Association of insulin resistance with delirium and CSF biomarkers of Alzheimer's disease in elderly patients with hip fracture.
Delirium is associated with dementia, which shares symptoms of cognitive dysfunctions. Notably, pathological mechanisms of Alzheimer's disease (AD) appear involved in both conditions. Insulin resistance has been reported to be a risk factor for AD, leading to neurodegeneration and cognitive impairment by affecting amyloid-beta (Aβ) metabolism, tau phosphorylation, and neuro-inflammation. Thus, insulin resistance may provide pathophysiological clues to the occurrence of delirium. To investigate the relationship between preoperative insulin resistance, insulin concentrations in the cerebrospinal fluid (CSF), and delirium in elderly patients with hip fracture. The study included 138 elderly patients with or without pre-existing dementia who underwent hip fracture surgery. Delirium was diagnosed with the confusion assessment method performed daily from pre-operation to 5 days post-operation. CSF and blood samples were collected at the beginning of spinal anesthesia. The concentrations of insulin, amyloid-beta1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)181 were determined by ELISA. Homeostasis model assessment (HOMA-IR) was used to assess insulin resistance. Sixty-one (44%) of 138 hip fracture patients developed delirium peri-operatively. Compared to non-delirium group, the preoperative HOMA-IR index in delirium was much higher (median 3.3 vs 2.8, p = 0.001), but the CSF insulin concentration was significantly decreased (median 1.5 vs 2.2 mU/L, p < 0.001). Binary logistic regression analysis showed that HOMA-IR index and CSF insulin concentration were independent risk factors for delirium (p < 0.05). HOMA-IR index was negatively correlated with CSF insulin concentrations (rho = - 0.55, p < 0.001). Multiple linear regression analysis showed that AD core biomarkers were significantly correlated with HOMA-IR index and CSF insulin level (p < 0.05). This study innovatively examined insulin concentrations in serum and cerebrospinal fluid in patients with delirium. Our findings suggest that preoperative insulin resistance may affect the occurrence of delirium. The potential association between insulin resistance and delirium may be related to insulin resistance affecting the metabolism of AD biomarkers.


Asthma induced myocardial infarction in a patient with normal coronary arteries: a case report and a pathogenetic hypothesis.
A 57 year old white woman is reported who developed a myocardial infarction during an attack of allergic asthma and was subsequently found to have a normal coronary arteriogram. The literature on myocardial ischemia and infarction associated with structurally normal coronary arteries is reviewed with particular reference to prostaglandin production, histamine release, platelet activation and the induction of coronary vasospasm. A hypothesis is constructed to explain asthma induced myocardial infarction in terms of interrelated pathogenetic mechanisms.


Evaluation of the Nissen fundoplication for treatment of hiatal hernia: use of parietal cell vagotomy without drainage as an adjunctive procedure.
Twenty-nine patients who underwent Nissen fundoplication for the treatment of symptomatic, sliding, esophageal hiatal hernia are reported. Fourteen of these patients also underwent parietal cell vagotomy (PCV) without a drainage procedure. Simulatenous cineradiography and manometric studies, esophagoscopy and gastric analysis were performed pre- and postoperatively. Esophageal acid clearing and pH reflux studies were performed postoperatively. All but 3 patients had reflux and/or esophagitis preoperatively. Cineradiography and the pH reflux test were the most reliable tests for diagnosis of reflux. There was no operative mortality. The mean followup period was 20 months. Dysphagia occurred in 5 patients. Correction of dysphagia in one patient required operation. The dysphagia in the remaining patients was temporary and mild, responding to dilatation. Two patients had mild diarrhea. One patient who had had a previous gastric resection developed severe diarrhea after bilateral truncal vagotomy. No patient developed the "bloat syndrome". A close correlation did not exist between reflux and preoperative sphincter pressure. The mean LES pressure increased 10 mmH2O postoperatively and the two patients with persistent reflux postoperatively had normal LES pressure. Correction of reflux after Nissen fundoplication is probably due to some mechanism other than increased LES pressure. Recurrent or persistent hiatal hernia was diagnosed in 4 patients by cineradiography. Two of these patients had reflux but only the patient who had undergone PCV was without symptoms or esophagitis. The technical performance of the Nissen hiatal hernia repair was greatly facilitat ed by PCV. This procedure also provided adequate treatment for patients with concomitant duodenal ulcer disease. PCV, unaccompanied by a drainage procedure, was not associated with increased morbidity, mortality or the adverse effects usually attributed to vagotomy. In the event of recurrent hernia and reflux, PCV may prevent the development of esophagitis.


Molecular cloning, expression pattern, and phylogenetic analysis of a tetraspanin CD82-like molecule in lamprey Lampetra japonica.
CD82, a member of the tetraspanins, is originally identified as an accessory molecule in T cell activation, and it participates in the formation of immune synapse both in T cells and antigen-presenting cells of jawed vertebrates. In the present study, a CD82 homologous complementary DNA (cDNA) sequence is identified in the lamprey Lampetra japonica. The open reading frame of this sequence is 801 bp long and encodes a 266-amino acid protein. The multialignment of this sequence with several typical CD82s and CD37s of jawed vertebrates shows that it also possesses their conserved four transmembrane domains and a six-cysteine motif Cys-Cys-Gly…Cys-Ser-Cys…Cys…Cys, which is a characteristic motif of CD82 and CD37 vertebrate tetraspanin sequences. Since it is close to CD82s in sequence similarity, we name it as Lja-CD82-like. From the distribution profile of the conserved motifs of CD82-like, CD82, and CD37 molecules from molluscas to mammals, it seems that the CD82s and CD37s evolved from a common ancestral gene through a gene duplication event to their modern forms by a short insertion or substitution approaches. The phylogenetic analysis indicated that CD82 and CD37 molecules of jawed vertebrates originated from a common ancestral gene which is close to agnathan CD82-like and evolved into two distinct paralogous groups maybe after the divergence of jawed and jawless vertebrates. An expression vector with trigger factor (TF) was constructed to ensure that Lja-CD82-like express in prokaryotic expression host. The expressions of Lja-CD82-like messenger RNA (mRNA) and protein in immune-related tissues of lamprey were detected by real-time quantitative polymerase chain reaction and western blotting. Results showed that the mRNA and the protein levels of Lja-CD82-like were significantly upregulated in lymphocyte-like cells, gills, and supraneural myeloid bodies after stimulation with mixed antigens, respectively. Our data provided a foundation for the further study of Lja-CD82-like and its role in immune response process of jawless vertebrates.


In vivo delivery of cell-permeable antisense hypoxia-inducible factor 1α oligonucleotide to adipose tissue reduces adiposity in obese mice.
Ongoing research has gradually recognized and understood the importance of adipose tissue (AT) angiogenesis as a key modulating factor of adipogenesis in the development of obesity. Previously, we carried out the first in vitro demonstration of the down-regulation of hypoxic angiogenesis during adipogenesis using cell-permeable chemical conjugates composed of antisense hypoxia-inducible factor 1α (HIF1α) oligonucleotide (ASO) and low-molecular weight protamine (LMWP). To further confirm the in vivo feasibility, we administered ASO-LMWP conjugates (AL) to diet-induced obese (DIO) mice by intraperitoneal injection (IP). Results showed that the AL conjugates significantly reduced the body weight, total fat tissue weight, and plasma lipid concentrations in the mice. Moreover, the AL conjugates not only decreased liver weight and hepatic triglyceride concentration but also significantly attenuated subcutaneous adipocyte cell size, which was conversely increased in the AL-untreated high-fat diet (HFD) group. Interestingly, more blood vessels were observed in the HFD group than in the lean group, indicating that blood vessel development could induce growth of the fat mass. This pattern was reversed in the AL-treated groups, which displayed a decrease in blood vessel density compared to the AL-untreated HFD group. This study presents the first in vivo evidence, in an obese mouse model, of the feasibility of achieving a biological treatment modality for obesity by blocking the angiogenic transcriptional factor HIF1α, thereby limiting angiogenesis, via the use of an adipose tissue-permeable ASO-LMWP.


Residential proximity to high-traffic roadways and poststroke mortality.
Living in areas with higher levels of ambient air pollution has been associated with a higher incidence of ischemic stroke and all-cause mortality but less is known about the relationship between traffic-related pollution and long-term survival after stroke. We identified consecutive patients admitted to Beth Israel Deaconess Medical Center with ischemic stroke between 1999 and 2008 and determined the distance to the nearest roadway with an average daily traffic count of more than 10,000 vehicles/day. Categories of residential proximity were defined as 100 m or less, 100-200 m, 200-400 m or less, or more than 400 m from a busy roadway. We identified deaths through June 2012 using the Social Security Death Index and used Cox proportional hazards models adjusted for medical history and socioeconomic factors to calculate hazard ratios for the association between residential proximity to a high-traffic roadway and all-cause mortality. Among 1683 stroke patients with complete data, there were 950 deaths (median follow-up=4.6 years). We observed higher poststroke mortality among people living closer to high-traffic roadways. Patients living 100 m or less from high-traffic roadways had a 20% (95% confidence interval: 1%, 43%) higher rate of poststroke mortality than patients living more than 400 m away (P trend=.02). In this study, living close to a high-traffic roadway was associated with an elevated mortality rate. This relationship remained statistically significant after adjustment for individual- and neighborhood-level factors, providing evidence that traffic-related pollution is associated with a higher mortality rate among stroke survivors.


The three 5S rRNA genes from the human malaria parasite Plasmodium falciparum are linked.
5S rRNA and rDNA from Plasmodium falciparum have been characterized. The 5S rRNA transcripts isolated from erythrocytic stage parasites are composed of three distinct subclasses, 117-119 nucleotides in length, which are identical in sequence with the exception of one or two additional uridine residues at the 3' terminus. Southern blot analysis of genomic DNA identified three 5S rRNA gene classes which are clustered within 1.5 kb of DNA. Cloning and sequence analyses of the 5S rDNA revealed identical coding regions surrounded by divergent extremely A+T rich flanking sequences (greater than 90%). Typical PolIII termination signals (6-8) T residues abut each coding region. Copy number analysis indicates that P. falciparum contains only three 5S rRNA genes, the lowest number reported for any organism.


