Supramolecular macrocycles reversibly assembled by Te ⋯ O chalcogen bonding

Organic molecules with heavy main-group elements frequently form supramolecular links to electron-rich centres. One particular case of such interactions is halogen bonding. Most studies of this phenomenon have been concerned with either dimers or infinitely extended structures (polymers and lattices) but well-defined cyclic structures remain elusive. Here we present oligomeric aggregates of heterocycles that are linked by chalcogen-centered interactions and behave as genuine macrocyclic species. The molecules of 3-methyl-5-phenyl-1,2-tellurazole 2-oxide assemble a variety of supramolecular aggregates that includes cyclic tetramers and hexamers, as well as a helical polymer. In all these aggregates, the building blocks are connected by Te(…)O-N bridges. Nuclear magnetic resonance spectroscopic experiments demonstrate that the two types of annular aggregates are persistent in solution. These self-assembled structures form coordination complexes with transition-metal ions, act as fullerene receptors and host small molecules in a crystal

Order 1/N corrections to the time-dependent Hartree approximation for a system of N+1 oscillators

We solve numerically to order 1/N the time evolution of a quantum dynamical system of N oscillators of mass m coupled quadratically to a massless dynamic variable. We use Schwinger's closed time path (CTP) formalism to derive the equations. We compare two methods which differ by terms of order 1/N^2. The first method is a direct perturbation theory in 1/N using the path integral. The second solves exactly the theory defined by the effective action to order 1/N. We compare the results of both methods as a function of N. At N=1, where we expect the expansion to be quite innacurate, we compare our results to an exact numerical solution of the Schroedinger equation. In this case we find that when the two methods disagree they also diverge from the exact answer. We also find at N=1 that the 1/N corrected evolutions track the exact answer for the expectation values much longer than the mean field (N= \infty) result.Comment: 14 pages, 11 figures. Submitted to Phys. Rev.

Pulmonary delivery of vancomycin dry powder aerosol to intubated rabbits

TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles were significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than the naked drug, and the drug clearance rate was 17.5-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment

Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed

Osjetljiva spektrofotometrijska metoda za određivanje antagonista H2-receptora uz uporabu N-bromsukcinimida i p-aminofenola

A simple, accurate and sensitive spectrophotometric method for determination of H2-receptor antagonists: cimetidine (CIM), famotidine (FAM), nizatidine (NIZ), and ranitidine hydrochloride (RAN) has been full developed and validated The method was based on the reaction of these drugs with NBS and subsequent measurement of the excess N-bromosuccinimide by its reaction with p-aminophenol to give a violet colored product (max at 552 nm). Decrease in the absorption intensity (A) of the colored product, due to the presence of the drug, was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under optimal conditions, linear relationships with good correlation coefficients (0.9988-0.9998) were found between A values and the corresponding concentrations of the drugs in a concentration range of 830, 622, 625, and 420 g mL1 for CIM, FAM, NIZ, and RAN, respectively. Limits of detection were 1.22, 1.01, 1.08, and 0.74 g mL1 for CIM, FAM, NIZ, and RAN, respectively. The method was validated in terms of accuracy, precision, ruggedness, and robustness; the results were satisfactory. The proposed method was successfully applied to the analysis of the above mentioned drugs in bulk substance and in pharmaceutical dosage forms; percent recoveries ranged from 98.5 0.9 to 102.4 0.8% without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.Razvijena je i validirana ispravna, jednostavna i osjetljiva spektrofotometrijska metoda za određivanje antagonista H2-receptora: cimetidina (CIM), famotidina (FAM), nizatidina (NIZ) i ranitidin hidroklorida (RAN). Metoda se temelji na reakciji tih ljekovitih tvari s N-bromsukcinimidom (NBS). Višak N-bromsukcinimida određuje se nakon reakcije s p-aminofenolom s kojim daje ljubičasti produkt (max pri 552 nm). Smanjenje apsorpcijskog intenziteta (A) obojenog produkta, zbog prisutnosti ljekovite tvari korelirano je s njegovom koncentracijom u otopini uzorka. Proučavane su različite varijable koje utječu na reakciju. Linearno koncentracijsko područje za CIM, FAM, NIZ i RAN, s koeficijentom korelacije od 0,9988 do 0,9998, iznosi 830, 622, 625 odnosno 420 g mL1. Granice detekcije bile su 1,23, 1,02, 1,09 i 0,75 g mL1 za CIM, FAM, NIZ, odnosno RAN. Predložena metoda je uspješno primijenjena za analizu navedenih ljekovitih tvari i ljekovitih pripravaka. Nepreciznost od 0,7 do 1,2% i visoka ispravnost (analitički povrat između 98,5 i 102,4%), bez interferencije uobičajenih pomoćnih tvari, ukazuju na dobru analitičku metodu. Rezultati dobiveni predloženom metodom usporedivi su s rezultatima dobivenim službenom metodom

Long-term results of breast conservation and immediate volume replacement with myocutaneous latissimus dorsi flap

<p>Abstract</p> <p>Background</p> <p>Published long-term outcomes of oncoplastic breast-conserving surgery are scarce and, specifically, aesthetic outcomes assessed with an objective method have not previously been published.</p> <p>Methods</p> <p>A cohort of 41 patients treated with a quadrantectomny and immediate reconstruction using a myocutaneous latissimus dorsi flap were analyzed and their aesthetic outcomes were evaluated objectively by BCCT.core software.</p> <p>Results</p> <p>At the end of a 58-month follow-up from the date of initial diagnosis, one patient (2.4%) developed an ipsilateral recurrence, six patients developed distant metastases and three patients died (7.3%) without ipsilateral recurrence, one of them presenting hepatic metastases at the time of the initial diagnosis. We were able to evaluate aesthetic results in 23 patients, 3 assessed as excellent, 12 good and 8 fair.</p> <p>Conclusion</p> <p>This oncoplastic volume replacement technique obtained a good local control and satisfactory and stable aesthetic results which have maintained unchanged after a long period of time.</p

Prevalence Distribution and Risk Factors for Schistosoma hematobium Infection among School Children in Blantyre, Malawi

Schistosoma hematobium infection is a parasitic infection endemic in Malawi. Schistosomiasis usually shows a focal distribution of infection and it is important to identify communities at high risk of infection and assess effectiveness of control programs. We conducted a survey in one district in Malawi to determine prevalence and factors associated with S. hematobium infection among primary school pupils. Using a questionnaire, information on history of passing bloody urine and known risk factors associated with infection was collected. Urine samples were collected and examined for S. hematobium eggs. One thousand one hundred and fifty (1,150) pupils were interviewed, and out of 1,139 pupils who submitted urine samples, 10.4% were infected. Our data showed that male gender, child's knowledge of an existing open water source (includes river, dam, springs, lake, etc.) in the area, history of urinary schistosomiasis in the past month, distance of less than 1 km from school to nearest open water source and age 8–10 years compared to those 14 years and older were independently associated with infection. These findings suggest that children attending schools in close proximity to open water sources are at increased risk of infection

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Innate PD-L1 limits T cell–mediated adipose tissue inflammation and ameliorates diet-induced obesity

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy