Anesthetic aspect of malaria disease: a brief review.
Malaria has caused an estimated 190-311 million cases in year 2008 alone and around 1500 patients are diagnosed with the disease annually in the United States. Out of these numbers, few of them have presented for surgery. Malaria disease is a multi-organ systemic disease that may affect significantly patient's outcome after surgery. It is therefore prudent for the anesthesiologists, from both the endemic and non-endemic area, to understand the implication of the disease during the preoperative, intraoperative and postoperative course. Google scholar, Medline and Cochrane data base search are performed using


Simple equation of state for hard disks on the hyperbolic plane.
A simple equation of state for hard disks on the hyperbolic plane is proposed. It yields the exact second virial coefficient and contains a pole at the highest possible packing. A comparison with another very recent theoretical proposal and simulation data is presented.


Macrophage function in vitamin C-deficient guinea pigs.
Guinea pigs were fed a vitamin C-deficient diet and at various time periods thereafter their peritoneal cells were tested for biological activity. The serum levels of vitamin C in the deficient animals indicated a progressive state of ascorbic acid deficiency with time and this correlated well with clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and in structural appearance under the phase contrast and light microscope they were smaller in size. They showed no significant impairment in phagocytosis of bacterial cells. The macrophages, however, exhibited significantly reduced migration on glass as compared to the normal cells. In vitro addition of vitamin C partially reversed this reduced migration.


Challenges in the Development of Antifungal Agents Against Candida: Scope of Phytochemical Research.
Infections caused by Candida have become a major source of morbidity and mortality. Limited numbers of drugs are available to treat these infections. Phytochemicals can be the major source of antifungal compounds. The aim of this publication was to review the current literature to assess the challenges and scope of phytochemical research in the development of new antifungal drugs. Literature describing cellular nature of Candida, the development of drug resistance and target sites for the new drugs were assessed. Publications reporting antifungal activities of crude extracts of plants, their essential oils and identified chemical constituents were also summarised. The results showed that the development of new antifungal agents from natural sources is a complex process due to the cellular nature of Candida and the types of infections caused, such as superficial to life threatening systemic mycosis which necessitate systemic and topical use of drugs. Efficacy of the drugs in the presence of body fluids, normal flora and medical devices can also pose a challenge. Synthetic, semi-synthetic and natural compounds can be screened for their antifungal activities against emerging target sites using new cost effective techniques to increase throughput. Their efficacy, substantivity and site specific desired drug delivery can be enhanced using nanotechnology, hydrogel formulation and bio-adhesive technology. Finally, partnership between academic research laboratories and pharmaceutical industries is also necessary. Many challenges are identified in the development of new antifungal drugs, however phytochemicals are still the major source of new antifungal drugs and should be strategically explored.


Randomised clinical trial of elective re-siting of intravenous cannulae.
Peripheral venous thrombophlebitis (PVT) represents a considerable source of iatrogenic morbidity, occurring in about 20% of hospital in-patients. The aim of this prospective randomised study was to investigate the effect of elective change of intravenous cannulae on the incidence of PVT in hospital in-patients. General medical and surgical inpatients requiring intravenous therapy were randomised into control (n = 26) or study (n = 21) groups. Cannulae in the control group were only removed if the site became painful, the cannula dislodged, or there were signs of PVT. Cannulae in the study group were changed electively every 48 h. All patients were examined daily for signs of PVT. Peripheral venous thrombophlebitis developed in 11/26 patients in the control group and 1/21 patients in the study group (P = 0.003). Elective change of cannulae did not significantly increase the total number of cannulae sited (41 cannulae in the control group versus 43 in the study group). Elective change of cannulae resulted in a significant reduction in the incidence of infusion phlebitis. The authors recommend that elective re-siting of intravenous cannulae becomes standard practice for all patients requiring intravenous therapy.


Plasmatic levels of theophylline in asthmatic patients. Comparative evaluations of two different methods.
There are several criteria to choose an analytical method for drug monitoring. Such methods have to comply with standard values and quality control as well as other subjective features such as cost and the time consumed to obtain quantification (TCOQ). The purpose of this work was to compare two methods used to quantify plasmatic levels of theophylline in asthmatic patients as support to choose the best method. We analyzed plasma samples from 30 asthmatic pediatric patients at the pediatric service of the Hospital General de México, who were under treatment with theophylline and whose monitoring of drug levels was indicated. Plasma samples were analyzed by liquid chromatography (HPLC) and by enzyme immunoassay (EMIT), and were then compared with respect to reliability, as well as cost and TCOQ. The difference of the plasmatic levels of theophylline quantified by both methods was not significant (p > 0.05); both showed a good correlation index (r = 0.995), and both were reliable based on other validity parameters. However, TCOQ for HPLC was 20.0 +/- 5.5 min (mean +/- SD) for each sample analyzed, and 2.3 +/- 0.5 for EMIT. With respect to the cost of each analysis, HPLC required 2.3 +/- 0.5 USD (mean +/- SD) and EMIT 4.5 +/- 0.3 USD. Analytical methods used to quantify plasmatic levels of theophylline based on HPLC and EMIT proved to be suitable, because they fulfilled the criteria and standard values regarding quality control, although laboratorists have to select subjectively the best method according to cost and TCOQ, since HPLC was less expensive, and EMIT was more rapid.


Optical Coherence Tomography Measurement and Visual Outcome in Acute Central Retinal Artery Occlusion.
This study investigated visual acuity (VA) values and differences depending on optical coherence tomography (OCT) findings in patients with acute central retinal artery occlusion (CRAO). A retrospective chart review was performed on patients with acute CRAO who underwent macular and disc OCT. We evaluated changes in macular thickness and retinal nerve fiber layer (RNFL) thickness after acute CRAO onset based on OCT. We also determined the association of thickness changes with VA improvement. This study involved both eyes in a total of 12 patients with acute CRAO. A significant increase was observed in foveal (1 mm) thickness (p = 0.002), parafoveal (3 mm) thickness (p = 0.002), and peripapillary RNFL thickness (p = 0.005) in affected eyes with CRAO, but not in central foveal thickness (p = 0.266). A significant small difference in both eyes (affected eye - fellow eye) was shown in foveal (1 mm) and mean parafoveal (3 mm) thickness in the improved VA group (p = 0.008 and p = 0.004, respectively), but not in central foveal or peripapillary RNFL thickness (both p = 0.283). Both macular and RNFL thickness increased in patients with acute CRAO. RNFL thickness decreased over time with progression of RNFL atrophy. Less macular damage caused by acute CRAO could be predicted by a small difference in macular thickness between eyes (affected eye - fellow eye). In such cases, patients had a greater chance of VA improvement.


Zero-shot-capable identification of phage-host relationships with whole-genome sequence representation by contrastive learning.
Accurately identifying phage-host relationships from their genome sequences is still challenging, especially for those phages and hosts with less homologous sequences. In this work, focusing on identifying the phage-host relationships at the species and genus level, we propose a contrastive learning based approach to learn whole-genome sequence embeddings that can take account of phage-host interactions (PHIs). Contrastive learning is used to make phages infecting the same hosts close to each other in the new representation space. Specifically, we rephrase whole-genome sequences with frequency chaos game representation (FCGR) and learn latent embeddings that 'encapsulate' phages and host relationships through contrastive learning. The contrastive learning method works well on the imbalanced dataset. Based on the learned embeddings, a proposed pipeline named CL4PHI can predict known hosts and unseen hosts in training. We compare our method with two recently proposed state-of-the-art learning-based methods on their benchmark datasets. The experiment results demonstrate that the proposed method using contrastive learning improves the prediction accuracy on known hosts and demonstrates a zero-shot prediction capability on unseen hosts. In terms of potential applications, the rapid pace of genome sequencing across different species has resulted in a vast amount of whole-genome sequencing data that require efficient computational methods for identifying phage-host interactions. The proposed approach is expected to address this need by efficiently processing whole-genome sequences of phages and prokaryotic hosts and capturing features related to phage-host relationships for genome sequence representation. This approach can be used to accelerate the discovery of phage-host interactions and aid in the development of phage-based therapies for infectious diseases.


Differential involvement of PU.1 and Id2 downstream of TGF-beta1 during Langerhans-cell commitment.
Langerhans cells (LCs) are highly abundant dendritic cells (DCs) in epidermal and mucosal tissues. The transcription factors PU.1 and Id2 have been implicated as positive regulators of LC development from hematopoietic progenitor cells. LC differentiation from progenitors is absolutely dependent on transforming growth factor beta 1 (TGF-beta1) in vitro as well as in vivo; however, downstream mechanisms are poorly defined. We found that both PU.1 and Id2 are induced by TGF-beta1 in human CD34+ monocyte/LC (M/LC) progenitor cells, and that neither ectopic PU.1 or Id2 alone, nor both together, could replace TGF-beta1 in its instructive function on LC commitment. However, both factors critically contributed to LC differentiation by acting at 2 distinct intersection points. Ectopic PU.1 strongly enhanced TGF-beta1-dependent LC development. Additionally, Notch-induced generation of interstitial-type DCs was associated with PU.1 up-regulation. Thus, PU.1 is generally increased during myeloid DC development. Ectopic Id2 inhibits the acquisition of early monocytic characteristics by cells generated in the absence of TGF-beta1 and also inhibits monocyte induction by alternative stimuli. Since TGF-beta1 represses a default monocyte pathway of common progenitor cells, PU.1 and Id2 seem to modulate lineage options of M/LC precursors, downstream of TGF-beta1.