Hemostaseological management of urological operations in patients taking aspirin using the Thrombostat 4000.
A clinical study was started in order to examine the suitability of the Thrombostat (in vitro bleeding test) (IVBT) as a diagnostic tool to prevent perioperative bleeding due to aspirin (ASA) and/or platelet function disorders of other origins. This report is based on preliminary data. Eighty three patients who had ingested ASA in the last two weeks and/or with a history of bleeding and/or documented hemorrhagic disorders requiring distinct urological operations, were included in the study. In all patients the IVBT with CaCl2, in addition to common coagulation tests, were performed. Thirteen patients stopped ASA ingestion until IVBT became normal and did not show any increased bleeding tendency. The residual patients were classified by the various operations. The following operation groups were formed: Male genitals (n = 11), inguinal/suprapubic operations (n = 7), transurethral tumor resections of the bladder (TURB) (n = 17), transurethral prostate resection (TURP) (n = 12), tumor nephrectomy (n = 8), radical prostatectomy (n = 9). Thirty six patients with a history of ASA use, but normal IVBT, served as control group (C). Thirty one patients with a history of ASA ingestion had normal in vivo bleeding times (BT) and abnormal IVBT with CaCl2 (A). Seven patients had a bleeding history and/or documented hemorrhagic disorders (B). None of the patients (A) with abnormal IVBT but normal BT displayed clinically relevant bleeding. However, the blood loss was somewhat higher compared to the controls (C), especially in patients with TURB and radical prostatectomy (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)


MicroRNA-377 Mediates Cardiomyocyte Apoptosis Induced by Cyclosporin A.
Cyclosporin A (CsA) is a potent immunosuppressant that has wide clinical applications for autoimmune disorders and prevention of rejection in organ transplantation. However, its liver, kidney, and heart toxicity has limited its use. In this study, we investigated the mechanism by which CsA induced cardiomyocyte apoptosis. Through microarray analysis, we found that the expression of microRNA (miR)-377 was regulated by CsA. Ectopic overexpression of miR-377 led to increased apoptosis in cardiomyocytes, as evidenced by an increased number of apoptotic cells, increased levels of proapoptotic proteins, decreased levels of antiapoptotic proteins, and elevated caspase pathway activity. We also found that miR-377 was required for CsA-induced apoptosis, because inhibition of miR-377 expression markedly reduced the ability of CsA to induce cardiomyocyte apoptosis. In addition, we identified XIAP and NRP2 as direct targets for miR-377. The expression levels of these 2 antiapoptotic proteins were negatively regulated by miR-377, as well as by CsA both in vitro and in vivo. Our data suggested that CsA induced cardiomyocyte apoptosis through the miR-377-XIAP/NRP2 axis.


Neuronavigation with the universal probe to access intracranial targets.
The universal probe is a tool devised to allow navigation-directed biopsies and drainage procedures to be performed in a simple manner using a single hardware and software. To assess the efficacy and safety of the universal probe. We used the universal probe in a total of 17 patients for 10 biopsies and 8 drainage procedures. We were able to achieve our set objectives in all 18 procedures. We did not encounter any complications using this device. The universal probe enabled a variety of navigation-based procedures to be carried out using only a single software and hardware.


Apoptosis is associated with triacylglycerol accumulation in Jurkat T-cells.
Magnetic resonance spectroscopy is increasingly used as a non-invasive method to investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. (1)H magnetic resonance spectra of live cells showed an increase in methylene signal as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h following induction of apoptosis. To explain this observation, (1)H magnetic resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/-7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of triacylglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal microscopy images of cells stained with the lipophilic dye Nile Red demonstrated the presence of lipid droplets in the cell cytoplasm. Quantification of the stained lipids by flow cytometry showed a good correlation with the magnetic resonance results (P > or =0.05 at 3, 5 and 7 h). (31)P magnetic resonance spectra showed a drop in phosphatidylcholine content of apoptosing cells, indicating that alteration in phosphatidylcholine metabolism could be the source of triacylglycerol accumulation during apoptosis. In summary, apoptosis is associated with an early accumulation of mobile triacylglycerols mostly in the form of cytoplasmic lipid droplets. This is reflected in an increase in the methylene/methyl ratio which could be detected by magnetic resonance spectroscopy.


The retention and metabolism of N tau-methylhistidine by cockerels: implications for the measurement of muscle protein breakdown determined from the excretion of N tau-methylhistidine in excreta.
Excreta were collected for four consecutive days from 4- to 18-week-old cockerels following subcutaneous injection of N tau-[14CH3]methylhistidine. The recoveries of radioactivity in excreta were incomplete and progressively decreased with increasing age. Most of the radioactivity not recovered in excreta after 4 d was found in skeletal muscle where greater than 55% of the radioactivity present was in the N tau-methylhistidine-containing dipeptide, balenine. This peptide appeared to be relatively stable so that most of the labelled N tau-methylhistidine incorporated was not released during the period of the recovery measurements. The total pool of non-protein bound N tau-methylhistidine (free (free N tau-methylhistidine + balenine) in pectoral and mixed thigh muscles increased with age and relative to the daily excretion of N tau-methylhistidine. At 18 weeks the pool was 3.3 times the daily excretion of N tau-methylhistidine. These observations account for the decreasing recoveries of radioactivity in excreta described previously, due to progressive dilution of labelled N tau-methylhistidine in an expanding pool of non-protein-bound N tau-methylhistidine, part of which was relatively stable. It is concluded that excretion of N tau-methylhistidine by 4- to 18-week-old cockerels cannot be used as a reliable index of muscle protein breakdown in vivo.


Impact of cholecystectomy on acute coronary syndrome according to metabolic condition: a nationwide population-based cohort study.
Gallbladder stones (GS) is associated with an increased risk of cardiovascular disease. However, the relationship between cholecystectomy for GS and acute coronary syndrome (ACS) is unknown. We investigated the ACS risk in patients with GS and its association with cholecystectomy. Data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013 was extracted. Overall, 64,370 individuals were selected through a 1:3 propensity score matching. Patients were stratified into two groups for comparison: the gallstone group, GS patients with or without cholecystectomy; and the control group, patients without GS or cholecystectomy. The gallstone group exhibited a higher risk of ACS than the control group (hazard ratio [HR], 1.30; 95% confidence interval [CI] 1.15-1.47; P < 0.0001). In the gallstone group, individuals without cholecystectomy had a higher risk of ACS development (HR: 1.35, 95% CI 1.17-1.55, P < 0.0001). Patients with GS with diabetes, hypertension, or dyslipidemia, had a higher risk of developing ACS than GS patients without the metabolic diseases (HR: 1.29, P < 0.001). The risk did not significantly differ after cholecystectomy compared to those without GS (HR: 1.15, P = 0.1924), but without cholecystectomy, the risk of ACS development was significantly higher than control group (1.30, 95% CI 1.13-1.50, P = 0.0004). Among patients without above metabolic disorders, cholecystectomy was still associated with increased ACS risk in the gallstone group (HR: 2.93, 95% CI 1.27-6.76, P = 0.0116). GS increased the risk of ACS. The effect of cholecystectomy on ACS risk differs according to the presence or absence of metabolic disorders. Thus, the decision to perform cholecystectomy for GS should consider both the ACS risk and the underlying disorders.


Study on a fluorescence-enhanced system of 1,2,4-trihydroxyanthroquinone-Be(2+)-DNA.
Fluorescence-enhancement of 1,2,4-trihydroxyanthroquinone (THAQ)-Be2+ complex enhanced by nucleic acid was studied. Experimental results revealed that double-stranded DNA can enhance remarkably the fluorescence intensity of THAQ-Be2+, while RNA cannot. Based on these results, a fluorescence method for the selective determination of DNA in the presence of RNA was developed. Maximum fluorescence intensity was found in the pH range 3.6-4.5 with maximum excitation and emission wavelengths at 510 and 565 nm, respectively. Under optimum conditions, the calibration graph was linear over the range 0.08-18 micrograms ml-1 for double-stranded fish sperm DNA (fsDNA) with the detection limit being 2.75 x 10(-8) g ml-1. The method was applied for the determination of DNA in synthetic samples. The relative S.D. for five replicates was within 4%. In addition, the interaction mechanism of THAQ-Be2+ with DNA was also discussed.


Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.
In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups.


Same day discharge after pediatric laparoscopic appendectomy in community hospitals.
Same-day discharge (SDD) protocols after pediatric laparoscopic appendectomy have not been well studied in a community hospital setting, especially when hospitals with low inpatient pediatric censuses are increasingly closing their pediatric units. This study evaluates the outcomes of a SDD protocol after pediatric appendectomy that was implemented across an integrated healthcare system in which hospitals experienced closure of pediatric units. Patients between ages 6 to 13 years-old who underwent laparoscopic appendectomy for uncomplicated appendicitis from January 1st 2015 to December 31st 2020 were reviewed. During the study period, an inter-hospital SDD protocol was introduced at nine hospitals, four of which closed their pediatric units. There were 1293 patients in the pre-protocol cohort and 953 patients in the post-protocol cohort. There were 588 (45.5%) patients who underwent SDD in the pre-protocol cohort, compared with 804 (84.4%) patients in the post-protocol cohort (p<0.00001). Postoperative narcotics were prescribed to 358 (27.7%) patients in the pre-protocol cohort, compared to 482 (50.6%) patients in the post-protocol cohort (P<0.00001). There was no difference in the 30-day emergency department visit rate or 30-day readmission rate between the two cohorts. A subgroup analysis comparing the surgical outcomes at community hospitals with and without pediatric units after implementation of the SDD protocol showed no difference. Same-day discharge after laparoscopic appendectomy for uncomplicated appendicitis in community hospitals, even after pediatric unit closure, is safe and feasible. The decrease in postoperative LOS and the increase in SDD are not associated with higher complication rates.


How often do women in the emergency department without intimate violence injuries return with such injuries?
To determine the rate at which a group of women visiting the ED for reasons other than intimate violence return to the ED at a later time for intimate-violence-related injuries. Retrospective cohort study of a group of women with intimate-violence-related injuries on an index visit and a matched comparison group. Return visit rates to the ED for intimate violence injuries over the next 5 years were then compared. The 95 women in each group were followed an average of 57 months. The return rates in the positive index case group and matched comparison group, respectively, for any reason were 74.9% vs 77.9% (p = 0.463) and for intimate violence injuries were 29.5% vs 18.9% (p = 0.118). Women in the ED without intimate violence injuries often return to the ED later with such injuries. This suggests the ED may play an important role in identifying women at risk for future intimate-violence-related injury.


Mild cognitive impairment and dementia in motor manifest Huntington's disease: Classification and prevalence.
To identify the characteristics and prevalence of mild cognitive impairment in patients with motor-manifest Huntington's disease (HD) and to propose a new mild cognitive impairment (HD-MCI) classification for HD. We included 307 motor-manifest HD participants from the ENROLL-HD study who completed the evaluation in four neurocognitive domains including executive functions, processing speed, language, and memory. Cognitive impairment in each domain was determined by age- and education-adjusted cutoffs (> 1.5 standard deviations below the mean). HD-MCI was defined as an impairment in at least one cognitive domain without a loss of functional independence (Function Independence Scale, FIS ≥85). Dementia (HD-Dem) was defined as at least two domains of cognitive impairment with functional impairment (FIS ≤80). At the onset of motor symptoms, MCI was present in 84% and dementia in 5% of patients. After 5 years of motor symptoms, 24% of participants met the criteria for MCI and 69% for dementia. Executive dysfunction was the most common impairment, being present in 70% of participants, followed by slowed processing speed in 67%. Language impairment was reported in 55% and memory deficits in 53%. MCI subtypes were classified as "Executive-predominant" (executive impairment and slowed processing speed), "Representational-predominant" (impaired language and memory) and "Mixed Executive-Representational". Executive-predominant MCI comprised 30%, Representational-predominant 15% and Mixed 55% of this cohort. MCI is highly prevalent in the early stage of motor-manifest HD. Three MCI subgroups are defined suggesting at the earlier stage of this disease the frontal-striatal-executive and/or the temporoparietal-representational functional network can be impaired.


Design, synthesis and biological activity of novel non-peptidyl endothelin converting enzyme inhibitors, 1-phenyl-tetrazole-formazan analogues.
A novel non-peptidyl endothelin converting enzyme inhibitor was obtained through a pharmacophore analysis of known inhibitors and three-dimensional structure database search. Analogues of the new inhibitor were designed using the structure-activity relationship of known inhibitors and synthesized. In anesthetized rats, intraperitoneal administration of the analogues suppressed the pressor responses induced by big endothelin-1.


Reactions of 1-methylbenzimidazole derivatives with m-chloroperoxybenzoic acid.
Oxidation of seven 1-methylbenzimidazole (MBI) derivatives (with pKa's ranging from 1.6 to 6.0) was carried out with m-chloroperoxybenzoic acid and structures of the products formed were identified. (Condensed benzene moiety-hydroxylated)-2-(m-chlorobenzyloxy)-MBIs and 2-oxo-MBIs were obtained from MBIs with pKa's of more than 5.6 and about 3.3, respectively.


Environmental stimuli affecting expression of the Ysa type three secretion locus.
Yersinia enterocolitica has two type III secretion systems (TTSS): The well characterized Ysc-Yop system and the relatively uncharacterized Ysa-Ysp system. Detection of Ysps in culture supernatants has only been observed in vitro when cultures are grown at low temperature (26 degrees C) and in high salt (290mM NaCl). Previous reports demonstrated that expression from the ysaE promoter was activated by high salt. In this study, we report a new environmental stimulus for ysa gene expression; in the presence of high salt, growth on solid surface stimulates expression 7-fold compared to growth in high salt broth. These new data indicate that, in the presence of salt, solid surface is an extremely robust signal for the Ysa system.


Determination of Endogenous Concentrations of Uracil and Dihydrouracil in Dried Saliva Spots by LC-MS/MS: Method Development, Validation, and Clinical Application.
The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the measurement of uracil (U) and dihydrouracil (UH2) concentrations in dried saliva spots (DSSs), for the evaluation of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Nine 18-mm diameter DSS discs were extracted with acetate:isopropyl alcohol (85:15, vol/vol) and analyzed by LC-MS/MS. The assay was linear in the range of 10-1000 ng·mL, with accuracy between 89% and 112% and precision between 5.7% and 13%. The metabolic ratio [UH2]/[U] was stable in DSS for up to 9 days at 45°C. Concentrations of U and UH2, as well as the metabolic ratio, were highly concordant between matrices. Using a metabolic ratio classification cutoff of 1.16 for the identification of slow DPD metabolizers, 98.7% concordance was achieved between SS and saliva. DSS samples could be a useful alternative for DPD activity screening, particularly in locations with limited access to highly equipped laboratories.


Unprecedented One-Pot Reaction towards Chiral, Non-Racemic Copper(I) Complexes of [2.2]Paracyclophane-Based P,N-Ligands.
Herein, we report a simple one-pot route to enantiopure copper(I) complexes featuring a unique [2.2]paracyclophane-based P,N-ligand system. Phosphine and pyridine moieties can be varied allowing the modular synthesis of these rigid and stable [2.2]paracyclophane-based P,N-ligands. These P,N-ligands are a new ligand class for different transition-metal complexes, which is shown exemplarily for palladium(II).


Transmission and contraction fatigue of rat motor units in relation to succinate dehydrogenase activity of motor unit fibres.
1. The fatigue in rat anterior tibial (a.t.) motor units was studied and related to microphotometric determinations of succinate dehydrogenase (SDH) activity of the motor unit muscle fibres. 2. Anterior tibial contains fast-twitch type II fibre units with an average contraction time of 11 msec and about 5% slow-twitch type I fibre units with an average contraction time of 20 msec. 3. In type II fibres stained for SDH, absorbance varied continuously from 0.046 to 0.569 and inversely to fibre size, except for the largest fibres. 4. Resistance to fatigue of fast motor units to 100 Hz intermittent stimulation varied continuously within a wide range in near linear relations to absorbance for SDH of unit fibres and inversely to tetanic tension, except for motor units with the largest fibres and the largest tetanic tension. 5. Neither resistance to fatigue nor SDH activity lent itself to any categorization of motor units or fibres into well demarcated functional or histochemical types, since both parameters varied continuously in the unit and fibre population of the muscle. 6. The direct relation between resistance to fatigue of fast-twitch motor units and SDH activity of unit fibres appeared valid for fatigue resistance of: (a) neuromuscular transmission, tested with 100 Hz intermittent stimulation which gave concomitant failure of electrical and mechanical response, (b) excitation--contraction coupling, demonstrated by post-stimulatory depression of twitch tension with preserved maximum tetanus tension and action potential, and (c) contractile mechanism; excitation--contraction coupling?, tested with low frequency stimulation which gave decline of twitch and maximum tetanus tension with preserved action potential. 7. It is suggested that the endurance of each link in the chain of events leading to contraction, including neuromuscular junction and the excitation--contraction coupling system, is under aerobic conditions matched to the contractile capacity of the fibre expressed by its oxidative enzyme activity.


Thermal nociception and TRPV1 function are attenuated in mice lacking the nucleotide receptor P2Y2.
Recent studies indicate that ATP and UTP act at G protein-coupled (P2Y) nucleotide receptors to excite nociceptive sensory neurons; nucleotides also potentiate signaling through the pro-nociceptive capsaicin receptor, TRPV1. We demonstrate here that P2Y(2) is the principal UTP receptor in somatosensory neurons: P2Y(2) is highly expressed in dorsal root ganglia and P2Y(2)-/- mice showed profound deficits in UTP-evoked calcium transients and potentiation of capsaicin responses. P2Y(2)-/- mice were also deficient in the detection of painful heat: baseline thermal response latencies were increased and mutant mice failed to develop thermal hypersensitivity in response to inflammatory injury (injection of complete Freund's adjuvant into the hindpaw). P2Y(2) was the only Gq-coupled P2Y receptor examined that showed an increase in DRG mRNA levels in response to inflammation. Surprisingly, TRPV1 function was also attenuated in P2Y(2)-/- mice, as measured by the frequency and magnitude of capsaicin responses in vitro and behavioral responses to capsaicin administration in vivo. However, TRPV1 mRNA levels and immunoreactivity were not reduced, and behavioral sensitivity to capsaicin could be largely restored in P2Y(2)-/- mice by pretreatment with bradykinin, suggesting that normal function of TRPV1 requires ongoing modulation by G protein-coupled receptors. These results indicate that nucleotide signaling through P2Y(2) plays a key role in thermal nociception.


Bone and the perimenopause.
Loss of ovarian function has a profound impact on female skeletal health. Bone mineral density findings from the Study of Women's Health Across the Nation demonstrate an accelerated rate of bone loss during the menopausal transition. The greatest reduction occurs in the year before the final menstrual period and the first 2 years thereafter. Clinical management includes maintenance of adequate dietary calcium and vitamin D intake, attention to modifiable risk factors, and osteoporosis screening. Indications, benefits, and risks of pharmacologic osteoporosis therapy should be assessed individually; there are currently no established guidelines addressing the treatment and prevention of osteoporosis in perimenopausal women.


