Clinical characteristics,molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015).

Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n?=?19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n?=?12), 35% for CD68 (n?=?8), 30% for CD34 (n?=?7), and 26% for lysozyme (n?=?6). Cytogenetic abnormalities were seen in 63% (n?=?12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n?=?3) or monosomal (n?=?2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p?=?0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p?Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.     

Isolated Pupil-Involving Third Nerve Palsy as the First Presentation of Sarcoidosis

Neurosarcoidosis is seen in 5–15% of patients with systemic sarcoidosis. The most common cranial nerve presentations are optic neuropathy and facial nerve palsy. The authors present a case of sarcoidosis presenting with a pupil-involving third nerve palsy. The patient responded to corticosteroid therapy with resolution of investigations her cranial nerve palsy but progressed to develop cerebellar signs. This is the first documented case of a pupil-involving third nerve palsy occurring as the first presentation of neurosarcoidosis. Although typically a pupil-involving third nerve palsy necessitates urgent neuroimaging to rule out a posterior communicating artery aneurysm, it is important to recognise inflammatory causes in the differential diagnosis.     

Recent progress in development of 2,3-diaminomaleonitrile (DAMN) based chemosensors for sensing of ionic and reactive oxygen species

2,3-Diaminomaleonitrile (DAMN) has proved to be a valuable organic π-conjugated molecule having many applications in the area of chemosensors for sensing of ionic and neutral species because of its ability to act as a building block for well-defined molecular architectures and scaffolds for preorganised arrays of functionality. In this article, we discussed the utilization of 2,3-diaminomaleonitrile (DAMN) for the design and development of chemosensor molecules and their application in the area of metal ion, anion and reactive oxygen species sensing. Along with these, we present different examples of DAMN based chemosensors for multiple ion sensing. We also discuss the ion sensing mechanism and potential uses in other related areas of research.

2,3-Diamniomaleonitrile (DAMN) is valuable π-conjugated organic scaffold molecule for designing of efficient chemosensors for sensing of ionic and Reactive Oxygen Species (ROS).     

