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The high prevalence of breast cancer is a global health concern, but there are no safe or effective treatments for it at its advanced stages. These facts urge the development of novel treatment strategies. Annexin A5 (ANXA5) is a natural human protein that binds with high specificity to phosphatidylserine, a phospholipid tightly maintained in the inner leaflet of the cell membrane on most healthy cells but externalized in tumor cells and the tumor vasculature. Here, we have developed a targeted photosensitizer for photothermal therapy (PTT) of solid tumors through the functionalization of single walled carbon nanotubes (SWCNTs) to ANXA5—the SWCNT-ANXA5 conjugate. The ablation of tumors through the SWCNT-ANXA5-mediated PTT synergizes with checkpoint inhibition, creating a systemic anti-cancer immune response. In vitro ablation of cells incubated with the conjugate promoted cell death in a dose-dependent and targeted manner. This treatment strategy was tested in vivo with the orthotopic EMT6 breast tumor model in female balb/cJ mice. Enhanced therapeutic effects were achieved by using intratumoral injection of the conjugate and treating tumors at a lower PTT temperature (45oC). When combined with checkpoint inhibition of anti-PD-1, SWCNT-ANXA5-mediated PTT increased survival and 80% of the mice survived for 100 days. Evidence of immune system activation by flow cytometry of splenic cells strengthens the hypothesis of an abscopal effect as a mechanism of prolonged survival.

This file contains includes 9 figures of supplementary data (S1-S9) and a description of live cell microscopy and the assessment of synergism for the combination therapies.

Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with Annexin A1 or Annexin A5. Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart nonnative methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of nontoxic selenomethionine. The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of nonnative proteins and/or DNA required with other enzyme prodrug systems. The enzyme fusion exhibits strong and stable in vitro binding with dissociation constants in the nanomolar range for both human and mouse breast cancer cells and in a cell model of tumor vascular endothelium. Daily administration of the therapy suppressed growth of highly aggressive triple-negative murine 4T1 mammary tumors in immunocompetent BALB/cJ mice and MDA-MB-231 tumors in SCID mice. Treatment did not result in the occurrence of negative side effects or the elicitation of neutralizing antibodies. On the basis of the vasculature-targeted nature of the therapy, combinations with rapamycin and cyclophosphamide were evaluated. Rapamycin, an mTOR inhibitor, reduces the prosurvival signaling of cells in a hypoxic environment potentially exacerbated by a vasculature-targeted therapy. IHC revealed, unsurprisingly, a significant hypoxic response (increase in hypoxia-inducible factor 1 α subunit, HIF1A) in the enzyme prodrug–treated tumors and a dramatic reduction of HIF1A upon rapamycin treatment. Cyclophosphamide, an immunomodulator at low doses, was combined with the enzyme prodrug therapy and rapamycin; this combination synergistically reduced tumor volumes, inhibited metastatic progression, and enhanced survival. Mol Cancer Ther; 16(9); 1855–65. ©2017 AACR.

Purpose: Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary. The purpose of this study is to evaluate and compare out-of-field doses in pediatric CSI treatment using conventional and advanced photon radiotherapy (RT) and advanced proton therapy. To our knowledge, it is the first such comparison based on in-phantom measurements. Additionally, for out-of-field doses during photon RT in this and other studies, comparisons were made using analytical modeling. Methods: In order to describe the out-of-field doses absorbed in a pediatric patient during actual clinical treatment, an anthropomorphic phantom which mimics the 10-year-old child was used. Photon 3D-conformal radiotherapy (3D-CRT) and two advanced, highly conformal techniques: photon volumetric modulated arc therapy (VMAT) and active pencil beam scanning (PBS) proton radiotherapy were used for CSI treatment. Radiophotoluminescent (RPL) and poly-allyl-diglycol-carbonate (PADC) nuclear track detectors were used for photon and neutron dosimetry in the phantom, respectively. Out-of-field doses from neutrons were expressed in terms of dose equivalent. A two-Gaussian model was implemented for out-of-field doses during photon RT. Results: The mean VMAT photon doses per target dose to all organs in this study were under 50% of the target dose (i.e., < 500 mGy/Gy), while the mean 3D-CRT photon dose to oesophagus, gall bladder and thyroid, exceeded that value. However, for 3D-CRT, better sparing was achieved for eyes and lungs. The mean PBS photon doses for all organs were up to 3 orders of magnitude lower compared to VMAT and 3D-CRT and exceeded 10 mGy/Gy only for the oesophagus, intestine and lungs. The mean neutron dose equivalent during PBS for 8 organs of interest (thyroid, breasts, lungs, liver, stomach, gall bladder, bladder, prostate) ranged from 1.2 mSv/Gy for bladder to 23.1 mSv/Gy for breasts. Comparison of out-of-field doses in this and other phantom studies found in the literature showed that a simple and fast two-Gaussian model for out-of-field doses as a function of distance from the field edge can be applied in a CSI using photon RT techniques. Conclusions: PBS is the most promising technique for out-of-field dose reduction in comparison to photon techniques. Among photon techniques, VMAT is a preferred choice for most of out-of-field organs and especially for the thyroid, while doses for eyes, breasts and lungs, are lower for 3D-CRT. For organs outside the field edge, a simple analytical model can be helpful for clinicians involved in treatment planning using photon RT but also for retrospective data analysis for cancer risk estimates and epidemiology in general.

