Recurrence of Guttae and Endothelial Dysfunction After Successful Descemet Stripping Only in Fuchs Dystrophy.

PURPOSE: There are limited data about long-term durability of endothelial rejuvenation after Descemet stripping only (DSO). This study reports a case of bilaterally recurrent endothelial dysfunction and guttae formation after initially successful DSO in combination with cataract extraction (DSO-CE). METHODS: This is a retrospective case report. A 49-year-old man with Fuchs endothelial corneal dystrophy with bilateral visually significant endothelial guttae (predominantly confluent centrally) and concomitant cataract underwent DSO-CE bilaterally. Postoperative course to long-term outcome at 6 years was analyzed. RESULTS: Baseline central corneal thickness (CCT) was 568 µm in OD and 582 µm in OS. Preoperatively, both eyes had no countable central endothelial cells but good peripheral endothelial mosaic. In both eyes, the cornea clinically cleared at approximately 1 month postoperatively after DSO-CE. In short-term follow-up (OD postoperative month 6 and OS postoperative month 3), CCT was 556 µm in OD and 561 µm in OS and central endothelial cell density was 1352 cells/mm 2 in OD and 880 cells/mm 2 in OS. The patient returned to our center in postoperative year 6 OU. At this time, OU had interval formation of guttae within the descemetorhexis, with increased CCT (OD 631 µm and OS 609 µm) and decreased central endothelial cell density (OD 728 cells/mm 2 and OS 609 cells/mm 2 ). CONCLUSIONS: After DSO, progressive endothelial dysfunction with new guttae formation can occur within the descemetorhexis region of repopulated endothelium. Larger analyses with longer follow-up are needed to better characterize long-term outcomes of DSO.

O-GlcNAcylation regulates OTX2's proteostasis.

O-GlcNAcylation is a key post-translational modification, playing a vital role in cell signaling during development, especially in the brain. In this study, we investigated the role of O-GlcNAcylation in regulating the homeobox protein OTX2, which contributes to various brain disorders, such as combined pituitary hormone deficiency, retinopathy, and medulloblastoma. Our research demonstrated that, under normal physiological conditions, the proteasome plays a pivotal role in breaking down endogenous OTX2. However, when the levels of OTX2 rise, it forms oligomers and/or aggregates that require macroautophagy for clearance. Intriguingly, we demonstrated that O-GlcNAcylation enhances the solubility of OTX2, thereby limiting the formation of these aggregates. Additionally, we unveiled an interaction between OTX2 and the chaperone protein CCT5 at the O-GlcNAc sites, suggesting a potential collaborative role in preventing OTX2 aggregation. Finally, our study demonstrated that while OTX2 physiologically promotes cell proliferation, an O-GlcNAc-depleted OTX2 is detrimental to cancer cells.

Socioeconomic Disparities in the Prevalence of Cardiometabolic Risk Factors in Ghanaian Women.

BACKGROUND: Recent trends toward urbanization in developing countries like Ghana, coupled with nutritional transition and aging populations, have led to a rapid increase in the prevalence of noncommunicable diseases such as obesity, diabetes, and hypertension. The purpose of this study was to evaluate the association between socioeconomic status and cardiometabolic risk factors among women in Ghana. METHODS: Data for this analysis were obtained from Wave 1 of the Ghana Study of Global Aging and Health, conducted in 2007, and included women 18 years and older. Survey weighted descriptive and multivariable linear regression models were used to examine the association between socioeconomic status and cardiometabolic risk factors. RESULTS: Among a total of 1988 women, 48% ages 40-64 years, almost half were overweight or obese (47%) and 21% had current hypertension, whereas only 4.3% and 2% of women self-reported a history of hypertension and diabetes, respectively. Multivariable adjusted analysis indicated that women with a high school education had 2-fold increased odds of being overweight or obese compared with those with no formal education (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20-3.42). Women employed in the public sector had almost a 5 times higher odds of being overweight or obese (OR: 4.94, 95% CI: 1.42-17.15), whereas those employed in the private sector or self-employed had reduced odds of diabetes (OR: 0.27, 95% CI: 0.10-0.70) and hypertension (OR: 0.43, 95% CI: 0.21-0.86). CONCLUSION: The prevalence of cardiometabolic risk factors varies by socioeconomic status among Ghanaian women. Targeted intervention programs to reduce overweight and obesity may begin among Ghanaian women employed in the public sector, and improved access to health care will be critical for timely diagnosis and management of other disease risk factors.

Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells.

Sphingosine kinase 2 (Sphk2) has an oncogenic role in cancer. A recently developed first-in-class Sphk2 specific inhibitor ABC294640 displays antitumor activity in many cancer models. However, the role of Sphk2 and the antitumor activity of its inhibitor ABC294640 are not known in cholangiocarcinoma. We investigated the potential of targeting Sphk2 for the treatment of cholangiocarcinoma. We found that Sphk2 is overexpressed in five established human cholangiocarcinoma cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient-derived cholangiocarcinoma cell line (LIV27) compared to H69 normal cholangiocytes. Inhibition of Sphk2 by ABC294640 inhibited proliferation and induced caspase-dependent apoptosis. Furthermore, we found that ABC294640 inhibited STAT3 phosphorylation, one of the key signaling pathways regulating cholangiocarcinoma cell proliferation and survival. ABC294640 also induced autophagy. Inhibition of autophagy by bafilomycin A1 or chloroquine potentiated ABC294640-induced cytotoxicity and apoptosis. In addition, ABC294640 in combination with sorafenib synergistically inhibited cell proliferation of cholangiocarcinoma cells. Strong decreases in STAT3 phosphorylation were observed in WITT and HuCCT1 cells exposed to the ABC294640 and sorafenib combination. These findings provide novel evidence that Sphk2 may be a rational therapeutic target in cholangiocarcinoma. Combinations of ABC294640 with sorafenib and/or autophagy inhibitors may provide novel strategies for the treatment of cholangiocarcinoma.