Triple intussusception involving heterotopic pancreatic tissue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Intussusception involving heterotopic pancreatic tissue is a rare condition where a portion of the bowel telescopes into an adjacent segment with intraluminal pancreatic tissue as the lead point. Cases of heterotopic pancreas are most often described in the upper intestinal tract, particularly the stomach.</p> <p>Case presentation</p> <p>We present the case of a five-month-old boy of Caucasian ethnicity suffering acute abdominal pain and vomiting with an abdominal mass in the upper right quadrant. Work-up including ultrasound scan confirmed the intussusception. Repeated attempts at radiological reduction and two laparoscopic procedures were performed within 24 hours, which eventually led to the diagnosis of a triple intussusception.</p> <p>Conclusion</p> <p>To our knowledge, such a case of triple intussusception involving isolated heterotopic pancreatic tissue is previously unreported.</p

Climate change adaptation and cross-sectoral policy coherence in southern Africa

To be effective, climate change adaptation needs to be mainstreamed across multiple sectors and greater policy coherence is essential. Using the cases of Malawi, Tanzania and Zambia, this paper investigates the extent of coherence in national policies across the water and agriculture sectors and to climate change adaptation goals outlined in national development plans. A two-pronged qualitative approach is applied using Qualitative Document Analysis of relevant policies and plans, combined with expert interviews from non-government actors in each country. Findings show that sector policies have differing degrees of coherence on climate change adaptation, currently being strongest in Zambia and weakest in Tanzania. We also identify that sectoral policies remain more coherent in addressing immediate-term disaster management issues of floods and droughts rather than longer-term strategies for climate adaptation. Coherence between sector and climate policies and strategies is strongest when the latter has been more recently developed. However to date, this has largely been achieved by repackaging of existing sectoral policy statements into climate policies drafted by external consultants to meet international reporting needs and not by the establishment of new connections between national sectoral planning processes. For more effective mainstreaming of climate change adaptation, governments need to actively embrace longer-term cross-sectoral planning through cross-Ministerial structures, such as initiated through Zambia’s Interim Climate Change Secretariat, to foster greater policy coherence and integrated adaptation planning

Descriptive epidemiology of stigma against depression in a general population sample in Alberta

<p>Abstract</p> <p>Background</p> <p>Mental health illnesses, such as depression, are responsible for a growing disease burden worldwide. Unfortunately, effective treatment is often impeded by stigmatizing attitudes of other individuals, which have been found to lead to a number of negative consequences including reduced help-seeking behavior and increased social distance. Despite the high prevalence of depression in Canada, little research has been conducted to examine stigma against depression in the Canadian general population. Such information is crucial to understanding the current state of stigmatizing attitudes in the Canadian communities, and framing future stigma reduction initiatives. The objectives of this study were to estimate the percentages of various stigmatizing attitudes toward depression in a general population sample and to compare the percentages by demographics and socioeconomic characteristics.</p> <p>Methods</p> <p>We conducted a cross-sectional telephone survey in Alberta, Canada, between February and June 2006. Random digit dialing was used to recruit participants who were aged 18-74 years old (n = 3047). Participants were presented a case vignette describing a depressed individual, and responded to a 9-item Personal Stigma questionnaire. The percentages of stigmatizing attitudes were estimated and compared by demographic and socioeconomic variables.</p> <p>Results</p> <p>Among the participants, 45.9% endorsed that depressed individuals were unpredictable and 21.9% held the view that people with depression were dangerous. Significant differences in stigmatizing attitudes were found by gender, age, education, and immigration status. A greater proportion of men than women held stigmatizing views on each stigma item. No consistent trend emerged by age in stigma against depression. Participants with higher levels of education reported less stigmatizing attitudes than those with less education. Participants who were not born in Canada were more likely to hold stigmatizing attitudes than those who were born in Canada.</p> <p>Conclusion</p> <p>In the general population, stigmatizing attitudes towards depression differ by demographic characteristics. Men, those with less education and immigrants should be the targets of stigma reduction campaigns.</p

Fermi surface instability at the hidden-order transition of URu2Si2

Solids with strong electron correlations generally develop exotic phases of electron matter at low temperatures. Among such systems, the heavy-fermion semi-metal URu2Si2 presents an enigmatic transition at To = 17.5 K to a `hidden order' state whose order parameter remains unknown after 23 years of intense research. Various experiments point to the reconstruction and partial gapping of the Fermi surface when the hidden-order establishes. However, up to now, the question of how this transition affects the electronic spectrum at the Fermi surface has not been directly addressed by a spectroscopic probe. Here we show, using angle-resolved photoemission spectroscopy, that a band of heavy quasi-particles drops below the Fermi level upon the transition to the hidden-order state. Our data provide the first direct evidence of a large reorganization of the electronic structure across the Fermi surface of URu2Si2 occurring during this transition, and unveil a new kind of Fermi-surface instability in correlated electron systemsComment: 15 pages, 5 figure

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells

BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells

Hsp40 Couples with the CSPα Chaperone Complex upon Induction of the Heat Shock Response

In response to a conditioning stress, the expression of a set of molecular chaperones called heat shock proteins is increased. In neurons, stress-induced and constitutively expressed molecular chaperones protect against damage induced by ischemia and neurodegenerative diseases, however the molecular basis of this protection is not known. Here we have investigated the crosstalk between stress-induced chaperones and cysteine string protein (CSPα). CSPα is a constitutively expressed synaptic vesicle protein bearing a J domain and a cysteine rich “string” region that has been implicated in the long term functional integrity of synaptic transmission and the defense against neurodegeneration. We have shown previously that the CSPα chaperone complex increases isoproterenol-mediated signaling by stimulating GDP/GTP exchange of Gαs. In this report we demonstrate that in response to heat shock or treatment with the Hsp90 inhibitor geldanamycin, the J protein Hsp40 becomes a major component of the CSPα complex. Association of Hsp40 with CSPα decreases CSPα-CSPα dimerization and enhances the CSPα-induced increase in steady state GTP hydrolysis of Gαs. This newly identified CSPα-Hsp40 association reveals a previously undescribed coupling of J proteins. In view of the crucial importance of stress-induced chaperones in the protection against cell death, our data attribute a role for Hsp40 crosstalk with CSPα in neuroprotection

Evolution of the human-specific microRNA miR-941

MicroRNA-mediated gene regulation is important in many physiological processes. Here we explore the roles of a microRNA, miR-941, in human evolution. We find that miR-941 emerged de novo in the human lineage, between six and one million years ago, from an evolutionarily volatile tandem repeat sequence. Its copy-number remains polymorphic in humans and shows a trend for decreasing copy-number with migration out of Africa. Emergence of miR-941 was accompanied by accelerated loss of miR-941-binding sites, presumably to escape regulation. We further show that miR-941 is highly expressed in pluripotent cells, repressed upon differentiation and preferentially targets genes in hedgehog- and insulin-signalling pathways, thus suggesting roles in cellular differentiation. Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling. Taken together, these results implicate miR-941 in human evolution, and provide an example of rapid regulatory evolution in the human linage

Defence Responses of Arabidopsis thaliana to Infection by Pseudomonas syringae Are Regulated by the Circadian Clock

The circadian clock allows plants to anticipate predictable daily changes in abiotic stimuli, such as light; however, whether the clock similarly allows plants to anticipate interactions with other organisms is unknown. Here we show that Arabidopsis thaliana (Arabidopsis) has circadian clock-mediated variation in resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with plants being least susceptible to infection in the subjective morning. We suggest that the increased resistance to Pst DC3000 observed in the morning in Col-0 plants results from clock-mediated modulation of pathogen associated molecular pattern (PAMP)-triggered immunity. Analysis of publicly available microarray data revealed that a large number of Arabidopsis defence-related genes showed both diurnal- and circadian-regulation, including genes involved in the perception of the PAMP flagellin which exhibit a peak in expression in the morning. Accordingly, we observed that PAMP-triggered callose deposition was significantly higher in wild-type plants inoculated with Pst DC3000 hrpA in the subjective morning than in the evening, while no such temporal difference was evident in arrhythmic plants. Our results suggest that PAMP-triggered immune responses are modulated by the circadian clock and that temporal regulation allows plants to anticipate and respond more effectively to pathogen challenges in the daytime