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases, in contrast to the single phase found for amantadine block of wild-type M2. Here, we evaluate the mechanism of block by copper adamantyl iminodiacitate and copper cyclooctyl iminodiacitate complexes and address whether the complexes can coordinate with one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper complex binding within the channel, and the slow step in the current block is the formation of a Cu-histidine coordination complex. Solution-phase isothermal titration calorimetry and density functional theory (DFT) calculations indicate that imidazole binds to the copper complexes. Structural optimization using DFT reveals that the complexes fit inside the channel and project the Cu(II) toward the His37 cluster, allowing one imidazole to form a coordination complex with Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant despite some crowding in the binding site by the glutamates.

Due to their non-toxicity and their ability to be functionalized, magnetite (Fe3O4) nanoparticles (NPs) are good candidates for a variety of biomedical applications. To better implement their applications, it is crucial to well understand the basic structural and magnetic properties of the NPs in correlation with their synthesis method. Here, we show interesting properties of Fe3O4 NPs of various sizes ranging from 5 to 100 nm and the dependence of these properties on particle size and preparation method. One synthetic method based on heating Fe(acac)3 with oleic acid consistently gives 5 ± 1 nm NPs. A second method using the thermal decomposition of Fe(oleate)3 in oleic acid led to larger NPs, greater than 8 nm in size. Increasing the amount of oleic acid caused the average NP size to slightly increase from 8 to 10 nm. Increasing both the reaction temperature and the reaction time caused the NP size to drastically increase from 10 to 100 nm. Powder X-ray diffraction and electron-microscopy imaging show a pure single crystalline Fe3O4 phase for all NPs smaller than 50 nm and spherical in shape. When the NPs get larger than 50 nm, they notably tend to form faceted, FeO core–Fe3O4 shell structures. Magnetometry data collected in various field-cooling conditions show a pure superparamagnetic (SPM) behavior for all NPs smaller than 20 nm. The observed blocking temperature, $T_{B}$ , gradually increases with NP size from about 25–150 K. In addition, the Verwey transition is observed with the emergence of a strong narrow peak at 125 K in the magnetization curves when larger NPs are present. Our data confirm the vanishing of the Verwey transition in smaller NPs. Magnetization loops indicate that the saturating field drastically decreases with NP size. While larger NPs show some coercivity ( $H_{c}$ ) up to 30 mT at 400 K, NPs smaller than 20 nm show no coercivity ( $H_{c} = 0$ ), confirming their pure SPM behavior at high temperature. Upon cooling below $T_{B}$ , some of the SPM NPs gradually show some coercivity, with $H_{c}$ reaching 45 mT at 5 K for the 10 nm NPs, indicating emergent interparticle couplings in the blocked state.

The gender and ethnicity attainment gap among undergraduate students in UK higher education is well documented. However, there is very little research examining the international attainment gap des...

Peer-assisted learning (PAL) involves a student peer providing some form of support to a student mentee, usually participating at an earlier point in the same programme of study. PAL has been shown...

