Prevalence of Cryptosporidium spp. infection in a working horse population in Egypt.
Working horses support the livelihoods of smallholder farmers in Egypt. No previous study has investigated the prevalence of cryptosporidiosis in working horses in Egypt. Faecal samples were collected from 607 working horses recruited from thirty-seven villages/areas in two Egyptian governorates and examined for Cryptosporidium spp. infection using the modified Zielh-Neelsen staining technique. Data on signalment, history of recent diarrhoea, and strongyle burden were collected. The prevalence of Cryptosporidium spp. infection was calculated using a bootstrap method and potential risk factors for infection were investigated using mixed-effects logistic regression models that included sampling location as a random-effects variable. The prevalence of Cryptosporidium spp. infection was 28.7% (95% confidence interval = 23.5-33.9). None of the variables investigated, which include age, sex of the animals, and strongyle burden, were associated with risk of infection. This study provided evidence-based information on the prevalence of Cryptosporidium spp. infection in the study area. However, the potential zoonotic risk of Cryptosporidium cannot be confirmed until further studies are conducted to genotype these parasites.


Prevalence of coeliac disease in Northwest China: heterogeneity across Northern Silk road ethnic populations.
Epidemiological data of coeliac disease are lacking from the central Asian region. To verify the occurrence of coeliac disease amongst four major ethnic groups of Xinjiang Uyghur Autonomus Region, China. 2277 in-patients with gastrointestinal symptoms (1391 Han, 608 Uyghur, 146 Kazakh and 132 Hui; mean age: 54 ± 12.8 years) were included. Total IgA, anti-deamidated gliadin peptide (DGP)-IgG, and anti-tissue transglutaminase (anti-tTG)-IgA were analysed. All antibody-positive subjects were further tested for endomysial (EMA) antibodies and were HLA genotyped. All subjects with antibody positivity were asked to undergo intestinal biopsy. In addition, a subset of antibody-negative subjects were tested for HLA-DQA1and DQB1. Among the 2277 subjects, 29 subjects were defined as coeliac disease autoimmune (positive results for anti-tTG IgA and EMA-IgA) (1.27%; 95% confidence interval, 0.81%-1.73%), eight of them underwent biopsy and all showed coeliac disease histology (0.35%; 95% Cl, 0.11%-0.59%). The frequency of coeliac disease autoimmunity was lowest among the Han (0.79%), followed by the Uyghur (1.81%), the Kazakh (2.05%) and the Hui (3.03%). The frequency of the HLA-DQ2 and/or DQ8 haplotype was highest in the Uyghur (52.1%), followed by the Hui (44.4%), the Kazakh (40.0%) and the Han (39.4%). Besides, a three times higher frequency of coeliac disease autoimmunity was found among rural living subjects with significantly higher wheat consumption compared to urban living subjects (3.16% vs 0.97%, P < 0.01). In Xinjiang, coeliac disease does occur, especially in the rural area. The HLA haplotype and environment play key roles in the development of coeliac disease.


Ideal Interactions: Perspectives of Parents and Teachers of Children With Autism Spectrum Disorder.
We conducted a qualitative study using key informant interviews with 18 teachers and 39 parents of children with autism spectrum disorder (ASD) about how they would envision their ideal interactions with each other. Four main themes emerged from our content analysis. Parents and teachers were concerned about different aspects of communication with each other. Neither party wanted to ask the other for more involvement, and both attributed resistance to a lack of confidence in their expertise. Parents and teachers valued parental presence, but teachers wanted parents to be active partners in the education of their children. The results suggest possible reasons why parents and teachers of children with ASD are often dissatisfied with their interactions. Discussion centers on similarities and differences with general education, as well as on practical solutions to promote more positive exchanges between parents and teachers of children with ASD in school-based contexts.


ZNF692 organizes a hub specialized in 40S ribosomal subunit maturation enhancing translation in rapidly proliferating cells.
Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit. ZNF692 forms a hub containing the exosome complex and ribosome biogenesis factors specialized in the final steps of 18S rRNA processing and 40S ribosome maturation in the granular component of the nucleolus. Highly proliferative cells are more reliant on ZNF692 than normal cells; thus, we conclude that effective production of small ribosome subunits is critical for translation efficiency in cancer cells.


Treatment of recurrent urinary infections with a combination of nitrofurantoin and sulphadiazine.
A combination of nitrofurantoin (100 mg) and sulphadiazine (300 mg) given 12-hourly for 7 days was used to treat 51 patients with recurrent urinary infections who were attending an out-patient clinic. Either nitrofurantoin or sulphadiazine was active in vitro against all the organisms isolated. The cure rate 1 week after the end of treatment was 82%; 10 patients relapsed during the following month, giving a cure rate 5 weeks after the end of treatment of 57%. Side effects, although relatively common (37%), were mild. The outcome of treatment with these two long-established drugs is thus as good as that obtained with some newer and more expensive preparations.


Transcriptome analysis of Phytophthora litchii reveals pathogenicity arsenals and confirms taxonomic status.
Litchi downy blight, caused by Peronophythora litchii, is one of the major diseases of litchi and has caused severe economic losses. P. litchii has the unique ability to produce downy mildew like sporangiophores under artificial culture. The pathogen had been placed in a new family Peronophytophthoraceae by some authors. In this study, the whole transcriptome of P. litchii from mycelia, sporangia, and zoospores was sequenced for the first time. A set of 23637 transcripts with an average length of 1284 bp was assembled. Using six open reading frame (ORF) predictors, 19267 representative ORFs were identified and were annotated by searching against several public databases. There were 4666 conserved gene families and various sets of lineage-specific genes among P. litchii and other four closely related oomycetes. In silico analyses revealed 490 pathogen-related proteins including 128 RXLR and 22 CRN effector candidates. Based on the phylogenetic analysis of 164 single copy orthologs from 22 species, it is validated that P. litchii is in the genus Phytophthora. Our work provides valuable data to elucidate the pathogenicity basis and ascertain the taxonomic status of P. litchii.


Diagnosis, treatment and outcome of Kawasaki disease in an Australian tertiary setting: a review of three years experience.
To examine the patient characteristics, diagnostic criteria, treatment, complications and outcomes of Kawasaki disease (KD) in children diagnosed and treated in an Australian tertiary hospital setting and compare this to previously reported experience. Data were collected prospectively for 14 patients in 2002 and retrospectively for 31 patients in 2000 and 2001. Demographics, clinical features, laboratory features, treatment and outcome details were collected, analysed and compared to previous experience. The median age at diagnosis was 2.77 years (0.28-8.84) and diagnosis was made after a mean 6.1 days of fever. Twenty-eight patients (62.2%) had classical KD and those with less than four criteria were younger than those with four or more criteria (P = 0.04). Patients were treated with intravenous immunoglobulin and aspirin. Twelve (26.7%) required re-treatment. Re-treatment was associated with treatment within 5 days of fever onset (P = 0.03). Twelve patients (27.3%) developed coronary artery abnormalities and the development of such abnormalities was associated with lower serum albumin at diagnosis (P = 0.008) and need for re-treatment (P = 0.03). There was no difference in coronary outcome between classical and incomplete presentations. Only two patients had coronary lesions at 12 months follow-up. We found a trend towards earlier diagnosis and treatment of KD in the tertiary hospital setting, which may reflect heightened physician awareness of the disease. Our study confirms that children who present with incomplete disease are at risk of coronary artery abnormality. We recommend that clinicians continue to maintain high levels of suspicion, even in the absence of the complete clinical picture of KD, particularly in infants below 1 year of age.


A serum proteomics approach to the diagnosis of ectopic pregnancy.
An ectopic pregnancy (EP) occurs when implantation of the embryo occurs outside of the uterus. If left untreated, the developing fetus will continue to grow, leading to life-threatening consequences for the mother. A major difficulty with the diagnosis of ectopic pregnancy is that methods of detection are limited, and some, such as ultrasound, are not very reliable in the earliest days of gestation. Currently, no effective serum test exists to distinguish an ectopic pregnancy from a normal intrauterine pregnancy. The incidence of ectopic pregnancy is increasing and has doubled in the last 20 years. It is now the second most common cause of maternal death in the first trimester of pregnancy. To address this issue, we initiated a project to identify serum markers of ectopic pregnancy. The subjects for these studies presented at the Hospital of the University of Pennsylvania. We obtained over 140 serum samples from women with suspected ectopic pregnancy: women presenting with pain and/or bleeding in the first trimester of pregnancy. The approximate racial breakdown of the subjects is as follows: African American, 36%; Caucasian, 3%; Asian, 2%; Hispanic, 1%; unknown, 58%. Serum samples from 139 women (62 with ectopic pregnancy and 77 with a normal intrauterine pregnancy) were applied to WCX2 (weak ion exchange) protein chip surfaces and analyzed for serum markers using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Several proteins in the 7500-18,000 Da mass range were identified that may discriminate an ectopic pregnancy from an intrauterine pregnancy. The most promising markers were analyzed using classification and regression tree analysis (CART) with and without clinical variables (serum hCG value, length of amenorrhea). Two different algorithms were developed that classify the patients on the basis of sensitivity (number of EPs who screen positive/# of EPs) or specificity (# of healthy patients who screen negative/# of healthy). Our current approach is to refine these two "rule sets" to segregate patients into three groups: those who need immediate intervention for a probable ectopic pregnancy, those who appear to have a normal pregnancy, and those who need further monitoring for diagnosis.


