Endocrine Mucin-Producing Sweat Gland Carcinoma and Primary Cutaneous Mucinous Carcinoma: A Case Series.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.

Optimisation of plutonium separations using TEVA cartridges and ICP-MS/MS analysis for applicability to large-scale studies in tropical soils.

The analysis of plutonium (Pu) in soil samples can inform the understanding of soil erosion processes globally. However, there are specific challenges associated for analysis in tropical soils and so an optimal analytical methodology ensuring best sensitivity is critical. This method aimed to demonstrate the feasibility of sample preparation and analysis of Pu isotopes in African soils, considering the environmental and cost implications applicable to low-resource laboratories. The separation procedure builds upon previous work using TEVA columns, further demonstrating their usefulness for the reduction of uranium (U) interference in ICP-MS analysis with enhanced selectivity for Pu. Here several steps were optimised to enhance Pu recovery, reducing method blank concentration, and improving the separation efficiency through the determination of the elution profiles of U and Pu. The elimination of the complexing agent in the eluent, increased the spike recovery by improving matrix tolerance of the plasma, and simplified the separation procedure, improving throughput by 20%. The subsequent method was validated through the analysis of Certified Reference Material IAEA-384, where high accuracy and improved precision of measurement were demonstrated (measured value 114 ± 12 versus certified value 108 ± 13 Bq kg-1). Optimisation of the column separation, along with the analysis of the samples using O2 gas in ICP-MS/MS mode to mass shift Pu isotopes away from interfering molecular U ions provided a simple, robust, and cost-effective method with low achievable method detection limits of 0.18 pg kg-1 239+240Pu, applicable to the detection of ultra-trace fallout Pu in African soils.

A Quantum Chemical Deep-Dive into the π-π Interactions of 3-Methylindole and Its Halogenated Derivatives-Towards an Improved Ligand Design and Tryptophan Stacking.

Non-covalent π-π stacking interactions often play a key role in the stability of the secondary and tertiary structures of peptides and proteins, respectively, and can be a means of ensuring the binding of ligands within protein and enzyme binding sites. It is generally accepted that minor structural changes to the aromatic ring, such as substitution, can have a large influence on these interactions. Nevertheless, a thorough understanding of underpinning phenomena guiding these key interactions is still limited. This is especially true for larger aromatic structures. To expand upon this knowledge, elaborate ab initio calculations were performed to investigate the effect of halogenation on the stability of 3-methylindole stacking. 3-Methylindole served as a representation of the tryptophan side chain, and is a frequently used motif in drug design and development. Moreover, an expression is derived that is able to accurately predict the interaction stability of stacked halogenated 3-methylindole dimers as well as halogenated toluene dimers, based on monomer level calculated DFT descriptors. We aim for this expression to provide the field with a straightforward and reliable method to assess the effect of halogenation on the π-π stacking interactions between aromatic scaffolds.

Identification and Characteristics of Fusion Peptides Derived From Enveloped Viruses.

Membrane fusion events allow enveloped viruses to enter and infect cells. The study of these processes has led to the identification of a number of proteins that mediate this process. These proteins are classified according to their structure, which vary according to the viral genealogy. To date, three classes of fusion proteins have been defined, but current evidence points to the existence of additional classes. Despite their structural differences, viral fusion processes follow a common mechanism through which they exert their actions. Additional studies of the viral fusion proteins have demonstrated the key role of specific proteinogenic subsequences within these proteins, termed fusion peptides. Such peptides are able to interact and insert into membranes for which they hold interest from a pharmacological or therapeutic viewpoint. Here, the different characteristics of fusion peptides derived from viral fusion proteins are described. These criteria are useful to identify new fusion peptides. Moreover, this review describes the requirements of synthetic fusion peptides derived from fusion proteins to induce fusion by themselves. Several sequences of the viral glycoproteins E1 and E2 of HCV were, for example, identified to be able to induce fusion, which are reviewed here.

Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.

One of the main challenges in contemporary medicinal chemistry is the development of safer analgesics, used in the treatment of pain. Currently, moderate to severe pain is still treated with the "gold standard" opioids whose long-term often leads to severe side effects. With the discovery of biased agonism, the importance of this area of pharmacology has grown exponentially over the past decade. Of these side effects, tolerance, opioid misuse, physical dependence and substance use disorder (SUD) stand out, since these have led to many deaths over the past decades in both USA and Europe. New therapeutic molecules that induce a biased response at the opioid receptors (MOR, DOR, KOR and NOP receptor) are able to circumvent these side effects and, consequently, serve as more advantageous therapies with great promise. The concept of biased signaling extends far beyond the already sizeable field of GPCR pharmacology and covering everything would be vastly outside the scope of this review which consequently covers the biased ligands acting at the opioid family of receptors. The limitation of quantifying bias, however, makes this a controversial subject, where it is dependent on the reference ligand, the equation or the assay used for the quantification. Hence, the major issue in the field of biased ligands remains the translation of the in vitro profiles of biased signaling, with corresponding bias factors to in vivo profiles showing the presence or the lack of specific side effects. This review comprises a comprehensive overview of biased ligands in addition to their bias factors at individual members of the opioid family of receptors, as well as bifunctional ligands.

