Intermolecular Catalytic Asymmetric Iodoetherification of Unfunctionalized Alkenes.

A newly prepared trinuclear Zn3-(R,S,S)-aminoiminobinaphthoxide complex (triZn-II) catalyzed the first general intermolecular asymmetric iodoetherification of unfunctionalized alkenes. Using triZn-II, the iodoetherification reaction of unfunctionalized alkenes with o-nitrophenols proceeded smoothly to give the products with up to 92.5:7.5 er, and diene substrates were converted to the products with up to 99:1 er with the formation of a meso-isomer (dl/meso = 78/22). The chiral iodoethers gave a new platform for the synthesis of chiral morpholines.

Catalytic Asymmetric Iodoesterification of Simple Alkenes.

Catalytic asymmetric iodoesterification of simple alkenes was achieved using a dinuclear zinc-3,3'-(R,S,S)-bis(aminoimino)binaphthoxide (di-Zn) complex. For iodoesterification using p-methoxybenzoic acid, the N-iodonaphthalenimide (NIN)-I2 system was effective for producing iodoesters in a highly enantioselective manner. The synthetic utility of chiral iodo-p-methoxybenzoates was also demonstrated. The quartet of metal ionic bond, hydrogen bond, halogen bond, and π-π stacking is harmonized on the single reaction sphere of di-Zn catalyst for enabling the highly enantioselective catalytic asymmetric iodoesterification of simple alkenes for the first time.

Subretinal and Retrolaminar Migration of Intraocular Silicone Oil Detected on CT.

BACKGROUND AND PURPOSE: Intraocular silicone oil injection has been used to treat complicated retinal detachments, and recently its retrolaminar and intracranial migration has been reported. The purpose of this study was to document the prevalence of posterior migration of intraocular silicone oil on head CT and describe the clinical and radiologic findings. MATERIALS AND METHODS: This retrospective study included 57 patients with intraocular silicone oil injection who underwent unenhanced head CT between November 2008 and July 2018. All images were visually evaluated for subretinal and retrolaminar migration of intraocular silicone oil involving the anterior visual pathway (optic nerve, optic chiasm, and optic tract) and the ventricular system. Attenuation values of those structures were measured and compared with those of the contralateral or adjacent normal structures. RESULTS: We detected subretinal and retrolaminar silicone oil migration in 7 of the 57 patients (12%), noting silicone oil at the optic nerve head (n = 2), retrolaminar optic nerve (n = 5), optic chiasm (n = 3), optic tract (n = 3), and in the lateral ventricles (n = 1). Attenuation values of the structures with silicone oil migration were significantly higher than those of the control regions (optic nerve head, 69.2 ± 12.4 vs 29.8 ± 10.2 HU, P < .001; retrolaminar optic nerve, 59.9 ± 11.6 vs 30.9 ± 8.6 HU, P < .001; optic chiasm, 74.2 ± 11.0 vs 25.6 ± 6.9 HU, P < .001; optic tract, 70.1 ± 4.7 vs 28.7 ± 7.2 HU, P < .001). No significant ophthalmic or neurologic complications were documented in the patients with silicone oil migration. CONCLUSIONS: Subretinal and retrolaminar migration of intraocular silicone oil is common. Although there were no apparent complications associated with silicone oil migration, the radiologist and clinician should be aware of this phenomenon.

Etiology-Specific Mineralization Patterns in Patients with Labyrinthitis Ossificans.

BACKGROUND AND PURPOSE: Our aim was to identify whether specific patterns of ossification in labyrinthitis ossificans are associated with the known risk factors. Labyrinthitis ossificans has been described as sequela of prior temporal bone trauma, prior infection, and other disorders including sickle cell disease. Specific patterns of mineralization in the membranous labyrinth associated with these risk factors has not been previously described. MATERIALS AND METHODS: This was a retrospective study evaluating temporal bone CT scans at our institution from November 2005 to May 2018 in patients with labyrinthitis ossificans. Membranous labyrinthine structures evaluated for ossification included the following: basal, middle, and apical cochlear turns; lateral, posterior, and superior semicircular canals; and the vestibule for both ears in all patients. These structures were assigned a severity score, 0-4, based on degree of mineralization. Clinical records were reviewed for potential labyrinthitis ossificans risk factors. Basic descriptive statistics and a mixed model were used to correlate the degree and patterns of ossification with clinical history. RESULTS: Forty-four patients (58 ears) with labyrinthitis ossificans were identified and evaluated. The most common risk factors were chronic otomastoiditis (n = 18), temporal bone surgery (n = 9), temporal bone trauma (n = 6), sickle cell disease (n = 5), and meningitis (n = 4). For all etiologies, the semicircular canals were most severely affected, and the vestibule was the least. In patients with prior temporal bone surgery, significantly greater mineralization was seen in the basal turn of the cochlea (P = .027), the vestibule (P = .001), and semicircular canals (P < .001-.008). No significant pattern was identified in patients with meningitis, sickle cell disease, or trauma. CONCLUSIONS: Significant patterns of mineralization in labyrinthitis ossificans were observed in patients with prior temporal bone surgery. For all etiologies, the semicircular canals were most severely affected. No significant mineralization pattern was observed in patients with chronic otomastoiditis, meningitis, sickle cell disease, or prior temporal bone trauma.

