Ultrastructural analysis of growth of Nocardia asteroides during invasion of the murine brain.
BALB/c mice were infected with 10(6) CFU of log-phase cells of Nocardia asteroides GUH-2 by tail vein injection (at this lethal inoculum dose, approximately 800 to 1,000 CFU becomes deposited in the brain). At 24 h after infection, the ultrastructural interactions of the nocardiae during growth within the murine brain were investigated. The nocardiae grew perivascularly in the pons, substantia nigra, hypothalamus, and thalamus portions of the brain, where they were either within or associated with most brain cell types. There appeared to be a propensity for growth within the soma of neurons and their axonal extensions. The nocardial cells were surrounded by 1 to 30 layers of membrane, and the innermost membrane was usually tightly adherent to the cell wall. This compartmentalization of nocardiae within brain cells could contribute to their failure to induce an inflammatory response or a cytopathic effect. Nevertheless, the bacteria were able to obtain adequate nutrients from the host to grow within the brain. The nocardiae were not completely inert, since some of the brain cells showed signs of degeneration. The myelin sheaths of axons were the most strongly affected, and there was evidence of demyelinization and axonal degeneration. Nocardiae growing within brain cells were phagocytized by compact, dense cells that were probably microglia. There was no ultrastructural evidence that the nocardiae were damaged by these phagocytes 24 h after infection; nevertheless, these cells may be important for the elimination of nocardiae from the brain during a nonlethal infection.


Downregulation of IL7R, CCR7, and TLR4 in the cord blood of children with respiratory syncytial virus disease.
The association between gene expression at birth of 11 candidate genes with important innate and adaptive immune functions and later respiratory syncytial virus (RSV) disease was investigated. Cord blood was collected from 2108 newborns. Forty-seven were subsequently RSV positive. Gene expression analysis by quantitative reverse transcription-polymerase chain reaction was compared to 17 controls. There was downregulation of interleukin 7 receptor (IL7R) (P = .0001) and chemokine receptor 7 (CCR7) (P = .002), and in the severe disease subcategory, downregulation of Toll-like receptor 4 (TLR4) (P = .003). IL7R and CCR7 facilitate communication between adaptive and innate immune systems. TLR4 activates the innate immune system on RSV exposure. Delayed innate and adaptive immune activation may predispose children to more severe RSV disease.


The effect of atropine used in dobutamine stress echocardiography on pupil diameter.
The use of atropine during dobutamine stress echocardiography (DSE) is contraindicated in persons with narrow angle glaucoma though there is limited evidence that low doses of intravenous atropine do not cause pupillary dilation. The aim of this study is to investigate whether atropine when administered in persons without glaucoma during dobutamine stress echocardiography causes pupillary dilation. Out of 144 patients without a history of glaucoma referred for DSE for clinical indications, 105 patients received intravenous atropine doses ranging from 0.1 mg to 1.25 mg (most patients received 0.25-0.75 mg). Pupil diameter of both eyes was measured under the same light conditions before and after the DSE using a CP-30 Optical Digital PD Ruler. For the total of 210 examined eyes pupil diameter remained unaltered after each DSE test (3.65 ± 0.799 mm before vs 3.63 ± 0.766 mm after, p = .737). Similarly, pupil diameter remained unchanged when left and right eyes were assessed separately (right eye: 3.770 ± 0.812 before vs 3.752 ± 0.745 mm after, p = .821 and left eye: 3.521 ± 0.770 before vs 3.499 ± 0.770 mm after, p = .806). Diameter of right and left pupil were also unaltered after grouping patients by sex and iris pigmentation. Age, weight, atropine dose and propranolol dose were not correlated with changes in pupil diameter. Intravenous atropine in usual doses administered in DSE does not cause mydriasis in adults without glaucoma. Future studies need to confirm our findings and expand the investigation regarding safety of atropine use during DSE in patients with narrow angle glaucoma.


Circulating Tumor DNA in Cancer Management.
Molecular techniques can be very useful in detecting a patient's tumor to guide treatment decisions is increasingly been applied in the care and management of cancer patients. Circulating tumor DNA (ctDNA) containing mutations can be identified in the plasma of cancer patients during the course of the disease. As a non-invasive "liquid biopsies",ctDNA is a potential surrogate for the entire tumor genome. The use of ctDNA might help to determine the disease prognosis,monitor disease progression,monitor the molecular resistance and monitor the tumor heterogeneity. Future developments will need to provide clinical standards to validate the ctDNA as a clinical biomarker and improve the reproducibility and accuracy,in order to be better exploited for personalized medicine.


Human mesenchymal stem cells overexpressing the IL-33 antagonist soluble IL-1 receptor-like-1 attenuate endotoxin-induced acute lung injury.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by pulmonary edema attributable to alveolar epithelial-interstitial-endothelial injury, associated with profound inflammation and respiratory dysfunction. The IL-33/IL-1 receptor-like-1 (ST2) axis plays a key role in the development of immune-inflammatory responses in the lung. Cell-based therapy has been recently proposed as an effective alternative for the treatment of ALI and ARDS. Here, we engineered human adipose tissue-derived mesenchymal stem cells (hASCs) overexpressing soluble IL-1 receptor-like-1 (sST2), a decoy receptor for IL-33, in order to enhance their immunoregulatory and anti-inflammatory properties when applied in a murine ALI model. We administered both hASCs and hASC-sST2 systemically at 6 hours after intranasal LPS instillation, when pathological changes had already occurred. Bioluminescence imaging, immunohistochemistry, and focused transcriptional profiling confirmed the increased presence of hASCs in the injured lungs and the activation of an immunoregulatory program (CXCR-4, tumor necrosis factor-stimulated gene 6 protein, and indoleamine 2,3-dioxygenase up-regulation) in these cells, 48 hours after endotoxin challenge. A comparative evaluation of hASCs and the actions of hASC-sST2 revealed that local sST2 overproduction by hASC-sST2 further prevented IL-33, Toll-like receptor-4, IL-1β, and IFN-γ induction, but increased IL-10 expression in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in protein content, differential neutrophil counts, and proinflammatory cytokine (TNF-α, IL-6, and macrophage inflammatory protein 2) concentrations in bronchoalveolar lavage fluid. In addition, hASC-sST2-treated ALI lungs showed preserved alveolar architecture, an absence of apoptosis, and minimal inflammatory cell infiltration. These results suggest that hASCs genetically engineered to produce sST2 could become a promising therapeutic strategy for ALI/ARDS management.


Regional, but not total, body composition changes in overweight and obese adults consuming a higher protein, energy-restricted diet are sex specific.
Secondary analyses of data from 2 studies were used to assess the effects of protein intake and sex on diet-induced changes in body composition. The primary hypothesis was that the changes of body composition via energy restriction (ie, lean body mass [LBM], fat mass [FM], and bone) would be sex and diet specific. For 12 weeks, 43 male (study 1) and 45 female (study 2) overweight and obese adults consumed an energy-deficit diet (750 kcal/d less than energy needs) containing either 0.8 (normal protein [NP], 21 men and 23 women) or 1.4 g protein∙kg(-1)∙d(-1) (high protein [HP], 22 men and 22 women). Body composition measurements were performed at preintervention and postintervention. Over time, all research participants lost weight, LBM, and FM. Independent of protein intake, the men lost more LBM in the trunk (-0.9 vs -0.5 kg) and less in the legs (-1.5 vs -1.1 kg) compared with the women (P < .05). Independent of sex, the HP group lost less LBM in the trunk and legs than the NP group. These sex and protein intake responses resulted in the NP men losing the most LBM in the legs and the NP women losing the most LBM in the trunk. Over time, men lost more FM (-5.0 vs -3.9 kg) from the trunk and less from legs (-1.7 vs -2.1 kg) than women (P < .05), which resulted in a greater decrease of the android-to-gynoid fat ratio for the men. Protein intake did not influence these sex-specific responses or have any independent effects on changes in FM. In addition, protein intake did not influence bone mineral density responses over time; bone mineral density was reduced in women, but not in men. These findings indicate that higher protein intake during weight loss promotes the retention of LBM in both the trunk and legs despite the sex-specific changes in these body regions.


Efficient Charge Separation in Plasmonic ZnS@Sn:ZnO Nanoheterostructure: Nanoscale Kirkendall Effect and Enhanced Photophysical Properties.
Tetravalent Sn doped ZnO nanocrystals show excellent plasmonic absorbance in the visible region. Plasmonic ZnS@Sn:ZnO core-shell heterostructures have been synthesized by the anion exchange process where the O2- is exchanged by S2- anion. An increase of sulfur concentration induces interior hollow structures arising from the different diffusion rates of O2- and S2- ions. Gradual transformation of wurtztie ZnO nanocrystals in the anion exchange process stabilizes the wurtzite crystalline phase of ZnS. Carrier concentration and various types of intrinsic defect states in both ZnO and ZnS result in ultraviolet, blue, and green emissions. The coexistence of exciton-plasmon coupling in the same nanoparticle and efficient electron-hole separation in type II heterostructure increases the photocatalytic activity and photo current gain.


Xenobiotic biotransformation in unicellular green algae. Involvement of cytochrome P450 in the activation and selectivity of the pyridazinone pro-herbicide metflurazon.
The N-demethylation of the pyridazinone pro-herbicide metflurazon into norflurazon implies a toxification in photosynthetic organisms. This is confirmed by quantitative structure activity relationships determined for two unicellular green algae, Chlorella sorokiniana and Chlorella fusca; however, the latter is 25 to 80 times more sensitive to metflurazon. This sensitivity is linked to differences in the N-demethylase activity of both algae, as determined by an optimized in vivo biotransformation assay. Apparent K(m) values of the metflurazon-N-demethylase indicate a 10-fold higher affinity for this xenobiotic substrate for Chlorella fusca. Furthermore, algal metflurazon-N-demethylation is characterized by distinct variations in activity, depending on the stage of cell development within the cell cycle. Several well-established inhibitors of cytochrome P450-mediated reactions, including piperonylbutoxide, 1-aminobenzotriazole, 1-phenoxy-3-(1H-1,2,4-triol-1yl)-4-hydroxy-5,5-dimethylhexane++ +, and tetcyclacis, as well as cinnamic acid, a potential endogenous substrate, inhibited the N-demethylation of metflurazon. The results suggest that the N-demethylation of metflurazon by both algae is mediated by a cytochrome P450 monooxygenase. The determination of antigenic cross-reactivity of algal proteins with heterologous polyclonal antibodies originally raised against plant P450s, anti-cinnamic acid 4-hydroxylase (CYP73A1), anti-ethoxycoumarin-O-dealkylase, anti-tulip allene oxidase (CYP74), and an avocado P450 (CYP71A1) or those of bacterial origin, CYP105A1 and CYP105B1, suggests the presence of distinct P450 isoforms in both algae.


