate essential hypertension and glucose intolerance.
The effect of perindopril, an angiotensin-converting enzyme inhibitor, on glucose and lipid metabolism was evaluated in 12 patients with mild-to-moderate essential hypertension and glucose intolerance. Perindopril was administered at a dosage of 2 to 8 mg once daily for 12 weeks. Both the systolic and diastolic blood pressures were significantly reduced throughout the treatment period. There were no significant changes in the insulinogenic index (delta plasma immunoreactive insulin/delta plasma glucose) calculated from the results of 75-g oral glucose tolerance tests performed before and after perindopril treatment. Serum levels of glycosylated hemoglobin, fructosamine, lipids, lipoproteins, and apolipoproteins were also not affected. These results suggest that perindopril can be used effectively to treat hypertension in patients with glucose intolerance without affecting glucose and lipid metabolism.


Transarterial angioembolization versus surgery after failed endoscopic therapy for non-variceal upper gastrointestinal bleeding.
To compare the outcome of transarterial angioembolization (TAE) and surgery with endoscopically unmanageable non-variceal hemorrhage of the upper gastrointestinal tract. A case note review of all patients treated for non-variceal upper gastrointestinal bleeding from January 2006 till January 2012 was performed. Fifty-four of 667 patients with non-variceal bleeding did not respond to endoscopic treatment. Nine of the 54 patients had incomplete data, leaving 45 patients in the study; 24 had angiography and another 21 had surgery. The two groups were broadly similar in terms of relevant clinical variables. Nineteen of 24 having angiography had embolisation. Re-bleeding recurred in 8 patients (33%) in the TAE group and 6 patients (28.6%) in the surgery group (p = 0.28). There was no statistically significant difference in post procedural complications (81% vs 62.5%, p = 0.17), 30-day mortality (33% vs 29.1%, p = 0.17 ) units of blood transfused (12.24 vs 8.92, p = 0.177) and mean hospital stay (30.7 vs 22.9 days, p = 0.281) observed in patients undergoing surgery as compared to TAE. TAE and surgery have similar outcomes in patients with endoscopically unmanageable non-variceal upper gastrointestinal haemorrhage.


Fetal rat intestinal absorption of horseradish peroxidase from swallowed amniotic fluid.
Horseradish peroxidase (HRP) injected into amniotic fluid is swallowed by rat fetuses and within 3-6 h reaches the gut lumen. This macromolecular protein is then absorbed by the columnar lining cells via a system of apical cytoplasmic tubules formed by invaginations of the plasma membrane. From cytoplasm subjacent to the brush border HRP is transported, within vacuoles, to the supranuclear region, where some is retained for at least 18 h, and to interepithelial spaces. Extracellular enzyme is then found throughout the epithelial basement membrane and between connective tissue cells of the mucosal and submucosal layers Finally, HRP can be detected within lumina of blood and lymphatic capillaries, strongly suggesting that it is transported from the intestine to the circulation.


The effect of environmental temperature and body weight on growth rate and feed:gain of male broilers.
High environmental temperatures are detrimental to the growth and feed:gain of broilers. The objective of this research was to determine the effects of incremental differences in environmental temperature on growth and feed:gain. The data are needed for decisions about the profitability of energy inputs when managing the housing environment. In Trial 1, broiler chicks were reared as a group to 21 d on litter with constant lighting and with water and feed available for ad libitum consumption. They were then moved to 10 environmental chambers. Each chamber was set at a different temperature ranging from 21.1 C to 31.1 C in 1.11 C increments. Weight gain and feed:gain were determined when the broilers were 28, 35, and 42 d old. In Trials 2 and 3, broilers were placed in the environmental chambers, and weight gain and feed:gain were determined for the 42 to 49 d period. The data were analyzed statistically, and regression equations were obtained for growth and feed:gain. Equations were based on body weight and temperature, and the body weight equation was plotted as grams gain per bird per day. Feed:gain was plotted for that body weight and temperature. Body weight gain per day increased to a maximum with increasing weight and then declined. The body weight at the maximum rate of gain was inversely related to temperature. Feed:gain increased as body weight increased. Feed:gain was directly related to temperature at weights above 800 g and the effect of temperature increased as body weight increased. The data will be useful for the evaluation of various management scenarios to determine the inputs that are profitable.