Exploring the links between audit and the research process.
The policy background The last decade has witnessed an explosion of activity among health professionals under the banner of audit and quality. Prior to the publication of Working for Patients ( 1 ) such activities were entirely optional, but the NHS Review ( 1 ) introduced a requirement to develop them. Since then the DoH has funded separate programmes of audit for the medical professions on the one hand, and the nursing and therapy professions on the other. Funds totalling more than £220 million ( 2 ) were distributed via two channels - through the regional health authorities for local bidding mainly among provider units, and through a central bidding process for national projects such as those sponsored by the royal colleges. This programme ended in 1995 when audit funds were devolved to health commissions to facilitate audit activities on a more local basis.


A review of the in vitro and in vivo valved holding chamber (VHC) literature with a focus on the AeroChamber Plus Flow-Vu Anti-static VHC.
Valved holding chambers (VHCs) reduce the need for inhalation-actuation coordination with pressurized metered dose inhalers (pMDIs), reduce oropharyngeal drug deposition and may improve lung deposition and clinical outcomes compared to pMDIs used alone. While VHCs are thus widely advocated for use in vulnerable patient groups within clinical and regulatory guidelines, there is less consensus as to whether the performance differences between different VHCs have clinical implications. This review evaluates the VHC literature, in particular the data pertaining to large- versus small-volume chambers, aerosol performance with a VHC adjunct versus a pMDI alone, charge dissipative/conducting versus non-conducting VHCs, and facemasks, to ascertain whether potentially meaningful differences between VHCs exist. Inconsistencies in the literature are examined and explained, and relationships between in vitro and in vivo data are discussed. A particular focus of this review is the AeroChamber Plus® Flow-Vu® Anti-static VHC, the most recent iteration of the AeroChamber VHC family.


The multiple roles of Id-1 in cancer progression.
Id-1 (Inhibitor of differentiation/DNA binding) is a member of the helix-loop-helix protein family expressed in actively proliferating cells. It regulates gene transcription by heterodimerization with the basic helix-loop-helix transcription factors and therefore inhibits them from DNA binding and transactivation of their target genes. Early studies showed that Id-1 functions mainly as a regulator in cellular differentiation of the muscle cells. The oncogenic role of Id-1 was revealed recently by the finding that Id-1 expression was able to induce cancer cell growth and promote cell survival. In addition, Id-1 protein was frequently overexpressed in over 20 types of cancer, supporting its role in the tumorigenesis of a wide range of tissues. However, the fact that Id-1 was able to activate multiple pathways involved in tumor progression suggests that Id-1 may in addition function in promotion of tumor development. For example, overexpression of Id-1 was found to induce expression of MT1-MMP protein, leading to invasion of breast cancer cells. A close association between Id-1 expression and angiogenesis has also been demonstrated recently in both normal and cancer cells. Accordingly, in prostate cancer cells, expression of Id-1 was able to activate EGF-R and nuclear factor-kappaB activities and resulted in progression to androgen independence. In addition, in both nasopharyngeal carcinoma and prostate cancer cells, Id-1 expression was found to protect the cells from chemotherapeutic drug-induced apoptosis through regulation of the Raf-1/MAPK and JNK pathways. This review will discuss recent evidence supporting the role of Id-1 in tumor progression and the mechanisms involved.


Improving anaemia diagnosis using peripheral blood smear with remote interpretation in adults living with HIV with moderate to severe anaemia: A prospective study nested within the Kilombero and Ulanga antiretroviral cohort.
In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia. We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0-9.9 g/dl) or severe (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care. Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35-46)), 65 (17%) had a body mass index <18.5 kg/m2, 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/μl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation. Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.


Design and Imaging of Ground-Based Multiple-Input Multiple-Output Synthetic Aperture Radar (MIMO SAR) with Non-Collinear Arrays.
Multiple-Input Multiple-Output (MIMO) radar provides much more flexibility than the traditional radar thanks to its ability to realize far more observation channels than the actual number of transmit and receive (T/R) elements. In designing the MIMO imaging radar arrays, the commonly used virtual array theory generally assumes that all elements are on the same line. However, due to the physical size of the antennas and coupling effect between T/R elements, a certain height difference between T/R arrays is essential, which will result in the defocusing of edge points of the scene. On the other hand, the virtual array theory implies far-field approximation. Therefore, with a MIMO array designed by this theory, there will exist inevitable high grating lobes in the imaging results of near-field edge points of the scene. To tackle these problems, this paper derives the relationship between target's point spread function (PSF) and pattern of T/R arrays, by which the design criterion is presented for near-field imaging MIMO arrays. Firstly, the proper height between T/R arrays is designed to focus the near-field edge points well. Secondly, the far-field array is modified to suppress the grating lobes in the near-field area. Finally, the validity of the proposed methods is verified by two simulations and an experiment.


Thermal conductivity of the Lennard-Jones chain fluid model.
Nonequilibrium molecular dynamics simulations have been performed to estimate, analyze, and correlate the thermal conductivity of a fluid composed of short Lennard-Jones chains (up to 16 segments) over a large range of thermodynamic conditions. It is shown that the dilute gas contribution to the thermal conductivity decreases when the chain length increases for a given temperature. In dense states, simulation results indicate that the residual thermal conductivity of the monomer increases strongly with density, but is weakly dependent on the temperature. Compared to the monomer value, it has been noted that the residual thermal conductivity of the chain was slightly decreasing with its length. Using these results, an empirical relation, including a contribution due to the critical enhancement, is proposed to provide an accurate estimation of the thermal conductivity of the Lennard-Jones chain fluid model (up to 16 segments) over the domain 0.8<or=T*<or=6 and 0<or=rho<or=1. Additionally, it has been noted that all reduced thermal conductivity values of the Lennard-Jones chain fluid model merge on the same "universal" curve when plotted as a function of the excess entropy. Furthermore, it is shown that the reduced configurational thermal conductivity of the Lennard-Jones chain fluid model is approximately proportional to the reduced excess entropy for all fluid states and all chain lengths.


[Identification of Cervus nippon, C.elaphus and their hybridize samples based on COI and SRY gene].
For rapid identification of Cervus nippon, C. elaphus and their hybridize samples, the specific PCR for mutual authentication of them was established based on the SNPs in COI and SRY sequence. C. nippon, C. elaphus and their hybridize samples were collected from different origins, total DNA of 24 identified samples were extracted, and the COI and SRY gene was seqenced. SNPs in the COI and SRY sequences of the samples were found by Clustul X 2.1 program. Primers for identifying C. nippon and C. elaphus were designed according to the SNP site, two multi-PCR reaction system were established to identify them. In addition, 24 samples which were randomly collected in different herbal medicine market were identified. The band special for C. nippon (232 bp)and band special for C. elaphus (518 bp) based on COI sequence,and the band special for C. nippon (803 bp)and band special for C. elaphus (425 bp) based on SRY sequence, were found using multi-PCR reaction, and three of the twenty-four samples were identified as the hybridize samples. The multi-PCR reaction system could be used to identify C. nippon, C. elaphus and their hybridize samples.


Renal vein reconstruction with interposition allografts in cadaveric renal transplantation.
The short or injured renal vein in cadaveric transplantation is a surgical challenge. Over a 2-year period, we have performed ex vivo renal vein lengthening with an interposition vascular allograft in 17 recipients of cadaveric kidneys. Indications for renal vein extension allografts were a short right renal vein (N = 12), procurement injury to the vein (N = 4), and double renal vein (N = 1). In six cases (35.3%), ex vivo renal artery reconstruction was performed in combination with the venous repair. Our preferred approach is to employ allograft material in ex vivo reconstruction under cold storage conditions. Bench surgery ranged from 10 to 30 min, and the mean in situ anastomosis time was 20 min. The mean length of renal vein prior to reconstruction was 12 mm, and the mean length of venous interposition allograft after revascularization was 27 mm. There were no episodes of vascular thrombosis or primary nonfunction. Three patients (17.6%) required postoperative hemodialysis for acute tubular necrosis, which was subsequently resolved. The mean serum creatine at 1 month post-transplant was 1.7 mg/dl. These preliminary results suggest that ex vivo renal vein reconstruction with an interposition allograft is a safe and effective modality which should be added to the transplant surgeon's armamentarium in select cases.


Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.
Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.


[Different scoring systems to evaluate the prognosis of Fournier's gangrene: A comparative study].
To sum up the experience in diagnosis and treatment of Fournier's gangrene and find an optimal evaluation tool for its prognosis by comparing currently used prognostic scoring systems. We retrospectively analyzed 16 cases of Fournier's gangrene diagnosed and surgically treated in our hospital between 2004 and 2012. Using Fournier's Gangrene Severity Index (FGSI), Uludag Fournier's Gangrene Severity Index (UFGSI), Age-Adjusted Charlson Comorbidity Index (ACCI), and Surgical Apgar Score (sAPGAR) , we obtained the prognostic scores of the patients and made comparisons among different scoring systems. FGSI, UFGSI, ACCI, and sAPGAR were all clinically used scoring systems. Statistically significant differences were found in the scores of ACCI and UFGSI but not in those of FGSI and sAPGAR between the death and survival groups, with the maximum area under the ROC curve and minimum standard error for the ACCI score. Both ACCI and UFGSI are useful for evaluating the prognosis of Fournier's gangrene. However, ACCI is even better for its higher sensitivity and specificity and easier clinical collection.


OGUMI-A new mobile application to conduct common-pool resource experiments in continuous time.
OGUMI is an Android-based open source mobile application for conducting Common-Pool Resource Experiments, Choice Experiments, and Questionnaires in the field, in the laboratory, and online. A main feature of OGUMI is its capacity to capture real-time changes in human behaviour in response to a dynamically varying resource. OGUMI is simple (for example, likewise other existing software, it does not require expertise in behavioural game theory), stable, and extremely flexible with respect to the user-resource model running in the background. Here we present the motivation for the development of OGUMI and we discuss its main features with an example application.


