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Background: HIV postexposure prophylaxis (PEP) following child sexual assault (CSA) is recommended in select cases. High rates of poor adherence to PEP are reported. We evaluated adherence to the recommended management of children following CSA at the tertiary pediatric facility in Western Australia and compared our approach with international guidelines., Methods: Medical records were reviewed for all children <16 years old assessed at Perth Children's Hospital between October 1, 2016 and November 30, 2020 following alleged CSA. Data, including exposure type, PEP adherence and follow-up, were collected. A review of contemporary national and international PEP guidelines was undertaken in parallel., Results: There were 511 alleged CSA events over the study period; 62/511 (12%) were appropriately risk-assessed as requiring PEP by the treating clinician. PEP was not prescribed in 8/62 (13%) events, with a reason documented for 6/8 (75%). Overall, less than half of children who were eligible for PEP were adherent to the 28-day regimen (23/54, 43%). Gastrointestinal upset contributed to early cessation in 5/54 (9%). Final 3-month blood-borne virus serology results were available in less than one in 3 children. A review of international clinical practice revealed significant heterogeneity of criteria for the provision of PEP and a paucity of pediatric-specific data., Conclusions: We identified several areas of our PEP management that required strengthening, with limited direction available in current international guidelines. We have adopted a broader use of fixed drug combinations and implemented a multifaceted follow-up program. It will be essential to review the impact of these changes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A young nurse braves a dangerous situation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The sigma amine-borane complexes [Rh(L1)(η 2 :η 2 -H 3 B⋅NRH 2 )][OTf] (L1=2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine, R=Me, Et, n Pr) are described, alongside [Rh(L1)(NMeH 2 )][OTf]. Using R=Me as a pre-catalyst (1 mol %) the dehydropolymerization of H 3 B ⋅ NMeH 2 gives [H 2 BNMeH] n selectively. Added NMeH 2 , or the direct use of [Rh(L1)(NMeH 2 )][OTf], is required for initiation of catalysis, which is suggested to operate through the formation of a neutral hydride complex, Rh(L1)H. The formation of small (1-5 nm) nanoparticles is observed at the end of catalysis, but studies are ambiguous as to whether the catalysis is solely nanoparticle promoted or if there is a molecular homogeneous component. [Rh(L1)(NMeH 2 )][OTf] is shown to operate at 0.025 mol % loadings on a 2 g scale of H 3 B ⋅ NMeH 2 to give polyaminoborane [H 2 BNMeH] n [M n =30,900 g/mol, Ð=1.8] that can be purified to a low residual [Rh] (6 μg/g). Addition of Na[N(SiMe 3 ) 2 ] to [H 2 BNMeH] n results in selective depolymerization to form the eee-isomer of N,N,N-trimethylcyclotriborazane [H 2 BNMeH] 3 : the chemical repurposing of a main-group polymer., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cancer stem cells (CSCs) are thought to be partly responsible for metastasis and cancer relapse. Currently, there are no effective therapeutic options that can remove CSCs at clinically safe doses. Here, we report the synthesis, characterisation, and anti-breast CSC properties of a series of copper(I) complexes, comprising of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands ( 1 - 3 ). The copper(I) complexes are able to reduce the viability of breast CSCs grown in two- and three-dimensional cultures at micromolar concentrations. The potency of the copper(I) complexes towards breast CSCs was similar to salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical). Cell-based studies showed that the copper(I) complexes are readily, and similarly, internalised by breast CSCs. The copper(I) complexes significantly increase the intracellular reactive oxygen species (ROS) levels in breast CSCs, and their ROS generation profile with respect to time is dependent on the NSAID component present. The generation of intracellular ROS by the copper(I) complexes could be part of the underlying mechanism by which they evoke breast CSC death. As far as we are aware, this is the first study to explore the anti-breast CSC properties of copper(I) complexes.