COVID-19 Vaccine-Induced Myocarditis: A Systemic Review and Literature Search.
Myocarditis is one of the complications reported with COVID-19 vaccines, particularly both Pfizer-BioNTech and Moderna vaccines. Most of the published data about this association come from case reports and series. Integrating the geographical data, clinical manifestations, and outcomes is therefore important in patients with myocarditis to better understand the disease. A thorough literature search was conducted in Cochrane library, PubMed, ScienceDirect, and Google Scholar for published literature till 30 March 2022. We identified 26 patients eligible from 29 studies; the data were pooled from these qualifying case reports and case series. Around 94% of patients were male in this study, the median age for onset of myocarditis was 22 years and 85% developed symptoms after the second dose. The median time of admission for patients to hospitals post-vaccination was three days and chest pain was the most common presenting symptom in these patients. Most patients had elevated troponin on admission and about 90% of patients had cardiac magnetic resonance imaging (CMR) that showed late gadolinium enhancement. All patients admitted with myocarditis were discharged home after a median stay of four days. Results from this current analysis show that post-mRNA vaccination myocarditis is mainly seen in young males after the second dose of vaccination. The pathophysiology of vaccine-induced myocarditis is not entirely clear and late gadolinium enhancement is a common finding on CMR in these patients that may indicate myocardial fibrosis or necrosis. Prognosis remains good and all patients recovered from myocarditis, however further studies are advisable to assess long-term prognosis of myocarditis.


Colonoscopy after Golytely preparation in acute rectal bleeding.
Thirty-five consecutive patients with acute hematochezia, negative gastric aspirates, and negative sigmoidoscopy underwent urgent colonoscopy after Golytely purgation. Mucosal visualization was excellent. Colonic bleeding lesions were identified in 24 of 35 patients, and hemorrhage originating proximal to the ileoceal valve was documented in three of these 35 patients. Therapeutic endoscopic electrocautery, employed in 12 of 35 patients, was effective in 11. The peroral preparation was well tolerated, and there were no complications of the preparation or of colonoscopy. The data suggest that urgent colonoscopy following Golytely purgation is a safe, sensitive, and specific diagnostic procedure that provides an opportunity for early nonoperative treatment of acute colonic hemorrhage.


Genetic Polymorphism of Aedes albopictus Population Inferred From ND5 Gene Variabilities In Subang Jaya, Malaysia.
This study was performed to establish the genetic variability of Aedes albopictus within Subang Jaya, Selangor, Malaysia, by using the nicotinamide adenine dinucleotide dehydrogenase 5 subunit (ND5) mitochondrial DNA (mtDNA) marker. A total of 90 samples were collected from 9 localities within an area of the Subang Jaya Municipality. Genetic variability was determined through the amplification and sequencing of a fragment of the ND5 gene. Eight distinct mtDNA haplotypes were identified. The evolutionary relationship of the local haplotypes alongside 28 reference strains was used to construct a phylogram, the analysis of which revealed low genetic differentiation in terms of both nucleotide and haplotype diversity. Bayesian method was used to infer the phylogenetic tree, revealing a unique relationship between local isolates. The study corroborates the reliability of ND5 to identify distinct lineages for polymorphism-based studies and supplements the existing body of knowledge regarding its genetic diversity. This in turn could potentially aid existing vector control strategies to help mitigate the risk and spread of the dengue virus.


Overexpression, purification, and refolding of link module from human TSG-6 in Escherichia coli: effect of temperature, media, and mutagenesis on lysine misincorporation at arginine AGA codons.
The Link module, a 98-amino-acid domain found in hyaluronan binding proteins of human tumor necrosis factor stimulated gene 6 was overexpressed in Escherichia coli. Electrospray ionization mass spectrometry revealed that only 50% of the expressed protein had the expected wild-type molecular weight, with the remaining material having between 1 and 4 arginine to lysine substitutions, arising due to misincorporation at AGA codons. The level of misincorporation was almost completely abolished by mutation of the 4 AGA codons to CGT. This mutation to high-usage arginine codons also increased the level of heterologous protein expression. Refolding of the Link module, which occurred during the purification procedure, gave two species with different disulfide bond organizations that could be separated by high-performance liquid chromatography. One of these had a disulfide bond arrangement consistent with that found in other Link modules and, by nuclear magnetic resonance spectroscopy, was shown to be folded.


[The role of prostaglandin D2 in food allergy and its potential for new diagnosis and therapy methods].
Food allergy is an immune-mediated adverse reaction to food. The patients with food allergy are increasing year by year. Since the mechanisms of food allergy are largely unknown, there are still no standardized diagnosis and treatment methods. Authors have investigated the role of prostaglandin D2 in food allergy and find some new insight that contribute to reveal the mechanisms of the onset and progression of food allergy. In this paper, I introduce our novel findings and recent understanding of basic mechanisms underlying food allergy.


Isolated intraventricular haemorrhage in adults.
While intraventricular haemorrhage is frequently found in association with intraparenchymal or subarachnoid haemorrhage, isolated intraventricular haemorrhage (iIVH) is rare in adults and seldom described. Awareness of possible causes is important in order to guide patient management. After elimination of a traumatic cause, numerous aetiologies remain possible. The most frequently found underlying lesions are arteriovenous malformations and aneurysms, but other vascular causes should also be sought, including cavernous malformations and moyamoya disease. Arterial hypertension, anticoagulant use, coagulopathies and certain toxic substances are also associated with iIVH. Finally, iIVH may be caused by intraventricular tumours. In a high number of cases, the cause remains unknown. Vascular and non-vascular causes should be searched through an imaging work-up (with CT angiography, MRI and catheter angiography when necessary) and correlation with clinical information to yield a diagnosis. The aim of this pictorial essay was to review the aetiologies of iIVH in adults.


Urinary biomarkers of phthalates exposure and risks of thyroid cancer and benign nodule.
Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends < 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.


Efficacy and Safety of Aspiration Sclerotherapy of Simple Hepatic Cysts: A Systematic Review.
Aspiration sclerotherapy is a percutaneous procedure indicated for treatment of symptomatic simple hepatic cysts. The efficacy and safety of this procedure have been sources of debate and disagreement for years. The purpose of this study was to assess the long-term efficacy and safety of aspiration sclerotherapy in a systematic review of the literature. A systematic search was conducted of the electronic databases PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library (until August 2015). Studies of proportional volume or diameter reduction after aspiration sclerotherapy of simple hepatic cysts were included for full-text evaluation. Case reports and case series were excluded. Risk of bias was assessed by use of the Newcastle-Ottawa scale. From 9357 citations, 100 were selected for full-text assessment. We included 16 studies, which included 526 patients with a total of 588 treated cysts. Overall, risk of bias was high, with 12 of 16 studies having a score of poor. Proportional cyst volume reduction ranged between 76% and 100% after a median follow-up period of 1-54 months. Change in symptoms was evaluated in 10 studies: 72-100% of patients reported symptom reduction, and 56-100% reported disappearance. Postprocedural pain occurred most frequently, at a rate of 5-90% among studies. Ethanol intoxication occurred in up to 93% of cases and was reported more frequently in studies with either high ethanol volumes (133.7-138.3 mL) or long sclerotherapy duration (120-180 minutes). We found excellent results with respect to long-term efficacy and safety after aspiration sclerotherapy of hepatic cysts. Nevertheless, because of the high risk of bias in the included studies, definite conclusions regarding efficacy cannot be drawn.


Low-cost fluorimetric determination of radicals based on fluorogenic dimerization of the natural phenol sesamol.
A novel fluorimetric method for determining radicals using the natural phenol sesamol as a fluorogenic reagent is reported. In this assay, sesamol was reacted with aqueous radicals to yield one isomer of a sesamol dimer exclusively. The dimer emitted purple fluorescence near 400 nm around neutral pH, where it assumed the monoanionic form. This method was applied to the straightforward detection of radical nitric oxide (NO). The ready availability of sesamol should enable rapid implementation of applications utilizing this new assay, particularly in high-throughput analysis or screening.


Low expression of ASH2L protein correlates with a favorable outcome in acute myeloid leukemia.
ASH2L encodes a trithorax group protein that is a core component of all characterized mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes. ASH2L protein levels in primary leukemia patient samples have not yet been defined. We analyzed ASH2L protein expression in 511 primary AML patient samples using reverse phase protein array (RPPA) technology. We discovered that ASH2L expression is significantly increased in a subset of patients carrying fms-related tyrosine kinase 3 (FLT3) mutations. Furthermore, we observed that low levels of ASH2L are associated with increased overall survival. We also compared ASH2L levels to the expression of 230 proteins previously analyzed on this array. ASH2L expression was inversely correlated with 32 proteins, mostly involved in cell adhesion and cell cycle inhibition, while a positive correlation was observed for 50 proteins, many of which promote cell proliferation. Together, these results indicate that a lower level of ASH2L protein is beneficial to AML patients.


Macrophages, reactive nitrogen species, and lung injury.
Evidence has accumulated over the past several years demonstrating that lung injury following inhalation of irritants like ozone is due, not only to direct effects of the chemical, but also indirectly to the actions of inflammatory mediators released by infiltrating macrophages. Among the mediators involved in the cytotoxic process, reactive nitrogen species (RNS) are of particular interest because of their well-documented cytotoxic potential. Findings that macrophage suppression blocks RNS production and ozone-induced toxicity provide strong support for a role of these cells and inflammatory mediators in lung injury. Recent investigations have focused on understanding pathways by which macrophages become activated to release RNS. One protein that has attracted considerable attention is caveolin-1, a membrane scaffolding molecule that functions to negatively regulate cell signaling. The fact that expression of caveolin-1 is down-regulated in macrophages after ozone inhalation suggests a mechanism controlling the release of cytotoxic mediators by these inflammatory cells.


[Skin symptoms of psoriasis associated with spondylarthropathies].
The term spondylarthropathy summarizes a heterogenous group of diseases with spinal involvement as the common denominator. In this paper, we will primarily focus on cutaneous manifestations of psoriasis, as this dermatosis is associated with psoriatic artrhritis, one of the major diseases classified as spondylarthropathy. We will describe the clinical manifestations of psoriasis as well as the underlying pathophysiology, the latter allowing to understand the differences in efficacy of numerous Disease Modifying Anti-Rheumatic Drugs (DMARDs) on joint versus skin symptoms. Additionally, we address the exacerbation of pre-existing psoriasis under DMARD therapy.


Human leukocyte antigen-DR expression on flow cytometry and tumor-associated macrophages in diffuse large B-cell lymphoma treated by rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cohort study.
Loss of human leukocyte antigen (HLA)-DR expression may be related to a poor prognosis of diffuse large B-cell lymphoma (DLBCL), and tumor-associated macrophages (TAMs) may influence tumor progression. We retrospectively reviewed 36 patients with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy at Kanagawa Cancer Center in Japan from 2004 to 2010. HLA-DR expression by lymphoma cells was evaluated using flow cytometry, and TAMs in lymphoma tissue were detected by immunohistochemistry for CD68 as a marker of macrophages and CD163 as a marker of M2 TAMs. Three-year overall survival was, respectively, 100% versus 69.6% in the HLA-DR "bright" and "not bright" groups (p = 0.012). Patients from the HLA-DR "not bright" group with strong CD163 expression had a much worse prognosis than other patients. The HLA-DR status shown by flow cytometry can be used to predict the prognosis of patients with DLBCL receiving R-CHOP therapy and prognostic accuracy can be increased by also assessing TAMs.


[The presence of glycosyltransferases on chromatin acceptors in monkey liver nuclear membranes (author's transl)].
Nuclei were prepared from monkey hepatocytes by centrifugation of the homogenate on a cushion of 2.3 M sucrose, during 45 min at 100000 X g. The yield was 2.2 x 10(7) nuclei per g of liver, and 70% of te homogenate DNA was recovered in these nuclei. An electron microscopic study as well as a biochemical analysis of marker enzymes showed that the nuclei are not contaminated by other subcellular fractions, especially endoplasmic reticulum. A mannosyltransferase and an N-acetylglucosaminyltransferase, working on endogenous glycoproteic acceptors, are present in the nuclei for 1.4 and 6.5% of the homogenate activities, respectively. The nuclei are hydrolysed by DNAse I. The suspension, adjusted in 1.9 M sucrose, was centrifuged for 2 h at 100000 X g, under buffer layer. Purified nuclear membranes were collected at the interface. These membranes did not contain any more endoplasmic reticulum enzyme activities, but the mannosyl and N-acetylglucosaminyltransferase activities were still present. They essentially work on an exogenous chromatin acceptor, prepared by lysis of the nuclei. The eventual role of these glycosyltransferases in the glycosylation of non-histone proteins is discussed.


CT and US findings of pancreatoblastoma.
Our goal was to evaluate US and CT findings of pancreatoblastoma. Three US and four CT scans before surgery and one follow-up CT after surgery were reviewed in four patients (two female, two male) with pathologically proven pancreatoblastoma. The mean age of the patients was 4 years (range 2-5 years). The masses were analyzed for origin, US and CT architecture, presence of calcification, enhancement pattern, and metastatic spread. In two patients, the tumors arose from the pancreatic head and in one patient from the pancreatic tail. The mean largest diameter of the masses was 10 cm, ranging from 5 to 14 cm. Sonography obtained from three cases showed mixed echogenic solid mass. On the CT scan, all tumors were huge, lobulated masses with heterogeneous attenuation. One tumor contained numerous foci of calcification. On the enhanced CT scan, three tumors showed multiloculated appearance by enhancing internal septations. There was no evidence of metastasis to distant organ or abdominal lymph node in any case. We suggest that the most common US finding of pancreatoblastoma is a mixed echogenic, solid mass inseparable from the pancreas, and the most common CT finding is a relatively well defined, lobulated, huge mass with multiloculated appearance by enhancing septae in or near the lesser sac.


Up-regulation of vinculin expression in 3T3 preadipose cells by growth hormone.
In an effort to define biochemical events relevant to the adipogenic action of GH, the effect of GH on expression of the cytoskeletal element vinculin was studied in 3T3-F442A preadipose cells. Results from Western blotting indicated that in serum-free medium 2 nM met-hGH induced an approximately 100% increase in vinculin expression relative to that in cells maintained in serum-free medium alone. GH-elicited alterations in vinculin expression were dose dependent. GH treatment elevated levels of tubulin to a lesser extent, whereas actin expression was unaffected by GH. Immunoprecipitation experiments revealed that GH treatment promoted a 200% increase in vinculin synthesis on day 4 relative to that in control cells. GH had no effect on phosphorylation of vinculin in 3T3-F442A cells. Based on Northern blotting, we noted that GH induced approximately a 200% increase in levels of vinculin mRNA on day 4. GH responsiveness as well as levels of vinculin were similar in 3T3-GI-16 (a highly adipogenic subclone of the 3T3-F442A cell) and 3T3-F442A cells. The GH-dependent increase in vinculin protein expression was not observed in nonadipogenic 3T3-C2 cells, suggesting that this effect of GH was related to the program of differentiation. Interestingly, levels of vinculin in nontreated 3T3-C2 cells were approximately 10-fold lower than levels in 3T3-F442A cells. GH-mediated alterations in vinculin expression in 3T3-F442A cells were abolished by treatment with fetal bovine serum, a potent mitogen. Our data indicate that increased expression of vinculin is a component of the GH-induced portion of the adipose differentiation program.


Splinting in the treatment of arthritis of the first carpometacarpal joint.
Although much has been written about surgical treatment of arthritis of the first carpometacarpal joint, no literature exists on splinting as a conservative treatment. One hundred fourteen patients (130 thumbs) were retrospectively reviewed to determine the efficacy of splinting. Patients were grouped according to their stage of disease and whether they had carpometacarpal joint surgery. Seventy-six percent of patients with stage I and II disease and 54% of patients with stage III and IV disease had improvement in their symptoms with splinting. There was no significant difference in the degree of improvement between the 2 groups. All patients who had initial improvement in their symptoms with splinting had between 54% and 61% average improvement in symptom severity 6 months after splinting. All groups were found to be equally tolerant of the splinting protocol and no group had a significantly higher rate of activity modification. Overall, splinting was found to be a well-tolerated and effective conservative treatment to diminish, but not completely eliminate, the symptoms of carpometacarpal joint arthritis and inflammation.


Assessing the Safety Risks of Civil Engineering Laboratories Based on Lab Criticity Index: A Case Study in Jiangsu Province.
With the rapid development of the construction industry, an increasing amount of attention were paid by universities to the development of civil engineering experiment courses so as to improve the practical research abilities of students. In recent years, due to the frequent occurrence of civil engineering laboratory accidents, it has become an urgent issue regarding on what factors influencing safety risks and how to assess and reduce the safety risks in civil engineering laboratories. Based on the lab criticity index (LCI) model, the research specificities of civil engineering laboratories were analyzed through literature review and expert interviews and 13 risk factors of civil engineering laboratories, from the four aspects of man, object, management, and environment, identified. The data for each parameter in the LCI model was obtained through a questionnaire survey, and finally the LCI value was calculated to evaluate priority. Among them, insufficient safety awareness of operators, danger due to equipment failure, imperfect management policies, and complex floor conditions were listed as the most common risk factors. Based on the LCI model, the worsening factors of these four risk factors were further analyzed. The LCI model is applied to the new research field of safety risk assessment in civil engineering laboratories that few researchers have studied before and a risk list for civil engineering laboratories was created. We revealed the safety status of civil engineering laboratories in Jiangsu Province and provided feasible suggestions for improving the management and supervision of civil engineering laboratories at universities. It can strengthen operator awareness of the risks in civil engineering laboratories and improve the social group's attention to the safety risks of the laboratories, thus reducing the accidents' possibility and seriousness of civil engineering laboratories.


The relation between disinhibition and emotion regulation in boys with attention deficit hyperactivity disorder.
This study examined group differences of 49 boys ages 6 to 11 years with and without attention deficit hyperactivity disorder (ADHD) in emotion regulation during frustrating peer competition. Half of all boys in each group were explicitly instructed to hide their feelings if they became upset during the competition. Behavioral inhibition, both before and after the competitive task, was examined using the Stop Signal Task (SST), and emotion regulation was assessed via structured observation data. Effect sizes indicated that impulsive ADHD boys displayed greater disinhibition and were less effective at emotion regulation than comparison boys. In addition, boys with ADHD were unsuccessful in masking their emotions even when instructed to do so. In contrast, comparison boys were more successful at emotion regulation when given instruction to self-regulate, and these regulatory attempts predicted later inhibitory control. Findings are discussed in the context of current ADHD-related theories of inhibitory deficit, and suggestions for future research are provided.


Refraction in juvenile chronic arthritis: a long-term follow-up study, with emphasis on myopia.
Assessment of refraction anomalies in juvenile chronic arthritis (JCA) on a long-term follow-up basis. Sixty-five adults, 52 females and 13 males, with a history of active JCA had a complete ophthalmic evaluation including subjective refractioning on average 26.4 years after JCA onset. The age range was 22-49 years. The refraction ranged from -8.12 D to +6.5 D with a mean (SD) of -0.64 (2.16) D. The mean refraction in the JCA group was significantly more towards myopia than that of a coeval adult hospital-based sample used as controls (p = 0.008). Twenty-eight out of the 65 (43%) had a negative refractive value of at least 0.37 D. Myopia onset age ranged from 8 to 31 years. In those able to specify their myopia onset by first purchase of spectacles (n = 25) the JCA onset had preceded the myopia, with a mean (SD) interval of 10.1 (5.4) years. The elevated myopia figure of 43% among JCA patients suggests an association between myopia and JCA. In lack of more precise indicators and in accordance with older literature, an explanation might be a weakening effect of chronic inflammation on scleral connective tissue.