Nutritional consequences of food processing.
A variety of methods are used to process foods: if they are not edible, to render them so; to permit storage; to alter texture and flavor; to destroy microorganisms and other toxins. These methods include heating (baking, cooking, frying, microwaving), freezing, and high pH. It is a paradox of nature that the processing of foods can improve, nutrition, quality, and safety; yet, occasionally these processing alternatives can lead to the formation of anti-nutritional and toxic compounds. These multi-faceted consequences of food processing result from molecular interactions among nutrients and with other food ingredients, both natural and added. This paper outlines the following aspects of processing-induced formation of novel food ingredients and the resulting consequences for nutrition: protein-polyphenol and protein-carbohydrate enzymatic and non-enzymatic browning reactions; formation of heterocyclic amines in meat; inactivation of soybean inhibitors of digestive enzymes; formation of lysinoalanine and D-amino acids in food proteins; and the stability of phenolic compounds to high pH. Possible approaches to prevent the formation of deleterious food ingredients are also addressed.


Photoluminescence of Dy3+ activator sensitized by Ce3+ in KNaSO4 microphosphor.
The KNaSO4 microphosphor doped with Ce or Ce and Dy prepared by a wet chemical method was studied by scanning electron microscopy (SEM) and characterized by photoluminescence (PL). KNaSO4 has a 5-µm particle size detected by SEM. The KNaSO4:Ce(3+) spectrum shows a single emission band at 327 nm for an excitation of 269 nm due to 5d → 4f transition of the Ce(3+) ion, indicating weak spin orbiting coupling of the Ce(3+) ground state. Efficient energy transfer takes place from Ce(3+) → Dy(3+) sublattices indicating that Ce(3+) could effectively sensitize Dy(3+) (orange emission) and that the Ce(3+) emission weakens significantly in KNaSO4. The powder form of prepared KNaSO4 show negligible change in morphologies and hence no effect on the particle size. The characteristics of this powder could provide improved luminescence properties. The development and understanding of this photoluminescence and the effect of Dy(3+) on KNaSO4:Ce(3+) are discussed.


Influence of photoinduced electron transfer on lanthanide-based coordination polymer luminescence: a comparison between two pseudoisoreticular molecular networks.
The luminescent properties of two families of heteronuclear lanthanide-containing coordination polymers are compared. These families have general chemical formulas [Ln2-2xLn'2x(ip)3(H2O)9·6H2O]∞ and [Ln2-2xLn'2x(aip)2(H2O)10·(aip)·4H2O]∞ where H2ip and H2aip stand for isophthalic acid and 5-amino-isophthalic acid, respectively, and where Ln and Ln' are one of the lanthanide ions between Sm(3+) and Dy(3+). Heteronuclear compounds that belong to each family are isostructural to the already reported homonuclear compounds [Gd2(ip)3(H2O)9·6H2O]∞ and [Eu2(aip)2(H2O)10·(aip)·4H2O]∞, respectively. These two crystal structures are very similar. However, despite similar chemical formulas, similar crystal structures, and similar hydration rates, these two families of compounds present very different luminescent properties that have thus been deeply investigated. This study demonstrates that these different optical behaviors can be attributed to the presence of a PET (photoinduced electron transfer) mechanism that is only present in the amino-isophthalate-containing coordination polymers.


Feline systemic reactive angioendotheliomatosis: eight cases and literature review.
A rare, multisystemic intravascular proliferative disorder was identified postmortem in eight cats. The majority of these cats died or were euthanized following episodes of dyspnea, lethargy, and anorexia. Microscopic examination revealed occlusive, intraluminal proliferations of spindle cells within small vessels. The heart was consistently involved, and myocardial dysfunction was the probable cause of illness in all cats. Immunohistochemically, the majority of intravascular cells expressed von Willebrand factor, and a smaller number expressed smooth muscle actin, compatible with a dual population of endothelial cells and pericytes, suggesting a reactive rather than a neoplastic process. Four cases of a similar feline vascular disorder from the veterinary literature are reviewed. The histopathology resembles reactive angioendotheliomatosis in humans, a benign cutaneous intravascular endothelial and pericytic proliferative condition. However, in contrast, this feline disease is multisystemic and fatal. We propose the name "feline systemic reactive angioendotheliomatosis" for this unique, idiopathic disorder of domestic cats.


Cholesterol is essential for macrophage inflammatory protein 1 beta binding and conformational integrity of CC chemokine receptor 5.
The chemokine receptor, CCR5, is used as a human immunodeficiency virus coreceptor in combination with CD4 during transmission and early infection. CCR5 has been shown to be palmitoylated and targeted to cholesterol- and sphingolipid-rich membrane microdomains termed "lipid rafts." However, the role of cholesterol and lipid rafts on chemokine binding and signaling through CCR5 remains unknown. We found that cholesterol extraction by hydroxypropyl-beta-cyclodextrin (BCD) significantly reduced the binding and signaling of macrophage inflammatory protein 1 beta (MIP-1 beta) using CCR5-expressing CEM-NKR T cells. Reloading treated cells with cholesterol but not 4-cholesten-3-one, an oxidized form of cholesterol, restored MIP-1 beta binding to BCD-treated cells. Antibodies specific for distinct CCR5 epitopes lost their ability to bind to the cell surface after cholesterol extraction to varying degrees. Moreover, cells stained with fluorescently labeled MIP-1 beta extensively colocalized with the GM1 lipid raft marker while using anti-CCR5 antibodies; most of CCR5 on these cells only partially colocalized with GM1, suggesting that active ligand binding facilitates receptor association with lipid rafts or that raft association promotes a higher affinity conformation of CCR5. Together, these data demonstrate that cholesterol and lipid rafts are important for the maintenance of the CCR5 conformation and are necessary for both the binding and function of this chemokine receptor.


Transactivation of the TPA-responsive element by the oncogenic C-erbB-2 protein is partly mediated by protein kinase C.
The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun/Fos-mediated transcriptional activation in nuclei.


Morphologic and cytochemical characteristics of amine-containing globule leukocytes in rat tracheal epithelium.
Amine-containing cells in the tracheal epithelium are typically of the small-granule type (diameter approximately 100 nm). However, in the rat, another amine-containing cell type has been identified that possesses the amine-handling features of the APUD-series of cells (amine precursor uptake and decarboxylation) but not the ultrastructural characteristics. It has been postulated that these cells may be related to cutaneous melanocytes. In this study, fluorescent cells were present in the laryngeal and tracheal epithelial lining of adult Sprague-Dawley rats following freeze-drying and exposure to formaldehyde vapor (FIF or formaldehyde-induced fluorescence). Microspectrofluorimetry revealed an emission maximum at 493 nm. The excitation maximum could not be calculated but appeared to be around or below 350 nm (to record spectra below requires the use of quartz optics). Yellow fluorescence also emanated from serotonin-containing mast cells (excitation and emission maxima: 401/515 nm). Tracheal segments processed according to the aqueous formaldehyde ( AFIF ) technique, for the demonstration of 5- hydroxytryptophan (5-HTP) or serotonin (5-HT), failed to identify fluorescent cells in the epithelial lining even though connective-tissue mast cells were evident. Subsequent treatment of AFIF -fixed sections with formaldehyde and HCl vapors ( AFIF -HCl) resulted in the formation of a fluorogenic compound within numerous cells in the tracheal lining (455/537 nm). This spectral shift and increase in intensity of fluorescence following acidification are characteristic for standards and/or cells that contain tryptamine, tryptophan, or peptides with NH2-terminal tryptophan and are markedly different from microspectrofluorimetric data reported for the phenylethylamines or serotonin. It is therefore postulated that these cells contain a closely related beta-(3-indolyl) ethylamine-like compound, serotonin excluded. The morphology of the fluorescent cells was similar when prepared according to the FIF or AFIF -HCl techniques. Conjunctive staining, the examination of a single section first by fluorescence microscopy and subsequently by other histochemical and cytochemical methods, demonstrated that the fluorescent granules were also methylene blue, alcian blue, periodic-acid Schiff, and ferric- fericyanide positive. Subsequent correlative electron microscopic examination of Epon-embedded AFIF -HCl-treated tracheal sections demonstrated that these amine-containing cells were globule leukocytes.


