Studies on seasonal dynamics of ticks of ogaden cattle and individual variation in resistance to ticks in eastern Ethiopia.
In this study the dominant tick species identified were Amblyomma cohaerens 52.2%, Rhipicephaluspravus 19.3% and A. variegatum 14.6%. A. cohaerens occurred throughout the sampling period and showed a peak during March. Their number declined significantly (P < 0.01) from August to December. R. pravus occurred from July to December only and peaking in September (P < 0.01). A. variegatum occurred in low numbers throughout the study period with a marked seasonal variation (P < 0.01) and abundant numbers of ticks were observed from May to July. The other tick species identified were Boophilus decoloratus, R. bergeoni and R. evertsi evertsi. Individual variation in tick infestation level was observed among the animals (P < 0.05). Since all the animals were of the same breed, age group and were managed similarly the selection of animals with low infestation level can be a component of tick control strategy.


[A technique for removal of entrapped intra-aortic balloon catheter through the left axillary artery].
A case of intra-aortic balloon pumping (IABP) entrapment in which the ruptured catheter could be removed through the left axillary artery was reported. A 68-year-old man was admitted with persistent chest pain, and because of his poor cardiac condition, an IAB catheter was inserted by the Seldinger technique. During attempted extraction of the IAB catheter resistance was encountered and it turned out to be entrapped. Then a guide-wire was passed through the IAB lumen to the left axillary artery, the artery was exposed, and the tip of the guide-wire and IAB catheter were led to the arteriotomy site. After the balloon was dissected, the IAB catheter could be removed through the axillary artery. Finally, left femoro-left branchial artery bypass was performed with e-PTFE graft because of the arterial injury and ischemia of the involved arm. The patient recovered from this episode.


Tau Protein and Its Role in Blood-Brain Barrier Dysfunction.
The blood-brain barrier (BBB) plays a crucial role in maintaining the specialized microenvironment of the central nervous system (CNS). In aging, the stability of the BBB declines and the permeability increases. The list of CNS pathologies involving BBB dysfunction is growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to a host of processes resulting in progressive synaptic, neuronal dysfunction, and detrimental neuroinflammatory changes. Such processes have been implicated in different diseases, including vascular dementia, stroke, Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, hypoxia, ischemia, and diabetes mellitus. The BBB damage is also observed in tauopathies that lack amyloid-β overproduction, suggesting a role for tau in BBB damage. Tauopathies represent a heterogeneous group of around 20 different neurodegenerative diseases characterized by abnormal deposition of the MAPT in cells of the nervous system. Neuropathology of tauopathies is defined as intracellular accumulation of neurofibrillary tangles (NFTs) consisting of aggregated hyper- and abnormal phosphorylation of tau protein and neuroinflammation. Disruption of the BBB found in tauopathies is driven by chronic neuroinflammation. Production of pro-inflammatory signaling molecules such as cytokines, chemokines, and adhesion molecules by glial cells, neurons, and endothelial cells determine the integrity of the BBB and migration of immune cells into the brain. The inflammatory processes promote structural changes in capillaries such as fragmentation, thickening, atrophy of pericytes, accumulation of laminin in the basement membrane, and increased permeability of blood vessels to plasma proteins. Here, we summarize the knowledge about the role of tau protein in BBB structural and functional changes.


Nonlinear optical processes in optically trapped InP nanowires.
We report on the observation of nonlinear optical excitation and related photoluminescence from single InP semiconductor nanowires held in suspension using a gradient force optical tweezers. Photoexcitation of free carriers is achieved through absorption of infrared (1.17 eV) photons from the trapping source via a combination of two- and three-photon processes. This was confirmed by power-dependent photoluminescence measurements. Marked differences in spectral features are noted between nonlinear optical excitation and direct excitation and are related to band-filling effects. Direct observation of second harmonic generation in trapped InP nanowires confirms the presence of nonlinear optical processes.


Structural and Biochemical Characterization of Thioredoxin-2 from Deinococcus radiodurans.
Thioredoxin (Trx), a ubiquitous protein showing disulfide reductase activity, plays critical roles in cellular redox control and oxidative stress response. Trx is a member of the Trx system, comprising Trx, Trx reductase (TrxR), and a cognate reductant (generally reduced nicotinamide adenine dinucleotide phosphate, NADPH). Bacterial Trx1 contains only the Trx-fold domain, in which the active site CXXC motif that is critical for the disulfide reduction activity is located. Bacterial Trx2 contains an N-terminal extension, which forms a zinc-finger domain, including two additional CXXC motifs. The multi-stress resistant bacterium Deinococcus radiodurans encodes both Trx1 (DrTrx1) and Trx2 (DrTrx2), which act as members of the enzymatic antioxidant systems. In this study, we constructed Δdrtrx1 and Δdrtrx2 mutants and examined their survival rates under H2O2 treated conditions. Both drtrx1 and drtrx2 genes were induced following H2O2 treatment, and the Δdrtrx1 and Δdrtrx2 mutants showed a decrease in resistance toward H2O2, compared to the wild-type. Native DrTrx1 and DrTrx2 clearly displayed insulin and DTNB reduction activity, whereas mutant DrTrx1 and DrTrx2, which harbors the substitution of conserved cysteine to serine in its active site CXXC motif, showed almost no reduction activity. Mutations in the zinc binding cysteines did not fully eliminate the reduction activities of DrTrx2. Furthermore, we solved the crystal structure of full-length DrTrx2 at 1.96 Å resolution. The N-terminal zinc-finger domain of Trx2 is thought to be involved in Trx-target interaction and, from our DrTrx2 structure, the orientation of the zinc-finger domain of DrTrx2 and its interdomain interaction, between the Trx-fold domain and the zinc-finger domain, is clearly distinguished from those of the other Trx2 structures.


CURVATURE-DRIVEN MOLECULAR FLOW ON MEMBRANE SURFACE.
This work presents a mathematical model for the localization of multiple species of diffusion molecules on membrane surfaces. Morphological change of bilayer membrane in vivo is generally modulated by proteins. Most of these modulations are associated with the localization of related proteins in the crowded lipid environments. We start with the energetic description of the distributions of molecules on curved membrane surface, and define the spontaneous curvature of bilayer membrane as a function of the molecule concentrations on membrane surfaces. A drift-diffusion equation governs the gradient flow of the surface molecule concentrations. We recast the energetic formulation and the related governing equations by using an Eulerian phase field description to define membrane morphology. Computational simulations with the proposed mathematical model and related numerical techniques predict (i) the molecular localization on static membrane surfaces at locations with preferred mean curvatures, and (ii) the generation of preferred mean curvature which in turn drives the molecular localization.


Analyses of subjects with hypokalemic metabolic alkolosis, Gitelman's and Bartter's syndrome.
The two most common forms of inherited normotensive hypokalemic metabolic alkalosis are Bartter's and Gitelman's syndromes. Bartter's is mostly seen in children, while Gittelman's is mostly seen in adolescents and adults. We analyze three subjects of adult-onset Gitelman's and Bartter's syndrome. The patients applied to our hospital due to severe hypokalemia with little clinical expression (paresthesia, cramp, polyuria, polydipsia, and/or weakness). All had normal blood pressure, hypokalemia, hyperreninemic hyperaldosteronism, and a decrease in the fractional chloride reabsorption. Key elements in differential diagnosis of chronic hypokalemia are blood pressure assessment, acid base equilibrium, serum calcium concentration, and 24-hour urine potassium and calcium excretion.


Long-term safety and efficacy of distal aneurysm treatment with flow diversion in the M2 segment of the middle cerebral artery and beyond.
Indications for flow diversion stent (FDS) treatment are expanding. However, there is still a lack of evidence for the long-term outcome in distally located aneurysms in the M2 segment of the middle cerebral artery (MCA) and beyond. Consecutive subjects (from June 2013 to August 2020) with MCA aneurysms in the M2 segment or beyond treated with FDS were reviewed retrospectively. The primary endpoints for clinical safety were the absence of mortality, stroke event, re-rupture of the aneurysm, and worsening of clinical symptoms. The primary endpoint for treatment efficacy was complete/near-complete occlusion at follow-up after 12 months. 23 patients were identified: 7 aneurysms were located in the M2 segment of the MCA, 4 in the M2-M3 bifurcation, 2 in M3, 3 in M3-4 branching, and 2 in M4; 5 aneurysms were located in M2 with extension into the M1-M2 bifurcation. 13 aneurysms were of fusiform morphology, 8 sacculofusiform, and 2 saccular. 16 aneurysms were of highly suspected dissecting etiology. The median diameter of the parent vessel was 2.1 mm proximally and 2 mm distally. The median time of the follow-up was 30 months (range 16 months to 6 years). Complete/near complete occlusion was observed in 14/20 patients (70%) and one stable remodeling (5%) was seen at 12 months. 22 patients (95.6%) had an excellent clinical outcome (mRS 0-1) at 6 months. Technical challenges associated with the deployment of FDS occurred in 8.7% of cases. Severe complications, intraparenchymal hemorrhage and re-rupture of the aneurysm occurred in 2 patients (8.7%). Flow diversion of distally located aneurysms is technically feasible with low morbidity and mortality.


Response of cyclin B1 to ionizing radiation: regulation by NF-kappaB and mitochondrial antioxidant enzyme MnSOD.
To understand the molecular response of tumor cells to therapeutic ionizing radiation (IR), we previously reported that human breast cancer cells derived following chronic exposure to fractionated ionizing radiation (MCF+FIR) showed a transient radioresistance. MCF+FIR cells also demonstrated increased activity of NF-kappaB, increased expression of the mitochondrial antioxidant enzyme (MnSOD), and increased expression of a cell cycle regulatory protein (Cyclin B1). The present studies were designed to determine the relationship of NF-kappaB, MnSOD and Cyclin B1 expression in cellular adaptive responses to ionizing radiation. The first intron of the cyclin B1 gene with a putative NF-kappaB element was cloned into the pGL3 luciferase reporter (pGL3CB1EI1). PGL3CB1EI1 and control NF-kappaB luciferase activities were determined in MCF-7 and MCF+FIR cells treated with a single dose of radiation, over expression of the dominant negative mutant IkB (mIkB) or over expression of the SOD2 gene. MCF+FIR cells derived from fractionated IR demonstrated increased transactivation of the pGL3CB1EI1 and NF-kappaB controlled reporter activities, relative to the parental cell line. Transfection of dominant negative mutant IkB that inhibits NF-kappaB nuclear translocation, inhibited pGL3CB1EI1 and NF-kappaB activity, indicating the NF-kappaB dependence of pGL3CB1EI1 mediated transcription. In addition, over expression of the human SOD2 gene (MnSOD) inhibited NF-kappaB and pGL3CB1EI1 activity, indicating that superoxide or some species derived from superoxide may have participated in the up-regulation of reporter activity in response to chronic exposure to fractionated ionizing radiation. These results provide evidence suggesting that a signaling pathway involving NF-kappaB and Cyclin B1 may contribute to adaptive radioresistance induced by chronic exposure to fractionated IR and support the conclusion that MnSOD appears to be a negative regulator of this pathway.


