Violent and Nonviolent Crimes Against Sex Workers: The Influence of the Sex Market on Reporting Practices in the United Kingdom.

Previous research has shown that sex workers experience extremely high rates of victimization but are often reluctant to report their experiences to the police. This article explores how the markets in which sex workers operate in the United Kingdom impact upon the violent and nonviolent crimes they report to a national support organization and their willingness to report victimization to the police. We use a secondary quantitative data analysis of 2,056 crime reports submitted to the U.K. National Ugly Mugs (NUM) scheme between 2012 and 2016. The findings indicate that although violence is the most common crime type reported to NUM, sex workers operating in different markets report varying relative proportions of different types of victimization. We also argue that there is some variation in the level of willingness to share reports with the police across the different sex markets, even when the types of crime, presence of violence, and other variables are taken into account. Our finding that street sex workers are most likely to report victimization directly to the police challenges previously held assumptions that criminalization is the key factor preventing sex workers from engaging with the police.

COVID-19 in Pediatric Long-Term Care: How Infection Control and Prevention Practices Minimized the Impact of the Pandemic on Healthcare Providers and Residents.

Children in pediatric long-term care (LTC) facilities are commonly infected with respiratory tract viruses as they have many high-risk co-morbidities and require significant interactions with the healthcare team. From previous studies, we know that infected staff can often be the source of transmission of infection to the children. If instituted quickly, infection control practices can help mitigate the spread of infection. We will describe how Sunshine Children's Home and Rehabilitation Center responded to federal and state infection control and prevention mandates in LTC for COVID-19. We will report our practice changes, staff and resident screening, and testing results as well as outcomes of the COVID-19-infected cases. The outcomes for COVID-19 infection among pediatric LTC staff and residents are in stark contrast to the data available for the adult providers and residents in adult nursing homes. Implementation and change in infection control practices and procedures resulted in much fewer cases of COVID-19 infection in our pediatric LTC residents.

Insulated conducting cantilevered nanotips and two-chamber recording system for high resolution ion sensing AFM.

Biological membranes contain ion channels, which are nanoscale pores allowing controlled ionic transport and mediating key biological functions underlying normal/abnormal living. Synthetic membranes with defined pores are being developed to control various processes, including filtration of pollutants, charge transport for energy storage, and separation of fluids and molecules. Although ionic transport (currents) can be measured with single channel resolution, imaging their structure and ionic currents simultaneously is difficult. Atomic force microscopy enables high resolution imaging of nanoscale structures and can be modified to measure ionic currents simultaneously. Moreover, the ionic currents can also be used to image structures. A simple method for fabricating conducting AFM cantilevers to image pore structures at high resolution is reported. Tungsten microwires with nanoscale tips are insulated except at the apex. This allows simultaneous imaging via cantilever deflections in normal AFM force feedback mode as well as measuring localized ionic currents. These novel probes measure ionic currents as small as picoampere while providing nanoscale spatial resolution surface topography and is suitable for measuring ionic currents and conductance of biological ion channels.

Graphene nanopore support system for simultaneous high-resolution AFM imaging and conductance measurements.

Accurately defining the nanoporous structure and sensing the ionic flow across nanoscale pores in thin films and membranes has a wide range of applications, including characterization of biological ion channels and receptors, DNA sequencing, molecule separation by nanoparticle films, sensing by block co-polymers films, and catalysis through metal-organic frameworks. Ionic conductance through nanopores is often regulated by their 3D structures, a relationship that can be accurately determined only by their simultaneous measurements. However, defining their structure-function relationships directly by any existing techniques is still not possible. Atomic force microscopy (AFM) can image the structures of these pores at high resolution in an aqueous environment, and electrophysiological techniques can measure ion flow through individual nanoscale pores. Combining these techniques is limited by the lack of nanoscale interfaces. We have designed a graphene-based single-nanopore support (∼5 nm thick with ∼20 nm pore diameter) and have integrated AFM imaging and ionic conductance recording using our newly designed double-chamber recording system to study an overlaid thin film. The functionality of this integrated system is demonstrated by electrical recording (<10 pS conductance) of suspended lipid bilayers spanning a nanopore and simultaneous AFM imaging of the bilayer.

Alzheimer's disease: which type of amyloid-preventing drug agents to employ?