Antidiabetic and antihyperlipidemic activities of Phyllanthus emblica L. extract in vitro and the regulation of Akt phosphorylation, gluconeogenesis, and peroxisome proliferator-activated receptor α in streptozotocin-induced diabetic mice.
The fruits of Phyllanthus emblica L. are high in nutrients and have excellent health care function and developmental value. There are many management strategies available for diabetes and hyperlipidemia. Nevertheless, there is a lack of an effective and nontoxic drug. The present study was designed to first screen four extracts of P. emblica L. on insulin signaling target gene expression levels, including glucose transporter 4 (GLUT4) and p-Akt/t-Akt. The ethyl acetate extract of P. emblica L. (EPE) exhibited the most efficient activity among the four extracts and was thus chosen to explore the antidiabetic and antihyperlipidemic activities in streptozotocin (STZ)-induced type 1 diabetic mice. All mice (in addition to one control (CON) group) were administered STZ injections (intraperitoneal) for 5 consecutive days, and then STZ-induced mice were administered EPE (at 100, 200, or 400 mg/kg body weight), fenofibrate (Feno) (at 250 mg/kg body weight), glibenclamide (Glib) (at 10 mg/kg body weight), or vehicle by oral gavage once daily for 4 weeks. Finally, histological examination, blood biochemical parameters, and target gene mRNA expression levels were measured, and liver tissue was analyzed for the levels of malondialdehyde (MDA), a maker of lipid peroxidation. EPE treatment resulted in decreased levels of blood glucose, HbA1C, triglycerides (TGs), and total cholesterol and increased levels of insulin compared with the vehicle-treated STZ group. EPE treatment decreased blood levels of HbA1C and MDA but increased glutathione levels in liver tissue, implying that EPE exerts antioxidant activity and could prevent oxidative stress and diabetes. The EPE-treated STZ mice displayed an improvement in the sizes and numbers of insulin-expressing β cells. EPE treatment increased the membrane expression levels of skeletal muscular GLUT4, and also reduced hepatic mRNA levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase thereby inhibiting hepatic gluconeogenesis. This resulted in a net glucose lowering effect in EPE-treated STZ mice. Furthermore, EPE increased the expression levels of p-AMPK/t-AMPK in both the skeletal muscle and liver tissue compared with vehicle-treated STZ mice. EPE-treated STZ mice showed enhanced expression levels of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα), but reduced expression levels of lipogenic genes including fatty acid synthase, as well as decreased mRNA levels of sterol regulatory element binding protein 1c (SREBP1c), apolipoprotein-CIII (apo-CIII), and diacylglycerol acyltransferase-2 (DGAT2). This resulted in a reduction in plasma TG levels. EPE-treated STZ mice also showed reduced expression levels of PPAR γ. This resulted in decreased adipogenesis, fatty acid synthesis, and lipid accumulation within liver tissue, and consequently, lower TG levels in liver tissue and blood. Furthermore, EPE treatment not only displayed an increase in the Akt activation in liver tissue, but also in C2C12 myotube in the absence of insulin. These results implied that EPE acts as an activator of AMPK and /or as a regulator of the insulin (Akt) pathway. Taken together, EPE treatment exhibited amelioration of the diabetic and hyperlipidemic state in STZ-induced diabetic mice.


Red cell dimorphism in a young man with a constitutional chromosomal translocation t(11;22)(p15.5;q11.21).
A constitutional, balanced chromosomal translocation t(11;22)(p15.5;q11.21) was discovered in a tall young man during investigation of a red cell dimorphism. The red cells are predominantly normochromic and normocytic with a small population of hypochromic, microcytic cells. Contained within the regions involved in the translocation are determinants of height (IGF2:11p15.5), red cell haemoglobinization (non-alpha globin gene complex: 11p15.5) and oncogenesis (cHa-Ras-1, Beckwith-Wiedemann syndrome: 11p15.5; BCR, Burkitts lymphoma, Ewings sarcoma: 22q11.21). To map these regions in the patient, somatic cell hybrids were generated and cell lines that segregated the chromosomes 11, 22 and 22q- were obtained. All 11p15.5 sequences investigated, in particular the whole of the non-alpha globin gene complex including its 5' and 3' regulatory sequences, were found to be translocated to 22q-. All chromosome 22 sequences studied were missing from the 22q- cell lines, including the proximal anonymous marker D22S24, and therefore assumed to be translocated to 11p+. These results suggest that the non-alpha globin gene complex has been moved close to the centromeric region of chromosome 22q-. It is postulated that such a positioning subjects the complex to a variegated position-effect bringing about a clonal exclusion of the complex and thus producing a beta-thalassaemia trait mosaic.


Coupling reaction and properties of poly(ethylene glycol)-linked phospholipases A2.
Secretory phospholipases A2 (PLA2) from Naja naja naja (cobra snake) venom, from Bothrops neuwiedii (crotalid snake) venom (two isoforms) and from bee venom were modified with tresylated monomethoxy poly(ethylene glycol) (TMPEG). The kinetic and inflammatory properties of the adducts (PEG-PLA2) were measured. As found by gel permeation chromatography, 95-100% of P-1 PLA2 from B. neuwiedii and PLA2 from N. naja naja venom change their chromatographic mobility after TMPEG treatment. By contrast, only 50-60% of both P-3-PLA2 from B. neuwiedii and PLA2 from bee venom modify their elution profile from Superdex 75. All the modified proteins preserved the enzymatic activity toward phospholipid monolayers, but with a reduced specific activity and greater lag times than the unmodified controls. These results suggest that the PEG-PLA2 complexes would have an altered interaction with lipid membranes. The PEG-linked proteins preserve their edema-inducing activity evaluated by the rat hind-paw edema test except for N. naja naja PEG-PLA2 in which inflammatory activity was significatively decreased. Altogether, the results show a partial dissociation of catalytic and inflammatory activities of Group II and III secretory PLA2s after their modification with PEG.


Learning to Identify Patients at Risk of Uncontrolled Hypertension Using Electronic Health Records Data.
Hypertension is a major risk factor for stroke, cardiovascular disease, and end-stage renal disease, and its prevalence is expected to rise dramatically. Effective hypertension management is thus critical. A particular priority is decreasing the incidence of uncontrolled hypertension. Early identification of patients at risk for uncontrolled hypertension would allow targeted use of personalized, proactive treatments. We develop machine learning models (logistic regression and recurrent neural networks) to stratify patients with respect to the risk of exhibiting uncontrolled hypertension within the coming three-month period. We trained and tested models using EHR data from 14,407 and 3,009 patients, respectively. The best model achieved an AUROC of 0.719, outperforming the simple, competitive baseline of relying prediction based on the last BP measure alone (0.634). Perhaps surprisingly, recurrent neural networks did not outperform a simple logistic regression for this task, suggesting that linear models should be included as strong baselines for predictive tasks using EHR.


Molecular epidemiology of Mycobacterium tuberculosis in western Sweden.
The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden.


Human Eosinophils Reduce Viral Titer, Secrete IL-8, and Increase RIG-I Expression in Response to Influenza A H1N1 pdm09.
Eosinophils participate in the immune response against many pathogens, including viruses. Since mouse eosinophils are susceptible to influenza A virus infection and possess antiviral activity, we evaluated the expression of sialic acid residues in human eosinophils and their response against influenza virus in vitro. We demonstrated that human eosinophils express α2,6- and α2,3-linked sialic acid, and drastically reduced influenza virus titer. After influenza virus exposure, eosinophils upregulated retinoic acid-inducible gene I (RIG-I) mRNA expression, but no other pattern recognition receptors. Finally, high concentrations of interleukin-8 (IL-8) were found in influenza virus-exposed eosinophil cultures. These data suggest that human eosinophils possess antiviral activity and may play a role in the innate immune response to influenza virus.


VOCAL DIALECTS AND THE STRUCTURE OF GEOGRAPHIC VARIATION IN MORPHOLOGICAL AND ALLOZYMIC CHARACTERS IN THE RUFOUS-COLLARED SPARROW, ZONOTRICHIA CAPENSIS.
The geographical patterns of variation shown at 20 allozyme and non-enzymatic protein-coding loci, in 8 external, and in 12 skeletal morphological characters in the rufous-collared sparrow, Zonotrichia capensis, were analyzed in order to test the local (genetic) adaptation hypothesis regarding the origin and maintenance of vocal dialects in birds. Approximately 20 males were collected from each of four sites within each of six different dialect zones. There was significant variability in both external and skeletal morphology among all 24 sites and among dialect groups. Average Wright's corrected fixation coefficient (FST ) was 0.118, indicating significant genetic differentiation among all sites, regardless of dialect. Hierarchical F statistics indicated that only 50% of among site variability was due to a dialect effect. Puna dialect sites were highly differentiated from all other sites with respect to both morphology (external and skeletal measures) and allozyme frequencies. Heterogeneity at the PGM-1 locus among puna scrub sites was the major cause of the high average FST across all sites, and within the puna scrub dialect. Average genetic differentiation among non-puna sites (FST = 0.018) was similar to differentiation among sites within each of the five non-puna dialect groups (mean FST = 0.0132 ± 0.0069). Hierarchical F statistics indicated that none of the among-site differentiation in this subset of samples was due to a dialect effect. These observations are not consistent with the local adaptation hypothesis. All significant genetic heterogeneity occurred among sites in mountainous habitats, and we suggest that topography and patchiness of habitat may have been major factors involved in population differentiation, rather than vocal dialects.


Adipokines in diabetes and cardiovascular diseases.
Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed.


Association of serum uric acid with prognosis in patients with myocardial infarction: an update systematic review and meta-analysis.
The prognostic significance of serum uric acid (SUA) in individuals who have experienced myocardial infarction (MI) remains a subject of academic debate. Thus, the aim of this study was to examine the occurrence of immediate and long-term adverse outcomes in individuals with elevated levels of uric acid (UA) following a diagnosis of MI. This study conducted a literature search from PubMed, Embase, Web of Science, Medline, Cochrane Library, Emcrae, and Scopus to perform a systematic review and meta-analysis of the prognostic impact of MI with a hyper SUA to assess short-term (30-day or in-hospital) and long-term mortality, the incidence of major adverse cardiovascular events (MACE), and its adverse event rate in relation to SUA. The literature search was conducted up until April 2023. A random effects model and risk ratio (RR) were used as epidemiological indicators. For indicators with low disease rates, treatment intensity was reduced and RR was considered equivalent to odds ratio (OR). Hazard Ratio (HR), RR, and OR extracted from the data were simultaneously subjected to multivariable adjustment for confounding factors. In addition, P values for all original hypotheses were extracted and a meta-analysis was conducted. High SUA was defined as SUA levels equal to or greater than 420 μmol/L (7.0 mg/dL) for males and equal to or greater than 357 μmol/L (6.0 mg/dL) for females. The quality of the literature was evaluated using the Newcastle-Ottawa Scale (NOS). This comprehensive study included a total of 41 investigations, involving a large sample size of 225,600 individuals who had experienced MI. The findings from the meta-analysis reveal that patients diagnosed with hyperuricemia have significantly increased rates of short-term mortality (RR = 2.14, 95% CI = 1.86, 2.48) and short-term incidence of MACE (RR = 1.94, 95% CI = 1.65-2.11). Furthermore, long-term adverse outcomes, including all-cause mortality (RR = 1.46, 95% CI = 1.40-1.51) and incidence of MACE (RR = 1.43, 95% CI = 1.35-1.52), were also found to be higher in this specific patient population. Patients diagnosed with MI and elevated SUA levels exhibit a heightened incidence of MACE during their hospital stay. Furthermore, these individuals also experience elevated rates of in-hospital mortality and mortality within one year of hospitalization. However, it is important to note that further randomized controlled trials are necessary to validate and authenticate these findings.