[A case of Ewing's sarcoma treated successfully by combination chemotherapy consisting of high-dose methotrexate, aclacinomycin-A and vindesine].
A 22-year-old man was admitted to Kyushu University Hospital because of high fever, and pain in the right foot and back. An X-ray examination revealed an osteolytic lesion on the 5th metatarsal bone of the right foot. Paraplegia and disturbance of bladder function occurred and compression of the spinal cord between T3 and L5 was found by myelography. An extradural tumor was removed by emergent laminectomy, and a histological examination of the tumor showed aggregations of small round cells, which suggested Ewing's sarcoma. Although T-9 protocol was started with initial effect, the tumor recurred during the therapy. The patient was then treated with HD-MTX, ACR and VDS, which induced a clinical improvement for 4 months without maintenance therapy. This result showed that HD-MTX, ACR and VDS warrant further consideration for the treatment of refractory Ewing's sarcoma.


Acute L-glutamine deprivation affects the expression of TP53-related protein genes in U87 glioma cells.
We have studied the effect of acute L-glutamine deprivation on the expression oftumor protein 53 (TP53)-related genes such as TOPORS (topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligase), TP53BPI (TP53 bindingprotein 1), TP53TG1 (TP53 inducible gene 1), SESN1 (p53 regulatedPA26 nuclear protein), NME6 (NME/NM23 nucleoside diphosphate kinase 6), and ZMAT3 (zinc finger Matrin-type 3) in glioma cells with ERN1 knockdown. It was shown that blockade of ERN1 finction in U87 glioma cells is induced the expression of RYBP and SESN1 genes, but decreased the expression of TP53BP1, TP53TG1, TOPORS, NME6, genes. Moreover, the expression levels ofRYBPI SESN1, TP53BP1, and ZMAT3 genes is increased in control glioma cells by L-glutamine deprivation condition but blockade of ERN1 signaling enzyme function significantly enhances this effect on the expression all of these genes. At the same time, the ERN1 knockdown eliminates the response TP53TG1 and TOPORS genes to L-glutamine deprivation condition. Results of this investigation clearly demonstrate that the expression most of genes encoding TP53-related factors depends upon acute L-glutamine deprivation condition as well as upon ERN1, the major signaling system of the endoplasmic reticulum stress.


Suppression of cellulase and polygalacturonase and induction of alcohol dehydrogenase isoenzymes in avocado fruit mesocarp subjected to low oxygen stress.
Expression of polygalacturonase and cellulase, two hydrolytic enzymes of avocado (Persea americana, cv Hass) fruit which are synthesized de novo during ripening, and alcohol dehydrogenase, a known anaerobic protein, were studied under different O(2) regimes. Low O(2) concentrations (2.5-5.5%) diminished the accumulation of polygalacturonase and cellulase proteins and the expression of their isoenzymes. This pattern of change in cellulase protein was also reflected in the steady-state amount of its mRNA. In contrast, 7.5 and 10% O(2) did not alter the changes observed in fruits ripened in air. On the other hand, alcohol dehydrogenase was induced in 2.5, 3.5, and 5.5% O(2) but not in 7.5 or 10% O(2). The recovery from the hypoxic stress upon returning the fruits back to air for 24 hours, was also a function of O(2) tensions under which the fruits were kept. Thus, the synthesis of polygalacturonase and cellulase was directly related to O(2) levels, while the activity of the isoenzymes of alcohol dehydrogenase was inversely related to O(2) levels. The results indicate that hypoxia exerts both negative and positive effects on the expression of certain genes and that these effects are initiated at the same levels of O(2).


The Role of Gut and Lung Microbiota in Susceptibility to Tuberculosis.
Tuberculosis is one of the most common infectious diseases and infectious causes of death worldwide. Over the last decades, significant research effort has been directed towards defining the understanding of the pathogenesis of tuberculosis to improve diagnosis and therapeutic options. Emerging scientific evidence indicates a possible role of the human microbiota in the pathophysiology of tuberculosis, response to therapy, clinical outcomes, and post-treatment outcomes. Although human studies on the role of the microbiota in tuberculosis are limited, published data in recent years, both from experimental and clinical studies, suggest that a better understanding of the gut-lung microbiome axis and microbiome-immune crosstalk could shed light on the specific pathogenetic mechanisms of Mycobacterium tuberculosis infection and identify new therapeutic targets. In this review, we address the current knowledge of the host immune responses against Mycobacterium tuberculosis infection, the emerging evidence on how gut and lung microbiota can modulate susceptibility to tuberculosis, the available studies on the possible use of probiotic-antibiotic combination therapy for the treatment of tuberculosis, and the knowledge gaps and future research priorities in this field.


Colorimetric assays for quantitative analysis and screening of epoxide hydrolase activity.
Focusing on directed evolution to tailor enzymes as usable biocatalysts for fine chemistry, we have studied in detail several colorimetric assays for quantitative analysis of epoxide hydrolase (EH) activity. In particular, two assays have been optimized to characterize variants issued from the directed evolution of the EH from Aspergillus niger. Assays described in this paper are sufficiently reliable for quantitative screening of EH activity in microtiter plates and are low cost alternatives to GC or MS analysis. Moreover, they are usable for various epoxides and not restricted to a type of substrate, such as those amenable to assay by UV absorbancy. They can be used to assay EH activity on any epoxide and to directly assay enantioselectivity when both (R) and (S) substrates are available. The advantages and drawbacks of these two methods to assay EH activity of a large number of natural samples are summarized.


LD, interpersonal understanding, and social behavior in the classroom.
This study used Baron and Kenny's (1986) criteria for mediation to investigate the extent to which interpersonal understanding mediates the relation between learning disabilities (LD) and social adaptation in the classroom. Twenty-two children with and 22 children without a diagnosis of LD completed a semistructured developmental clinical interview measure of interpersonal understanding. They were also rated by their fourth- and fifth-grade teachers on a measure of social adaptation in the classroom. Interpersonal understanding and social adaptation in the classroom were found to be positively correlated. Children with LD exhibited less interpersonal understanding and social adaptation. Although this group difference on social adaptation was greatly reduced when interpersonal understanding was statistically controlled, it remained statistically significant. These results suggest that reduced social adaptation in the classroom and lower interpersonal understanding are both associated with a diagnosis of LD. However, they do not conclusively support the claim that interpersonal understanding mediates the relation between LD and social adaptation. Thus, whether the social difficulties of people with LD stem from the same complex phenomena that produce these people's learning problems remains an open question.


An appreciation of Ralph Marvin Steinman (1943–2011).
Ralph Steinman, an editor at the Journal of Experimental Medicine since 1978, shared the 2011 Nobel Prize in Physiology or Medicine for his discovery of dendritic cells (DCs) and their role in immunity. Ralph never knew. He died of pancreatic cancer on September 30, 3 days before the Nobel announcement. Unaware of his death at the time of their announcement, the Nobel Committee made the unprecedented decision that his award would stand. Ralph was the consummate physician-scientist to the end. After his diagnosis, he actively participated in his 4.5 years of treatments, creating experimental therapies using his own DCs in conjunction with the therapies devised by his physicians, all the while traveling, lecturing, and most of all pursuing new investigations in his laboratory. For 38 years—from his discovery of DCs to his Nobel Prize—Ralph pioneered the criteria and methods used to identify, isolate, grow, and study DCs. He and his colleagues demonstrated that DCs are initiators of immunity and regulators of tolerance. In his most recent studies, Ralph was harnessing the specialized features of DCs to design improved vaccines. The following synopsis describes some of his seminal discoveries.


B7H3 expression and significance in idiopathic pulmonary fibrosis.
The clinical significance of B7H3 (CD276) and its cleavage product soluble B7H3 (sB7H3) in idiopathic pulmonary fibrosis (IPF) is unknown. Mounting evidence suggests the potential utility of peripheral blood myeloid cell enumeration to predict disease outcome and indicate active lung disease. Here we hypothesized that sB7H3 is involved in regulation of circulating myeloid cells in pulmonary fibrosis. In support of this possibility, both plasma sB7H3 and B7H3+ cells were elevated in IPF patient blood samples, which correlated negatively with lung function. To analyze its function, the effects of sB7H3 on naïve or bleomycin-treated mice were examined. The results revealed that sB7H3 injection induced an influx of myeloid-derived suppressor cells (MDSCs) and Ccl2 expression in lung tissue of naïve mice, accompanied by enhanced overall inflammation. Additionally, sB7H3 caused accumulation of MDSCs in bone marrow with increased expression of inflammatory cytokines. Notably, in vitro assays revealed chemotaxis of MDSCs to sB7H3, which was dependent on TLT-2 (TREML2), a putative receptor for sB7H3. Thus, increased circulating sB7H3 and/or B7H3+ cells in IPF patient blood samples correlated with lung function decline and potential immunosuppressive status. The correlation of sB7H3 with deterioration of lung function might be due to its ability to enhance inflammation and recruitment of MDSCs into the lung and their expansion in the bone marrow, and thus potentially contribute to IPF exacerbation. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers.
Pluronic block copolymers are recognized pharmaceutical excipients listed in the US and British Pharmacopoeia. The incorporation of drugs into Pluronic micelles results in increased solubility and stability of drugs. Consequently, the micelles are used for delivery of drugs in the body. Pluronic unimers sensitize multidrug-resistant cells by inhibiting drug efflux transporters. This allows for the development of formulations for the treatment of multidrug-resistant and metastatic tumors. Furthermore, these formulations can be used to enhance brain and oral bioavailability of various drugs. Finally, Pluronic formulations were shown to enhance transgene expression in the body. This opens new possibilities for the use of Pluronic in gene therapies.


