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: Introduction: Person‐centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient−provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient−provider interactions and how these interventions have improved HIV care continuum outcomes and person‐reported outcomes (PROs) among people living with HIV in low‐ and middle‐income countries. Methods: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient‐Centeredness by Scholl. We included person‐centred interventions aiming to enhance the patient−provider interactions. We included HIV care continuum outcomes and PROs. Results: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient−provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient‐led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient‐centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. Discussion: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long‐term retention or viral suppression. Conclusions: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation., INTRODUCTION Person‐centred care (PCC) offers principles that promise to improve HIV prevention and care, potentially even in resource‐constrained and public health settings that typically emphasize standardization and scale. The initial [...]

Next-generation sequencing of human tumours has refined our understanding of the mutational processes operative in cancer initiation and progression, yet major questions remain regarding the factors that induce driver mutations and the processes that shape mutation selection during tumorigenesis. Here we performed whole-exome sequencing on adenomas from three mouse models of non-small-cell lung cancer, which were induced either by exposure to carcinogens (methyl-nitrosourea (MNU) and urethane) or by genetic activation of Kras ([Kras.sup.LA2]). Although the MNU-induced tumours carried exactly the same initiating mutation in Kras as seen in the [Kras.sup.LA2] model (G12D), MNU tumours had an average of 192 non-synonymous, somatic single-nucleotide variants, compared with only six in tumours from the [Kras.sup.LA2] model. By contrast, the [Kras.sup.LA2] tumours exhibited a significantly higher level of aneuploidy and copy number alterations compared with the carcinogen-induced tumours, suggesting that carcinogen-induced and genetically engineered models lead to tumour development through different routes. The wild-type allele of Kras has been shown to act as a tumour suppressor in mouse models of non-small-cell lung cancer. We demonstrate that urethane-induced tumours from wild-type mice carry mostly (94%) Kras Q61R mutations, whereas those from Kras heterozygous animals carry mostly (92%) Kras Q61L mutations, indicating a major role for germline Kras status in mutation selection during initiation. The exomewide mutation spectra in carcinogen-induced tumours overwhelmingly display signatures of the initiating carcinogen, while adenocarcinomas acquire additional C > T mutations at CpG sites. These data provide a basis for understanding results from human tumour genome sequencing, which has identified two broad categories of tumours based on the relative frequency of single-nucleotide variations and copy number alterations (1), and underline the importance of carcinogen models for understanding the complex mutation spectra seen in human cancers., Sequencing studies of human cancers have identified a number of mutation 'signatures', suggesting that tumours carry an imprint of the environmental agents to which patients were exposed (2-4). At present, [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.socscimed.2010.03.017 Byline: Sunny C. Collings, Christopher G. Kemp Abstract: Health, government, and media organizations around the world have responded to research demonstrating the imitative effects of suicide coverage in the news media by developing guidelines to foster responsible reporting. Implementation of these guidelines has encountered some resistance, and little is known about the media perspective on suicide coverage and its effects on guideline use. This qualitative study provides an in-depth appreciation of this perspective by investigating the experiences of journalists covering suicide in New Zealand. Fifteen newspaper, television and radio journalists were interviewed between December 2008 and March 2009 and transcripts were analyzed using a grounded hermeneutic editing approach. Five themes were identified: public responsibility, media framing of suicide, professional practice, personal experience of suicide reporting, and restricted reporting. Participants asserted the role of the media in the protection of the public good. Though this stance aligns them with the goals of health policymakers, it is derived from a set of professional mores at odds with the perceived paternalism of suicide reporting guidelines. Participants were stakeholders in the issue of suicide coverage. We conclude that policymakers must engage with the news media and acknowledge the competing imperatives that provide the context for the application of suicide reporting guidelines by individual journalists. Collaborative guideline development will be vital to effective implementation. Author Affiliation: Social Psychiatry & Population Mental Health Research Unit, University of Otago, Wellington, 23a Mein St., Newtown, Wellington South, New Zealand Article Note: (footnote) [star] We thank the University of Otago Summer Studentship Programme for its sponsorship of this project. We are grateful to the busy participants for their generous donation of time and thoughtful consideration of the issues. Susan Kemp, Barry Taylor, Courtney Macdonald, and June Atkinson provided useful comments on earlier drafts.

The billions of specimens in natural-history museums are becoming more useful for tracking Earth's shrinking biodiversity. But the collections also face grave threats. Oicardo Moratelli surveys several hundred dead bats--their [...]

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity., Introduction The regulation of body weight occurs through the integration of peripheral and central signals reflecting available energy. Nutritional status is a key component of this process and is sensed [...]

TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in established tumor cell lines but not nontransformed cells. Herein, we demonstrate a role for the apoptosis-inducing TRAIL receptor (TRAIL-R) as a metastasis suppressor. Although mouse models employing tumor transplantation have shown that TRAIL can reduce tumor growth, autochthonous tumor models have generated conflicting results with respect to the physiological role of the TRAIL system during tumorigenesis. We used a multistage model of squamous cell carcinoma to examine the role of TRAIL-R throughout all steps of tumor development. DMBA/TPA-treated TRAIL-R-deficient mice showed neither an increase in number or growth rate of benign papillomas nor an increase in the rate of progression to squamous cell carcinoma. However, metastasis to lymph nodes was significantly enhanced, indicating a role for TRAIL-R specifically in the suppression of metastasis. We also found that adherent TRAIL-R-expressing skin carcinoma cells were TRAIL resistant in vitro but were sensitized to TRAIL upon detachment by inactivation of the ERK signaling pathway. As detachment from the primary tumor is an obligatory step in metastasis, this provides a possible mechanism by which TRAIL-R could inhibit metastasis. Hence, treatment of cancer patients with agonists of the apoptosis-inducing receptors for TRAIL may prove useful in reducing the incidence of metastasis., Introduction Along with CD95 ligand (CD95L/FasL) and TNF, TNF-related apoptosis-inducing ligand (TRAIL) belongs to a subset of the TNF superfamily of cytokines known as "death ligands." The members of this [...]

Several growth factors are trophic for the gastrointestinal tract and able to reduce the degree of intestinal damage caused by cytotoxic agents. However, studies of epidermal growth factor (EGF) for chemotherapy-induced intestinal injury are conflicting. The development of a transgenic mouse that specifically overexpresses EGF in the small intestine provided a unique opportunity to assess the contribution of EGF in mucositis. After a course of fluorouracil, transgenic mice fared no better than control mice. Weight recovery was inferior, and mucosal architecture was not preserved. Apoptosis was not decreased and proliferation was not increased in the crypts. To corroborate the findings in transgenic mice, ICR mice were treated with exogenous EGF after receiving fluorouracil. Despite ileal upregulation of native and activated EGF receptor, the mice were not protected from intestinal damage. No benefits were observed with different EGF doses or schedules or routes of EGF administration. Finally, mucositis was induced in mutant mice with specific defects of the EGF signaling axis. Compared with control mice, clinical and histological parameters of intestinal injury after fluorouracil were no different in waved-2 mice, which have functionally diminished EGF receptors, or waved-1 mice, which lack transforming growth factor-[alpha], another major ligand for the EGF receptor. These findings do not support a critical role for EGF or its receptor in chemotherapy-induced intestinal injury. intestinal mucosa; fluorouracil; enteritis; transgenic mouse; transforming growth factor-[alpha]

P27kip can inhibit cyclin-dependent kinases and stop cell proliferation. The p27 protein is found in abnormally low levels in human carcinomas, although a causal link between p27 and tumour suppression has not been possible. It has been shown that both p27 nullizygous and p27 heterozygous mice were predisposed to multiple tissue tumours when challenged with a chemical carcinogen or gamma-irradiation, indicating that P27 is a tumour suppressor in mice.

The character portrayed by Sylvester Stallone in the first two Rambo films, 'First Blood' and 'Rambo: First Blood Part II', is an icon of individual heroism akin to Milton's depiction of Samson in 'Samson Agonistes.' The success these films enjoyed suggests that the Rambo character's mix of patriotic heroism, radicalism and mistrust of technology reflected some of the values of the movie-going public. 'Rambo III' departed from the formula established in the first two films and was not as well-received.

An electronic energy term for transition metals (copper and nickel complex) was constructed for extending Molecular Mechanics (MM) to open-shell, Werner-type coordination compounds. Cellular Ligand Field Stabilization (CLFSE) was computed by calculating the d-orbital energies generated from a ligand field. Copper complexes are intrinsically flexible and with the Jahn-Teller effect can undergo large geometrical changes from relatively minor crystal packing effects.

The investigations of the functional properties of the p53 tumor suppressor gene in initiation promotion and progression of carcinogenesis is facilitated by the availability of p53 knockout mice generated by gene targeting. There is no increase in the growth rate of benign papillomas in the p53 heterozygous mice. A reduction in the papillomas yield is exhibited by the p53 null mice, though these were subjected to a malignant progression. In these mice, poorly differentiated carcinomas developed only after 10 weeks of promotion. The heterozygous mice exhibit a larger progression rate than the wild type mice.

Two knock-in mouse models were created to study the mechanisms that regulate p27 in normal cells and cause misregulation of p27 in tumors. These two mutant alleles identify steps in a pathway that controls the proteasomal degradation of p27 uniquely in quiescent cells.

Stern, Lawrence E., Richard A. Falcone, Jr., Christopher J. Kemp, Margaret C. Braun, Christopher R. Erwin, and Brad W. Warner. Salivary epidermal growth factor and intestinal adaptation in male and female mice. Am J Physiol Gastrointest Liver Physiol 278: G871-G877, 2000. --Salivary epidermal growth factor (sEGF) levels are increased in male mice after small bowel resection (SBR) and may be important during intestinal adaptation. Since males have greater sEGF than females, the influence of sex on postresection adaptation was tested. Females had lower sEGF; however, sEGF substantially increased in both sexes after a massive (50%) SBR. Adaptive increases in DNA and protein content, villus height, and crypt depth, as well as crypt cell proliferation rates in the remnant ileum, were not different between males and females. Although significant postresection increases in sEGF were identified, EGF mRNA and protein did not change within the submandibular gland. Glandular kallikrein-13 and ileal EGF receptor expression were greater after SBR in female mice. Intestinal adaptation is equivalent in female and male mice after SBR. Despite lower sEGF, females demonstrated increased expression of a kallikrein responsible for sEGF precursor cleavage as well as amplified ileal EGF receptor expression. These results endorse an important differential response between sexes regarding sEGF mobilization and intestinal receptor availability during adaptation. small bowel resection; kallikrein; salivary gland

Mutations in palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme that removes fatty acyl groups from cysteine residues in modified proteins, cause the fatal inherited neurodegenerative disorder infantile neuronal ceroid lipofuscinosis. The accumulation of undigested substrates leads to the formation of neuronal storage bodies that are associated with the clinical symptoms. Less severe forms of PPT1 deficiency have been found recently that are caused by a distinct set of PPT1 mutations, some of which retain a small amount of thioesterase activity. We have determined the crystal structure of PPT1 with and without bound palmitate by using multiwavelength anomalous diffraction phasing. The structure reveals an [Alpha]/[Beta]-hydrolase fold with a catalytic triad composed of Ser115-His289-Asp233 and provides insights into the structural basis for the phenotypes associated with PPT1 mutations.

Shin, Cathy E., Richard A. Falcone, Jr., Christopher J. Kemp, Christopher R. Erwin, David A. Litvak, B. Mark Evers, and Brad W. Warner. Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G717-G724, 1999.--Adaptation following small bowel resection (SBR) signals enterocyte proliferation and apoptosis. Because p53-induced [p21.sup.waf1/cip1] may be important for apoptosis in many cells, we hypothesized that these genes are required for increased enterocyte apoptosis during adaptation. Male C57BL/6 (wild-type) or p53-null mice underwent 50% proximal SBR or sham operation (bowel transection-reanastomosis). Adaptation (DNA-protein content, villus height-crypt depth, enterocyte proliferation), appearance of apoptotic bodies, and p53 and [p21.sup.waf1/cip1] protein expression were measured in the ileum after 5 days. Adaptation was equivalent after SBR in both wild-type and p53-null mice as monitored by significantly increased ileal DNA-protein content, villus height, and enterocyte proliferation. The number of crypt apoptotic bodies increased significantly after SBR evenly in both wild-type and p53-null mice. In the p53-null mice, SBR substantially induced the expression of [p21.sup.waf1/cip1] protein in villus enterocytes. The p53-independent induction of [p21.sup.waf1/cip1] may account for the similar intestinal response to SBR between wild-type and p53-null mice. Intestinal adaptation and increased enterocyte apoptosis following intestinal resection occur via a p53-independent mechanism. enterectomy; mice; intestinal resection; short-gut syndrome; programmed cell death

In May 2012, Mark Armitage made a discovery that he had dreamed of for years. While digging in Montana, he uncovered one of the largest triceratops horns ever found in [...]

In the Methods section titled 'Fatty acid infusion,' the dose of fatty acids delivered centrally was given incorrectly. The correct sentence appears below. The cannula was connected via a polyethylene [...]

The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 Å resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design., Angiogenesis, the growth of new blood vessels, is a pathological determinant in tumor progression, diabetic retinopathy, and rheumatoid arthritis (1). The serendipitous discovery that fumagillin, a fungal metabolite, potently inhibits [...]