Can Technology-Based Social Memory Aids Improve Social Engagement? Perceptions of a Novel Memory Aid for Persons With Memory Concerns.
Social withdrawal and isolation are frequently experienced among people with cognitive impairment, Alzheimer's disease, and Alzheimer's disease related dementias. Few assistive technologies exist to support persons with memory concerns' (PWMC) continuing social engagement. This study aimed to understand PWMC and family caregivers' initial perspectives on the feasibility and utility of a wearable technology-based social memory aid. We recruited 20 dyads, presented the memory aid, and conducted semi-structured interviews from June to August 2020 over Zoom video conferencing. Interviews were transcribed and analyzed using thematic analysis. Overall, participants anticipated the technology could reduce socializing-related stress now and in the future for both members of the care dyad. However, certain features of the memory aid (e.g., visitors must have the app), could limit utility, and participants provided recommendations to enhance the tool. Our findings will inform future technology-enabled social memory aid development for PWMC and family caregivers.


C-reactive protein and carotid intimal medial thickness in a community population.
C-reactive protein (CRP) has been linked to cardiovascular disease and atherosclerosis. Large-scale epidemiological studies have shown a correlation of CRP level with risk of stroke, myocardial infarction and peripheral arterial disease. Nevertheless, the question whether serum CRP itself is an independent indicator of the atherosclerotic process remains unanswered. In a community-based sample free of advanced atherosclerotic disease (n = 1018; mean age +/- SD, 54.1 +/- 12.0 years; 49.7% women) we examined the relationship between carotid intimal medial thickness (IMT), conventional vascular risk factors (that is, smoking, obesity, elevated blood pressure, diabetes mellitus, hypercholesterolaemia) and serum CRP. We found an association between increasing IMT values with increasing CRP values for all sites within the carotid system (for example, common carotid artery [CCA-] IMT, beta = 0.174, P < 0.001). The relationship was weakened after accounting for the above-mentioned conventional risk factors (linear regression), particularly body mass index, but remained significant (for example, mean CCA-IMT beta = 0.02, P = 0.042). Including fibrinogen in the regression made the relationship no longer significant (mean CCA-IMT beta = 0.01, P = 0.277). It is unlikely that CRP per se is a major independent cause of early arteriosclerosis. Elevations of CRP, or less specifically chronic inflammation, may mediate the effect of certain conventional risk factors on promoting atherogenesis, especially obesity.


Effects of bilingualism and biliteracy on children's emerging concepts of print.
Three groups of 4- and 5-year-old children were examined for their concepts of how print refers to language. All of the children could identify printed letters and their sounds but not read alone. The groups studied were monolingual speakers of English, bilingual speakers of French and English, and bilingual speakers of Chinese (Mandarin) and English. Bilingual children were equally proficient in both languages and were familiar with print and storybooks in both languages. The tasks assessed children's understanding of the general correspondence between print and language in which the printed form represents a word and the specific correspondence between a constituent of print and one of language that determines representation in a given writing system. The general correspondence relation applies to all writing systems, but the specific correspondence relation changes for different kinds of writing systems. Bilingual children understood better than monolingual children the general symbolic representation of print. The older Chinese-English bilingual children also showed advanced understanding of the specific correspondence relations in English print.


The role of the motor cortex in the control of vigour of locomotor movements in the cat.
1. The impulse activity of single neurones in the motor cortex (MC) was recorded extracellularly using movable varnish-insulated tungsten microelectrodes in four adult freely moving cats. The cats walked inside the experimental box with various loadings in the swing or stance phases of the step cycle. The mean discharge rate (mR) and the depth of frequency modulation (dM) in each neurone were estimated over 10-100 steps. 2. The activity of thirty-one cells (including eighteen pyramidal tract neurones (PTNs)) was recorded during uphill walking on a 10 deg inclined floor. The mR in 68%, and the dM in 77% of neurones changed by less than 20% during uphill locomotion compared to walking on a level surface. 3. The activity of the same neurones was also recorded during downhill walking, also on a 10 deg inclined plane. The mR in 69% and the dM in 78% of neurones changed by less than 20% during downhill locomotion compared with walking on a level surface. 4. The activity of twenty-three (the left hemisphere) cells (sixteen PTNs) during walking with the floor swaying to the right (R) and to the left (L) was compared to activity during locomotion on a stable surface. The mR in 83% and the dM in 83% of cells in R-steps, and in 82 and 77% of cells, respectively, in L-steps changed by less than 20%. 5. The activity of thirty-seven cells was studied during locomotion at various speeds. The mR in 68% and the dM in 38% of cells changed by less than 20% during fast and slow locomotion compared to middle-speed locomotion. The dM in 46% of neurones increased with the transfer from slow to fast walking. 6. The activity of thirty-one MC cells was recorded during locomotion with loads of 85 g attached to the distal part of each elbow. The mR in 52% and the dM in 48% of neurones changed by more than 20%. 7. The activity of twenty-eight cells (six PTNs) was studied in steps when an animal turned. The swing of the limb contralateral to the recorded MC was shorter (condition 1) in turning steps in one direction, and was longer (condition 2) in turning steps in the opposite direction. The mR in 50% and the dM in 50% of cells in condition 1 and in 52% and 59%, respectively, of cells in condition 2 changed by more than 20%.(ABSTRACT TRUNCATED AT 400 WORDS)


EVALUATION OF ANTIBACTERIAL, ANTITUMOR, ANTIOXIDANT ACTIVITIES AND PHENOLIC CONSTITUENTS OF FIELD-GROWN AND IN VITRO-GROWN LYSIMACHIA VULGARIS L.
Lysimachia vulgaris L. (Yellow loosestrife) is a medicinal plant in the family Myrsinaceae. It has been used in the treatment of fever, ulcer, diarrhea and wounds in folk medicine. It has also analgesic, expectorant, astringent and anti-inflammatory activities. Two different sources of the plant (field-grown and in vitro-grown) were used to evaluate the biological activities (antibacterial, antitumor and antioxidant) of L. vulgaris. In vitro-grown plant materials were collected from L. vulgaris plants that were previously regenerated in our laboratory. Plant materials were extracted with water, ethanol and acetone. For antibacterial test, disc diffusion method and 10 different pathogenic bacteria were used. Antioxidant activity was indicated by using DPPH method. The total phenol amount by using Folin-Ciocaltaeu method and the total flavonoid amount by using aluminum chloride (AlCl3) colorimetric method were determined. Generally, yellow loosestrife extracts demonstrated antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, S. epidermidis and Streptococcus pyogenes). Strong antitumor activity of yellow loosestrife was observed via potato disc diffusion bioassay. Nine different phenolics were also determined and compared by using High-Performance Liquid Chromatography (HPLC). Future investigations should be focused on fractionation of the extracts to identify active components for biological activity.


The Lp_3561 and Lp_3562 Enzymes Support a Functional Divergence Process in the Lipase/Esterase Toolkit from Lactobacillus plantarum.
Lactobacillus plantarum species is a good source of esterases since both lipolytic and esterase activities have been described for strains of this species. No fundamental biochemical difference exists among esterases and lipases since both share a common catalytic mechanism. L. plantarum WCFS1 possesses a protein, Lp_3561, which is 44% identical to a previously described lipase, Lp_3562. In contrast to Lp_3562, Lp_3561 was unable to degrade esters possessing a chain length higher than C4 and the triglyceride tributyrin. As in other L. plantarum esterases, the electrostatic potential surface around the active site in Lp_3561 is predicted to be basic, whereas it is essentially neutral in the Lp_3562 lipase. The fact that the genes encoding both proteins were located contiguously in the L. plantarum WCFS1 genome, suggests that they originated by tandem duplication, and therefore are paralogs as new functions have arisen during evolution. The presence of the contiguous lp_3561 and lp_3562 genes was studied among L. plantarum strains. They are located in a 8,903 bp DNA fragment that encodes proteins involved in the catabolism of sialic acid and are predicted to increase bacterial adaptability under certain growth conditions.


Impact of tigecycline versus imipenem-cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study.
The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem-cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem-cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem-cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p < 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p < 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p < 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p < 0.001). In conclusion, compared to imipenem-cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.