High-resolution MRI in evaluation of the surgical anatomy of the esophagus and posterior mediastinum.
The purpose of this study was to use high-resolution MRI to evaluate the surgical anatomy of the posterior mediastinum, in particular the esophagus and its relation to the surrounding structures. The aim was to familiarize radiologists with the appearance of structures considered important in planning surgical resection of the esophagus. The thoraces of two cadavers were imaged with a 1.5-T magnet using a high-resolution T2-weighted sequence. Axial cadaveric sections of the posterior mediastinum were cut with a band saw at levels determined from the MR images, and histologic whole-mount sections of the esophagus and surrounding tissue were prepared from the cadaveric sections. The appearance of structures identified on the MR images was compared with the findings on corresponding gross anatomic and histologic whole-mount sections. The MR images depicted the esophagus and structures in close anatomic relation: the pleural reflections and pericardium. The technique enabled visualization of structures to our knowledge not previously described on cross-sectional imaging: the individual layers of the esophageal wall, the thoracic duct, a connective tissue layer attaching the esophagus to the anterior wall of the aorta, and a fascial plane passing between layers of the right and left parietal pleura posterior to the esophagus. High-resolution MRI of the posterior mediastinum provides detailed anatomic information, delineating structures not visible on other forms of cross-sectional imaging. It can provide important information for planning surgical intervention.


The relationship between crystal structure and methyl and t-butyl group dynamics in van der Waals organic solids.
We report x-ray diffractometry in a single crystal of 2-t-butyl-4-methylphenol (TMP) and low-frequency solid state nuclear magnetic resonance (NMR) proton relaxometry in a polycrystalline sample of TMP. The x-ray data show TMP to have a monoclinic, P2(1)/c, structure with eight molecules per unit cell and two crystallographically inequivalent t-butyl group (C(CH(3))(3)) sites. The proton spin-lattice relaxation rates were measured between 90 and 310 K at NMR frequencies of 8.50, 22.5, and 53.0 MHz. The relaxometry data is fitted with two models characterizing the dynamics of the t-butyl groups and their constituent methyl groups, both of which are consistent with the determined x-ray structure. In addition to presenting results for TMP, we review previously reported x-ray diffractometry and low-frequency NMR relaxometry in two other van der Waals solids which have a simpler structure. In both cases, a unique model for the reorientational dynamics was found. Finally, we review a similar previously reported analysis in a van der Waals solid with a very complex structure in which case fitting the NMR relaxometry requires very many parameters and serves mainly as a flag for a careful x-ray diffraction study.


Recent strategies to develop polysaccharide-based nanomaterials for biomedical applications.
Polysaccharides are abundant in nature, renewable, nontoxic, and intrinsically biodegradable. They possess a high level of functional groups including hydroxyl, amino, and carboxylic acid groups. These functional groups can be utilized for further modification of polysaccharides with small molecules, polymers, and crosslinkers; the modified polysaccharides have been used as effective building blocks in fabricating novel biomaterials for various biomedical applications such as drug delivery carriers, cell-encapsulating biomaterials, and tissue engineering scaffolds. This review describes recent strategies to modify polysaccharides for the development of polysaccharide-based biomaterials; typically self-assembled micelles, crosslinked microgels/nanogels, three-dimensional hydrogels, and fibrous meshes. In addition, the outlook is briefly discussed on the important aspects for the current and future development of polysaccharide-based biomaterials, particularly tumor-targeting intracellular drug delivery nanocarriers.


Unilateral and pruritic papules: segmental Darier-White disease.
Darier-White disease is an uncommon disorder, which presents in a localized pattern in about 10% of patients, usually without nail, mucosa, or acral involvement. Type-1 is the most common of the segmental Darier-White disease types: papules have unilateral distribution along Blaschko lines. A 36-year-old woman diagnosed with type-1 segmental Darier-White disease is reported herein.


Microwave thawing and green tea extract efficiency for the formation of acrylamide throughout the production process of chicken burgers and chicken nuggets.
Initially, we measured the acrylamide (AA) levels of chicken burgers (CBs) and chicken nuggets (CNs) purchased from fast food restaurants. After the determination of AA in these products, we aimed to investigate whether the use of green tea extract in the covering material, and microwave thawing before frying, mitigated the formation of AA in CBs and CNs during the production process. According to our study, AA concentrations of CBs and CNs purchased from fast food restaurants were in the range of 13.43-118.97 and 32.92-134.90 ng g-1 coating, respectively. In our experiment, AA levels varied between 19.61 and 40.08 ng g-1 coating for CBs and 7.92-49.60 ng g-1 coating for CNs. Green tea extract reduced the AA formation in CBs and CNs at the pan frying and steam oven cooking heat treatment steps (P < 0.05). However, microwave thawing did not affect AA level of CBs and CNs. When the AA levels of commercial CBs and CNs are compared with those produced in our experiment, the use of green tea extract could be a novel, easy and practical application for fast food producers to minimise AA levels in the first two steps of the production without changes to the sensory properties of the final products. © 2016 Society of Chemical Industry.


Ectopic pregnancy: features at transvaginal sonography.
A retrospective review of the transvaginal sonograms of 50 women with laparoscopically confirmed ectopic pregnancy was performed to determine whether certain sonographic findings can be detected to confirm the diagnosis. Forty-seven of the 50 pregnancies were tubal. A tubal ring (a 1-3-cm mass consisting of a 2-4-mm concentric, echogenic rim of tissue surrounding a hypoechoic center) was seen in 23 of 34 (68%) ectopic pregnancies in which the fallopian tube had not ruptured, and the tubal ring could be distinguished from a corpus luteum cyst in most cases. Transvaginal sonography also depicted simple (n = 22) or particulate (bloody) (n = 13) peritoneal fluid associated with ectopic pregnancy. In each case in the series, at least one abnormal uterine, adnexal, or peritoneal finding was detected at transvaginal sonography. Because of its improved resolution of uterine and adnexal structures, transvaginal sonography is recommended as a means for detailed evaluation of patients suspected of having an ectopic pregnancy.


An Automated MR Image Segmentation System Using Multi-layer Perceptron Neural Network.
Brain tissue segmentation for delineation of 3D anatomical structures from magnetic resonance (MR) images can be used for neuro-degenerative disorders, characterizing morphological differences between subjects based on volumetric analysis of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF), but only if the obtained segmentation results are correct. Due to image artifacts such as noise, low contrast and intensity non-uniformity, there are some classification errors in the results of image segmentation. An automated algorithm based on multi-layer perceptron neural networks (MLPNN) is presented for segmenting MR images. The system is to identify two tissues of WM and GM in human brain 2D structural MR images. A given 2D image is processed to enhance image intensity and to remove extra cerebral tissue. Thereafter, each pixel of the image under study is represented using 13 features (8 statistical and 5 non- statistical features) and is classified using a MLPNN into one of the three classes WM and GM or unknown. The developed MR image segmentation algorithm was evaluated using 20 real images. Training using only one image, the system showed robust performance when tested using the remaining 19 images. The average Jaccard similarity index and Dice similarity metric for the GM and WM tissues were estimated to be 75.7 %, 86.0% for GM, and 67.8% and 80.7%for WM, respectively. The obtained performances are encouraging and show that the presented method may assist with segmentation of 2D MR images especially where categorizing WM and GM is of interest.