Quantum Monte Carlo ground state energies for the singly charged ions from Li through Ar.
Nonrelativistic frozen nucleus all-electron Quantum Monte Carlo ground state energies of positive and negative ions Li(+) to Ar(+) and Li(-) to Cl(-), respectively, are reported. Explicitly correlated wave functions with a single configuration model function times a Jastrow factor are employed for all of the systems studied. The accuracy obtained for the ions in the third period is similar to that reached for the ions in the second one. For those ions with a stronger multiconfiguration nature a restricted multiconfiguration expansion has been employed. The ground state energy here obtained for the charged species shows a similar quality to that reached for neutral atoms. Starting from those results, ionization potentials and electron affinities are calculated.


The Effect of Preprocedural Anxiety on General Anesthesia Management: A Case Report.
Preoperative anxiety occurs in many surgical patients and yet there are no clear recommendations on how to provide the best evidence-based care to these patients during a general anesthetic. The following case report describes a complex case of a 35-year-old female who presented for imaging under general anesthesia with high preoperative anxiety. She displayed fluctuations in hemodynamics, an increased induction dose of propofol, and vasopressor support throughout the intraoperative phase of care. This case report describes the current evidence for considerations of high anxiety operative patients, which may include an increased induction and total dose of propofol, increased analgesic requirement, and an individualized preoperative assessment to establish a baseline anxiety level and proper education.


Fiber Nanoarchitectonics for Pre-Treatments in Facile Detection of Short-Chain Fatty Acids in Waste Water and Faecal Samples.
Short-chain fatty acids (SCFAs) are among the active metabolites in biological process both in the intestinal tract and the bioconversion of organic wastes, which has resulted in various human diseases and environmental problems. In order to accurately detect SCFAs, we introduced a novel extraction sorbent. Electrospun polyacrylonitrile (PAN) nanofiber membrane was synthesized, then poly (3, 4-Ethylenedioxythiophene) (PEDOT) was deposited onto the surface of electrospun PAN nanofibers by in situ polymerization. The morphology of the composite PAN/PEDOT nanofiber was characterized by scanning electronic microscopy (SEM) and FTIR spectrum. PAN/PEDOT was used to isolate and concentrate the SCFAs in waste water and fecal samples before gas chromatography mass spectrometry (GC-MS) analysis. The analytical method was evaluated systematically, and low limits of detection (LODs) of 0.34-0.87 μg/L and good linearity (R2 ≥ 0.9953) were obtained. The method was applied successfully for the determination of SCFAs in waste water and fecal samples, with good recovery (87.5-104.6%) and satisfactory reproducibility (relative standard deviation: 6.5-14.1%). The results indicated that the proposed method can be used as a potential approach for the determination of SCFAs with high sensitivity in waste water and biological samples.


VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses.
Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two structurally-related neuropeptides with widespread expression in the central and peripheral nervous systems. Although these peptides have been repeatedly shown to exert potent anti-inflammatory actions when administered in animal models of inflammatory disease, mice deficient in VIP and PACAP were recently shown to exhibit different phenotypes (ameliorated and exacerbated, respectively) in response to experimental autoimmune encephalomyelitis (EAE). Therefore, elucidating what are the specific immunoregulatory roles played by each of their receptor subtypes (VPAC1, VPAC2, and PAC1) is critical. In this study, we found that mice with a genetic deletion of VIPR2, encoding the VPAC2 receptor, exhibited exacerbated (MOG35-55)-induced EAE compared to wild type mice, characterized by enhanced clinical and histopathological features, increased proinflammatory cytokines (TNF-α, IL-6, IFN-γ (Th1), and IL-17 (Th17)) and reduced anti-inflammatory cytokines (IL-10, TGFβ, and IL-4 (Th2)) in the CNS and lymph nodes. Moreover, the abundance and proliferative index of lymph node, thymus and CNS CD4(+)CD25(+)FoxP3(+) Tregs were strikingly reduced in VPAC2-deficient mice with EAE. Finally, the in vitro suppressive activity of lymph node and splenic Tregs from VPAC2-deficient mice was impaired. Overall, our results demonstrate critical protective roles for PACAP and the VPAC2 receptor against autoimmunity, promoting the expansion and maintenance of the Treg pool.


Insect frass as a pathway for transmission of bacterial wilt of cucurbits.
Insects that vector diseases of plants are of critical concern to agriculture, but relationships between the vectors and pathogens often are poorly understood. In this study, we present research on vector relationships between the striped cucumber beetle, Acalymma vittatum (F.) (Coleoptera: Chrysomelidae), and the pathogen that causes bacterial wilt of cucurbits, Erwinia tracheiphila (Smith) (Enterobacteriales: Enterobacteriaceae). We studied how the bacteria were retained in the gut of the beetle by developing a polymerase chain reaction (PCR)-based technique for extracting and identifying bacterial DNA in the frass. Bacterial DNA usually was present in the frass for 24 h after beetles had consumed inoculum but diminished quickly and was undetectable within 96 h. The amount of time that bacterial DNA could be detected in frass increased with the amount of inoculum and the length of time that beetles were exposed to inoculum and also varied with the strain of bacterium. Frass that tested positive for bacterial DNA also was infective to cucumber plants, confirming that DNA was indicative of viable bacteria and that frass could be a pathway for transmission of the pathogen. This research suggests that few cucumber beetles serve as long-term vectors of the pathogen and that aggregation of the beetle on host plants may be critical for initiating plant infections in spring.


[Total synthesis of an analogue of schizandrin].
A schizandrin analogue 9, 1, 2, 3, 10, 11, 12-hexamethoxy-6,7-dihydroxy-cis-6,7-dimethyl dibenzocyclooctadiene, is one of the metabolites of schizandrin with comparable anti-convulsion activity. In this paper, compound 9 was synthesized from gallic acid through the following sequence of reactions: methylation, Henry condensation, reduction with Fe-FeCl3-HCl, intermolecular reductive coupling and intramolecular nonphenolic oxidative coupling, totally in seven steps. The intermediate 1,4-diaryl-2,3-dimethyl-2,3-butanediol (7) which is a mixture of erythro and threo isomers was converted by DDQ in TFA into compound 9 and another new compound 10 via a different reaction path.


Dissociation of water over Ti-decorated C60.
Using first-principles calculations we have studied the reactions of water over Ti-decorated C(60) in order to assess the possibility of using this system as a catalyst for water dissociation. Our results show that a single water molecule dissociates exothermically with a small energy barrier on a single Ti atom adsorbed on C(60). After dissociation, both H(+) and OH(-) ions bind strongly to the Ti atom, which serves as an effective reactive center that facilitates further water splitting. When a second water molecule is introduced, we observe the formation of a hydrogen molecule with a comparably small activation barrier. When the coverage of Ti on C(60) is increased, the formation of Ti dimer does not change the catalytic effect of TiC(60) complex very much. Our results provide fundamental insights into the mechanisms of water dissociation on such a prototypical nanostructure and suggest that Ti-decorated C(60) could be exploited as a catalyst for water splitting to generate hydrogen.


Transport Properties of CO2 in Different Reactivity Coke Solution Loss Reaction Based on Stefan Flow Theory.
In this paper, the influence of Stefan flow on different reactivity coke solution loss reaction (Ccoke + CO2 = 2CO) at different temperatures were analyzed and compared to deeply understand the mechanism of the coke solution loss reaction. Isothermal experiments of carbon dioxide gasification with Coke A (low reactivity), Coke B (medium reactivity), and Coke C (high reactivity), respectively, were carried out at 1100-1300 °C. After calculation, it is concluded that the external diffusion coefficients and the mass transfer coefficients with Stefan flow of three kinds of coke were decreased, and their minimum average deviations with and without Stefan flow were 44.57/43.27/43.23 and 42.57/39.47/39.15%, respectively. As the coke reactivity increased, the diffusion and mass transfer capacity of carbon dioxide with Stefan flow in the boundary layer decreased. The carbon dioxide concentration on the outer surface of three kinds of coke with Stefan flow was less than that without Stefan flow. The influence of Stefan flow on carbon dioxide concentration on the outer surface of coke was increased with the increase of coke reactivity. The area of carbon dioxide concentration region in the three kinds of coke declined after modification, and the deviations of the carbon dioxide concentration region area before and after modification of three kinds of coke ranged from 6.62 to 22.85%, 7.74 to 25.17%, and 8.62 to 26.74%. The influence of Stefan flow on the carbon dioxide concentration region increased as coke reactivity increased.


Adaptive response of Rhodococcus opacus PWD4 to salt and phenolic stress on the level of mycolic acids.
Mycolata form a group of Gram-positive bacteria with unique cell envelope structures that are known for their high tolerance against antibiotics and both aromatic and aliphatic hydrocarbons. An important part of the unique surface structure of the mycolata is the presence of long chain α-alkyl-β-hydroxy fatty acids, the mycolic acids. In order to investigate the adaptive changes in the mycolic acid composition, we investigated the composition of mycolic acids during the response both to osmotic stress caused by NaCl and to 4-chlorophenol in Rhodococcus opacus PWD4. This bacterium was chosen as it is known to adapt to different kinds of stresses. In addition, it is a potential biocatalyst in bioremediation as well as for biotechnological applications. In the present study, cells of R. opacus PWD4, grown in liquid cultures, responded to toxic concentrations of NaCl by increasing the ratio between mycolic acids and membrane phospholipid fatty acids (MA/PLFA-ratio). Cells reacted to both NaCl and 4-chlorophenol by decreasing both the average chain length and the unsaturation index of their mycolic acids. These changes in mycolic acid composition correlated with increases in cell surface hydrophobicity and saturation of membrane fatty acids, demonstrating the relation between mycolic acid and phospholipid synthesis and their contribution to cell surface properties of R. opacus PWD4.