The research protocol described aims to examine and establish the health outcomes of children and young people living in Out-of-Home Care (OOHC) in Perth, Western Australia (WA) from the perspective of the care recipients and service providers. A Study Advisory Panel (SAP) will be established comprised of Aboriginal Elders (because of the over-representation of Aboriginal children in OOHC), health professionals and other relevant stakeholders to help co-design all phases of the study. Mixed methods will be used in data collection and analysis. In the quantitative phase, it is proposed to collect retrospective data from three WA Department of Communities (DOC) districts. The data proposed to be collected includes: the number of children who received initial and annual health assessments, the health needs identified, and interventions put in place to address these needs. The qualitative phase will consist of interviews with service recipients (young people who have exited OOHC and Carers), health service providers (Community Health Nurses, School Nurses, General Practitioners and Paediatricians) and OOHC Case Workers. The research will provide an overview of the current health needs of children and young people in OOHC in WA and the perspectives of these young people, their Carers and service providers on current processes for accessing healthcare. It is anticipated that the study will provide valuable evidence for quality improvement in health service delivery to better meet the health needs of children and young people in OOHC.

The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1-8 are reported. The most effective gold(i)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training.With this imperative, the Association for Nutrition established an Interprofessional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service (NHS), royal colleges, medical schools and universities, government public health departments, learned societies, medical students, and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors.Through an iterative and transparent consultative process, thirteen key nutritional competencies, to be achieved through mastery of eleven graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skill acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council (GMC) Outcome for Graduates.As nutrition is an integrative science, the AfN IPG recommends that the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden for teaching staff.The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip frontline staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered associate nutritionist/registered nutritionist (ANutr/RNutr) or registered dietitian (RD) where this is likely to be beneficial.

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training. With this imperative, the Association for Nutrition established the Inter-Professional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service, royal colleges, medical schools and universities, government public health departments, learned societies, medical students and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors. Through an iterative and transparent consultative process, 13 key nutritional competencies, to be achieved through mastery of 11 graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skills acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council Outcomes for Graduates. As nutrition is an integrative science, the AfN IPG recommends the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden to teaching staff. The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip front-line staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered nutritionist (RNutr)/registered associate nutritionist (ANutr) or a registered dietitian (RD) where this is likely to be beneficial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical Relevance: Eye injuries, both accidental and non-accidental, are a significant cause of long-term visual impairment in children. An understanding of when and how such injuries occur is key to development of adequate prevention strategies., Background: To evaluate accidental and non-accidental eye injuries in children presenting to the major tertiary emergency department and outpatient ophthalmology clinic in Western Australia during the nationwide COVID-19 lockdown and to determine whether the frequency or nature of these injuries differed from pre-pandemic presentations., Methods: Retrospective review of the medical records of paediatric patients presenting to the emergency department and specialist ophthalmology clinic with an ocular injury and those presenting to the hospital Child Protection Unit with physical injuries during March-August 2020 and the same period in 2019., Results: There was no significant difference in the total number of accidental eye injury presentations during the lockdown period despite a significant decrease in emergency department attendance overall. Closed-globe injuries were the most common accidental eye injury presentation during lockdown (70/110, 64%), followed by adnexal injuries (39/110, 35%) and open-globe injuries (1/110, 1%). In contrast, referrals to the hospital Child Protection Unit for suspicious injuries declined during lockdown., Although eye injury presentations have changed in other parts of the world since the start of the pandemic, during COVID-19 lockdown in Western Australia, accidental paediatric ocular and adnexal trauma sustained at home continues to be a significant cause for hospital attendance. Public education regarding in-home eye injury prevention must be ongoing.

Copper(II) coordination compounds have been investigated for their anticancer properties for decades, however, none have reached advanced human clinical trials. The poor translation of copper(II) complexes from in vitro studies to (pre)clinical studies can be attributed to their limited efficacy in animal models, which is largely associated with copper leaching and speciation (in biological fluids). Here we report a biologically stable copper(II) complex based on the active site of Type I Cu electron transport proteins. The copper(II) complex 1 comprises of dithiacyclam (with soft and hard donor atoms) and two diclofenac units, a nonsteriodial anti-inflammatory drug (NSAID). Extensive biophysical and electrochemical studies show that the solid state structure of 1 is preserved in solution and that it can access both copper(I) and copper(II) oxidation states without leaching copper or undergoing speciation (in the presence of a cellular reductant). Cell studies show that 1 kills bulk breast cancer cells and highly resistant breast cancer stem cells (CSCs) at micromolar concentrations, and is significantly less toxic towards a panel of non-cancerous cells. Clinically relevant spheroid studies show that 1 is able to inhibit breast CSC-enriched mammosphere formation to a similar extent as salinomycin, a gold standard anti-CSC agent. Mechanistic studies show that 1 evokes breast CSC death by elevating intracellular reactive oxygen species (ROS) and inhibiting cyclooxygenase-2 (COX-2) activity. The former leads to the activation of stress pathways (JNK and p38), which culminates in caspase-dependent apoptosis. This study reinforces the therapeutic potential of copper(II)-NSAID complexes and provides a bioinspired route to develop stable, ROS-generating copper-based anti-CSC drug candidates.