Intrathyroidal thyroglossal duct cyst presenting as a thyroid nodule.
A 50-year-old woman presented with a lateral neck swelling, clinically indistinguishable from solitary thyroid nodule. A right hemithyroidectomy was performed and microscopy revealed an intrathyroidal thyroglossal cyst. Intrathyroidal thyroglossal cyst should be considered in the differential diagnosis of a thyroid nodule.


Gd³⁺ Tethered Gold Nanorods for Combined Magnetic Resonance Imaging and Photo-Thermal Therapy.
Near infrared (NIR) mediated photothermal therapy and magnetic resonance imaging (MRI) are promising treatment and imaging modalities in the field of cancer theranostics. Gold nanorods are the first choice of materials for NIR-mediated photothermal therapy due to their strong localized surface plasmon resonance (LSPR) at NIR region. Similarly, gadolinium based MRI contrast agents have an ability to increase the ionic and molecular relaxivity, thereby enhancing the solvent proton relaxation rate resulting in contrast enhancement. Herein, the effort has been made to engineer a dual front theranostic agent with combined photothermal and magnetic resonance imaging capacity using gadolinium tethered gold nanorods (Gd3+-AuNR). NIR-responsive gold nanorods were surface fabricated by means of Au-thiol interaction using a thiolated macrocyclic chelator that chelates Gd3+ ions, and further stabilized by thiolated polyethylene glycol (PEG-SH). The magnetic properties of the Gd3+-AuNR displayed an enhanced r 1 relaxivity of 12.1 mM–1s–1, with higher biological stability, and contrast enhancement in both solution state and in cell pellets. In-vitro (cell-free) and ex-vivo (on pig skin) analysis of the Gd3+-AuNR shows enhanced photothermal properties as equivalent to that of the raw AuNR. Furthermore, Gd3+-AuNR showed competent cellular entry and intracellular distribution as revealed by hyperspectral microscopy. In addition, Gd3+-AuNR also exhibits significant thermal ablation of B16–F10 cells in the presence of NIR. Thus, Gd3+-AuNR features a significant theranostic potential with combined photothermal and imaging modality, suggesting a great potential in anticancer therapy.


Effect of clear speech on acoustic measures of dysprosody in Parkinson disease for different reading tasks.
The purpose of the study was to determine the effect of clear speech instruction on acoustic measures of dysprosody between reading passages of differing linguistic content for speakers with and without Parkinson Disease (PD). Ten speakers with PD and 10 controls served as participants and read five simple and three standard reading stimuli twice. First, speakers read habitually and then following clear speech instruction. Acoustic measures of fundamental frequency variation (semitone standard deviation, STSD), articulation rate, and between-complex pause durations were calculated. Results indicated speakers with PD exhibited less fundamental frequency variation than controls across reading stimuli and instructions. All speakers exhibited lower STSD and longer between-complex pause durations for the standard compared to simple reading stimuli. For clear speech, all speakers reduced articulation rate and increased between-complex pause durations in both simple and standard reading stimuli. However, speakers with PD exhibited a significantly less robust reduction in articulation rate for clear speech than control speakers for all reading stimuli. Linguistic content of reading stimuli contributes to differences in fundamental frequency variation and pause duration for all speakers. All speakers reduced articulation rate for clear speech compared to habitual instruction, but speakers with PD did so to a lesser extent than controls. Linguistic content of reading stimuli to examine dysprosody in PD should be considered for clinical application.


The pulpless abutment.
The use of preformed metallic anchorages inserted in satisfactorily treated teeth for increased stabilization and retention in complete and partial dentures is demonstrated. An additonal advantage is the retention of proprioceptive guidance in mastication with complete dentures. A number of clinical examples are illustrated.