In Silico Prediction of the Toxic Potential of Neuroprotective Bifunctional Molecules Based on Chiral N-Propargyl-1,2-amino Alcohol Derivatives.
N-Propargylamines are useful synthetic scaffolds for the synthesis of bioactive molecules, and in addition, they possess important pharmacological activities. We obtained several neuroprotective molecules, chiral 1,2-amino alcohols and 1,2-diamines, able to reduce by almost 70% the rotenone and oligomycin A-induced damage in SH-SY5Y cells. Furthermore, some molecules assessed also counteracted the toxicity evoked by the Ser/Thr phosphatase inhibitor okadaic acid. Before extrapolating these data to preclinical studies, we analyze the molecules through an in silico prediction system to detect carcinogenicity risk or other toxic effects. In light of these promising results, these molecules may be considered as a lead family of neuroprotective and relatively safe compounds.


[Mature teratoma of the posterior mediastinum].
Mature teratoma is the most frequent primary germ-cell occurring in the anterior mediastinum. We report a case of a 67-year-old man with mature teratoma of the posterior mediastinum. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification.


The relationship of headache symptoms with severity and duration of attacks.
Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache.


Polyclonal anti-idiotypes induce antibody responses protective against ricin cytotoxicity.
Protein G-purified goat anti-ricin IgG, previously demonstrated to protect against ricin toxicity in vitro and in vivo, was used to raise BALB/c mouse and New Zealand White rabbit polyclonal anti-idiotypic antibodies. The generated anti-idiotypic sera were repeatedly absorbed over agarose conjugated to normal goat immunoglobulins, and purified by protein A-agarose affinity chromatography. Immunization of BALB/c mice with BALB/c anti-idiotypes did not result in a significant anti-ricin antibody response. However, injection of BALB/c mice with BALB/c anti-idiotypes conjugated to keyhole limpet haemocyanin (KLH) or with unconjugated rabbit anti-idiotypes resulted in specific and anti-ricin immune responses. The anti-idiotype-induced anti-ricin antibody responses protected against the in vitro cytotoxicity of ricin, a potent plant-derived protein synthesis inhibitor, as assessed by the murine EL-4 leukaemia cell assays. Thus, anti-idiotype-based vaccines may represent an alternative, safe and effective means of inducing protective immunity against toxins such as ricin, whose extreme in vivo toxicity render them unsafe as immunogens.


Both substance P and its receptor are expressed in mouse intestinal T lymphocytes.
Substance P (SP), one of the most prevalent neuropeptides in gut, has been reported to have potent immune modulatory effects as a proinflammatory agent. The synthesis of SP and SP receptor expression in intraepithelial and lamina propria T lymphocytes of mouse intestine was investigated. Using RT-PCR analysis, it was demonstrated that SP receptor mRNA was exclusively expressed in intraepithelial and lamina propria T lymphocytes as well as their purified CD4+, CD8+ and CD4-CD8-CD3+ subsets. Messenger RNAs (mRNAs) for the two precursors of SP, beta and gamma-preprotachykinin-A, were also detected. These results were consistent in lymphocytes from both epithelium and lamina propria of small and large intestines, although the frequencies and/or intensities of mRNA expression varied. However, none of the findings could be repeated in splenic T lymphocytes. Activation of splenocytes with anti-CD3epsilon-chain mAb and PMA did not induce expression of SP or its receptor mRNAs. Furthermore, both cytoplasmic and surface-bound SP was demonstrated in intestinal T lymphocytes using dual color immunocytochemistry and immunoflow cytometry. In vitro treatment with SP did not significantly change the size of the SP-immunoreactive T cell population, indicating the presence of SP receptor on intestinal T lymphocytes as well as in vivo binding of endogenously released SP. Our data suggest that SP production and SP receptor expression are distinctive for mouse intestinal mucosal immunity and that SP may act as a modulator of an ongoing controlled inflammation in normal gut, by acting through its specific receptor on T lymphocytes in an autocrine and/or paracrine pattern.


Psychomimetic reactions after neurolept and propofol anaesthesia.
The purpose of this study was to compare the frequency of psychomimetic reactions after 24 h and 3 months following total intravenous anaesthesia with propofol and neurolept anaesthesia. Forty otherwise healthy female patients were randomly divided into two groups. All were undergoing elective gynaecological laparotomy for non-malignant disease. Nineteen patients were anaesthetized with droperidol, fentanyl, pancuronium, N2O/O2. Twenty patients received total intravenous anaesthesia with propofol, fentanyl and pancuronium. Twenty-four hours after the anaesthesia the patients were interviewed about their subjective experiences of anaesthesia and recovery. Three months after the operation the patients were sent a questionnaire concerning ability to work, sleep and memory disorders. After 24 h the anaesthesia was judged as good by 18 patients receiving propofol and 13 patients receiving NLA (n.s.). The recovery was judged as good by 16 patients in the propofol group and six patients in the NLA group (P < 0.05). Locked-in feelings were reported by one patient in the propofol group and ten patients in the NLA group (P < 0.01). Impairment of memory was reported by one patient in the propofol group and seven patients in the NLA group (P < 0.01). A questionnaire used after 3 months was answered by 18 patients in the propofol group and 17 patients in the NLA group. There were few complaints, and no differences were found between the two groups. In conclusion, total intravenous anaesthesia with propofol seems more acceptable than anaesthesia with neurolept as judged by the patients 24 h after anaesthesia. There were no differences between the two groups concerning psychomimetic reactions 3 months after anaesthesia.


Generation of dyskeratosis congenita-like hematopoietic stem cells through the stable inhibition of DKC1.
Dyskeratosis congenita (DC) is a rare telomere biology disorder, which results in different clinical manifestations, including severe bone marrow failure. To date, the only curative treatment for the bone marrow failure in DC patients is allogeneic hematopoietic stem cell transplantation. However, due to the toxicity associated to this treatment, improved therapies are recommended for DC patients. Here, we aimed at generating DC-like human hematopoietic stem cells in which the efficacy of innovative therapies could be investigated. Because X-linked DC is the most frequent form of the disease and is associated with an impaired expression of DKC1, we have generated DC-like hematopoietic stem cells based on the stable knock-down of DKC1 in human CD34+ cells with lentiviral vectors encoding for DKC1 short hairpin RNAs. At a molecular level, DKC1-interfered CD34+ cells showed a decreased expression of TERC, as well as a diminished telomerase activity and increased DNA damage, cell senescence, and apoptosis. Moreover, DKC1-interfered human CD34+ cells showed defective clonogenic ability and were incapable of repopulating the hematopoiesis of immunodeficient NSG mice. The development of DC-like hematopoietic stem cells will facilitate the understanding of the molecular and cellular basis of this inherited bone marrow failure syndrome and will serve as a platform to evaluate the efficacy of new hematopoietic therapies for DC.


Mathematical Modeling of Proliferative Immune Response Initiated by Interactions Between Classical Antigen-Presenting Cells Under Joint Antagonistic IL-2 and IL-4 Signaling.
During an adaptive immune response from pathogen invasion, multiple cytokines are produced by various immune cells interacting jointly at the cellular level to mediate several processes. For example, studies have shown that regulation of interleukin-4 (IL-4) correlates with interleukin-2 (IL-2) induced lymphocyte proliferation. This motivates the need to better understand and model the mechanisms driving the dynamic interplay of proliferation of lymphocytes with the complex interaction effects of cytokines during an immune response. To address this challenge, we adopt a hybrid computational approach comprising of continuous, discrete and stochastic non-linear model formulations to predict a system-level immune response as a function of multiple dependent signals and interacting agents including cytokines and targeted immune cells. We propose a hybrid ordinary differential equation-based (ODE) multicellular model system with a stochastic component of antigen microscopic states denoted as Multiscale Multicellular Quantitative Evaluator (MMQE) implemented using MATLAB. MMQE combines well-defined immune response network-based rules and ODE models to capture the complex dynamic interactions between the proliferation levels of different types of communicating lymphocyte agents mediated by joint regulation of IL-2 and IL-4 to predict the emergent global behavior of the system during an immune response. We model the activation of the immune system in terms of different activation protocols of helper T cells by the interplay of independent biological agents of classic antigen-presenting cells (APCs) and their joint activation which is confounded by the exposure time to external pathogens. MMQE quantifies the dynamics of lymphocyte proliferation during pathogen invasion as bivariate distributions of IL-2 and IL-4 concentration levels. Specifically, by varying activation agents such as dendritic cells (DC), B cells and their joint mechanism of activation, we quantify how lymphocyte activation and differentiation protocols boost the immune response against pathogen invasion mediated by a joint downregulation of IL-4 and upregulation of IL-2. We further compare our in-silico results to in-vivo and in-vitro experimental studies for validation. In general, MMQE combines intracellular and extracellular effects from multiple interacting systems into simpler dynamic behaviors for better interpretability. It can be used to aid engineering of anti-infection drugs or optimizing drug combination therapies against several diseases.


Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort.
Ultra-processed food (UPF) consumption has increased drastically worldwide and already represents 50%-60% of total daily energy intake in several high-income countries. In the meantime, the prevalence of overweight and obesity has risen continuously during the last century. The objective of this study was to investigate the associations between UPF consumption and the risk of overweight and obesity, as well as change in body mass index (BMI), in a large French cohort. A total of 110,260 adult participants (≥18 years old, mean baseline age = 43.1 [SD 14.6] years; 78.2% women) from the French prospective population-based NutriNet-Santé cohort (2009-2019) were included. Dietary intakes were collected at baseline using repeated and validated 24-hour dietary records linked to a food composition database that included >3,500 different food items, each categorized according to their degree of processing by the NOVA classification. Associations between the proportion of UPF in the diet and BMI change during follow-up were assessed using linear mixed models. Associations with risk of overweight and obesity were assessed using Cox proportional hazard models. After adjusting for age, sex, educational level, marital status, physical activity, smoking status, alcohol intake, number of 24-hour dietary records, and energy intake, we observed a positive association between UPF intake and gain in BMI (β Time × UPF = 0.02 for an absolute increment of 10 in the percentage of UPF in the diet, P < 0.001). UPF intake was associated with a higher risk of overweight (n = 7,063 overweight participants; hazard ratio (HR) for an absolute increase of 10% of UPFs in the diet = 1.11, 95% CI: 1.08-1.14; P < 0.001) and obesity (n = 3,066 incident obese participants; HR10% = 1.09 (1.05-1.13); P < 0.001). These results remained statistically significant after adjustment for the nutritional quality of the diet and energy intake. Study limitations include possible selection bias, potential residual confounding due to the observational design, and a possible item misclassification according to the level of processing. Nonetheless, robustness was tested and verified using a large panel of sensitivity analyses. In this large observational prospective study, higher consumption of UPF was associated with gain in BMI and higher risks of overweight and obesity. Public health authorities in several countries recently started to recommend privileging unprocessed/minimally processed foods and limiting UPF consumption. ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).