Novel Biomarkers for Non-functioning Invasive Pituitary Adenomas were Identified by Using Analysis of microRNAs Expression Profile.
The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future.


A non-stereotaxic method for olfactory bulb kindling reveals distinct kindling rates among inbred mouse strains.
A simple method for olfactory bulb kindling in the unrestrained mouse is described. Twisted wire electrodes attached to a dip-socket head assembly were implanted in the olfactory bulb. A ground lead was secured to a single skull screw and implantation was visually guided into the olfactory bulb. In all properly implanted preparations, stimulation produced an afterdischarge with behavioral responses which progressed to fully kindled convulsions. Location within the olfactory bulb did not affect the kindling rate. With this technique, mice from the C57BL/6J, C3H/He and DBA/2 inbred strains were kindled. Within each strain, kindling parameters were closely distributed about the group mean. Kindling rates in C3H and DBA inbred strains were significantly different from each other, but not significantly different from those reported in amygdala kindling.


Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse.
Spermiogenesis is the differentiation of spermatids into motile sperm consisting of a head and a tail. The head harbors a condensed elongated nucleus partially covered by the acrosome-acroplaxome complex. Defects in the acrosome-acroplaxome complex are associated with abnormalities in sperm head shaping. The head-tail coupling apparatus (HTCA), a complex structure consisting of two cylindrical microtubule-based centrioles and associated components, connects the tail or flagellum to the sperm head. Defects in the development of the HTCA cause sperm decapitation and disrupt sperm motility, two major contributors to male infertility. Here, we provide data indicating that mutations in the gene Coiled-coil domain containing 42 (Ccdc42) is associated with malformation of the mouse sperm flagella. In contrast to many other flagella and motile cilia genes, Ccdc42 expression is only observed in the brain and developing sperm. Male mice homozygous for a loss-of-function Ccdc42 allele (Ccdc42(KO)) display defects in the number and location of the HTCA, lack flagellated sperm, and are sterile. The testes enriched expression of Ccdc42 and lack of other phenotypes in mutant mice make it an ideal candidate for screening cases of azoospermia in humans.


[Adult prostate sarcoma: a report of 6 cases with clinical analysis].
To investigate the diagnosis, treatment and prognosis of sarcoma of the adult prostate. We reported 6 cases of sarcoma of the adult prostate, of which 3 were leiomyosarcoma, 2 rhabdomyosarcoma and 1 malignant neurilemoma, 2 at Ghavimi Stage II, 3 at Stage III and 1 at Stage IV. The patients were aged from 18 to 44 years (mean 31 years) and their disease course ranged from 3 to 12 months (mean 7 months). Five of them received operation, radiotherapy and / or chemotherapy and 1 underwent cystostomy only. Immunohistochemical dyeing showed vimentin to be positive while PSA and PAP negative in all the 6 cases, actin (HHF35) positive in the cases of leiomyosarcoma and rhabdomyosarcoma, and S-100 and lysozyme positive in the case of malignant neurilemoma. One case failed to be followed up, and the other 5 died 2-11 months after the operation. Sarcoma of the adult prostate initiates with the symptom of progressive dysuria, which can be diagnosed by DRE test and confirmed by needle biopsy. Early diagnosis and radical surgical resection may offer the best chance of survival, but with poor prognosis.


Transcardiac passage of thrombus--ultrasonographic visualization.
A patient is described in whom a right atrial thrombus was seen, by two-dimensional echocardiography, in the act of embolizing into the pulmonary circulation.


[Erythrocyte concentrates as substitutes of whole blood; changes in transfusion methods in a regional hospital (author's transl)].
In Switzerland the amount of blood donations is determined by the demands for plasma; as a result there is a surplus of erythrocyte concentrates for which more uses should be found. Trials in a regional general hospital proved that these concentrates can be advantageously employed in the field of surgery and anasthesia: due to close cooperation between the clinical department and the blood donor sevice the demand for erythrocyte concentrates rose from 5 per cent to 80 per cent within 5 years.


[Stduy on flavonoids in Ligustrum lucidum].
To study chemical constituents of fruits of Ligustrum lucidum. The chemical components were isolated and purified by silica gel and sephadex LH-20 column chromatogram. The chemical structures were elucidated on the basis of physic-chemical properities and spectral data. Seven flavonoids were isolated and identified as apigenin(I), cosmosiin(II), apigenin-7-O-acetyl-beta-D-glucoside(III), apigenin-7-O-beta-D-lutinoside (IV), luteolin (V), luteolin-7-O-beta-D-glucopyranoside (VI), quercetin(II). Compounds II, IV, V were obtained from the fruits of the plant for the first time.


[Evaluation of Detectability in Clinical Practice of Metal Detectors, etc. for Magnetic Resonance Imaging].
In order to prevent magnetic materials from being brought into the magnetic resonance imaging (MRI) examination room, many facilities have metal detectors, etc., but there are various types of equipment with different performance and characteristics. The purpose of this study was to evaluate each detector in actual clinical practice. At multiple facilities, gate-type magnetic detectors, pole-type magnetic detectors, handy-type magnetic detectors, and handy-type metal detectors were used to identify 9 types of objects that may be brought into the MRI examination room. We performed evaluation of detection distance measurement assuming actual operation. The gate type was only able to detect objects with strong magnetism. With the pole type, the closer the measurement distance was to the pole, the more objects could be detected, and the lower the pole, the shorter the detection distance. With the handy type, there were many objects that could be detected when the device and the object were brought into close contact. The detectability of the instruments varied depending on the size and type of the object. It is important to understand the characteristics of each device and use it according to the purpose in carrying-in confirmation before the examination.


Increased vitamin D-binding protein and decreased free 25(OH)D in obese women of reproductive age.
Obese subjects have lower circulating 25-hydroxyvitamin D (25(OH)D) than normal-weight subjects. Knowledge is scarce regarding differences in vitamin D-binding protein (DBP), free 25(OH)D, and intake of vitamin D between normal-weight and obese subjects. The purpose of this study was to examine intake and vitamin D status in obese compared with normal-weight women. Between September 2009 and October 2011, 43 obese and 43 normal-weight women, 22-45 years of age, mean BMI of 39.1 ± 4.6 and 21.6 ± 1.8 kg/m(2), respectively, were recruited in the western Sweden region (latitude 57°N). Blood samples, data regarding diet, and sun exposure were collected. DBP concentrations were 320 ± 121 and 266 ± 104 μg/mL (P = 0.02) in obese and normal-weight women, respectively. Calculated free 25(OH)D was 13.3 ± 5.5 (obese) and 23.7 ± 10.7 (normal-weight) (P < 0.001). The obese women had a 20.1 nmol/L lower mean 25(HO)D concentration compared to normal-weight women (P < 0.001). 56 % of obese women and 12 % of normal-weight women had 25(OH)D concentrations ≤50 nmol/L. There was no statistically significant difference in total vitamin D intake between the groups. 39 % of the women had a total vitamin D intake <7.5 μg/day, the current national recommendation for vitamin D in Sweden. Obese women had higher DBP concentrations compared with normal-weight women and lower free 25(OH)D. The obese women were more likely to have 25(OH)D concentrations that could be considered suboptimal. Vitamin D intake was generally low in normal-weight and obese women of childbearing age.


Sb2S3 nanoparticles anchored on SnO2 nanofibers: a high-performance hybrid electrocatalyst toward ammonia synthesis under ambient conditions.
Herein, we report a novel transition-metal-based electrocatalyst, Sb2S3 nanoparticles, which exhibits electrocatalytic activity toward ammonia synthesis under ambient conditions. These Sb2S3 nanoparticles are further anchored on SnO2 nanofibers, which act as an active substrate to prevent them from aggregation while enhancing the electrocatalytic activity. The obtained Sb2S3@SnO2 nanofibers deliver excellent ammonia yield (22.0 μg h-1 mgcat-1) and faradaic efficiency (15.1%) at -0.4 V vs. RHE in 0.1 M Na2SO4.


Teenagers' knowledge about HPV infection and HPV vaccination in the first year of the public vaccination programme.
The aim of this study was to assess teens' knowledge of HPV infection and vaccination one year after the initiation of the public vaccination programme and information campaign on the disease and the opportunity of vaccination. Between 15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending high schools in a town in the northeast of Italy by means of an anonymous and unannounced questionnaire covering the knowledge of HPV infection, transmission, prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew what HPV infection is (92% of girls vs 51% of boys, p < 0.001); only 70% knew that it is a sexually-transmitted infection. Only 69.3% associated condoms with HPV disease prevention (72.6% girls vs 61.5% boys, p = 0.002). About 18.8% of girls and 33.2% of boys believe that HPV can lead to AIDS (p < 0.001). Among teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it can prevent AIDS (p < 0.001). Only 75.5% of girls and 51.1% of boys (p < 0.001) believe that condom use remains useful for HPV prevention after vaccination. The need for regular pap smears after vaccination is reported by 93.3% of girls. Teens' knowledge about HPV infection and vaccination remains insufficient, despite a broad information campaign. Erroneous information may increase risky sexual behaviours. Without complete information about HPV infection and vaccination and information about other sexually-transmitted diseases, the latter might become difficult to control among teenagers, while some misunderstandings about the usefulness of secondary prevention might linger.


Brachycephalic Obstructive Airway Syndrome.
Dogs presenting with brachycephalic obstructive airway syndrome suffer from multilevel obstruction of the airway as well as secondary structural collapse. Stenotic nares, aberrant turbinates, nasopharyngeal collapse, soft palate hyperplasia, macroglossia, tonsillar hypertrophy, laryngeal collapse, and left bronchial collapse are described as the most common associated anomalies. Rhinoplasty and palatoplasty as well as newer surgical techniques and prudent preoperative and postoperative care strategies have resulted in significant improvement even in middle-aged dogs.


Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry.
Determination of quantitative changes in the pattern of serum bile acids is important for the monitoring of diseases affecting bile acid metabolism. A sensitive and specific high-performance liquid chromatography (HPLC)-MS/MS method was developed for the differentiated quantification of unconjugated as well as glycine- and taurine-conjugated cholic, chenodeoxycholic (CDCA), deoxycholic (DCA), ursodeoxycholic (UDCA) and lithocholic acid (LCA) in serum samples. After solid-phase extraction and reversed-phase HPLC separation, detection of the conjugated bile acids was performed using electrospray ionization (ESI)-MS/MS and selected reaction monitoring mode, whereas unconjugated bile acids were determined by ESI-MS and selected ion monitoring mode. The within-day and between-day coefficients of variation were below 7% for all bile acids and the recovery rates of the extraction procedure were between 84.9 and 105%. The developed method was applied to a group of 21 healthy volunteers and preliminary reference intervals in serum were established. In patients with drug-induced cholestasis, an elevation of primary bile acids has been shown.


Power and sample size calculation for incremental net benefit in cost effectiveness analyses with applications to trials conducted by the Canadian Cancer Trials Group.
Historically, a priori power and sample size calculations have not been routinely performed cost-effectiveness analyses (CEA), partly because the absence of published cost and effectiveness correlation and variance data, which are essential for power and sample size calculations. Importantly, the empirical correlation between cost and effectiveness has not been examined with respect to the estimation of value-for-money in clinical literature. Therefore, it is not well established if cost-effectiveness studies embedded within randomized-controlled-trials (RCTs) are under- or over-powered to detect changes in value-for-money. However, recently guidelines (such as those from ISPOR) and funding agencies have suggested sample size and power calculations should be considered in CEAs embedded in clinical trials. We examined all RCTs conducted by the Canadian Cancer Trials Group with an embedded cost-effectiveness analysis. Variance and correlation of effectiveness and costs were derived from original-trial data. The incremental net benefit method was used to calculate the power of the cost-effectiveness analysis, with exploration of alternative correlation and willingness-to-pay values. We identified four trials for inclusion. We observed that a hypothetical scenario of correlation coefficient of zero between cost and effectiveness led to a conservative estimate of sample size. The cost-effectiveness analysis was under-powered to detect changes in value-for-money in two trials, at willingness-to-pay of $100,000. Based on our observations, we present six considerations for future economic evaluations, and an online program to help analysts include a priori sample size and power calculations in future clinical trials. The correlation between cost and effectiveness had a potentially meaningful impact on the power and variance of value-for-money estimates in the examined cost-effectiveness analyses. Therefore, the six considerations and online program, may facilitate a priori power calculations in embedded cost-effectiveness analyses in future clinical trials.


Interaction between 30 S ribosomal components in a viomycin resistant mutant of Mycobacterium smegmatis.
A high level viomycin resistant mutant of Mycobacterium smegmatis ATCC 14468 (AC16) was analyzed genetically and biochemically in an attempt to understand the mechanisms of expression of high level viomycin resistance and co-resistance to kanamycin and streptomycin. Genetic analysis has shown that at least three different genes (vicC, str, and kan) were involved in the phenotypic expression of drug resistance in AC16, and high level resistance to viomycin was due to interactions between the products of these genes.


Highly purified mussel adhesive protein to secure biosafety for in vivo applications.
Unique adhesive and biocompatibility properties of mussel adhesive proteins (MAPs) are known for their great potential in many tissue engineering and biomedical applications. Previously, it was successfully demonstrated that redesigned hybrid type MAP, fp-151, mass-produced in Gram-negative bacterium Escherichia coli, could be utilized as a promising adhesive biomaterial. However, purification of recombinant fp-151 has been unsatisfactory due to its adhesive nature and polarity which make separation of contaminants (especially, lipopolysaccharide, a toxic Gram-negative cell membrane component) very difficult. In the present work, we devised a high resolution purification approach to secure safety standards of recombinant fp-151 for the successful use in in vivo applications. Undesirable impurities were remarkably eliminated as going through sequential steps including treatment with multivalent ion and chelating agent for cell membrane washing, mechanical cell disruption, non-ionic surfactant treatment for isolated inclusion body washing, acid extraction of washed inclusion body, and ion exchange chromatography purification of acid extracted sample. Through various analyses, such as high performance liquid chromatographic purity assay, limulus amoebocyte lysate endotoxin assay, and in vitro mouse macrophage cell tests on inflammation, viability, cytotoxicity, and apoptosis, we confirmed the biological safety of bacterial-derived purified recombinant fp-151. Through this purification design, recombinant fp-151 achieved 99.90% protein purity and 99.91% endotoxin reduction that nearly no inflammation response was observed in in vitro experiments. Thus, the highly purified recombinant MAP would be successfully used as a safety-secured in vivo bioadhesive for tissue engineering and biomedical applications.


Bioindication: a short review on the use of plants as indicators of heavy metals.
This paper discusses some fundamental principles of bioindication. The presentation follows a classification of methods based on the different levels of organization implied in the various approaches. Special references are made to plants that accumulate heavy metals.


Brain lesions with elevated lactic acid peaks on magnetic resonance spectroscopy.
Magnetic resonance (MR) spectroscopy is a noninvasive imaging tool that provides information on various metabolite concentrations within brain lesions. The biochemical information obtained with MR spectroscopy, along with the morphologic appearance of a lesion on MR imaging, allows for better characterization and improved diagnostic ability. Lactic acid is an end product of anaerobic metabolism. Under conditions of anaerobic metabolism or inflammation, lactate levels become elevated and a characteristic peak at 1.3 ppm is detected on MR spectroscopy. This review will discuss the significance of lactate as a metabolite and will describe various brain lesions and disease conditions in which elevated lactate levels are detected.


The disturbed blood-brain barrier in human glioblastoma.
The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. The main clinical problem of human gliomas is the edematous swelling and the dramatic increase of intracerebral pressure, also compromising healthy areas of the brain. According to our concept, one of the main reasons on the cellular level for these clinical problems is the loss or reduction of astroglial polarity. Astroglial polarity means the specific accumulation of potassium and water channels in the superficial and perivascular astroglial endfeet membranes. The most important water channel in the CNS is the astroglial water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically spectacular way, the so-called orthogonal arrays of particles (OAPs) to be observed in freeze-fracture replicas. In brain tumors, but also under conditions of trauma or inflammation, these OAPs are redistributed to membrane domains apart from endfeet areas. Probably, this dislocation might be due to the degradation of the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised directionality of water transport out of the cell, finally to cytotoxic edema. This in turn is hypothesized to lead to a breakdown of the BBB characterized by disturbed tight junctions, and thus to the development of vasogenic edema. However, the mechanism how the loss of polarity is related to the disturbance of microvascular tight junctions is completely unknown so far.


The dimensions of the problem of eye disease among the elderly.
America is aging rapidly. Within the next 30 years, those over 65 years of age will grow to form 17% of the population of the United States; the number of people over 85 will more than double. Currently, the rates of eye disease such as cataract, macular degeneration, diabetic retinopathy, and glaucoma are highest in the older group. The risk of blindness is ten times greater for those over age 65 than for younger individuals. This combination of high rates of disease in the fastest growing segment of the population means that the demand for eye care services will increase dramatically. Undoubtedly, new approaches will appear to deal with the epidemiologic reality.


Light-Intensity Physical Activity and Medical Multimorbidity.
No study has examined the association between objectively measured light-intensity physical activity (LIPA) and multimorbidity (≥2 chronic diseases) in a national sample of US adults. I undertook this examination. Data from the 2005-2006 National Health and Nutrition Examination Survey were used (N = 2048 adults 20 years old and older). Physical activity was assessed via accelerometry, with multimorbidity assessed via physician diagnosis and biometric screening. In a multivariable linear regression and after adjustments, for every 60-minute/day increase in LIPA, participants had a lower multimorbidity index (βadjusted = -0.09, 95% confidence interval -0.12 to -0.05, P < 0.001). In a multivariable logistic regression and after adjustments, for every 60-minute/day increase in LIPA, participants had 13% (odds ratioadjusted 0.87, 95% confidence interval 0.79-0.96, P = 0.01) reduced odds of being multimorbid (ie, having ≥2 morbidities). LIPA, independent of moderate-to-vigorous physical activity, is associated with reduced odds of multimorbidity. As such, promotion of LIPA, as well as moderate-to-vigorous physical activity, may be a sensible strategy to help prevent and treat multimorbidity.


Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy.
Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.


New posteriorly located retinal breaks after pneumatic retinopexy.
Pneumatic retinopexy is a new procedure that is effective in treating many uncomplicated cases of rhegmatogenous retinal detachment (RD). It may be done in the office using a cryoprobe or laser and an expanding gas bubble and for this reason has become popular among RD surgeons. Reports of associated complications are limited. Three patients who had remarkably posterior retinal breaks after pneumatic retinopexy are presented with evidence that these breaks are a direct complication of this procedure. A possible explanation as to the pathogenesis of pneumatic retinopexy-associated posteriorly located retinal tears, as well as suggestions regarding prophylactic measures that may be taken to avoid this complication, are also presented.


Neuromuscular electrical stimulation on hearing loss caused by skull base fracture: A protocol for systematic review of randomized controlled trial.
This systematic review aims to investigate the effectiveness and safety of neuromuscular electrical stimulation (NMES) on hearing loss (HL) caused by skull base fracture (SBF). We will retrieve the following electronic databases of Cochrane Library, PUBMED, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from the inception to January 1, 2019 for relevant RCTs of NMES for HL caused by SBF. Two experienced authors will independently perform the study selection, data extraction, and methodology quality assessment. A 3rd author will solve any disagreements between 2 authors through discussion. This study will provide a high-quality synthesis of latest evidence of NMES for HL caused by SBF from comprehensive assessments, including hearing loss evaluation, hearing threshold, quality of life, and any relevant adverse events. The expected results of this systematic review will provide the up-to-date evidence to assess the effectiveness and safety of NEMS for patients with HL caused by SBF. The results of this study will be disseminated through publication in a peer-reviewed journal or will be presented at an associated conference meeting. This study will not use individual patient data, thus, the ethical approval is not needed. PROSPERO CRD42019120195.