Protection of mice against mouse hepatitis virus by Corynebacterium parvum.
C57BL/6 mice that are highly susceptible to infection with mouse hepatitis virus type 3 were protected against intraperitoneal viral infection by simultaneous intraperitoneal injection of Corynebacterium parvum. No protection was observed when C. parvum was given intravenously or when it was injected intraperitoneally 3 days before viral infection. Protective effects were, however, consistently found when C. parvum was given 2 h before or 2 h after viral infection. Activity was seen only against 10 50% lethal doses and not against 100 50% lethal doses. C. parvum also caused a significant decrease of virus type 3. These data suggest a direct effect of C. parvum on virus-susceptible cells. Injection of C. parvum in mice caused activation of natural killer (NK) cells and of interferon production. However, these two effects were equally demonstrable at high and low doses of C. parvum, whereas protection against mouse hepatitis virus type 3 was not demonstrable at low doses of C. parvum. Thus, antiviral protection may be dissociated from activation of NK cells and induction of interferon.


Simple synthesis of an allenylidene heptavalent rhenium(d0) complex.
This paper reports a simple way to synthesize an allenylidene rhenium(VII) complex. The diimido adamantyl-thiolato allenylidene rhenium(VII) complex 2 was obtained through a metathetical reaction of phosphonioalkylidyne rhenium complex 1 with diphenylketene and also structurally analyzed with X-ray diffraction. Complex 2 is the first d0 allenylidene complex with structure information.


Clinical Outcome of Modified Laparoscopy-Assisted Proximal Gastrectomy Compared to Conventional Proximal Gastrectomy or Total Gastrectomy for Upper-Third Early Gastric Cancer with Special References to Postoperative Reflux Esophagitis.
This study evaluated the functional and oncological outcomes of proximal gastrectomy (PG) in comparison with total gastrectomy (TG) for upper-third early gastric cancer (EGC). The medical records of upper-third EGC patients who had undergone PG (n=192) or TG (n=157) were reviewed. The PG group was further subdivided into patients who had undergone conventional open PG (cPG; n=157) or modified laparoscopy-assisted PG (mLAPG; n=35). Patients who had undergone mLAPG had a longer portion of their intra-abdominal esophagus preserved than patients who had undergone cPG. Surgical morbidity, recurrence, long-term nutritional status, and the incidence of reflux esophagitis were compared between the groups. The rate of postoperative complications was significantly lower for PG than TG (16.7% vs. 31.2%), but the five-year overall survival rate was comparable between the two groups (99.3% vs. 96.3%). Postoperative levels of hemoglobin and albumin were significantly higher for patients who had undergone PG. However, the incidence of reflux esophagitis was higher for PG than for TG (37.4% vs. 3.7%; P<0.001). mLAPG was related to a lower incidence of reflux esophagitis after PG (P<0.001). Compared to TG, PG showed an advantage in terms of postoperative morbidity and nutrition, and there was a comparable prognosis between the two procedures. Preserving the intra-abdominal esophagus may lower the incidence of reflux esophagitis associated with PG.


The role of the cholecystokinin-B/gastrin receptor transmembrane domains in determining affinity for subtype-selective ligands.
We have examined the role of transmembrane domain amino acids in conferring subtype-selective ligand affinity to the human cholecystokinin-B (CCK-B)/gastrin receptor. Fifty-eight residues were sequentially replaced by the corresponding amino acids from the pharmacologically distinct CCK-A receptor subtype. 125I-CCK-8 competition binding experiments were performed to compare all mutant CCK-B/gastrin receptor constructs with the wild type control. Affinities for the nonselective agonist, CCK-8, as well as the subtype-selective peptide (gastrin), peptide-derived (PD135,158), and nonpeptide (L365,260) and L364,718) ligands were assessed. All of the mutants retained relatively high affinity for CCK-8, suggesting that the tertiary structure of these receptors was well maintained. Only eight of the amino acid substitutions had a significant effect on subtype selective binding. When compared with the wild type, single point mutations in the CCK-B/gastrin receptor decreased affinity for gastrin, L365,260, and PD135,158 up to 17-,23-, and 61-fold, respectively. In contrast, the affinity for L364,718 increased up to 63-fold. None of the single amino acid substitutions, however, was sufficient to fully account for the subtype selectivity of any tested compound. Rather, CCK-B/gastrin receptor affinity appears to be influenced by multiple residues acting in concert. The 8 pharmacologically important amino acids cluster in the portion of the transmembrane domains adjacent to the cell surface. The spatial orientation of these residues was analyzed with a rhodopsin-based three-dimensional model of G-protein coupled receptor structure (Baldwin, J.M. (1993) EMBO J. 12, 1693-1703). This model predicts that the 8 crucial residues project into a putative ligand pocket, similar to the one which is well established for biogenic amine receptors (Caron, M. G., and Lefkowitz, R.J. (1993) Recent Prog. Horm. Res. 48, 277-290; Strader, C.D., Sigal, I.S., and Dixon, R.A. (1989) Trends Pharmacol. Sci. 10, Dec. Suppl., 26-30).


Amyotrophic lateral sclerosis surveillance in Baltimore and Philadelphia.
Limited epidemiological data on amyotrophic lateral sclerosis (ALS) exist in defined geographic areas in the United States. Neurologists submitted case reports for patients under their care between January 1, 2009, and December 31, 2011, who met the El Escorial criteria. Diagnosis was confirmed for a sample of cases by the consulting neurologist. Death certificate data were used for supplemental case identification. The 248 reported cases were most likely to be 50-69 years old, men, white, and non-Hispanic. The total crude average annual incidence rate was 1.46 per 100,000 person-years. The reported demographic characteristics were consistent with previously published findings. The crude annual incidence was slightly lower than the expected rate of 1.6 but was within the range reported previously (0.7-2.5). These findings help quantify the burden of ALS in the United States.


Coronary artery bypass grafting with single cross-clamp results in fewer persistent neuropsychological deficits than multiple clamp or off-pump coronary artery bypass grafting.
In coronary artery bypass grafting (CABG) patients, neuropsychological deficits that are present from the time of the operation through 6 months postoperatively are considered permanent and represent organic brain damage related to the operation. We hypothesized that changes in our surgical method would reduce persistent deficits. From 1999 to 2004, consenting CABG patients were randomly assigned to multiple aortic cross-clamp or single aortic cross-clamp technique. An additional contemporary group of patients treated with off-pump CABG was studied. All patients underwent an 11-part neuropsychologic examination preoperatively, and at 1 week, 6 weeks, and 6 months postoperatively. One hundred seven patients with no postoperative neurologic deficits had neuropsychologic examinations at all four testing periods. Off-pump CABG patients were significantly younger (60 +/- 11 years) than multiple aortic cross-clamp (66 +/- 8 years) and single aortic cross-clamp (64 +/- 9 years; p < 0.05) patients. At 6 months, 26% of 27 multiple aortic cross-clamp patients had neuropsychological deficits, 27% of 26 off-pump CABG patients had neuropsychological deficits, and only 9% of 54 single aortic cross-clamp patients had neuropsychological deficits (p = 0.067 versus multiple aortic cross-clamp and off-pump CABG). These results suggest that surgical technique is very important in determining cognitive outcome after CABG. Cardiopulmonary bypass is not the most important factor in determining outcome and when carefully performed with single cross-clamp and minimal aortic manipulation is equal or may be superior to off-pump operation. We suspect that mild hypothermia in on-pump surgery is additionally neuroprotective, a factor that should be taken into account when planning an operation.


Psychoanalytic peregrination VI: "the effect on countertransference of the collapse of civilization".
There is an aspect to countertransference that has not been discussed very much in the literature of psychoanalysis, one that is becoming increasingly important. This centers around the effect on the analyst's countertransference of the deterioration of the culture in which he or she is immersed. I discuss the decline of Western civilization as it is described by a number of contemporary authors in order to show how changes in the value system of the psychoanalyst or his or her turning a blind eye to the injustices and barbarism of the cultural surround both affect the capacity to immerse in the creative process of psychoanalysis, and send a tacit message to the patient about the permissability of hiding certain material. All this contradicts the "fundamental rule" of psychoanalysis, and disturbs the analyst's listening process. The impact of the dumbing down and deterioration of the educational, cultural, and home upbringing milieu of the new generation of psychoanalysts will be profound in influencing the future practice of psychoanalysis.


Consensus statement: patient safety, healthcare-associated infections and hospital environmental surfaces.
Healthcare-associated infections have serious implications for both patients and hospitals. Environmental surface contamination is the key to transmission of nosocomial pathogens. Routine manual cleaning and disinfection eliminates visible soil and reduces environmental bioburden and risk of transmission, but may not address some surface contamination. Automated area decontamination technologies achieve more consistent and pervasive disinfection than manual methods, but it is challenging to demonstrate their efficacy within a randomized trial of the multiple interventions required to reduce healthcare-associated infection rates. Until data from multicenter observational studies are available, automated area decontamination technologies should be an adjunct to manual cleaning and disinfection within a total, multi-layered system and risk-based approach designed to control environmental pathogens and promote patient safety.


A DFT study of the NO dissociation on gold surfaces doped with transition metals.
The NO dissociation on a series of doped gold surfaces (type TM(n)@Au(111) or TM(n)@Au(110), with TM(n) = Ni, Ir, Rh, or Ag and referring n to the number of dopant atoms per unit cell) was investigated through periodic density functional theory calculations. Generally, doping of Au(111) and Au(110) matrices was found to strengthen the interaction with NO species, with the exception of Ag, and was found to increase the energy barrier for dissociation, with the exception of Ni on Au(111). The calculations suggest that the NO dissociation is only possible in the case of the Ir@Au(110) bimetallic surface but only at high temperatures. The increase of the contents of Ir on Au(110) was found to improve significantly the catalytic activity of gold towards the NO dissociation (E(act) = ∼1 eV). Nevertheless, this energy barrier is almost the double of that calculated for NO dissociation on pure Ir(110). However, mixing the two most interesting dopant atoms resulted in a catalyst model of the type Ir@Ni(110) that was found to decrease the energy barrier to values close to those calculated for pure Ir surfaces, i.e., ∼0.4 eV, and at the same time the dissociation reaction became mildly exothermic.


