MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy.
Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group). Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene), and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy.


p53siRNA therapy reduces cell proliferation, migration and induces apoptosis in triple negative breast cancer cells.
p53 protein is probably the best known tumor suppressor. Earlier reports proved that human breast cancer cells expressing mutant p53 displayed resistance to apoptosis. This study is intended to investigate, the potential applications of RNA interference (RNAi) to block p53 expression, as well as its subsequent effect on cell growth, apoptosis and migration on a triple negative human breast cancer cell line (Hs578T). p53siRNA significantly reduced cell index (CI) compared to the control and we observed an inhibition of cellular migration in the interval of time between 0 and 30 h, as shown in the data obtained by dynamic evaluation using the xCELLigence System. Also, by using PCR-array technology, a panel of 84 key genes involved in apoptosis was investigated. Our studies indicate that the knockdown of p53 expression by siRNA modulates several genes involved in cell death pathways and apoptosis, showing statistically significant gene expression differences for 22 genes, from which 18 were upregulated and 4 were downregulated. The present research also emphasizes the important role of BCL-2 pro-apoptotic family of genes (Bim, Bak, and Bax) in activating apoptosis and reducing cell proliferation by p53siRNA treatment. Death receptors cooperate with BCL-2 pro-apoptotic genes in reducing cell proliferation. The limited success may be due to the activation of the antiapoptotic gene Mcl-1, and it may be associated with the resistance of triple negative breast cancer cells to cancer treatment. Thus, targeting p53siRNA pathways using siRNA may serve as a promising therapeutic strategy for the treatment of breast cancers.


Light-hearted negative terminology used in computer education and related skill of noncomputer users.
Theory suggests that light-hearted but negative phrases and terminology used in computer literature and course titles may have a negative effect on noncomputer users. This study tested the effect of providing the suggestion of a negative dimension of computer ability labelled with a category of "Computer Dummy" a also the relation between computer ability and computer anxiety. The study incorporated 37 noncomputer users, 17 men and 20 women whose mean age was 52.1 yr. Scores on a self-report questionnaire indicated that 23 of the nonusers responded on the negative dimension of computer ability and included themselves in the category of "Computer Dummy." Also, belief about ability and belief about computer training were associated with computer anxiety for noncomputer users.


Ingestion of bar soap may produce serious injury: clinical effects and risk factors.
Most household and body soaps have an alkaline pH (9-12). In addition to their foaming effect, they irritate the skin. This study aims to review soap exposure reported to the Angers Poison Control Centre. A retrospective study of accidental or deliberate oral exposure to solid soaps reported to the Angers Poison Control Centre between 1 January 2000 and 1 April 2015. Poisoning severity was reassessed for each case according to the Poisoning Severity Score (PSS). 553 cases of exposure were recorded. In more than 40% of cases (n = 226), exposure occurred in community settings (retirement homes, nursing homes). Patients had a history of dementia in 220 cases (40%). The most common symptoms were labial oedema (28%, n = 153), oropharyngeal irritation (10%, n = 56), salivation (10%, n = 53), vomiting (9%, n = 48) and cough (8%, n = 45). Among symptomatic patients (n = 276), one patient died from aspiration pneumonia and one patient died from a cardiogenic shock following oropharyngeal oedema, vomiting, cough and bronchial obstruction. Patients with dementia were more often symptomatic (75% vs 34%, p < .001) and more frequently hospitalised (22% vs 0.8%, p < .001). They experienced more moderate to severe symptoms (8% vs 0%, p < .001). Mildly severe (PSS2, n = 14), highly severe (PSS3, n = 1) and fatal (PSS4, n = 2) poisoning were observed only in patients with dementia. Ingestion of soap bars is potentially serious, especially in patients with dementia. This type of soap should not be available to them in community settings and close monitoring should be considered in the event of oral exposure.


Importance of NAB2-STAT6 Fusion in the Diagnosis of Pancreatic Solitary Fibrous Tumor with Hamartoma-Like Features: A Case Report and Review of the Literature.
We report a case of pancreatic hamartoma-like solitary fibrous tumor which was differentiated from pancreatic hamartoma with the detection of NAB2-STAT6 fusion, a specific mutation for solitary fibrous tumors. A pancreatic well-demarcated solid nodule, 21 × 17 mm, of 82-year-old man was surgically enucleated. Microscopic findings were close to a pancreatic hamartoma that consisted of sparsely distributed pancreatic ducts and acini in heavily collagenized fibrous stroma. Neither islet nor peripheral nerve existed in the tumor. The fibroblastic cells in the stroma were immune-positive for CD34, CD99, and bcl-2. But these expressions were not decisive in the differentiation between solitary fibrous tumor and pancreatic hamartoma, because CD34 was positive for both tumors, and CD99 and bcl-2 expressions were not elucidated in the previous cases of pancreatic hamartomas. Thus, we evaluated NAB2-STAT6 fusion. The fibroblastic cells were positive for STAT6 and sequencing analysis revealed the gene fusion between NAB2 exon 4 and STAT6 exon 2, with which the final diagnos is of solitary fibrous tumor was achieved. In conclusion, detection of NAB2-STAT6 fusion has a great diagnostic value for pancreatic solitary fibrous tumors with hamartoma-like features.


Amylase in fallopian tube and serous ovarian neoplasms: immunohistochemical localization.
We studied the cellular localization of amylase in normal Fallopian tubes and serous ovarian neoplasms using an indirect immunoperoxidase technique. The primary antiserum was against human pancreatic amylase, and was found to inhibit ovarian tumor amylase as well. Amylase was present in normal endosalpingeal epithelium and in the epithelial cells of benign, borderline, and malignant serous ovarian tumors. A mucinous cystadenoma was also studied and contained no amylase. This localization suggests that amylase production by serous ovarian neoplasms reflects the endosalpingeal differentiation of these tumors. Antibody to amylase may be potentially useful in distinguishing serous ovarian tumors from other forms of ovarian neoplasia.


Existence of a neuropathic pain component in patients with osteoarthritis of the knee.
Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman's correlation coefficient by rank test. Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.


Substance abuse among general psychiatric patients: place of presentation, diagnosis, and treatment.
This paper reviews the literature on patients presenting for general psychiatric treatment who are also substance abusers. Place of presentation, diagnosis, and treatment are considered. A considerable portion of patients seen in emergency rooms, as much as half in some settings, are substance abusers, and over a third of general psychiatry admissions have been found to have their presenting problems materially influenced or precipitated by substance abuse. Substance abuse is also frequently found among psychiatric inpatients. Diagnostically, the differentiation of general psychiatric and addictive syndromes can be difficult: primary and secondary affective disorder from consequences of long-term substance abuse; and self-medication patterns from primary general psychiatric syndromes. Treatment studies are often focused on concomitant psychotherapeutic management for patient being treated for addiction. Often, emphasis is placed on pharmacotherapy for enhancing outcome in the dually diagnosed. Qualitatively, new options tailored to this population still remain to be studied, however, as do the changes necessary in the treatment system to assure proper long-term management.


Synthesis and Evaluation of New Quinoxaline Derivatives of Dehydroabietic Acid as Potential Antitumor Agents.
A series of new quinoxaline derivatives of dehydroabietic acid (DAA) were designed and synthesized as potential antitumor agents. Their structures were characterized by IR, ¹H-NMR, 13C-NMR, and MS spectra and elemental analyses. All the new compounds were screened for their in vitro antiproliferative activities against three human cancer cell lines (MCF-7, SMMC-7721 and HeLa) and noncancerous human hepatocyte cells (LO2). A cytotoxic assay manifested that compound 4b showed the most potent cytotoxic activity against the three cancer cell lines, with IC50 values of 1.78 ± 0.36, 0.72 ± 0.09 and 1.08 ± 0.12 μM, respectively, and a substantially lower cytotoxicity to LO2 cells (IC50: 11.09 ± 0.57 μM). Moreover, the cell cycle analysis suggested that compound 4b caused cell cycle arrest of SMMC-7721 cells at the G0/G1 phase. In a Hoechst 33258 staining assay, compound 4b caused considerable morphological changes of the nuclei of SMMC-7721 cells, correlated with cell apoptosis. In addition, an Annexin V-FITC/PI dual staining assay confirmed that compound 4b could induce the apoptosis of SMMC-7721 cells in a dose-dependent manner.


Generalized transduction between Salmonella typhi and Salmonella typhimurium by phage j2 and characterization of the j2 plasmid in Escherichia coli.
Phage j2, a P1-like phage in Salmonella typhi, was heteroimmune to phage P1 and existed in the lysogenic state as a plasmid of molecular size 58.6 MDal. The phage j2 plasmid was incompatible with the P1 plasmid (IncY group). A j2-sensitive mutant of Salmonella typhimurium LT2 was isolated by transduction of j2Ap phage into LT2 followed by curing of the prophage. The mutant was used to demonstrate transduction between S. typhi and S. typhimurium by phage j2.


Potential signature of a Kosterlitz-Thouless transition in BaNi2V2O8.
ESR measurements are reported for the quasi-two-dimensional honeycomb antiferromagnet BaNi2V2O8. Planar anisotropic properties are confirmed by angular dependent investigations of resonance field and linewidth. The divergence of the temperature-dependent linewidth on approaching T(N) from above is described in terms of the Kosterlitz-Thouless transition, the critical behavior close to long-range magnetic order, and the 2D Heisenberg antiferromagnet. We provide arguments that the Kosterlitz-Thouless scenario is compatible with the observed critical exponent and suggest BaNi2V2O8 is a weakly anisotropic 2D Heisenberg antiferromagnet.