Early pharmacologic conversion of atrial fibrillation after off-pump coronary artery bypass grafting.
The aim of this study was to evaluate the efficacy of early amiodarone-based pharmacological cardioversion for postoperative atrial fibrillation (POAF) following off-pump coronary bypass grafting (OPCAB). A total of 507 patients who underwent OPCAB between 2015 and 2017 were categorized into POAF (n=94) and no-POAF (n=413) groups. Patients in the POAF group were treated according to the following institutional protocol: 150 mg loading dose of intravenous amiodarone, followed by oral administration with sequential maintenance doses at 600, 400, and 200 mg per day. If sinus rhythm was restored before discharge, patients were discharged without amiodarone or anticoagulants, except for dual antiplatelets. Before discharge at index hospitalization, 97.8% of POAF patients had restored sinus rhythm. Independent risk factors for POAF were age, unstable angina, prior percutaneous transluminal coronary angioplasty, and left atrial diameter. The mean follow-up duration was 41.1±12.8 months. Freedom from overall mortality and composite events, including mortality, major bleeding requiring admission and cerebrovascular events, were similar between the 2 groups. Results were consistent after propensity-score matching. Amiodarone-based rapid pharmacological cardioversion of POAF resulted in a high sinus rhythm conversion rate (97.9%). Rate of late adverse cardiovascular events including stroke, were low even without anticoagulation. As optimal treatment and anticoagulation guidelines for POAF after OPCAB have not yet been established, amiodarone-based treatment protocols may be considered as a useful option.


Traumatic leaflet injury during the use of percutaneous valves: a comparative study of balloon- and self-expandable valved stents.
No comparison of balloon- or self-expandable valved stents (VSs) regarding tissue injury (if any) has been reported yet. The objective was to evaluate the occurrence and compare the severity of traumatic injury to leaflets from balloon- or self-expandable VSs. Twelve homemade VSs were used for this experiment. These three-leaflet bovine pericardial bioprostheses had either a stainless steel (Group A) or a nitinol stent (Group B). After a 30-min period of compression (external diameter of VS reduced to 7 mm), the prostheses were deployed by balloon inflation (Group A) or by unsheathing (Group B). After H&E staining, pericardial leaflets were subsequently analyzed qualitatively and quantitatively for microscopic lesions. Non-crimped pericardial leaflets were used as a control group (Group C). All deployed VSs had microscopic lesions evocating traumatic injury to pericardial leaflets. Transverse fractures and longitudinal cleavages were the two main lesions encountered. Transverse fractures (no. per field) were significantly more frequent in the VS in comparison with the control group: 5 (range: 0-13), 4 (range: 0-9) and 0 (range: 0-1) in Groups A, B and C, respectively (P < 0.001). Cleavages (no. per field) were also more frequent with balloon-expandable VSs compared with self-expandable VSs [3 (range: 0-7) vs 1(range: 0-8); P = 0.03]. Traumatic injury to the pericardial leaflets does occur during crimping and deployment of balloon- or self-expandable VSs. Injury may be more severe with the balloon-expandable VSs. The impact of such an injury on prosthesis durability requires a further investigation.


Back propagation neural network in the discrimination of benign from malignant lower urinary tract lesions.
We investigated the potential value of morphometry and artificial intelligence tools to discriminate between benign and malignant lower urinary tract lesions. The lesions included lithiasis in 50 cases, inflammation in 61, benign prostatic hyperplasia in 99, carcinoma in situ in 5, and grade I and grades II and III transitional cell carcinoma of the bladder in 71 and 184, respectively. Images of routine processed voided urine smears stained by the Giemsa technique were analyzed using a custom image analysis system, providing a data set of 45,452 cells. A neural net model of the back propagation type was used to discriminate benign from malignant cells based on the extracted morphometric and textural features. Data from 13,636 randomly selected cells (30% of the total data) were used as a training set and the data from the remaining 31,816 cells comprised the test set. In a similar attempt to discriminate at the patient level data on 30% of those randomly selected were used to train a back propagation neural net and data on the remaining 329 were used for testing. Application of the back propagation neural net enabled the correct classification of 95.34% of benign and 86.71% of malignant cells with overall 90.57% accuracy. At the patient level the back propagation neural net enabled the correct classification of 100% of those with benign and 94.51% of those with malignant disease with overall 96.96% accuracy. The use of neural nets and image morphometry may increase the speed of cytological diagnosis and the diagnostic accuracy of voided urine cytology.


Dual effect of temperature on the human epithelial Na+ channel.
The amiloride-sensitive epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption in the distal segments of the nephron, in the colon and in the airways. Its activity is regulated by intracellular and extracellular factors but the mechanisms of this regulation are not yet completely understood. Recently, we have shown that the fast regulation of ENaC by the extracellular [Na+], a phenomenon termed self-inhibition, is temperature dependent. In the present study we examined the effects of temperature on the single-channel properties of ENaC. Single-channel recordings from excised patches showed that the channel open probability (Po, estimated from the number of open channels N.Po, where N is the total number of channels) increased on average two- to threefold while the single-channel conductance decreased by about half when the temperature of the perfusion solution was lowered from approximately 30 to approximately 15 degrees C. The effects of temperature on the single-channel conductance and Po explain the changes of the macroscopic current that can be observed upon temperature changes and, in particular, the paradoxical effect of temperature on the current carried by ENaC.


Electrocardiographic ST segment elevation: left ventricular aneurysm.
Left ventricular aneurysm (LVA), also described as dyskinetic left ventricular segment, is defined as a localized area of infarcted myocardium that bulges outward during both systole and diastole. LVAs most often are noted after large anterior wall events but may also be encountered status after inferior and posterior wall injuries. In most cases, LVA is manifested electrocardiographically by varying degrees of ST segment elevation (STE), which may be difficult to distinguish from ST segment changes caused by acute myocardial infarction. The STE is generally associated with well-developed, completed Q waves in the anterior precordial leads, and there will not be reciprocal ST depression in the contralateral leads. This article focuses on the electrocardiographic findings useful in making the diagnosis of left ventricular aneurysm as well as distinguishing LVA from other STE syndromes.


Incidence Trends of Cervical Cancer in Adolescents and Young Adults: Brazilian Population Based Data.
High incidence rates for cervical cancer in adolescents and young adults (AYAs: 15-29 years) make this the most common carcinoma in Brazil. Our aim was to analyze the incidence trends for cervical cancer (CC) and in situ neoplasia (IsN) among this age group. Incidence data were extracted from 21 Brazilian population-based cancer registries (PBCRs). Tumors with behavior code/3 (malignant) were classified as CC. Tumors with behavior code/2 were classified as IsN. Age-adjusted and age-specific incidence rates were calculated for individuals aged 15-19 years, 20-24 years, and 25-29 years. Incidence trends were evaluated by joinpoint regression analyses. The median incidence rate of CC for AYA in Brazil was 3.63 per 100,000, with the highest rate observed in Recife (27.50 per 100,000). Significant increase in incidence for CC was identified in two PBCRs, with decreased rates for three PBCRs. The median incidence rate of IsN was 16.78 per 100,000 and was highest in Roraima (93.37 per 100,000). Increased incidence rates for IsN were identified in six PBCRs, with significant decreases in two PBCRs. The incidence rate for CC among AYA in Brazil is high and warrants intervention in terms of both prevention and control.


Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma.
Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies. To compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed. Comparing AIP and PDAC patients' serum, significantly higher concentrations were found in AIP for interleukins IL-1β, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1β when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC. The cytokines IL-1β, IL-7, and G-CSF can be routinely measured in patients' serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.


Compact Multi-Layered Symmetric Metamaterial Design Structure for Microwave Frequency Applications.
Metamaterial analysis for microwave frequencies is a common practice. However, adopting a multi-layered design is unique in the concept of miniaturisation, thus requiring extensive research for optimal performance. This study focuses on a multi-layered symmetric metamaterial design for C- and X-band applications. All simulation analyses were performed analytically using Computer Simulation Technology Studio Suite 2019. The performances of the proposed metamaterial design were analysed through several parametric studies. Based on the observation, the proposed metamaterial unit cell design manifested resonant frequencies at 7.63 GHz (C-band) and 9.56 GHz (X-band). Moreover, the analysis of effective medium parameters was also included in this study. High-Frequency Simulation 15.0 and Advanced Design System 2020 software validated the transmission coefficient results. Simultaneously, the proposed multi-layered metamaterial design with Rogers RO3006 substrate material exhibited a unique transmission coefficient using double, triple, and quadruple layers. The two resonant frequencies in the unit cell design were successfully increased to three in the double-layer structure at 6.34 GHz (C-band), 8.46 and 11.13 GHz (X-band). The proposed unit cell design was arranged in an array structure to analyse the performance changes in the transmission coefficient. Overall, the proposed metamaterial design accomplished the miniaturisation concept by arranging unit cells in a multi-layer structure and possesses unique properties such as a highly effective medium ratio and left-handed characteristics.


Roseomonas deserti sp. nov., isolated from crude oil contaminated desert sand.
Two dark pink pigmented bacterial strains (M3T and M11) were isolated from crude oil contaminated desert sand from Kuwait. Both strains were Gram-stain-negative and small-rod to oval-shaped bacteria. Strains M3T and M11 grew at 13-42 °C (optimum, 30-35 °C) and pH 6.5-9.0 (optimum, 7.0-7.5). No additional NaCl was required for the growth of both strains. The genomic DNA G+C content of strains M3T and M11 were 69.5 and 69.0 mol%, respectively. Both strains were closely related and the mean DNA-DNA hybridization value was 92±1 %. 16S rRNA gene sequence comparisons of both strains indicated that they belong to the genus Roseomonas. Strains M3T and M11 had a sequence similarity of 97.3 and 97.4 % with Roseomonas oryzae JC288T, respectively. Both strains had <97 % 16S rRNA gene sequence similarity with other members of the genus Roseomonas. Strain M3T showed 18±2 and 13±2 % reassociation (based on DNA-DNA hybridization) with R. oryzae KCTC 42542T and Roseomonas cervicalis KACC 11686T, respectively. The major cellular fatty acids (>5 %) were identified as C18 : 1ω6c/C18 : 1ω7c, C16 : 1ω6c/C16 : 1ω7c and C16 : 0 in both strains. Both strains showed diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl-ethanolamine, phosphatidylcholine and unidentified glycolipid as major polar lipids. Based on distinct phenotypic, genotypic and phylogenetic differences from the previously described taxa, we propose the classification of strains M3T and M11 as representative of a novel species in the genus Roseomonas, for which the name Roseomonas deserti sp. nov. is suggested. The type strain is M3T (=KEMB 2255-459T=JCM 31275T).


