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Ectoparasites are pathogens that can infect the skin and cause immense pain, discomfort, and disease. They are typically managed with insecticides. However, the fast-emerging antimicrobial resistance and the slow rate of development of new bio-actives combined with environmental and health concerns over the continued use of neurotoxic insecticides warrant newer and alternative methods of control. Tea tree oil (TTO), as an alternative agent, has shown remarkable promise against ectoparasites in recent studies. To our knowledge, this is the first systematic review to assess preclinical and clinical studies exploring the antiparasitic activity of TTO and its components against clinically significant ectoparasites, such as Demodex mites, scabies mites, house dust mites, lice, fleas, chiggers, and bed bugs. We systematically searched databases, including PubMed, MEDLINE (EBSCOhost), Embase (Scopus), CENTRAL, Cochrane Library, CINAHL, ScienceDirect, Web of Science, SciELO, and LILACS in any language from inception to 4 April 2022. Studies exploring the therapeutic activity of TTO and its components against the ectoparasites were eligible. We used the ToxRTool (Toxicological data reliability assessment) tool, the Joanna Briggs Institute (JBI) critical appraisal tools, and the Jadad scale to assess the methodological qualities of preclinical (in vitro and in vivo) studies, non-randomised controlled trials (including cohort, case series, and case studies), and randomised controlled trials, respectively. Of 497 identified records, 71 studies were included in this systematic review, and most (66%) had high methodological quality. The findings of this review revealed the promising efficacy of TTO and its components against ectoparasites of medical importance. Most importantly, the compelling in vitro activity of TTO against ectoparasites noted in this review seems to have translated well into the clinical environment. The promising outcomes observed in clinical studies provide enough evidence to justify the use of TTO in the pharmacotherapy of ectoparasitic infections. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental conditions. Significant barriers prevent family access to FASD-informed care. To improve accessibility, a scalable mobile health intervention for caregivers of children with FASD is under development. The app, called Families Moving Forward (FMF) Connect, is derived from the FMF Program, a parenting intervention tailored for FASD. FMF Connect has 5 components: Learning Modules, Family Forum, Library, Notebook, and Dashboard. Objective: This study assesses the feasibility of FMF Connect intervention prototypes. This includes examining app usage data and evaluating user experience to guide further refinements. Methods: Two rounds of beta-testing were conducted as part of a systematic approach to the development and evaluation of FMF Connect: (1) an iOS prototype was tested with 20 caregivers of children (aged 3-17 years) with FASD and 17 providers for the first round (April-May 2019) and (2) iOS and Android prototypes were tested with 25 caregivers and 1 provider for the second round (November-December 2019). After each 6-week trial, focus groups or individual interviews were completed. Usage analytics and thematic analysis were used to address feasibility objectives. Results: Across beta-test trials, 84% (38/45) of caregivers and 94% (17/18) of providers installed the FMF Connect app. Technological issues were tracked in real time with updates to address problems and expand app functionalities. On use days, caregivers averaged 20 minutes using the app; most of the time was spent watching videos in Learning Modules. Caregiver engagement with the Learning Modules varied across 5 usage pattern tiers. Overall, 67% (30/45) of caregivers posted at least once in the Family Forum. Interviews were completed by 26 caregivers and 16 providers. App evaluations generally did not differ according to usage pattern tier or demographic characteristics. Globally, app users were very positive, with 2.5 times more positivethan negative-coded segments across participants. Positive evaluations emphasized the benefits of accessible information and practical utility of the app. Informational and video content were described as especially valuable to caregivers. A number of affective and social benefits of the app were identified, aligning well with the caregivers' stated motivators for app use. Negative evaluations of user experience generally emphasized technical and navigational aspects. Refinements were made on the basis of feedback during the first beta test, which were positively received during the second round. Participants offered many valuable recommendations for continuing app refinement, which is useful in improving user experience. Conclusions: The results demonstrate that the FMF Connect intervention is acceptable and feasible for caregivers raising children with FASD. They will guide subsequent app refinement before large-scale randomized testing. This study used a systematic, user-centered design approach for app development and evaluation. The approach used here may illustrate a model that can broadly inform the development of mobile health and digital parenting interventions. [ABSTRACT FROM AUTHOR]