Dysregulation of apoptosis and a novel mechanism of defective apoptotic signal transduction in human B-cell neoplasms.
Apoptotic cell death is essential for normal B-cell development and for shaping the B-cell repertoire. Dysregulation of the Bcl-2 related proteins and alterations of the p53/p14ARF pathway are implicated in the pathogenesis and treatment resistance in human B-cell malignancies. We found a novel mechanism of dysregulated apoptosis in human B lymphoma Raji cells that differs from that of altered Bcl-2 and p53 functions. This cell line was resistant to nuclear apoptosis induced by various stimuli, and neither mitochondrial activation nor activation of caspase-3 led to DNA fragmentation. DNA in purified Raji nuclei was degraded in the presence of lysates from the apoptosis-sensitive cell line HL-60, whereas Raji cell lysates did not induce DNA fragmentation in HL-60 nuclei. Cleavage of ICAD/DFF-45 was normal. These results indicate that the apoptosis signal transduction pathway is defective downstream of caspase-3 in Raji cell cytoplasm. Therefore, exploring the molecular mechanism in this system should provide insight into apoptosis resistance in human B-cell malignancies.


Photoselective vaporization of the prostate in men taking clopidogrel.
To evaluate the peri-operative morbidity of men taking clopidogrel who underwent photoselective vaporisation of the prostate (PVP). A prospective database was collected. Between March 2005 and July 2010, 480 men underwent PVP. Of these, 18 men underwent PVP treatment while on clopidogrel. The surgery was carried out with either an 80W KTP laser or a 120W lithium triborate laser. In the peri-operative period there were no complications related to PVP. There were no urinary tract infections, nor did any patient require bladder re-catheterisation. No cardiovascular events were reported within 3 months of the procedure. At 3 months post operatively, the International Prostate Symptom Score±standard deviation had improved from was 17.5±10.6 to 9.2±6.1 P<0.05. While the Quality of Life±standard deviation improved from 4.7±1.2 to 2.2±1.5 P<0.01. The maximum flow rate (Qmax), and post void residual volume (PVR) improved from 6.2±3.0 mL/s to 19.7±9.1 mL/s (P<0.01), and 140±102 mL to 59±77 mL (P<0.05), respectively. PVP is a safe and efficacious in the treatment of high risk patients with bladder outlet obstruction. Further, the ability to continue therapeutic anticoagulation and anti-platelet agents, is a significant advantage over Holmium enucleation of the prostate and conventional transurethral resection of the prostate. Larger studies with greater numbers of patients are required prior to PVP becoming the gold standard for high-risk patients with bladder outlet obstruction.


Crosstalk of PmCBFs and PmDAMs Based on the Changes of Phytohormones under Seasonal Cold Stress in the Stem of Prunus mume.
Plants facing the seasonal variations always need a growth restraining mechanism when temperatures turn down. C-repeat binding factor (CBF) genes work essentially in the cold perception. Despite lots of researches on CBFs, the multiple crosstalk is still interesting on their interaction with hormones and dormancy-associated MADS (DAM) genes in the growth and dormancy control. Therefore, this study highlights roles of PmCBFs in cold-induced dormancy from different orgens. And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this process, jointly regulated by six PmCBFs and PmDAM4-6. Meantime, GA3 and ABA showed negative and positive correlation with PmCBFs expression levels, respectively. We also find a high correlation between IAA and PmDAM1-3. Finally, we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1. These results can disclose another view of molecular mechanism in plant growth between cold-response pathway and dormancy regulation together with genes and hormones.


The Study of Tacrolimus-Loaded Polyion Complex Micelles for Oral Delivery.
In the present study, polyion complex micelles based on pluronic F127-chitosan (F127-CS) and sodium deoxycholate (NaDC) were prepared to improve the oral absorption of tacrolimus (FK506) by increasing its aqueous solubility and enhancing its absorption in the gastrointestinal (GI) tract. FK506-loaded F127-CS/NaDC micelles were prepared by the thin film hydration method and had a high drug-loading capacity (8.93±1.47%) and a small particle size (55.77±2.23 nm). The low critical micelle concentration (2.65 × 10-3 mol/L) and the stability test results indicated that F127-CS/NaDC micelles have an enhanced stability against the dilution of GI fluid or blood. Tests of cell uptake showed that F127-CS/NaDC micelles exerted a comparable P-glycoprotein inhibition to verapamil. Compared with FK506 solution, the time to peak (tmax) of FK506 in F127-CS/NaDC micelles decreased from 3 to 1 h and the half-life was prolonged from 16.09 h to 18.00 h. Moreover, drug-time area under the curve was increased by 39.3%, from 533.79 to 742.11 ng/mL·h, which indicated enhanced oral absorption of FK506 in FK506-loaded F127-CS/NaDC micelles. Furthermore, the immunosuppressive effect of FK506-loaded F127-CS/NaDC micelles in a rat liver transplantation model was better than that of FK506 solution. All these results showed that FK506-loaded F127-CS/NaDC micelles are a promising approach for oral delivery of FK506.


Future self-continuity and depression among college students: The role of presence of meaning and perceived social support.
Future self-continuity has been shown to have a protective effect against depression. This study aims to investigate the longitudinal relationship between future self-continuity and depression among college students, and to explore the mediating role of the presence of meaning and the moderating role of perceived social support. We conducted two studies in China in 2022 and 2023. Study 1 was a longitudinal cross-lagged study that examined the relationship between future self-continuity and depression among 173 participants (49.13% females, Mage = 19.39, SD = 1.63). Study 2 was a cross-sectional study that explored the mediating role of the presence of meaning and the moderating role of perceived social support among 426 participants (48.59% females, Mage = 19.30, SD = 1.60). Study 1 showed that future self-continuity (T1) could significantly predict depression (T2), but depression (T1) could not predict future self-continuity (T2). Study 2 showed that after controlling for gender, the presence of meaning mediated the relationship between future self-continuity and depression, whereas perceived social support moderated the first half of the mediated model's pathway and the direct pathway. These findings suggest that enhancing the future self-continuity of college students and increasing the level of presence of meaning are effective measures for alleviating depression. Meanwhile, educators and families are called upon to provide more social support to college students.


Insights from genomes of representatives of the human gut commensal Bifidobacterium bifidum.
Bifidobacteria are bacterial gut commensals of mammals, birds and social insects that are perceived to influence the metabolism/physiology of their host. In this context, members of the Bifidobacterium bifidum species are believed to significantly contribute to the overall microbiota of the human gut at infant stage. However, the molecular reasons for their adaptation to this environment are poorly understood. In this study, we analysed the pan-genome of B. bifidum species by decoding genomes of 15 B. bifidum strains, which highlighted the existence of a conserved gene uniquely present in this bifidobacterial taxon, underscoring a nutrient acquisition strategy that targets host-derived glycans, such as those present in mucin. Growth experiments and corresponding transcriptomic analyses confirmed the in silico data and supported these intriguing and unique host glycan-specific saccharolytic features. The ubiquity of the genetic features of B. bifidum for the breakdown of host glycans was confirmed by interrogating metagenomic datasets, thereby supporting the notion that metabolic access to host-derived glycans is a potent evolutionary force that has shaped B. bifidum genomes and consequently the ecology of the infant intestinal microbiota.


[Glucagon-like peptide 1 analogues in the treatment of type 2 diabetes mellitus].
A Cochrane analysis concluded that glucagon-like peptide-1 (GLP-1) analogues were effective for the improvement of glycaemic control in patients with type 2 diabetes. What is the significance for the treatment of Danish patients with type 2 diabetes? In Denmark, two drugs exist, exenatid and liraglutid, and they both reduce HbA1c with approx. 1%. Compared with sulfonylurea and insulin, the advantage of GLP-1 analogues is not only that they rarely induce hypoglycaemia, but also that body weight is reduced. On the other hand, no long-term results exist with regard to impact on the cardiovascular system, and no complete overview of possible side effects has been presented either.


Wilson's disease.
Wilson's disease is an autosomal, recessive-inherited disorder of impaired biliary copper excretion that results in the accumulation of copper in various organs including the liver, the cornea and the brain. The Wilson's disease gene on chromosome 13 codes for a copper transporting P-type ATPase-ATP7B. More than 60 mutations of this gene have been described. The diagnosis of Wilson's disease is based on clinical findings and laboratory abnormalities and can be made if two of the following symptoms are present: Kayser-Fleischer rings; topical neurologic symptoms; and low serum ceruloplasmin levels. In less typical cases diagnosis requires various other tests of copper metabolism. Effective medical treatment with copper chelators (D-penicillamine, trientine) or zinc results in symptomatic improvement and normal life expectancy. Orthotopic liver transplantation is indicated in advanced cases with hepatic decompensation or in patients with fulminant Wilson's disease.


Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function.
IDIOTYPY HAS BEEN STUDIED IN ANTIBODIES AGAINST A PROTEIN ANTIGEN: hen ovalbumin. Various fractions of antisera to hen ovalbumin have been compared from the standpoint of the idiotypic specificities found on the immunoglobulins that they contain. Idiotypic specificities were found to be common to (a) antibodies that were not eluted from the same immunoadsorbent by the same MgCl(2) concentration, but by four different concentrations. (b) Antibodies that were precipitable only by hen ovalbumin, only by hen and turkey ovalbumin, or also by duck ovalbumin. (c) Antibodies that were precipitated or not precipitated by the homologous ovalbumin, and proteins apparently devoid of antiovalbumin antibody function. These findings are discussed from the standpoint of (i) the differences in function between the various fractions with the same idiotypic specificities, and (ii) what may be common in the cellular origin of immunoglobulins with a common idiotypic specificity, and what may be different in immunoglobulins with different antibody functions or without antibody function. The same idiotypic specificities have been found in certain IgG and IgM antiovalbumin antibodies.