Copper transfer from the Cu(I) chaperone, CopZ, to the repressor, Zn(II)CopY: metal coordination environments and protein interactions.
Extracellular copper regulates the DNA binding activity of the CopY repressor of Enterococcus hirae and thereby controls expression of the copper homeostatic genes encoded by the cop operon. CopY has a CxCxxxxCxC metal binding motif. CopZ, a copper chaperone belonging to a family of metallochaperones characterized by a MxCxxC metal binding motif, transfers copper to CopY. The copper binding stoichiometries of CopZ and CopY were determined by in vitro metal reconstitutions. The stoichiometries were found to be one copper(I) per CopZ and two copper(I) per CopY monomer. X-ray absorption studies suggested a mixture of two- and three-coordinate copper in Cu(I)CopZ, but a purely three-coordinate copper coordination with a Cu-Cu interaction for Cu(I)2CopY. The latter coordination is consistent with the formation of a compact binuclear Cu(I)-thiolate core in the CxCxxxxCxC binding motif of CopY. Displacement of zinc, by copper, from CopY was monitored with 2,4-pyridylazoresorcinol. Two copper(I) ions were required to release the single zinc(II) ion bound per CopY monomer. The specificity of copper transfer between CopZ and CopY was dependent on electrostatic interactions. Relative copper binding affinities of the proteins were investigated using the chelator, diethyldithiocarbamic acid (DDC). These data suggest that CopY has a higher affinity for copper than CopZ. However, this affinity difference is not the sole factor in the copper exchange; a charge-based interaction between the two proteins is required for the transfer reaction to proceed. Gain-of-function mutation of a CopZ homologue demonstrated the necessity of four lysine residues on the chaperone for the interaction with CopY. Taken together, these results suggest a mechanism for copper exchange between CopZ and CopY.


Combining functional and structural brain magnetic resonance imaging in Huntington disease.
To concurrently investigate with magnetic resonance (MR) the brain activation and regional brain atrophy in patients with Huntington disease (HD). Nine symptomatic HD patients and 11 healthy subjects underwent an MR study including functional MR acquisition during finger tapping of the right hand and high-resolution T1-weighted images. Functional and structural data were analyzed using Statistical Parametric Mapping 2 software. As compared with control subjects, HD patients showed decreased activation in the left caudate nucleus and medial frontal and anterior cingulate gyri and increased activation in the right supplementary motor area and supramarginal gyrus and left intraparietal sulcus. The pattern of atrophy included thinning of the gray matter (GM) in the insula, inferior frontal gyrus, caudate, lentiform nucleus, and thalamus, bilaterally, in the left middle frontal, middle occipital, and middle temporal gyri, and of periventricular, subinsular, right temporal lobe, and left internal capsule white matter. Only the decreased activation in the caudate nucleus correlated topographically with the caudate GM loss. The cortical areas of functional changes do not correspond to those of GM atrophy in patients with HD and are likely to reflect decreased output of the motor basal ganglia-thalamo-cortical circuit and compensatory recruitment of accessory motor pathways.


The coiled-coil domain is required for HS1 to bind to F-actin and activate Arp2/3 complex.
HS1 (hematopoietic lineage cell-specific protein 1), a substrate of protein tyrosine kinases in lymphocytes, binds to F-actin, and promotes Arp2/3 complex-mediated actin polymerization. However, the mechanism for the interaction between HS1 and F-actin has not yet been fully characterized. HS1 contains 3.5 tandem repeats, a coiled-coil region, and an SH3 domain at the C terminus. Unlike cortactin, which is closely related to HS1 and requires absolutely the repeat domain for F-actin binding, an HS1 mutant with deletion of the repeat domain maintains a significant F-actin binding activity. On the other hand, deletion of the coiled-coil region abolished the ability of HS1 to bind to actin filaments and to activate the Arp2/3 complex for actin nucleation and actin branching. Furthermore, a peptide containing the coiled-coil sequence only was sufficient for F-actin binding. Within cells overexpressing green fluorescent protein-tagged HS1 proteins, wild type HS1 co-localizes with cortical F-actin at the cell leading edge, whereas mutants with deletion of either the coiled-coil region or the repeat domain diffuse in the cytoplasm. Immunoprecipitation analysis reveals that the coiled-coil deletion mutant binds poorly to F-actin, whereas the mutant without the repeat domain fails to bind to both Arp2/3 complex and F-actin. These data suggest that the HS1 coiled-coil region acts synergistically with the repeat domain in the modulation of the Arp2/3 complex-mediated actin polymerization.


Reconstructive Microsurgery in the COVID-19 Environment.
The COVID-19 pandemic has presented unique challenges to the plastic surgery field. Substantial changes have been incorporated in hospital and practice protocols in all branches of medicine. Organic medical teams were placed on scheduled shifts to prevent cross-infection, and some working teams were discontinued. Remote technology consultations and deliberations were instituted in hospitals and community medical services to maintain the flow of information on patient status. Several mitigation strategies were implemented during these times throughout medical facilities. We present those implemented in our facility to ensure adequate labor, resources, and facilities along with proper protocols for patient selection and management according to predetermined risk assessment criteria with the hope to assist the healthcare staff to minimize mortality risks.


Repeat Closed-Head Injury in Male Rats Impairs Attention but Causes Heterogeneous Outcomes in Multiple Measures of Impulsivity and Glial Pathology.
Repetitive mild traumatic brain injury, or concussion, can lead to the development of long-term psychiatric impairments. However, modeling these deficits is challenging in animal models and necessitates sophisticated behavioral approaches. The current set of studies were designed to evaluate whether a rubberized versus metal impact tip would cause functional deficits, the number of injuries required to generate such deficits, and whether different psychiatric domains would be affected. Across two studies, male rats were trained in either the 5-choice serial reaction time task (5CSRT; Experiment 1) to assess attention and motor impulsivity or concurrently on the 5CSRT and the delay discounting task (Experiment 2) to also assess choice impulsivity. After behavior was stable, brain injuries were delivered with the Closed-head Injury Model of Engineered Rotational Acceleration (CHIMERA) either once per week or twice per week (Experiment 1) or just once per week (Experiment 2). Astrocyte and microglia pathology was also assayed in relevant regions of interest. CHIMERA injury caused attentional deficits across both experiments, but only increased motor impulsivity in Experiment 1. Surprisingly, choice impulsivity was actually reduced on the Delay Discounting Task after repeat injuries. However, subsequent analyses suggested potential visual issues which could alter interpretation of these and attentional data. Subtle changes in glial pathology immediately after the injury (Experiment 1) were attenuated after 4 weeks recovery (Experiment 2). Given the heterogenous findings between experiments, additional research is needed to determine the root causes of psychiatric disturbances which may arise as a results of repeated brain injuries.


Melittin-Containing Hybrid Peptide Hydrogels for Enhanced Photothermal Therapy of Glioblastoma.
The design of biocompatible and efficacious anticancer biomaterials to achieve relatively low tumor recurrence rates is the main pursuit of cancer photothermal therapy (PTT). RADA16-I is a synthetic amphiphilic peptide with the sequence RADARADARADARADA that can self-assemble into a peptide nanofiber hydrogel. In this study, we synthesized a novel melittin-RADA32-indocyanine green (ICG) hydrogel ("MRI hydrogel"), which contains melittin in the peptide hydrogel backbone and ICG in the hydrogel matrix, for enhanced PTT of glioblastomas. The MRI hydrogel exhibited physiologic characteristics similar to those of the RADA16 hydrogel, while displaying concentration-dependent cytotoxicity to C6 glioma cells and photothermal effects. The in vivo biodistribution of the MRI hydrogel was visualized by near-infrared fluorescence and photoacoustic imaging. More importantly, in vivo PTT provided by the MRI hydrogel significantly reduced the tumor size and the tumor recurrence rate compared with the RADR16-ICG hydrogel and other controls, suggesting a synergistic effect of MRI hydrogel-carried melittin and ICG-based PTT treatment. Thus, MRI provides an alternative tool for the safe and efficient PTT treatment of tumors.


Incidence of diseases of the lower respiratory tract in family practice and low level air pollution.
A simple contact registration in family practices in an urban area in the Netherlands was shown to be a suitable instrument for measuring and analysing the incidence of diseases of the lower respiratory tract. This incidence showed a topographical and a temporal variation. The topographical component was related to the sulphur dioxide (SO2) air pollution in the different districts. The temporal component consisted partly of seasonal variations and partly of short-term variations. A moderate effect of the SO2 air pollution on the temporal variation was observed, but it was weak, possibly owing to the relatively low levels of SO2 in Amsterdam. The present study shows that contact registration in family practices may yield useful data for epidemiological analysis.