Organic pollutants, heavy metals and toxicity in oil spill impacted salt marsh sediment cores, Staten Island, New York City, USA.

Sediment cores from Staten Island's salt marsh contain multiple historical oil spill events that impact ecological health. Microtox solid phase bioassay indicated moderate to high toxicity. Multiple spikes of TPH (6524 to 9586 mg/kg) and Σ16 PAH (15.5 to 18.9 mg/kg) were co-incident with known oil spills. A high TPH background of 400-700 mg/kg was attributed to diffuse sources. Depth-profiled metals Cu (1243 mg/kg), Zn (1814 mg/kg), Pb (1140 mg/kg), Ni (109 mg/kg), Hg (7 mg/kg), Cd 15 (mg/kg) exceeded sediment quality guidelines confirming adverse biological effects. Changes in Pb206/207 suggested three metal contaminant sources and diatom assemblages responded to two contamination events. Organic and metal contamination in Saw Mill Creek Marsh may harm sensitive biota, we recommend caution in the management of the 20-50 cm sediment interval because disturbance could lead to remobilisation of pre-existing legacy contamination into the waterway.

Pruritic rash on chest and back.

Was a recent change in diet to blame for this patient's rash?

A master equation for a two-sided optical cavity.

Quantum optical systems, like trapped ions, are routinely described by master equations. The purpose of this paper is to introduce a master equation for two-sided optical cavities with spontaneous photon emission. To do so, we use the same notion of photons as in linear optics scattering theory and consider a continuum of travelling-wave cavity photon modes. Our model predicts the same stationary state photon emission rates for the different sides of a laser-driven optical cavity as classical theories. Moreover, it predicts the same time evolution of the total cavity photon number as the standard standing-wave description in experiments with resonant and near-resonant laser driving. The proposed resonator Hamiltonian can be used, for example, to analyse coherent cavity-fiber networks [E. Kyoseva et al., New J. Phys. 14, 023023 (2012)].

Soil type influences crop mineral composition in Malawi.

Food supply and composition data can be combined to estimate micronutrient intakes and deficiency risks among populations. These estimates can be improved by using local crop composition data that can capture environmental influences including soil type. This study aimed to provide spatially resolved crop composition data for Malawi, where information is currently limited. Six hundred and fifty-two plant samples, representing 97 edible food items, were sampled from >150 sites in Malawi between 2011 and 2013. Samples were analysed by ICP-MS for up to 58 elements, including the essential minerals calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se) and zinc (Zn). Maize grain Ca, Cu, Fe, Mg, Se and Zn concentrations were greater from plants grown on calcareous soils than those from the more widespread low-pH soils. Leafy vegetables from calcareous soils had elevated leaf Ca, Cu, Fe and Se concentrations, but lower Zn concentrations. Several foods were found to accumulate high levels of Se, including the leaves of Moringa, a crop not previously been reported in East African food composition data sets. New estimates of national dietary mineral supplies were obtained for non-calcareous and calcareous soils. High risks of Ca (100%), Se (100%) and Zn (57%) dietary deficiencies are likely on non-calcareous soils. Deficiency risks on calcareous soils are high for Ca (97%), but lower for Se (34%) and Zn (31%). Risks of Cu, Fe and Mg deficiencies appear to be low on the basis of dietary supply levels.

A new sentinel surveillance system for severe influenza in England shows a shift in age distribution of hospitalised cases in the post-pandemic period.

BACKGROUND: The World Health Organization and European Centre for Disease Prevention and Control have highlighted the importance of establishing systems to monitor severe influenza. Following the H1N1 (2009) influenza pandemic, a sentinel network of 23 Trusts, the UK Severe Influenza Surveillance System (USISS), was established to monitor hospitalisations due to confirmed seasonal influenza in England. This article presents the results of the first season of operation of USISS in 2010/11. METHODOLOGY/PRINCIPAL FINDINGS: A case was defined as a person hospitalised with confirmed influenza of any type. Weekly aggregate numbers of hospitalised influenza cases, broken down by flu type and level of care, were submitted by participating Trusts. Cases in 2010/11 were compared to cases during the 2009 pandemic in hospitals with available surveillance data for both time periods (n = 19). An unexpected resurgence in seasonal A/H1N1 (2009) influenza activity in England was observed in December 2010 with reports of severe disease. Reported cases over the period of 4 October 2010 to 13 February 2011 were mostly due to influenza A/H1N1 (2009). One thousand and seventy-one cases of influenza A/H1N1 (2009) occurred over this period compared to 409 at the same Trusts over the 2009/10 pandemic period (1 April 2009 to 6 January 2010). Median age of influenza A/H1N1 (2009) cases in 2010/11 was 35 years, compared with 20 years during the pandemic (p = <0.0001). CONCLUSIONS/SIGNIFICANCE: The Health Protection Agency successfully established a sentinel surveillance system for severe influenza in 2010/11, detecting a rise in influenza cases mirroring other surveillance indicators. The data indicate an upward shift in the age-distribution of influenza A/H1N1 (2009) during the 2010/11 influenza season as compared to the 2009/10 pandemic. Systems to enable the ongoing surveillance of severe influenza will be a key component in understanding and responding to the evolving epidemiology of influenza in the post-pandemic era.