Melioidosis in New Caledonia: a dominant strain in a transmission hotspot.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases and B. pseudomallei isolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group of B. pseudomallei that is phylogenetically related to Australian strains.

The melioidosis agent Burkholderia pseudomallei and related opportunistic pathogens detected in faecal matter of wildlife and livestock in northern Australia.

The Darwin region in northern Australia has experienced rapid population growth in recent years, and with it, an increased incidence of melioidosis. Previous studies in Darwin have associated the environmental presence of Burkholderia pseudomallei, the causative agent of melioidosis, with anthropogenic land usage and proximity to animals. In our study, we estimated the occurrence of B. pseudomallei and Burkholderia spp. relatives in faecal matter of wildlife, livestock and domestic animals in the Darwin region. A total of 357 faecal samples were collected and bacteria isolated through culture and direct DNA extraction after enrichment in selective media. Identification of B. pseudomallei, B. ubonensis, and other Burkholderia spp. was carried out using TTS1, Bu550, and recA BUR3-BUR4 quantitative PCR assays, respectively. B. pseudomallei was detected in seven faecal samples from wallabies and a chicken. B. cepacia complex spp. and Pandoraea spp. were cultured from wallaby faecal samples, and B. cenocepacia and B. cepacia were also isolated from livestock animals. Various bacteria isolated in this study represent opportunistic human pathogens, raising the possibility that faecal shedding contributes to the expanding geographical distribution of not just B. pseudomallei but other Burkholderiaceae that can cause human disease.

Parental relationships beyond the grave: Adolescents' descriptions of continued bonds.

OBJECTIVE: Many people experience an ongoing relationship with a deceased loved one. This is called a "continued bond." However, little is known about the adolescent experience with continued bonds once a parent has died. This study describes three ways that adolescents continue their relationship with a parent after that parent's death. METHOD: Individual semistructured interviews were conducted with nine adolescent children of deceased hospice patients from a large hospice in northeastern Ohio as part of a larger grounded-theory study. The interviews were audiotaped, transcribed verbatim, and analyzed using a conventional content analysis approach. RESULTS: Adolescents continued their bonds with deceased parents in one of three ways: experiencing encounters with the deceased parent, listening to the inner guide of the parent, and keeping mementos to remind them of the parent. SIGNIFICANCE OF RESULTS: The ways that the adolescents continued their bond with a deceased parent assisted them in creating meaning out of their loss and adjusting to life without that parent. Our results can be used by health professionals and parents to help adolescents after a parent has died.

Two worlds: Adolescents' strategies for managing life with a parent in hospice.

OBJECTIVE: This study aimed to generate an explanatory model of the coping strategies that adolescents employ to manage the stressors they experience in the final months of their ill parent's life and shortly after their death. METHOD: The sample included 26 families of adolescents with a parent receiving care in a large hospice program in northeastern Ohio. A semistructured interview was conducted with 14 ill parents, 17 well parents/guardians, and 30 of their adolescent children before the parent's death and, additionally, with 6 of these families after the death. The interviews were audiotaped, transcribed verbatim, and analyzed using a grounded-theory approach. RESULTS: The participants described two worlds that constituted the lives of the adolescents: the well world of normal adolescence and the ill world of having a parent near the end of life. The adolescents experienced a common challenge of living in two worlds and responded to the challenge with a process we labeled "managing two worlds." Five stages through which adolescents manage their worlds were identified: keeping the ill world and the well world separate; having the ill world intrude into the well world; moving between the ill world and the well world; being immersed in the ill world; and returning to the well world having been changed by the ill world. SIGNIFICANCE OF RESULTS: The explanatory model of "managing two worlds" outlines a complex and nuanced process that changes over time. The model can be used by health professionals who seek to help adolescents navigate this critical time when their parents are dying or have recently died. These results can also be used to inform the development of interventions that assist families with strategies tailored to an adolescent's specific needs. Future research should investigate associations among the process of "managing two worlds" and outcomes related to adolescent bereavement.

Short range order in elemental liquids of column IV.

The short range order (SRO) in liquid elements of column IV is analysed within the quasi-crystalline model across a wide range of temperatures. It is found that l-Si, Ge, and Sn are well described with a beta-tin like SRO. In contrast, Pb retains a bcc-like SRO similar to other simple elemental liquids. However, a distinction is found between the SRO in Si and Ge and that in Sn, where the latter has a more rigid structure. This difference persists across the entire temperature range examined but is overcome in Si at pressures above 8 GPa, where the liquid structure evolves towards that of Sn.

