Synthesis of new chiral organosulfur donors with hydrogen bonding functionality and their first charge transfer salts

The syntheses of a range of enantiopure organosulfur donors with hydrogen bonding groups are described including TTF related materials with two, four, six and eight hydroxyl groups and multiple stereogenic centres and a pair of chiral N-substituted BEDT-TTF acetamides. Three charge transfer salts of enantiopure poly-hydroxy-substituted donors are reported, including a 4:1 salt with the meso stereoisomer of the dinuclear [Fe2(oxalate)5 ]4- anion in which both cation and anion have chiral components linked together by hydrogen bonding, and a semiconducting salt with triiodide

Tris-ureas as transmembrane anion transporters

Nine tris-urea receptors (L1–L9) have been synthesised and shown to coordinate to a range of anionic guests both by 1H NMR titration techniques and single crystal X-ray structural analysis. The compounds have been shown to be capable of mediating the exchange of chloride and nitrate and also chloride and bicarbonate across POPC or POPC : cholesterol 7 : 3 vesicle bilayer membranes at low transporter loadings. An interesting dependency of anion transport on the nature of the cation is evidence to suggest that a M+/Cl− cotransport process may also contribute to the release of chloride from the vesicles

Classification of facial periâ implant soft tissue dehiscence/deficiencies at single implant sites in the esthetic zone

BackgroundThe incidence of a periâ implant soft tissue dehiscence/deficiency (PSTD) is not a rare finding. Despite multiple previous attempts aimed at correcting the PSTDs, a classification of these conditions has not yet been proposed. This lack in the literature may also lead to discrepancies in the reported treatment outcomes and thus misinform the clinician or the readers. The aim of the present article was therefore to present a classification of periâ implant PSTD at a single implant site.MethodsFour classes of PSTDs were discussed based on the position of the gingival margin of the implantâ supported crown in relation to the homologous natural tooth. In addition, the buccoâ lingual position of the implant head was also taken into consideration. Each class was further subdivided based on the height of the anatomical papillae.ResultsSubsequently, for each respective category a surgical approach (including bilaminar techniques, the combined prostheticâ surgical approach or soft tissue augmentation with a submerged healing) was also suggested.ConclusionThis paper provides a new classification system for describing PSTDs at single implant sites, with the appropriate recommended treatment protocol.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/1/jper10351_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/2/jper10351.pd

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Is a soft tissue graft harvested from the maxillary tuberosity the approach of choice in an isolated site?

Soft tissue augmentation procedures are becoming more popular these days. Different soft tissue graft harvesting approaches have been proposed. Nonetheless, the location of the donor site (whether anterior-, lateral-, superficial-, deep-palate or the maxillary tuberosity) can affect the graft shape and its composition. Soft tissue grafts from the maxillary tuberosity are rich in connective tissue fibers, with minimal presence of fatty or glandular components. Clinical, histological, and molecular evidence shows that a soft tissue graft obtained from the maxillary tuberosity has unique properties. In addition, harvesting from this area presents minimal risk for intra- or postoperative complications, leading to reduced patient morbidity. The aim of this commentary is to discuss the advantages and disadvantages of harvesting a soft tissue graft from the tuberosity and to compare it with the traditional palatal graft, while highlighting functional, esthetic, and patient-related outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151301/1/jper10300_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151301/2/jper10300.pd

A need for the standardization of the pharmaceutical sector in Libya

Medicines are health technologies that can translate into tangible benefits for numerous acute as well as chronic health conditions. A nation's pharmaceutical sector needs to be appropriately structured and managed in order to ensure a safe, effective and quality supply of medicines to society. The process of medicines management involves the sequential management of five critical activity areas; namely; registration, selection, procurement, distribution and use. Formalized and standardized management of all five critical activity areas positively influences the availability, quality and affordability of medicines and ultimately increases the reliability and quality of the national healthcare system

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Power estimation of tests in log-linear non-uniform association models for ordinal agreement

<p>Abstract</p> <p>Background</p> <p>Log-linear association models have been extensively used to investigate the pattern of agreement between ordinal ratings. In 2007, log-linear non-uniform association models were introduced to estimate, from a cross-classification of two independent raters using an ordinal scale, varying degrees of distinguishability between distant and adjacent categories of the scale.</p> <p>Methods</p> <p>In this paper, a simple method based on simulations was proposed to estimate the power of non-uniform association models to detect heterogeneities across distinguishabilities between adjacent categories of an ordinal scale, illustrating some possible scale defects.</p> <p>Results</p> <p>Different scenarios of distinguishability patterns were investigated, as well as different scenarios of marginal heterogeneity within rater. For sample size of N = 50, the probabilities of detecting heterogeneities within the tables are lower than .80, whatever the number of categories. In additition, even for large samples, marginal heterogeneities within raters led to a decrease in power estimates.</p> <p>Conclusion</p> <p>This paper provided some issues about how many objects had to be classified by two independent observers (or by the same observer at two different times) to be able to detect a given scale structure defect. Our results also highlighted the importance of marginal homogeneity within raters, to ensure optimal power when using non-uniform association models.</p