Mechanical perturbation of jaw movements during speech: effects on articulation and phonation.
12 subjects uttered the testword/papapas/repeatedly with three different speech rates and two stress patterns. On 17% randomly chosen trials, a mechanical load was applied unpredictably to the jaw in the direction of the opening movement. Load onset was triggered by the start of the first phonation. Analysis showed that the opening and closing displacements of the jaw movement in the first syllable were not influenced significantly by the perturbation. The load application prolonged the duration of the jaw movement in unstressed syllables but not in stressed syllables. Further, the mechanical perturbation of the jaw led to increased duration of phonation in unstressed syllables only, the effect for duration of phonation being greater at higher speech rates. These results demonstrate a coupling between articulation and phonation.


Understanding the mental health of doctoral researchers: a mixed methods systematic review with meta-analysis and meta-synthesis.
Data from studies with undergraduate and postgraduate taught students suggest that they are at an increased risk of having mental health problems, compared to the general population. By contrast, the literature on doctoral researchers (DRs) is far more disparate and unclear. There is a need to bring together current findings and identify what questions still need to be answered. We conducted a mixed methods systematic review to summarise the research on doctoral researchers' (DRs) mental health. Our search revealed 52 articles that were included in this review. The results of our meta-analysis found that DRs reported significantly higher stress levels compared with population norm data. Using meta-analyses and meta-synthesis techniques, we found the risk factors with the strongest evidence base were isolation and identifying as female. Social support, viewing the PhD as a process, a positive student-supervisor relationship and engaging in self-care were the most well-established protective factors. We have identified a critical need for researchers to better coordinate data collection to aid future reviews and allow for clinically meaningful conclusions to be drawn. PROSPERO registration CRD42018092867.


Femtosecond pump-probe measurements of solvation by hydrogen-bonding interactions.
An additional ultrafast blue shift in the transient absorption spectra of hydrogen-bonding complexes of a strong photoacid, 8-hydroxypyrene 1,3,6-trisdimethylsulfonamide (HPTA), over the solvation response of the uncomplexed HPTA and also over that of the methoxy derivative of the photoacid (MPTA) in the presence of the hydrogen-bonding base was observed on optical excitation of the photoacid. The additional 55 +/- 10 fs solvation response was found to be about 35 % and 19% of the total C(t) of HPTA in dichloromethane (DCM) when it was hydrogen-bonded to dimethylsulfoxide (DMSO) and dioxane, respectively, and about 29% of the total C(t) of HPTA in dichloroethane (DCE) when it was hydrogen-bonded to DMSO. We have assigned this additional dynamic spectral shift to a transient change in the hydrogen bond (O-H...O) that links HPTA to the complexing base, after the electronic excitation of the photoacid.


Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation.
Dendritic cells (DCs) play a key role in the activation and regulation of B and T lymphocytes. Production of indoleamine 2, 3-dioxygenase (IDO) by macrophages has recently been described to result in inhibition of T cell proliferation through tryptophan degradation. Since DCs can be derived from monocytes, we sought to determine whether DCs could produce IDO which could potentially regulate T cell proliferation. Northern blot analysis of RNA from cultured monocyte-derived human DC revealed that IDO mRNA was induced upon activation with CD40 ligand and IFN-gamma. IDO produced from activated DCs was functionally active and capable of metabolizing tryptophan to kynurenine. Activated T cells were also capable of inducing IDO production by DCs, which was inhibited by a neutralizing Ab against IFN-gamma. DC production of IDO resulted in inhibition of T cell proliferation, which could be prevented using the IDO inhibitor 1-methyl-dl -tryptophan. These results suggest that activation of DCs induces the production of functional IDO, which causes depletion of tryptophan and subsequent inhibition of T cell proliferation. This may represent a potential mechanism for DCs to regulate the immune response.


Exploring the active site in UDP-glucose pyrophosphorylase by affinity labelling and site-directed mutagenesis.
UDP-glucose pyrophosphorylase catalyses the reversible uridylyl transfer from UDP-glucose to MgPPi, forming glucose 1-phosphate and MgUTP. We have identified, by using uridine di- and tri-phosphopyridoxals, five lysyl residues located at or near the UDP-glucose-binding site. Another reactive analogue, pyridoxal diphosphoglucose, also modified the same set of lysyl residues. Based on the amounts of labels incorporated into each lysyl residue, we have provided a hypothetical model for possible locations of the five lysyl residues around the substrates bound to the enzyme. This model was consistent with the results of the mutagenesis studies. Lys367 is essential for the catalysis, whereas Lys263 may participate in the binding of PPi and/or glucose 1-phosphate in the binary complex. On the other hand, the results of affinity labelling with pyridoxal 5'-diphosphate suggest the role of Lys329 in the direct interaction with PPi in the enzyme-UDP-glucose complex.


Treatment of generalized anxiety disorder: a comprehensive review of the literature for psychopharmacologic alternatives to newer antidepressants and benzodiazepines.
Generalized anxiety disorder (GAD) is common, chronic, and debilitating. Treatment with benzodiazepines and newer antidepressants is often inadequate. This article reviews the effectiveness of alternative and augmenting medications, such as older antidepressants, antipsychotics, anticonvulsants, and β-blockers. A search using MEDLINE (1980 to week 4 of May 2010) with the key words generalized anxiety disorder or GAD and therapeutics or treatment was conducted. Articles included adult patients with a GAD diagnosis that established chronicity of illness. These included a small number of studies that used DSM-III criteria but added a chronicity of symptoms and included all studies that used DSM-III-R and DSM-IV criteria. Articles that did not include medications or that exclusively focused on newer antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, and mirtazapine), buspirone, benzodiazepines, or herbal or investigational medications were excluded. Review articles and non-English-language articles were also excluded. Thirty-six studies were reviewed. All of the references were then analyzed, and key portions were extracted. Many studies were open trials. Double-blind, placebo-controlled studies with imipramine, risperidone, olanzapine, hydroxyzine, ondansetron, tiagabine, valproate, and pregabalin had been conducted. Imipramine, hydroxyzine, valproate, and pregabalin were the most effective, although risperidone, olanzapine, ziprasidone, and aripiprazole may also reduce symptoms. Several medication strategies can be considered as promising alternatives or augmenting to antidepressant or benzodiazepine therapy in GAD.


Two genes encoding midgut-specific maltase-like polypeptides from Anopheles gambiae.
Full-length cDNA clones of two genes have been isolated from the African malaria vector mosquito, Anopheles gambiae. These genes, designated Agm1 and Agm2, encode maltase-like polypeptides of 498 and 599 residues, respectively. Deduced amino acid sequences contain a putative signal peptide sequence and four potential glycosylation sites. Agm1 and Agm2 show highest similarities to the Mal1 gene from Aedes aegypti and three clustered maltase genes from Drosophila melanogaster. Both genes are located at position 46D, in the terminal division of the left arm of the third chromosome. Agm2 has very strict tissue and temporal specificity, being expressed exclusively in the adult midgut. The specificity of Agm1 is similar but appears slightly broader; transcripts of this gene are detected at a low level in the pupae, and occasionally in the adult carcass after removal of the midgut.


[Mast cells in chronic gastritis of children].
Mast cell involvement in chronic gastritis in children was analyzed. 25 children with normal mucosa (controls), 20 children with chronic gastritis and 28 children with chronic gastritis and infected Helicobacter pylori were included to the study. Bioptic material from antrum and corpus of the stomach were stained with toluidine blue and anti-human mast cell tryptase to evaluate mast cell density. Changes in mast cells number were also estimated in 7 children before and after successful eradication of Helicobacter pylori infection. Mast cell density was significantly greater in children with chronic gastritis with or without Helicobacter pylori infection when compared to the controls. Mast cell degranulation was demonstrated by electron microscopy in children with chronic gastritis and infected Helicobacter pylori. Mast cell through it's numerous mediators may play a key role in chronic gastritis especially when Helicobacter pylori infection is present.


[Extensive cutaneous candidiasis revealing cutaneous T-cell lymphoma: 2 cases].
During the course of immunodeficiency diseases, severe candidiasis can occur with extensive cutaneous and mucous membrane lesions. However, blood dyscrasias are very rarely revealed by diffuse candidiasis. We report two case of cutaneous T-cell lymphoma revealed by extensive and atypical cutaneous candidiasis. Case No. 1:A 72-year-old woman presented a pruritic rash of circinate, serpiginous patches on glabrous skin and skinfolds with multiple intertrigo and rapidly worsening palmoplantar keratoderma. All mycological skin specimens tested positive for Candida albicans. Histological examination of a biopsy sample from a serpiginous patch revealed the presence of fungal elements while palmoplantar keratoderma biopsy showed an epidermotropic lymphocytic infiltrate in the superficial dermis evocative of mycosis fungoides. Blood tests showed a white cell count of 28 600/mm3 with 14% circulating Sezary cells and a T-cell clone. The T-cell lymphoma was treated with methotrexate, but the disease worsened a few months later, progressing to CD30- large T-cell pleomorphic lymphoma. The patient died of severe sepsis. Case No 2:A 60-year-old man presented a macular rash over the face, trunk and skinfolds as well as erythematous scaly annular plaques of the glabrous skin with lymphadenopathy. Cultures of skin scrapings were all positive for Candida albicans. Blood tests showed a white cell count of 15 000/mm3 with 30% circulating Sezary cells. A trunk patch biopsy revealed the histological appearance of mycosis fungoides. There was a T-cell clone in the peripheral blood and skin. In both cases, the patients presented with widespread annular and erythematous scaly lesions of the glabrous skin and skinfolds with evidence of Candida albicans on fungal tests of all skin scrapings. The discovery of circulating Sezary cells on a systematic smear for hyperleukocytosis led us to suspect underlying cutaneous T-cell lymphoma, which was confirmed by biopsy of the skin lesions accompanying the mycoses. Widespread cutaneous candidiasis can occur in patients with cell-mediated immunodepression. Cutaneous T-cell lymphoma can enhance such candidiasis through interference with skin integrity and impairment of cell-mediated immunity, with large amounts of IL10 and TGF-B, increased secretion of soluble interleukin-2 receptors (CD25) and impaired CD8 suppressor cell function.