CT Texture Analysis of Cervical Lymph Nodes on Contrast-Enhanced [18F] FDG-PET/CT Images to Differentiate Nodal Metastases from Reactive Lymphadenopathy in HIV-Positive Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: Differentiating nodal metastases from reactive adenopathy in HIV-infected patients with [18F] FDG-PET/CT can be challenging because lymph nodes in HIV-positive patients often show increased [18F] FDG uptake. The purpose of this study was to assess CT textural analysis characteristics of HIV-positive and HIV-negative lymph nodes on [18F] FDG-PET/CT to differentiate nodal metastases from disease-specific nodal reactivity. MATERIALS AND METHODS: Nine HIV-positive patients with head and neck squamous cell carcinoma (7 men, 2 women; 29-62 years of age; median age, 48 years) with 22 lymph nodes (≥1 cm) who underwent contrast-enhanced CT with [18F] FDG-PET followed by pathologic evaluation of cervical lymph nodes were retrospectively reviewed. Twenty-six HIV-negative patients with head and neck squamous cell carcinoma with 61 lymph nodes were evaluated as a control group. Each lymph node was manually segmented, and an in-house-developed Matlab-based texture analysis program extracted 41 texture features from each segmented volume. A mixed linear regression model was used to compare the pathologically proved malignant lymph nodes with benign nodes in the 2 enrolled groups. RESULTS: Thirteen (59%) lymph nodes in the HIV-positive group and 22 (36%) lymph nodes in the HIV-negative control group were confirmed as positive for metastases. There were 7 histogram features (P = .017-0.032), 3 gray-level co-occurrence features (P = .009-.025), and 9 gray-level run-length features (P < .001-.033) that demonstrated a significant difference in HIV-positive patients with either benign or malignant lymph nodes. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method of obtaining additional quantitative information to differentiate nodal metastases from disease-specific nodal reactivity in HIV-positive patients with head and neck squamous cell carcinoma.

Significant increase of Echinococcus multilocularis prevalence in foxes, but no increased predicted risk for humans.

The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent of alveolar echinococcosis (AE), poses a public health risk. A previously designed risk map model predicted a spread of E. multilocularis and increasing numbers of alveolar echinococcosis patients in the province of Limburg, The Netherlands. This study was designed to determine trends in the prevalence and worm burden of E. multilocularis in foxes in a popular recreational area in the southern part of Limburg to assess the risk of infection for humans and to study the prevalence of E. multilocularis in dogs in the adjacent city of Maastricht. Thirty-seven hunted red foxes were tested by the intestinal scraping technique and nested PCR on colon content. Additionally, 142 fecal samples of domestic dogs from Maastricht were analyzed by qPCR for the presence of E. multilocularis. In foxes, a significantly increased prevalence of 59% (95% confidence interval 43-74%) was found, compared to the prevalence of 11% (95% CI 7-18%) in 2005-2006. Average worm burden increased to 37 worms per fox, the highest since the first detection, but consistent with the prediction about the parasite population for this region. Updated prediction on the number of AE cases did not lead to an increase in previous estimates of human AE cases up to 2018. No dogs in the city of Maastricht tested positive, but results of questionnaires showed that deworming schemes were inadequate, especially in dogs that were considered at risk for infection.

Distinguishing adrenal adenomas from non-adenomas on dynamic enhanced CT: a comparison of 5 and 10 min delays after intravenous contrast medium injection.