Gut Microbiota and Type 1 Diabetes Mellitus: The Effect of Mediterranean Diet.
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting from a complex interplay between genetic susceptibility and environmental factors. Regarding the latter, gut microbiota has a pivotal role in the pathogenesis of T1DM, by affecting intestinal permeability, molecular mimicry, and modulating innate and adaptive immune system, as described in several previous studies. The composition of the gut microbiota is largely influenced by diet. Some observational studies have shown that a low fiber intake is associated with the development of many inflammatory and immune-mediated diseases. In this context, the Mediterranean diet (MD), which is based on high consumption of cereals (preferably as whole grains), legumes, nuts, vegetables, fruits, olive oil, and fish, could play a protective role. Many of the characteristic components of MD have functional characteristics with positive effects on health and well-being. Eating habits are the main significant determinants of the microbial multiplicity of the intestine and the food components influence both microbial populations and their metabolic activities from the early stages of life. Moreover, food metabolites influence the immune response. The intestine is considered the primary site where food metabolites mediate their effects, through epithelial integrity or mucosal immunity. The compromised epithelial integrity allows the translocation of bacteria and/or the diffusion of their products, such as food antigens and lipopolysaccharides, from the intestinal lumen to the tissues, which could enhance the stimulation of immune cells, contributing to the pathogenesis of autoimmune diseases, such as T1DM. The intake of a high amount of fiber and therefore of prebiotics with MD allows the microbiota to have a good microbial balance. Moreover, as more dietary fibers are ingested, a higher amount of short-chain fatty acids (SCFAs) is produced by anaerobic gut microbiota, promoting gut homeostasis, to which also contribute tryptophan metabolites and omega-3-fatty acids. Furthermore, the higher intake of polyunsaturated fatty acids and omega-3-fatty-acids contribute to a better metabolic control. In this review we report the relationship between gut microbiota and T1DM and we explore the effects of Mediterranean diet on microbiota as a potential therapeutic strategy, aimed at preventing or delaying progression of T1DM and its complications.


Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.
Bleeding complications are the most common and unwanted side-effect of oral anticoagulant therapy. We report three patients in whom mutations in the factor IX (FIX) propeptide were found to cause severe bleeding during coumarin therapy. Strikingly, the bleeding occurred within the therapeutic ranges of the prothrombin time (PT) and international normalized ratio (INR). In all three patients coumarin therapy caused an unusually selective decrease of FIX activity (FIX:C) to levels below 1-3%. Upon withdrawal of coumarin, FIX:C increased to subnormal or normal values of 55%, 85% and 125%, respectively. Analysis of the FIX gene revealed two different missense mutations affecting the Ala-10 residue in the propeptide coding region: Ala[GCC] to Val[GTC] in two patients and Ala[GCC] to Thr[ACC] in one patient. No further mutation was detected by screening 195 random blood donors for mutations at Ala-10, thus excluding a frequent polymorphism at this position. The mutation in the FIX propeptide at a position which is essential for the carboxylase recognition site causes a reduced affinity of the carboxylase enzyme to the propeptide. This effect leads to an impaired carboxylase epoxidase reaction which is decisively triggered by the vitamin K concentration. Determination of FIX and APTT in addition to PT and INR is therefore recommended in coumarin-treated patients with an uncommon bleeding pattern.


Molecular markers for discrimination of benign and malignant follicular thyroid tumors.
To identify molecular markers useful for the diagnostic discrimination of benign and malignant follicular thyroid tumors. A panel of thyroid tumors was characterized with expression profiling using cDNA microarrays. A robust algorithm for gene selection was developed to identify molecular markers useful for the classification of heterogeneous tumor classes. The study included tumor tissue specimens from 10 patients with benign follicular adenomas and from 10 with malignant tumors. The malignant tumors mainly consisted of clinically relevant minimally invasive follicular carcinomas. The mRNA expression level of a candidate gene, FHL1, was evaluated in an independent series of 61 tumors. 22 gene expression markers were identified as differentially expressed. Several of the identified genes, for example DIO1, CITED1, CA12 and FN1, have previously been observed as differentially expressed in various thyroid tumors. FHL1 was significantly underexpressed in carcinomas compared to adenomas in the independent panel of tumors. The results indicate that a small number of genes can be useful to distinguish follicular adenomas from follicular carcinomas. Our findings clearly corroborate previous studies and identify novel candidate molecular markers. These genes have the potential for molecular classification of follicular thyroid tumors and for providing improved understanding of the molecular mechanisms involved in thyroid malignancies.


Maize root growth and localized indol-3yl-acetic Acid treatment: a new methodological approach.
Resin beads loaded with indol-3yl-acetic acid (IAA) were used as asymmetrical donors along the elongation zone of intact primary Zea mays L. roots. A strong curvature, towards and above the bead, occurred when IAA was applied at a mean distance of 2.20 mm from the tip. No curvature was detected after applications at 3.89 and 5.71 mm from the tip. Correspondence analysis, a new methodological approach in plant hormone studies, permitted the evaluation of the relative influence of several factors on the curvature observed for each root. The parameters considered were the initial growth rate, the exact location of the bead (1.64-2.73 millimeters from tip) and the quantity of IAA absorbed. Roots which grew rapidly bent earlier than slowly growing ones and the more basal the treatment was, the less curvature occurred. Surprisingly, the amount of IAA taken up (between 1.2 and 2.2 times the endogenous IAA content) was found to have no influence on either the time-course or the magnitude of this growth inhibition (curvature). The usefulness of this multivariate analysis is also discussed.


Cryo-EM structure of hexameric yeast Lon protease (PIM1) highlights the importance of conserved structural elements.
Lon protease is a conserved ATP-dependent serine protease composed of an AAA+ domain that mechanically unfolds substrates and a serine protease domain that degrades these unfolded substrates. In yeast, dysregulation of Lon protease (PIM1) attenuates lifespan and leads to gross mitochondrial morphological perturbations. Although structures of the bacterial and human Lon protease reveal a hexameric assembly, yeast PIM1 was speculated to form a heptameric assembly and is uniquely characterized by a ∼50-residue insertion between the ATPase and protease domains. To further understand the yeast-specific properties of PIM1, we determined a high-resolution cryo-electron microscopy structure of PIM1 in a substrate-translocating state. Here, we reveal that PIM1 forms a hexamer, conserved with that of bacterial and human Lon proteases, wherein the ATPase domains form a canonical closed spiral that enables pore loop residues to translocate substrates to the protease chamber. In the substrate-translocating state, PIM1 protease domains form a planar protease chamber in an active conformation and are uniquely characterized by a ∼15-residue C-terminal extension. These additional C-terminal residues form an α-helix located along the base of the protease domain. Finally, we did not observe density for the yeast-specific insertion between the ATPase and protease domains, likely due to high conformational flexibility. Biochemical studies to investigate the insertion using constructs that truncated or replaced the insertion with a glycine-serine linker suggest that the yeast-specific insertion is dispensable for PIM1's enzymatic function. Altogether, our structural and biochemical studies highlight unique components of PIM1 machinery and demonstrate evolutionary conservation of Lon protease function.


Two Spanish sibs with familial amyloidotic polyneuropathy homozygous for the V30M-TTR gene.
Two Spanish sibs with familial amyloidotic polyneuropathy (FAP) homozygous for the V30M-TTR gene, were diagnosed by DNA and protein analyses. Their clinical picture was very similar to the Majorcan FAP heterozygous patients except for the sensorimotor syndrome which was more aggressive. Noteworthy were clinical differences between the sibs concerning autonomic involvement, cranial neuropathy and kidney disturbances. These differences can be due to genetic and/or environmental factors.


Simultaneous interferometric and polarimetric strain measurements on composites using a fiber-optic strain gauge.
A fiber-optic Michelson interferometer is used for remote sensing of the bending-induced surface strain (up to 2500 microepsilon) of plates made from carbon-fiber composites. The double-polarization method is used for eliminating the ambiguity of fringe counting. Simultaneous measurement of the birefringencedependent phase offset yields an additional analog (polarimetric) signal, which allows for initialization of the incremental readout. The measured dependence of surface strain on plate bending agrees with the theoretically expected linear relationship, and it agrees with the gauge sensitivity published by Valis et al. [Proc. Soc. Photo-Opt. Instrum. Eng. 1170, 495 (1989)]. The observed hysteresis and temperature sensitivity are significantly smaller than the same effects in an electrical strain gauge.


piezo2b regulates vertebrate light touch response.
The sense of touch allows an organism to detect and respond to physical environmental stimuli. Mechanosensitive proteins play a crucial role in this process by converting the mechanical cue into a biological response. Recently, the Piezo family of stretch-activated ion channels has been identified as genuine mechanosensitive proteins. We set out to determine whether any of these genes are involved in touch response during zebrafish development. In situ hybridization indicates that piezo2b is specifically expressed in a subset of neurons (Rohon-Beard cells) responsible for detecting light touch. Using morpholino-mediated knockdown, we specifically targeted piezo2b and determined that it is involved in mediating touch-evoked response.


Post-stroke pure apraxia of speech - A rare experience.
Apraxia of speech (AOS) is a motor speech disorder, most typically caused by stroke, which in its "pure" form (without other speech-language deficits) is very rare in clinical practice. Because some observable characteristics of AOS overlap with more common verbal communication neurologic syndromes (i.e. aphasia, dysarthria) distinguishing them may be difficult. The present study describes AOS in a 49-year-old right-handed male after left-hemispheric stroke. Analysis of his articulatory and prosodic abnormalities in the context of intact communicative abilities as well as description of symptoms dynamics over time provides valuable information for clinical diagnosis of this specific disorder and prognosis for its recovery. This in turn is the basis for the selection of appropriate rehabilitative interventions.