Central nervous system recurrence ten years after remission of acute lymphoblastic leukemia.
Therapy with vincristine and prednisone achieved a complete remission in a 10-year-old Caucasian girl with acute lymphoblastic leukemia. Maintenance therapy with 6-mercaptopurine was then administered for seven years, but prophylactic intrathecal chemotherapy and central nervous system (CNS) radiation were never given the patient. Ten years from the time of diagnosis, she presented with signs of increased intracranial pressure and a diagnosis of CNS leukemia was confirmed. At this time, however, no leukemia was detected on examination of her blood and bone marrow. She was successfully treated with intrathecal methotrexate and radiation therapy. After a careful search of the literature it has been concluded that this is the first reported case of such a long remission of acute lymphoblastic leukemia with subsequent relapse.


Immunohistochemical examination of olfactory mucosa in patients with olfactory disturbance.
The olfactory mucosa was examined by immunohistochemistry in patients with olfactory disturbance: anosmia due to choanal atresia and chronic sinusitis, early-stage common cold, late-stage common cold, and head trauma. The results indicate that the olfactory mucosa of patients with olfactory disturbance shows specific kinds of immunoreactive patterns and that immunohistochemistry is useful for examining the degree of degeneration of pathologic human olfactory mucosa and for clarification of prognosis.


Time-Dependent Colorful Circularly Polarized Organic Ultralong Room Temperature Phosphorescence from a Single-Component Chiral Molecule.
Colorful circularly polarized organic ultralong room temperature phosphorescence (CP-OURTP) materials have attracted much attention due to their superior optoelectronic properties for various applications. However, the development of colorful CP-OURTP materials in a single-component molecular system is currently facing great challenges. Herein, a feasible strategy is proposed to develop colorful CP-OURTP material from a single-component chiral molecule by introducing a chiral unit into the phosphorescence chromophore. A dual CP-OURTP band originated from inherent triplet excitons emission showing a lifetime of 946.44 ms and triplet-triplet annihilation induced delayed emission with a short lifetime of 209.91 ms as well as maximum asymmetry factors of ≈10-3 are realized. Owing to the changed OURTP intensity ratios between inherent CP-OURTP and delayed emission at different delayed times, time-dependent colorful CP-OURTP turned from yellow to green is obtained. This study provides a potential platform to prepare circularly polarized material systems showing colorful luminescent properties.


Skeletal muscle myosin monomer in equilibrium with filaments forms a folded conformation.
Rabbit skeletal myosin forms stable filaments under physiological conditions, and only a small amount stays as a monomer in equilibrium with filaments. The myosin monomers were observed in two conformational states, as extended and folded forms upon electron microscopy and gel filtration high performance liquid chromatography. The fraction of monomers in the folded conformation increased with a decrease in the concentration of NaCl below 0.2 M, and the conformational state was affected neither by the presence of ATP nor by the phosphorylation of regulatory light chain. In most of the folded monomers, the tail bent back toward the heads at one region, 45 nm apart from the head-tail junction, and the remaining tail portion containing the C-terminal tip appeared to interact with the head-tail junction. Only a small percentage of the folded monomers was in a more compact conformation close to the 10 S conformation of vertebrate smooth muscle and non-muscle myosins. The folded monomers, however, may not trap the products of ATP hydrolysis as assessed by single turnover experiments. The percentage of monomers in the 10 S-like conformation was increased by the exchange of a regulatory light chain with the smooth muscle light chain, indicating the participation of head-tail junction, including the regulatory light chain in the formation of folded conformation. The folded conformation may be common to various myosin IIs, suggestive of common roles for the folded monomers.


Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine.
Our objective was to elucidate the mechanism of pharmacokinetic interaction between lidocaine and mexiletine, because an unexpected increase in plasma lidocaine concentration accompanied by severe side effects was observed when mexiletine was administered to a patient with dilated cardiomyopathy. Plasma concentrations of lidocaine, its major metabolites, and mexiletine were measured in a patient with dilated cardiomyopathy. The lidocaine-mexiletine interaction was evaluated by examination of the effects of mexiletine on plasma concentration and the tissue distribution of lidocaine in rabbits in vivo, as well as on the in vitro lidocaine binding to phosphatidylserine, a binding constituent for weakly basic drugs. Plasma lidocaine concentrations increased significantly when the oral dose of mexiletine was increased. This pharmacokinetic interaction was not attributable to a metabolic interaction as evaluated by plasma lidocaine metabolites concentrations. In rabbits, mexiletine seemed to decrease the total plasma clearance of lidocaine, resulting in increased plasma lidocaine concentrations. Mexiletine significantly reduced the tissue distribution of lidocaine to the kidneys and lungs. A strong displacing effect of mexiletine on the binding of lidocaine to phosphatidylserine was observed in vitro. A drug interaction derived from the displacement of lidocaine from tissue binding sites by mexiletine that resulted in the increased plasma lidocaine concentrations was shown. This observation had implications for loading doses and acute effects of lidocaine in the concurrent therapy of lidocaine and mexiletine.


Ten years of the Peruvian Society of the History of Psychology.
This article briefly reviews the development of the history of psychology as a specialized discipline in Peru, in order to learn about the emergence, organization and productivity of the Peruvian Society of the History of Psychology (SPHP), which was founded in 2012. Previously, by way of introduction, the advances in the institutionalization of the history of psychology in Latin America and the development of the historiography of psychology in Peru are described. Seminars, journals, and books edited by the SPHP are discussed, as well as new projects and the challenges that must be faced for a greater dissemination of the history of psychology in Peru. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Arginase-1 and P-glycoprotein are downregulated in canine hepatocellular carcinoma.
Hepatocellular carcinoma is the most common primary hepatic malignancy in humans and dogs. Several differentially expressed molecules have been studied and reported in human hepatocellular carcinoma and non-neoplastic liver lesions. However, studies on the features of canine hepatocellular carcinoma are limited, especially related to the differential characteristics of neoplastic and non-neoplastic lesions. The study's objective was 1) to examine and evaluate the expression of arginase-1, P-glycoprotein, and cytokeratin 19 in canine liver tissues and 2) to investigate the differential features of hepatocellular carcinomas, liver tissue with non-neoplastic lesions, and paracancerous liver tissues in dogs. The expression levels of three markers underwent immunohistochemical analysis in 40 non-neoplastic liver tissues, 32 hepatocellular carcinoma tissues, and 11 paracancerous liver tissues. Scoring of each marker was performed semi-quantitatively. Arginase-1 and P-glycoprotein were significantly downregulated in hepatocellular carcinoma, compared with hepatic tissues with non-neoplastic diseases (p < 0.001). Expression levels of arginase-1 and P-glycoprotein were also significantly lower in hepatocellular carcinoma than in paracancerous liver tissues (arginase-1, p = 0.0195; P-glycoprotein, p = 0.047). Few cytokeratin 19-positive hepatocytes were detected and only in one hepatocellular carcinoma and one cirrhotic liver sample. The results of this study suggest that downregulation of arginase-1 and P-glycoprotein is a feature of canine hepatocellular carcinoma; thus, those markers are potential candidates for use in differentiating hepatocellular carcinomas from non-neoplastic liver lesions in dogs.


[Let us Ask the Consumer].
Our study explores possibilities to do quality management by routinely assessing patient satisfaction in hospital. Which aspects of treatment and setting are vital for patients and how do they evaluate them? Do hospital departments differ concerning profiles of patient satisfaction? Does the analysis over time reveal relevant differences in quality? Which use can be made of the results in terms of quality management? We report results of routine assessment of patient satisfaction by means of a questionnaire with adequate teststatistical properties. 2858 patients could be included. Interpersonal aspects of treatment are vital for patients. We find differences between departments and over time. Feedback to the therapeutic teams have a practical impact. It is possible to integrate routine assessment of patient satisfaction into quality management.


Para-phenylenediamine deteriorates oocyte quality by impairing mitochondrial function.
Several studies demonstrate that para-phenylenediamine (PPD) is often added to permanent oxidative hair dyes. Sub-chronic topical exposure to PPD in male rats damages their testicular function; however, little is known about the effects of PPD exposure on the female reproductive system, especially on oocyte quality. In this study, we found that PPD can affect the meiotic capacity of oocytes and their fertilization potential. In particular, PPD can damage the spindle/chromosome structure and prevent oocytes from developing and maturing normally. Furthermore, PPD exposure compromised the dynamics of cortical granules and their component, ovastacin. In addition to the protein level of Juno, the sperm receptors on the egg membrane, were substantially impaired in PPD-administered oocytes, thus leading to fertilization failure. Finally, we found that PPD exposure resulted in abnormal mitochondrial function, which led to oocyte degeneration, apoptosis, and increased ROS levels. Altogether, our study illustrates that mitochondrial dysfunction and redox perturbation are the major causes of the poor quality of oocytes exposed to PPD.


Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index.
Despite efforts spanning four decades, the therapeutic potential of thyroid hormone receptor (TR) agonists as lipid-lowering and anti-obesity agents remains largely unexplored in humans because of dose-limiting cardiac effects and effects on the thyroid hormone axis (THA), muscle metabolism, and bone turnover. TR agonists selective for the TRbeta isoform exhibit modest cardiac sparing in rodents and primates but are unable to lower lipids without inducing TRbeta-mediated suppression of the THA. Herein, we describe a cytochrome P450-activated prodrug of a phosphonate-containing TR agonist that exhibits increased TR activation in the liver relative to extrahepatic tissues and an improved therapeutic index. Pharmacokinetic studies in rats demonstrated that the prodrug (2R,4S)-4-(3-chlorophenyl)-2-[(3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxy)methyl]-2-oxido-[1,3,2]-dioxaphosphonane (MB07811) undergoes first-pass hepatic extraction and that cleavage of the prodrug generates the negatively charged TR agonist (3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxy)methylphosphonic acid (MB07344), which distributes poorly into most tissues and is rapidly eliminated in the bile. Enhanced liver targeting was further demonstrated by comparing the effects of MB07811 with 3,5,3'-triiodo-l-thyronine (T(3)) and a non-liver-targeted TR agonist, 3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (KB-141) on the expression of TR agonist-responsive genes in the liver and six extrahepatic tissues. The pharmacologic effects of liver targeting were evident in the normal rat, where MB07811 exhibited increased cardiac sparing, and in the diet-induced obese mouse, where, unlike KB-141, MB07811 reduced cholesterol and both serum and hepatic triglycerides at doses devoid of effects on body weight, glycemia, and the THA. These results indicate that targeting TR agonists to the liver has the potential to lower both cholesterol and triglyceride levels with an acceptable safety profile.