Critical issues in the development of health information systems in supporting environmental health: a case study of ciguatera.
Emerging environmental pressures resulting from climate change and globalization challenge the capacity of health information systems (HIS) in the Pacific to inform future policy and public health interventions. Ciguatera, a globally common marine food-borne illness, is used here to illustrate specific HIS challenges in the Pacific and how these might be overcome proactively to meet the changing surveillance needs resulting from environmental change. We review and highlight inefficiencies in the reactive nature of existing HIS in the Pacific to collect, collate, and communicate ciguatera fish poisoning data currently used to inform public health intervention. Further, we review the capacity of existing HIS to respond to new data needs associated with shifts in ciguatera disease burden likely to result from coral reef habitat disruption. Improved knowledge on the ecological drivers of ciguatera prevalence at local and regional levels is needed, combined with enhanced surveillance techniques and data management systems, to capture environmental drivers as well as health outcomes data. The capacity of public HIS to detect and prevent future outbreaks is largely dependent on the future development of governance strategies that promote proactive surveillance and health action. Accordingly, we present an innovative framework from which to stimulate scientific debate on how this might be achieved by using existing larger scale data sets and multidisciplinary collaborations.


Current perspectives on the clinical management of cryptogenic stroke.
Cryptogenic stroke is a heterogeneous entity defined as an ischemic stroke for which no probable cause is identified despite thorough diagnostic evaluation. Since about a quarter of all ischemic strokes are classified as cryptogenic, it is a commonly encountered problem for providers as secondary stroke prevention is guided by stroke etiology. In this review, the authors provide an overview of stroke subtype classification schemes and diagnostic evaluation in cryptogenic stroke. They then detail putative cryptogenic stroke mechanisms, their therapeutic implications, and ongoing research. This review synthesizes the available evidence on PubMed up to December 2022. Cryptogenic stroke is an evolving concept that changes with ongoing research. Investigations are focused on improving our diagnostic capabilities and solidifying useful constructs within cryptogenic stroke that could become therapeutically targetable subgroups within an otherwise nonspecific entity. Advances in technology may help move specific proposed cryptogenic stroke mechanisms from undetermined to known source of ischemic stroke.


The evaluation of reduction of Fe(III) in 3-hydroxy-4-nitroso-2,7-naphthalene disulphonic medium as an alternative ferric reducing activity power assay.
The growing interest in determination of anti-oxidant capacity through non-labour, effective and less costly methods encouraged the development of the spectrophotometric procedure presented in this study. To investigate the reduction reaction of Fe(III) in 3-hydroxy-4-nitroso-2,7-naphthalenedisulphonic anion (NRS) medium as an alternative ferric reducing activity power (FRAP) assay for determining the total reduction capacity (RC). The absorbance values at 730 nm were used to determine the RC of aqueous extracts of nine Brazilian plants. The results were compared with the values obtained with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and with the total polyphenol content (TPC). The RCs of phenolic derivatives, flavonoids, amino acids and other anti-oxidant compounds were determined. Paired t-test with RC values obtained with both assays (proposed FRAP and DPPH) showed no statistically significant difference. In addition, the RC values from the proposed FRAP assay are proportional to those found with TPC values (r =0.916). In addition, the conditional reduction potential of the Fe(III)/Fe(II) couple (0.685 V vs NHE (normal hydrogen electrode)) and the molar absorptivities at 730 nm of the Fe(NRS)(3)(3-) and Fe(NRS)(3)(4-) complexes (1.88 × 10(3) and 1.77 × 10(4) L/cm × mol, respectively) were calculated because these values were not available. The proposed assay is adequate for determination of the RC of plant extracts, and the results infer that other samples derived from plants (e.g. beers and wines) and even biological samples (e.g. serum and urine) also could be analysed.


Deep-Time Convergence in Rove Beetle Symbionts of Army Ants.
Recent adaptive radiations provide striking examples of convergence [1-4], but the predictability of evolution over much deeper timescales is controversial, with a scarcity of ancient clades exhibiting repetitive patterns of phenotypic evolution [5, 6]. Army ants are ecologically dominant arthropod predators of the world's tropics, with large nomadic colonies housing diverse communities of socially parasitic myrmecophiles [7]. Remarkable among these are many species of rove beetle (Staphylinidae) that exhibit ant-mimicking "myrmecoid" body forms and are behaviorally accepted into their aggressive hosts' societies: emigrating with colonies and inhabiting temporary nest bivouacs, grooming and feeding with workers, but also consuming the brood [8-11]. Here, we demonstrate that myrmecoid rove beetles are strongly polyphyletic, with this adaptive morphological and behavioral syndrome having evolved at least 12 times during the evolution of a single staphylinid subfamily, Aleocharinae. Each independent myrmecoid clade is restricted to one zoogeographic region and highly host specific on a single army ant genus. Dating estimates reveal that myrmecoid clades are separated by substantial phylogenetic distances-as much as 105 million years. All such groups arose in parallel during the Cenozoic, when army ants diversified into modern genera [12] and rose to ecological dominance [13, 14]. This work uncovers a rare example of an ancient system of complex morphological and behavioral convergence, with replicate beetle lineages following a predictable phenotypic trajectory during their parasitic adaptation to host colonies.


Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer.
Esophageal cancer is often marked by aggressive tumor growth and poor prognosis. Patient groups who benefit from perioperative therapy are not yet defined. The tumor microenvironment and circulating factors as possible predictors of response and prognosis gain interest. This study aimed to investigate cytokines in patients' serum and tumor tissue with regard to response and prognosis. Median survival between SCC and AC was not different (published previously). Lower levels of CCL11 (Eotaxin-1) and CXCL10 (IP-10) in the tumor tissue were associated with a better prognosis (p = 0.022; p = 0.002). In the AC subgroup higher concentrations of TGF-β3 in serum and corresponding tumor tissue were associated with adverse prognosis (p = 0.035; p = 0.006). An association with histopathological response was found for IL-12(p70) and CXCL10 in patients' sera (p = 0.041; p = 0.032). The tissue levels of TGF-β1 and TGF-β2 were significantly lower in histopathological responders than in nonresponders (p = 0.033; p = 0.007). A similar trend was seen for TGF-β3, without statistical significance (p = 0.097). Preoperative serum samples and corresponding tumor tissue (n = 54), only serum (n = 20) or only tissue (n = 4) were collected from patients undergoing surgery for cT3/4 esophageal squamous cell cancer (SCC) (n = 34) and adenocarcinoma (AC) (n = 44). All samples were taken after neoadjuvant treatment. All patients received perioperative chemo(radio)therapy. Cytokine levels of 17 different cytokines were measured by multiplex immunoassay and correlated with clinicopathological factors. Two chemokines (CCL11 and CXCL10) in posttherapeutic tumor tissue were associated with prognosis in patients with esophageal cancer, lower levels indicating a better prognosis. Lower levels of TGF-β were associated with better response and prognosis in patients with AC.


Topiramate: a new antiepileptic drug.
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage of topiramate are reviewed. Topiramate is indicated for use in the adjunctive treatment of adult partial-onset epilepsy. A sulfamate-substituted monosaccharide, it is structurally distinct from other antiepileptic agents. Topiramate acts by blocking the spread of seizures. Oral topiramate has high bioavailability and low protein binding, and as monotherapy its half-life permits once- or twice-daily administration. The drug is excreted largely unchanged in the urine. Clinical trials have shown that topiramate is effective as adjunctive therapy in treating adult partial-onset epilepsy with or without secondarily generalized seizures. In adults with refractory partial epilepsy, topiramate has shown efficacy when carbamazepine or phenytoin has failed. Topiramate may also be effective against partial-onset epilepsy and Lennox-Gastaut syndrome in children, but more pediatric studies are needed. CNS adverse effects are the most common; weight loss and nephrolithiasis have also been reported. The drug does not appear to interact significantly with other antiepileptic agents, but enzyme inducers like phenytoin and carbamazepine can decrease serum topiramate levels by 50%. The initial dosage is 50 mg nightly for seven nights, followed by an increase weekly to 400 mg/day in two divided doses. Topiramate is more costly than other anticonvulsants; however, drug therapy accounts for less than 10% of the total direct cost of epilepsy treatment. Topiramate offers an effective, well-tolerated option in patients with adult partial-onset seizures.


The novel carbohydrate tumor antigen C2-O-sLe x is upregulated in canine gastric carcinomas.
Sialyl Lewis x-modified core 2 branched O-glycans (C2-O-sLe(x)) on human leukocytes mediate much higher-affinity adhesion to selectins on activated vascular endothelium than does sialyl Lewis x on other structures. In some canine and human carcinomas, high expression of sLe(x)-decorated carbohydrates has been associated with metastasis and, in humans, a poor prognosis, but detection in canine gastric carcinomas is unreported. The authors hypothesized that these carbohydrates are highly expressed in more malignant types of canine gastric carcinomas, they promote metastasis, and they are associated with a poorer prognosis for dogs. The objectives were to determine the presence and importance of C2-O-sLe(x) expression in canine gastric carcinomas. Routine histological sections of 16 canine gastric carcinomas were categorized on the basis of 3 classification schemes: World Health Organization, Lauren, and Goseki. Serial sections were stained with antibodies directed against C2-O-sLe(x) (CHO-131 monoclonal antibody), cytokeratin (Lu-5 monoclonal antibody), and stains to detect neutral and acid mucins (periodic acid-Schiff and alcian blue). Whereas normal gastric mucosal epithelial cells were negative for C2-O-sLe(x), 56% of the tumors examined were positive for C2-O-sLe(x). Importantly, the majority of more poorly differentiated tumor types had more numerous and larger intensely stained areas of C2-O-sLe(x) expression compared with moderate to well-differentiated tumor types. Signet ring-type carcinomas had markedly higher distribution and intensity of periodic acid-Schiff and alcian blue staining than did tubular carcinomas. These findings suggest that C2-O-sLe(x) is a tumor-associated antigen that may play a role in the invasiveness and metastatic potential of certain types of canine gastric carcinomas.


Further evidence for a central stimulatory action of catecholamines on adrenocorticotropin release in the rat.
Catecholamines may stimulate ACTH secretion during stress. To investigate the nature and site of such an action, plasma ACTH was measured in four groups of unanesthetized adult female rats with an indwelling carotid cannula. Sequential 300-microliter blood samples were taken 60 min, 30 min, and immediately before an intracerebroventricular (icv) infusion of 2.5 microliter adrenaline or noradrenaline and 5, 15, 45, 60, and 120 min after the infusion. The four groups were: 1) intact rats; 2) rats infused 7 days after undergoing a discrete bilateral lesion of the ventral noradrenergic ascending bundle caused by 6-hydroxydopamine, which depleted their hypothalamic adrenaline and noradrenaline levels by 90% and 80%, respectively; 3) rats infused 30 min after pretreatment via the icv route with either prazosin or propranolol; and 4) rats infused 16 and 2 h after two successive intracarotid injections of an anti-rCRH-41 serum. In another group, the effects of icv catecholamine administration were compared with those of an intracerebral (ic) microinfusion close to a single paraventricular nucleus (PVN). Finally, in two additional groups blood was sampled at the above-mentioned times before and after a 2-min ether inhalation by intact rats or prazosin- and/or propranolol-pretreated rats. In the intact rats (group 1), a stress-like stimulatory dose response was noted after both adrenaline and noradrenaline infusions, with a half-maximal effect at concentrations of about 0.6 nmol and a maximal effect at 2.7 nmol or more. At maximally effective doses, adrenaline was significantly more active than noradrenaline. In the rats with ventral noradrenergic ascending bundle lesions (group 2), 2.7 nM adrenaline or noradrenaline stimulated ACTH release as in the controls without lesions. In group 3, prazosin blocked the ACTH responses to both adrenaline and noradrenaline, whereas propranolol only blocked the response to adrenaline. In group 4, i.e. rats pretreated with an anti-rCRH-41 serum, the amplitude of the ACTH surge after icv adrenaline or noradrenaline infusion was halved. A unilateral ic catecholamine microinfusion next to the PVN (half the icv dose given in group 1) led to a rapid ACTH release that peaked at half the response measured in the icv infused rats. Ether stress-induced ACTH release was decreased by 50-60% after icv pretreatment with 1 or 10 micrograms prazosin, 1 or 6.5 micrograms propranolol, or a combined dose comprising 1 microgram of both. The following conclusions were reached.(ABSTRACT TRUNCATED AT 400 WORDS)


[Not Available].
Around 1800 the relationship between doctors and patients was determined by two opposing therapeutic principles, both of which were able to look back on a long tradition. On the one hand, the Enlightenment period lent prominence to the principle of correction, as can be traced paradigmatically in the field of orthopaedics. In this case medical treatment was closely linked to the conception of education. This approach emerged around 1800, particularly in the form of Brownianismus - in the field of psychiatry among others. At the same time the therapeutic principle of sympathy, which has its roots in magic healing, gained fresh impetus in the "electric age" of the Enlightenment, particularly through mesmerism (animal magnetism). Here it is a question of the hidden interdependence in nature, which gained considerable importance especially in the field of psychology on the early nineteenth century (in the context of the so-called Romantic Medicine). It is this area of tension, the combination of external correction and internal sympathy, which makes the period between Enlightenment and Romantic such a fascinating subject in the history of medicine.


Miniaturized multiphoton microscope with a 24Hz frame-rate.
With miniaturized tube lenses and a micro-electro-mechanical system (MEMS) mirror, we constructed a miniaturized multiphoton microscope system. Through a two-dimensional asynchronous scanning of the MEMS mirror, 24Hz frame rate can be realized. With a high numerical aperture objective, sub-micron resolution can also be achieved at the same time.


[Substernal goiter: pre-, intra- and postoperative problems].
The Authors report their experience with problems in treating substernal goiter. They then explain at length the complex haemodynamic or respiratory situations encountered and the therapeutic management of the condition. Also discussed are technical surgical problems, and the prevention and therapy of possible complications. They conclude by stating that thanks to all the technical means currently available complete patient control can be achieved before, during and after the operation, thus significantly contributing to the successful outcome of surgical treatment.


Mucinous adenocarcinoma arising from a suprapubic cystostomy site without bladder involvement.
Carcinoma arising from a suprapubic cystostomy site in patients with spinal cord injury has been infrequently described. In all previously reported cases, they have been squamous cell carcinomas. Our patient is a 68 year old male with T10 complete thoracic paraplegia who presented with an exophytic mass extending from his suprapubic cystostomy tract. Biopsy revealed mucinous adenocarcinoma. Carcinoma of the suprapubic cystostomy tract should be considered in those patients who present with bloody drainage and/or masses arising from the suprapubic cystostomy site.


Evidence for arrogance: On the relative importance of expertise, outcome, and manner.
Arrogant behavior is as old as human nature. Nonetheless, the factors that cause people to be perceived as arrogant have received very little research attention. In this paper, we focused on a typical manifestation of arrogance: dismissive behavior. In particular, we explored the conditions under which a person who dismissed advice would be perceived as arrogant. We examined two factors: the advisee's competence, and the manner in which he or she dismissed the advice. The effect of the advisee's competence was tested by manipulating two competence cues: relative expertise, and the outcome of the advice dismissal (i.e., whether the advisee was right or wrong). In six studies (N = 1304), participants made arrogance judgments about protagonists who dismissed the advice of another person while the advisees' relative expertise (compared to the advisor), their eventual correctness, and the manner of their dismissal were manipulated in between-participant designs. Across various types of decisions and advisee-advisor relationships, the results show that less expert, less correct, and ruder advisees are perceived as more arrogant. We also find that outcome trumps expertise, and manner trumps both expertise and outcomes. In two additional studies (N = 101), we examined people's naïve theories about the relative importance of the aforementioned arrogance cues. These studies showed that people overestimate the role of expertise information as compared to the role of interpersonal manner and outcomes. Thus, our results suggest that people may commit arrogant faux pas because they erroneously expect that their expertise will justify their dismissive behavior.


Optical transparent metamaterial with multi-band compatible camouflage based on inverse design.
Infrared (IR) thermal camouflage and management are deeply desirable in the field of military and astronomy. While IR compatible with laser camouflage technology is extensively studied to counter modern detection systems, most existing strategies for visible light camouflage focus on color matching, which is not suitable for scenarios requiring transparency. In this work, we propose an optically transparent metamaterial with multi-band compatible camouflage capability based on the inverse design. The metamaterial consists of Ag grating, Si3N4 dielectric spacer layer, Ag reflection layer, and Si3N4 anti-reflective layer. An ideal multi-band compatible spectrum is involved in the inverse design algorithm. Calculated results demonstrate high transmittance (T0.38-0.78µm = 0.70) in the visible region, low reflectance (R1.55µm = 0.01) in laser working wavelength, high reflectance (R3-5µm = 0.86 and R8-14µm = 0.92) in the dual-band atmospheric window, and high emissivity (ɛ5-8µm = 0.61) for the non-atmospheric window. The radiative heat flux in the detected band is 31W/m2 and 201W/m2 respectively. Furthermore, the incident and polarized insensitivity of the proposed metamaterial supports applicability for practical situations. This work, emphasizes an effective strategy for conducting optically transparent design with compatible IR-laser camouflage as well as radiative cooling properties by an automated design approach.


Breastfeeding in chronic illness: the voices of women with fibromyalgia.
To describe what it is like for women with fibromyalgia (FM) to breastfeed their infants. Nine women with FM who chose to breastfeed their infants were the sample for this qualitative study. van Manen's phenomenological method of reflection, writing, and rewriting was used to analyze the data collected through in-depth tape-recorded interviews and written stories. All nine women felt that they were not successful in their attempts to breastfeed, and felt frustrated. Themes included (a) muscle soreness, pain, and stiffness made it difficult to breastfeed the baby; (b) fatigue interfered with the breastfeeding process; (c) the need for medication, perceived insufficient milk supply, and sore nipples led to forced unplanned weaning; and (d) being forced to wean the infant when not ready to do so created sadness and a feeling of depression. Nurses who work with women with FM who choose to breastfeed need to be proactive in providing informational, emotional, and physical support to facilitate a successful breastfeeding experience for these women. Knowing that the pain, muscle soreness, stiffness, and fatigue of FM may affect breastfeeding can direct nurses to help women with FM plan for support after childbirth and learn techniques to control/reduce the muscle pain and stiffness. Nurses are encouraged to refer breastfeeding women with FM to lactation consultants and support groups for encouragement and validation regarding their concerns about breastfeeding. It is important that nurses continue to serve as advocates for breastfeeding women with FM and keep other healthcare providers informed about the issues related to breastfeeding for women with FM.


Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?
Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis.


Indoor low-volume insecticide spray for the control of Anopheles albimanus in southern Mexico. Village-scale trials of bendiocarb, deltamethrin and cyfluthrin.
A comparative insecticide village-scale trial was carried out to determine the efficacy of low-volume (LV) indoor spray of bendiocarb, deltamethrin and cyfluthrin for the control of Anopheles albimanus in a coastal plain of southern Mexico. Low-volume spray was conducted with knapsack mist-blowers, giving an average discharge rate of 215 ml/min, which deposited droplets of 50-100 microns. Using this technique, 25 houses were treated/sprayman/day as compared with 8 houses/sprayman/day using conventional hand compression pumps. Indicators of LV mortality showed a residual activity of 10 wk as compared with 13 wk of activity for wettable powder (WP) (bendiocarb). When comparing expenditures, LV spray costs were 43% less when using bendiocarb, 83% less with deltamethrin and 74% less with cyfluthrin with respect to the conventional WP spray of the same insecticides. Low-volume spray time was reduced by one-third, with respect to WP. Malaria incidence was reduced by 53 and 56%, respectively, in the bendiocarb LV and deltamethrin LV treated villages as compared with the untreated village.


Utility of Computed Tomography following Anterior Cervical Diskectomy and Fusion.
Study Design Retrospective case series. Objective To assess the utility of postoperative computed tomography (CT) following anterior cervical diskectomy and fusion (ACDF) and to determine the clinical circumstances most likely to lead to an abnormal CT scan. Methods Patients who underwent ACDF at a tertiary center over a span of 5 years were investigated. Only patients who had a minimum of 6 months' postoperative follow-up and a CT within 2 years after the surgery were included in the study group. All the postoperative notes were reviewed to determine indications for the CT, abnormalities identified, and whether the scan led to an alteration in the treatment course. Results The charts of 690 patients who underwent ACDF were reviewed. Of the 690 patients, 45 (7%) had postoperative CTs. These patients accounted for 53 postoperative CT scans, 45 (85%) of which were taken for patients who expressed persistent postoperative symptoms and/or had abnormal imaging. There were no indications for 8 (15%) of the CTs. Patients who had a CT for persistent symptoms and/or abnormal preliminary imaging were significantly more likely to have an abnormal CT (p = 0.03) and/or an alteration in treatment course (p = 0.04) compared with those with no symptomatic or radiologic indication for CT. Conclusions CT is associated with minimal utility regarding the alteration of treatment course when employed in asymptomatic patients. Postoperative CT should be ordered solely for symptomatic patients or those with other abnormal preliminary imaging. Judicious use of postoperative CT will limit the radiation exposure and cost.


In silico toxicologic profile and in vivo trypanocidal activity of estafietin, a sesquiterpene lactone isolated from Stevia alpina Griseb.
Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from Stevia alpina with in vitro activity against T. cruzi and low cytotoxicity against mammalian cells. The aim of this work was to predict the toxicologic profile of estafietin by in silico methods and assess its in vivo activity on a murine model of Chagas disease. Estafietin showed low toxicity according to pkCSM web tool and passed the PAINS filter from PAINS-remover web server. The treatment of infected mice with 1 mg/Kg/day of estafietin for five consecutive days administrated by intraperitoneal route significatively decreased parasitemia levels and reduced inflammatory infiltrates and myocyte damage on muscle tissue. These results suggest that estafietin had effect both on acute and chronic stages of the infection.


Fecundity-reducing pheromone in Argas (Persicargas) arboreus (Ixodoidea: Argasidae).
Fed adult Argas (Persicargas) arboreus produce a fecundity-reducing pheromone which affects all or most females in crowded conditions. Unfed adults and unfed and fed nymphs do not produce this pheromone. The effect of this pheromone is probably additive, increasing with additional crowding of adults. Mechanical disturbance is excluded as the cause of fecundity reduction. Fed females separated by a perforated barrier from crowded adults also exhibit very low fecundity. Adult excretory materials used 31 days post-feeding do not contain the fecundity-reducing pheromone. Preliminary experiments suggest that this pheromone is spatially limited in action, does not affect gonadotropic hormone synthesis and/or release, and does not induce oviposition deterrence behaviour. This may be considered to be a primer pheromone, causing alteration in normal vitellogenin synthesis and/or uptake and deposition in oocytes. The source and chemical nature of this pheromone should be investigated.


The social determinants of inequalities in self-reported health in Europe: findings from the European social survey (2014) special module on the social determinants of health.
Health inequalities persist between and within European countries. Such inequalities are usually explained by health behaviours and according to the conditions in which people work and live. However, little is known about the relative contribution of these factors to health inequalities in European countries. This paper aims to investigate the independent and joint contribution of a comprehensive set of behavioural, occupational and living conditions factors in explaining social inequalities in self-rated health (SRH). Data from 21 countries was obtained from the 2014 European Social Survey and examined for respondents aged 25-75. Adjusted rate differences (ARD) and adjusted rate risks (ARR), generated from binary logistic regression models, were used to measure health inequalities in SRH and the contribution of behavioural, occupational and living conditions factors. Absolute and relative inequalities in SRH were found in all countries and the magnitude of socio-economic inequalities varied considerably between countries. While factors were found to differentially contribute to the explanation of educational inequalities in different European countries, occupational and living conditions factors emerged as the leading causes of inequalities across most of the countries, contributing both independently and jointly with behavioural factors. The observed shared effects of different factors to health inequalities points to the interdependent nature of occupational, behavioural and living conditions factors. Tackling health inequalities should be a concentred effort that goes beyond interventions focused on single factors.


The role of oxidative stress in antipsychotics induced ovarian toxicity.
This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1μM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed. The effect of antioxidants (reduced glutathione (GSH) and quercetin) on the APs-induced cytotoxicity on TICs was investigated. MTT assay showed all APs to reduce TICs viability. CPZ, HAL and CLZ significantly increased the activity of caspases-3, -8 and -9 (P<0.0001, <0.0001 and <0.01, respectively). All APs at IC50s significantly (P<0.0001) increased ROS production, decreased total intracellular glutathione and increased LPO. MTT assay in the presence of antioxidants (reduced GSH (5mM) or quercetin (50mM)) showed each antioxidant to significantly inhibit the effects of APs at their IC50s on TICs viability. In conclusion, oxidative stress seems to be a possible mechanism for APs-induced ovarian and reproductive toxicity.


Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.
Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and upregulated by mutated TP53, a gene commonly altered in ovarian cancer. Pitavastatin-induced apoptosis was blocked by geranylgeraniol and mevalonate, products of the HMGCR pathway, confirming that pitavastatin causes cell death through inhibition of HMGCR. Solvent extracts of human and mouse food were also able to block pitavastatin-induced apoptosis, suggesting diet might influence the outcome of clinical trials. When nude mice were maintained on a diet lacking geranylgeraniol, oral pitavastatin caused regression of Ovcar-4 tumour xenografts. However, when the animal diet was supplemented with geranylgeraniol, pitavastatin failed to prevent tumour growth. This suggests that a diet containing geranylgeraniol can limit the anti-tumour activity of pitavastatin and diet should be controlled in clinical trials of statins.


From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS).
Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties. Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of 'drug-targeting opportunities' give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.


Long-term performance and microbial dynamics of an up-flow fixed bed reactor established for the biodegradation of fluorobenzene.
An up-flow fixed bed reactor (UFBR) was established to investigate the biodegradation of fluorobenzene (FB) under a number of operating conditions, which included variation in the concentration of FB in the feed stream (up to 180 mg l(-1)) and temporary suspension of feeding. Degradation of FB was followed for a period of 8 months under a continuous flow regime. During the operation of the UFBR, FB was never detected in the reactor effluent, being biodegraded by the microbial biofilm or adsorbed to the granular activated carbon (GAC). Biodegradation of FB was observed from the beginning of the reactor operation, and overall, it accounted for 50% of the total amount fed to the bioreactor. High organic loads of FB (210-260 mg d(-1) dm(-3)) were found to affect the biological removal efficiency, possibly due to an inhibitory effect caused by the higher FB concentrations fed to the bioreactor (149-179 mg l(-1)). When FB feeding was suspended for 1 month, biodegradation continued, indicating that the adsorbed FB became bioavailable. Biofilm bacterial dynamics were followed throughout the UFBR operation by denaturing gradient gel electrophoresis and plate-counting techniques, showing that a quite stable community was found in the bioreactor, and this was mainly attributed to the high selective pressure exerted by the presence of FB.


Diagnostic value of event-related evoked potentials N200 and P300 subcomponents in early diagnosis of Alzheimer's disease and mild cognitive impairment.
Event-related potentials (ERPs) have a large application in the evaluation of cognitive processes, particularly in Alzheimer's disease (AD). The aim of the present study was to evaluate the clinical relevance of event-related evoked potentials (N2 and P3 subcomponents) in early diagnosis of AD and mild cognitive impairment (MCI). We prospectively studied 60 subjects. They all underwent the following investigations: neurologic and neuropsychological examination; functional evaluation, i.e., ERPs; cerebral imagery (morphologic and functional). Subjects were classified into 3 groups: group 1: 30 dementia of Alzheimer type (NINCDS-ADRDA, DSM-IV criteria); group 2: 20 MCI; and group 3: 10 control subjects. ERPs were significantly different between the groups (AD, MCI, control subjects), with a marked increase of P3 latencies, particularly when compared with N2 latencies (P < 0.0001). Furthermore, sensitivity was 87% to 95% for the differentiation of AD patients from MCI and control subjects, using prolonged P3 latencies (specificity, 90% to 95%), whereas using N2 prolonged latencies, sensitivity was 70% to 75% (specificity, 70% to 90%). Moreover, in the MCI group, N2 latencies strongly discriminated MCI from control subjects, with 90% sensitivity and 70% specificity and correctly categorized 80% of MCI subjects against 73% for P3. The abnormalities of N2 and P3 components may be linked, in AD and MCI, to an alteration of automatic and controlled attention processing.