Peripheral target identification performance modulates eye movements.
We often shift our eyes to an interesting stimulus, but it is important to inhibit that eye movement in some environments (e.g., a no-look pass in basketball). Here, we investigated participants' ability to inhibit eye movements when they had to process a peripheral target with a requirement to maintain strict fixation. An array of eight letters composed of four characters was briefly presented and a directional cue was centrally presented to indicate the target location. The stimulus onset asynchrony (SOA) between the cue and the stimulus array was chosen from six values, consisting of pre-cue conditions (-400 and -200ms), a simultaneous cue condition (0ms), and post-cue conditions (200, 400, and 800ms). We found the following: 1) participants shifted their eyes toward the cued location even though the stimulus array was absent at the onset of eye movements, but the eye movement amplitude was smaller than the actual location of the target; 2) eye movements occurred approximately 150ms after the onset of stimulus array in the pre-cue conditions and 250ms after cue onset in the simultaneous and post-cue conditions; and 3) eye movement onsets were delayed and their amplitudes were smaller in correct trials than incorrect trials. These results indicate that the inhibitory process controlling eye movements also compete for cognitive resources like other cognitive processes.


Diversity of clinical isolates of Aspergillus terreus in antifungal susceptibilities, genotypes and virulence in Galleria mellonella model: Comparison between respiratory and ear isolates.
We analyzed the antifungal susceptibility profiles, genotypes, and virulence of clinical Aspergillus terreus isolates from six university hospitals in South Korea. Thirty one isolates of A. terreus, comprising 15 respiratory and 16 ear isolates were assessed. Microsatellite genotyping was performed, and genetic similarity was assessed by calculating the Jaccard index. Virulence was evaluated by Galleria mellonella survival assay. All 31 isolates were susceptible to itraconazole, posaconazole, and voriconazole, while 23 (74.2%) and 6 (19.4%) showed amphotericin B (AMB) minimum inhibitory concentrations (MICs) of ≤ 1 mg/L and > 4 mg/L, respectively. Notably, respiratory isolates showed significantly higher geometric mean MICs than ear isolates to AMB (2.41 vs. 0.48 mg/L), itraconazole (0.40 vs. 0.19 mg/L), posaconazole (0.16 vs. 0.08 mg/L), and voriconazole (0.76 vs. 0.31 mg/L) (all, P <0.05). Microsatellite genotyping separated the 31 isolates into 27 types, but the dendrogram demonstrated a closer genotypic relatedness among isolates from the same body site (ear or respiratory tract); in particular, the majority of ear isolates clustered together. Individual isolates varied markedly in their ability to kill infected G. mellonella after 72 h, but virulence did not show significant differences according to source (ear or respiratory tract), genotype, or antifungal susceptibility. The current study shows the marked diversity of clinical isolates of A. terreus in terms of antifungal susceptibilities, genotypes and virulence in the G. mellonella model, and ear isolates from Korean hospitals may have lower AMB or triazole MICs than respiratory isolates.


Early-adolescent dual language learners' reading comprehension: Influences of teacher questions and language efficacy.
This study examined the relation between middle school Dual Language Learners' (DLLs'; N = 413; M age = 11.66 years old; 87.1% Latino; female = 234, male = 179) reading comprehension skills and their teachers' (N = 32; M age = 36.53 years; 81.3% Caucasian; female = 27, male = 5) questioning practices across the school year. This study also examined relations between DLLs' engagement in high-quality discussion practices, language efficacy (i.e., beliefs about their capabilities to use language), and reading comprehension. Results demonstrated that teachers' use of authentic (open-ended) questions was positively related to their DLL students' reading comprehension; teachers' questioning practices were consistent across the year. Results also revealed a positive interaction between DLLs' high-quality discussion practices and their language efficacy in predicting reading comprehension. That is, when DLLs had higher language efficacy, there was a more positive effect of their high-quality discussion practices on their Spring reading comprehension scores. These findings suggest that teachers' questioning practices are important in creating classroom environments that promote DLLs' reading comprehension. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Impact of the Built Environment and the Neighborhood in Promoting the Physical Activity and the Healthy Aging in Older People: An Umbrella Review.
(1) Background: The aim of this study is to establish which specific elements of the built environment can contribute to improving the physical activity of self-sufficient, noninstitutionalized and living in the city adults > 65 years. (2) Methods: An extensive literature search was conducted in several database. Umbrella review methodology was used to include the reviews that presented a sufficient methodological quality. (3) Results: Eleven reviews were included. The elements positively associated with physical activity in older adults were: walkability; residential density/urbanization; street connectivity; land-use mix-destination diversity; overall access to facilities, destinations and services; pedestrian-friendly infrastructures; greenery and aesthetically pleasing scenery; high environmental quality; street lighting; crime-related safety; traffic-related safety. The elements that were negatively associated with physical activity were: poor pedestrian access to shopping centers; poor pedestrian-friendly infrastructure and footpath quality; barriers to walking/cycling; lack of aesthetically pleasing scenery; crime-related unsafety; unattended dogs; inadequate street lighting and upkeep; traffic; littering, vandalism, decay; pollution; noise. (4) Conclusions: Evidence shows that specific elements of the built environment can contribute to promoting older people's physical activity. The city restructuring plans should take into consideration these factors.


Management of crossing vessels in children and adults: A multi-center experience with the transperitoneal laparoscopic approach.
Crossing vessels (CVs) are common in older children and adults with hydronephrosis but no gold standard exists on how to treat this condition. The final decision is made intraoperatively by the surgeon. To assess the outcome of the laparoscopic dismembered pyeloplasty with translocation of the CVs in children and adults. Prospectively collected data from 3 departments was reviewed. Inclusion criteria were: 1) a transperitoneal laparoscopic approach; 2) dismembered pyeloplasty; and 3) the same operating pediatric urologist (RC) or urologist (TS). In the case of CVs, pyeloplasty with vessel transposition (children) or with cephalad translocation (adults) was performed. Forty-eight children and 41 adults met these criteria. Patients were divided into 4 groups: children with (group 1A) and without (group 1B) CVs, and adults with (group 2A) and without (group 2B) CVs. Any surgical reintervention at the uretero-pelvic junction (UPJ) was deemed a failure. The overall reintervention rate was 3/48 (6.25%) in children and 2/41 (4.9%) in adults (p > 0.05), and involved the following: 4 endopyelotomies and 1 redo pyeloplasty. Crossing vessels were identified in 28/48 (58%) children and 12/41 (29%) adults. The mean operation time was 152 min in group 1A and 161 min in group 2A (p > 0.5). Reintervention was needed in 2/28 patients in group 1A and in 1/12 patients in group 2A (p > 0.05). There was no difference in the failure rate between group 1A and group 1B, nor between group 2A and group 2B (p > 0.05). Crossing vessels should be meticulously looked for during pyeloplasty in older children and adults. Dismembered laparoscopic pyeloplasty (LP) with dorsal transposition or cephalad translocation are comparable methods in terms of success rate for the treatment of UPJ obstruction in these patients.


Fragmentation investigation of brassinosteroid compounds by ion trap and quadrupole time-of-flight mass spectrometry.
The fragmentation mechanisms of three types of brassinosteroids (BRs), 23,24-tris-epicastasterone, epicastasterone, tris-epicastasterone, 24-epibrassinolide and 6-deoxo-24-epicastasterone, have been extensively investigated by tandem mass spectrometry (MS(n), n = 1, 2, 3, 4, 5) with the assistance of high mass accuracy quadrupole time-of-flight mass spectrometry (QToF MS). The electrospray ionization (ESI) mass spectrometric fragmentation pathways of these five BRs were comprehensively elucidated for the first time. Cleavages of side chains, neutral losses of water or other molecules and opening of a ring induce the main fragmentation patterns. The results from the present study can potentially afford important guidance for the structural elucidation of different BRs and provide some fundamental data for metabolomic analysis of BRs.


Clinical analysis of percutaneous computed tomography-guided injection of cyanoacrylate for localization of 115 small pulmonary lesions in 113 asymptomatic patients.
This study was performed to assess the clinical feasibility, safety, and effectiveness of a computed tomography (CT)-guided cyanoacrylate injection system and investigate the relationship between clinical features and pathologic characteristics of diminutive pulmonary lesions. In total, 115 pulmonary nodules from 113 patients (63 female, 50 male) with a diameter of <20 mm were percutaneously localized with a CT-guided cyanoacrylate injection system and then resected. Of the pure ground-glass opacities (GGOs), 16.0% were atypical adenomatous hyperplasia (AAH), 18.7% were adenocarcinoma in situ (AIS), 49.3% were lung adenocarcinoma (ADC), and 16.0% were benign inflammatory fibrosis/fibrotic scars. Of the mixed GGOs, 18.2% were AAH, 22.7% were AIS, 22.7% were ADC, and 36.4% were benign lesions. Lesions of >10 mm and those located in relation to vessels were significantly more likely to be malignant. The success rate of both the cyanoacrylate injection system and video-assisted thoracoscopic surgery was 100% with no severe complications. Preoperative localization of small pulmonary nodules using a cyanoacrylate injection system is a safe, simple, and useful technique.


Assessing the impact of digital patient monitoring on health outcomes and healthcare resource usage in addition to the feasibility of its combination with at-home treatment, in participants receiving systemic anticancer treatment in clinical practice: protocol for an interventional, open-label, multicountry platform study (ORIGAMA).
Digital patient monitoring (DPM) tools can enable more effective clinical care and improved patient outcomes in cancer. However, their broad adoption requires ease of use and demonstration of real-world clinical utility/impact. ORIGAMA (MO42720) is an interventional, open-label, multicountry platform study investigating the clinical utility of DPM tools and specific treatments. ORIGAMA will begin with two cohorts that aim to assess the impact of the atezolizumab-specific Roche DPM Module (hosted on the Kaiku Health DPM platform (Helsinki, Finland)) on health outcomes and healthcare resource usage, and its feasibility to support at-home treatment administration, in participants receiving systemic anticancer treatment. Other digital health solutions may be added to future cohorts. In Cohort A, participants with metastatic non-small cell lung cancer (NSCLC), extensive-stage SCLC or Child Pugh A unresectable hepatocellular carcinoma will be randomised to a locally approved anticancer regimen containing intravenous atezolizumab (TECENTRIQ, F. Hoffmann-La Roche Ltd/Genentech) and local standard-of-care support, with/without the Roche DPM Module. Cohort B will assess the feasibility of the Roche DPM Module in supporting administration of three cycles of subcutaneous atezolizumab (1875 mg; Day 1 of each 21-day cycle) in the hospital, followed by 13 cycles at home by a healthcare professional (ie, flexible care), in participants with programmed cell-death ligand 1-positive, early-stage NSCLC. The primary endpoints are the mean difference in change of the participant-reported Total Symptom Interference Score at Week 12 from baseline (Cohort A) and flexible care adoption rate at Cycle 6 (Cohort B). This study will be conducted according to the Declaration of Helsinki, and/or the applicable laws and regulations of the country in which the research is conducted, whichever affords the greater protection to the individual. The study received its first Ethics Committee approval in Spain in October 2022. Participants will provide written informed consent in a face-to-face setting. The results of this study will be presented at national and/or international congresses and disseminated via publication in peer-reviewed journals. NCT05694013.


Treatment Approach to Patients With Severe Insulin Resistance.
In Brief Patients with severe insulin resistance require >2 units/kg of body weight or 200 units/day of insulin. Yet, many patients do not achieve glycemic targets despite using very high doses of insulin. Insulin can cause weight gain, which further contributes to worsening insulin resistance. This article describes the pharmacological options for managing patients with severe insulin resistance, including the use of U-500 insulin and newer agents in combination with insulin.


Reactivity toward Unsaturated Small Molecules of Thiolate-Bridged Diiron Hydride Complexes.
In the presence of 1 equiv of tBuNC, the homolytic cleavage of the FeIII-H bond in the diiron terminal hydride complex [Cp*Fe( t-H)(μ-η2:η4-bdt)FeCp*][BF4] (1[BF4]) smoothly took place to release 1/2 H2, followed by binding of a tBuNC group to the unsaturated FeII center. Interestingly, upon exposure of 1[BF4] to 1 atm of acetylene, the isomerization process of the hydride ligand from the terminal to bridging coordination site was unaffected. Upon treatment of the diiron hydride bridged complex 2[BF4] with acetylene at 30 °C, two FeIII-H bonds were broken, and then an acetylene molecule was coordinated to the diiron centers in a novel μ-η2:η2 side-on fashion. In the above reaction system, the hydride ligands whether terminal or bridging all play a role as the electron donor for the reduction of the diiron centers from FeIIIFeIII to FeIIIFeII. These reaction patterns are reminiscent of the vital E4 state responsible for N2 binding and H2 liberation in the catalytic cycle of nitrogenase, which contains two {Fe-H-Fe} motifs as electron reservoirs for the reduction of the iron centers. Differently, when treating 1[BF4] with TMSN3, the terminal hydride ligand was inserted into the azide group to give a diiron amide complex 4[BF4] in moderate yield.


The Family Physician's Role During Disasters.
Family physicians can encourage disaster planning and mock disaster exercises in their community. If involved in an actual disaster, the family physician can be helpful as a triage officer in emergency, in initial resuscitation, in minor treatment, in discharging stable patients, and in counselling victims of post-traumatic shock syndrome. The key to effective performance is being prepared beforehand to cope with the stress and confusion of the incident. Use of laboratory and diagnostic imaging must be curtailed until all severely injured patients are treated.


[Radiological evaluation of intraductal papillary mucinous neoplasm].
The intraductal papillary mucinous neoplasm (IPMN) is the most frequent cystic neoplasm of the pancreas. Due to the widespread use of cross-sectional imaging IPMN is being incidentally recognized with increasing frequency. The most common type is branch- duct IPMN which occurs multifocally in about 20-30%. Patients with IPMN may present with symptoms resembling chronic pancreatitis and episodes of acute pancreatitis are increasingly being reported which usually have a mild course. The most important diagnostic technique is contrast-enhanced multidetector computed tomography (MDCT), which most frequently allows the differentiation from other cystic lesions and enables the attribution to branch duct or main duct IPMN. Magnetic resonance imaging (MRI) in combination with magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound are superior in depicting the fine architecture of cystic tumors. Particularly for evaluation of malignant transformation and extent of malignant disease, high resolution imaging is essential. Whereas main duct IPMN is an indication for resection therapy for small and asymptomatic branch duct IPMN periodic surveillance at 6-12 month intervals is recommended.


Is tau aggregation toxic or protective?
Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species.


Cyclotriveratrylene-Containing Porphyrins.
The C3-symmetric cyclotriveratrylene (CTV) was covalently bonded via click chemistry to 1, 2, 3, and 6 zinc(II) porphyrin units to various host for C60. The binding constants, Ka, were measured from the quenching of the porphyrin fluorescence by C60. These constants vary between 400 and 4000 M(-1) and are considered weak. Computer modeling demonstrated that the zinc(II) porphyrin units, [Zn], exhibit a strong tendency to occupy the CTV cavity, hence blocking the access for C60 to land on this site. Instead, the pincer of the type [Zn]----[Zn] and in one case [Zn]----CTV, were found to be the most probable geometry to promote host-guest associations in these systems.


Laser radiation at various wavelengths for decompression of intervertebral disk. Experimental observations on human autopsy specimens.
The interaction of laser radiation with the nucleus pulposus from autopsy specimens of human intervertebral disks was evaluated at different wavelengths (193 nm, 488 nm & 514 nm, 1064 nm, 1318 nm, 2150 nm, 2940 nm, and 10600 nm). A significant correlation of linear least squares fit of the mass ablated as a function of incident energy was found for all lasers used except the Excimer at 193 nm. The 2940-nm Erbium:YAG laser was most efficient in terms of mass of disk ablated per joule in the limited lower range where this wavelength was observed. At higher energy levels, the CO2 laser in the pulsed mode was most efficient. However, the Nd:YAG 1064-nm and 1318-nm lasers are currently best suited for percutaneous laser disk decompression because of the availability of usable waveguides. Carbonization of tissue with the more penetrating Nd:YAG 1064-nm laser increases the efficiency of tissue ablation and makes it comparable to the Nd:YAG 1318-nm laser.


Isolation, purification and labeling of mouse bone marrow neutrophils for functional studies and adoptive transfer experiments.
Neutrophils are critical effector cells of the innate immune system. They are rapidly recruited at sites of acute inflammation and exert protective or pathogenic effects depending on the inflammatory milieu. Nonetheless, despite the indispensable role of neutrophils in immunity, detailed understanding of the molecular factors that mediate neutrophils' effector and immunopathogenic effects in different infectious diseases and inflammatory conditions is still lacking, partly because of their short half life, the difficulties with handling of these cells and the lack of reliable experimental protocols for obtaining sufficient numbers of neutrophils for downstream functional studies and adoptive transfer experiments. Therefore, simple, fast, economical and reliable methods are highly desirable for harvesting sufficient numbers of mouse neutrophils for assessing functions such as phagocytosis, killing, cytokine production, degranulation and trafficking. To that end, we present a reproducible density gradient centrifugation-based protocol, which can be adapted in any laboratory to isolate large numbers of neutrophils from the bone marrow of mice with high purity and viability. Moreover, we present a simple protocol that uses CellTracker dyes to label the isolated neutrophils, which can then be adoptively transferred into recipient mice and tracked in several tissues for at least 4 hr post-transfer using flow cytometry. Using this approach, differential labeling of neutrophils from wild-type and gene-deficient mice with different CellTracker dyes can be successfully employed to perform competitive repopulation studies for evaluating the direct role of specific genes in trafficking of neutrophils from the blood into target tissues in vivo.


Clinico-epidemiological profile of COVID-19 patients admitted during third wave of pandemic in a tertiary care hospital in New Delhi, India.
Even nearly two years after the first reported case, the novel coronavirus (SARS-CoV-2) continues to ebb and flow around the world. A retrospective cohort study was carried out to determine the clinico-epidemiological profile and outcome of the cases. The study analyzed secondary data from 827 patients who presented to our center with COVID-19-related illnesses between December 15, 2021, and February 15, 2022 (third wave in India). There was a significant difference in the vaccination status of patients treated at home and those admitted, with 87.9% having received two doses compared to 74% in the second group being unvaccinated. Patients who were isolated at home recovered at a rate of 99.4%, while hospitalized patients died at a rate of 26.5%. Vaccination reduces the severity of COVID-19; however, constant vigilance for new variants, precautionary measures, and increased vaccination drives are critical moving forward. *Other members of the Safdarjung Hospital COVID-19 working group: B. Lal (Medicine), Harish Sachdeva (Anaesthesiology), Santvana Kohli (Anaesthesiology), Amandeep Jaswal (Anaesthesiology), Sumitra Bachani (Obstetrics and Gynecology), Ajay Kumar (Pediatrics), Rohit Kumar (Pulmonary Medicine), Vidya Sagar Chaturvedi (Surgery), Vinod Chaitanya (Medicine).


Guard cell protoplasts: isolation, culture, and regeneration of plants.
Guard cell protoplasts have been used extensively in short-term experiments designed to elucidate the signal transduction mechanisms that regulate stomatal movements. The utility of uard cell protoplasts for other types of longer-term signal transduction experiments is just now being realized. Because highly purified, primary isolates of guard cell protoplasts are synchronous initially, they are uniform in their responses to changes in culture conditions. Such isolates have demonstrated potential to reveal mechanisms that underlie hormonal signalling for plant cell survival, cell cycle re-entry, reprogramming of genes during dedifferentiation to an embryogenic state, and plant cell thermotolerance. Plants have been regenerated from cultured guard cell protoplasts of two species: Nicotiana glauca (Graham), tree tobacco, and Beta vulgaris, sugar beet. Plants genetically engineered for herbicide tolerance have been regenerated from cultured guard cell protoplasts of B. vulgaris. The method for isolating, culturing, and regenerating plants from guard cell protoplasts of N. glauca is described here. A recently developed procedure for large-scale isolation of these cells from as many as nine leaves per experiment is described. Using this protocol, yields of 1.5-2 x 10(7) per isolate may be obtained. Such yields are sufficient for standard methods of molecular, biochemical, and proteomic analysis.