Clinical characteristics of women with chlamydial cervicitis.
Four hundred ninety-three women were examined, had a cervical culture done for Chlamydia trachomatis and completed a questionnaire. Sixty-one, or 12.4%, were positive for Chlamydia on culture. Infected women were more likely to be younger, to be unmarried, to have had more sexual partners, to have had past abnormal cytology, to have spotting or postcoital bleeding, to have a mucoid or purulent cervical discharge and to have signs of cervical inflammation, especially friability. No characteristic finding in the past history, symptoms or physical examination combined sufficient sensitivity and specificity to serve by itself as a basis for selective testing for C trachomatis. It appears that multiple characteristics--including history, symptoms, physical examination and cytologic results--must be utilized to select patients for testing.


Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men.
Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.


[Remote wireless monitoring].
The increasing device implantations to treat cardiovascular diseases such as arrhytmias and heart failures, aging of the population, and the growing number of patients with access to new therapies as well as the wider access to health systems are the reasons why the number of new implantations carried out each year is rising. Hence, we should have an equipment that can control these patients at a distance, making the follow-up closer. The answer to this enormous challenge is the remote monitoring of these devices. Biotronik is a pioneer in this task and since 2001 it has been comercializing pacemakers and portable wireless monitors (CardioMessenger). Currently, there are more than 100,000 installed systems. Thanks to the continuous and completely automatized follow-up, as well as the wireless net, the system integrity can be confirmed, and then proceed to adjust the therapies in an optimized manner according to each patient's needs; also take action to prevent the development of some arrhytmias, or even the evolution of a heart failure. Likewise, the system can improve the clynical efficiency of the treatment and help to economize to the Ministry of Healthcare.


Rhythmic pore dynamics in a shrinking lipid vesicle.
The rhythmic motion of membrane pore behavior under nonequilibrium conditions was studied. Application of the surfactant triton X-100 (TX-100) caused lipid vesicles to exhibit two types of shrinking dynamics with pore generation, which depended on both the size of the vesicles and the concentration of added TX-100. Small vesicles and the addition of a low concentration of TX-100 resulted in rhythmic-pore dynamics, where a transient pore was generated within a vesicle in a repetitive manner. In contrast, large vesicles and a high concentration of TX-100 led to continuous-pore dynamics, where the vesicle maintained an open pore during the shrinking process. In the rhythmic-pore membrane, long-cycle oscillation was observed with large vesicles and a low concentration TX-100. The period of one cycle decreased with a decrease in the vesicle size and an increase in the TX-100 concentration. We discuss the mechanism of these trends by considering the elastic free energy of the membrane.


Diabetes as a risk factor for periodontal disease: current status and future considerations.
Over the past decade, there has been an emerging interest in the interrelationship between systemic conditions and oral health. Diabetes is perhaps one of the best documented conditions that have been closely linked with periodontal disease. This paper reviews the role of diabetes as a risk factor in periodontal disease. The treatment implications in the management of periodontal disease as an integral component of diabetes care is also discussed in light of the current understanding of the pathogenesis of these 2 chronic conditions. Epidemiological, clinical and laboratory studies examining the relationship between diabetes and periodontal diseases were selected from both medical and dental journals. The severity of periodontal destruction has been shown to be related to the direct and indirect effects of glycaemic control, with other factors also being implicated. Although some studies have pointed towards a bi-directional relationship between glycaemic control and periodontal health, it is still not clear if improvement in periodontal health could lead to improved metabolic control. Diabetes and periodontal disease are closely related in many ways, though the effect of periodontal disease on diabetes control remain to be determined, with larger intervention studies. In light of the increasing evidence of the relationship between diabetes and periodontal disease, management of oral health should form an integral part of diabetes management.


Clinico-pathological follow-up after total colectomy and straight ileo-anal anastomosis done for ulcerative colitis.
Restorative proctocolectomy is used as surgical treatment for ulcerative colitis. We have earlier documented adaptative changes in the terminal ileum after total colectomy, and straight ileo-anal anastomosis. To correlate the morphologic and functional changes in the ileal mucosa after total colectomy and hand-sewn straight ileo-anal anastomosis for ulcerative colitis. Thirty consecutive patients (age range 15-50 years, 24 men) who had undergone total colectomy, rectal mucosectomy and hand-sewn straight ileo-anal anastomosis for ulcerative colitis were included in the study. These patients were followed up at 3-monthly intervals following surgery for two years and later once every year for a median duration of 9.5 (range 1-17) years. The clinical parameters studied were weight gain, frequency of stools, nature of stools, nocturnal stool frequency and need for antidiarrheal drugs. At each follow-up visit they were subjected to per rectal ileoscopy with ileal biopsy and barium enema. Ileal biopsy was analyzed histologically and histochemically. The clinical features improved over time, with average weight gain of 5 (range 1-7) Kg at one year. Frequency of stools decreased from 8-10 per day to 2-3 per day. The stools became semisolid and there was no need for antidiarrheal drug by the end of one year. All the patients showed adaptative changes in the ileum. The ileal mucosa was completely transformed into colonic type by the end of one year, colonoscopically (spacious lumen characteristic of colon), radiologically (disappearance of ileal characteristics with rectosigmoid-like appearance), histologically (blunting of villi with increase in goblet cells), and histochemically (sialomucin pattern to sulfomucin pattern). The ileum undergoes adaptative changes with corresponding improvement of clinical parameters over time, after proctocolectomy and ileoanal anastomosis for ulcerative colitis.


Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling.
Germ-free (GF) mice have increased bone mass that is normalized by colonization with gut microbiota (GM) from conventionally raised (CONV-R) mice. To determine if innate immune signaling pathways mediated the effect of the GM, we studied the skeleton of GF and CONV-R mice with targeted inactivation of MYD88, NOD1 or NOD2. In contrast to WT and Myd88-/- mice, cortical bone thickness in mice lacking Nod1 or Nod2 was not increased under GF conditions. The expression of Tnfα and the osteoclastogenic factor Rankl in bone was reduced in GF compared to CONV-R WT mice but not in Nod1-/- or Nod2-/- mice indicating that the effect of the GM to increase Tnfα and Rankl in bone and to reduce bone mass is dependent on both NOD1 and NOD2 signaling.


Differential criteria for binge eating disorder and food addiction in the context of causes and treatment of obesity.
To establish the differential criteria for Binge Eating Disorder (BED) and Food Addiction (FA). We performed a detailed analysis of comparative diagnostic criteria for BED and Substance use disorder contained in the Diagnostic and Statistical Manual of Mental Disorders DSM-V. We applied the diagnostic criteria for both disorders to scientific publications on the issue of excessive eating in obese people, during the years 2005-2016, available on PubMed. We isolated specific similarities and differences between Binge Eating Disorder and Food Addiction. We formulated differential criteria for BED and FA. In BED as well as FA the following characteristics are apparent: preoccupation with food, excessive eating, loss of control over the amount of food and manner of eating, inability to change behavior, continuing behavior despite negative consequences, increased impulsiveness and emotional imbalance. Differences between BED and FA relate to the function of food, reaction to omitted food, psychological mechanisms of coping with excessive eating and body image, the issue of tolerance, withdrawal syndrome and the correlation between excessive eating and other areas of life. The criteria of differentiation between BED and FA concern the following: function of food, eating circumstances, reaction to the unavailability of food, awareness of the problem. Appropriate diagnosis of these disorders and their differentiation increases the chances of adequate treatment of obese patients.


Electronic and atomic structure of the Al(n)H(n+2) clusters.
The electronic and atomic structure of the family of hydrogenated Al clusters Al(n)H(n+2) with n=4-11 has been studied using the density functional theory with the generalized gradient approximation (GGA) for exchange and correlation. All these clusters have substantial gaps between the highest occupied and the lowest unoccupied molecular orbitals (HOMO-LUMO) and, consequently, they are chemically very stable. The largest gap of 2.81 eV occurs for Al(6)H(8). Five clusters of the family, Al(4)H(6), Al(5)H(7), Al(6)H(8), Al(7)H(9), and Al(10)H(12), fulfill the Wade-Mingos rule. That is, in Al(n)H(n+2), the Al matrix forms a polyhedron of n vertices and n H atoms form strong H-Al terminal bonds; one pair of electrons is involved in each of those bonds. The remaining n+1 electron pairs form a delocalized cloud over the surface of the Al cage. The clusters fulfilling the Wade-Mingos rule have wider HOMO-LUMO gaps and are chemically more stable. The trends in the gap have some reflections in the form of the photoabsorption spectra, calculated in the framework of time-dependent density functional theory using the GGA single-particle energies and orbitals and a local density approximation exchange-correlation kernel.