[Allelic variants of immune response genes in children with infectious complications during the treatment of acute leukemia].
Infectious complications that arise during the treatment of children with acute leukemia with chemotherapeutic agents at high doses represent a serious problem in oncohematology. To find genetic conditions that may lead to the development of postchemotherapy infections, the genomes of 12 children with acute leukemia who had severe infectious complications during therapy were examined. At the same time, the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing. The analysis revealed 39 nonsynonymous SNPs that lead to amino acid substitutions, including the following informative genetic markers: PTPN22 c.1858C>T (rs2476601), TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791), IL7R c.197T>C (rs1494555) and IL7R c.412G>A (rs1494558). The results of massive parallel sequencing were validated by Sanger sequencing. The identification of genetic markers associated with the predisposition to infectious complications may allow one to assess the individual risk of the severe infection development in children with acute leukemia during the treatment with chemotherapeutic agents and to begin the development of personalized approaches to anticancer therapy.


Multicolor tuning of aggregation-induced emission through substituent variation of diphenyl-o-carborane.
We demonstrate multicolor tuning of aggregation-induced emission (AIE) derived from o-carborane. Both electron-donating and electron-accepting arylacetylenes underwent efficient palladium coupling reaction with bis(4-bromophenyl)-o-carborane, resulting in moderate yields. The emission spectra of these compounds span almost the entire visible spectrum (λ(max) = 452-662 nm). Study on AIE mechanism indicated that CT-based emission of o-carborane derivatives was enhanced by the restriction of molecular motions. The computational study also suggests the possibility of precise color-control of AIE through substituent variation.


Irreversible Humidity-Responsive Phosphorescence Materials from Cellulose for Advanced Anti-Counterfeiting and Environmental Monitoring.
Organic phosphorescence materials have many unique advantages, such as a large Stokes shift, high signal-to-noise ratio, and no interference from background fluorescence and scattered light. But, they generally lack responsiveness. Herein, we developed a new type of biopolymer-based phosphorescence materials with excellent processability and irreversible humidity-responsiveness, via introducing the imidazolium cation to cellulose chain. In the resultant cellulose derivatives, the imidazolium cation promotes the intersystem crossing, meanwhile the cation, chloride anion, and hydroxyl group form multiple hydrogen bonding interactions and electrostatic attraction interactions, which successfully inhibit the nonradiative transitions. As a result, the ionic cellulose derivatives exhibit green phosphorescence at room temperature and can be processed into phosphorescent films, coatings, and patterns. More interestingly, their phosphorescence emission changes when the different processing solvents are used. The ionic cellulose derivatives processed with acetone have a negligible phosphorescence, while they give an irreversible humidity-responsive phosphorescence, which means that the ionic cellulose derivatives processed with acetone exhibit significantly enhanced phosphorescence once they meet water vapor. Such novel irreversible responsive phosphorescence materials have huge potential in advanced anticounterfeiting, information encryption, molecular logic gates, smart tags, and process monitoring.


[Catalase in the blood and leukocytes of patients with nuclear schizophrenia].
The presentation deals with catalase activity in the whole blood and in the leukocytes of patients with nuclear schizophrenia. The catalase activity in the whole blood was higher than in normals. During insulin shock the enzyme activity both in the blood and leukocytes was significantly higher. A low catalase activity in the blood leukocytes in patients with nuclear schizophrenia may be conditioned by a drop in the aerobe respiration and oxidative phosphorilyzing of leukocyte mitochondria.


[Antisense oligodeoxynucleotide therapy for castration-resistant prostate cancer].
Because of recent advances in the field of nucleic-acid chemistry, antisense oligodeoxynucleotide (AS ODN) technology can offer an attractive strategy to specifically inhibit expression of target genes causing a wide variety of diseases, including cancers. In prostate cancer (PC), several genes, involved in the acquisition of castration-resistant (CR) phenotype, have been identified, some of which, such as clusterin and heat shock protein 27, are intensively investigated as optimal targets for AS ODN therapy. In this review, we attempted to summarize the progress in the novel therapeutic strategy using AS ODN against CRPC, and to discuss the data of the recently completed and currently conducting clinical trials using AS ODNs as well as the future prospects of this therapy for treating CRPC.


Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine.
We have previously demonstrated that the copper chelator tetraethylenepentamine (TEPA) enables preferential expansion of early hematopoietic progenitor cells (CD34+CD38-, CD34+CD38-Lin-) in human umbilical cord blood (CB)-derived CD34+ cell cultures. This study extends our previous findings that copper chelation can modulate the balance between self-renewal and differentiation of hematopoietic progenitor cells. In the present study we established a clinically applicative protocol for large-scale ex vivo expansion of CB-derived progenitors. Briefly, CD133+ cells, purified from CB using Miltenyi Biotec's (Bergisch Gladbach, Germany) CliniMACS separation device and the anti-CD133 reagent, were cultured for 3 weeks in a clinical-grade closed culture bag system, using the chelator-based technology in combination with early-acting cytokines (SCF, thrombopoietin, IL-6 and FLT-3 ligand). This protocol was evaluated using frozen units derived from accredited cord blood banks. Following 3 weeks of expansion under large-scale culture conditions that were suitable for clinical manufacturing, the median output value of CD34+ cells increase by 89-fold, CD34+CD38- increase by 30-fold and CFU cells (CFUc) by 172-fold over the input value. Transplantation into sublethally irradiated non-obese diabetic (NOD/SCID) mice indicated that the engraftment potential of the ex vivo expanded CD133+ cells was significantly superior to that of unexpanded cells: 60+/-5.5% vs. 21+/-3.5% CD45+ cells, P=0.001, and 11+/-1.8% vs. 4+/-0.68% CD45+CD34+ cells, P=0.012, n=32, respectively. Based on these large-scale experiments, the chelator-based ex vivo expansion technology is currently being tested in a phase 1 clinical trial in patients undergoing CB transplantation for hematological malignancies.


[Large urethral stones: a case report].
The article describes a clinical observation of a 68 y/o patient with large stones of the urethra, reaching 5 cm in length and located in the penile urethra. The patient underwent a three-stage treatment: the first stage consisted of drainage of the urinary bladder, the second stage of the urethrolithotomy and a double-barreled fistula, the third was an anastomotic urethroplasty. After removing the cystostomic drainage tube, normal urination was restored.


Effects of fixed- and varied-context repetition on associative recognition in amnesia.
This study compared the effects of fixed- and varied-context repetition on associative recognition in amnesia. Controls and amnesic participants were presented with a set of three-word phrases. Each was presented three times. In the varied-context condition, the verb changed with each presentation; in the fixed-context condition, it remained constant. At test, participants performed an associative-recognition task in which they were shown pairs of words from the study phase and asked to distinguish between intact and recombined pairs. For corrected recognition (hits - false alarms), controls performed better in the varied-context than in the fixed-context repetition condition, whereas amnesic participants' performance did not differ between conditions. Similarly, controls had lower false-alarm rates in the varied-context condition, but there was no significant effect of condition for the amnesic participants. Thus, varied-context repetition does not improve amnesic participants' performance on a recollection-dependent associative-recognition task, possibly because the amnesic participants were unable to take advantage of the additional cues that the varied-context encoding condition provided.


The Collaborative Assessment and Management of Suicidality compared to enhanced treatment as usual for inpatients who are suicidal: A randomized controlled trial.
Although use of inpatient crisis hospital intervention for suicide risk is common, the evidence for inpatient treatments that reduce suicidal thoughts and behaviors is remarkably limited. To address this need, this novel feasibility pilot randomized controlled trial compared the use of the Collaborative Assessment and Management of Suicidality (CAMS) to enhanced treatment as usual (E-TAU) within a standard acute inpatient mental health care setting. We hypothesized that CAMS would be more effective than E-TAU in reducing suicidal thoughts and behaviors. As secondary outcomes we also investigated depressive symptoms, general symptom burden, reasons for living, and quality of the therapeutic relationship. All patients were admitted due to acute suicidal thoughts or behaviors. They were randomly assigned to CAMS (n = 43) or E-TAU (n = 45) and assessed at four time points (admission, discharge, 1 month and 5 months after discharge). We used mixed-effects models, effect sizes, and reliable change analyses to compare improvements across and between treatment groups over time. Intent-to-treat analyses of 88 participants [mean age 32.1, SD = 13.5; n = 47 (53%) females] showed that both groups improved over time across all outcome measures with no significant between-group differences in terms of change in suicidal ideation, depression, reasons for living, and distress. However, CAMS showed larger effect sizes across all measures; for treatment completers CAMS patients showed significant improvement in suicidal ideation (p = 0.01) in comparison to control patients. CAMS patients rated the therapeutic relationship significantly better (p = 0.02) than E-TAU patients and were less likely to attempt suicide within 4 weeks after discharge (p = 0.05). CAMS and E-TAU were both effective in reducing suicidal thoughts and symptom distress. Within this feasibility RCT the pattern of results was generally supportive of CAMS suggesting that inpatient use of CAMS is both feasible and promising. However, our preliminary results need further replication within well-powered multi-site randomized controlled trials. DRKS-ID/ICTRP-ID: DRKS00013727. The trial was retrospectively registered in the German Clinical Trials Register, registration code/ DRKS-ID: DRKS00013727 on 12.01.2018 and also in the International Clinical Trials Registry Platform of the World Health Organization (identical registration code).


Living-related renal transplantation in a patient with nail-patella syndrome.
Living-related renal transplantation was performed successfully in a patient with nail-patella syndrome. Graft biopsy 18 months post-transplantation showed normal glomerular basement membrane by electron microscopy. Dystrophic nails of both index fingers had also regrown, suggesting the donor kidney might replenish deficient factors.