Occupational Therapy After Breast Cancer Reconstructive Surgery: A Predictor for Opioid Prescriptions.

Occupational therapy practitioners have a unique and vital role among interprofessional health care teams toward facilitating occupational participation among breast cancer survivors. This study investigated the relationship between acute medicine occupational therapy services after breast cancer reconstructive surgeries (BCRS) and a number of prescription refills 90 days after surgery. This retrospective study ran binary logistic regression analyses on 562 women after BCRS for refills of opioid and non-opioid medication. Both models were statistically significant, χ2(7df) = 23.001, p = .002; χ2(7df) = 32.312, p < .001, indicating the ability to distinguish who received opioid or non-opioid refills, respectively. While younger age was a significant predictor across both models, occupational therapy was only significant for opioid refills; each was associated with fewer refills. Early occupational therapy treatment after BCRS is associated with fewer opioid prescriptions 90 days after surgery, therefore enhancing occupation throughout this timeframe is beneficial.

Indole Inhibitors of MMP-13 for Arthritic Disorders.

Here, we described the design, by fragment merging and multiparameter optimization, of selective MMP-13 inhibitors that display an appropriate balance of potency and physicochemical properties to qualify as tool compounds suitable for in vivo testing. Optimization of potency was guided by structure-based insights, specifically to replace an ester moiety and introduce polar directional hydrogen bonding interactions in the core of the molecule. By introducing polar enthalpic interactions in this series of inhibitors, the overall beneficial physicochemical properties were maintained. These physicochemical properties translated to excellent drug-like properties beyond potency. In a murine model of rheumatoid arthritis, treatment of mice with selective inhibitors of MMP-13 resulted in a statistically significant reduction in the mean arthritic score vs control when dosed over a 14 day period.

Prolonged Bat Call Exposure Induces a Broad Transcriptional Response in the Male Fall Armyworm (Spodoptera frugiperda; Lepidoptera: Noctuidae) Brain.

Predation risk induces broad behavioral and physiological responses that have traditionally been considered acute and transitory. However, prolonged or frequent exposure to predators and the sensory cues of their presence they broadcast to the environment impact long-term prey physiology and demographics. Though several studies have assessed acute and chronic stress responses in varied taxa, these attempts have often involved a priori expectations of the molecular pathways involved in physiological responses, such as glucocorticoid pathways and neurohormone production in vertebrates. While relatively little is known about physiological and molecular predator-induced stress in insects, many dramatic insect defensive behaviors have evolved to combat selection by predators. For instance, several moth families, such as Noctuidae, include members equipped with tympanic organs that allow the perception of ultrasonic bat calls and facilitate predation avoidance by eliciting evasive aerial flight maneuvers. In this study, we exposed adult male fall armyworm (Spodoptera frugiperda) moths to recorded ultrasonic bat foraging and attack calls for a prolonged period and constructed a de novo transcriptome based on brain tissue from predator cue-exposed relative to control moths kept in silence. Differential expression analysis revealed that 290 transcripts were highly up- or down-regulated among treatment tissues, with many annotating to noteworthy proteins, including a heat shock protein and an antioxidant enzyme involved in cellular stress. Though nearly 50% of differentially expressed transcripts were unannotated, those that were are implied in a broad range of cellular functions within the insect brain, including neurotransmitter metabolism, ionotropic receptor expression, mitochondrial metabolism, heat shock protein activity, antioxidant enzyme activity, actin cytoskeleton dynamics, chromatin binding, methylation, axonal guidance, cilia development, and several signaling pathways. The five most significantly overrepresented Gene Ontology terms included chromatin binding, macromolecular complex binding, glutamate synthase activity, glutamate metabolic process, and glutamate biosynthetic process. As a first assessment of transcriptional responses to ecologically relevant auditory predator cues in the brain of moth prey, this study lays the foundation for examining the influence of these differentially expressed transcripts on insect behavior, physiology, and life history within the framework of predation risk, as observed in ultrasound-sensitive Lepidoptera and other 'eared' insects.

At the confluence of vicariance and dispersal: Phylogeography of cavernicolous springtails (Collembola: Arrhopalitidae, Tomoceridae) codistributed across a geologically complex karst landscape in Illinois and Missouri.

