Acalculous Cholecystitis in a Pediatric Patient With Plasmodium Falciparum Infection: A Case Report and Literature Review.

Malaria has been associated with acute acalculous cholecystitis, a very uncommon complication in children. We present a 5-year-old girl, originally from Equatorial-Guinea, diagnosed with severe malaria with acute kidney injury, thrombocytopenia and acute acalculous cholecystitis. She was treated with intravenous quinine and clindamycin, plus cefotaxime and metronidazole with a full resolution without surgery.

Edema de Calabar en una niña guineana: loasis / Guinean child with Calabar swelling: Loiasis

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Common pathways regulate Type III TGFß receptor-dependent cell invasion in epicardial and endocardial cells.

Epithelial-Mesenchymal Transformation (EMT) and the subsequent invasion of epicardial and endocardial cells during cardiac development is critical to the development of the coronary vessels and heart valves. The transformed cells give rise to cardiac fibroblasts and vascular smooth muscle cells or valvular interstitial cells, respectively. The Type III Transforming Growth Factor ß (TGFßR3) receptor regulates EMT and cell invasion in both cell types, but the signaling mechanisms downstream of TGFßR3 are not well understood. Here we use epicardial and endocardial cells in in vitro cell invasion assays to identify common mechanisms downstream of TGFßR3 that regulate cell invasion. Inhibition of NF-κB activity blocked cell invasion in epicardial and endocardial cells. NF-κB signaling was found to be dysregulated in Tgfbr3(-/-) epicardial cells which also show impaired cell invasion in response to ligand. TGFßR3-dependent cell invasion is also dependent upon Activin Receptor-Like Kinase (ALK) 2, ALK3, and ALK5 activity. A TGFßR3 mutant that contains a threonine to alanine substitution at residue 841 (TGFßR3-T841A) induces ligand-independent cell invasion in both epicardial and endocardial cells in vitro. These findings reveal a role for NF-κB signaling in the regulation of epicardial and endocardial cell invasion and identify a mutation in TGFßR3 which stimulates ligand-independent signaling.

Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study.

BACKGROUND: Neuroimaging studies in younger adults have demonstrated sex differences in brain processing of painful experimental stimuli. Such differences may contribute to findings that women suffer disproportionately from pain. It is not known whether sex-related differences in pain processing extend to older adults. METHODS: This cross-sectional study investigated sex differences in pain reports and brain response to pain in 12 cognitively healthy older female adults and 12 cognitively healthy age-matched older male adults (age range 65-81, median = 67). Participants underwent psychophysical assessments of thermal pain responses, functional MRI, and psychosocial assessment. RESULTS: When compared to older males, older females reported experiencing mild and moderate pain at lower stimulus intensities (i.e., exhibited greater pain sensitivity; Cohen's d = 0.92 and 0.99, respectively, p < 0.01) yet did not report greater pain-associated unpleasantness. Imaging results indicated that, despite the lower stimulus intensities required to elicit mild pain detection in females, they exhibited less deactivations than males in regions associated with the default mode network (DMN) and in regions associated with pain affect (bilateral dorsolateral prefrontal cortex, somatomotor area, rostral anterior cingulate cortex (rACC), and dorsal ACC). Conversely, at moderate pain detection levels, males exhibited greater activation than females in several ipsilateral regions typically associated with pain sensation (e.g., primary (SI) and secondary somatosensory cortices (SII) and posterior insula). Sex differences were found in the association of brain activation in the left rACC with pain unpleasantness. In the combined sample of males and females, brain activation in the right secondary somatosensory cortex was associated with pain unpleasantness. CONCLUSIONS: Cognitively healthy older adults in the sixth and seventh decades of life exhibit similar sex differences in pain sensitivity compared to those reported in younger individuals. However, older females did not find pain to be more unpleasant. Notably, increased sensitivity to mild pain in older females was reflected via less brain deactivation in regions associated with both the DMN and in pain affect. Current findings elevate the rACC as a key region associated with sex differences in reports of pain unpleasantness and brain deactivation in older adults. Also, pain affect may be encoded in SII in both older males and females.

BMP2 signals loss of epithelial character in epicardial cells but requires the Type III TGFß receptor to promote invasion.

Coronary vessel development depends on a subpopulation of epicardial cells that undergo epithelial to mesenchymal transformation (EMT) and invade the subepicardial space and myocardium. These cells form the smooth muscle of the vessels and fibroblasts, but the mechanisms that regulate these processes are poorly understood. Mice lacking the Type III Transforming Growth Factor ß Receptor (TGFßR3) die by E14.5 due to failed coronary vessel development accompanied by reduced epicardial cell invasion. BMP2 signals via TGFßR3 emphasizing the importance of determining the relative contributions of the canonical BMP signaling pathway and TGFßR3-dependent signaling to BMP2 responsiveness. Here we examined the role of TGFßR3 in BMP2 signaling in epicardial cells. Whereas TGFß induced loss of epithelial character and smooth muscle differentiation, BMP2 induced an ALK3-dependent loss of epithelial character and modestly inhibited TGFß-stimulated differentiation. Tgfbr3(-/-) cells respond to BMP2 indicating that TGFßR3 is not required. However, Tgfbr3(-/-) cells show decreased invasion in response to BMP2 and overexpression of TGFßR3 in Tgfbr3(-/-) cells rescued invasion. Invasion was dependent on ALK5, ALK2, ALK3, and Smad4. Expression of TGFßR3 lacking the 3 C-terminal amino acids required to interact with the scaffolding protein GIPC (GAIP-interacting protein, C terminus) did not rescue. Knockdown of GIPC in Tgfbr3(+/+) or Tgfbr3(-/-) cells rescued with TGFßR3 decreased BMP2-stimulated invasion confirming a requirement for TGFßR3/GIPC interaction. Our results reveal the relative roles of TGFßR3-dependent and TGFßR3-independent signaling in the actions of BMP2 on epicardial cell behavior and demonstrate the critical role of TGFßR3 in mediating BMP2-stimulated invasion.