The dual effect of the ubiquitous inflammatory cytokine transforming growth factor B1 (TGFB) on cellular proliferation and tumor metastasis is intriguing but complex. In epithelial cell -and neural cell -derived tumors, TGFB serves as a growth inhibitor at the beginning of tumor development but later becomes a growth accelerator for transformed tumors. The somatostatin (SST) signaling pathway is a well-established antiproliferation signal, and in this report, we explore the interplay between the SST and TGFB signaling pathways in the human neuroendocrine tumor cell line BON. We defined the SST signaling pathway as a determinant for neuroendocrine tumor BON cells in responding to TGFB as a growth inhibitor. We also determined that TGFB induces the production of SST and potentially activates the negative growth autocrine loop of SST, which leads to the downstream induction of multiple growth inhibitory effectors: protein tyrosine phosphatases (i.e., SHPTP1 and SHPTP2), p21Waf1/Cip1 , and p27 Kip1 . Concurrently, TGFB down-regulates the growth accelerator c-Myc protein and, collectively, they establish a firm antiproliferation effect on BON cells. Additionally, any disruption in the activation of either the TGFB or SST signaling pathway in BON leads to ''reversible'' neuroendocrinemesenchymal transition, which is characterized by the loss of neuroendocrine markers (i.e., chromogranin A and PGP 9.5), as well as the altered expression of mesenchymal proteins (i.e., elevated vimentin and Twist and decreased E-cadherin), which has previously been associated with elevated metastatic potential. In summary, TGFB-dependent growth inhibition and differentiation is mediated by the SST signaling pathway. Therefore, any disruption of this TGFB-SST connection allows BON cells to respond to TGFB as a growth accelerator instead of a growth suppressor. This model can potentially apply to other cell types that exhibit a similar interaction of these pathways.

The ECL2 is an important ectodomain for G protein-coupled receptor activation and required for ligand binding selectivity. The anti-SSTR2, anti-SSTR3, and anti-SSTR5 ECL2 antibodies independently inhibited BON proliferation and decreased hormone secretion. Unlike octreotide, our antibodies do not interfere with SST-SSTR binding.

Background. Naegleria Fowleri is a single-cell, thermophilic amphizoid amoeba, and a rare known causative agent for primary amoebic meningoencephalitis with >97% mortality rate. The amoeba resides in freshwater lakes and ponds but can also survive in inadequately chlorinated pools and recreational waters. The mode of infection includes activities such as diving or jumping into freshwater or submerging the head under the water. Although most commonly seen in the southern United States, it is essential to keep this clinical suspicion in mind regardless of geography, as presenting symptoms can be very similar to classic bacterial meningitis. Case Summary. We report the first-ever case in the state of New Jersey of a 29-year-old male presented after a visit to a recreational water park in Texas five days before his presentation with altered mental status. In ICU, his ICP remained refractory to multiple therapies, including antibiotics and antivirals, external ventriculostomy drain, hypertonic saline, pentobarbital-induced coma, and bilateral hemicraniectomies. The CSF analysis revealed trophozoites indicating a protozoan infection, which we diagnosed in the neurocritical unit, and the patient was then immediately started with treatment that included amphotericin B, rifampin, azithromycin, and fluconazole. This suspicion was promptly confirmed by the Center for Disease Control (CDC). Unfortunately, despite all the aggressive intervention by the multidisciplinary team, the patient did not survive. Conclusion. As per the CDC, only four people out of 143 known infected individuals in the United States from 1962 to 2017 have survived. Symptoms start with a median of 5 days after exposure to contaminated water. Given the rarity of this case and its very high mortality rate, it is crucial to diagnose primary amoebic meningoencephalitis accurately as its presentation can mimic bacterial meningitis. It is vital to obtain a careful and thorough history, as it can aid in prompt diagnosis and treatment.

HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.