The processes of vicariance and dispersal are central to our understanding of diversification, yet determining the factors that influence these processes remains a significant challenge in evolutionary biology. Caves offer ideal systems for examining the mechanisms underlying isolation, divergence, and speciation. Intrinsic ecological differences among cavernicolous organisms, such as the degree of cave dependence, are thought to be major factors influencing patterns of genetic isolation in caves. Using a comparative phylogeographic approach, we employed mitochondrial and nuclear markers to assess the evolutionary history of two ecologically distinct groups of terrestrial cave-dwelling springtails (Collembola) in the genera Pygmarrhopalites (Arrhopalitidae) and Pogonognathellus (Tomoceridae) that are codistributed in caves throughout the Salem Plateau-a once continuous karst region, now bisected by the Mississippi River Valley in Illinois and Missouri. Contrasting phylogeographic patterns recovered for troglobiotic Pygmarrhopalites sp. and eutroglophilic Pogonognathellus sp. suggests that obligate associations with cave habitats can restrict dispersal across major geographic barriers such as rivers and valleys, but may also facilitate subterranean dispersal between neighboring cave systems. Pygmarrhopalites sp. populations spanning the Mississippi River Valley were estimated to have diverged 2.9-4.8 Ma, which we attribute to vicariance resulting from climatic and geological processes involved in Mississippi River Valley formation beginning during the late Pliocene/early Pleistocene. Lastly, we conclude that the detection of many deeply divergent, morphologically cryptic, and microendemic lineages highlights our poor understanding of microarthropod diversity in caves and exposes potential conservation concerns.

Comments on the neglected nymphs of mud crickets in the genus Mirhipipteryx (Caelifera: Tridactyloidea: Ripipterygidae).

Mud crickets (family Ripipterygidae) comprise a small family of orthopterans distributed throughout much of the Neotropics, but knowledge of this groups' biology, ecology and distribution remains poor in comparison to most orthopteran taxa. Here we review the state of knowledge of nymphs in the genus Mirhipipteryx Günther 1969 and report the genus from Belize for the second time in 86 years. Because information about nymphs in this family is so scarce and nymphs are often neglected in species descriptions, we include comments on the coloration of nymphs for Mirhipipteryx pulicaria (Saussure 1896). Caution is suggested for the use of adult characters for the identification of immatures stages in the group. Nymphs of Mirhipipteryx pulicaria pulicaria are similar in coloration patterns to the adults, but lighter. Mirhipipteryx lobata Günther 1977 is designated a nomen nudum.

Nine true bugs (Heteroptera) newly-discovered in Illinois.

Six heteropteran species are reported for the first time from Illinois based on recently caught specimens from various bioinventories: the flat bug Neuroctenus pseudonymus Bergroth (Aradidae: Mezirinae), the stilt bug Metacanthus multispinus (Ashmead) (Berytidae: Metacanthinae), the leaf-footed bugs Anasa repetita Heidemann and Chelinidea vittiger Uhler (Coreidae: Coreinae), the ambush bug Phymata fasciata fasciata (Gray) (Reduviidae: Phymatinae), and the scentless plant bug Arhyssus nigristernum (Signoret) (Rhopalidae: Rhopalinae). Additionally, three more records for the flat bug Nannium pusio Heidemann (Aradidae) and the scentless plant bugs Aufeius impressicollis Stål and Niesthrea louisianica Sailer (Rhopalidae) are newly-reported for the state based on material in the Illinois Natural History Insect Collection (INHS). Supplementing these notes are dichotomous keys to the species of Mezirinae, Berytidae, Coreidae, Phymatinae, and Rhopalidae of Illinois.

A reassessment of the phylogenetic utility of genus-level morphological characters in the family Bogidiellidae (Crustacea, Amphipoda), with description of a new species of Eobogidiella Karaman, 1981.

Bogidiellidae is the most diverse and cosmopolitan family of stygobiotic amphipods, and inhabits a variety of subterranean biotopes, especially interstitial habitats. While the family is characterized by considerable sexual dimorphism, this dimorphism has adversely affected our understanding of the systematics of the group. Most species have restricted geographic ranges and occur in difficult to sample habitats, so it is common for individual species descriptions to be based on a single sex. In this work we revisit an analysis of morphological characters in an attempt to clarify their phylogenetic utility in resolving taxonomic relationships among genera by introducing a new species, two additional characters, and phylogenetic statistical support values. Eobogidiella venkataramani sp. n., from a spring fed brook in the Shirawati River basin along the escarpment of the Western Ghats (Karnataka, India) differs from the only known congener, Eobogidiella purmamarcensis, from Argentina, in the structure of mouthparts, the shape and ornamentation on gnathopods and characters of the telson. Our phylogenetic analyses indicate that the available morphological characters are not sufficient to resolve phylogenetic relationships within Bogidiellidae, thus these characters alone cannot be used to determine the phylogenetic placement of Eobogidiella venkataramani sp. n. within the family. Nevertheless, Eobogidiella venkataramani sp. n. shares diagnostic characters with Eobogidiella, supporting placement of the new species in this genus. Our findings point towards a critical need to resolve relationships within the family using molecular approaches, along with the development of a suite of additional morphological characters for Bogidiellidae. This is the third species of Bogidiellidae from southern India.