Predicting the environmental suitability and population at risk of podoconiosis in Africa.
Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes.


Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers.
It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [3H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [3H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.


[The incidence of irregular antibodies in pregnancy: a prospective study in the region of the 's-Hertogenbosch].
To determine the incidence and clinical relevance of irregular erythrocyte antibodies (IEA), in multiparous women and in primigravidal with a history of blood transfusion. Prospective longitudinal cohort study. In the 's-Hertogenbosch area, the Netherlands, both primigravidae with a previous blood transfusion and multiparous women were tested for IEA in addition to the regular blood tests during the first trimester of pregnancy. If IEA were discovered, the partners were tested for the presence of the antigen involved. Blood samples of children of positive fathers were tested immediately post partum for signs of haemolytic disease of the newborn (HDN). During a 2.5-year period (August 1995-January 1998) a total of 2392 pregnant women were screened for IEA: 2204 multiparous women and 188 primigravidae women. In 65 women 81 IEA were discovered. In the group of 30 children positive for the antigen involved, 12 (40%) had clinical symptoms of HDN; intrauterine death was diagnosed once, one child died immediately after delivery. One child had signs of hydrops fetalis and two children needed an exchange transfusion. Phototherapy and/or regular blood transfusion were given to 7 children. Most cases of HDN were caused by anti-D, anti-Kell and anti-c antibodies. Non-RhD-IEA were found in 1.6% of pregnant women screened. First-trimester screening for IEA is recommended as it can be of help in early diagnosis and treatment of HDN.


Femoral Vein Catheter is an Important Risk Factor for Catheter-related Thrombosis in (Near-)term Neonates.
Central venous catheters (CVCs) in neonates are associated with an increased risk of thrombosis. Most reports focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs), whereas data available on femoral venous catheters (FVCs) are limited. We performed a retrospective cohort study in all neonates (gestational age ≥34 wk) with CVCs. The primary outcome was the occurrence of thrombosis in CVCs. The secondary outcomes were possible risk factors for thrombosis, the thrombotic incidence in FVCs, UVCs, and PICCs, and clinical aspects of thrombosis in these groups. A total of 552 neonates received a total of 656 catheters, including 407 (62%) UVCs, 185 (28%) PICCs, and 64 (10%) FVCs. Thrombosis was detected in 14 cases, yielding an overall incidence of 2.1% or 3.6 events per 1000 catheter days. FVC was significantly associated with the occurrence of thrombosis when compared with UVC (P=0.02; odds ratio, 3.8; 95% confidence interval, 1.2-12.0) and PICC (P=0.01; odds ratio, 8.2; 95% confidence interval, 1.6-41.7). The incidence of thrombosis was higher in FVCs than in UVCs and PICCS, that is, 7.8% (5/64), 1.7% (7/407), and 1.1% (2/185), respectively (P<0.01). The number of thrombotic events per 1000 catheter days was 12.3 in FVCs, 3.2 in UVCs, and 1.5 in PICCs (P<0.05). We concluded that thrombosis occurs more frequently in FVCs than in other CVCs.


The actin cytoskeleton is required for the trafficking of the B cell antigen receptor to the late endosomes.
The B cell antigen receptor (BCR) plays two central roles in B cell activation: to internalize antigens for processing and presentation, and to initiate signal transduction cascades that both promote B cells to enter the cell cycle and facilitate antigen processing by accelerating antigen transport. An early event in B cell activation is the association of BCR with the actin cytoskeleton, and an increase in cellular F-actin. Current evidence indicates that the organization of actin filaments changes in response to BCR-signaling, making actin filaments good candidates for regulation of BCR-antigen targeting. Here, we have analyzed the role of actin filaments in BCR-mediated antigen transport, using actin filament-disrupting reagents, cytochalasin D and latrunculin B, and an actin filament-stabilizing reagent, jasplakinolide. Perturbing actin filaments, either by disrupting or stabilizing them, blocked the movement of BCR from the plasma membrane to late endosomes/lysosomes. Cytochalasin D-treatment dramatically reduced the rate of internalization of BCR, and blocked the movement of the BCR from early endosomes to late endosomes/lysosomes, without affecting BCR-signaling. Thus, BCR-trafficking requires functional actin filaments for both internalization and movement to late endosomes/lysosomes, defining critical control points in BCR-antigen targeting.


Efficient formation of the tandem thymine glycol/8-oxo-7,8-dihydroguanine lesion in isolated DNA and the mutagenic and cytotoxic properties of the tandem lesions in Escherichia coli cells.
Reactive oxygen species can induce the formation of not only single-nucleobase lesions, which have been extensively studied, but also tandem lesions. Herein, we report a high frequency of formation of a type of tandem lesion, where two commonly observed oxidatively induced single-nucleobase lesions, that is, thymidine glycol (Tg) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), are vicinal to each other in calf thymus DNA upon exposure to Cu(II)/ascorbate along with H(2)O(2) or gamma-rays. We further explored how the tandem lesions perturb the efficiency and fidelity of DNA replication by assessing the replication products formed from the propagation, in Escherichia coli cells, of the single-stranded pYMV1 shuttle vectors containing two tandem lesions [5'-(8-oxodG)-Tg-3' and 5'-Tg-(8-oxodG)-3'] or an isolated Tg or 8-oxodG. The bypass efficiencies for the two tandem lesions were approximately one-half of those for the two isolated single-nucleobase lesions. The presence of an adjacent Tg could lead to significant increases in G-->T transversion at the 8-oxodG site as compared to that of a single 8-oxodG lesion; the frequencies of G-->T mutation were approximately 18, 32, and 28% for 8-oxodG that is isolated, in 5'-(8-oxodG)-Tg-3' and in 5'-Tg-(8-oxodG)-3', respectively. Moreover, both pol IV and pol V are involved, in part, in bypassing the Tg, either present alone or as part of the tandem lesions, in E. coli cells. Together, our results support that complex lesions could exert greater cytotoxic and mutagenic effects than when the composing individual lesions are present alone.


Increased bone strontium levels in hemodialysis patients with osteomalacia.
In this study, we report on the association between increased bone strontium levels and the presence of osteomalacia in end-stage renal failure patients treated by hemodialysis. We performed a histologic examination and determined the strontium content and strontium/calcium ratios in bone biopsies of 100 hemodialysis patients recruited from various centers all over the world. Aside from the bone strontium concentration, the bone aluminum content was assessed. The bone zinc concentration, a nonrelevant element for bone toxicity, was also measured. Bone strontium levels and bone strontium/calcium ratios were increased in subjects with osteomalacia when compared with those with the other types of renal osteodystrophy. Bone strontium and bone calcium levels correlated with each other. The slope of the linear regression curve correlating these parameters was much steeper in the osteomalacic group (Y = 2.22X - 120) as compared with the other types of renal osteodystrophy (Y = 0.52X - 5.7). Within the group of patients with osteomalacia, bone strontium levels also significantly correlated with the bone aluminum content (r = 0.72, P = 0.018). No such correlation was found for the other types of renal osteodystrophy. The bone zinc concentration of subjects with normal renal function did not differ significantly from the values noted for the various types of renal osteodystrophy taken as separate groups, nor could increased bone zinc concentrations be associated with a particular bone lesion. Our data demonstrate an association between osteomalacia and increased bone strontium concentrations in dialysis patients. Further studies are warranted to establish whether strontium plays either a primary, secondary, or contributive role in the development of the latter type of renal osteodystrophy.


A Combination of Visudyne and a Lipid-anchored Liposomal Formulation of Benzoporphyrin Derivative Enhances Photodynamic Therapy Efficacy in a 3D Model for Ovarian Cancer.
A major objective in developing new treatment approaches for lethal tumors is to reduce toxicity to normal tissues while maintaining therapeutic efficacy. Photodynamic therapy (PDT) provides a mechanistically distinct approach to treat tumors without the systemic toxicity of chemotherapy drugs. PDT involves the light-based activation of a small molecule, a photosensitizer (PS), to generate reactive molecular species (RMS) that are toxic to target tissue. Depending on the PS localization, various cellular and subcellular components can be targeted, causing selective photodamage. It has been shown that targeted lysosomal photodamage followed by, or simultaneous with, mitochondrial photodamage using two different PS results in a considerable enhancement in PDT efficacy. Here, two liposomal formulations of benzoporphyrin derivative (BPD): (1) Visudyne (clinically approved) and (2) an in-house formulation entrapping a lipid conjugate of BPD are used in combination with direct PS localization to mitochondria, endoplasmic reticulum and lysosomes, enabling simultaneous photodamage to all three organelles using a single wavelength of light. Building on findings by our group, and others, this study demonstrates, for the first time in a 3D model for ovarian cancer, that BPD-mediated photodestruction of lysosomes and mitochondria/ER significantly enhances PDT efficacy at lower light doses than treatment with either PS formulation alone.