The layered crisis of the primary care medical workforce in the European region: what evidence do we need to identify causes and solutions?
Primary care services are key to population health and for the efficient and equitable organisation of national health systems. This is why they are often financed through public funds. Primary care doctors are instrumental for the delivery of preventive services, continuity of care, and for the referral of patients through the system. These cadres are also the single largest health expenditure at the core of such services. Although recruitment and retention of primary care doctors have always been challenging, shortages are now exacerbated by higher demand for services from aging populations, increased burden of chronic diseases, backlogs from the COVID-19 pandemic, and patient expectations. At the same time, the supply of primary care physicians is constrained by rising retirement rates, internal and external migration, worsening working conditions, budget cuts, and increased burnout. Misalignment between national education sectors and labour markets is becoming apparent, compounding staff shortages and maldistribution. With their predominantly publicly funded health systems and in the aftermath of COVID-19, countries of the European region appear to be now on the cusp of a multi-layered, slow-burning primary care crisis, with almost every country reporting long waiting lists for doctor appointments, shortages of physicians, unfilled vacancies, and consequently, added pressures on hospitals' Accident and Emergency services. This articles collection aims at pulling together the evidence from countries of the European Region on root causes of such workforce crisis, impacts, and effectiveness of existing policies to mitigate it. Original research is needed, offering analysis and fresh insights into the primary care medical workforce crisis in wider Europe. Ultimately, the aim of this articles collection is to provide an evidence basis for the identification of policy solutions to present and future primary health care crises in high as well as lower-income countries.


Sequencing of caprine alpha-S1 casein cDNAs confirms the accuracy of the RT-PCR approach for detecting of the variants of the gene.
Polymorphism of the casein gene in goats determines milk processing quality and cheese flavour. The main 7 alleles belong to 4 groups: strong alleles A, B, C (which code for 3.6 g/l), medium allele E (1.6 g/1), weak alleles F and D (0.6 g/1) and zero allele, connected with lack of alphaS1 casein in milk. Milk cells (mononuclear milk cells plus epithelium cells) and peripheral blood mononuclear cells were mRNA sources for reverse transcription. Three specific primers were used for polymerase chain reaction, which enabled to differentiate between alleles from four expression groups. The length of PCR products varied since allele F has a 111- nucleotide (nt) deletion of exons 9-11, allele D has a deletion of 36 nt (exon 9), and the medium allele E is associated with a 457 nt insertion in the 19th non-coding exon. Sequencing of amplified fragments, performed on PCR products isolated from milk, confirmed the correctness of the RT-PCR - based alphaS1 casein genotyping method.


Developmental outcome in 49,XXXXY Klinefelter syndrome.
The developmental histories of two males who have 49 XXXXY Klinefelter syndrome are described. Now aged 16 and six, they have been followed since the ages of four and two, respectively. They have many of the typical physical characteristics described in the literature, but their mental retardation is not as severe as has been reported. Both are moderately delayed in their general development and their personalities and learning styles are more similar to XXY Klinefelter individuals. These two case studies demonstrate previously unreported potential in individuals with this disorder, and the authors discuss the implications of this finding.


Luminescence nanocrystals for solar cell enhancement.
Semiconductor nanocrystals (NCs) prepared by wet-chemical routes have been proposed as an attractive candidate for fabrication of the third-generation thin-film solar cells due to their quantum confinement effects and excellent dispersion ability in polymer films. However, to date, a solar cell incorporating semiconductor NCs in the photoactive layer still has rather low efficiency due to the low carrier mobility of the non-continued NC phase and the possible radiative recombination in NCs. To avoid these disadvantages, NCs have been proposed and applied as a luminescent species in a passive photon converting layer to modify the solar spectrum before the light enters the photovoltaic device. Photon conversion processes, including up-conversion, down-conversion, and down-shifting, have been observed in various colloidal NC samples and have great potential to enhance photovoltaic performance when applied to the existing single-junction solar cells or narrow-band molecular-based devices.