Brillouin Frequency Shift of Fiber Distributed Sensors Extracted from Noisy Signals by Quadratic Fitting.
It is a basic task in Brillouin distributed fiber sensors to extract the peak frequency of the scattering spectrum, since the peak frequency shift gives information on the fiber temperature and strain changes. Because of high-level noise, quadratic fitting is often used in the data processing. Formulas of the dependence of the minimum detectable Brillouin frequency shift (BFS) on the signal-to-noise ratio (SNR) and frequency step have been presented in publications, but in different expressions. A detailed deduction of new formulas of BFS variance and its average is given in this paper, showing especially their dependences on the data range used in fitting, including its length and its center respective to the real spectral peak. The theoretical analyses are experimentally verified. It is shown that the center of the data range has a direct impact on the accuracy of the extracted BFS. We propose and demonstrate an iterative fitting method to mitigate such effects and improve the accuracy of BFS measurement. The different expressions of BFS variances presented in previous papers are explained and discussed.


The alpha protein ICP0 does not appear to play a major role in the regulation of herpes simplex virus gene expression during infection in tissue culture.
The herpes simplex virus type 1 (HSV-1) alpha protein ICP0 trans-activates HSV-1 early genes in transient expression assays. To investigate the function of ICP0 during HSV-1 infection, we have lowered the level of ICP0 by use of a recombinant plasmid that has been engineered to express the antisense message. Cell lines were constructed which stably carry the antisense plasmid. Total protein profiles from infected antisense cell lines showed that the level of ICP0 was reduced to less than 10% of the wild type level in two of the cell lines. However, reducing the level of ICP0 did not have a significant effect on the expression of HSV-1 early or late genes. The polypeptide patterns for the remaining infected cell polypeptides were similar in that no bands were absent although there were some quantitative differences. The level of two early proteins, glycoprotein B and glycoprotein D was reduced in one of the cell lines, however, levels were nearly equivalent to the control infection for two other cell lines tested. Virus yields were the same for the antisense cell lines and for parent cells. Decreased ICP0 levels did not lead to more restrictive phenotypes for an alpha 4 or alpha 27 mutant as protein patterns were similar for these mutants in antisense and parent cells. Therefore, while ICP0 has been demonstrated to be a strong inducer of gene expression in transient expression assays, it does not appear to have a major role as an activator during the productive infection of tissue culture cells.


Adolescent and therapist perception of barriers to outpatient substance abuse treatment.
Attrition is one of the most vexing problems for the effective delivery of behavioral health services. Most prior studies focus on patient demographics and psychopathology factors predicting dropout. We examined patient and therapist post-treatment reports of barriers to attending treatment. Six hundred adolescents and their therapists completed the Perceived Barriers to Treatment scale (PBT) at discharge from a brief substance abuse intervention. After adjusting for covariates, results suggest that perceived barriers, in particular, practical obstacles, lack of treatment readiness, relevance, and compatibility, are related to sessions attended. Shifting to a more patient-centered approach for understanding treatment retention is discussed.


[Intraarterial chemotherapy for patients with invasive bladder cancer--clinical effects and preliminary results in bladder preservation].
Preoperative intraarterial chemotherapy including cisplatin, etoposide and adriamycin was performed for 16 patients with invasive bladder cancer between April, 1989 and September, 1993. Of 16 patients, radical cystectomy was done in 12 patients and the bladder was preserved by a transurethral resection in 4. Of 12 patients treated with cystectomy, complete response was achieved in 2 cases and partial response in 4 (response rate: 50%). Pathological evaluation of resected specimens revealed significant downstage of the tumors in 8 of 12 patients (67%). At follow-up 4 patients had recurrent and/or distant metastasis. Three of these four patients died of cancer progression and one survived with cancer. Of 4 patients with preserved bladder, complete response was achieved in one case and partial response in 3. Pathological specimens evaluated by transurethral resection showed significant downstage of tumors in all cases. One patient had an invasive, recurrent tumor in the preserved bladder and was treated with radical cystectomy 6 months after initiation of the therapy. All patients tolerated the treatment well. Intraarterial chemotherapy seems to be effective for invasive bladder cancer, but the true success of bladder-preserving treatment by a transurethral resection, chemotherapy and other therapy will require further study.


Perturbation of transmembrane signaling mechanisms in acute and chronic endotoxemia.
Our results reviewed here may be summarized as follows: 1. Continuous endotoxemia significantly interferes with Ca2+-dependent information flow in the liver. 2. The subcellular sites where these molecular lesions can be localized include: a.) the plasma membrane-there are effects at the level of alpha 1-adrenergic and vasopressin binding, and also in the coupling of receptor activation to inositol lipid metabolism in terms of PIP2 degradation and resynthesis b.) the endoplasmic reticulum in terms of Ca2+ release and PI synthesis. Another one of the sequelae of Ca2+-associated receptor activation, namely, cytosolic ionized Ca2+ concentration is also affected. 3. Finally, in addition to seeing the impact of acute or continuous endotoxemia at the level of receptor activation and signal generation, we can also document alterations in the expression of physiologic function subserved by these Ca2+- and inositol lipid-associated signaling processes--i.e. in glycogen phosphorylase activity-being consistent with the above described changes. In conclusion, we state that a causal link is shown between receptor binding, agonist-induced phosphoinositide hydrolysis, intracellular Ca2+ mobilization and activation of phosphorylase a in the liver, suggesting that these alterations may underlie some of the metabolic consequences of chronic sepsis.


Alr Gene in Brucella suis S2: Its Role in Lipopolysaccharide Biosynthesis and Bacterial Virulence in RAW264.7.
Brucella suis, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase (alr) gene, which encodes alanine racemase in Brucella, remains unclear. Here, we analyzed an alr deletion mutant and a complemented strain of Brucella suis S2. The knockout strain displayed an unaltered, smooth phenotype in acriflavine agglutination tests but lacked the core polysaccharide portion of lipopolysaccharide (LPS). Genes involved in the LPS synthesis were significantly upregulated in the deletion mutant. The alr deletion strain exhibited reduced intracellular viability in the macrophages, increased macrophage-mediated killing, and upregulation of the apoptosis markers. Bcl2, an anti-apoptotic protein, was downregulated, while the pro-apoptotic proteins, Bax, Caspase-9, and Caspase-3, were upregulated in the macrophages infected with the deletion strain. The infected macrophages showed increased mitochondrial membrane permeability, Cytochrome C release, and reactive oxygen species, activating the mitochondrial apoptosis pathway. These findings revealed that alanine racemase was dispensable in B. suis S2 but influenced the strain's rough features and triggered the mitochondrial apoptosis pathway during macrophage invasion. The deletion of the alr gene reduced the intracellular survival and virulence. This study enhances our understanding of the molecular mechanism underlying Brucella's survival and virulence and, specifically, how alr gene affects host immune evasion by regulating bacterial LPS biosynthesis.


Advances in midface reconstruction: beyond the reconstructive ladder.
This article reviews the anatomy and function of the midface, defect classifications and the breadth of common and novel reconstructive techniques including medical modeling, dental splints, and dental rehabilitation. Historically many classification systems for midface and maxillary defects exist but most defects are unique and an individualized approach is required. There has been an increased interest in using regional pedicled flaps with bone for reconstruction. Free flap reconstruction with the osteocutaneous radial forearm and fibula flap have been recently modified to increase the success of osseointegrated implants. Scapular free flap reconstruction has become increasingly popular because of the versatility, good bony contour match, and long pedicle length with the scapular tip flap. Dental splints are more cost effective than medical modeling and cutting guides but both techniques are complimentary in complex reconstruction. Midface reconstruction is a unique and challenging surgery demonstrated by the numerous classification systems and techniques available to reconstruct. Recent developments have further augmented these challenging reconstructions.


The proteomic profile of the acquired enamel pellicle according to its location in the dental arches.
This study evaluated the variation in the protein profile of the acquired enamel pellicle (AEP) formed in vivo according to its location in the dental arches. The AEP was formed for 120min in 9 volunteers. Pellicle formed at upper+lower anterior facial (ULAFa; teeth 13-23 and 33-43), upper anterior palatal (UAPa; teeth 13-23), lower anterior lingual (LALi; teeth 33-43), upper+lower posterior facial (ULPFa; teeth 14-17 24-27, 34-37 and 44-47), upper posterior palatal (UPPa; teeth 14-17 and 24-27) and lower posterior lingual (LPLi; teeth 34-37 and 44-47) regions were collected separately and processed for analysis by label-free LC-ESI-MS/MS. Three-hundred sixty three proteins were identified in total, twenty-five being common to all the locations, such as Protein S100-A8, Lysozyme C, Lactoferrin, Statherin, Ig alpha-2, ALB protein, Myeloperoxidase and SMR3B. Many proteins were found exclusively in the AEP collected from one of the regions (46-UAPa, 33-LALi, 59-ULAFa, 31-ULPFa, 44-LPLi and 39-UPPa). The protein composition of the AEP varied according to its location in the dental arches. These results provide important insights for understanding the differential protective roles of the AEP as a function of its location in the dental arches.


[Epilepsy with onset between the ages of 3 and 12 months. Our experience gained over a 10-year period].
The prognosis of epilepsy is essentially determined by its aetiology and a poorer prognosis is generally associated with an early onset of the seizures. In this study we review our experience in epilepsies in children born after 1st January 1997 and who had their first acute non-symptomatic seizure before 31st March 2007 and between the ages of 3 and 12 months. Special attention is given to the analysis of cases of remote non-symptomatic epilepsies. Of the children born in that period, 267 were diagnosed with epilepsy, and the first seizure occurred between 3 and 12 months of age in 69 cases: 39 of which were symptomatic and 30 were cryptogenic and idiopathic epilepsies. West's syndrome/childhood spasms were observed in 20 cases (17 of the symptomatic cases and three of the cryptogenic and idiopathic patients). The cryptogenic and idiopathic cases were divided into three groups depending on their electroencephalogram pattern: nine generalised, 18 with no generalised alterations and three hypsarrhythmias. In addition, the three groups were analysed taking into account three degrees of psychomotor development: normal, slight retardation and moderate/severe retardation. None of the non-generalised cases presented severe psychomotor retardation, whereas 78% of the generalised and 33% of those with West's syndrome developed an important degree of retardation in their course. Our experience is compatible with the existence of epilepsies that have their onset in the early months of life and a good prognosis, which is important when it comes to the information and therapeutic approaches in cases of remote non-symptomatic epilepsy.