Occlusion of interatrial communications with the Amplatzer device: experience in 48 consecutive patients.
Both secundum atrial septal defect (ASD) and patent foramen ovale (PFO) have been closed interventionally using several different occluding devices. At a single institution we strived for interventional occlusion of interatrial communications using the Amplatzer device exclusively. During a study period of 22 months, we studied 48 patients ranging in age from 1 to 48 years with an ASD (n = 45) or a PFO (n = 3). Successful implantation of an Amplatzer device was possible in 92% of the patients, and 95% of these patients had a complete early closure of their defect. There were no complications related to the procedure. We conclude that interventional closure of interatrial communications with the Amplatzer device is feasible and safe for selected patients.


A qualitative study of anterior resection syndrome: the experiences of cancer survivors who have undergone resection surgery.
This study aimed to explore how individuals recovered and adapted following surgical resection of their rectal cancer and the syndrome that occurs as a consequence of this operation. This syndrome, 'anterior resection syndrome', consists of frequency, urgency, fragmentation and incontinence of faeces, and is thought to occur in 90% of patients who have received this type of surgery. Little qualitative research has been undertaken in this area, and this study adds to current quality of life data and explores supportive care strategies that nurses could use to assist patients. This study uses a grounded theory approach and in-depth interviews to explore patient's experiences. Participants were recruited from a cancer unit within the UK. Participants were recruited from a total population sample of 27 patients who had received surgery from 2001 to 2002. Following eligibility criteria to exclude those who had disease progression, seven patients were identified 1 year following surgery. Interviews were used to explore the experience of the syndrome. Three categories were identified: adapting to the physical changes, psychological adaptation and stigma. A secondary theme, running throughout all these categories, was the feeling of confidence and normality. Although the physical changes were expected as a consequence of surgery, most participants described the difficulty in controlling and managing symptoms in their period of recovery. Developing a philosophical stance was important in managing the lack of control and returning to perceived normality, despite the social stigma of bowel problems. Information on a range of strategies to manage physical symptoms is helpful in providing supportive care. Understanding that patients often rely on inappropriate strategies for management and are reluctant to discuss symptoms is important. The specialist nurse has a role in providing supportive care in managing chronic symptoms following cancer treatment.


Prevalence of Mycoplasma genitalium among HIV-infected men in São Paulo city detected by realtime polymerase chain reaction.
Genital mycoplasmas are natural inhabitants of the male urethra and are potentially pathogenic species playing an aetiological role in both genital infections and male infertility. This study aims to determine the presence of Mycoplasma genitalium DNA in urine samples of HIV-1-infected men in São Paulo city. Realtime polymerase chain reaction (PCR) was performed using the primers My-ins and Mgso-2 and the Taqman probe Mgen-P1 as described previously. A total of 223 HIV-1-infected men were tested with a mean age of 44 years. Thirteen (5.8%) presented M. genitalium in urine and the co-infection was more common among homosexual men (76.9% versus 51.9%, P < 0.26). In conclusion, realtime PCR was a useful and rapid method for detecting M. genitalium DNA in urine samples. Further studies should be conducted to assess the clinical significance of these results on HIV transmission and its impact on HIV viral load.


Encoder response of isolated frog muscle spindle elicited by pseudorandom noise stimuli.
The present experiments investigated the signal transfer in the isolated frog muscle spindle by using pseudorandom noise (PRN) as the analytical probe. In order to guarantee that the random stimulus covered the entire dynamic range of the receptor, PRN stimuli of different intensities were applied around a constant mean length, or PRN stimuli of the same intensity were used while varying the mean length of the spindle. Subthreshold receptor potentials, local responses, and propagated action potentials were recorded simultaneously from the first Ranvier node of the afferent stem fiber, thus providing detailed insight into the spike-initiating process within a sensory receptor. Relevant features of the PRN stimulus were evaluated by a preresponse averaging technique. Up to tau = 2 ms before each action potential the encoder selected a small set of steeply rising stretch transients. A second component of the preresponse stimulus ensemble (tau = 2-5 ms) opposed the overall stretch bias. Since each steeply rising stretch transient evoked a steeply rising receptor potential that guaranteed the critical slope condition of the encoding site, this stimulus profile was most effective in initiating action potentials. The dynamic range of the muscle spindle receptor extended from resting length, L0, to about L0 + 100 microns. At the lower limit (L0) the encoding membrane was depolarized to its firing level and discharged action potentials spontaneously. When random stretches larger than the upper region of the dynamic range were applied, the spindle discharged at the maximum impulse rate and displayed no depolarization block or "overstretch" phenomenon. Random stretches applied within the dynamic range evoked regular discharge patterns that were firmly coupled to the PRN. The afferent discharge rate increased, and the precision of phase-locking improved when the intensity of the PRN stimulus was increased around a constant mean stretch; or the mean prestretch level was raised to higher values while the intensity of the PRN stimulus was kept constant. In the case when the PRN stimulus covered the entire dynamic range, the temporal pattern of the afferent discharge remained constant for at least 10 consecutive sequences of PRN. A spectral analysis of the discharge patterns averaged over several sequences of PRN was employed. At the same stimulus intensity the response spectra displayed low-pass filter characteristics with a 10-dB bandwidth of 300 Hz and a high-frequency slope of -12 dB/oct. Increasing the mean intensity of the PRN stimulus or raising the prestretch level increased the response power.(ABSTRACT TRUNCATED AT 400 WORDS)


Assessment of health-related quality of life in chronic dialysis patients with the COOP/WONCA charts.
The aim of the present work was to determine the health-related quality of life (HRQOL) of our patients on hemodialysis using the COOP/WONCA charts. A further aim was to explore its psychometric characteristics. The present study included all patients attending the hemodialysis unit of our hospital. The comparative study of the results was conducted with other population groups in which this questionnaire has been applied previously (primary-care patients, their accompanying persons, pregnant women, Alzheimer patient carers and drug addicts). The dimensional structure of the questionnaire was explored by factorial analysis of principal components, and internal consistency was evaluated with the Cronbach alpha factor. Concurrent validity was determined by comparative analysis of the results of the COOP/WONCA charts with those of another questionnaire, the 36-item short form of the Quality of Life Score (SF-36). To do so, 60 randomly chosen patients completed both questionnaires. 98.9% of patients completed the COOP/WONCA charts in their entirety. The mean scores of all the charts, with the exception of overall health, are in the range of what could be called 'favorable area of quality of life' (below 3). With respect to the rest of the groups, the dialysis patients had the best scores on the 'feelings' and 'social activities' charts and none of the worst ones. The joint factorial analysis revealed that the questionnaire has a 3-factor structure: factor 1 or daily functioning, factor 2 or quality of life and health, factor 3 or the psychosocial factor. The Cronbach alpha value for the 9 charts was 0.766. All the correlations between equivalent dimensions of questionnaires COOP/WONCA and SF-36 were statistically significant (p < 0.01). The convergent validity mean was 0.57 and the discriminant validity mean was 0.22, appreciably lower than convergent validity. This study shows that the process of psychological adaptation to problems deriving from dialysis is satisfactory. Moreover, the COOP/WONCA charts are a useful instrument for the determination of the HRQOL in hemodialysis patients without losing psychometric quality.


Depression, physical function, and risk of mortality: National Diet and Nutrition Survey in adults older than 65 years.
the authors used an objective assessment of physical function and a range of sociodemographic, dietary, and health behaviors to explore the possible factors that could explain the association between depression and mortality in community-dwelling elderly participants aged 65 years and older. prospective follow-up of the National Diet and Nutrition Survey in older adults. community sample. a total of 1,007 participants (522 men, 485 women; mean age: 76.4 ± 7.3 years). : Depression was assessed from the 15 item Geriatric Depression Scale (GDS) and physical function using hand grip strength. Participants were followed up for death over an average of 9.2 years. : At baseline, 20.9% of participants demonstrated depression (GDS-15 score ≥ 5). Depressed participants were at a higher relative risk of all cause mortality during follow-up (age- and sex-adjusted hazard ratio = 1.24, 95% confidence interval: 1.04-1.49). Other risk factors for depression also related to mortality included smoking, physical inactivity, and low grip strength. These factors collectively explained an estimated 54% of the association between depression and mortality. Low-grade inflammation and low plasma vitamin C were also independently associated with depression and mortality but did not explain any of the association between depression and mortality. late-life depression is associated with a higher risk of mortality. Physical inactivity and physical dysfunction might partly mediate this association, although further longitudinal studies are required to fully elucidate these mechanisms.


Expression of heat shock protein 70 in the cochlea in experimental autoimmune inner ear disease.
To explore whether the immune response of the inner ear could induce heat shock protein 70 (hsp70) in the guinea pig cochlea, we established a model of autoimmune inner ear disease (AIED) by systemically immunizing guinea pigs with homologous crude inner ear antigen (CIEAg). The immunized cochleas and normal control cochleas were examined for the expression of hsp70 by immunohistochemical analysis and in situ hybridization. It was found that 10 of 28 ears showed significant increases in hearing thresholds after the animals had been sensitized with CIEAg, and 67.9% of the ears from the immunized animals had modiolar vasculitis. The hsp70-like proteins were basically expressed in the normal cochleas, but dramatically increased expressions of hsp70 (perhaps also including hsp70-like molecules) and its messenger RNA were observed in the cochleas of the AIED models. The results suggest that the immune response of the inner ear induced the expression of hsp70 in the guinea pig cochleas.