Prenatal diagnosis and genetic discoveries of an intracranial mixed neuronal-glial tumor: A case report and literature review.
Congenital intracranial tumors as a group are quite rare, representing only 0.5% to 1.5% of all pediatric brain neoplasms. We reported a case of congenital mixed neuronal-glial tumor detected by ultrasound at 30 weeks of gestation. It showed that the tumor was 2.5 × 2.3 × 2.1 cm in size, located in the sellar region, regular shape, and slightly heterogeneous solid mass with a little cystic component. No color flow was present inside the tumor, but the peripheral encirclement by arterial circle of Willis. No other associated malformations were detected. Prenatal magnetic resonance imaging (MRI) which was taken subsequently confirmed the result of ultrasound and provided more detailed information such as fetal brain dysplasia.The fetal chromosomal karyotype analysis is normal. Single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) detected a 0.72-Mb duplication at 4q35.2 in fetus which was associated with epilepsy and cardiac anomalies. It also revealed a 0.13-Mb deletion at 6q26 located in PARK2 gene, and the mutation of the gene is known to be related to autosomal recessive juvenile Parkinson disease.The parents chose termination of pregnancy (TOP). The histological examination showed a mixed neuronal-glial tumor. Prenatal detection of mixed neuronal-glial tumor is very rare. Ultrasound is of critical importance to detect the intracranial tumors, and MRI can give us some detailed information about the tumors. However, the precise histologic type was depended on the pathological examination. CMA should be necessary for the fetuses with congenital intracranial tumors, especially when the fetal chromosomal karyotype analysis is normal.


Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa.
The goal of this study was to explore the applicability of surface plasmon resonance (SPR)-based fragment screening to identify compounds that bind to factor VIIa (FVIIa). Based on pharmacophore models virtual screening approaches, we selected fragments anticipated to have a reasonable chance of binding to the S1-binding pocket of FVIIa and immobilized these compounds on microarrays. In affinity fingerprinting experiments, a number of compounds were identified to be specifically interacting with FVIIa and shown to fall into four structural classes. The results demonstrate that the chemical microarray technology platform using SPR detection generates unique chemobiological information that is useful for de novo discovery and lead development and allows the detection of weak interactions with ligands of low molecular weight.


Visual storytelling: a beneficial but challenging method for health research with young people.
Visual storytelling is a new research approach drawing on established methods of photovoice and photo elicitation. It appears well suited to research with young people. We explored the feasibility of this approach, reflecting on benefits and challenges encountered while using it during a study of chronic disease self-management in adolescents. During in-depth interviews, 68 participants were questioned about the value of visual storytelling. Thematic analysis was applied. Visual storytelling was valued for (a) being a draw card during recruitment and increasing positive feelings about the research; (b) being fun; (c) promoting self-understanding; and (d) promoting expression, communication, and focus during interviews. Deciding what to photograph was difficult. More time and effort was required by researchers than for a standard qualitative interview study. The technique facilitated rich interviews, drawing into focus details of young peoples' lives that otherwise might not have been discussed.


Contribution of Temperature Increase to Restrain the Transmission of COVID-19.
The COVID-19 outbreak has already become a global pandemic and containing this rapid worldwide transmission is of great challenge. The impacts of temperature and humidity on the COVID-19 transmission rate are still under discussion. Here, we elucidated these relationships by utilizing two unique scenarios, repeated measurement and natural experiment, using the COVID-19 cases reported from January 23 - February 21, 2020, in China. The modeling results revealed that higher temperature was most strongly associated with decreased COVID-19 transmission at a lag time of 8 days. Relative humidity (RH) appeared to have only a slight effect. These findings were verified by assessing SARS-CoV-2 infectivity under the relevant conditions of temperature (4°C-37°C) and RH (> 40%). We concluded that temperature increase made an important, but not determined, contribution to restrain the COVID-19 outbreak in China. It suggests that the emphasis of other effective controlling polices should be strictly implemented to restrain COVID-19 transmission in cold seasons.


pH Dependence of the Km(CO(2)) of Ribulose 1,5-Diphosphate Carboxylase.
The Km(CO(2)) values of ribulose 1,5-diphosphate carboxylase in freshly ruptured spinach (Spinacia oleracea L.) chloroplasts and in the purified form isolated from spinach leaves were found to be pH dependent. Raising the pH of the assay solution produced a substantial decrease in the Km(CO(2)) of both enzyme systems. In freshly ruptured chloroplasts at pH 7.2 the Km(CO(2)) was 25 mum, at pH 8 it decreased to 19 mum, and at pH 8.8 a further decrease to 7 mum was found. With the purified enzyme at pH 7.2 the Km(CO(2)) was 147 mum, while the corresponding Km values for pH 8 and 8.8 were 34 and 15 mum CO(2), respectively. The latter figure approximates the physiological Km(CO(2)) of 10 mum estimated for photosynthesizing leaves and intact chloroplasts. The maximum velocity for both enzyme systems at optimum substrate levels was at pH 8, but the highest calculated rate of CO(2) uptake at atmospheric CO(2) levels occurred at pH 8.8. These results support the proposal that the light-induced efflux of protons out of the chloroplast stroma may be a major factor involved with the reported in vivo light activation of ribulose 1,5-diphosphate carboxylase.


Clinical profile and outcome in enteric fever.
Sixty five blood culture positive cases of S. typhi were studied for clinical profile. A total of 64.6% were multidrug resistant and 35.4% were chloramphenicol sensitive. In patients with multidrug resistant S. typhi the age was higher (p < 0.01), and incidence of complications such as shock (35.7%), encephalopathy (42.9%), myocarditis (14.3%) and gastric hemorrhage (4.7%) were more frequent, compared to chloramphenicol sensitive group. Cases with multidrug resistant S. typhi (MDRST) were treated with oral ciprofloxacin; the period of defervescence of fever was significantly less (p < 0.05) compared to the chloramphenicol group. Our study suggests the use of ciprofloxacin in the treatment of MDRST without any side effects.


Physiological, vestibulo-ocular and cervicogenic post-concussion disorders: an evidence-based classification system with directions for treatment.
To present a novel pathophysiological approach to acute concussion and post-concussion syndrome (PCS). Review of the literature. PubMed searches were performed to identify articles related to the pathophysiology and treatment of concussion and PCS. Relevant articles that contributed to the primary objective of the paper were included. This paper presents an evidence-based approach to acute concussion and PCS that focuses on the identification of specific post-concussion disorders (PCDs) caused by impairments in global brain metabolism (Physiologic PCD) or neurological sub-system dysfunction (Vestibulo-ocular PCD and Cervicogenic PCD) that can be distinguished by features of the clinical history, physical examination and treadmill exercise testing. This novel approach also allows for the initiation of evidence-based, multi-disciplinary therapeutic interventions that can improve individual symptoms and promote efficient neurological recovery. Future studies incorporating neuro-imaging and exercise science techniques are underway at the author's institutions to validate this novel pathophysiological approach to acute concussion and PCS.


Electronic medical record phenotyping using the anchor and learn framework.
Electronic medical records (EMRs) hold a tremendous amount of information about patients that is relevant to determining the optimal approach to patient care. As medicine becomes increasingly precise, a patient's electronic medical record phenotype will play an important role in triggering clinical decision support systems that can deliver personalized recommendations in real time. Learning with anchors presents a method of efficiently learning statistically driven phenotypes with minimal manual intervention. We developed a phenotype library that uses both structured and unstructured data from the EMR to represent patients for real-time clinical decision support. Eight of the phenotypes were evaluated using retrospective EMR data on emergency department patients using a set of prospectively gathered gold standard labels. We built a phenotype library with 42 publicly available phenotype definitions. Using information from triage time, the phenotype classifiers have an area under the ROC curve (AUC) of infection 0.89, cancer 0.88, immunosuppressed 0.85, septic shock 0.93, nursing home 0.87, anticoagulated 0.83, cardiac etiology 0.89, and pneumonia 0.90. Using information available at the time of disposition from the emergency department, the AUC values are infection 0.91, cancer 0.95, immunosuppressed 0.90, septic shock 0.97, nursing home 0.91, anticoagulated 0.94, cardiac etiology 0.92, and pneumonia 0.97. The resulting phenotypes are interpretable and fast to build, and perform comparably to statistically learned phenotypes developed with 5000 manually labeled patients. Learning with anchors is an attractive option for building a large public repository of phenotype definitions that can be used for a range of health IT applications, including real-time decision support.


Melanotic neuroectodermal tumor of infancy: A rare entity.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm with a predilection for the head-and-neck region. Approximately 472 cases reported in literature till date. We report an unusual case of MNTI in a 1-month old child. A 10 cm × 5 cm × 5 cm nontender, firm, deep-seated swelling was seen involving the right zygomatic and maxillary region. Magnetic resonance imaging was suggestive of rhabdomyosarcoma and immunomorphological assessment of the excision specimen revealed the final diagnosis of MNTI. On follow-up, the patient developed recurrence 4 months after surgery and was reoperated. The present case emphasizes that albeit rare, pediatric surgeons and pathologists must always keep in mind the possibility of MNTI while dealing with maxillofacial tumors in infants. Owing to rather nonspecific clinicoradiological features, histopathology supplemented with immunohistochemistry remains the gold standard for diagnosis. Although considered to be a benign tumor, close clinicoradiological follow-up is strongly recommended given the significant risk of recurrence as highlighted by our case.


A randomized-controlled trial of arginine infusion in severe sepsis on microcirculation and metabolism.
Sepsis is hypothesized as an arginine deficient state, with lack of nitric oxide (NO) for adequate microcirculation and local perfusion. This study aimed to investigate if prolonged (72-h) intravenous l-arginine administration in sepsis patients improves microcirculation. Secondly, effects on arginine and protein metabolism, and organ function were studied. Critically ill patients with a diagnosis of septic shock participated in a long-term (72 h) randomized double-blind placebo-controlled parallel-group study. l-arginine-HCl (1.2 μmol kg-1 min-1; n = 9) or l-alanine (isocaloric control: 2.4 μmol kg-1 min-1; n = 9) was continuously infused. Primary study outcome was microcirculation, assessed as gastric mucosal perfusion by gastric tonometry (Pr-aCO2 gap) and skin perfusion by Laser Doppler flowmetry. Secondary endpoints were whole body (WB) arginine and protein metabolism, organ function and clinical outcomes. We measured global hemodynamics continuously for safety monitoring. Statistical analyses were performed by mixed model for repeated measures with treatment by time interaction as estimate for between-group difference. Pr-aCO2 increased only in the l-arginine group (p = 0.006), without a significant between-group difference (p = 0.17). We found no significant differences in skin perfusion parameters. l-arginine infusion resulted in a larger increase of plasma arginine and ornithine concentrations (p < 0.01), WB (endogenous) arginine appearance (p < 0.001), WB NO synthesis (p = 0.027) and WB arginine to urea conversion (p < 0.001) than infusion of l-alanine. We found no effect on global hemodynamics, and protein metabolism by l-arginine infusion. Organ function parameters were unaffected, except for a significant difference between groups in intra-abdominal pressure over time (p = 0.029). Prolonged intravenous l-arginine administration does not improve local perfusion and organ function despite an increase in WB NO synthesis. Administration is safe with regard to global hemodynamics, but the observed increase in Pr-aCO2 and intra-abdominal pressure warrants careful application of l-arginine infusion and further research, especially in the early stage of septic shock.