Ficolins: structure, function and associated diseases.
Innate immunity relies upon the ability of a few pattern recognition molecules to sense molecular markers. Ficolins are humoral molecules of the innate immune systems which recognize carbohydrate molecules on pathogens, apoptotic and necrotic cells. Three ficolins have been identified in humans: L-ficolin, H-ficolin and M-ficolin (also referred to as ficolin-2, -3 and -1, respectively). They are soluble oligomeric defence proteins with lectin-like activity and they are structurally similar to the human collectins, mannan-binding lectin (MBL) and surfactant protein A and D. Upon recognition of the infectious agent, the ficolins act through two distinct routes: initiate the lectin pathway of complement activation through attached serine proteases (MASPs), and a primitive opsonophagocytosis thus limiting the infection and concurrently orchestrating the subsequent adaptive clonal immune response. Recently a lot of reports showed that dysfunction or abnormal expressions of ficolins may play crucial roles in the pathogenesis of human diseases including: (1) infectious and inflammatory diseases, e.g., recurrent respiratory infections; (2) apoptosis, and autoimmune disease; (3) systemic lupus erythematosus; (4) IgA nephropathy; (5) clinical syndrome of preeclampsia; (6) other diseases associated factor e.g. C-reactive protein. Precise identification of ficolins functions will provide novel insight in the pathogenesis of these diseases and may provide novel innate immune therapeutic options to treat disease progression. This review discusses the structures, functions, and clinical implications of ficolins and summarizes the reports on the roles of ficolins in human diseases.


Endovascular management of fusiform aneurysms in the posterior circulation: the era of flow diversion.
Fusiform aneurysms are uncommon compared with their saccular counterparts, yet they remain very challenging to treat and are associated with high rates of rebleeding and morbidity. Lack of a true aneurysm neck renders simple clip reconstruction or coil embolization usually impossible, and more advanced techniques are required, including bypass, stent-assisted coiling, and, more recently, flow diversion. In this article, the authors review posterior circulation fusiform aneurysms, including pathogenesis, natural history, and endovascular treatment, including the role of flow diversion. In addition, the authors propose an algorithm for treatment based on their practice.


[Preventive effect and clinical significance of garlicin injection on mechanical ventilator-associated low respiratory tract deep-seated fungal infection].
To investigate the preventive effect and clinical significance of garlicin injection on ventilator-associated low respiratory tract deep-seated fungal infection (VRFI) as pneumonia. Retrospectively analysis on 147 patients underwent mechanical ventilation in our Intensive Care Unit (ICU) in recently 3 years was conducted. According to the garlicin injection administration was used or not, 79 patients with WVUH (West Virgina University Hospital) score > or = 25 points were selected and divided into the preventive group and the control group, and the differences in baseline conditions, incidence of VRFI and hospital outcome between the two groups were compared. There was no significant difference between the two groups in baseline data as age, sex, APACHE II score, SAPS II score and WVUH score. But the incidence of VRFI in the preventive group was significantly lower than that in the control group (P<0.01). The relative risk in the latter was 2.06 (95% CI, 1.25-3.38). No significant difference was found between the two groups in hospital mortality (P>0.05). Garlicin injection can effectively reduce the incidence of VRFI, and is inexpensive, it is an ideal prophylactic anti-fungal drug.


Novel reassortant of H1N1 swine influenza virus detected in pig population in Russia.
Pigs play an important role in interspecies transmission of the influenza virus, particularly as "mixing vessels" for reassortment. Two influenza A/H1N1 virus strains, A/swine/Siberia/1sw/2016 and A/swine/Siberia/4sw/2017, were isolated during a surveillance of pigs from private farms in Russia from 2016 to 2017. There was a 10% identity difference between the HA and NA nucleotide sequences of isolated strains and the most phylogenetically related sequences (human influenza viruses of 1980s). Simultaneously, genome segments encoding internal proteins were found to be phylogenetically related to the A/H1N1pdm09 influenza virus. In addition, two amino acids (129-130) were deleted in the HA of A/swine/Siberia/4sw/2017 compared to that of A/swine/Siberia/1sw/2016 HA.


The photodissociation of N,N-dimethylnitrosamine at 355 nm: The effect of excited-state conformational changes on product vector correlations.
In a photodissociation experiment, the dynamics associated with creating reaction products with specific energies can be understood by a study of the product vector correlations. Upon excitation to the S1 state, N,N-dimethylnitrosamine (DMN) undergoes an excited-state geometry change from planar to pyramidal around the central N. The significant geometry change affects the vector correlations in the photoproducts. Using polarized lasers for 355 nm photodissociation of DMN and for NO photoproduct excitation in a velocity-mapped ion imaging apparatus reveals new vector correlation details among the parent transition dipole (μ), photofragment velocity (v), and photofragment angular momentum (j). The dissociation of DMN displays some μ-v correlation [β02(20)=-0.2], little μ-j correlation [β02(02)∼0], and, surprisingly, a v-j [β00(22)] correlation that depends on the NO lambda doublet probed. The results point to the importance of the initial excited-state conformational change and uncover the presence of two photolysis channels.


Growth assessment: how do we measure up?
Measurement of children's height and weight at regular intervals is important for identifying growth problems as well as for planning health promotion interventions for those at risk from under or over nutrition. Opportunistic measurement is recommended when children are seen by healthcare professionals for other reasons. Identification of variations in practice around measurement of height and weight in a children's unit led to the development of guidelines, purchase of new equipment, implementation of educational strategies and introduction of a growth link nurse role. Repeat audit revealed that these approaches did not bring about the desired changes in practice. Growth assessment is a quick, non invasive procedure that can provide valuable information about the general health and well being of the child but is perceived as a low priority by some healthcare professionals. Different approaches are needed to improve this important aspect of health care for children.


Sorption pH dependance of strontium/calcium by sodium nonatitanate.
Sodium nonatitanate powder is a layered material containing some potential exchangeable sodium ions between layers. In this work, sorption mechanism of this material has been studied and modeled at the solid-liquid interface. In particular, the ion-exchange mechanism is up to now not entirely known and especially the role of the pH on sorption properties. To investigate this latter, the solid is first equilibrated with inert acidic and base (nitric acid and triethylamine) for which the co-ions nitrate and triethylammonium do not penetrate the solid. The exchange between proton or divalent ions (strontium or calcium), and the sodium initially located in the sodium nonatitanate, is characterized through capillary ionic chromatography and conductivity experiments. To understand and explain the sorption properties, we modeled the equilibrium constant of different exchange reactions as a function of the solution pH. The equilibrium constants of the strontium/sodium and the calcium/sodium exchange have been obtained. We have shown the important role of the pH on the sorption rate of the strontium and moreover the hydrolysis rate of the sodium nonatitanate is calculated. We found that one eighth of sodium is spontaneously hydrolysed in aqueous phase whereas seven-eighths are exchanged by different divalent cations (strontium or calcium). Strontium and calcium exhibit similar exchange curves and competition with the proton adsorbed is modeled with global equilibrium constant. The prediction is in agreement with the conductivity experiments and the global extraction isotherms.


[Development and Effects of Smartphone App-Based Walking Exercise Program for Taxi Drivers: Based on Bandura's Self Efficacy Theory].
The purpose of this study was to examine the effects of smart-phone app-based walking exercise programs for taxi drivers on self-efficacy and outcome expectations for exercise, health-related quality of life, walking as an exercise, and physiological indexes. A nonequivalent control group with a pre-post-test design was used. The subjects were recruited in G metropolitan city. Subjects were assigned to the experimental (n=31) or control groups (n=30). The smart phone app-based walking exercise program consisted of educations via the app, twelve short message services, and one individual telephone counseling session, which was spread over 12 weeks. Self-efficacy, outcome expectations, and health-related quality of life had significantly higher pre-post test differences in scores in the experimental group. Additionally, blood pressure, body mass index, and waist circumference had significantly decreased pre-post-test difference levels in the experimental group. Walking as an exercise (which consisted of days walked, number of steps walked, and amount of time walked) had significantly increased in the experimental group after 7~12 weeks in the period following the intervention program rather than 1~6 weeks after the program. The smart phone app-based walking exercise program based on the self-efficacy theory demonstrates a significant effect on improving self-efficacy, outcome expectations physical activities, and health-related quality of life for taxi drivers. Therefore, it is recommended to actively use the program as a tool to promote self-efficacy, physical activities, and health behaviors in taxi drivers.


A hospital based surveillance of metallo-beta-lactamase producing gram negative bacteria in Nepal by imipenem-EDTA disk method.
A rising threat of the rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of public health concern worldwide. Hence, for a low income nation like Nepal, surveillance data on MBL producing clinical isolates via a cost effective technique is necessary to prevent their dissemination as well as formulation and regulation of antimicrobial stewardship policy. The prospective study was conducted at Nepal Medical College, Kathmandu from May to October, 2014 to assess the prevalence of MBL production among ceftazidime-resistant Gram-negative rods (GNRs) isolates. The samples were processed according to standard microbiological procedure following the Manual of clinical Microbiology. Isolated GNRs were subjected to susceptibility testing against the selected panel of antibiotics by Kirby- Bauer disc diffusion method and interpretation made in conformity with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Ceftazidime-resistant isolates were subjected to the detection of MBL production by imipenem-EDTA combined disc (CD) method. Among the Gram-negative isolates, 5.80% (21/362) were found to be MBL positive with Acinetobacter spp. showing the highest prevalence i.e. 85.71% (18/21), followed by P. aeruginosa i.e. 14.29% (3/21). None of the other cefazidime resistant gram negative bacteria tested were found to be positive for MBL production with all the positive isolates determined to be Multidrug resistant (MDR) strains. This study demonstrated a higher rate of resistance among P. aeruginosa and Acinetobacter spp. to a wide variety of antibiotic categories with an additional burden of MBL production within them, warranting a need for strict surveillance and rapid detection of MBL production among the GNRs.