Genotoxicity and bioaccumulation of methyl mercury and mercuric chloride in vivo in the newt Pleurodeles waltl.
Larvae and embryos of the urodele amphibian Pleurodeles waltl were raised for several days in water containing low concentrations of methyl mercuric chloride (CH3HgCl) or mercuric chloride (HgCl2). Examination of squash preparations from treated embryos showed that both compounds induced chromosome breaks and c-mitosis. Examination of blood smears from the larvae demonstrated a higher level of micronucleated erythrocytes in the animals raised in the mercury-containing water than in controls raised in uncontaminated water. The bioaccumulation of both compounds was evaluated by determination of mercury levels in the larvae. After 12 days of treatment, concentration factors (concentration in the organism/concentration in the water) of approximately 1200 and approximately 600 were found for methyl mercury and mercuric chloride, respectively.


In vivo muscle force and muscle power during near-maximal frog jumps.
Frogs' outstanding jumping ability has been associated with a high power output from the leg extensor muscles. Two main theories have emerged to explain the high power output of the frog leg extensor muscles, either (i) the contractile conditions of all leg extensor muscles are optimized in terms of muscle length and speed of shortening, or (ii) maximal power is achieved through a dynamic catch mechanism that uncouples fibre shortening from the corresponding muscle-tendon unit shortening. As in vivo instantaneous power generation in frog hind limb muscles during jumping has never been measured directly, it is hard to distinguish between the two theories. In this study, we determined the instantaneous variable power output of the plantaris longus (PL) of Lithobates pipiens (also known as Rana pipiens), by directly measuring the in vivo force, length change, and speed of muscle and fibre shortening in near maximal jumps. Fifteen near maximal jumps (> 50cm in horizontal distance) were analyzed. High instantaneous peak power in PL (536 ± 47 W/kg) was achieved by optimizing the contractile conditions in terms of the force-length but not the force-velocity relationship, and by a dynamic catch mechanism that decouples fascicle shortening from muscle-tendon unit shortening. We also found that the extra-muscular free tendon likely amplifies the peak power output of the PL by modulating fascicle shortening length and shortening velocity for optimum power output, but not by releasing stored energy through recoiling as the tendon only started recoiling after peak PL power had been achieved.


Energy expenditure and substrate metabolism in patients with cirrhosis of the liver: effects of the pattern of food intake.
Patients with liver cirrhosis are often undernourished. In healthy subjects, the pattern of food intake is one of the variables that can influence energy balance and substrate metabolism. The short term (two day) effect of the pattern of food intake in patients with cirrhosis and controls was compared. In a respiration chamber, eight patients with cirrhosis of the liver and 23 controls were fed to estimated energy balance in two meals daily ('gorging' pattern) and four to seven meals daily ('nibbling' pattern). Twenty four hour energy expenditure, expressed as a multiple of the sleeping metabolic rate, was reduced in patients with cirrhosis (1.31 (0.03) v 1.44 (0.02) for controls; p < 0.01) because of an increased sleeping metabolic rate per kg fat free mass in these patients. In both patients and controls, the respiratory quotient was significantly lower during the morning preprandial period (9.00-12.00) on the gorging pattern, reflecting a higher oxidation ratio of fat to carbohydrate compatible with a more catabolic state. For patients with cirrhosis, a nibbling pattern of food intake, including a good breakfast and a late evening meal, would be preferable, in order to have shorter episodes of catabolism during the day.


Expanding the clinical spectrum of ocular anomalies in Noonan syndrome: Axenfeld-anomaly in a child with PTPN11 mutation.
Ocular anomalies have been frequently reported in Noonan syndrome. Anterior segment anomalies have been described in 57% of PTPN11 positive patients, with the most common findings being corneal changes and in particular, prominent corneal nerves and cataracts. We report on a neonate with a confirmed PTPN11 mutation and ocular findings consistent with Axenfeld anomaly. The patient initially presented with non-immune hydrops and subsequently developed hypertrophic cardiomyopathy and dysmorphic features typical of Noonan syndrome. While a pathogenic mutation in PTPN11 was confirmed, prior testing for the two common genes associated with Axenfeld-Rieger syndrome, PITX2, and FOXC1 was negative. This finding expands the spectrum of anterior chamber anomalies seen in Noonan syndrome and perhaps suggests a common neural crest related mechanism that plays a critical role in the development of the eye and other organs.


[Radiotherapy in breast cancer: standards and new directions, accelerated partial breast irradiation].
Radiotherapy as a part of the breast cancer treatment has evolved in the last decades. Post-mastectomy radiotherapy produces a substantial reduction in the risk of local recurrence as well as a moderate, but definitive reduction in long-term breast cancer mortality in women at high risk of locoregional failure. Whole-breast irradiation, as part of breast-conservation therapy, has well-established results with good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This has led investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) is a collection of radiotherapy techniques that deliver higher daily doses of radiation to the surgical cavity with margin over a shorter time than whole breast irradiation (from 6-6.5 weeks to 1 week). Early results of this approach have demonstrated excellent local control, minimal acute toxicity, and are more convenient for the patient. Phase III randomized clinical trials are currently underway to assess local control, acute and chronic toxicities. APBI extend the choise of breast conservation.


The role of thrombophilia in patients with retinal vein occlusion and no systemic risk factors.
The role of thrombophilia in the etiology of retinal vein occlusion (rVO) has not been adequately clarified. The aim of this study was to examine the prevalence of thrombophilia among RVO patients with and without systemic risk factors and among patients younger and older than 50 years. Prospective case-control study. One hundred and twenty one patients with RVO, including 92 with acquired risk factors (hypertension, hyperlipidemia, and diabetes mellitus) and 29 without these factors. The control group included 60 persons matched for age, sex, and risk factors. All participants were screened for Leiden mutation (FV Leiden), hyperprothrombinemia (20210 G/A mutation) and deficiency of protein C, S, and antithrombin. The prevalence of FV Leiden was significantly higher among RVO patients without risk factors (24.1%) than among controls without risk factors (0%; p = 0.034) and among RVO patients with acquired disorders (4.3%; p = 0.001). No significant differences were found in the prevalence of the other investigated thrombophilic factors. In all, 37.9% patients without acquired risk factors were positive for at least 1 thrombophilic factor compared with 7.6% RVO patients with acquired risk factors (p < 0.001) and 8.3% of the controls (p < 0.001). There was no significant difference in the prevalence of thrombophilic disorders among RVO patients according to age. FV Leiden is significantly more frequent among RVO patients without acquired risk factors. Thrombophilia plays a much more important role in the pathogenesis of RVO in patients without acquired risk factors. Screening for thrombophilia is thus indicated only for patients in whom these factors have been excluded.


Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children.
For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.


A novel lectin from Sarcophaga. Its purification, characterization, and cDNA cloning.
A novel C-type lectin that agglutinates rabbit red cells was purified from NIH-Sape-4 cells derived from the flesh fly (Sarcophaga peregrina), and its cDNA was isolated. This lectin, named granulocytin, appeared to be a trimer of a 20-kDa subunit consisting of 151 amino acid residues. The gene for granulocytin was activated in third instar larvae, and its expression was enhanced when the larval body wall was injured. In third instar larvae, granulocytin was found to be synthesized by hemocytes and secreted into the hemolymph. The molecular mass and gene expression patterns of granulocytin were very similar to those of Drosophila lectin that we reported previously (Haq, S., Kubo, T., Kurata, S., Kobayashi, A., and Natori, S. (1996) J. Biol. Chem. 271, 20213-20218). However, these two lectins showed amino acid identities of 20% at most, and no significant hapten sugar for granulocytin was identified.


Electron Transfer of Cytochrome c on Surface-Enhanced Raman Scattering-Active Substrates: Material Dependence and Biocompatibility.
Surface-enhanced Raman spectroscopy (SERS) represents a powerful approach for studying the structure and reaction of proteins in fundamental and applied sciences. The surface properties of SERS-active materials determine important parameters such as Raman enhancement ability, biocompatibility, and electronic communication between supports and proteins. Here, electron transfer (ET) of Cyt c on noble metals and transition metals is investigated by SERS spectroscopy. The results here indicate that the ET occurs from the reduced state of Cyt c to silver substrate, depending on the laser wavelengths. Nickel and cobalt can directly transfer electrons to the oxidized state of Cyt c, which enables a reductive activity of these transition metal nanoparticles (NPs). This study demonstrates the role of transition metals as electron donors for Cyt c and has proved that the charge transfer theory for SERS is applicable for explanation of the ET between Cyt c and Ag NPs.


Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer.
Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be utilized for extended release analgesia in patients undergoing radiation (RT) for head-and-neck cancer (HNC) and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. We performed a prospective trial that enrolled participants > 18 years with histologically confirmed HNC who were scheduled to receive RT. Analgesia was prescribed in accordance with the WHO pain ladder. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30 mg of morphine sulfate equivalent and was titrated weekly during RT. Pain level and effect on quality of life were assessed using the Brief Pain Inventory. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. Twenty-six eligible patients were enrolled. Microsphere oxycodone was initiated in 16 (61.5%) patients. Six (23.1%) patients utilized a gastrostomy tube to administer microsphere oxycodone during all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy. No patients were discontinued due to toxicity or difficulty with administration. Ratings for average pain was 3.1 (± 3.4) at enrollment, 4.0 (± 2.4) at week 6 of RT, and 1.8 (± 2.2) at 3-month follow-up. These results support the feasibility and safety of microsphere oxycodone for extended release analgesia among patients with HNC undergoing RT.


Super-resolution imaging of mitochondrial cristae using a more hydrophobic far-red Si-rhodamine probe.
Mitochondrial probe SiRPFA was synthesized by attaching a long perfluoroalkyl chain on Si-rhodamine cationic dye. High lipophilicity endowed SiRPFA with mitochondrial membrane potential independent properties. Under stimulated emission depletion microscopy, SiRPFA clearly revealed changes in mitochondrial cristae morphology during autophagy induced by starvation or apoptosis.


Primary yolk sac tumor in the abdominal wall in a 20-year-old woman: A case report.
Extragonadal yolk sac tumors (YSTs) are rare, with only a low reported tumor occurrence outside the gonads locally and abroad. Extragonadal YSTs are usually a diagnostic challenge, because they are infrequent, but also because a thoughtful and detailed differential diagnostic process must be performed. Here we present a case of an abdominal wall YST in a 20-year-old woman admitted with a tumor in the lower abdomen close to the umbilicus. The tumorectomy was performed. The histological examination revealed characteristic findings such as Schiller-Duval bodies, loose reticular structures, papillary structures, and eosinophilic globules. According to the immunohistochemical staining, the tumor tissue was positive for broad-spectrum cytokeratin, Spalt-like transcription factor 4, glypican-3, CD117, and epithelial membrane antigen. Based on the clinical information, histological features, and immunohistochemical staining profile, the tumor was diagnosed as a YST present in the abdominal wall. Based on the clinical information, histological features, and immunohistochemical staining profile described above, the tumor was diagnosed as a primary YST in the abdominal wall.


[Transcranial micropolarization in the treatment of specific speech disorders in children].
Efficacy of transcranial micropolarization (TCMP) was studied in the treatment of 34 children aged 3-6 years with disorders of expressive speech (DES). The course of TCMP improved speech activity, increased active vocabulary and listening attention. Children who were able to use phrases in their speech used longer phrases after the therapy. The analysis of quantitative EEG demonstrated potentiation of alpha-rhythm power in the temporal and occipital areas, attenuation of the power in theta-band (4-8.5 Hz) in the central and frontal zones of the cortex after TCMP treatment.


Understanding the dynamics of seasonal influenza in Italy: incidence, transmissibility and population susceptibility in a 9-year period.
Influenza surveillance systems have been established in many countries in the world, yielding timely information about the intensity and features of seasonal outbreaks. Such data have also been used to estimate epidemiological parameters and to evaluate the effect of factors on infection dynamics. However, little is known about the extent of under-reporting in surveillance data, and thus of the true influenza incidence in the population. Through mathematical and statistical modelling, we analysed Italian epidemiological and virological surveillance data collected together with serological data derived from influenza vaccine clinical trials performed in Italy. Depending on the season, the reporting rate estimates ranged between 20% and 33% of the total incidence with higher reporting rates in seasons dominated by A/H3N2 virus. Despite a generally higher number of individuals immune against A/H3N2 viruses, effective reproduction ratios were quite similar in all seasons varying between 1·2 and 1·4. We observed an age-dependent transmissibility for different subtypes: susceptible children were more likely than susceptible adults and elderly to get infected when A/H1N1 or B strains were circulating, while no clear age-dependence was found for A/H3N2. We also perform sensitivity analysis under different assumptions for vaccine effectiveness, generation time (GT) and model variants; we found that the overall results in predicted patterns were extremely similar, with a slightly better fit obtained with shorter GTs. Our results provide relevant information on the influenza dynamics to fine-tune intervention strategies and for data collection improvement.


Optimization of the Electrospray Process to Produce Lignin Nanoparticles for PLA-Based Food Packaging.
The development of new processing methods is required in order to meet the continuous demand for thinner films with excellent barrier properties for food packaging and other applications. In this study, rice husk organosolv lignin nanoparticles were prepared using the electrospray method, which were applied to produce polylactic acid (PLA)-based films for food packaging. The effect of the following electrospray parameters has been investigated: lignin concentration (LC) ranging from 5-50 mg/mL, flow rate (FR) from 0.5-1 mL/min, applied voltage from 10-30 kV, and tip-to-collector distance (TCD) from 10-25 cm, on the morphology, size, polydispersity index (PDI), and Zeta potential (ZP) of lignin nanoparticles (LNPs). The response surface methodology with a Box-Behnken design was applied to optimize these parameters, while dynamic light scattering (DLS) and scanning electron microscopy (SEM) analyses were used to characterize the controlled LNPs. The results showed that the LNPs shape and sizes represent a balance between the solvent evaporation, LC, applied voltage, TCD and FR. The application of optimal electrospray conditions resulted in the production of LNPs with a spherical shape and a minimal size of 260 ± 10 nm, a PDI of 0.257 ± 0.02, and a ZP of -35.2 ± 4.1 mV. The optimal conditions were achieved at LC = 49.1 mg/mL and FR = 0.5 mL/h under an applied voltage of 25.4 kV and TCD = 22 cm. Then, the optimized LNPs were used to improve the properties of PLA-based films. Three types of PLA-lignin blend films were casted, namely lignin/PLA, LNPs/PLA and PLA-grafted LNPs. PLA-grafted LNPs exhibited a more uniform dispersion in PLA for lignin contents of up to 10% than other composite samples. Increasing the lignin content from 5% to 10% in PLA-grafted LNPs resulted in a significant increase in elongation at break (up to four times higher than neat PLA). The presence of PLA-grafted lignin led to a substantial reduction in optical transmittance in the UV range, dropping from 58.7 ± 3.0% to 1.10 ± 0.01%, while maintaining excellent transparency to visible light compared to blends containing lignin or LNPs. Although the antioxidant capacity of unmodified lignin is well-known, a substantial increase in antioxidant capacity was observed in LNPs and PLA-grafted LNP films, with values exceeding 10 times and 12 times that of neat PLA, respectively. These results confirm the significant potential of using studied films in food packaging applications.


Ultrasound-guided percutaneous transhepatic cholangiography and drainage in patients with hilar cholangiocarcinoma.
The use of ultrasound-guided PTCD in 49 patients with hilar cholangiocarcinoma was evaluated. In 11 patients PTCD was performed as a preoperative measure either to outline tumor extension or to treat cholangitis. Postoperatively, the catheters were used to stent bilioenteric anastomoses and served to guide iridium wires for radiotherapy in nine patients with nonresectable tumor or tumor residue after resection. In 20 inoperable patients with tumor diameter smaller than 3 cm and in whom at least one catheter could be manipulated through the tumor, PTCD was combined with internal and external radiotherapy. The remaining 18 patients were palliated with PTCD only. In 29 patients (59%) complete drainage of the biliary system was achieved. Twenty-seven of these had complete internal drainage using endoprostheses. Two had a combination of an endoprosthesis and external catheter drainage. Of the 20 patients (41%) with incomplete drainage, 12 had endoprostheses, four had a catheter and an endoprosthesis, and in the remaining four external catheter drainage was the optimum result. PTCD was successful in treating eight of ten patients with cholangitis and 12 of 16 patients with pruritus. Procedure-related complication occurred in 11 patients (22%). With the exception of one, all complications could be classified as minor, requiring only conservative measures. A major complication was seen in a patient with ascitic fluid and severe cholangitis. PTCD caused a bacterial peritonitis, of which the patient died. The median survival of patients treated with PTCD alone only was 4 months. A significant increase in survival was noted in patients treated with PTCD and radiotherapy (median survival 8 months).(ABSTRACT TRUNCATED AT 250 WORDS)


Models of retinal diseases and their applicability in drug discovery.
The impact of vision debilitating diseases is a global public health concern, which will continue until effective preventative and management protocols are developed. Two retinal diseases responsible for the majority of vision loss in the working age adults and elderly populations are diabetic retinopathy (DR) and age-related macular degeneration (AMD), respectively. Model systems, which recapitulate aspects of human pathology, are valid experimental modalities that have contributed to the identification of signaling pathways involved in disease development and consequently potential therapies. Areas covered: The pathology of DR and AMD, which serve as the basis for designing appropriate models of disease, is discussed. The authors also review in vitro and in vivo models of DR and AMD and evaluate the utility of these models in exploratory and pre-clinical studies. Expert opinion: The complex nature of non-Mendelian diseases such as DR and AMD has made identification of effective therapeutic treatments challenging. However, the authors believe that while in vivo models are often criticized for not being a 'perfect' recapitulation of disease, they have been valuable experimentally when used with consideration of the strengths and limitations of the experimental model selected and have a place in the drug discovery process.


Mitochondrial dysfunction, oxidative stress and neurodegeneration.
Mitochondria play a critical role in several metabolic processes and apoptotic pathways, regulating life cycle from the cradle to the grave. Despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question "is mitochondrial dysfunction a necessary step in neurodegeneration?" is still unanswered. Moreover, a growing body of evidence seems to indicate that oxidative stress, which is increased in damaged mitochondria, is an earlier event associated with neurodegeneration. Here we examine the current evidences in this field, which indicate a key role of mitochondria and oxidative stress in contributing to the neurodegenerative processes.