Rhodium-alkene complexes of the pincer ligand κ 3 -C 5 H 3 N-2,6-(OP i Pr 2 ) 2 (PONOP- i Pr) have been prepared and structurally characterized: [Rh(PONOP- i Pr)(η 2 -alkene)][BAr F 4 ] [alkene = cyclooctadiene (COD), norbornadiene (NBD), ethene; Ar F = 3,5-(CF 3 ) 2 C 6 H 3 ]. Only one of these, alkene = COD, undergoes a reaction with H 2 (1 bar), to form [Rh(PONOP- i Pr)(η 2 -COE)][BAr F 4 ] (COE = cyclooctene), while the others show no significant reactivity. This COE complex does not undergo further hydrogenation. This difference in reactivity between COD and the other alkenes is proposed to be due to intramolecular alkene-assisted reductive elimination in the COD complex, in which the η 2 -bound diene can engage in bonding with its additional alkene unit. H/D exchange experiments on the ethene complex show that reductive elimination from a reversibly formed alkyl hydride intermediate is likely rate-limiting and with a high barrier. The proposed final product of alkene hydrogenation would be the dihydrogen complex [Rh(PONOP- i Pr)(η 2 -H 2 )][BAr F 4 ], which has been independently synthesized and undergoes exchange with free H 2 on the NMR time scale, as well as with D 2 to form free HD. When the H 2 addition to [Rh(PONOP- i Pr)(η 2 -ethene)][BAr F 4 ] is interrogated using p H 2 at higher pressure (3 bar), this produces the dihydrogen complex as a transient product, for which enhancements in the 1 H NMR signal for the bound H 2 ligand, as well as that for free H 2 , are observed. This is a unique example of the partially negative line-shape effect, with the enhanced signals that are observed for the dihydrogen complex being explained by the exchange processes already noted.

A cancer stem cell (CSC) active, solution stable, silver(i) polymeric complex bearing a dithiacyclam ligand is reported. The complex displays similar potency towards CSCs to salinomycin in monolayer and three-dimensional cultures. Mechanistic studies suggest CSC death results from cytosol entry, an increase in intracellular reactive oxygen species, and caspase-dependent apoptosis.

We report the anti-breast cancer stem cell (CSC) properties of a series of Group 10-bis(azadiphosphine) complexes 1-3 under exclusively three-dimensional cell culture conditions. The breast CSC mammosphere potency of 1-3 is dependent on the Group 10 metal present, increasing in the following order: 1 (nickel complex) <2 (palladium complex) <3 (platinum complex). Notably, 3 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-active compound, or any reported anti-CSC metal complex tested under similar conditions. Mechanistic studies suggest that the most effective complexes 2 and 3 readily penetrate CSC mammospheres, enter CSC nuclei, induce genomic DNA damage, and trigger caspase-dependent apoptosis. To the best of our knowledge, this is the first study to systematically probe the anti-CSC activity of a series of structurally related Group 10 complexes and to be conducted entirely using three-dimensional CSC culture conditions., (© 2020 Wiley-VCH GmbH.)

Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4, capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub-micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage-associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

We report the breast cancer stem cell (CSC) potency of two nickel(II)-3,4,7,8-tetramethyl-1,10-phenanthroline complexes, 1 and 3, containing the non-steroidal anti-inflammatory drugs (NSAIDs), naproxen and indomethacin, respectively. The nickel(II) complexes, 1 and 3 kill breast CSCs and bulk breast cancer cells in the micromolar range. Notably, 1 and 3 display comparable or better potency towards breast CSCs than salinomycin, an established CSC-active agent. The complexes, 1 and 3 also display significantly lower toxicity towards non-cancerous epithelial breast cells than breast CSCs or bulk breast cancer cells (up to 4.6-fold). Mechanistic studies suggest that 1 and 3 downregulate cyclooxygenase-2 (COX-2) in breast CSCs and kill breast CSCs in a COX-2 dependent manner. Furthermore, the potency of 1 and 3 towards breast CSCs decreased upon co-treatment with necroptosis inhibitors (necrostatin-1 and dabrafenib), implying that 1 and 3 induce necroptosis, an ordered form of necrosis, in breast CSCs. As apoptosis resistance is a hallmark of CSCs, compounds like 1 and 3, which potentially provide access to alternative (non-apoptotic) cell death pathways could hold the key to overcoming hard-to-kill CSCs. To the best of our knowledge, 1 and 3 are the first compounds to be associated to COX-2 inhibition and necroptosis induction in CSCs., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Yldiides have unique electronic properties and donor abilities, but as ligands in transition metal complexes they are scarcely represented in the literature. Here, the controlled synthesis of a series of polynuclear gold yldiide complexes derived from triphenyl(cyanomethyl)phosphonium bromide, [Ph 3 PCH 2 CN]Br, under mild conditions is described. Anionic dinuclear NBu 4 [(AuX) 2 {C(CN)PPh 3 }] (X=Cl, C 6 F 5 ) or trinuclear derivatives NBu 4 [Au 3 X 2 {C(CN)PPh 3 }] bearing terminal chloride or pentafluorophenyl groups and bridging yldiide ligands have been prepared. These compounds evolve in solution giving rise to the formation of an unprecedented tetrameric gold cluster, [Au 4 {C(CN)PPh 3 } 4 ], by the loss of the gold complex NBu 4 [AuX 2 ]. This gold cluster can also be prepared in high yield by a transmetalation reaction from the analogous tetrameric silver cluster, and two geometric isomers have been characterised, their formation dependent on the synthetic route. The triphenylphosphonium cyanomethyldiide ligand has also been used to build different dinuclear and trinuclear cationic complexes bearing phosphine or diphosphine ancillary ligands and bridging yldiide moieties. Further coordination through the cyano group of the yldiide ligand gives heterometallic trinuclear or pentanuclear derivatives. Structural characterisation of many of these compounds reveals the presence of complex molecular systems stabilised by gold⋅⋅⋅gold interactions and bridging yldiide ligands., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Several propargyl functionalised substrates with different heteroatoms (N, O or S) have been used for the preparation of propargyl gold(i) phosphine complexes. The complexes were prepared in high yields either by reaction of the substrate with [Au(acac)PPh3] or by reaction of [AuCl(PPh3)] with potassium hydroxide and the substrate in methanol. Several of the complexes have been characterised by X-ray diffraction showing the presence of secondary bonds such as π-stacking and aurophilic interactions. The reaction of the propargyl gold(i) phosphine complexes with [Cu(NO3)(PPh3)2] or [Ag(OTf)(PPh3)2] afforded heterobimetallic complexes with π-coordination of {Cu(PPh3)2} or {Ag(PPh3)2} to the alkyne bond. When the substituent of the propargyl unit contained more strongly coordinating pyridine moieties, [(PyCH2)2NCH2C[triple bond, length as m-dash]CAuPPh3], coordination of the heterometal to the pyridine units occurred, displacing the phosphine groups and giving rise to a dimeric structure. The antiproliferative activity of the complexes against cisplatin resistant lung cancer cell line A549 was determined by MTT assay. The mononuclear gold complexes showed excellent activities with IC50 values < 14 μM. Coordination of copper of silver to the alkynyl fragment resulted in a significant increase in activity suggesting a synergistic effect between the two metal centres.

A multi-nuclear, triangular-shaped palladium(ii) complex is shown to equipotently kill bulk cancer cells and cancer stem cells (CSCs) in the micromolar range. The palladium(ii) complex evokes CSC apoptosis by entering CSC nuclei and damaging genomic DNA.

There is limited information on the effects of stress and/or physiological manipulation on plasma concentrations of corticosterone (CORT) in turkeys. Under basal conditions, there was evidence for episodic release of CORT in turkeys. The present studies determine the effects of handling, herding, herding, the administration of Escherichia coli endotoxin, and challenge with turkey adrenocorticotropic hormone (ACTH) on plasma concentrations of CORT in market-weight male turkeys. Plasma concentrations of CORT were increased after challenge with turkey ACTH, handling together with saline injection or herding (moving birds from one pen to another). There were no effects on plasma concentrations of CORT of the following putative stressors: handling per se, endotoxin challenge, or of placing in an inverted position on simulated shackles., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A simple Co(ii)-based amine-borane dehydropolymerisation catalyst system is reported that operates at low loadings, to selectively give (H2BNMeH)n polymer on scale, with catalyst control over Mn, narrow dispersities and low residual metal content.

There is limited information on the effects of stress and/or physiological manipulation on either plasma concentrations of corticosterone (CORT) and/or heterophil: lymphocyte (H : L) ratios in turkeys. The present studies examine the effects of catching/transportation/lairage in a holding shed and shackling on plasma concentrations of CORT and H : L ratios in male market weight turkeys. Plasma concentrations of CORT were increased after transportation and lairage but not further elevated by shackling, irrespective of its duration up to 240 s. In one study, there were increased H : L ratios following catching/placing birds into transportation cages/transportation/lairage. In one study, H : L ratios declined following shackling. It is concluded that while moving turkeys from the farm to immediately before the shackling line is stressful, shackling for up to 4 min was not perceived as more stressful in turkeys. There were also differences between farms/houses for both plasma concentrations of CORT and H : L ratios., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

H3B·NMe3 σ-complexes of d8 [(L1)Rh][BArF4] and d10 [(L1)Ag][BArF4] (where L1 = 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine) have been prepared and structurally characterised. Analysis of the molecular and electronic structures reveal important but subtle differences in the nature of the bonding in these σ-complexes, which differ only by the identity of the metal centre and the d-electron count. With Rh the amine-borane binds in an η2:η2 fashion, whereas at Ag the unsymmetrical {AgH3B·NMe3} unit suggests a structure lying between the η2:η2 and η1 extremes.

The reactivity of the phosphonium salt (cyanomethyl)triphenylphosphonium chloride and the ylide (triphenylphosphonio)cyanomethanide towards Group 11 metal complexes is described. Mononuclear neutral gold(I) and gold(III) complexes of the type [AuX{CH(CN)PPh 3 }] or [AuX 3 {CH(CN)PPh 3 }] and cationic derivatives such as [AuL{CH(CN)PPh 3 }]X have been prepared. Surprisingly, the cationic gold species could only be prepared with ligands with a large steric hindrance, such as bulky NHCs or the JohnPhos phosphine, in contrast to silver and copper derivatives, which have dimeric structures through the coordination of the metal to the cyano group of the ylide of a second complex. Bis(ylide) metal complexes have also been synthesised in which a different structure is observed for the gold complexes compared with the copper and silver complexes. Although gold forms mononuclear species, the silver complex presents a two-dimensional polymeric structure as a result of further coordination of the silver centre to the nitrogen atoms of cyano groups of further silver complexes. These complexes possess two chiral centres; the gold compound was obtained as a mixture of diastereoisomers, whereas the copper and silver derivatives afford only one diastereoisomer. These compounds were screened for their in vitro cytotoxic activity against the human lung carcinoma cell line (A549). The IC 50 values reveal an excellent cytotoxic activity for these metal complexes compared with cisplatin., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To assess changes in the use of essential maternal and child health services in Konobo, Liberia, after implementation of an enhanced community health worker (CHW) programme., Methods: The Liberian Ministry of Health partnered with Last Mile Health, a nongovernmental organization, to implement a pilot CHW programme with enhanced recruitment, training, supervision and compensation. To assess changes in maternal and child health-care use, we conducted repeated cross-sectional cluster surveys before (2012) and after (2015) programme implementation., Findings: Between 2012 and 2015, 54 CHWs, seven peer supervisors and three clinical supervisors were trained to serve a population of 12 127 people in 44 communities. The regression-adjusted percentage of children receiving care from formal care providers increased by 60.1 (95% confidence interval, CI: 51.6 to 68.7) percentage points for diarrhoea, by 30.6 (95% CI: 20.5 to 40.7) for fever and by 51.2 (95% CI: 37.9 to 64.5) for acute respiratory infection. Facility-based delivery increased by 28.2 points (95% CI: 20.3 to 36.1). Facility-based delivery and formal sector care for acute respiratory infection and diarrhoea increased more in agricultural than gold-mining communities. Receipt of one-or-more antenatal care sessions at a health facility and postnatal care within 24 hours of delivery did not change significantly., Conclusion: We identified significant increases in uptake of child and maternal health-care services from formal providers during the pilot CHW programme in remote rural Liberia. Clinic-based services, such as postnatal care, and services in specific settings, such as mining areas, require additional interventions to achieve optimal outcomes.

A simple, efficient and sustainable method for the general synthesis of NHC gold(i) complexes is described. The reaction of imidazolium salts, of different electronic and steric requirements, with [AuX(tht)] (tht = tetrahydrothiophene) derivatives, in the presence of NBu4(acac), in air and at room temperature leads to the NHC gold species in good yields and with very short reaction times.

The synthesis of tetranuclear gold complexes, a structurally unprecedented octanuclear complex with a planar [Au(I) 8 ] core, and pentanuclear [Au(I) 4 M(I) ] (M=Cu, Ag) complexes is presented. The linear [Au(I) 4 ] complex undergoes C-H functionalization of carbonyl compounds under mild reaction conditions. In addition, [Au(I) 4 Ag(I) ] catalyzes the carbonylation of primary amines to form ureas under homogeneous conditions with efficiencies higher than those achieved by gold nanoparticles., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: Adolescent health assessments are recommended to identify health-risk behaviours. Adolescents who experience maltreatment are more likely to engage in such behaviours. This study (i) describes the frequency of health-risk behaviours amongst adolescents attending a hospital-based child protection unit (CPU) and (ii) determines whether use of a health assessment questionnaire increases the identification of these behaviours., Methods: A retrospective audit was performed of case notes of adolescents (aged ≥ 12 years) presenting to the CPU over 5 years (2007-2011). Data regarding health-risk behaviours were extracted. In 2012, following the introduction of a standardised HEADSS-based four-page questionnaire, health-risk data were collected prospectively over 18 months. The proportion of subjects reporting health-risk behaviours, before and after questionnaire introduction, was analysed., Results: Two hundred fifty-eight subjects, median age 13 (range 12-18) years, 78% female, were included in the pre-questionnaire period; and 85 subjects, median age 14 (range 12-17) years, 86% female, were included following introduction of the questionnaire. Questionnaire use was associated with an increase in the frequency of health-risk behaviours identified in the following domains: Education (odds ratio 4.48 [confidence interval 2.56-7.96] P < 0.001), Activities (16.18 [6.70-42.74] P < 0.001), Drugs/alcohol (4.00 [2.23-7.16] P < 0.001) and Suicidality (8.27 [4.59-14.92] P < 0.001). Participants reported higher rates of health-risk behaviours than the national population., Conclusion: Adolescents attending a hospital-based CPU report high rates of health-risk behaviours. A standardised questionnaire results in increased identification of such behaviours., (© 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Unprecedented allenyl gold complexes have been achieved starting from triphenylpropargylphosphonium bromide. Two different coordination modes of the allene isomer of triphenylphosphoniumpropargylide to gold have been found depending on the gold oxidation state. Bromo-, pentafluorophenyl-, and triphenylphosphine-gold(I) allenyl complexes were prepared in which the α carbon coordinates to the gold(I) center. A chiral pentafluorophenyl-gold(III) allenyl complex with the gold atoms coordinated to the γ carbon was also prepared. All the complexes have been structurally characterized by X-ray diffraction showing the characteristic distances for a C═C═C unit.

We describe the case of a 5-week-old infant boy presenting with purpura and oedema to both hands and torso. He was otherwise well, with no antecedent history of illness or trauma. Laboratory investigations were within normal limits. A review by the Child Protection Unit was organised during his admission for consideration of inflicted trauma as a cause of the lesions; this was felt most unlikely. A clinical diagnosis, following a dermatology consultation, of acute haemorrhagic oedema of infancy (AHO) was made., (© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Objectives: There are few published data on the efficacy of ibuprofen in the most immature infants and no data on repeated courses. Our objectives were to describe PDA closure rates in a population of infants <1000 g birth weight after repeated courses of ibuprofen, to examine the effect of gestation, and to document plasma markers of renal function and platelet counts., Methods: This was a single center observational study. We collected data on infants weighing <1000 g at birth who were treated with ibuprofen for a clinically significant PDA. A successful outcome was defined as resolution of clinical symptoms such that no additional treatment was required. Serum biochemistry and hematology data were analyzed and compared with controls., Results: We identified 160 infants with a mean +/- SD birth weight of 757 +/- 127 g and gestation of 25.6 +/- 1.4 weeks. Seventy infants closed their PDA after a single course of ibuprofen (45%) and 32/80 (40%) following a second. Infants of <26 weeks' gestation (n = 83) were less likely to respond after both the first (27.7% vs 63.6%; P < .001) and second (30.9% vs 60.0%; P = .026) courses. The postnatal decrease in plasma creatinine was delayed by ibuprofen treatment, while platelet counts and other plasma markers were unaffected., Conclusions: In our study population, PDA closure was gestation dependant, with a cumulative closure rate of 65%. A similar proportion of infants closed their PDA following the first and second courses regardless of gestation. These data suggest that a second course of ibuprofen may be effective in closing a PDA in even the most preterm infant.

Dietary restriction (DR) extends lifespan in a wide range of organisms. DR also reduces daily and lifetime fecundity. The latter may be an evolutionary adaptation to survive periods of food shortage. Reproductive rate is often negatively correlated with lifespan, and a reduced cost of reproduction could be the mechanism by which DR extends lifespan. We tested this hypothesis in Drosophila melanogaster females, by directly suppressing different aspects of reproduction and measuring the effect on the response of lifespan and age-specific mortality to DR. DR resulted in lifespan extension in females kept with males, in females kept without males, in females with vitellogenesis blocked by the mutant ovoD1 and in females with no germline as a result of X-irradiation. Moreover, rapid (48 h) changes in age-specific mortality, previously seen in fertile females switched between full feeding and DR, were also seen in ovoD1 females. Furthermore, these rapid changes in age-specific mortality in cohorts of fertile wild type females were not accompanied by concurrent changes in egg-production. These results indicate either that reduced reproduction is not necessary for lifespan extension by DR in Drosophila females, or that the relevant aspects of reproduction act upstream of our interventions and were therefore not blocked in our experiments.

Unlabelled: Our aim was to determine whether the chest radiograph appearance at 7 days predicted chronic lung disease development (oxygen dependency at 36 weeks post-menstrual age) or death before discharge and if it was a better predictor than readily available clinical data. Two consecutive studies were performed. In both, chest radiographs taken at 7 days for clinical purposes were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation and data were collected regarding gestational age, birth weight, use of antenatal steroids and post-natal surfactant and requirement for ventilation at 7 days. Oxygenation indices were calculated in the first study (study A) at 120 h and in the second (study B) at 168 h. In study A, there were 59 infants with a median gestational age of 26 weeks (range 24 to 28 weeks) and in study B, 40 infants with a median gestational age of 27 weeks (range 25-31 weeks). In both studies, infants who developed chronic lung disease had a significantly higher total chest radiograph score, with a higher score for fibrosis/interstitial shadowing than the rest of the cohort. Infants who died before discharge differed significantly from the rest with regard to significantly higher scores for cysts. In both studies, the areas under the receiver operator characteristic curves with regard to prediction of chronic lung disease were higher for the total chest radiograph score compared to those for readily available clinical data., Conclusion: In infants who require a chest radiograph for clinical purposes at 7 days, the chest radiograph appearance can facilitate prediction of outcome of infants born very prematurely.

Objectives: To assess whether 2 different D-dimer fibrin degradation assays-a second-generation latex immunosorbent agglutination (LIA) and an enzyme-linked immunosorbent assay (ELISA)-are predictive for the development of deep venous thrombosis (DVT) at the currently accepted level of 500 microg/L of D-dimer assay during the first weeks after traumatic brain injury (TBI) and to correlate over 8 weeks the second-generation LIA assay with the ELISA assay after acute TBI., Design: A case series of persons with TBI were screened for DVT at 2 weeks (+/-3d) using real-time, spectral Doppler ultrasound, as well as D-dimer fibrin split products. All persons were rescreened at 4, 6, and 8 weeks (+/-3d) after injury using D-dimer LIA and ELISA assays., Setting: A university hospital with a directly connected comprehensive in- and outpatient rehabilitation center that are part of the Traumatic Brain Injury Model Systems., Participants: Over 3 years, 35 TBI subjects with a mean Glasgow Coma Scale score of 6.5 were consecutively enrolled into the trial while on acute care. Persons were at least 16 years of age with no history of treatment for DVT., Interventions: Not applicable., Main Outcome Measures: Data were analyzed for the levels of D-dimer and risk as established by a predictive value of 500 microg/L. Changes in D-dimer values over time and within subjects were assessed by analysis of variance (ANOVA) with repeated measures, and the methods were correlated., Results: The mean LIA level at 2 weeks was 4.3mg/L and averaged 1.6 mg/L at 8 weeks from injury (P=.012, ANOVA), and the ELISA dropped from 4,748 microg/L to 1.695 microg/L (P=.0022, ANOVA). Except for 1 ELISA value in 1 patient, D-dimer levels were elevated beyond 500 microg/L at 2 weeks. There was a very good correlation between the LIA and the ELISA at 2, 4, 6, and 8 weeks after TBI (P<.0001). In individual cases, there were only occasional discrepancies between the LIA and ELISA methods. There were no positive DVTs at 2 weeks using ultrasound, so prediction of the sensitivity and the specificity of D-dimer with DVT was not possible., Conclusion: Using the currently recommended levels of D-dimer to predict DVT is not clinically useful in the acute TBI population.

Background: There remains uncertainty concerning the safety and efficacy of high-frequency oscillatory ventilation as compared with those of conventional ventilation for the respiratory support of very preterm infants. We conducted a multicenter trial to determine whether early intervention with high-frequency oscillatory ventilation reduced mortality and the incidence of chronic lung disease among newborns with a gestational age of 28 weeks or less., Methods: We randomly assigned preterm infants with a gestational age of 23 to 28 weeks to either conventional ventilation or high-frequency oscillatory ventilation within one hour after birth. Randomization was stratified according to center and gestational age (23 to 25 weeks or 26 to 28 weeks)., Results: A total of 400 infants were assigned to high-frequency oscillatory ventilation, and 397 were assigned to conventional ventilation. The composite primary outcome (death or chronic lung disease, diagnosed at 36 weeks of postmenstrual age) occurred in 66 percent of the infants assigned to receive high-frequency oscillatory ventilation and 68 percent of those in the conventional-ventilation group (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.98; 95 percent confidence interval, 0.89 to 1.08). Similar proportions of infants died or had chronic lung disease in each gestational-age group. In both treatment groups treatment failure occurred in 10 percent of infants (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.99; 95 percent confidence interval, 0.66 to 1.50). There were no significant differences between the groups in a range of other secondary outcome measures, including serious brain injury and air leak., Conclusions: The results obtained with high-frequency oscillatory ventilation and conventional ventilation do not differ significantly in the early treatment of respiratory disease in very preterm infants. Assessment of long-term effects will require additional follow-up., (Copyright 2002 Massachusetts Medical Society)

Background: Traumatic brain injury (TBI) caused by a high-speed transportation accident results in a mechanism of injury commonly described as diffuse axonal injury (DAI), which is associated with a reduction in dopamine turnover in the brain. Because of its affect on both dopamine and N-methyl-D-aspartate (NMDA) channels, amantadine has been the subject of considerable interest and clinical use in acute TBI., Participants: In this study, 35 subjects, who had a TBI in a transportation accident and were initially seen with a Glasgow Coma Scale score of 10 or less within the first 24 hours after admission, were randomly assigned to a double-blind, placebo-controlled, crossover design trial., Main Outcome Measures: Amantadine, 200 mg, or placebo was each administered for 6 weeks (12 weeks total) to patients who were recruited consecutively., Results: There was an improvement in the Mini-Mental Status (MMSE) scores of 14.3 points (P =.0185), Disability Rating Scale (DRS) score of 9.8 points (P =.0022), Glasgow Outcome Scale (GOS) score of 0.8 points (P =.0077), and in the FIM Cognitive score (FIM-cog) of 15.1 points (P =.0033) in the group that received amantadine during the first 6 weeks (group 1), but there was no improvement in the second 6 weeks on placebo (P >.05). In group 2 (active drug second 6 weeks), there was an improvement in the MMSE of 10.5 points, in the DRS of 9.4 points (P =.0006), in the GOS of 0.5 points (P =.0231), and in the FIM-cog of 11.3 points (P =.0030, Wilcoxon signed rank) spontaneously in the first 6 weeks on placebo (P =.0015). However, group 2 gained a statistically significant additional 6.3 points of recovery in the MMSE (P =.0409), 3.8 points in the DRS (P =.0099), 0.5 points in the GOS (P =.4008), and 5.2 points in the FIM-cog (P =.0173, Wilcoxon signed rank) between the sixth week and the twelfth week of treatment on the active drug., Conclusions: There was a consistent trend toward a more rapid functional improvement regardless of when a patient with DAI-associated TBI was started on amantadine in the first 3 months after injury.