Facial Skin Revitalization with Cohesive Polydensified Matrix-HA20G: Results from a Randomized Multicenter Clinical Study.
There is a growing interest in the application of hyaluronic acid (HA) derivatives in skin quality improvement. The aim of this study was to confirm safety and effectiveness of cohesive polydensified matrix-hyaluronic acid + glycerol (CPM-HA20G; Belotero Revive) in revitalization of early-onset photodamaged facial skin. A total of 159 subjects with early signs of facial photodamaged skin were randomized in a 2:1 ratio to multiple- or single-dose treatment with CPMHA20G. Effectiveness assessments included biophysical measurements of skin hydration; elasticity, firmness, and roughness; investigator- and subject-assessed Global Aesthetic Improvement Scales; and FACE-Q Skin Changes and Treatment Satisfaction questionnaires. In both treatment groups, skin hydration improved from baseline to all follow-up visits in subjects with dry or very dry skin. This improvement was significant at week 16 after initial treatment in the multiple-dose group (P = 0.0013). Investigator- and subject-reported outcomes showed that the majority of subjects across all skin hydration types benefited from treatment, with higher satisfaction rates observed in the multiple-dose group. According to investigator-assessed Global Aesthetic Improvement Scale, 90.7% of subjects at week 12 in the multiple-dose and 74.6% of subjects at week 4 in the single-dose group were rated as at least "improved." All related treatment-emergent adverse events were transient, expected injection-site reactions of mild to moderate intensity. Effectiveness of CPM-HA20G for skin hydration in subjects with dry or very dry skin was demonstrated up to 9 months after last injection. Overall, CPM-HA20G demonstrated effective and safe use in facial skin revitalization among subjects with early-onset photodamaged skin.


Dynamic contrast-enhanced MR imaging findings of bone metastasis in patients with prostate cancer.
To evaluate the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings of bone metastasis in prostate cancer patients. Sixteen men with a diagnosis of metastatic prostate cancer to bones were examined with DCE-MRI at 1.5 Tesla. The mean contrast agent concentration vs time curves for bone metastasis and normal bone were calculated and K(trans) and ve values were estimated and compared. An early significant enhancement (wash-out: n = 6, plateau: n = 8 and persistent: n = 2) was detected in all bone metastases (n = 16). Bone metastasis from prostate cancer showed significant enhancement and high K(trans) and ve values compared to normal bone which does not enhance in the elderly population. The mean K(trans) was 0.101/min and 0.0051/min (P < 0.001), the mean ve was 0.141 and 0.0038 (P < 0.001), for bone metastases and normal bone, respectively. DCE-MRI and its quantitative perfusion parameters may have a role in improving the detection of skeletal metastasis in prostate cancer patients.


Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse and human tissues.
Protein histidine phosphorylation accounts for about 6% of the total protein phosphorylation in eukaryotic cells; still details concerning histidine phosphorylation and dephosphorylation are limited. A mammalian 14-kDa phosphohistidine phosphatase, also denominated PHPT1, was found 6 years ago that provided a new tool in the study of phosphohistidine phosphorylation. The localization of PHPT1 mRNA by Northern blot analysis revealed high expression in heart and skeletal muscle. The main object of the present study was to determine the PHPT1 expression on protein level in mouse tissues in order to get further information on the physiological role of the enzyme. Tissue samples from adult mice and 14.5-day-old mouse embryos were processed for immunostaining using a PHPT1-specific polyclonal antibody. The same antibody was also provided to the Swedish human protein atlas project (HPR) (http://www.proteinatlas.org/index.php). The results from both studies were essentially consistent with the previously reported expression of mRNA of a few human tissues. In addition, several other tissues, including testis, displayed a high protein expression. A salient result of the present investigation was the ubiquitous expression of the PHPT1 protein and its high expression in continuously dividing epithelial cells.


[Multivariate analysis of mortality in combined trauma of the abdomen].
The methods of multivariate analysis of lethality in combined trauma of the abdomen with the use of standardized measurement systems (STS) severity of the injury, including anatomical and functional assessment scales for prognostic survival probability victims in representative groups (by gender and age, mechanism and type of injury, clinical and nosological characteristics of damage).


Efficacy of external cold and a vibrating device in reducing pain and anxiety during local anaesthesia.
To evaluate and compare the efficacy of external cold and a vibrating device in reducing the pain and anxiety amidst children receiving maxillary infiltration anaesthesia over conventional methods. A sum of thirty subjects aged between 5 and 10 years who had undergone dental procedures requiring maxillary infiltration were enrolled in the current split-mouth randomised control study. The control intervention constitutes infiltration of 1.8 mL of 2% lignocaine in addition to 1:100,000 adrenaline (Lox, Neon Laboratories Mumbai, India) whereas, the experimental group used external cold and a vibrating device (Buzzy®, MMJ Labs, Atlanta, GA, USA) in annexation to the control protocol. Simultaneous to LA administration, pulse rate was employed as an objective measure and the subjective measure was recorded using RMS Pictorial Scale (RMS-PS) for the child's discomfort. To document the child's pain as anticipated by the dentist the revised face, limbs, arms, cry and consolability (FLACC-R) scale was employed. Lower pain sensation and anxiety was recorded in the experimental group using Buzzy when compared to control. External cold in adjacent with vibrations might be efficient in lowering pain as well as anxiety in children experiencing infiltration dental anaesthesia though further research work is requisite with a larger sample size.


Amino Acids Translocated from Turgid and Water-stressed Barley Leaves: I. Phloem Exudation Studies.
The phloem exudation technique of King and Zeevaart (Plant Physiol 1974 53: 96-103) was modified for use with barley plants, to investigate the effect of water stress upon amino acid translocation at seedling and grainfilled stages.Seedling leaves and flag leaves from unstressed and moderately water-stressed plants exuded (14)CO(2) assimilates, sugars, and amino acids when their sheaths were cut and immersed in a 5 millimolar solution of Na(2)EDTA (pH 7.0). By including PEG 6000 (-10 bars) in the Na(2)EDTA solution, leaves severed from moderately water-stressed plants could be maintained in a wilted state. Such leaves produced about as much exudate as turgid leaves of unstressed plants.The following observations suggest a phloem origin for most of the exudate. Exudation was markedly stimulated by light and by CO(2) enrichment. The release of NO(3) (-) declined after cutting, and did not parallel exudation of (14)CO(2) assimilates, sugar, and amino acids. The relative quantities and specific radioactivities of sugars and amino acids in the exudate differed from those of sugars and amino acids extracted from sheath tissue.Major amino acids in exudate from unstressed seedling and flag leaves were glutamine, glutamate, serine, alanine, and aspartate; proline was virtually absent. Exudate from water-stressed leaves contained relatively more serine, and also some proline and gamma-aminobutyric acid.


Immunodeficiency of aging: restorative effects of phorbol ester combined with calcium ionophore.
Current models for lectin-induced T cell proliferation suggest that activation of protein kinase C (PK-C) and elevation of cytoplasmic Ca2+ may both play important roles in the earliest phases of signal transduction. To learn more about the relative inability of T cells from old mice to proliferate in response to mitogenic stimuli, we attempted to stimulate T cells by the synergistic effects of a PK-C activator, phorbol myristate acetate (PMA), and the calcium ionophore ionomycin. T cells from young mice respond as well to optimal combinations of these agents as they do to the strong polyclonal activator Con A, but T cells from old mice respond much better to PMA plus ionomycin than they do to Con A. This result suggests that an inability to transduce the signal supplied by extracellular ligands into the intracellular signals represented by Ca2+ and PK-C activators may underlie the age-associated loss of T cell reactivity. We also found evidence for a second defect in old T cells related to their response to elevated intracellular Ca2+: old T cells, compared with young, required higher levels of ionomycin for maximal proliferation.


The neonatal Fc receptor is not required for mucosal infection by mouse mammary tumor virus.
The milk-borne mouse mammary tumor virus (MMTV) infects newborn mice via the intestine. Infection is initially restricted to Peyer's patches and later spreads to the epithelial cells of the mammary gland. The receptor that mediates uptake and transport of MMTV across the intestinal barrier has not yet been identified, The neonatal Fc receptor (nFcR), which is expressed by enterocytes during the first two weeks of life, is downregulated at weaning, and its disappearance correlates with the onset of intestinal resistance to MMTV. To test whether the nFcR mediates transport and allows infection, we foster nursed on infected MMTV mothers beta2 microglobulin-deficient (beta2m-deficient) newborn mice that are unable to express the nFcR at the surface of their enterocytes. Exposure of beta2m-deficient mice to milk-borne virus resulted in the deletion of peripheral blood T cells reactive to the superantigen encoded by MMTV. Since beta2m-deficient newborn mice are susceptible to MMTV infection despite the lack of the nFcR, we conclude that the nFcR is not required for MMTV transport.


Posttraumatic stress disorder is associated with emotional eating.
The present study investigated the relationship between posttraumatic stress disorder (PTSD) and emotional eating in a sample of medically healthy and medication-free adults. Participants with PTSD (n = 44) and control participants free of lifetime psychiatric history (n = 49) completed a measure of emotional eating. Emotional eating is the tendency to eat or overeat in response to negative emotions. PTSD participants exhibited greater emotional eating than control participants (η(2) = .20) and emotional eating increased with higher PTSD symptom severity (R(2) = .11). Results supported the stress-eating-obesity model whereby emotional eating is a maladaptive response to stressors. Over time, this could lead to weight gain, particularly abdominal stores, and contribute to higher risk for comorbid medical disorders. Findings suggest the importance of future longitudinal research to understand whether emotional eating contributes to the high rates of obesity, diabetes, and heart disease in PTSD.


Inhibition of ethylene biosynthesis in carnation petals by cytokinin.
Pretreatment of detached carnation petals (Dianthus caryophyllus cv White Sim) for 24 hours with 0.1 millimolar of the cytokinins n(6)-benzyl-adenine (BA), kinetin, and zeatin blocked the conversion of externally supplied 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene and delayed petal senescence by 8 days. The normal enhanced wilting and increase in endogenous levels of ACC and ethylene production following exposure of petals to ethylene (16 mul/l for 10 hours), were not observed in BA-pretreated petals. In carnation foliage leaves pretreated with 0.1 mm BA, a reduction rather than inhibition of the conversion of exogenous ACC to ethylene was observed. This indicates that foliage leaves respond to cytokinins in a different way than petals. A constant 24-hour treatment with BA (0.1 mm) was not able to reduce ethylene production of senescing carnation petals, while 2 mm aminoxyacetic acid, a known inhibitor of ACC synthesis, or 10 mm propyl gallate, a free radical scavenger, decreased ethylene production significantly.


Who watches the watchmen? An appraisal of benchmarks for multiple sequence alignment.
Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies-based on simulation, consistency, protein structure, and phylogeny-and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application-with a keen awareness of the assumptions underlying each benchmarking strategy.