[Effectiveness of laparoscopic repair of primary strictures of ureteropelvic junction].
To evaluate the effectiveness of laparoscopic repair of primary strictures of ureteropelvic junction (UPJ) depending on baseline renal function of the ipsilateral kidney. The study analyzed results of 134 patients (78 women and 56 men, age from 18 to 56 years) who underwent various types of laparoscopic repair of the UPJ stricture from 2012 to 2015. Depending on the surgical technique all patients were divided into three groups: group 1 (n=34) underwent spiral flap technique by Culp and DeWeerd, group 2 (n=59) - Anderson-Hynes pyeloplasty and group 3 (n=41) had antevasal dismembered pyeloplasty. All interventions ended with internal ureteral stenting for up to 6-8 weeks. Also, all patients were divided into three subgroups, depending on the degree of renal function deficiency - less than 25%, 25-50%, and 51-75%. Treatment effectiveness criteria included the following parameters: complete relief of the pain syndrome, a decrease in the degree of pyeloectasia, stabilization or improvement of the functional state of the renal parenchyma (according to radioisotope renography), and the absence of recurrence of the UPJ stricture. The overall effectiveness of UPJ laparoscopic reconstruction was 94.7% (127 of 134). The effectiveness of the treatment was independent of the surgical technique, the initial thickness of the renal parenchyma and the degree of PCS dilatation. There was an inverse correlation between the treatment effectiveness the degree of kidney function deficiency. In patients with hydronephrosis secondary to UPJ stricture, the effectiveness of surgical treatment is mainly determined by its timeliness. The best treatment results were observed in patients with better renal function. The degree of renal function deficiency should be considered the main prognostic factor for the effectiveness of the forthcoming operation.


Comparison of the 2005 Montreal Criteria and the 2019 Cirrhotic Cardiomyopathy Consortium Criteria for the Diagnosis of Cirrhotic Cardiomyopathy.
The comparison between the diagnostic criteria for cirrhotic cardiomyopathy (CCM) first proposed in 2005 (2005 Montreal criteria), and those redefined in the 2019 Cirrhotic Cardiomyopathy Consortium (2019 CCC criteria) has generated significant controversy. Importantly, the predictive value of these criteria in cirrhotic patients (CPs) remains unclear to this date. Thus, the present study aims to compare the 2 sets of criteria and investigate their predictive value in CPs. Between April 2021 and April 2023, a total of 104 CPs with an average age of 46.4 ± 8.9 years, who had no history of other cardiac diseases or malignancies were enrolled in this prospective single-center observational cohort study, conducted at the Third Affiliated Hospital of Sun Yat-Sen University. Various echocardiographic indicators were measured and assessed for their prognostic value and association with clinical outcomes. The prevalence of CCM was found to be comparable when evaluated using both the 2019 CCC and 2005 Montreal criteria (54.8% vs 44.2%, p = 0.161). However, the diagnosis of systolic dysfunction was significantly different between the 2 criteria (52.9% vs 1.0%, p <0.001). Among patients with systolic dysfunction, 27.9% had reduced left ventricular global longitudinal strain, while 25% had increased left ventricular global longitudinal strain. Moreover, fewer patients were diagnosed with diastolic dysfunction (DD) using the 2019 CCC criteria (4.8% vs 44.2%, p <0.001). Multivariate Cox analysis revealed that CPs who had encephalopathy, a high model for end-stage liver disease score, and DD diagnosed using the 2019 CCC criteria exhibited a poorer prognosis. In conclusion, although the prevalence of CCM according to both criteria is similar, the consistency is poor, indicating that they are not the same group of patients. Importantly, CPs with DD diagnosed according to the 2019 CCC criteria might be associated with increased adverse events.


Plasma free tryptophan variation during oestrous cycle of the rat.
The concentration of plasma free tryptophan was shown to undergo a regular and statistically significant fluctuation through the four phases of the oestrous cycle of the rat. The highest concentration of plasma free tryptophan was observed during oestrus. During metoestrus the concentration of plasma free tryptophan decreased by 25% to the lowest observed level; thereafter it gradually increased during dioestrus and pro-oestrus. The concentration of plasma total tryptophan was found to be unchanged during the oestrous cycle of the rat.


Dynamic Interface Pressure Monitoring System for the Morphological Pressure Mapping of Intermittent Pneumatic Compression Therapy.
Intermittent pneumatic compression (IPC) is a proactive compression therapeutic technique in the prophylaxis of deep vein thrombosis, reduction of limb edema, and treatment of chronic venous ulcers. To appropriately detect and analyze biomechanical pressure profiles delivered by IPC in treatment, a dynamic interface pressure monitoring system was developed to visualize and quantify morphological pressure mapping in the spatial and temporal domains in real time. The system comprises matrix soft sensors, a smart IPC device, a monitoring and analysis software, and a display unit. The developed soft sensor fabricated by an advanced screen printing technology was used to detect intermitted pressure by an IPC device. The pneumatic pressure signals inside the bladders of the IPC were also transiently collected by a data acquisition system and then transmitted to the computer through Bluetooth. The experimental results reveal that the developed pressure monitoring system can perform the real-time detection of dynamic pressures by IPC and display the morphological pressure mapping multi-dimensionally. This new system provides a novel modality to assist in the effective evaluation of proactive compression therapy in practice. The study results contribute to understanding the working mechanisms of IPC and improving its functional design based on intuitive biomechanical characteristics of compression delivery profiles.


Improving communication with low-income women using today's technology.
The authors of this article examine reasons for missed appointments and preferences for appointment reminders among inner city obstetrics and gynecology clinic patients having a high missed-appointment rate. Sixty low-income women, including African Americans, Caucasians, and members of other ethnic groups, with a mean age of 27 years, were interviewed by telephone. The most frequently cited reason for missed appointments was forgetfulness. Almost all study participants indicated that they would like a text message reminder of upcoming appointments along with telephone and/or postal letter reminders. In this article the authors review the literature addressing both missed appointments and trends in mobile technologies, report their study of missed appointments, and conclude that text messaging appointment reminders can decrease missed appointments among young, low-income women.


Digital sun sensor multi-spot operation.
The operation and test of a multi-spot digital sun sensor for precise sun-line determination is described. The image forming system consists of an opaque mask with multiple pinhole apertures producing multiple, simultaneous, spot-like images of the sun on the focal plane. The sun-line precision can be improved by averaging multiple simultaneous measures. Nevertheless, the sensor operation on a wide field of view requires acquiring and processing images in which the number of sun spots and the related intensity level are largely variable. To this end, a reliable and robust image acquisition procedure based on a variable shutter time has been considered as well as a calibration function exploiting also the knowledge of the sun-spot array size. Main focus of the present paper is the experimental validation of the wide field of view operation of the sensor by using a sensor prototype and a laboratory test facility. Results demonstrate that it is possible to keep high measurement precision also for large off-boresight angles.


Co-injection of anti-HER2 antibody Trastuzumab does not increase efficacy of [177Lu]Lu-PSMA-617 therapy in an animal model of prostate cancer.
One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [177Lu]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Trastuzumab gave less proliferation of irradiated tumor cells in vitro, and when using radionuclide therapy, also in vivo. The aim of this study is to determine whether the same holds true in PSMA-expressing PC-3 PIP cells using [177Lu]Lu-PSMA-617 radionuclide therapy. PC-3 PIP and 22Rv1 prostate cancer cells were tested in vitro, treated with 6 Gy of x-rays with or without Trastuzumab incubation. We measured uptake of HER2-targeting affibody [68Ga]Ga-ABY-025 and cell survival, e.g. using the WST-1 assay. Three groups (n=10 each) of male nude Balb/c mice were inoculated with PC-3 PIP xenograft tumors and treated with just [177Lu]Lu-PSMA-617 (20 MBq), [177Lu]Lu-PSMA-617 (20 MBq) and Trastuzumab (4 × 5 mg/kg), or left untreated. Tumor sizes and animal survival was observed. In vitro, x-ray irradiation did reduce survival in 22Rv1 but not PC-3 PIP cells, and there was no significant effect of Trastuzumab treatment. Cells expressed HER2 but not significantly elevated post irradiation. In vivo, mice co-treated with Trastuzumab had significantly longer survival than untreated mice, but not than only [177Lu]Lu-PSMA-617. Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.


Cutaneous Neurofibroma of the Lacrimal Caruncule: A Case Report.
We describe the case of a neurofibroma on the lacrimal caruncle of a female patient with neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant genetic disease with a wide variety of clinical manifestations, one of the most common of which is neurofibroma. The lesion was removed surgically under general anesthesia and sent to histopathological analysis, which confirmed the clinical diagnosis of a neurofibroma.