Poly(2-hydroxyethyl methacrylate) hydrogels incorporating copper nanoparticles (Cu-PHEMA) were prepared by a two-step process. In the first step, porous PHEMA hydrogels containing aqueous Cu(II) were formed by photo-induced phase separation polymerization in aqueous formulations containing 2-hydroxyethyl methacrylate (HEMA), a photoinitator, a cross-linker, and CuSO4. In the second step, the Cu(II) ions were reduced to Cu(0) (Cu NPs) by hydrazine. The Cu-PHEMA hydrogels were red-brown due to the presence of the Cu NPs, and X-ray diffraction studies confirmed the NPs were crystalline Cu and not CuO. The porous PHEMA and Cu-PHEMA hydrogels exhibited the polymer droplet morphology characteristic of sponges formed by induced phase separation polymerization of HEMA in water. The Cu NPs were stable inside the hydrogel, and leaching of Cu NPs into water was very slow. Leached Cu NPs moderately inhibited the growth of Escherichia coli or Staphylococcus aureus bacteria in the surrounding medium. Incorporation of Cu NPs inside PHEMA hydrogels did not change compression strength of hydrogels. [ABSTRACT FROM AUTHOR]

Poly-(2-hydroxyethyl methacrylate) sponges doped with silver nanoparticles (Ag NP-PHEMA) were prepared by irradiation of aqueous solutions containing 2-hydroxyethyl methacrylate (HEMA) and silver nitrate in the presence of a cross-linking agent and a photoinitiator. The Ag NP-PHEMA sponges had polymer droplet morphology with interconnected pores, characteristic of PHEMA sponges prepared by polymerization-induced phase separation. The Ag NP-PHEMA sponges were yellow-brown, whereas PHEMA sponges were white. For formation of Ag NP-PHEMA, the size of the polymer droplets was larger and the rate of polymerization was increased compared to PHEMA sponges formed under similar conditions but in the absence of silver nitrate. Mechanical strength, as indicated by compression testing, was similar for Ag NP-PHEMA and PHEMA sponges. Nanoparticles slowly leached out of Ag NP-PHEMA sponges, exerting antibacterial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. Notably, Ag NPs that leached were nontoxic to human corneal epithelial (HCE-T) cells. [ABSTRACT FROM AUTHOR]

Introduction In remote Aboriginal communities in Australia, scabies affects 7 out of 10 children before their first birthday. This is more than six times the rate seen in the rest of the developed world. Scabies infestation is frequently complicated by bacterial infection, leading to the development of skin sores and other more serious consequences, such as septicaemia and chronic heart and kidney diseases. Tea tree oil (TTO) has been used as an antimicrobial agent for several decades with proven clinical efficacy. Preclinical investigations have demonstrated superior scabicidal properties of TTO compared with widely used scabicidal agents, such as permethrin 5% cream and ivermectin. However, current data are insufficient to warrant a broad recommendation for its use for the management of scabies because previous studies were small or limited to in vitro observations. Methods and analysis A pragmatic first trial will examine the clinical efficacy of a simple and low-cost TTO treatment against paediatric scabies and the prevention of associated secondary bacterial infections, with 1:1 randomisation of 200 participants (Aboriginal children, aged 5–16 years and living in remote Australia) into active control (permethrin 5% cream) and treatment (5% TTO gel) groups. The primary outcome for the study is clinical cure (complete resolution). Secondary outcome measures will include relief of symptoms, recurrence rate, adverse effects, adherence to treatment regimen and patient acceptability. Ethics and dissemination The project has received approvals from the University of Canberra Human Research Ethics Committee (HREC 16-133), Wurli-Wurlinjang Health Service Indigenous subcommittee and the Aboriginal Medical Services Alliance Northern Territory reference group. The results of this study will be published in core scientific publications, with extensive knowledge exchange activities with non-academic audiences throughout the duration of the project. [ABSTRACT FROM AUTHOR]

Empyema is defined by the presence of bacteria and/or pus in pleural effusions. However, the biology of bacteria within human pleural fluid has not been studied. Streptococcus pneumoniae is the most common cause of pediatric and frequent cause of adult empyema. We investigated whether S. pneumoniae can proliferate within human pleural fluid and if growth is affected by the cellular content of the fluid and/or characteristics of pneumococcal surface proteins. Invasive S. pneumoniae isolates (n = 24) and reference strain recovered from human blood or empyema were inoculated (1.5×106CFU/mL) into sterile human malignant pleural fluid samples (n = 11). All S. pneumoniae (n = 25) strains proliferated rapidly, increasing by a median of 3009 (IQR 1063–9846) from baseline at 24hrs in all pleural effusions tested. Proliferation was greater than in commercial pneumococcal culture media and concentrations were maintained for 48hrs without autolysis. A similar magnitude of proliferation was observed in pleural fluid before and after removal of its cellular content, p = 0.728. S. pneumoniae (D39 strain) wild-type, and derivatives (n = 12), each with mutation(s) in a different gene required for full virulence were inoculated into human pleural fluid (n = 8). S. pneumoniae with pneumococcal surface antigen A (ΔpsaA) mutation failed to grow (2207-fold lower than wild-type), p<0.001, however growth was restored with manganese supplementation. Growth of other common respiratory pathogens (n = 14) across pleural fluid samples (n = 7) was variable and inconsistent, with some strains failing to grow. We establish for the first time that pleural fluid is a potent growth medium for S. pneumoniae and proliferation is dependent on the PsaA surface protein and manganese. [ABSTRACT FROM AUTHOR]

The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value < 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. p-values of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells. [ABSTRACT FROM AUTHOR]

Background: Scabies is an ancient disease (documented as far back as 2500 years ago). It affects about 300 million people annually worldwide, and the prevalence is as high as about 60 % in Indigenous and Torres Strait Islander children in Australia. This is more than six times the rate seen in the rest of the developed world. Scabies is frequently complicated by bacterial infection leading to the development of skin sores and other more serious consequences such as septicaemia and chronic heart and kidney diseases. This causes a substantial social and economic burden especially in resource poor communities around the world. Discussion: Very few treatment options are currently available for the management of scabies infection. In this manuscript we briefly discuss the clinical consequences of scabies and the problems found (studies conducted in Australia) with the currently used topical and oral treatments. Current scabies treatment options are fairly ineffective in preventing treatment relapse, inflammatory skin reactions and associated bacterial skin infections. None have ovicidal, antibacterial, anti-inflammatory and/or anti-pruritic properties. Treatments which are currently available for scabies can be problematic with adverse effects and perhaps of greater concern the risk of treatment failure. The development of new chemical entities is doubtful in the near future. Though there may be potential for immunological control, the development of a vaccine or other immunotherapy modalities may be decades away. Summary: The emergence of resistance among scabies mites to classical scabicides and ineffectiveness of current treatments (in reducing inflammatory skin reactions and secondary bacterial infections associated with scabies), raise serious concerns regarding current therapy. Treatment adherence difficulties, and safety and efficacy uncertainties in the young and elderly, all signal the need to identify new treatments for scabies. [ABSTRACT FROM AUTHOR]

Objectives Test data were used to explore the neurocognitive processing of a group of children with cochlear implants (CIs) whose language development is below expectations. Methods This cross-sectional study examines the relationship between neurocognitive processing, as assessed by the Kaufman Assessment Battery for Children-Second Edition, and verbal language standard scores, assessed using either the Comprehensive Assessment of Spoken Language or the Clinical Evaluation of Language Fundamentals in 22 school-age children with CIs. Processing scores of CI recipients with language scores below expectations were compared to those of children meeting or exceeding language expectations. Multiple linear regression estimated the associations of simultaneous and sequential processing with language scores. Results Though simultaneous processing scores between the two groups were similar, the mean sequential processing score (91.2) in the below expectations group (n = 13) was significantly lower (P = 0.002) than that of children (n = 9) meeting expectations (110.8). After adjusting for age at implantation, a 10-point higher sequential processing score was associated with a 7.4 higher language score (P = 0.027). Discussion Simultaneous processing capacity was at least within the average range of cognitive performance, and was not associated with language performance in children with CIs. Conversely, reduced sequential processing capacity was significantly associated with lower language scores. Conclusion Neurocognitive skills, specifically cognitive sequencing, serial ordering, and auditory-verbal memory may be targets for therapeutic intervention. Intensive cognitive and educational habilitation and in milieu intervention may improve language learning in children with CIs. [ABSTRACT FROM AUTHOR]

• This qualitative study explored digital information usage in the context of the BNF. • More driving than resisting forces to digital usage were identified. • The COVID-19 pandemic has expedited the digital transition in BNF/BNFc usage. • Many organisations lack the required digital infrastructure for widespread digital usage. • Future efforts should focus on the digital technology, and on upskilling staff to use it. : To explore the driving and resisting forces to the use of digital medicines information in the context of the British National Formulary (BNF) and British National Formulary for Children (BNFc). : Qualitative semi-structured interviews were carried out with 25 doctors, pharmacists and nurses. Data were analysed via thematic analysis. : Key drivers identified included organisations making digital use of BNF/BNFc easier through measures such as electronic prescribing systems, compatible handheld devices and training/induction sessions for staff. The COVID-19 pandemic had expedited the shift to digital BNF/BNFc usage in some settings. A strong driver of digital usage was the desire by staff to use the most up-to-date information. Reduced access to print copies was a common initial driver of digital usage, whilst ease of searching and speed of access often acted to consolidate digital usage. Important resisting forces included lack of supporting organisational digital infrastructure and an onus on individuals to obtain access to digital platforms, particularly through personal smartphones. Poor prior experience of earlier digital BNF/BNFc platforms had also prevented participants from using them again. : More driving than resisting forces were identified and, in most settings, a transition to digital BNF/BNFc usage is underway, which has been expedited by the COVID-19 pandemic. However, this is not happening uniformly across the NHS and there continue to be strong resisting forces to digital BNF/BNFc usage, particularly at organisational level. : The British National Formulary (BNF) and British National Formulary for Children (BNFc) provide information about all medicines prescribed in the UK. They are available as a book, a website and an app. As healthcare information becomes increasingly digital, it is important to understand how this is used by healthcare staff and we spoke to doctors, nurses and pharmacists about how they use the BNF/BNFc. We found that staff are increasingly using the digital BNF/BNFc and that the COVID-19 pandemic has speeded up this transition. Staff are likely to use the digital BNF/BNFc where their organisation makes it easy to do so, such as through access to IT equipment and electronic prescribing systems. However, many NHS organisations lack the facilities for widespread digital usage and staff are not routinely trained in using digital resources. Future efforts should focus on the digital technology itself, and on upskilling healthcare staff to use it. [ABSTRACT FROM AUTHOR]

Purpose: To examine the impact of cochlear implant (CI) intervention on health-related quality of life (HRQOL) assessed by both self- and parent-reported measures. Methods: In this national study of children implanted between ages 6 months and 5 years, HRQOL of 129 children 6-year post-CI was compared to 62 internal study (NH1) and 185 external (NH2) samples of hearing children frequency-matched to the CI group on sociodemographic variables. HRQOL ratings of children and their parents in each group, measured using the Child Health and Illness Profile-Child Edition, were compared, and their associations with the Family Stress Scale were investigated. Results: CI children reported overall and domain-specific HRQOL that was comparable to both NH1 and NH2 peers. CI parents reported worse child scores than NH1 parents in Achievement, Resilience, and Global score ( p's < 0.01) but similar or better scores than socioeconomically comparable NH2 parents. Higher family stress was negatively associated with all parent-reported HRQOL outcomes ( p's < 0.01). Parent-child correlations in HRQOL global scores trended higher in CI recipients ( r = 0.50) than NH1 ( r = 0.42) and NH2 ( r = 0.35) controls. Conclusions: CI recipients report HRQOL comparable to NH peers. These results, from both child and parent perspective, lend support to the effectiveness of CI intervention in mitigating the impact of early childhood deafness. Family stress was associated with worse HRQOL, underscoring a potential therapeutic target. Parent-child agreement in HRQOL scores was higher for CI families than NH families, which may reflect higher caregiver insight and involvement related to the CI intervention. [ABSTRACT FROM AUTHOR]

This study investigated the effects of the volatile terpene-rich oil from Melaleuca alternifolia (tea tree oil) on the formation of biofilms and the adhesion of C. albicans cells to both biotic and abiotic surfaces. Biofilm formation on polystyrene was significantly inhibited for 70% of the isolates at the lowest test concentration of 0.016% of tea tree oil (TTO) when quantified by XTT and 40% of isolates when measured by crystal violet staining. Adhesion to polystyrene, quantified by crystal violet staining, was significantly reduced for 3 isolates at 0.031%, 6 isolates at 0.062% and 0.125% and for all 7 isolates at 0.25% TTO. Reductions in adhesion were not due to loss of viability (at concentrations of ≤ 0.125%) or interactions between the TTO and polystyrene. Similarly, adhesion to buccal epithelial and HeLa cells was also significantly reduced in the presence of 0.016-0.062% TTO. Treatment with 0.125% TTO, but not 0.062%, decreased the cell surface hydrophobicity of C. albicans, indicating one potential mechanism by which adhesion may be reduced. These data demonstrate that sub-inhibitory TTO reduces the adhesion of C. albicans to both human cells and polystyrene, inhibits biofilm formation and decreases cell surface hydrophobicity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the antimicrobial activity of a range of commercially available tea tree oil (TTO) products and to evaluate whether formulation plays a significant part in their antiseptic activity. Methods: The antimicrobial activity of the purchased products and control TTO solutions was assessed against Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans using well diffusion, broth microdilution, and broth macrodilution assays. Results: Zone sizes obtained by the agar well diffusion assay ranged from 0 to 49.8 mm, with the more viscous and lipophilic products producing the smallest zones. Micro- and macrodilution methods showed that eight products had minimum inhibitory concentrations that were lower than the nonformulated TTO control. The remaining three products showed activity equivalent to the TTO control. Conclusions: In general, the commercially available antiseptic TTO products showed antimicrobial activity that was equivalent to, or greater than the nonformulated TTO control. This suggests that the TTO within these products has retained its antimicrobial activity. Furthermore, the enhanced activity of the products may be attributed to other antimicrobial excipients within the products such as preservatives, or to synergistic antimicrobial interactions between the TTO and other product excipients. The observation that the commercially available antiseptic TTO products tested in this study retained adequate antimicrobial activity emphasizes the importance of considering how product bases and excipients may interact with the active compound during formulation to ensure efficacy of the final product. Finally, the current data suggest that these TTO products may also be active in vivo. However, this can only be determined through further studies and in clinical trials. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis exit site infections caused by Pseudomonas spp. are difficult to treat and can lead to peritonitis and/or modality failure. Effective alternative or adjunct non-antibiotic antimicrobial agents could improve treatment as well as reduce the use of antibiotics and contribute to a reduction in antibiotic selection pressure and the further development of antibiotic resistance. Vinegar is popularly promoted as a topical antimicrobial agent and has been recommended as an adjunct treatment for Pseudomonas exit site infections in PD patients. Systematic empirical data on the susceptibility of pseudomonads to vinegar are lacking. This study aimed to determine the susceptibility to vinegar of 57 isolates of Pseudomonas. The MICs and MBCs of four vinegars were determined for clinical, environmental and/or reference isolates of P. aeruginosa ( n = 34), P. fluorescens ( n = 11) and P. putida ( n = 12) using a broth microdilution method. The MIC90 and MBC90 were also determined for each species. The MIC90 of all four vinegars against P. aeruginosa was 2% (vol/vol). The MBC90 was 8%. The MIC90s for P. fluorescens and P. putida were also 2%. The MIC90s were 4%. Dilutions of vinegar recommended for the treatment of Pseudomonas exit site infections have in vitro activity against these notoriously resistant bacteria. In light of increasing rates of antibiotic resistance and the need to reduce antibiotic selection pressure as part of good antibiotic stewardship, the efficacy of vinegar, or its active constituent acetic acid, for the treatment of Pseudomonas exit site infections should be investigated further. [ABSTRACT FROM AUTHOR]

Purpose: Systemic toxicity coupled with long treatment regimes of approved topical chemotherapeutic agents such as imiquimod and 5-fluorouracil (5-FU) are limiting. There is now more focus on the potential use of topical terpene agents as skin cancer treatments. Here, we show for the first time that topical Melaleuca alternifolia (tea tree) oil (TTO), abundant in terpenes, has in vivo antitumour activity. Method: Topical TTO formulations applied to immunocompetent tumour-bearing mice were assessed for antitumour efficacy by monitoring tumour growth and by histological analysis following treatment. Results: Four, daily, topical treatments of 10% TTO/DMSO regressed subcutaneous AE17 mesotheliomas in mice for a period of 10 days and significantly retarded the growth of subcutaneous B16-F10 melanomas. The antitumour effect of topical 10% TTO/DMSO was accompanied by skin irritation similar to other topical chemotherapeutic agents, but unlike other approved topical agents, quickly and completely resolved. Furthermore, we show that topical 10% TTO/DMSO caused an influx of neutrophils and other immune effector cells in the treated area, with no evidence of systemic toxicity. Conclusion: TTO combined with an effective carrier significantly inhibited the growth of aggressive, subcutaneous, chemo-resistant tumours in immunocompetent mice. Taken together, these findings highlight the potential of topical TTO as an alternative topical antitumour treatment. [ABSTRACT FROM AUTHOR]

The antimicrobial activity of five samples of Taxandria fragrans essential oil was evaluated against a range of Gram-positive ( n= 26) and Gram-negative bacteria ( n= 39) and yeasts ( n= 10). The majority of organisms were inhibited and/or killed at concentrations ranging from 0.06–4.0% v/v. Geometric means of MIC were lowest for oil Z (0.77% v/v), followed by oils X (0.86%), C (1.12%), A (1.23%) and B (1.24%). Despite differences in susceptibility data between oils, oils A and X did not differ when tested at 2% v/v in a time kill assay against Staphylococcus aureus. Cytotoxicity assays using peripheral blood mononuclear cells demonstrated that T. fragrans oil was cytotoxic at 0.004% v/v but not at 0.002%. Exposure to one or more of the oils at concentrations of ≤0.002% v/v resulted in a dose responsive reduction in the production of proinflammatory cytokines IL-6 and TNF-α, regulatory cytokine IL-10, Th1 cytokine IFN-γ and Th2 cytokines IL-5 and IL-13 by PHA stimulated mononuclear cells. Oil B inhibited the production of all cytokines except IL-10, oil X inhibited TNF-α, IL-6 and IL-10, oil A inhibited TNF-α and IL-6, oil C inhibited IL-5 and IL-6 and oil Z inhibited IL-13 only. IL-6 production was significantly inhibited by the most oils (A, B, C and X), followed by TNF-α (oils A, B and X). In conclusion, T. fragrans oil showed both antimicrobial and anti-inflammatory activity in vitro, however, the clinical relevance of this remains to be determined. [ABSTRACT FROM AUTHOR]

Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis after target removal (bulbectomy), in which axonal caspase-9 and caspase-3 activation leads to terminal apoptosis in ORN soma of the olfactory epithelium. Here, we show that caspase-8 can act as an initiator of ORN apoptosis after bulbectomy and also after synaptic instability is induced by NMDA-mediated excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and caspase-3 are sequentially activated within ORN presynaptic terminals, and caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is transported retrogradely, preceding axonal caspase-3 activation and apoptosis of ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death. Caspase-8 activation and retrograde transport after NMDA lesion is similarly reduced in mice null for p75, the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs thus involves a novel mechanism that used p75 in the local activation of caspase-8. Once caspase-8 is maximally activated in the presynaptic terminal, it is transported retrogradely by the motor complex dynactin/dynein, a process that can be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage and the loss of olfactory bulb target neurons. [ABSTRACT FROM AUTHOR]

As advances are made in understanding the human genome, newborn screening for a variety of different diseases becomes more prevalent. Although this screening can provide a number benefits, it also may be associated with various negative psychosocial consequences. including heightened uncertainty and anxiety about the child's health. Relying on videotaped interactions between health care providers and families whose child received a positive newborn screening test for cystic fibrosis (CF, N 17), in this article we report on how the respective parties manage uncertainty. Although the goal of the providers appears to he one of reducing uncertainty, all parties to the interaction engage in behaviors that both manage and negotiate as opposed to just reduce uncertainty. Implications for theorizing about uncertainty management are discussed. [ABSTRACT FROM AUTHOR]

With the tremendous expansion of knowledge that will come from advances in the Human Genome Project, the question of how to effectively communicate genetic risk information will assume increasing importance. This article reports research intended to provide a descriptive foundation for future inquiry. Drawing on information from medical professionals and videotaped interactions of families whose infant has tested positive for cystic fibrosis, the authors present an analysis of the phases of communication following newborn screening. From this analysis. it can be seen that genetic counseling is best viewed as pan of' a larger process of risk communication. [ABSTRACT FROM AUTHOR]

The current study proposes that recipients' aversive reactions to complaints are a function of perceived face threat. One hundred and ninety-nine college students completed a survey asking them to describe in detail a recent complaint they had received from a friend or romantic partner, and to describe their response to that complaint. Respondents completed measures designed to assess their reactions to the complaint, including perceived face threat, negative affect, fairness, and damage to the relationship. As predicted, dispositional complaints were perceived to be more face threatening than nondispositional complaints, and complaints delivered in public were more face threatening than complaints delivered in private. Both positive and negative face threat were associated with the complaint recipient's anger/hurt and defensiveness. Perceptions of positive face threat also were associated with perceptions of less fairness and greater perceived damage to the relationship, whereas perceived threat to negative face predicted the recipient's feelings of embarrassment and anxiety/depression. The findings indicate that the face-threatening nature of complaints is associated with adverse relational consequences. Perceived threats to positive face, which tend to convey relational devaluation, were more strongly associated with relational damage than were threats to negative face. [ABSTRACT FROM AUTHOR]

Investigates the role of perceived face threat in explaining the consequences of managerial reproaches. Perspectives used in examining face threat; Key components of face management theory; Connection between the nature and severity of a reproach message.

This study examines factors predicted to influence individuals' responses to romantic jealousy. Participants completed scales measuring relationship-specific linking (i.e., believing that a specific relationship is essential to one's happiness), relationship-specific rumination, possessiveness, trust, and communicative responses to jealousy. Contrary to expectations, relationship-specific linking and relationship-specific rumination were not correlated. Relationship-specific linking was weakly associated with possessiveness, compensatory restoration, negative affect expression, and violence toward objects, but not associated any of the other variables. As predicted, relationship-specific rumination was negatively associated with trust, and positively associated with possessiveness, surveillance/restriction, manipulation, relationship threat, rival contact, compensatory restoration, negative affect expression, signs of possession, derogation of competitors, distributive communication, violent communication, violence toward objects, active distancing, and avoidance/denial. The hypothesis that relationship-specific rumination associates with integrative communication was not supported. The findings suggest that jealous rumination is an important cognitive mechanism that motivates some individuals to enact counterproductive communicative responses to jealousy. [ABSTRACT FROM AUTHOR]

SUMMARY There are limited reports of the prevalence of positive reactions in healthy adults to patch tests with standard allergens; there are no recent comprehensive studies from Australia. Healthy adult volunteers (n = 219) from the Western Australian community were patch tested using the European standard series of allergens. Seventy-seven (35%) reacted to at least one allergen, positive patch tests being most prevalent to nickel sulfate (20%), potassium dichromate (9%), cobalt chloride (6%) and fragrance mix (4%). Prevalence of positive patch tests to nickel and chromate was higher than that reported for another healthy population, which may stem from self-selection of volunteers or geographical differences, including extent of exposure to allergens. [ABSTRACT FROM AUTHOR]

Methionine synthase, a critical enzyme in deoxyribonucleotide biosynthesis for DNA replication, requires vitamin B[sub 12] as a cofactor. We have tested the hypothesis that depletion of cells of vitamin B[sub 12] would block growth of neoplastic cells and divert them into apoptosis and could form the basis of a new therapeutic strategy for cancer treatment. Using nitrous oxide to inactivate vitamin B[sub 12] we show that, in a variety of cell lines in vitro, methionine synthase is rapidly inhibited, the cells cease proliferation and undergo apoptosis. The kinetics of cell death, once started, are similar to those observed following methotrexate treatment or serum withdrawal. This is the first observation of apoptosis being induced following depletion of an essential metabolite as opposed to the more conventional strategy of adding a toxic drug to damage cells thereby triggering apoptosis. Moreover, vitamin B[sub 12] depletion has no effect on the non-proliferating cell population. [ABSTRACT FROM AUTHOR]

Recent reports have implicated ciprofloxacin as a cause of Clostridium difficile-associated diarrhoea. This problem was examined in three ways. First, the MIC of ciprofloxacin for C. difficile was determined. The MIC range was 8-32 mg/L, with C. difficile were 'treated' with ciprofloxacin and clindamycin in a test-tube, and the growth of C. difficile monitored. The clindamycin-treated emulsions supported growth of C. difficile, while the ciprofloxacin-treated and control emulsions did not differ significantly and failed to support the growth of C. difficile. Finally, 213 patients on ciprofloxacin monotherapy were investigated. Twenty-nine patients were given ciprofloxacin as treatment for diarrhoea, while a further 15 patients developed diarrhoea while being treated. None of these 44 patients harboured C. difficile. Faecal samples from 73 of the remaining 169 patients who did not have or develop diarrhoea were investigated for C. difficile, but none was positive. It was concluded that ciprofloxacin is unlikely to promote C. difficile-associated diarrhoea. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented commenting on an article appearing in the December 31, 2014 issue which dealt with the intrapartum care guideline released by the British National Institute for Health and Care Excellence.