[Surgical jejunostomy as digestive tube access in the long-term].
Home enteral nutrition (HEN) is the choice for patients who can not mantain oral intake but have a functioning gastrointestinal tract when it isn't justify keeping the patient in the hospital. The results of the HEN registry of the NADYA group in 2010 shows information related to the enteral acces route: 51% of the cases used nasogastric tubes, 27% gastrostomies, 10% oral route and 3% jejunostomies. Placement of a needle catheter jejunostomy is recommended for candidates for enteral nutrition undergoing major abdominal surgery, but publications about long-term use of this acces are scarce. We report same cases of patients whom the selected enteral acces was surgical jejunostomy. They represents the 1,14% of our patients with HEN at this moment, with a mean dwelling time of 210 ± 222 days. There has been frequent complications, but they were sligh.


A Smartphone-Based Near-Vision Testing System: Design, Accuracy, and Reproducibility Compared With Standard Clinical Measures.
Ophthalmologic telemedicine has emerged during the COVID-19 pandemic. The objective of this study is to assess the accuracy and reproducibility of a smartphone-based home vision monitoring system (Sightbook) and to compare it with existing clinical standards. Near Snellen visual acuity (VA) was measured with Sightbook and compared with conventional measurements for distance and near VA at an academic medical center ophthalmology clinic in 200 patients with a variety of different specified preexisting ocular conditions. Measurements of contrast sensitivity were also compared by using an existing commercially available chart system in 15 normal patients and 15 patients with age-related macular degeneration. Sightbook VA tests were reproducible (SD = ±0.054 logMAR), and correlation with standard VA methods was significant (R > 0.87 and P < .001). Sightbook contrast sensitivity measurements were reproducible (SD/mean ratio, 0.02 to 0.04), yielding results similar to those of standard tests (R2 > 0.87 and P < .001). Smartphone-based VA and contrast sensitivity are highly correlated with standard charts and may be useful in augmenting limited inoffice care. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:79-84.].


Structuring the bacterial genome: Y1-transposases associated with REP-BIME sequences.
REPs are highly repeated intergenic palindromic sequences often clustered into structures called BIMEs including two individual REPs separated by short linker of variable length. They play a variety of key roles in the cell. REPs also resemble the sub-terminal hairpins of the atypical IS200/605 family of insertion sequences which encode Y1 transposases (TnpA(IS200/IS605)). These belong to the HUH endonuclease family, carry a single catalytic tyrosine (Y) and promote single strand transposition. Recently, a new clade of Y1 transposases (TnpA(REP)) was found associated with REP/BIME in structures called REPtrons. It has been suggested that TnpA(REP) is responsible for REP/BIME proliferation over genomes. We analysed and compared REP distribution and REPtron structure in numerous available E. coli and Shigella strains. Phylogenetic analysis clearly indicated that tnpA(REP) was acquired early in the species radiation and was lost later in some strains. To understand REP/BIME behaviour within the host genome, we also studied E. coli K12 TnpA(REP) activity in vitro and demonstrated that it catalyses cleavage and recombination of BIMEs. While TnpA(REP) shared the same general organization and similar catalytic characteristics with TnpA(IS200/IS605) transposases, it exhibited distinct properties potentially important in the creation of BIME variability and in their amplification. TnpA(REP) may therefore be one of the first examples of transposase domestication in prokaryotes.


Alzheimer's disease: nursing interventions for clients and caretakers.
1. Senile dementia Alzheimer's type (SDAT), a progressive, degenerative disorder, affects tissues of the brain, causing a loss of neurons. This process results in brain atrophy, specifically in the frontal and temporal regions where integration of new information and memory retrieval occur. 2. Increasing age is the single most well-established risk factor for the development of SDAT (Brody, 1989). Because increasing age is the primary risk factor for the development of SDAT and because the elder population is increasing, the number of afflicted persons will probably rise (Ham, 1990). 3. The objectives of nursing interventions are to assist the client in remaining as independent as possible; to function at the highest possible cognitive, physical, emotional, and social levels; and to support the family and/or significant others in effectively carrying out their functions and goals.


Challenges in examining area effects across the life course on physical capability in mid-life: findings from the 1946 British Birth Cohort.
A major limitation of past work linking area socioeconomic conditions to health in mid-life has been the reliance on single point in time measurement of area. Using the MRC National Survey of Health and Development, this study for the first time linked place of residence at three major life periods of childhood (1950), young adulthood (1972), and mid-life (1999) to area-socioeconomic data from the nearest census years. Using objective measures of physical capability as the outcome, the purpose of this study was to highlight four methodological challenges of attrition bias, secular changes in socio-economic measures, historical data availability, and changing reporting units over time. In general, standing balance and chair rise time showed clear cross-sectional associations with residing in areas with high deprivation. However, it was the process of overcoming the methodological challenges, which led to the conclusion that in this example percent low social class occupations was the most appropriate measure to use when extending cross-sectional analysis of standing balance and chair rise to life course investigation.


Endodyogony and cyst formation of Sarcocystis gongyli (Trinci 1911) from the skink Chalcides ocellatus.
The heteroxenous life cycle of S. gongyli comprising both the skink Chalcides ocellatus (intermediate host) and the snake Spalerosophis diadema, herewith the process of cyst formation was followed by means of light and electron microscopy after experimental infection. Following migration of the merozoites to muscle fibres, they changed into globular metrocytes, meanwhile a parasitophorous vacuole enclosing them. As development proceeded the wall of the parasitophorous vacuole is thickened in the form of striated protrusions as well as the metrocytes underwent endodyogony producing large numbers of banana-shaped merozoites in the centre of the cyst. Mature microscopic sarcocyst appeared at 120 days p.i, and these were characterized by presence of stalky leaf-like protrusions in their primary cyst wall. Asexual multiplication of metrocytes occurred through endodyogony in which always the mother metrocyte produced two opposite merozoites.


Molecular changes induced in rat liver by hemorrhage and effects of melanocortin treatment.
Melanocortin peptides improve hemodynamic parameters and prevent death during severe hemorrhagic shock. In the present research we determined influences of a synthetic melanocortin 1/4 receptor agonist on the molecular changes that occur in rat liver during hemorrhage. Controlled-volume hemorrhage was performed in adult rats under general anesthesia by a stepwise blood withdrawal until mean arterial pressure fell to 40 mmHg. Then rats received either saline or the synthetic melanocortin 1/4 receptor agonist Butir-His-D-Phe-Arg-Trp-Sar-NH2 (Ro27-3225; n = 6-8 per group). Hemogasanalysis was performed throughout a 60-min period. Gene expression in liver samples was determined at 1 or 3 h using quantitative real-time polymerase chain reaction. At 1 h, in saline-treated shocked rats, there were significant increases in activating transcription factor 3 (Atf3), early growth response 1 (Egr1), heme oxygenase (decycling) 1 (Hmox1), FBJ murine osteosarcoma viral oncogene homolog (Fos), and jun oncogene (Jun). These changes were prevented by Ro27-3225 (mean ± SEM: Atf3 152.83 ± 58.62 vs. 579.00 ± 124.13, P = 0.002; Egr1 13.21 ± 1.28 vs. 26.63 ± 1.02, P = 0.001; Hmox1 3.28 ± 0.31 vs. 166.54 ± 35.03, P = 0.002; Fos 4.36 ± 1.03 vs. 14.90 ± 3.44, P < 0.001; Jun 6.62 ± 1.93 vs. 15.07 ± 2.09, P = 0.005; respectively). Increases in alpha-2-macroglobulin (A2m), heat shock 70kD protein 1A (Hspa1a), erythropoietin (Epo), and interleukin-6 (Il6) occurred at 3 h in shocked rats and were prevented by Ro27-3225 treatment (A2m 6.90 ± 0.82 vs. 36.73 ± 4.00, P < 0.001; Hspa1a 10.34 ± 3.28 vs. 25.72 ± 3.64, P = 0.001; Epo 0.49 ± 0.13 vs. 2.37 ± 0.73, P = 0.002; Il6 1.05 ± 0.15 vs. 1.88 ± 0.23, P < 0.001; respectively). Further, at 3 h in shocked rats treated with Ro27-3225 there were significant increases in tight junction protein 1 (Tjp1; 27.30 ± 2.43 vs. 5.03 ± 1.68, P < 0.001) and nuclear receptor subfamily 4, group A, member 1 (Nr4a1; 91.03 ± 16.20 vs. 30.43 ± 11.0, P = 0.01) relative to sham animals. Treatment with Ro27-3225 rapidly restored blood pressure, hemogasanalysis parameters, and lactate blood levels. Melanocortin treatment significantly prevents most of the systemic and hepatic detrimental changes induced by hemorrhage.


Accurate detection of low-level mosaic mutations in pediatric acute lymphoblastic leukemia using single molecule tagging and deep-sequencing.
Pathogenic mutations in relapse-associated genes in pediatric acute lymphoblastic leukemia may improve risk stratification when detected at subclonal levels at primary diagnosis. However, to detect subclonal mutations upfront, a deep-sequencing approach with high specificity and sensitivity is required. Here, we performed a proof-of-principle study to detect low-level mosaic RAS pathway mutations by deep sequencing using random tagging-based single molecule Molecular Inversion Probes (smMIPs). The smMIP-based approach could sensitively detect variants with allele frequency as low as 0.4%, which could all be confirmed by other techniques. In comparison, with standard deep-sequencing techniques we reached a detection threshold of only 2.5%, which hampered detection of seven low-level mosaic mutations representing 24% of all detected mutations. We conclude that smMIP-based deep-sequencing outperforms standard deep-sequencing techniques by showing lower background noise and high specificity, and is the preferred technology for detecting mutations upfront, particularly in genes in which mutations show limited clustering in hotspots.