Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability

We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike. An increased release of lactate dehydrogenase that followed exposure to hypoxia was attenuated in rat islets which had been pre-cultured at half standard glucose. In INS-1 cells exposure to half standard glucose attenuated hypoxia-induced effects on several viability parameters (MTT, cell number and incremental apoptotic DNA). Thus culture at reduced glucose of pancreatic islets and clonal β cells leads to mitochondrial adaptions which possibly lessen the negative impact of hypoxia on β cell viability. These findings appear relevant in the search for optimization of pre-transplant conditions in a clinical setting.     

Non-response for health-related quality of life outcomes in ICU patients: A systematic review of the reporting in randomised trials

Background

Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.

Methods

We conducted a systematic review and meta-analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate.

Results

We included 196 outcomes from 88 RCTs published in the years 2002–2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow-up, median 27% (interquartile range 14%–39%) of patients had died, and median 20% (9%–38%) of survivors did not respond across outcomes. Analyses of 80% of outcomes were restricted to complete cases only. The handling of non-survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non-survivors (using the value zero or the worst possible score).

Conclusion

For HRQoL outcomes in ICU trials, we found that mortality at time of follow-up was high and non-response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.     

Occult Contralateral Lateral Lymph Node Metastases in Unilateral N1b Papillary Thyroid Carcinoma

World Journal of Surgery - Therapeutic lateral neck dissection (ND) is recommended for N1b papillary thyroid carcinoma (PTC), while prophylactic contralateral lateral ND is not. Given the paucity...     

Melatonin promotes sorafenib‐induced apoptosis through synergistic activation of JNK/c‐jun pathway in human hepatocellular carcinoma

Melatonin has been shown to exert anticancer activity on hepatocellular carcinoma (HCC) through its antiproliferative and pro‐apoptotic effect in both experimental and clinical studies, and sorafenib is the only approved drug for the systemic treatment of HCC. Thus, this study was designed to investigate the combined effect of melatonin and sorafenib on proliferation, apoptosis, and its possible mechanism in human HCC. Here, we found that both melatonin and sorafenib resulted in a dose‐dependent growth inhibition of HuH‐7 cells after 48 hours treatment, and the combination of them enhanced the growth inhibition in a synergistic manner. Colony formation assay indicated that co‐treatment of HuH‐7 cells with melatonin and sorafenib significantly decreased the clonogenicity compared to the treatment with single agent. Furthermore, FACS and TUNEL assay confirmed that melatonin synergistically augmented the sorafenib‐induced apoptosis after 48 hours incubation, which was in accordance with the activation of caspase‐3 and the JNK/c‐jun pathway. Inhibition of JNK/c‐jun pathway with its inhibitor SP600125 reversed the phosphorylation of c‐jun and the activation of caspase‐3 induced by co‐treatment of HuH‐7 cells with melatonin and sorafenib in a dose‐dependent manner. Furthermore, SP600125 exhibited protective effect against apoptosis induced by the combination of melatonin and sorafenib. This study demonstrates that melatonin in combination with sorafenib synergistically inhibits proliferation and induces apoptosis in human HCC cells; therefore, supplementation of sorafenib with melatonin may serve as a potential therapeutic choice for advanced HCC.     

Maternally acquired genotoxic Escherichia coli alters offspring’s intestinal homeostasis

The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood.     

Nematodes as bioindicators of soil degradation due to heavy metals

The effect of distance from a heavy metal pollution source on the soil nematode community was investigated on four sampling sites along an 4?km transect originating at the Kovohuty a.s. Krompachy (pollution source). The soil nematode communities were exposed to heavy metal influence directly and through soil properties changes. We quantified the relative effects of total and mobile fraction of metals (As, Cd, Cr, Cu, Pb, and Zn) on soil ecosystem using the nematode community structure (trophic and c-p groups,) and ecological indices (Richness of genera, H′, MI2-5, etc.). Pollution effects on the community structure of soil free living nematodes was found to be the highest near the pollution source, with relatively low population density and domination of insensitive taxa. A decrease in heavy metals contents along the transect was linked with an increase in complexity of nematode community. The majority of used indices (MI2-5, SI, H′) negatively correlated (P?<?0.05 or P?<?0.01) with heavy metals content and were sensitive to soil ecosystem disturbance. Contamination by heavy metals has negatively affected the soil environment, which resulted in nematode community structure and ecological indices changes. Results showed that the free-living nematodes are useful tools for bioindication of contamination and could be used as an alternative to the common approaches based on chemical methods.     

Tuberculous peritonitis with infracarinal mass and elevated CA-125 in a 13-year-old girl

A 13-year-old girl with weight loss and ascites was admitted with suspicion of a malignant disease. Abdominal magnetic resonance imaging indicated extensive peritonitis and showed no evidence of a solid tumor. As a new imaging observation, thoracic computed tomography showed a lymphoma-like infracarinal mass and further enlarged lymph nodes in the pathway of draining lymph ducts. A tuberculin skin test and an interferon-gamma blood test were positive, and the tumor marker CA-125 was elevated. Histology of a peritoneal biopsy showed infectious granulomas with central necrosis, and Mycobacterium tuberculosis could be cultured, leading to the diagnosis of a tuberculous peritonitis. The girl received multi-drug anti-tuberculous treatment and subsequently recovered. At follow-up the peritonitis and the infracarinal mass had vanished. In conclusion, tuberculous peritonitis is a rare but relevant differential diagnosis in peritonitis of unknown origin. Its diagnosis is facilitated by imaging, by tuberculosis skin and blood tests, and by clinical interpretation.