The current paradigm in the amyloid hypothesis brands small ß-amyloid (Aß) oligomers as the toxic species in Alzheimer's disease (AD). These oligomers are fibril-like; contain ß-sheet structure, and present exposed hydrophobic surface. Oligomers with this motif are capable of penetrating the cell membrane, gathering to form toxic ion channels. Current agents suppressing precursor Aß cleavage have only met partial success; and to date, those targeting the peptides and their assemblies in the aqueous environment of the extracellular space largely fail in clinical trials. One possible reason is failure to reach membrane-embedded targets of disease-'infected' cells. Here we provide an overview, point to the need to account for the lipid environment when aiming to prevent the formation of toxic channels, and propose a combination therapy to target the species spectrum.

Mechanisms for the Insertion of Toxic, Fibril-like ß-Amyloid Oligomers into the Membrane.

Amyloid-ß (Aß) oligomers destabilize cellular ionic homeostasis, mediating Alzheimer's disease (AD). It is still unclear whether the mechanism (i) is mediated by cell surface receptors; (ii) is direct, with Aß oligomers interacting with membrane lipids; or (iii) both mechanisms take place. Recent studies indicate that Aß oligomers may act by either of the last two. Little is known about the oligomers' structures and how they spontaneously insert into the membrane. Using explicit solvent molecular dynamics (MD) simulations, we show that fibril-like Aß(17-42) (p3) oligomer is capable of penetrating the membrane. Insertion is similar to that observed for protegrin-1 (PG-1), a cytolytic ß-sheet-rich antimicrobial peptide (AMP). Both Aß and PG-1 favor the amphipathic interface of the lipid bilayer in the early stage of interaction with the membrane. U-shaped Aß oligomers are observed in solution and in the membrane, suggesting that the preformed seeds can be shared by amyloid fibrils in the growth phase and membrane toxicity. Here we provide sequential events in possible Aß oligomer membrane-insertion pathways. We speculate that for the U-shaped motif, a trimer is the minimal oligomer size to insert effectively. We propose that monomers and dimers may insert in (apparently on-pathway) aggregation-intermediate ß-hairpin state, and may (or may not) convert to a U-shape in the bilayer. Together with earlier observations, our results point to a non-specific, broadly heterogeneous landscape of membrane-inserting oligomer conformations, pathways, and membrane-mediated toxicity of ß-rich oligomers.

All-d-Enantiomer of ß-Amyloid Peptide Forms Ion Channels in Lipid Bilayers.

Alzheimer's disease (AD) is the most common type of senile dementia in aging populations. Amyloid ß (Aß)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aß-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aß binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aß peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aß effects even in the absence of receptor-peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aß isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aß isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aß isomer channels, and the d-isomer channel conductance is blocked by Zn(2+), a known blocker of l-Aß isomer channels. MD simulations further verify formation of ß-barrel-like Aß channels with d- and l-isomers, illustrating that both d- and l-Aß barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca(2+) leaking, unregulated channels in AD, and suggest that Aß toxicity is mediated through a receptor-independent, nonstereoselective mechanism.

Effects of point substitutions on the structure of toxic Alzheimer's ß-amyloid channels: atomic force microscopy and molecular dynamics simulations.

Alzheimer's disease (AD) is a misfolded protein disease characterized by the accumulation of ß-amyloid (Aß) peptide as senile plaques, progressive neurodegeneration, and memory loss. Recent evidence suggests that AD pathology is linked to the destabilization of cellular ionic homeostasis mediated by toxic pores made of Aß peptides. Understanding the exact nature by which these pores conduct electrical and molecular signals could aid in identifying potential therapeutic targets for the prevention and treatment of AD. Here using atomic force microscopy (AFM) and molecular dynamics (MD) simulations, we compared the imaged pore structures with models to predict channel conformations as a function of amino acid sequence. Site-specific amino acid (AA) substitutions in the wild-type Aß(1-42) peptide yield information regarding the location and significance of individual AA residues to its characteristic structure-activity relationship. We selected two AAs that our MD simulation predicted to inhibit or permit pore conductance. The substitution of Phe19 with Pro has previously been shown to eliminate conductance in the planar lipid bilayer system. Our MD simulations predict a channel-like shape with a collapsed pore, which is supported by the AFM channel images. We suggest that proline, a known ß-sheet breaker, creates a kink in the center of the pore and prevents conductance via blockage. This residue may be a viable target for drug development studies aiming to inhibit Aß from inducing ionic destabilization toxicity. The substitution of Phe20 with Cys exhibits pore structures indistinguishable from the wild type in AFM images. MD simulations predict site 20 to face the solvated pore. Overall, the mutations support the previously predicted ß-sheet-based channel structure.