Meditation and the brain - Neuronal correlates of mindfulness as assessed with near-infrared spectroscopy.
Mindfulness meditation as a therapeutic intervention has been shown to have positive effects on psychological problems such as depression, pain or anxiety disorders. In this study, we used functional near-infrared spectroscopy (fNIRS) to detect differences in hemodynamic responses of meditation experts (14 participants) and a control group (16 participants) in a resting and a mindfulness condition. In both conditions, the sound of a meditation bowl was used to find group differences in the auditory system and adjacent cortical areas. Different lateralization patterns of the brain were found in expert meditators while being in a resting state (amplified left hemisphere) or being in mindfulness state (amplified right hemisphere). Compared to the control group, meditation experts had a more widespread pattern of activation in the auditory cortex, while resting. In the mindfulness condition, the control group showed a decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the meditation experts had a significant increase in those areas. In addition, meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond the meditative task itself, indicating possible long-term changes in the brain and their positive effects on empathy, meta cognitive skills and health.


[The second generation of gastric antisecretory agents: omeprazole].
Omeprazole is the first representative of a new class of gastric acid secretion inhibitors. It acts by specific and prolonged inhibition of H+K+ ATPase, or proton pump, which is the terminal and compulsory stage of acid secretion by the parietal cells. The drug therefore inhibits both basal and stimulated secretion. It appears from therapeutic trials that omeprazole administered in doses of 20 mg a.m. once a day is superior to the H2-receptor antagonists in the healing of active duodenal ulcers and ulcerated reflux oesophagitis. It is as active or slightly more active than histamine inhibitors in gastric ulcers. Finally, it is the treatment of choice to prevent ulcerations in Zollinger-Ellison syndrome. These are the 4 indications for omeprazole at the moment. The use of that drug for periods of a few weeks has not given rise to any significant side-effect.


Effect of N6-methyladenosine methylation-related gene signature for predicting the prognosis of hepatocellular carcinoma patients.
Hepatocellular carcinoma (HCC) is a common cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is linked to the occurrence and development of cancer. We then developed a prognostic model as an independent risk factor with which predict the prognosis of HCC. We obtained the gene expression and clinical data of HCC patients from the TCGA databases. The prognostic value of m6A methylation-related genes in patients who had HCC were subjected to comprehensive bioinformatics analysis. We use Risk Score = ∑ i = 1 n Coe f i × X i to construct the risk scoring formula. We collected pathological specimens from 68 patients who had HCC, and conducted immunohistochemical staining experiments on the specimens. There was a significant correlation between candidate m6A methylation-related genes (YTHDF2, METTL14 and ZC3H13) overall survival of HCC patients. Among the 68 HCC patient specimens that underwent immunohistochemical staining, all cancer tissues were positive for METTL14, YTHDF2, and ZC3H13 staining in contrast to the adjacent tissues. We conducted a Kaplan-Meier survival analysis. The results showed that patients who had low METTL14 expression had a longer survival time than those of patients who had high METTL14 expression. Also, patients with low YTHDF2 expression had a longer survival time than patients with high YTHDF2 expression. Finally, patients with high ZC3H13 expression lived longer than those with low ZC3H13 expression. This result is consistent with the bioinformatics analysis conclusion above. Generally, the prognostic model that was based on m6A methylation-related genes in this study can effectively predict the prognosis of HCC patients.


A new type of high affinity folic acid transporter in the protozoan parasite Leishmania and deletion of its gene in methotrexate-resistant cells.
The protozoan parasite Leishmania is a folate auxotroph and thus depends on the uptake of folate from the environment to meet its folate requirement. We show here that Leishmania contains several putative pteridine transporter genes. Some of these genes are deleted in methotrexate-resistant Leishmania cells where there is no measurable uptake of methotrexate. Transport studies suggest that Leishmania has more than one active folate transporter, and one of these, named FT5, corresponds to a very high affinity folate transporter (K(m) 84 nm). The uptake of both folate and methotrexate was impaired in an FT5 null mutant at low substrate concentrations (50 nm), although transport properties at higher concentrations (1000 nm) were not statistically different between wild-type and the FT5 null mutant. Modulation of the expression of FT5 also changes the susceptibility of Leishmania cells to methotrexate. These results have permitted the characterization of a novel class of folate transporters and suggest that the parasite Leishmania has several gene products possibly transporting folates and related molecules under varying conditions.


[Acute natural death in adults with special reference to the under-50 age group].
The cases of acute natural death of persons in the age group below 50 years were analysed in relation to the whole number of autopsies performed in the district of Leipzig (German Democratic Republic) in 1980. From a total of 137 cases, 103 (75.2%) were males and 34 (24.8%) females. The incidence per 100,000 inhabitants was 14.8 in males and 4.9 in females. The most common cause of death in the male group was the chronic ischemic heart disease ( CIHD ) with its complications. In females the noncoronarogenic death dominated. In contrast to other publications, we found only few thromboses (11%). Especially high was the number of embolia of the lung and the frequency of ruptured cerebral aneurysms in females. Of special interest are high physical activity in sports in combination with CIHD , anomalies of the coronary arteries, and hypertrophic cardiomyopathy which often causes sudden unexpected death. The results are discussed and other rare causes of acute death summarized. It seems from the literature also important to investigate histologically the heart muscle in all cases of unknown causes of acute death.


Staphylococcus aureus strains associated with food poisoning outbreaks in France: comparison of different molecular typing methods, including MLVA.
Staphylococcal food poisoning outbreaks (SFPOs) are frequently reported in France. However, most of them remain unconfirmed, highlighting a need for a better characterization of isolated strains. Here we analyzed the genetic diversity of 112 Staphylococcus aureus strains isolated from 76 distinct SFPOs that occurred in France over the last 30 years. We used a recently developed multiple-locus variable-number tandem-repeat analysis (MLVA) protocol and compared this method with pulsed field gel electrophoresis (PFGE), spa-typing and carriage of genes (se genes) coding for 11 staphylococcal enterotoxins (i.e., SEA, SEB, SEC, SED, SEE, SEG, SEH, SEI, SEJ, SEP, SER). The strains known to have an epidemiological association with one another had identical MLVA types, PFGE profiles, spa-types or se gene carriage. MLVA, PFGE and spa-typing divided 103 epidemiologically unrelated strains into 84, 80, and 50 types respectively demonstrating the high genetic diversity of S. aureus strains involved in SFPOs. Each MLVA type shared by more than one strain corresponded to a single spa-type except for one MLVA type represented by four strains that showed two different-but closely related-spa-types. The 87 enterotoxigenic strains were distributed across 68 distinct MLVA types that correlated all with se gene carriage except for four MLVA types. The most frequent se gene detected was sea, followed by seg and sei and the most frequently associated se genes were sea-seh and sea-sed-sej-ser. The discriminatory ability of MLVA was similar to that of PFGE and higher than that of spa-typing. This MLVA protocol was found to be compatible with high throughput analysis, and was also faster and less labor-intensive than PFGE. MLVA holds promise as a suitable method for investigating SFPOs and tracking the source of contamination in food processing facilities in real time.


Self-assembly of functional molecules into 1D crystalline nanostructures.
Self-assembled functional nanoarchitectures are employed as important nanoscale building blocks for advanced materials and smart miniature devices to fulfill the increasing needs of high materials usage efficiency, low energy consumption, and high-performance devices. One-dimensional (1D) crystalline nanostructures, especially molecule-composed crystalline nanostructures, attract significant attention due to their fascinating infusion structure and functionality which enables the easy tailoring of organic molecules with excellent carrier mobility and crystal stability. In this review, we discuss the recent progress of 1D crystalline self-assembled nanostructures of functional molecules, which include both a small molecule-derived and a polymer-based crystalline nanostructure. The basic principles of the molecular structure design and the process engineering of 1D crystalline nanostructures are also discussed. The molecular building blocks, self-assembly structures, and their applications in optical, electrical, and photoelectrical devices are overviewed and we give a brief outlook on crucial issues that need to be addressed in future research endeavors.


Recovery of an Injured Cingulum via the Lateral Cholinergic Pathway in a Patient with Traumatic Brain Injury.
We report on a patient with traumatic brain injury who showed recovery of an injured cingulum via the lateral cholinergic pathway, using diffusion tensor tractography (DTT). A 63-year-old man underwent craniotomy for subarachnoid hemorrhage and subdural hemorrhage in both frontotemporal lobes, which occurred by hitting his head against a floor after falling from approximately 2 m. The Wechsler Intelligence Scale and the Seoul neuropsychological screening battery were used for evaluation of cognitive function. At 4 weeks after onset, the patient exhibited mild cognitive impairment (total IQ, 85; verbal immediate recall, 26.76 percentile; visual immediate recall, 29.81 percentile; verbal delayed recall, 24.51 percentile; visual delayed recall, 11.70 percentile). By contrast, at the 9-month evaluation, the cognitive impairment had improved as much as total IQ, 96; verbal immediate recall, 56.75 percentile; visual immediate recall, 89.49 percentile; verbal delayed recall, 78.23 percentile; and visual delayed recall, 89.07 percentile. On 4-week DTT, discontinuations were observed superior to the genu of the corpus callosum in both cingula. However, on 9-month DTT, the discontinued anterior part of the right cingulum was elongated inferoposteriorly through an unusual neural tract, which ran through the external capsule and the white matter of the temporo-occipital lobes. The results of this study seem to suggest a mechanism for recovery of an injured cingulum after brain injury.