PurposeThis study aims to characterize the neutron radiation field inside a scanning proton therapy treatment room including the impact of different pediatric patient sizes.Materials and MethodsWorking Group 9 of the European Radiation Dosimetry Group (EURADOS) has performed a comprehensive measurement campaign to measure neutron ambient dose equivalent, H*(10), at eight different positions around 1-, 5-, and 10-year-old pediatric anthropomorphic phantoms irradiated with a simulated brain tumor treatment. Several active detector systems were used.ResultsThe neutron dose mapping within the gantry room showed that H*(10) values significantly decreased with distance and angular deviation with respect to the beam axis. A maximum value of about 19.5 µSv/Gy was measured along the beam axis at 1 m from the isocenter for a 10-year-old pediatric phantom at 270° gantry angle. A minimum value of 0.1 µSv/Gy was measured at a distance of 2.25 m perpendicular to the beam axis for a 1-year-old pediatric phantom at 140° gantry angle.The H*(10) dependence on the size of the pediatric patient was observed. At 270° gantry position, the measured neutron H*(10) values for the 10-year-old pediatric phantom were up to 20% higher than those measured for the 5-year-old and up to 410% higher than for the 1-year-old phantom, respectively.ConclusionsUsing active neutron detectors, secondary neutron mapping was performed to characterize the neutron field generated during proton therapy of pediatric patients. It is shown that the neutron ambient dose equivalent H*(10) significantly decreases with distance and angle with respect to the beam axis. It is reported that the total neutron exposure of a person staying at a position perpendicular to the beam axis at a distance greater than 2 m from the isocenter remains well below the dose limit of 1 mSv per year for the general public (recommended by the International Commission on Radiological Protection) during the entire treatment course with a target dose of up to 60 Gy. This comprehensive analysis is key for general neutron shielding issues, for example, the safe operation of anesthetic equipment. However, it also enables the evaluation of whether it is safe for parents to remain near their children during treatment to bring them comfort. Currently, radiation protection protocols prohibit the occupancy of the treatment room during beam delivery.

Background Antibiotics have led to considerable increases in life expectancy. However, over time, antimicrobial resistance has accelerated and is now a significant global public health concern. Understanding societal preferences for the use of antibiotics as well as eliciting the willingness to pay for future research is crucial. Objective To investigate preferences for different strategies to optimize antibiotic use and to understand the willingness to pay for future research in antimicrobial resistance and antimicrobial drug development. Methods A discrete-choice experiment was administered to a sample of the UK general population. Respondents were asked to make nine choices, each offering three options—two hypothetical “doctor and antibiotics” and one “no doctor—no antibiotics”—defined by five attributes: treatment, days needed to recover, risk of bacterial infection that needs antibiotics, risk of common side effects, and risk of antimicrobial resistance by 2050. Data were analyzed using random parameters logit models. A double-bounded contingent valuation was also included in the survey to explore the willingness to pay for policies to contain antimicrobial resistance. Results Among the 2579 respondents who completed the survey, 1151 always selected “no doctor—no antibiotics” and 57 never varied their choices; therefore, 1371 responses were used in the analysis. Risk of antimicrobial resistance by 2050 was the most important attribute and the “treatment” was the least important attribute, although this was sensitive to a higher risk of bacterial infection. The aggregate annual willingness to pay for containing antimicrobial resistance was approximately £8.35 billion (~£5–£10 billion). Conclusions The antimicrobial resistance risk is relevant and important to the general public. The high willingness to pay suggests that large investments in policies or interventions to combat antimicrobial resistance are justified. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01076-9.

Background Non-communicable diseases (NCDs) are a growing burden which affects every part of the world, including developing countries. Chronic kidney disease (CKD) has varied etiology which can result from or complicate other NCDs such as diabetes and cardiovascular diseases. The growing prevalence of NCDs coupled with the increasing age in most developing countries, has seen a marked increase of CKD in these settings. CKD has been described as “the most neglected NCD” and greatly affects the quality of life of patients. It also places a huge economic burden on societies. However, few epidemiological data exist, particularly in sub-Saharan Africa. Assessment of the prevalence of albuminuria as a marker of kidney damage and CKD progression and its main risk factors was thus needed in Rwanda. Methods This study analyzed data collected during the first STEPwise approach to NCD risk factor Surveillance (STEPS) survey in Rwanda, conducted from 2012 to 2013, to assess the prevalence of albuminuria. A multistage cluster sampling allowed to select a representative sample of the general population. Furthermore, descriptive, as well as univariable analyses and multiple logistic regression were performed to respond to the research question. Results This survey brought a representative sample of 6,998 participants, among which 4,384 (62.65%) were female. Median age was 33 years (interquartile range, IQR 26-44), and over three quarters (78.45%) lived in rural areas. The albuminuria prevalence was 105.9 per 1,000 population. Overall, semi-urban and urban residency were associated with lower odds of CKD (odds ratio, OR 0.36, CI 0.23-0.56, ppp=0.031) and OR 1.62 (CI 1.06-2.48, p=0.026), respectively) of CKD than being single. Odds of positive albuminuria were also greater among participants living with human immunodeficiency virus (HIV) (OR 1.64, CI 1.09- 2.47, p=0.018). Gender, age group, smoking status and vegetable consumption, body mass index (BMI) and hypertension were not associated with albuminuria. Conclusion The albuminuria prevalence was estimated at 105.9 per 1,000 in Rwanda. Rural residence, partnered status and HIV positivity were identified as main risk factors for albuminuria. Increased early screening of albuminuria to prevent CKD among high-risk groups, especially HIV patients, is therefore recommended.

Identifying a universal biomarker for cancer treatment remains a major challenge in cancer therapy. Extracellular exposure of phosphatidylserine (PS) is tightly regulated and is an "eat me" signal for phagocytosis in healthy cells. Although cancer cells and vasculature express high levels of externalized PS, they do not undergo apoptosis, making them a promising biomarker for cancer treatment. Annexin A5 (ANXA5) is the native binding partner of PS and can actively target and deliver chemotherapies to the tumor microenvironment (TME) via PS expression. ANXA5 acts as a bridge between the innate and adaptive immune systems and contributes to an immunostimulatory profile in the TME. ANXA5-enzyme prodrug therapies allow for systemic delivery of prodrugs and targeted killing at the tumor site. ANXA5-carbon nanotube conjugates have been used to physically ablate tumors via photothermal therapy. This review aims to explore the expression of PS in cancer cells and how ANXA5 has been used as a chemotherapeutic and targeting agent for cancer.

The COVID-19 (2019 novel coronavirus) pandemic has had a significant economic, social, emotional, and public health impact in the United States. A disturbing trend is that Black, Indigenous, and/or People of Color (BIPOC) are disproportionately contracting coronavirus, as well as dying from COVID-19. Objective/Methods The pandemic has the potential to entrench and magnify existing health disparities and families marginalized across multiple demographic intersections such as race/ethnicity, class, immigration status, are especially vulnerable. These inequities have been further underscored by the recent murders of Black Americans by police and a resulting spotlight on racial injustice in the United States. Results Efforts to lessen the spread of the virus, have resulted in changes in pediatric primary and subspecialty service delivery which may affect access for BIPOC communities. BIPOC trainees including those with debt or caregiving responsibilities may be faced with new barriers resulting in delays in completion of their training. Further, clinical, community-based, and translational research has been disrupted by heightened safety precautions and social distancing which may affect BIPOC representation in research downstream. Conclusion In our roles as clinicians, supervisors, trainees, and researchers in primary and subspecialty care as well as in academia, pediatric psychologists have an ethical responsibility to address the disproportionate burden of this pandemic on vulnerable communities and to allocate our time and resources to ensuring health equity now and in the aftermath of COVID-19.

Resorcinarene-based deep cavitands including glutamic acid methyl resorcinarene (GMA) and glutamic acid undecyl resorcinarene (GUA) have been synthesised and their amine binding properties analysed. The cavitands are designed with hydrogen bonding groups on their upper rim (glutamic acids) and hydrophobic groups, on their lower rims. Along with the aromatic groups of the resorcinarene, these cavitands have many sites for guest binding. The cavitands form kite-like structures in dimethylsulfoxide, acetone, and water. The binding of GMA with amines, including guanidine containing drug compounds, was studied in DMSO by UV-vis titration and compared to that of phthalyl glutamic acid. The obtained binding constants for GMA to amines (K values) were in the range of 12–136 × 103 M−1 for benzyl amines and 4.3–153 × 103 M−1 for guanidine compounds. GMA shows a binding preference for more basic and less sterically encumbered amines and slightly stronger binding to S-enantiomers.

The magnetic properties of ${\mathrm{Fe}}_{3}{\mathrm{O}}_{4}$ nanoparticle assemblies have been investigated in detail through a combination of vibrating sample magnetometry (VSM) and muon spin relaxation ($\ensuremath{\mu}\mathrm{S}\mathrm{R}$) techniques. Two samples with average particle sizes of 5 and 20 nm, respectively, were studied. For both samples, the VSM and $\ensuremath{\mu}\mathrm{S}\mathrm{R}$ results exhibit clear signatures of superparamagnetism at high temperature and magnetic blocking at low temperature. The $\ensuremath{\mu}\mathrm{S}\mathrm{R}$ data demonstrate that the transition from the superparamagnetic to the blocked state occurs gradually throughout the sample volume over an extended temperature range due to the finite particle size distribution of each nanoparticle batch. The transition occurs between approximately 3 and 45 K for the 5-nm nanoparticles and 150 and 300 K for the 20-nm nanoparticles. The VSM and $\ensuremath{\mu}\mathrm{S}\mathrm{R}$ data are further analyzed to yield estimates of microscopic magnetic parameters including the nanoparticle spin-flip activation energy ${E}_{A}$, magnetic anisotropy $K$, and intrinsic nanoparticle spin reversal attempt time ${\ensuremath{\tau}}_{0}$. These results highlight the complementary information about magnetic nanoparticles that can be obtained by bulk magnetic probes such as magnetometry and local magnetic probes such as $\ensuremath{\mu}\mathrm{S}\mathrm{R}$.

The greatest contributors to cancer mortality are metastasis and the consequences of its treatment. Here, we present a novel treatment of metastatic breast cancer that combines photothermal therapy with targeted single-walled carbon nanotubes (SWCNTs) and immunostimulation with a checkpoint inhibitor. We find that the selective near-infrared photothermal ablation of primary orthotopic EMT6 breast tumors in syngeneic BALB/cJ mice using an annexin A5 (ANXA5) functionalized SWCNT bioconjugate synergistically enhances an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4)-dependent abscopal response, resulting in an increased survival (55%) at 100 days after tumor inoculation. In comparison, there was no survival at 100 days for either photothermal therapy by itself or immunostimulation by itself. Prior to photothermal therapy, the SWCNT-ANXA5 bioconjugate was administered systemically at a relatively low dose of 1.2 mg/kg, where it then accumulated in tumor vasculature via ANXA5-dependent binding. During photothermal therapy, the average maximum temperature in the tumor reached 54 °C (duration 175 s). The mechanism of prolonged survival resulting from combinatorial photothermal ablation and immune stimulation was evaluated by flow cytometric quantification of splenic antitumoral immune effector cells and serum cytokine quantification.

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases in contrast to the single phase found for amantadine block of WT M2. Here we evaluate the mechanism of block by copper adamantyl iminodiacitate (Cu(AMT-IDA)) and copper cyclooctyl iminodiacitate (Cu(CO-IDA)) complexes and address whether the complexes can covalently bind to one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper-complex binding within the channel and the slow step in the current block is the covalent bond formation between copper complex and histidine. Isothermal titration calorimetry (ITC) indicates that a single imidazole binds strongly to the copper complexes. Structural optimization using density functional theory (DFT) reveals that the complexes fit inside the channel and project the Cu(II) towards the His37 cluster allowing one imidazole to form a covalent bond with the Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant in spite of some crowding in the binding site by the glutamates.

Technetium poses an environmental hazard because of its radioactivity and long half-life. It exists in the form of pertechnetate in the environment and can be modeled by the nonradioactive ion perrhenate, since pertechnetate and perrhenate have the same geometry and similar chemical properties. In this research, a new zinc cyclen resorcinarene cavitand (ZCR) column was used in ion chromatography (IC) to efficiently separate perrhenate. Ion chromatography has the advantage of requiring almost no sample preparation for water samples. The ZCR column demonstrated the ability to separate anions: fluoride, chloride, nitrate, sulfate, phosphate, perchlorate, and perrhenate by gradient 2–60 mM NaOH. Unlike other columns, the new column material was selective in retaining perrhenate. The ZCR column also gave a linear range from 2.0 to 1000 mg L−1 for perrhenate with R2 > 0.997. There was a logarithmic relationship between the concentration of perrhenate and its retention time. Excellent perrhenate recovery was achieved on the ZCR column when river water was spiked with perrhenate and perrhenate was preconcentrated. The efficient separations of perrhenate by the ZCR column will potentially assist in pertechnetate separations.

This study validates bacterial anionic phospholipids (APs) as a putative molecular target in a novel antibiotic treatment against the Gram-positive bacterium Listeria monocytogenes and the Gram-negative bacterium Escherichia coli. Bacterial AP expression was targeted with its associated protein-ligand partner, annexin A5 (ANXA5). This protein was functionalised with the covalent addition of the antibiotic ampicillin (AMP) and separately with the antibiotic moxifloxacin (MOX). Functionalised ANXA5 serves as a delivery vehicle, directing the antibiotic to bacterial AP expression. The results presented here suggest that this ANXA5-AMP bioconjugate participates in a positive feedback loop where APs, the target of the delivery vehicle ANXA5, are upregulated by the chemotherapeutic payload of the bioconjugate. Importantly, the ANXA5 delivery vehicle is non-toxic to bacterial cells by itself and neither is the ANXA5–antibiotic bioconjugate toxic to human vascular endothelial cells. As measured by the IC50, conjugation to ANXA5 resulted in increasing the antibiotic activity of AMP against L. monocytogenes and E. coli by more than 4 and 3 orders of magnitude, respectively, compared with free AMP, whilst the activity of MOX against L. monocytogenes is increased by 4 orders of magnitude. Given the conservation of AP expression in pathologies such as oncogenesis and other bacterial/viral/parasitic infections, we hypothesise that a therapeutic modality targeting AP expression may be a viable chemotherapeutic strategy in many infectious diseases.

Since their discovery in the 1990s, carbon nanotubes have been intensively studied in several different fields, including recently for the treatment of cancer. A property of carbon nanotubes that has been used extensively in cancer treatment studies is their strong absorbance of light in the near-infrared range (700–1400 nm). This strong absorbance of light leads to heating of the nanotubes and destruction of cancer cells that have taken up or are in the vicinity of nanotubes. Photothermal therapy studies for cancer treatment both in vitro and in vivo will be discussed, including the functionalization of the nanotubes for targeting and also the in vivo coadministration of other agents such as antibodies to stimulate the immune system and thereby increase the therapeutic response. For the work in vivo, research will be discussed about the biodistribution of carbon nanotubes after being injected and their elimination and/or degradation, including toxicology evaluations.

Online distance-learning (ODL) programmes in higher education enable students to remain in their domicile country to study with institutions based in other countries. ODL students can find themselves studying with others from many different countries, adding greater heterogeneity of personal, environmental and cultural perspectives compared with on-campus education. This is likely to impact the learners’ experience in different ways. The current research examined the experience of students living outside of the European Union, who were registered with an ODL programme with a higher education institution based in the European Union. The research identified a number of important factors that influenced the students’ experience in different ways. The results emphasise the need for ODL programmes to fully consider individual students’ contexts, regardless of where they are in the world, and for these needing to be embedded in a pedagogical framework that gives due consideration to globally diverse cohorts of students.

A new sensor for Hg2+ and cysteine detection has been synthesized and tested. The sensor based on cinamaldehyde and pyrimidine absorbs visible light when exposed to Hg2+ and becomes colored. The sensor only changes color due to Hg2+ and does not change when exposed to some other metal ions. Calculations show the change in color is due to lowering of the HOMO-LUMO transition. Titrations show the sensor-Hg2+ complex is composed of two sensor molecules per Hg2+. The limit of detection for Hg2+ is 0.39 μM. The sensor-Hg2+ complex selectively responds to cysteine (Cys), but does not show a color change due to other amino acids. The limit of detection of Cys by the sensor-Hg2+ complex is 0.10 μM.

Hypochlorite is used as a water disinfectant and it is also produced by biological organisms. Its detection and quantification is important and could lead to its mechanism of reactivity in cells. We have synthesized a new fluorescence sensor for hypochlorite based on bithiophene and furan-carbohydrazide. The sensor shows increased fluorescence as a function of hypochlorite and is selective for hypochlorite. Fluorescence enhancement due to hypochlorite is observed when the sensor is used in aqueous solutions at neutral pH values. Using the sensor, the detection limit for hypochlorite is 4.2 µM, making the sensor practical to determine hypochlorite in water. Applying the sensor to aide in the detection of hypochlorite in zebrafish, showed localization of ClO−/HClO in the air bladders and eyes of zebrafish.

New M2 blockers effective against the ubiquitous amantadine-resistant S31N M2 mutation in influenza A are needed. Six copper complexes, 2, 4, 6, 8, 9, and 10, were synthesized and found to block both wild type and S31N M2. Free Cu2+ also blocks M2 S31N but not S31N/H37A. The copper complexes do not block M2 H37A (either S31 or S31N). The complexes were effective against three influenza A strains in cell-culture assays, but less toxic to cells than CuCl2. For example 4, Cu(cyclooctylamineiminodiacetate), which was stable at pH > 4 in the buffers used, had an EC50 against A/Calif/07/2009 H1N1 of 0.7 ± 0.1 μM with a CC50 of 147 μM (therapeutic index, averaged over three strains, 67.8). In contrast, CuCl2 had an EC50 of 3.8 ± 0.9 μM and CC50 of 19 μM. Because M2 H37 is highly conserved, these complexes show promise for further testing as drugs against all strains of influenza A.

Formation of crystalline hexagonal ZnO prisms from a sol–gel method is presented. The method requires zinc acetate, water, and diethanolamine to create a zinc hydroxide/zinc hydroxide acetate gel, which in the presence of water and upon heating forms hexagonal prisms. Ethanolamines were found to be critical for gel and prism formation, while other bases such NaOH and triethylamine produce nanoparticles. Scanning electron microscope images showed hexagonal prisms with uniform size (approx. 0.5 × 2 µm) and very distinct edges. Transmission electron microscope and electron diffraction images showed that the prisms were highly crystalline with rough surfaces. Transmission electron microscope also showed a change from randomly oriented particles in the gel to ordered crystals after heating. Using an X-ray diffraction high-temperature chamber to characterize the gel, it was determined that it formed ZnO at 100 °C. Along with heating, acetate and water were found to be necessary for prism formation. In a potential application, the prisms efficiently acted as a photocatalyst in the degradation of organic dye.

Education is a key to creating solidary among the professionals who advance public health’s interdisciplinary mission. Our assumption is that if all those who work in public health shared core knowledge and the skills for interdisciplinary interaction, collaboration across disciplines, venues, and countries would be facilitated. Evaluation of education is an essential element of pedagogy to ensure quality and consistency across boundaries, as articulated by the UNESCO education standards. Our study examined the evaluation studies done by programs that educate public health professionals. We searched the peer reviewed literature published in English between 2000-2017 pertaining to the education of the public health workforce at a degree-granting level. The 2442 articles found covered ten health professions disciplines and had lead authors representing all continents. Only 86 articles focused on evaluation. The majority of the papers examined either a single course, a discipline-specific curriculum or a teaching method. No consistent methodologies could be discerned. Methods ranged from sophisticated regression analyses and trends tracked over time to descriptions of focus groups and interviews of small samples. We found that evaluations were primarily discipline-specific, lacked rigorous methodology in many instances, and that relatively few examined competencies or career expectations. The public health workforce enjoys a diversity of disciplines but must be able to come together to share diverse knowledge and skills. Evaluation is critical to achieving a workforce that is well trained in the competencies pertinent to collaboration. This study informs the pedagogical challenges that must be confronted going forward, starting with a commitment to shared core competencies and to consistent and rigorous evaluation of the education related to training public health professionals. Key messages Rigorous evaluation is not sufficiently used to enhance the quality of public health education. More frequent use of rigorous evaluation in public health education would enhance the quality of public health workforce, and enable cross-disciplinary and international collaboration for solidarity.

"Organization and Strategy, Roger G. Harrison Analytical Considerations in the Development of Protein Purification Processes, Vincent Anicetti and William S. Hancock Cell Breakage, Cady R. Engler Crossflow Membrane Filtration, Zhi-Guo Su and Clark K. Cotton Liquid-Liquid Extraction, Dennis J. Kubek Differential Precipitation of Proteins: Science and Technology, Fred Rothstein Conventional Chromatography, John M. Simpson Biospecific Affinity Chromatography, Nikos K. Harakas Freeze Drying: A Practical Overview, Larry A. Gatlin and Steven L. Nail "

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio–nano papers, the community responds.

Background The purpose of this article is to identify and describe key components of research into the teaching methods of public health to postgraduate students. Study design This is a systematic review of the published literature. Methods A detailed search of the literature based on keywords, Boolean operators, and free-text terms, identified from PubMed, Scopus and ERIC, published in the English language, between January 2000 and December 2017, was made. Teams of independent pairs agreed studies eligible for the review and performed data extraction. Results Of the 2,442 potential studies on education of public health professionals, 86 met all the inclusion criteria. Specific study designs, data collection, and techniques for data analysis varied widely across the individual studies, and there was a lack of consistency on the whole. The number of students in each study ranged from ten to 1,300. Forty-seven studies used quantitative methods to assess the effectiveness of teaching. Curriculum evaluation was the most common focus (n = 33), followed by course evaluation (n = 22). Few studies considered inequalities in terms of the types of students registered on the different courses/programs, with just three evaluating strategies to increase students from minority ethnic groups. Most studies evaluated short-term or medium-term outcomes rather than long-term impacts of education on students' careers or the relationship of education in meeting future public health workforce demands. Conclusions This comprehensive systematic review identified a dearth of the literature on evaluations of approaches for teaching public health to health professions students. Those studies that had been published varied to such an extent in terms of their aims, methods, analysis, and results such that it was impossible to make any consistent comparisons of the observations reported in the studies. We conclude that evidence-based approaches for teaching public health to health professions students are either not sought by faculty and programs or, if conducted, not shared. As such, there are likely to be missed opportunities for ensuring that future graduates of health professions programs are as well prepared as possible to contribute to the health of the public.

A series of novel chloro-complexes of Mn2+, Co2+, Ni2+ and Fe3+ with 2,4,6-tris-(2-pyridyl)-1,3,5-triazine (L1) and thiourea (L2) with the formulae, [Mn(L1)Cl2(EtOH)]L2 (1), [Co(L1)Cl2(H2O)]L2.1/2H2O (2), [Ni(L1)Cl2(H2O)]L2.1/2H2O (3) and [Fe(L1)Cl3]L2 (4) were investigated utilizing convenient methods. Conversely, similar reaction resulted in complex with structure [Mn(L1)(OAc)(H2O)Cl]·H2O (5) in presence of sodium acetate. Pentagonal-bipyramidal geometry around Mn2+ ion is suggested. The solid state ESR spectra of Mn2+, Co2+ and Ni2+ complexes parameters show g|| > g┴ > 2.0023 indicating that the ground state is dx2-y2. Electronic spectra of two Mn2+ and the other complexes and the values of magnetic moments suggest octahedral geometry for complexes while pentagonal-pyramidal for [Mn(L1)Cl2(EtOH)]L2. Biological activity of complexes was tested versus alpathogenic bacteria (E. Coli, S. Aureus and C. Albicans). Further, the cytotoxic activity was screened for in vitro against (HeLa), (MCF-7), (HePG2) and (HeP-2). The role of ionic radii of the metal ion on the biological activity was investigated.

WHAT IS KNOWN ON THE SUBJECT?: There are high rates of tobacco smoking in people living with mental illness, and rates are much higher than the general population. People living with mental illness experience high rates of cardiovascular disease and other physical health problems as a result of tobacco smoking. There is a lack of evidence on successful interventions for reducing the rates of smoking in people living with mental illness. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: A meta-synthesis of data from a number of studies to support mental health nurses to access data quickly and support the translation of findings into practice. Studies found staff working in mental health services expressed they did not have the confidence to adequately address smoking cessation for people living with mental illness. People living with mental illness would like support and encouragement support to help them achieve successful smoking cessation. People living with mental illness want support from mental health service staff to increase their confidence in smoking cessation rather than mainstream smoking cessation services. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Existing evidence-based interventions for smoking cessation has had limited impact on the smoking rates of people living with mental illness. Research is needed into innovative smoking cessation interventions and the service delivery of these interventions for people living with mental illness. Interventions to support people living with mental illness in smoking cessation could be part of mainstream mental health service delivery. Opportunities for smoking cessation training for mental health service staff could be provided. ABSTRACT Introduction People with mental illness are up to three times more likely to smoke and experience greater challenges and less success when trying to quit and therefore have higher risk of smoking-related morbidity and mortality. There is a lack of evidence on successful interventions to reduce the smoking rates in people living with serve mental illness. A meta-synthesis was undertaken to summarize the data from multiple studies to inform the development of future smoking cessation intervention studies. Methods MEDLINE, PsycINFO, Embase and CINAHL were searched in March 2017. A total of 965 titles and abstracts were screened for inclusion with 29 papers reviewed in full and 15 studies that met inclusion criteria. Included studies were assessed for quality using the Critical Appraisal Skills Programme tool. Key data across studies were examined and compared, and a thematic analysis was conducted. Results Analysis and synthesis developed five analytical themes: environmental and social context, living with a mental health illness, health awareness, financial awareness and provision of smoking cessation support. Themes generated the interpretive construct: "Whose role is it anyway?" which highlights tensions between staff perspectives on their role and responsibilities to providing smoking cessation support and support service users would like to receive. Relevance to mental health nursing Routine smoking cessation training for mental health professionals and research on innovative smoking cessation interventions to support people living with mental illness are needed. The Cochrane tobacco group has not found sufficient direct evidence of existing evidence-based interventions that have beneficial effect on smoking in people living with mental illness. With this in mind, mental health professionals should be encouraged to engage in future research into the development of new interventions and consider innovative harm reduction strategies for smoking into their practice, to reduce the morbidity and mortality many people living with mental illness experience from tobacco smoking.

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The aim of this scoping review was to identify and characterize the recent literature pertaining to the education of the public health workforce worldwide. The importance of preparing a public health workforce with sufficient capacity and appropriate capabilities has been recognized by major organizations around the world (1). Champions for public health note that a suitably educated workforce is essential to the delivery of public health services, including emergency response to biological, manmade, and natural disasters, within countries and across the globe. No single repository offers a comprehensive compilation of who is teaching public health, to whom, and for what end. Moreover, no international consensus prevails on what higher education should entail or what pedagogy is optimal for providing the necessary education. Although health agencies, public or private, might project workforce needs, the higher level of education remains the sole responsibility of higher education institutions. The long-term goal of this study is to describe approaches to the education of the public health workforce around the world by identifying the peer-reviewed literature, published primarily by academicians involved in educating those who will perform public health functions. This paper reports on the first phase of the study: identifying and categorizing papers published in peer-reviewed literature between 2000 and 2015.