RbB3O4F2: a rubidium fluorooxoborate with an unprecedented [B3O5F2]3- functionalized unit and a large birefringence.
A new rubidium fluorooxoborate, RbB3O4F2, was structurally designed and synthesized by using the strategy of fluorine-introduction into borates. Interestingly, RbB3O4F2 presents the novel [B3O4F2]- chains formed by the unprecedented [B3O5F2]3- fundamental building block. More importantly, RbB3O4F2 has a large birefringence and a deep-UV cutoff edge. The finding of novel [B3O5F2]3- FBB and [B3O4F2]- chains in RbB3O4F2 greatly enriches the structural diversity of fluorooxoborates.


Role of excitatory amino acids in rat vagal and sympathetic baroreflexes.
Vagal baroreflexes were studied by measuring the atropine-sensitive cardioinhibition produced by raising arterial pressure with phenylephrine in anesthetized rats pretreated with the beta-adrenergic receptor antagonist nadolol. Sympathetic baroreflexes were determined in halothane-anesthetized rats by measuring the inhibition of lumbar sympathetic discharge produced by elevating arterial pressure with gradual aortic constriction. Both reflexes were drastically reduced by bilateral injections of 2.2 nmol of the glutamate receptor antagonist kynurenic acid (KYN) into either the nucleus of the solitary tract (NTS) or the ventrolateral medulla between 0 and 1 mm posterior to the level of the obex. Injections of KYN elsewhere in the medulla were generally ineffective and injections of 8-OH kynurenate (an inactive analog) into the ventrolateral medulla or NTS were also without effect. KYN injections (2.2 nmol) into the intermediate portion of the NTS produced small increases in mean arterial pressure (0-15 mm Hg) and no change in heart rate while injections of similar amounts into the ventrolateral medulla at obex level were followed by large (35-116 mm Hg) increases in pressure and bradycardia. Both types of injections produced a similar degree of blockade of vagal and sympathetic baroreflexes. These results support previous evidence that baroreceptor primary afferents may release a glutamate-like transmitter in the NTS and indicate that a similar type of excitatory transmitter is involved at the level of the ventrolateral medulla in mediating or modulating both vagal and sympathetic baroreflexes. Finally the bradycardia and hypertension produced by blocking amino acid receptors in the ventrolateral medulla appear largely unrelated to the disruption of peripheral baroreceptor inputs.


Maternal diet, nutritional status and infant birth weight in Malaysia: a scoping review.
Women's diet and nutritional status during pregnancy are important in influencing birth outcomes. We conducted a systematic scoping review of the best available evidence regarding dietary intake of Malaysian pregnant women, and the associations of maternal diet, anthropometry, and nutrition-related co-morbidities with the infant's birth weight (IBW). The study objectives were to examine: (1) the adequacy of micronutrient intake among pregnant women; and (2) the association of maternal factors (anthropometry, diet, plasma glucose and blood pressure) during pregnancy with IBW. Eleven search engines such as Proquest, EbscoHost, Scopus, Cochrane Library, Science Direct, Wiley Online Library, PubMed, Google Scholar, MyJournal, BookSC and Inter Library Loan with Medical Library Group were extensively searched to identify the primary articles. Three reviewers independently screened the abstracts and full articles based on the inclusion and exclusion criteria. Extracted data included details about the population characteristics, study methods and key findings related to the review objectives. Seventeen studies published from 1972 to 2021 were included, following the PRISMA-ScR guideline. Studies showed that maternal micronutrient intakes including calcium, iron, vitamin D, folic acid, and niacin fell short of the national recommendations. Increased maternal fruit intake was also associated with increased birth weight. Factors associated with fetal macrosomia included high pre-pregnancy body mass index (BMI), excess gestational weight gain (GWG) and high blood glucose levels. Low pre-pregnancy BMI, inadequate GWG, intake of confectioneries and condiments, and high blood pressure were associated with low birth weight. This review identified several factors such as the mother's food habits, comorbidities, BMI and gestational weight gain as the determinants of low birth weight. This implies that emphasis should be given on maternal health and nutrition for the birth outcome.


Oviducal gland transcriptomics of Octopus maya through physiological stages and the negative effects of temperature on fertilization.
Elevated temperatures reduce fertilization and egg-laying rates in the octopus species. However, the molecular mechanisms that control the onset of fertilization and egg-laying in the octopus' oviducal gland are still unclear; and the effect of temperature on the expression of key reproductive genes is unknown. This study aims to better understand the molecular bases of octopus fertilization and egg-laying, and how they are affected by elevated temperatures. RNA-seq of oviducal glands was performed for samples before, during, and after fertilization and their transcriptomic profiles were compared. Also, at the fertilization stage, the optimal and thermal-stress conditions were contrasted. Expression levels of key reproductive genes were validated via RT-qPCR. In mated females before egg-laying, genes required for the synthesis of spermine, spermidine, which may prevent premature fertilization, and the myomodulin neuropeptide were upregulated. Among the genes with higher expression at the fertilization stage, we found those encoding the receptors of serotonin, dopamine, and progesterone; genes involved in the assembly and motility of the sperm flagellum; genes that participate in the interaction between male and female gametes; and genes associated with the synthesis of eggshell mucoproteins. At temperatures above the optimal range for reproduction, mated females reduced the fertilization rate. This response coincided with the upregulation of myomodulin and APGW-amide neuropeptides. Also, genes associated with fertilization like LGALS3, VWC2, and Pcsk1 were downregulated at elevated temperatures. Similarly, in senescent females, genes involved in fertilization were downregulated but those involved in the metabolism of steroid hormones like SRD5A1 were highly expressed.


An internet-based survey on the circumstances of food-induced reactions following the diagnosis of IgE-mediated food allergy.
Despite careful avoidance measures, food allergic patients have a significant risk of anaphylactic episodes. Risk situations need to be identified for more efficient preventive measures. Responders to an internet-based survey on the awareness of food anaphylaxis were invited to relate the circumstances of their most severe reaction following the diagnosis of IgE-mediated food allergy. Items of the questionnaire included the circumstances of the reaction and the treatment, as well as questions related to reactions occurring at specific categories of sites (i.e. home, schools, or restaurants). Fifty-one of the returned questionnaires (34.1%) corresponded to the study criteria. The median age of the subjects was 7 years (range 0.5-61), with 33/51 (64.7%) being less than 16 years of age. Reactions were reported to peanuts (24/51; 47.1%), milk (12/51; 23.5%), tree nuts (6/51; 11.8%), fish and shellfish (5/51; 9.8%), and others (3/51; 5.8%). Reactions occurred at home (13/51; 25.5%), in restaurants (9/51; 17.6%), at school or daycare or kindergarten (8/51; 15.7%), at a relative or friend's home (7/51; 13.7%), at sites of leisure activities (6/51; 11.8%), at work (3/51; 5.9%), in church or a hospital ward (2/51; 3.9% each), or in a food store (1/51; 2.0%). In severe reactions (37/51; 72.5%) epinephrine was administered in 28/37 (75.7%) of the responders. Finally, while most reactions happened after ingestion of the food (40/51; 78.4%), others were reported after skin contact exclusively (8/51; 16%), or after inhalation (3/51; 5.9%). Food induced-anaphylaxis in patients aware of their allergy happens most often at sites considered as safe (i.e. home, schools, workplace, hospitals). Better strategies to avoid accidental reactions include clear labelling of forbidden foods and increased information at all levels. These might dramatically reduce the risk of food-induced anaphylaxis in food allergy sufferers.


Characterization of a cold-adapted debranching enzyme and its role in glycogen metabolism and virulence of Vibrio vulnificus MO6-24/O.
Vibrio vulnificus MO6-24/O has three genes annotated as debranching enzymes or pullulanase genes. Among them, the gene encoded by VVMO6_03032 (vvde1) shares a higher similarity at the amino acid sequence level to the glycogen debranching enzymes, AmyX of Bacillus subtilis (40.5%) and GlgX of Escherichia coli (55.5%), than those encoded by the other two genes. The vvde1 gene encoded a protein with a molecular mass of 75.56 kDa and purified Vvde1 efficiently hydrolyzed glycogen and pullulan to shorter chains of maltodextrin and maltotriose (G3), respectively. However, it hydrolyzed amylopectin and soluble starch far less efficiently, and β-cyclodextrin (β-CD) only rarely. The optimal pH and temperature of Vvde1 was 6.5 and 25°C, respectively. Vvde1 was a cold-adapted debranching enzyme with more than 60% residual activity at 5°C. It could maintain stability for 2 days at 25°C and 1 day at 35°C, but it destabilized drastically at 40°C. The Vvde1 activity was inhibited considerably by Cu2+, Hg2+, and Zn2+, while it was slightly enhanced by Co2+, Ca2+, Ni2+, and Fe2+. The vvde1 knock-out mutant accumulated more glycogen than the wild-type in media supplemented with 1.0% maltodextrin; however, the side chain length distribution of glycogen was similar to that of the wild-type except G3, which was much more abundant in the mutant. Therefore, Vvde1 seemed to debranch glycogen with the degree of polymerization 3 (DP3) as the specific target branch length. Virulence of the pathogen against Caenorhabditis elegans was attenuated significantly by the vvde1 mutation. These results suggest that Vvde1 might be a unique glycogen debranching enzyme that is involved in both glycogen utilization and shaping of glycogen molecules, and contributes toward virulence of the pathogen.


On-line identification of secondary metabolites in freshwater microalgae and cyanobacteria by combined liquid chromatography-photodiode array detection-mass spectrometric techniques.
The analysis and identification of a wide range of secondary metabolites biosynthesized by different algal taxa and cyanobacteria has been performed through a selective and sensitive methodology, mainly based on reversed-phase HPLC coupled both to UV photodiode array detection and to atmospheric pressure mass spectrometric techniques (HPLC-DAD-APIMS). Results are reported here with special attention to the analyses carried out both on the natural phytoplankton (mixed populations) of Lake Tovel (Northern Italy, Brenta Dolomites) and on enclosure-produced biomass of the dinoflagellate Glenodinium sanguineum Marchesoni (1941). This analytical procedure might represent a powerful tool for the fast screening of the taxonomic composition (broad groups, e.g. divisions) of natural mixed populations of phytoplankton, by providing a reliable distribution of accessory pigments extracted from microalgae, such as carotenoids and chlorophyll derivatives. Furthermore, we showed that in the same chromatographic analysis other classes of natural products, such as galactolipids, alkaloids, sterols and mycosporine-like amino acids, can be detected by using combined optical and mass spectrometric techniques. These metabolites represent distinctive biochemical signatures, sometimes even at the species level.


Molecular diagnostic testing for inherited thrombophilia using Invader.
Physicians in the United States and Europe began testing patients who had idiopathic thrombotic events for inherited risk factors in 1990s. The College of American Pathologists (CAP) offered proficiency testing for molecular genetic screening for thrombophilia in 1997. Today, a hypercoagulable workup including screening for inherited thrombophilia defects is becoming part of the standard of care in many parts of the world (1). Who, what, and when to test continue to be controversial and challenging questions (2); however, laboratories developing new or improved mutation detection methodologies have used the most commonly screened inherited thrombophilia polymorphism, factor V Leiden (R506Q), for many years (3). In the most recent CAP survey (MGL-A 2003), the most commonly employed method used in one-third of all participating clinical laboratories testing for factor V Leiden and prothrombin G20210A was the non-PCR-based method called Invader, developed by Third Wave Technologies. The remainder of the clinical laboratories reported testing for these variants using PCR-restriction fragment length polymorphism (RFLP), allele-specific PCR, and allele-specific hybridization. Emerging mutation detection technologies include DNA resequencing approaches such as pyrosequencing (4) fluorescence polarization detection (5), genotyping on microelectronic DNA chips like Nanogen's nanochip (6), and oligonucleotide hybridization with photocrosslinking (7). Invader technology is currently a medium-throughput, 96-well plate format assay that is sufficient for most hospital clinical laboratories. Although this assay format is not currently performed in a microarray format, Invader is amenable to performance on a solid support; specifically, the reaction can be performed on the surface of microspheres and the resulting fluorescence measured using flow cytometry (8). This chapter presents the method as well as some suggestions for utilizing the Invader system for mutation/polymorphism screening in general and for thrombophilia testing in particular.


Development of CD4+ effector T cells and susceptibility to infectious diseases.
The mechanisms by which naive helper T cells differentiate into potent cytokine-expressing effectors remain critical to understanding both successful and aberrant immune responses. Studies using Leishmania major infection of mice have revealed genetic contributions to factors that influence this differentiative process. Further, antigen recognition at the level of the T cell repertoire can also profoundly affect the outcome of disease and the appearance of discrete T cell subsets. It is likely that such mechanisms also underpin genetic susceptibility to diverse other infectious and autoimmune diseases.


Redox regulation of AMP synthesis in yeast: a role of the Bas1p and Bas2p transcription factors.
Expression of yeast AMP synthesis genes (ADE genes) was severely affected when cells were grown under oxidative stress conditions. To get an insight into the molecular mechanisms of this new transcriptional regulation, the role of the Bas1p and Bas2p transcription factors, known to activate expression of the ADE genes, was investigated. In vitro, DNA-binding of Bas1p was sensitive to oxidation. However, this sensitivity could not account for the regulation of the ADE genes because we showed, using a BAS1-VP16 chimera, that Bas1p DNA-binding activity was not sensitive to oxidation in vivo. Consistently, a triple cysteine mutant of Bas1p (fully resistant to oxidation in vitro) was unable to restore transcription of the ADE genes under oxidative conditions. We then investigated the possibility that Bas2p could be the oxidative stress responsive factor. Interestingly, transcription of the PHO5 gene, which is dependent on Bas2p but not on Bas1p, was found to be severely impaired by oxidative stress. Nevertheless, a Bas2p cysteine-free mutant was not sufficient to confer resistance to oxidative stress. Finally, we found that a Bas1p-Bas2p fusion protein restored ADE gene expression under oxidative conditions, thus suggesting that redox sensitivity of ADE gene expression could be due to an impairment of Bas1p/Bas2p interaction. This hypothesis was further substantiated in a two hybrid experiment showing that Bas1p/Bas2p interaction is affected by oxidative stress.


Long-term sequelae of group B streptococcal meningitis in infants.
The long-term outcome and admission features predictive of outcome were determined for 61 patients with group B streptococcal meningitis treated between 1974 and 1979. Infection was rapidly fatal in 13 patients (21%). Among the 48 survivors, 38 (79%) 3 years of age or older were available for comprehensive evaluation. Excluding five who had died before age 3 years, the mean age at evaluation was 6.0 years (range 3.3 to 9.0 years). Among survivors, 11 (29%) had severe neurologic sequelae, eight (21%) had mild to moderate deficits, and 19 (50%) were functioning normally. Analysis of predictive features revealed a significant risk of death or severe impairment among infants who at hospital admission were comatose or semicomatose, had decreased perfusion, total peripheral WBC less than 5,000/mm3, absolute neutrophil count less than 1000/mm3, and CSF protein greater than 300 mg/dl (P less than or equal to 0.05). These data indicate that, although mortality from group B streptococcal meningitis has declined, approximately half of the survivors of acute infection have some degree of morbidity when evaluated at ages permitting the detection of language delay and borderline or mild mental retardation.


Fabrication of chondroitin sulfate calcium complex and its chondrocyte proliferation in vitro.
Chondroitin sulfate (CS)-calcium complex (CSCa) was fabricated, and the structural characteristics of CSCa and its proliferative bioactivity to the chondrocyte were investigated in vitro. Results suggested calcium ions could bind CS chains forming polysaccharide-metal complex, and the maximum calcium holding capacity of CSCa reached 4.23 %. Characterization of CSCa was performed by EDS, AFM, FTIR, UV, XRD and 1H-NMR. It was found that calcium ions were integrated with CS by binding the sulfate or carboxyl groups. The thermal properties analysis indicated CSCa had a good thermal stability by TGA and DSC. CSCa could interact the calcium-sensing receptor increasing the intracellular calcium ions and influence the cell cycle. The TGF-β1 secretion induced by CSCa could activate the TGF-β/Smads pathway and change the genes associated proliferation expression ultimately leading to the chondrocyte proliferation. This research probably has an important implication for understanding the effect of CSCa on bone care as food supplements.


Intimal macrophages develop from circulating monocytes during vasculitis.
Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune-privileged site during vasculitis. We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these 'intimal macrophages' did not express markers of resident cardiac macrophages, such as Lyve-1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration.


P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome.
To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.


Behavior changes in patients with diabetes and hypertension after experiencing shared medical appointments.
This project examined recently implemented shared medical appointments (SMAs) at a free clinic for patients with diabetes and/or hypertension. Changes in patients' self-managing behaviors, specifically exercise and goal-setting activity, were explored after participating in SMAs for 4 months. The study employed a pretest-posttest quasi-experimental design. Participants completed a questionnaire of their self-managing behaviors and a behavioral action plan at each SMA. The SMAs were facilitated in English, Spanish, and bilingually (English and Spanish) with a total of 37 participants. Descriptive analysis showed a significant increase in exercise time with a mean increase of 86 min per week at post-SMA (p= .002, 95% confidence interval [CI]). Each participant identified a measurable goal, and 97% of participants reported achieving or almost achieving their goals. Males reported a significantly (p= .002, 95% CI) larger increase in exercise time than women. Variance of self-managing behaviors among the English, Spanish, and bilingual SMAs was statistically not significant. Though much evidence exists demonstrating that SMAs provide effective quality care, literature is lacking in examining patients' self-managing behaviors after participation in language-specific SMAs. Understanding patients' response to programs that address the needs of the individual leads to more effective programs.


Postpartum psychiatric disorders : guidelines for management.
Psychiatric disorders, in particular depression, are common Postpartum and have potential long term implications for the woman and her family. Critical to management is identification and early intervention. Management needs to be multifaceted, including hospitalisation in severe cases, psychotherapy (supportive at least) and organisation of community support. A number of factors need to be considered with respect to medication, in particular if the woman is breastfeeding. Women with puerperal psychosis may require antipsychotics, antidepressants and mood stabilisers; ECT achieves good results when available and acceptable. Women with postpartum depression can generally be managed with antidepressants alone. Management needs to take into account that these disorders may be long lasting, with risk of recurrence after subsequent childbirth, and may have significant effects on child development.


Label-free quantitative proteomic analysis of drought stress-responsive late embryogenesis abundant proteins in the seedling leaves of two wheat (Triticum aestivum L.) genotypes.
Late embryogenesis abundant (LEA) proteins are highly hydrophilic proteins with key roles in environmental stress responses. In this study, we performed the first survey of the LEA proteome in seedling leaves from two wheat genotypes subjected to drought stress, i.e., Shaanhe 6 (SH, drought-tolerant) and Zhengyin 1 (ZY, drought-sensitive). After isolating the LEA subpopulation by treating total soluble proteins with heating combined with 1% trichloroacetic acid treatment that was assessed by Western blotting of dehydrins, label-free proteomic analysis identified 38 LEA proteins or homologues belonging to seven LEA subfamilies in the two genotypes. The abundances of over half of the LEA proteins changed significantly after drought stress and they were involved in protection against drought, with at least 20 in SH and 14 in ZY. We found that the common differentially expressed LEA proteins increased in abundance more in the SH genotype compared with the ZY genotype, and six LEA proteins were significantly upregulated exclusively in the SH genotype, which may contribute to higher drought tolerance in SH. We also identified 221 non-LEA proteins from 12 functional categories. Our results provide a deeper understanding of the LEA expression patterns in response to drought stress in two wheat genotypes. We identified 38 LEA proteins or homologues from different LEA families in two wheat genotypes, thereby indicating the complex and versatile protective roles of LEA proteins in drought stress resistance. Moreover, the abundance of differentially expressed LEA proteins increased more in the SH genotype compared with the ZY genotype, and several LEA proteins with significant upregulation only in the SH genotype may contribute to its higher tolerance of drought stress. 221 non-LEA proteins were differentially accumulated in at least one of the SH and ZY genotypes. They are involved mainly with 12 biological functions and they might explain different drought responses of the two genotypes. The differentially expressed LEA and non-LEA proteins may be potential markers of drought tolerance to facilitate wheat breeding, particularly those that were specifically upregulated in the SH genotype, or with opposing expression patterns in the two genotypes.


Laparoscopic left adrenalectomy during Roux-en-Y gastric bypass using a supragastric approach.
A 54-year-old female had a BMI of 44 kg/m(2), biliary colic, gastro-eophageal reflux disease, joint pain, hyperlipidemia, and diabetes type 2. Her medical history included complete remission of non-Hodgkin's lymphoma and prolactinoma since 1999. An abdominal CT scan demonstrated an incidental left adrenal tumor, which had increased in diameter from 2 cm to 3 cm in 6 months. A laparoscopic Roux-en-Y gastric bypass with ultrasonography and supragastric left adrenalectomy were performed successfully. Combined surgical procedures appear to be suitable for treatment of coexisting abdominal pathologic findings with minimally invasive surgery. A supragastric approach should be considered when planning a simultaneous gastric bypass and left adrenalectomy.


Neurobehavioural Toxicity of Iron Oxide Nanoparticles in Mice.
Iron oxide nanoparticles (Fe2O3-NPs) are widely used in various biomedical applications, extremely in neurotheranostics. Simultaneously, Fe2O3-NP usage is of alarming concern, as its exposure to living systems causes deleterious effects due to its redox potential. However, study on the neurobehavioural impacts of Fe2O3-NPs is very limited. In this regard, adult male mice were intraperitoneally administered with Fe2O3-NPs (25 and 50 mg/kg body weight) once a week for 4 weeks. A significant change in locomotor behaviour and spatial memory was observed in Fe2O3-NP-treated animals. Damages to blood-brain barrier permeability by Fe2O3-NPs and their accumulation in brain regions were evidenced by Evan's blue staining, iron estimation and Prussian blue staining. Elevated nitric oxide, acetylcholinesterase, lactate dehydrogenase leakage and demyelination were observed in the Fe2O3-NP-exposed brain tissues. Imbalanced levels of ROS generation and antioxidant defence mechanism (superoxide dismutase and catalase) cause damages to lipids, proteins and DNA. PARP and cleaved caspase 3 expression levels were found to be increased in the Fe2O3-NP-exposed brain regions which confirms DNA damage and apoptosis. Thus, repeated Fe2O3-NP exposure causes neurobehavioural impairments by nanoparticle accumulation, oxidative stress and apoptosis in the mouse brain.


Simultaneous second-stage norwood operation and tracheoplasty.
Tracheal stenosis is a rare complication that follows operations for congenital heart disease in the newborn period. We report the case of an infant with hypoplastic left heart syndrome who developed symptomatic tracheal stenosis 5 months after a first-stage Norwood operation. The combined surgical procedure of a bidirectional Glenn anastomosis and a tracheoplasty under cardiopulmonary bypass was undertaken.


NLRP3 inflammasome activation determines the fibrogenic potential of PM2.5 air pollution particles in the lung.
Airborne fine particulate matter (PM2.5) is known to cause respiratory inflammation such as chronic obstructive pulmonary disease and lung fibrosis. NLRP3 inflammasome activation has been implicated in these diseases; however, due to the complexity in PM2.5 compositions, it is difficult to differentiate the roles of the components in triggering this pathway. We collected eight real-life PM2.5 samples for a comparative analysis of their effects on NLRP3 inflammasome activation and lung fibrosis. In vitro assays showed that although the PM2.5 particles did not induce significant cytotoxicity at the dose range of 12.5 to 100 µg/mL, they induced potent TNF-α and IL-1β production in PMA differentiated THP-1 human macrophages and TGF-β1 production in BEAS-2B human bronchial epithelial cells. At the dose of 100 µg/mL, PM2.5 induced NLRP3 inflammasome activation by inducing lysosomal damage and cathepsin B release, leading to IL-1β production. This was confirmed by using NLRP3- and ASC-deficient cells as well as a cathepsin B inhibitor, ca-074 ME. Administration of PM2.5 via oropharyngeal aspiration at 2 mg/kg induced significant TGF-β1 production in the bronchoalveolar lavage fluid and collagen deposition in the lung at 21 days post-exposure, suggesting PM2.5 has the potential to induce pulmonary fibrosis. The ranking of in vitro IL-1β production correlates well with the in vivo total cell count, TGF-β1 production, and collagen deposition. In summary, we demonstrate that the PM2.5 is capable of inducing NLRP3 inflammasome activation, which triggers a series of cellular responses in the lung to induce fibrosis.


Reaching a moveable visual target: dissociations in brain tumour patients.
Damage to the posterior parietal cortex (PPC) can lead to Optic Ataxia (OA), in which patients misreach to peripheral targets. Recent research suggested that the PPC might be involved not only in simple reaching tasks toward peripheral targets, but also in changing the hand movement trajectory in real time if the target moves. The present study investigated whether patients with a lesion arising from operation for prefrontal, premotor or parietal tumours are selectively impaired in three experimental pointing conditions: (i) pointing to peripheral targets, (ii) pointing to fixatable targets, and (iii) pointing to moved targets (on-line movement corrections). The study confirmed the selective importance of the parietal cortex in all three tasks. Surprisingly, given clinical claims about OA, the degree of peripheral reaching errors correlated strongly in parietal patients with that to fixatable targets. However, there was no relation between peripheral reaching errors and the 'shift cost' of making on-line correction to moved targets, and classical double dissociations between the two skills were observed. The findings suggest that deficits in pointing to peripheral and to moved targets reflect two at least partly independent processes.


[Apical root resorption during orthodontic treatment].
Pre- and posttreatment radiographs of 2050 orthodontically treated patients were examined and apical root resorptions of more than 2 mm were identified. 30 patients (211 teeth) were affected. Treatment characteristics and objectives of this group (with severe apical root resorption) were compared to a treated group of 30 patients (with no resorption) to determine clinical risk factors. Extrusion, but especially jiggling and a long treatment period were found to be significantly more frequent in the group exhibiting resorption than in the control group. Pathogenesis of treatment-induced root resorption is discussed in respect to histological results.


Manipulating microobject by using liquid droplet as a transporting vehicle.
Liquid droplets are proposed as transport vehicles for manipulating microobjects. An atomic force microscope (AFM) cantilever is used as a gripper to pick-up a droplet and then a particle from a hydrophobic substrate. The droplet and the particle are then released to a hydrophilic substrate from the cantilever. During the pick-up and release, the liquid bridge that formed between the gripper and the substrate is studied. The efficiency of micromanipulation is quantified by the term "volumetric distribution ratio," which is the liquid volume retained by the substrate divided by the whole volume of the droplet during the rupture of the liquid bridge. Based on the theoretical analysis, an optimized micromanipulation is suggested which could achieve 100% efficiency by carefully controlling the wetting properties of the gripper and the substrate.


Five-year follow-up of a one-year self-management program for patients with COPD.
Investigate long-term effects 4 years after the end of a 1-year self-management program (SMP) with 30 hours of education and 16 hours of physical activity in patients with chronic obstructive pulmonary disease (COPD). Prospective observational outcome study. SMP focused on improving disease related self-care skills. Main outcome measures were health-related quality of life, HRQoL, (St Georges Respiratory Questionnaire, SGRQ total) and exercise capacity (6-minute walk test, 6MWT). Thirty patients participated, 47% women. Baseline mean age was 67 years and mean pre-bronchodilator FEV(1) (forced expiratory volume in 1 second) percentage predicted was 41.3. HRQoL showed a statistical significant improvement during the 1-year intervention. Four years after the end of the program SGRQ total was similar to baseline value, 1.4 points (95% CI: -3.6 to 6.3, P = 0.580). Also 6MWT was similar to baseline value at the same test point, -10 m (95% CI: -27 to 8, P = 0.262), and 63% reported having continued to exercise regularly a minimum of three times per week during the follow-up period. The participants in a 1-year self-management program with additional training had maintained their pre-intervention level of HRQoL and exercise capacity 4 years after the end of the program. Two out of three participants had continued to exercise regularly.


Gradual regime shifts in fairy circles.
Large responses of ecosystems to small changes in the conditions--regime shifts--are of great interest and importance. In spatially extended ecosystems, these shifts may be local or global. Using empirical data and mathematical modeling, we investigated the dynamics of the Namibian fairy circle ecosystem as a case study of regime shifts in a pattern-forming ecosystem. Our results provide new support, based on the dynamics of the ecosystem, for the view of fairy circles as a self-organization phenomenon driven by water-vegetation interactions. The study further suggests that fairy circle birth and death processes correspond to spatially confined transitions between alternative stable states. Cascades of such transitions, possible in various pattern-forming systems, result in gradual rather than abrupt regime shifts.