Atomic force microscopy and MD simulations reveal pore-like structures of all-D-enantiomer of Alzheimer's ß-amyloid peptide: relevance to the ion channel mechanism of AD pathology.

Alzheimer's disease (AD) is a protein misfolding disease characterized by a buildup of ß-amyloid (Aß) peptide as senile plaques, uncontrolled neurodegeneration, and memory loss. AD pathology is linked to the destabilization of cellular ionic homeostasis and involves Aß peptide-plasma membrane interactions. In principle, there are two possible ways through which disturbance of the ionic homeostasis can take place: directly, where the Aß peptide either inserts into the membrane and creates ion-conductive pores or destabilizes the membrane organization, or, indirectly, where the Aß peptide interacts with existing cell membrane receptors. To distinguish between these two possible types of Aß-membrane interactions, we took advantage of the biochemical tenet that ligand-receptor interactions are stereospecific; L-amino acid peptides, but not their D-counterparts, bind to cell membrane receptors. However, with respect to the ion channel-mediated mechanism, like L-amino acids, D-amino acid peptides will also form ion channel-like structures. Using atomic force microscopy (AFM), we imaged the structures of both D- and L-enantiomers of the full length Aß(1-42) when reconstituted in lipid bilayers. AFM imaging shows that both L- and D-Aß isomers form similar channel-like structures. Molecular dynamics (MD) simulations support the AFM imaged 3D structures. Previously, we have shown that D-Aß(1-42) channels conduct ions similarly to their L- counterparts. Taken together, our results support the direct mechanism of Aß ion channel-mediated destabilization of ionic homeostasis rather than the indirect mechanism through Aß interaction with membrane receptors.

With "equal regard": an overview of how Ellen Pence focused the supervised visitation field on battered women and children.

Ellen Pence has changed the framework for doing supervised visitation and safe exchanges in cases of domestic violence. Ellen challenged the basic tenets of "neutrality" and a primary focus on "safety for children" in the supervised visitation field. By incorporating equal regard for the safety of adult victims of domestic violence and children, Ellen challenged supervised visitation centers to reexamine their mission, role, intake/orientation, documentation, and rules for their programming. She designed services for supervised visitation that would account for battering of women and children while not being excessively policing and providing a respectful and fair atmosphere for men who batter.

Relative quantum yield measurements of coumarin encapsulated in core-shell silica nanoparticles.

Fluorescent silica nanoparticles encapsulating organic fluorophores provide an attractive materials platform for a wide array of applications where high fluorescent brightness is required. We describe a class of fluorescent silica nanoparticles with a core-shell architecture and narrow particle size distribution, having a diameter of less than 20 nm and covalently incorporating a blue-emitting coumarin dye. A quantitative comparison of the scattering-corrected relative quantum yield of the particles to free dye in water yields an enhancement of approximately an order of magnitude. This enhancement of quantum efficiency is consistent with previous work on rhodamine dye-based particles. It provides support for the argument that improved brightness over free dye in aqueous solution is a more general effect of covalent incorporation of fluorescent organic dyes within rigid silica nanoparticle matrices. These results indicate a synthetic route towards highly fluorescent silica nanoparticles that produces excellent probes for imaging, security, and sensing applications.

Antibiofouling, sustained antibiotic release by Si nanowire templates.

Loading or filling nanostructures with antibiotics can be one of the relevant approaches for obtaining a controlled drug release rate. Vertically aligned silicon nanowire (SiNW) arrays with 10-40 nm diameter wires having 1-3 microm in length obtained by the electroless etching (EE) technique are used in this study as novel nanostructures for mediating drug delivery. Here we report controlled antibiotic activity and sustained bioavailability from SiNW arrays and also show microstructural manipulations for a tunable release rate. As well, we have demonstrated biodegradability of SiNWs in phosphate buffer saline (PBS) solution. Strikingly suppressed cell and protein adhesion was observed on our SiNW surface, which indicates a reduced probability for biofouling and drug release impediments. Such antibiotic release from the nanowire-structured surface can provide more reliable antibiotic protection at a targeted implantation or biosensor site.