The ACS-TQIP palliative care guidelines at two level I trauma centres: a prospective study of patient and caregiver satisfaction.
To measure trauma patient and caregiver satisfaction before and after implementation of standardised palliative care (PC) guidelines. Prospective pre-post study at two level-I trauma centres. PC satisfaction surveys were administered prior to discharge for consented trauma patients (Family Satisfaction with Advanced Cancer Scale, Patient (FAMCARE-P13) survey)≥55 years, and their caregivers (FAMCARE survey), from 1 November 2016 to 30 November 2018. Standardised PC guidelines were implemented January 2018 and included consultations, prognostication assessments, identification of proxies, review of advanced directives and do not resuscitate orders within 24 hours of admission, while advanced goals of care, formal family meetings and spiritual care support were recommended within 72 hours of admission. Generalised linear models were used to determine whether differences in patient or caregiver satisfaction existed pre versus post implementation. There were 572 patients (299 pre; 273 post) and 595 caregivers (334 pre; 261 post) included. Overall patient satisfaction significantly increased post implementation (82.0 vs 86.0, p=0.001). After adjustment, the implementation of the guidelines was an independent predictor of higher overall patient satisfaction (least squares mean (LSM= (83.8% (95%CI 81.2%-86.5%) vs 80.3% (77.7%-82.9%), p=0.003)). Compared with preimplementation, patient satisfaction was significantly higher post implementation in the following domains: information giving (80.9 vs 85.5, p=0.001), followed by physical care (82.2 vs 86.0, p=0.002), availability of care (83.4 vs 86.8, p=0.007) and psychosocial care (84.7 vs 87.6, p=0.04). No significant differences in caregiver satisfaction were found before or after adjustment (LSMpre: 83.1% (95%CI 80.9%-85.3%) vs. post: 82.4% (80.3%-84.5%), p=0.56)) CONCLUSIONS: Our data suggest that the implementation of PC guidelines significantly improved patient satisfaction following traumatic injury, while maintaining robust caregiver satisfaction.


SURE Estimates for a Heteroscedastic Hierarchical Model.
Hierarchical models are extensively studied and widely used in statistics and many other scientific areas. They provide an effective tool for combining information from similar resources and achieving partial pooling of inference. Since the seminal work by James and Stein (1961) and Stein (1962), shrinkage estimation has become one major focus for hierarchical models. For the homoscedastic normal model, it is well known that shrinkage estimators, especially the James-Stein estimator, have good risk properties. The heteroscedastic model, though more appropriate for practical applications, is less well studied, and it is unclear what types of shrinkage estimators are superior in terms of the risk. We propose in this paper a class of shrinkage estimators based on Stein's unbiased estimate of risk (SURE). We study asymptotic properties of various common estimators as the number of means to be estimated grows (p → ∞). We establish the asymptotic optimality property for the SURE estimators. We then extend our construction to create a class of semi-parametric shrinkage estimators and establish corresponding asymptotic optimality results. We emphasize that though the form of our SURE estimators is partially obtained through a normal model at the sampling level, their optimality properties do not heavily depend on such distributional assumptions. We apply the methods to two real data sets and obtain encouraging results.


Oxidant-induced signaling: effects of peroxynitrite and singlet oxygen.
Following the requirement for cells to cope with oxidative stress, there are cellular adaptation mechanisms at the level of gene expression. Much of what is known about oxidant-induced signaling in mammalian cells was found in experiments using hydrogen peroxide as an oxidant. However, since the biochemical reactivities of various oxidants significantly differ, 'oxidative stress' is not necessarily identical independent of the oxidant employed to bring it about. Here, the biological actions of peroxynitrite and singlet oxygen are presented, focusing on signaling effects. Peroxynitrite is generated in biological systems in the diffusion-controlled reaction of superoxide with nitrogen monoxide and is thus likely to be produced in the vicinity of activated macrophages. Singlet oxygen is generated by stimulated neutrophils in vivo and may further be generated photochemically, e.g. upon exposure of cells to ultraviolet A radiation. Exposure of cells to either of these oxidants elicits a cellular stress response, entailing the activation of signaling cascades that regulate proliferative and apoptotic responses, such as mitogen-activated protein kinase cascades or the phosphoinositide 3-kinase/Akt cascade. Two mechanisms for the oxidant-induced activation of a signaling cascade may be envisaged: (i) the indirect targeting of the cascade by interrupting negative regulation, and (ii) an activating oxidation of one of the constituting components of the cascade. Examples for both mechanisms in relation to peroxynitrite and singlet oxygen are discussed.


Action potentials reconstructed in normal and myotonic muscle fibres.
1. Muscle fibres from goats with myotonia congenita show characteristic responses to stimulation with intracellular currents (Adrian & Bryant, 1974). To test whether the reduced surface chloride conductance can account for these myotonic discharges, we have calculated responses of a model 'muscle fibre' to intracellular current of long duration (greater than 100 msec), assuming that the current is applied at the end of the fibre, that the fibre is of finite length, that a regenerative action potential occurs in the transverse tubular system as well as the surface, and that the potassium current in the wall of the transverse tubular system raises the potassium in the tubular lumen. In the absence of information about the kinetic parameters of the ionic currents in mammalian muscle we have used numerical values from frog muscle (Adrian, Chandler & Hodgkin, 1970). 2. In calculations with a normal surface chloride conductance a long maintained current gives only one action potential. Reduction of the chloride conductance to a half produces repetitive firing during the current; reduction to a tenth produces repetitive firing during and a small number of action potentials after the end of the current. Elimination of the tubular potassium accumulation from the calculation reduces the number but does not eliminate action potentials arising after the end of the applied current. 3. With a tenth of the normal chloride conductance calculated responses show maintained firing following a constant current if the deactivating rate of the sodium channels (betam) is reduced by 25%. As before, eliminating potassium accumulation reduces the number of post-stimulus action potentials, but it does not eliminate them altogether. 4. We conclude that in the absence of a surface chloride conductance tubular potassium accumulation could certainly contribute to the instability of the membrane, but it is clear that potassium accumulation is not the only reason for the instability of myotonic muscle fibres. The kinetics of the sodium channels are important and we do not know that they are the same in normal and myotonic fibres. Nevertheless the presence of a surface chloride conductance does stabilize the response of a fibre to constant current or to repetitive stimulation, and its absence could be a sufficient condition for myotonic behaviour.


Upgrade and absolute calibration of the JET scintillator-based fast-ion loss detector.
The JET FILD is a scintillator-based Fast-ion Loss Detector optimized to measure fusion-born alpha-particle losses. This work covers its upgrade and absolute calibration in preparation for the following JET DT experiments. A fast scintillator material (TG-Green) has been installed in the JET FILD. A heater jacket is installed around the fiber bundle, responsible for transmitting the light from the scintillator plate, to anneal the fiber obscuring due to neutron damage. The JET FILD has been upgraded with a 1 Mpx camera and 2 MHz photomultiplier data acquisition hardware. Full-orbit simulations give an estimate of the shading effects on the scintillator plate of the first wall structures and provide a synthetic signal of the JET FILD. A detector instrument function enables absolute values of fast-ion losses using calibration factors. The calibration factors are made available in a shot-to-shot basis for the characterized species and energies and with corrections for the diagnostic conditions. The fast acquisition system sets the Nyquist frequency (1 MHz) above the typical mode frequencies (≈102 kHz), thus making it possible to identify MHD-induced fast-ion losses.


AsnB is responsible for peptidoglycan precursor amidation in Clostridium difficile in the presence of vancomycin.
Clostridium difficile 630 possesses a cryptic but functional gene cluster vanGCd homologous to the vanG operon of Enterococcus faecalis. Expression of vanGCd in the presence of subinhibitory concentrations of vancomycin is accompanied by peptidoglycan amidation on the meso-DAP residue. In this paper, we report the presence of two potential asparagine synthetase genes named asnB and asnB2 in the C. difficile genome whose products were potentially involved in this peptidoglycan structure modification. We found that asnB expression was only induced when C. difficile was grown in the presence of vancomycin, yet independently from the vanGCd resistance and regulation operons. In addition, peptidoglycan precursors were not amidated when asnB was inactivated. No change in vancomycin MIC was observed in the asnB mutant strain. In contrast, overexpression of asnB resulted in the amidation of most of the C. difficile peptidoglycan precursors and in a weak increase of vancomycin susceptibility. AsnB activity was confirmed in E. coli. In contrast, the expression of the second asparagine synthetase, AsnB2, was not induced in the presence of vancomycin. In summary, our results demonstrate that AsnB is responsible for peptidoglycan amidation of C. difficile in the presence of vancomycin.


Immittance screening for aural problems in school children.
The predominant aural health problem in school-age children is middle ear inflammation with effusion. The conventional hearing screening method has ineffectively detected half of those school children with middle ear problems. Acoustic immittance measurements, recently added to the audiologist's battery of tests, effectively and economically screens middle ear effusion. Unfortunately, acoustic immittance does not screen hearing sensitivity as does the conventional pure-tone sweep check. This article describes the principles of acoustic immittance and compares it with pure-tone audiometry; discusses current immittance screening practices; and outlines how acoustic immittance can be included in a school hearing conservation program.


Lycopene regulates the mitochondrial unfolded protein response to prevent DEHP-induced cardiac mitochondrial damage in mice.
Lycopene (LYC), as a kind of carotene, has antioxidant effects. Di(2-ethylhexyl) phthalate (DEHP) was used to improve the flexibility of plastics. However, the potential role of LYC in DEHP induced cardiac injury in mice remains unclear. Therefore, the aim of this study was to investigate the role and mechanism of LYC in DEHP induced cardiac injury. Male ICR mice were treated with DEHP (500 or 1000 mg per kg BW per day) and/or LYC (5 mg per kg BW per day) for 28 days. The results of histopathology and ultrastructure showed that LYC relieved the decrease of mitochondrial volume density and myocardial fibre disorder induced by DEHP. Subsequently, LYC attenuated DEHP-induced mitochondrial damage, mitochondrial unfolded protein response (UPRmt) activation, nuclear factor erythroid 2-related factor 2 (Nrf2) mediated oxidative stress and heat shock response (HSR) activation induced by DEHP. LYC regulates UPRmt to prevent DEHP-induced cardiac mitochondrial damage. Thus, this study provided new evidence of UPRmt as a target for LYC treatment preventing DEHP-induced cardiac disease.