Human preferences for sexually dimorphic faces may be evolutionarily novel

A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from large-scale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development and, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples.Inspired by evidence from nonhuman species indicating that exaggerated sex-typical traits (e.g., large antlers, peacock tails) are often attractive to mates or intimidating to rivals (1, 2), morphological sex typicality in humans (masculinity in men and femininity in women) has been the focus of considerable research into attractiveness judgments (3, 4). Facial attractiveness research has been revolutionized by this explanatory framework from the biological sciences, which proposes that attractive human faces honestly signaled mate value within ancestral environments.An influential proposal is that facial femininity is a signal of fertility in human female faces (4–9) because, within same-age women, it is associated with estrogens (10), which, in turn, are related to measures of reproductive health (11). Like ovarian function, facial femininity declines with age in adulthood (12, 13). The proposal that fertile women should be attractive to men is seemingly uncontroversial because males who discriminatively mate with fertile females should achieve a straightforward reproductive advantage over those males who do not, with all other factors being equal (6). Although direct associations between facial femininity and fertility have not been demonstrated, the consensus from Western preferences, and from the limited cross-cultural data available, is that femininity is attractive, as predicted by the fertility hypothesis (14–17). In environments where fertility is high and variable, this relationship should be even more apparent.In male faces, masculinity has been variously proposed to signal heritable disease resistance (“good genes” or “immunocompetence”) (4, 15, 18–22) and/or perceived as a cue of aggressiveness and, consequently, intrasexual competitiveness (22, 23). The “honesty” of face shape as an indicator of immunocompetence is proposed to be the result of an immunosuppressive effect of testosterone. Because testosterone influences the growth of sex-typical traits in many species (24, 25), masculine facial shape is proposed to be a costly, and thus honest, signal of male quality (22). The hypothesis that cues of heritable health should be attractive to females is widely accepted (26), although the evidence for a link between heritable health and masculinity in humans is tentative at best (22).Support for a link between masculinity and aggression is largely indirect, and it consists of an association between testosterone and both aggressive behavior (27, 28) and face shape (25), in addition to the fact that honest signaling of dominance is commonly observed in nonhuman species (3). Masculine faces are perceived as aggressive in those groups (i.e., urban, Western) where the relationship has been tested (29). Because masculinity may signal both (desirable) immunity and (potentially costly) aggression in humans, some authors have proposed that preferences for masculinity reflect women trading-off benefits of traits putatively associated with health against those traits associated with prosocial behaviors, such as parental investment (23, 30, 31).Consistent with both of these proposals, data indicate that preferences for masculinity are stronger in circumstances where indirect benefits (heritable quality) can be realized without accompanying direct costs (aggression and low paternal investment). Such circumstances include judging attractiveness in the context of a short-term (vs. a long-term) relationship (32) and in the follicular phase of the menstrual cycle when conception following intercourse is most likely (33). Masculinity is also reported to be more strongly preferred in environments with relatively high pathogen burdens (19, 30) and in environments with higher local homicide rates (23), which has been interpreted as a response to variation in the benefits of heritable disease resistance (19) and in the net benefits conferred by aggressive males under varying levels of male–male competition (23).All of this supporting evidence comes with a very important caveat; although there has been some cross-cultural work in this area (34), the majority of studies have been conducted in Western, often student, populations characterized by high levels of development and urbanization [Western, educated, industrialized, rich, and democratic; so-called WEIRD participants (35)]. Research on preferences in other groups is scant and methodologically inconsistent, using Internet-based designs or a limited cross-cultural component (7, 15–18). Because there are differences between Western/non-Western and industrial/small-scale societies in many behaviors, including aspects of visual perception and mate choice (35), this over-representation greatly limits generalizability. Perhaps most importantly, large-scale (post)industrial societies present inhabitants with large numbers of unfamiliar faces and provide venues for the efficient exchange of (visual) social information (e.g., posters, television, Internet); these factors may be instrumental in the acquisition and reinforcement of preferences (36–39). It is possible therefore that rather than being a legacy of ancestral selection pressures, preferences for dimorphism emerge in large urban groups as a byproduct of the information-processing strategies used to process large amounts of social information or in response to arbitrary cultural norms.Development also introduces an increased presence of highly differentiated social roles that arise from a greater division of labor, along with opportunities to acquire prestige without strength or aggression. Because partner preferences have been proposed to develop in response to sex-typical social roles (40, 41), it is possible that increasingly differentiated roles could influence masculinity preferences if desirable social roles not present in less developed groups are associated with facial appearance.We assessed preferences for, and trait attributions made to, faces varying in dimorphism in a cross-cultural sample of 12 groups, including non-Western, nonstudent, and small-scale societies (n = 962; Tables S1 and S2). We tested the predictions, derived from the immunocompetence handicapping hypothesis, that (i) preferences for dimorphism will be stronger in less developed groups and (ii) masculine faces would be perceived as aggressive in all populations, with perceptions in low-development groups at least as strong as in groups with high development. We estimated social development with the Human Development Index (HDI), which is a composite indicator compiled by the United Nations Development Program. To investigate which aspects of development were associated with variation in perception of our facial stimuli, we took the World Health Organization measures of years lost to disease and United Nations (UN) measures of homicide rates as proxy measures of disease burden and male intrasexual competition, respectively (both log-transformed), and UN measures of levels of urbanization. Using these national statistics almost certainly underestimates disease burden in the small-scale societies in our sample, which is a conservative estimate with regard to our hypotheses.

Table 1.

Summary information for the groups tested

In vivo contribution of nestin‐ and GLAST‐lineage cells to adult hippocampal neurogenesis

Radial glia‐like cells (RGCs) are the hypothesized source of adult hippocampal neurogenesis. However, the current model of hippocampal neurogenesis does not fully incorporate the in vivo heterogeneity of RGCs. In order to better understand the contribution of different RGC subtypes to adult hippocampal neurogenesis, we employed widely used transgenic lines (Nestin‐CreER^T2 and GLAST::CreER^T2 mice) to explore how RGCs contribute to neurogenesis under basal conditions and after stimulation and depletion of neural progenitor cells. We first used these inducible fate‐tracking transgenic lines to define the similarities and differences in the contribution of nestin‐ and GLAST‐lineage cells to basal long‐term hippocampal neurogenesis. We then explored the ability of nestin‐ and GLAST‐lineage RGCs to contribute to neurogenesis after experimental manipulations that either ablate neurogenesis (i.c.v. application of the anti‐mitotic AraC, cytosine‐β‐D‐arabinofuranoside) or stimulate neurogenesis (wheel running). Interestingly, in both ablation and stimulation experiments, labeled RGCs in GLAST::CreER^T2 mice appear to contribute to neurogenesis, whereas RGCs in Nestin‐CreER^T2 mice do not. Finally, using NestinGFP reporter mice, we expanded on previous research by showing that not all RGCs in the adult dentate gyrus subgranular zone express nestin, and therefore RGCs are antigenically heterogeneous. These findings are important for the field, as they allow appropriately conservative interpretation of existing and future data that emerge from these inducible transgenic lines. These findings also raise important questions about the differences between transgenic driver lines, the heterogeneity of RGCs, and the potential differences in progenitor cell behavior between transgenic lines. As these findings highlight the possible differences in the contribution of cells to long‐term neurogenesis in vivo, they indicate that the current models of hippocampal neurogenesis should be modified to include RGC lineage heterogeneity. © 2013 Wiley Periodicals, Inc.     

Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery

Introduction: Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years.

Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters.

Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.