AIM: To evaluate the usefulness of several parameters of 5 min compared to 10 min delayed contrast-enhanced CT in distinguishing adenomas from non-adenomas. MATERIALS AND METHODS: The study population consisted of 94 patients (52 men and 42 women; mean age 62 years) with 103 adrenal lesions (75 adenomas and 28 non-adenomas). In each patient, unenhanced CT was followed by early, 5 and 10 min enhanced CT. Diagnostic parameters included delayed enhanced attenuation at 5 and 10 min, washout attenuation (WO) at 5 and 10 min, absolute percentage washout (APW) at 5 and 10 min, and relative percentage washout (RPW) at 5 and 10 min. The accuracy of each parameter for diagnosing adenomas from non-adenomas was calculated using receiver operating characteristic (ROC) analysis. RESULTS: Upon comparison between 5 and 10 min delayed contrast-enhanced CT for differentiating total adenomas or lipid-poor adenomas from non-adenomas, there was no significant difference in the area under the binomial ROC curve (Az) values of delayed enhanced attenuation (total adenomas versus non-adenomas, p = 0.164; lipid-poor adenomas versus non-adenomas, p = 0.178), WO (total adenomas versus non-adenomas, p = 0.216; lipid-poor adenomas versus non-adenomas, p = 0.230), APW (total adenomas versus non-adenomas, p = 0.401; lipid-poor adenomas versus non-adenomas, p = 0.870), or RPW (total adenomas versus non-adenomas, p = 0.160; lipid-poor adenomas versus non-adenomas, p = 0.780). CONCLUSION: Five minute contrast-enhanced CT was as useful as 10 min contrast-enhanced CT for differentiation of adrenal adenomas from non-adenomas.

Mapping the increasing risk of human alveolar echinococcosis in Limburg, The Netherlands.

The parasite Echinococcus multilocularis was first detected in The Netherlands in 1996 and repeated studies have shown that the parasite subsequently spread in the local population of foxes in the province of Limburg. It was not possible to quantify the human risk of alveolar echinococcosis because no relationship between the amount of parasite eggs in the environment and the probability of infection in humans was known. Here, we used the spread of the parasite in The Netherlands as a predictor, together with recently published historical records of the epidemiology of alveolar echinococcosis in Switzerland, to achieve a relative quantification of the risk. Based on these analyses, the human risk in Limburg was simulated and up to three human cases are predicted by 2018. We conclude that the epidemiology of alveolar echinococcosis in The Netherlands might have changed from a period of negligible risk in the past to a period of increasing risk in the forthcoming years.

Human beings are highly susceptible to low doses of Trichinella spp.

Trichinella is an important foodborne pathogen causing considerable morbidity and mortality. To prevent human trichinellosis, meat inspection for Trichinella spp. at slaughter is a key instrument. Current testing is based on minimal infectious dose in humans, but a scientific basis for this approach is lacking. To this end, a dose-response model must be developed, allowing translation of exposure into disease burden at the population level. We developed novel methods for dose-response assessment using outbreak data incorporating sexual reproduction of the parasite. A selection of suitable outbreak studies, reporting numbers exposed and infected, as well as estimated doses, was collated from a literature study. Humans appear to be highly susceptible: exposure to low doses (few larvae) is associated with a considerable risk of infection. As a consequence, levels of Trichinella in meat must be low to maintain acceptable health risks.

Public health risk analysis of European bat lyssavirus infection in The Netherlands.

We present the frequency and the nature of contact incidents of the Serotine bat, Eptesicus serotinus, with humans and with companion animals (specifically cats and dogs), in The Netherlands between 2000 and 2005. Out of 17 bats in bite contact with humans, five tested positive for European bat lyssavirus (EBLV) type 1a. Cats had the most numerous contacts with bats (49 times) but a relatively low number of these bats were EBLV positive (six times). We estimated that the average incidence of human bat rabies infection might be between once per year and once per 700 years, depending mainly on the number of infectious viral particles in bat saliva. The risk of bat rabies is higher between April and October, and in the northern half of the country. This is the first study in Europe describing the risk of human bat rabies after bat contact incidents.

Transmission dynamics of Echinococcus multilocularis; its reproduction number, persistence in an area of low rodent prevalence, and effectiveness of control.

On the basis of high prevalences of Echinococcus multilocularis in the growing fox populations in Central Europe, its total biomass may have increased significantly in the past 20 years. E. multilocularis is now also found in areas outside the known endemic area in Central Europe. Therefore, E. multilocularis, the causative agent of a serious parasitic zoonosis, might be of major concern for public health and a challenge to control. Some experimental field trials to control E. multilocularis using an anti-worm drug reduced parasite burden in a contaminated region during the control campaign, but failed to eradicate the parasite completely. It was our aim to develop a mathematical model describing the biomass of egg, larval, and adult worm stages of the E. multilocularis life-cycle, and simulate a hypothetical control campaign. Additionally, we derived the reproduction number of this parasite and explored conditions for the persistence of the parasite's life-cycle. Our model shows that while control campaigns rapidly reduce the worm burden in the definitive host, and consequently eggs in the environment, the pool of larvae in the intermediate host remains large. The parasite's life-cycle persists in a region where prevalence in the intermediate host is low (approximately 1%). Therefore, we conclude that the parasite is likely to re-emerge if control is discontinued on the basis of reduced worm population. Continued treatment of the definitive host is required to eradicate the larval stage of the parasite from the intermediate host population.

The adaptive response of Escherichia coli O157 in an environment with changing pH.

AIMS: To predict and validate survival of non-acid adapted Escherichia coli O157 in an environment mimicking the human stomach. METHODS AND RESULTS: Survival was predicted mathematically from inactivation rates at various, but constant pH values. Predictions were subsequently validated experimentally in a pH-controlled fermentor. Contrary to prediction, acid-sensitive cultures of E. coli O157 survived for a long period of time and died as rapidly as acid-resistant cultures. Experimental results showed that in an environment with changing pH, acid-sensitive cultures became acid-resistant within 17 min. Cyclo fatty acids was reported to be a factor in acid resistance. As synthesis of cyclo fatty acids does not require de novo enzyme synthesis and thus requires little time to develop, we analysed the membrane fatty acid composition of E. coli O157 during adaptation. No changes in membrane fatty acid composition were observed. CONCLUSIONS: Acid adaptation of E. coli O157 can occur during passage of the human gastric acid barrier, which can take up to 4 h. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability of acid-adapted bacteria to survive the human stomach is an important virulence factor. The ability of non-acid adapted E. coli O157 to adapt within a very short period of time under extreme conditions further contributes to the virulence of E. coli O157.

A rat model for dose-response relationships of Salmonella Enteritidis infection.

AIMS: To develop an animal model to study dose-response relationships of enteropathogenic bacteria. METHODS AND RESULTS: Adult, male Wistar Unilever rats were exposed orally to different doses of Salmonella enterica serovar Enteritidis after overnight starvation and neutralization of gastric acid by sodium bicarbonate. The spleen was the most sensitive and reproducible organ for detection of dose-dependent systemic infection. Illness was only observed in animals exposed to doses of 10(8) cfu or more. At lower doses, histopathological changes in the gastro-intestinal tract were observed, but these were not accompanied by illness. Marked changes in numbers and types of white blood cells, as well as delayed-type hyperresponsiveness, indicated a strong, dose-dependent cellular immune response to Salm. Enteritidis. CONCLUSION: The rat model is a sensitive and reproducible tool for studying the effects of oral exposure to Salm. Enteritidis over a wide dose range. SIGNIFICANCE AND IMPACT OF THE STUDY: The rat model allows controlled quantification of different factors related to the host, pathogen and food matrix on initial stages of infection by food-borne bacterial pathogens.

Modelling inactivation of Escherichia coli by low pH: application to passage through the stomach of young and elderly people.

AIM: To estimate the survival of enteropathogenic Escherichia coli after passage through the stomach of young and elderly people. METHODS AND RESULTS: Using enterohaemorrhagic E. coli O157 and a non-pathogenic laboratory strain, inactivation in a pH range between 1.5 and 4.0 was experimentally quantified. Gastric pH and transport have previously been studied in human volunteers following consumption of a solid meal. Combining all these findings, time series of surviving bacteria were mathematically predicted and subsequently, the predictions were validated with in vitro experiments using a pH-controlled fermentor. On average, 20-80% of ingested E. coli are estimated to arrive in the small intestine without inactivation by low pH. The mean overall gastric passage was similar for young and elderly subjects. CONCLUSIONS: The tested E. coli strains can survive the human stomach with a high probability. SIGNIFICANCE AND IMPACT OF THE STUDY: Survival of E. coli under conditions of changing pH in the stomach may be predicted by batch experiments at constant pH. The effectiveness of the gastric acid barrier strongly depends on buffering effects of food.

Efficient extraction and some properties of storage proteins (prolamin and glutelin) in ancient rice cultivars.

Two typical storage proteins (prolamin and glutelin) in a total of 14 samples of ancient rice cultivars were examined for their accumulation in the endosperms during days after flowering (DAF), extraction efficiency with various solvents, and variations in polypeptide components or amino acid compositions. There was little difference in accumulation profiles between this and previous observations, in which glutelin appeared on 5-7 DAF and prolamin on 7-9 DAF. As for the extraction of prolamin and glutelin, it was most effectively attained by sequential usage of 55% propanol and 21% SDS. As a result of SDS-PAGE, prolamin and glutelin proved to be composed mainly of a single polypeptide with a molecular weight (MW) of 15 kDa and two subunits with MWs of 21 kDa (alpha) and 32 kDa (beta), respectively. A comparison between the ancient and modern rice cultivars revealed the same physicochemical properties in either case of prolamin or glutelin. Additionally, a good relationship was observed on the total protein and glutelin (but not prolamin) contents in the ancient rice cultivar.

Structural and immunochemical homologies between foxtail millet glutelin 60 kDa and starch granule-bound starch synthase proteins from rice, barley, corn and wheat grains.

Foxtail millet glutelin 60 kDa (MG60) was purified by preparative SDS-PAGE, and the N-terminal amino acid sequence was determined within 20 residues. The result demonstrated that the primary structure at N-terminal of MG60 was almost identical to those of the granule-bound starch synthase (GBSS) proteins from rice, barley, corn, wheat and potato. The existence of common epitopes among MG60 and GBSS proteins from these starch-storing cereals were corroborated by immunoblot analysis using antisera raised against MG60. These facts strongly suggest a close relationship between MG60-like glutelins and GBSS proteins.

Bactericidal activities of essential oils of basil and sage against a range of bacteria and the effect of these essential oils on Vibrio parahaemolyticus.

Basil and sage essential oils were examined for bactericidal activity against a range of Gram-positive and Gram-negative bacteria by viable count determinations. Generally, Gram-positive bacteria showed higher resistance to basil and sage essential oils than Gram-negative bacteria. Vibrio species showed a high sensitivity to both essential oils. Stationary growth phase cells of selected bacteria showed higher resistance to these essential oils than exponential growth phase cells. Basil-resistant (b21) and sage-resistant (s20) strains of Vibrio parahaemolyticus were isolated. Both strains showed higher resistance to heat and H2O2 than parent strain. Conversely, heat-adapted V. parahaemolyticus also showed a higher resistance to these essential oils than nonadapted cells.

Evolution of the immune repertoire with and without somatic DNA recombination.

Repertoire of an immune system is a set of antigen receptors each having a unique specificity to bind an antigen. In many vertebrate species, antigen receptors are produced via combinatorial arrangements of DNA segments in specialized immune cells. Due to this molecular mechanism, repertoire of vertebrate species is potentially very large. The diversity of repertoire is thought to guarantee recognition of most ill-causing micro-organisms. In vertebrate species however, similar editing of DNA segments has not been demonstrated to take place. Immune system of invertebrate species therefore seems to operate in a distinct manner from that of vertebrate species. Using an evolutionary model in which organisms struggle to fight infections, we attempt to understand why some species use a more diverse set of antigen receptors than others. Individuals in our model either use somatic DNA recombination to produce antigen receptors (as in vertebrates) or do not use such a mechanism (as in vertebrates). We found that individuals having an invertebrate-like immune system came to employ only a few antigen receptors to recognize a set of pathogens whereas those with a vertebrate-like immune system use a larger set of more specific antigen receptors to recognize the same set of pathogens. Our interpretation of this finding is that because the genetics of the immune system imposed different constraints on the evolutionary process, two distinct recognition strategies have been adapted by these species.

Antibacterial activity of Lactobacillus species against Vibrio species.

Forty-one Lactobacillus strains were tested for antagonistic activity against nine strains of Vibrio. L. plantarum and L. casei were the most effective, and L. brevis was the least effective in inhibiting the growth of Vibrio species. L. gasseri and L. helveticus strains showed higher activity, while L. reuteri and L. fermentum showed lower inhibitory activity against Vibrio species. L. acidophilus strains exhibited various degrees of antagonistic activities against Vibrio species. However, none of the Lactobacillus species were able to inhibit the growth of Salmonella enteritidis, S. typhimurium, Escherichia coli, and Staphylococcus aureus. Inhibition of the Vibrio species was probably due to the production of organic acids by the Lactobacillus species.

Self assertion modeled as a network repertoire of multi-determinant antibodies.

We study repertoire selection in a network of natural antibodies that is maintained by stimulatory idiotypic interactions. The natural antibody repertoire develops in an environment of self epitopes to which the self-reactive B cell clones are completely tolerant. For the modeling formalism, we extend the shape space framework so that each antibody is represented by several randomly chosen shapes. B cell clones are generated stochastically and are removed whenever their density falls below an extinction threshold. The idiotypic interactions are governed by a log bell-shaped interaction function. The natural antibody repertoire in the model is formed by percolation: the network is autonomously activated following a point stimulation. Our main conclusion is that the natural antibody repertoire organizes itself in such a way that most self epitopes are included in the repertoire. We find an over-representation of antibody determinants that are similar to self epitopes. We speculate that the network forms a "smoke screen" covering the somatic self.