Compartmentalization of microbial communities that inhabit the hindguts of millipedes.

The gut lumen of the arthropod detritivore provides hospitable and multifaceted environments for diverse assemblages of microbes. Many microbes, including trichomycetes fungi, bacteria, and archaea establish stable, adherent communities on the cuticular surface secreted by the hindgut epithelium. Regional differences in the surface topography within the hindgut of a given millipede are reflected in differing and diverse microbial assemblages. The spirostreptid millipede Cambala speobia is a detritivore found on the floors of Texas caves. This millipede species has a very circumscribed distribution in North America and a diet confined to the limited litter that accumulates on floors of these caves while the common julid millipede Cylindroiulus caeruleocinctus, an introduced European species, feeds on the diverse litter found in organic soils throughout North America. In both millipedes, the gut lumina are inhabited along their entire lengths by microbes, with the highest microbial densities in the hindguts. The anterior third of the hindgut with its distinctive six-fold symmetry is lined by cuticle having fine polarized scales, and the posterior-most third is lined by smooth cuticle. Trichomycetes only inhabit the anterior third of the hindgut, and scattered patches of filamentous bacteria along with their smaller adherent microbes occupy the posterior third. The densest populations of microbes inhabit the central region of the hindgut. Over the cuticular surface of this hindgut region, uniformly distributed indentations mark possible channels for nutrient and water exchange between the hindgut lumen and host hemolymph. Films of microbes are adherent to the cuticle that lines the hindgut while those microbes in the remainder of the gut (i.e., foregut + midgut) represent mostly unattached inhabitants.

Insanity, philanthropy and emigration: dealing with insane children in late-nineteenth-century north-west England.

The historiography of asylums and insanity is dense, and some topics have received much scholarly attention but others, such as insanity among children, have been largely neglected. Children by no means formed the majority of asylum populations, but they still suffered from mental impairment and were admitted to these institutions in significant numbers. Identifying the various experiences of insane children is the central goal of this research, but the asylum will not be the sole emphasis. The focus is to place child mental deficiency within a broader context of extramural care. By examining workhouses, the role of family, and philanthropic attempts to deal with insane children, this article will move beyond current historical thinking on the topic; traditional views of childhood, insanity and charity will be challenged, and will show that a much wider world than the locality was accessible to the insane child.

Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus.

Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.

The dorsal chaetotaxy of Trogolaphysa (Collembola, Paronellidae), with descriptions of two new species from caves in Belize.

Species diagnosis in Trogolaphysa has been based, until now, almost exclusively on number of eyes and shape of claws and mucro. Chaetotaxy, a character system important to diagnose species in other genera of scaled Entomobryoidea, has been described only for a few Trogolaphysa species. Here the complete dorsal chaetotaxy of six species of Trogolaphysa is described using the AMS and Szeptycki's systems for head and body, respectively. A morphology-based parsimony analysis was performed to evaluate whether chaetotaxic characters overcome the influence of putatively cave adaptive convergent characters to resolve species level relationships, and to evaluate the evolution of the dorsal macrochaetae of the head. Phylogenetic analysis using only putative cave-adaptive characters support clades of unrelated taxa, but the addition of chaetotaxy overcomes the influence of convergent characters. A phylogeny based on all characters supports a trend towards reduced head macrochaetae number. Head macrochaetae are lost beginning with A3 and followed, in order, by S5, S3 and M3. In addition, a checklist of New World Trogolaphysa is provided and two new species, Trogolaphysa giordanoae sp. n. and Trogolaphysa jacobyi sp. n., are described on the basis of material collected in six caves in southern Belize.

A new species of Tarsonops (Araneae, Caponiidae) from southern Belize, with a key to the genera of the subfamily Nopinae.

A new species of Caponiidae, Tarsonops irataylori sp. n. is described from southern Belize, and a key to the genera of the subfamily Nopinae is provided.

Discovery of potent, selective chymase inhibitors via fragment linking strategies.

Chymase plays an important and diverse role in the homeostasis of a number of cardiovascular processes. Herein, we describe the identification of potent, selective chymase inhibitors, developed using fragment-based, structure-guided linking and optimization techniques. High-concentration biophysical screening methods followed by high-throughput crystallography identified an oxindole fragment bound to the S1 pocket of the protein exhibiting a novel interaction pattern hitherto not observed in chymase inhibitors. X-ray crystallographic structures were used to guide the elaboration/linking of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over cathepsin G and that mitigated a number of liabilities associated with poor physicochemical properties of the series it was derived from.

Deconstruction of sulfonamide inhibitors of the urotensin receptor (UT) and design and synthesis of benzylamine and benzylsulfone antagonists.

Potent small molecule antagonists of the urotensin receptor are described. These inhibitors were derived via systematically deconstructing a literature inhibitor to understand the basic pharmacophore and key molecular features required to inhibit the protein receptor. The series of benzylamine and benzylsulfone antagonists herein reported display a combination of nanomolar molecular and cellular potency as well as acceptable in vitro permeability and metabolic stability.

A new species of Ripipteryx from Belize with a key to the species of the Scrofulosa Group (Orthoptera, Ripipterygidae).

A new species of the genus Ripipteryx (Orthoptera: Tridactyloidea: Ripipterygidae) from the Toledo District of southern Belize is described and illustrated. Ripipteryx mopanasp. n. is placed in the Scrofulosa Group based on its elaborately ornamented frons and is readily distinguished from its congeners by the fusion of the superior and inferior frontal folds to form a nasiform median process, the epiproct with both anterior and posterior margins emarginate, the subgenital plate with distinct lateroapical depressions either side of the median line, the basal plate of the phallus strongly bilobed apically, and the development of well-demarcated denticular lobes in the dorsal endophallic valves. A preliminary key to the species of the Scrofulosa Group is provided.

Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13.

Matrix metalloproteases (MMPs) play an important role in cartilage homeostasis under both normal and inflamed disease states and, thus, have become attractive targets for the treatment of arthritic diseases. Herein, we describe the identification of a potent, selective MMP-13 inhibitor, developed using fragment-based structure-guided lead identification and optimization techniques. Virtual screening methods identified a novel, indole-based MMP-13 inhibitor that bound into the S1' pocket of the protein exhibiting a novel interaction pattern hitherto not observed in MMP-13 inhibitors. X-ray crystallographic structures were used to guide the elaboration of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over nine other MMP isoforms tested.

Soil Bacteria and Fungi Respond on Different Spatial Scales to Invasion by the Legume Lespedeza cuneata.

The spatial scale on which microbial communities respond to plant invasions may provide important clues as to the nature of potential invader-microbe interactions. Lespedeza cuneata (Dum. Cours.) G. Don is an invasive legume that may benefit from associations with mycorrhizal fungi; however, it has also been suggested that the plant is allelopathic and may alter the soil chemistry of invaded sites through secondary metabolites in its root exudates or litter. Thus, L. cuneata invasion may interact with soil microorganisms on a variety of scales. We investigated L. cuneata-related changes to soil bacterial and fungal communities at two spatial scales using multiple sites from across its invaded N. American range. Using whole-community DNA fingerprinting, we characterized microbial community variation at the scale of entire invaded sites and at the scale of individual plants. Based on permutational multivariate analysis of variance, soil bacterial communities in heavily invaded sites were significantly different from those of uninvaded sites, but bacteria did not show any evidence of responding at very local scales around individual plants. In contrast, soil fungi did not change significantly at the scale of entire sites, but there were significant differences between fungal communities of native versus exotic plants within particular sites. The differential scaling of bacterial and fungal responses indicates that L. cuneata interacts differently with soil bacteria and soil fungi, and these microorganisms may play very different roles in the invasion process of this plant.

The genus Camptochaeta in Nearctic caves, with the description of C. prolixa sp. n. (Diptera, Sciaridae).

Camptochaeta prolixasp. n. (Diptera, Sciaridae) is described from caves in Nevada, and three other congeneric species are recorded from caves in Nevada and Arkansas, United States. The new species shows some indication to a subterranean mode of life, including long antenna and legs, and in some specimens, reduction of the eye bridge.