Uncertainties experienced by family members when one parent is dying.

PURPOSE: This research examined uncertainty as a salient theme for families in which a parent was dying while receiving hospice care. METHODS: Interviews were conducted with 61 participants from 26 families in the parent study to explore the strategies used by adolescents with a parent in a hospice. Second interviews were conducted with 15 original participants after the death of their parent. Conventional content analysis was used to analyse data. RESULTS: Uncertainty was a prevalent and salient theme in the participants' stories revealing patterns about the causes, barriers, effects and strategies used to manage uncertainty. CONCLUSION: Uncertainties associated with the end of life can be problematic for some people, requiring attention by health professionals.

Exploring family relationships through associations of comfort, relatedness states, and life closure in hospice patients: A pilot study.

OBJECTIVE: Research at the end of life tends to focus on the dying patient's symptoms, often overlooking issues associated with family interactions. However, many families struggle just to maintain or initiate these valuable connections. The purpose of our pilot study was to explore family relationships at the end of life and investigate associations among perceived comfort, relatedness states, and life closure. METHOD: This descriptive study used a cross-sectional design, and a convenience sample (n = 30; 18 women; mean age = 71 years) was recruited from patients admitted to a large not-for-profit hospice in northeastern Ohio. In-person interviews using the Hospice Comfort Questionnaire, Relatedness States Visual Analog Scales, and the Life-Closure Scale provided data for analyses. RESULTS: Family interactions that were not associated with the physical tasks of caregiving were related to life closure (r = 0.36, p = 0.001), and life closure and comfort were highly correlated (r = 0.69, p < 0.001). Participants residing in an inpatient setting had higher levels of involvement (t[18] = -2.07, p = 0.05) and comfort in relationships (t[28] = -2.06, p = 0.05) than those in the home setting. SIGNIFICANCE OF RESULTS: This is the first known study investigating the associations among comfort, relatedness, and life closure at the end of life. The majority of participants had high levels of involvement and comfort in their relationships, and they preferred interactions that required minimal effort. Studies that focus on both patients' and family members' perceptions of relationships are needed as well as outcome studies that test simple interventions.

Liquid structure and temperature invariance of sound velocity in supercooled Bi melt.

Structural rearrangement of liquid Bi in the vicinity of the melting point has been proposed due to the unique temperature invariant sound velocity observed above the melting temperature, the low symmetry of Bi in the solid phase and the necessity of overheating to achieve supercooling. The existence of this structural rearrangement is examined by measurements on supercooled Bi. The sound velocity of liquid Bi was measured into the supercooled region to high accuracy and it was found to be invariant over a temperature range of ∼60°, from 35° above the melting point to ∼25° into the supercooled region. The structural origin of this phenomenon was explored by neutron diffraction structural measurements in the supercooled temperature range. These measurements indicate a continuous modification of the short range order in the melt. The structure of the liquid is analyzed within a quasi-crystalline model and is found to evolve continuously, similar to other known liquid pnictide systems. The results are discussed in the context of two competing hypotheses proposed to explain properties of liquid Bi near the melting: (i) liquid bismuth undergoes a structural rearrangement slightly above melting and (ii) liquid Bi exhibits a broad maximum in the sound velocity located incidentally at the melting temperature.

Remote delivery of a weight management intervention for adults with intellectual disabilities: Results from a randomized non-inferiority trial.

BACKGROUND: Remote delivery of multi-component weight management interventions results in clinically meaningful weight loss in adults without intellectual disabilities (ID), but the effectiveness of remotely delivered weight management interventions in adults with ID has not previously been evaluated. OBJECTIVE: To determine if a weight management intervention delivered remotely could achieve weight loss (kg) at 6 months that is non-inferior to in-person visits in adults with ID and overweight or obesity (BMI ≥25 kg/m2). METHODS: Participants were randomized to a 24-mo. trial (6 mos weight loss,12 mos weight maintenance, 6 mos. no-contact follow up) to compare weight loss achieved with the same multicomponent intervention delivered to individual participants in their home either remotely (RD) or during face-to-face home visits (FTF). RESULTS: One hundred twenty adults with ID (∼32 years of age, 53 % females) were randomized to the RD (n = 60) or the FTF arm (n = 60). Six-month weight loss in the RD arm (-4.9 ± 7.8 kg) was superior to 6-month weight loss achieved in the FTF arm (-2.1 ± 6.7 kg, p = 0.047). However, this may be partially attributed to the COVID-19 pandemic, since weight loss in the FTF arm was greater in participants who completed the intervention entirely pre-COVID (n = 33,-3.2 %) compared to post-COVID (n = 22, -0.61 %). Weight loss across did not differ significantly between intervention arms at 18 (p = 0.33) or 24 months (p = 0.34). CONCLUSION: Our results suggest that remote delivery is a viable option for achieving clinically relevant weight loss and maintenance in adults with ID. NCT REGISTRATION: NCT03291509.

Identification of a DNA segment exhibiting rearrangement modifying effects upon transgenic delta-deleting elements.

Control of the rearrangement and expression of the T cell receptor alpha and delta chains is critical for determining T cell type. The process of delta deletion is a candidate mechanism for maintaining separation of the alpha and delta loci. Mice harboring a transgenic reporter delta deletion construct show alpha/beta T cell lineage-specific use of the transgenic elements. A 48-basepair segment of DNA, termed HPS1A, when deleted from this reporter construct, loses tight lineage-specific rearrangement control of transgenic elements, with abundant rearrangements of transgenic delta-deleting elements now in gamma/delta T cells. Furthermore, HPS1A augments recombination frequency of extrachromosomal substrates in an in vitro recombination assay. DNA binding proteins recognizing HPS1A have been identified and are restricted to early B and T cells, during the time of active rearrangement of endogenous TCR and immunoglobulin loci. These data are consistent with delta deletion playing an important role in maintaining separate TCR alpha and delta loci.

Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription.

NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression.

Association of the melioidosis agent Burkholderia pseudomallei with water parameters in rural water supplies in Northern Australia.

We analyzed water parameters and the occurrence of the melioidosis agent Burkholderia pseudomallei in 47 water bores in Northern Australia. B. pseudomallei was associated with soft, acidic bore water of low salinity but high iron levels. This finding aids in identifying water supplies at risk of contamination with this pathogenic bacterium.

The 5-D itch scale: a new measure of pruritus.

BACKGROUND: Itching is a subjective and multidimensional experience which is difficult to quantify. Most methodologies to assess itching suffer from being unidimensional, for example only measuring intensity without impact on quality of life, or only measuring scratching activity. None has actually been demonstrated to be able to detect change over time, which is essential to using them as an outcome measure of response to an intervention. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials. The five dimensions are degree, duration, direction, disability and distribution. OBJECTIVES: To study the 5-D with respect to validity, reliability and response to change. METHODS: The 5-D was administered to 234 individuals with chronic pruritus due to liver disease (n = 63), kidney disease (n = 36), dermatological disorders (n = 56), HIV/AIDS (n = 28) and burn injuries (n = 51). The 5-D was administered at baseline and after a 6-week follow-up period. A subset of 50 untreated patients was retested after 3 days to assess test-retest reliability. RESULTS: The 5-D score correlated strongly with a visual analogue score: r = 0.727 at baseline (P < 0.0001), r = 0.868 at the 3-day repeat (P < 0.0001), and r = 0.892 at the 6-week follow-up (P < 0.0001). There was no change in mean 5-D score between day 1 and day 3 in untreated individuals (intraclass correlation coefficient = 0.96, P < 0.0001). The 5-D did, however, detect significant changes in pruritus over the 6-week follow-up period (P < 0.0001). Subanalysis of the different patient groups revealed similar response patterns and scores, with the exception of lower total scores for the burn victims due to lower scores on the distribution domain because they itched only at the site of their burn. CONCLUSIONS: The 5-D, therefore, is a reliable, multidimensional measure of itching that has been validated in patients with chronic pruritus to able to detect changes over time. The 5-D should be useful as an outcome measure in clinical trials.

Polarons and charge carrier solvation on conjugated carbon chains: a comparative ab initio study.

We study accommodation of an excess charge carrier on long even-N polyynic oligomers C(N)H(2) due to displacements of the underlying carbon lattice and polarization of the surrounding solvent in the context of carrier self-localization into a polaronic state. Spatial patterns of bond-length alternation, excess charge and spin densities are compared as derived with Hartree-Fock and two hybrid density functional theory methods (BHandHLYP and B3LYP) in conjunction with the polarizable continuum model. Quite distinct resulting pictures of carrier accommodation are found when contributions from different interactions are analyzed. Solvation robustly acts to promote excess charge localization.

A comparative ab initio study of neutral and charged kink solitons on conjugated carbon chains.

The ground state of odd-N polyynic oligomers C(N)H(2) features kink solitons in carbon-carbon bond-length alternation (BLA) patterns. We perform a systematic first-principles computational study of neutral and singly charged kinks in long oligomers addressing relationships between BLA patterns, electron energy gaps, and accompanying distributions of spin and charge densities, both in vacuum and in the screening solvent environment. A quantitative comparison is made of the results derived with four different ab initio methods: from pure density-functional theory to pure Hartree-Fock (HF) and including two popular hybrid density functionals, B3LYP and BHandHLYP. A clear correlation is demonstrated between the derived spatial extent of kinks and the amount of HF exchange used in the functionals. For charged kinks, we find a substantial difference in the behavior of charge and spin densities.

Decoding collective communications using information theory tools.

Organisms have evolved sensory mechanisms to extract pertinent information from their environment, enabling them to assess their situation and act accordingly. For social organisms travelling in groups, like the fish in a school or the birds in a flock, sharing information can further improve their situational awareness and reaction times. Data on the benefits and costs of social coordination, however, have largely allowed our understanding of why collective behaviours have evolved to outpace our mechanistic knowledge of how they arise. Recent studies have begun to correct this imbalance through fine-scale analyses of group movement data. One approach that has received renewed attention is the use of information theoretic (IT) tools like mutual information, transfer entropy and causation entropy, which can help identify causal interactions in the type of complex, dynamical patterns often on display when organisms act collectively. Yet, there is a communications gap between studies focused on the ecological constraints and solutions of collective action with those demonstrating the promise of IT tools in this arena. We attempt to bridge this divide through a series of ecologically motivated examples designed to illustrate the benefits and challenges of using IT tools to extract deeper insights into the interaction patterns governing group-level dynamics. We summarize some of the approaches taken thus far to circumvent existing challenges in this area and we conclude with an optimistic, yet cautionary perspective.

Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription.

Wnt signaling plays a critical role in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of Wnt signaling, little is known regarding Wnt signaling modification of the cell death machinery. Given that numerous oncogenes transform cells by providing cell survival function, we hypothesized that Wnt signaling may inhibit apoptosis. Here, we report that cells expressing Wnt-1 were resistant to cancer therapy-mediated apoptosis. Wnt-1 signaling inhibited the cytochrome c release and the subsequent caspase-9 activation induced by chemotherapeutic drugs, including both vincristine and vinblastine. Furthermore, we found that Wnt-1-mediated cell survival was dependent on the activation of beta-catenin/T cell factor (Tcf) transcription. Inhibition of beta-catenin/Tcf transcription by expression of the dominant-negative mutant of Tcf-4 blocked Wnt-1-mediated cell survival and rendered cells sensitive to apoptotic stimuli. These results provide the first demonstration that Wnt-1 inhibits cancer therapy-mediated apoptosis and suggests that Wnt-1 may exhibit its oncogenic potential through a mechanism of anti-apoptosis.

TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB.

Many cells are resistant to stimuli that can induce apoptosis, but the mechanisms involved are not fully understood. The activation of the transcription factor nuclear factor-kappa B (NF-kappaB) by tumor necrosis factor (TNF), ionizing radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to protect from cell killing. Inhibition of NF-kappaB nuclear translocation enhanced apoptotic killing by these reagents but not by apoptotic stimuli that do not activate NF-kappaB. These results provide a mechanism of cellular resistance to killing by some apoptotic reagents, offer insight into a new role for NF-kappaB, and have potential for improvement of the efficacy of cancer therapies.

NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.

NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.

Tumor necrosis factor alpha (TNF-alpha) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-kappaB), which suppresses apoptosis by an unknown mechanism. The activation of NF-kappaB was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-kappaB transcriptional activity. In cells in which NF-kappaB was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-kappaB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-alpha-mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis.