Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3-7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8-10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10-14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.

A review of the uses of fluoride and outcomes of dental caries control in singapore.

In 1958, Singapore was the first country in Asia to implement a community water fluoridation program covering 100% of its population. There were no reports of anti-fluoridation activities or calls for referenda then; and at present, there is only mild opposition to water fluoridation. The water was initially fluoridated at 0.7 ppm but was gradually adjusted downwards to 0.6 ppm in January 1992, with a further reduction to 0.5 ppm in January 2008 where it has since remained unchanged. Fluoride varnishes and gels are also available for use by the professional for judicious application in individuals who are at high-risk of dental caries. In addition, fluoridated dentifrices and mouth rinses are also readily available over the counter for home use. In addition to the use of fluorides, the following factors also contribute to the high level of oral health in Singapore: (i) a highly educated populace; (ii) public health education to increase awareness and literacy is routinely carried out by the Health Promotion Board; (iii) the School Dental Service provides 'free' dental care to school children up to 18 years of age; and (iv) primary dental care is also readily accessible by the general public by an extensive network of private and public sector dental clinics.

Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.

Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non-small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.

Bio-Inspired NanoVilli Chips for Enhanced Capture of Tumor-Derived Extracellular Vesicles: Toward Non-Invasive Detection of Gene Alterations in Non-Small Cell Lung Cancer.

Tumor-derived extracellular vesicles (EVs) present in bodily fluids are emerging liquid biopsy markers for non-invasive cancer diagnosis and treatment monitoring. Because the majority of EVs in circulation are not of tumor origin, it is critical to develop new platforms capable of enriching tumor-derived EVs from the blood. Herein, we introduce a biostructure-inspired NanoVilli Chip, capable of highly efficient and reproducible immunoaffinity capture of tumor-derived EVs from blood plasma samples. Anti-EpCAM-grafted silicon nanowire arrays were engineered to mimic the distinctive structures of intestinal microvilli, dramatically increasing surface area and enhancing tumor-derived EV capture. RNA in the captured EVs can be recovered for downstream molecular analyses by reverse transcription Droplet Digital PCR. We demonstrate that this assay can be applied to monitor the dynamic changes of ROS1 rearrangements and epidermal growth factor receptor T790M mutations that predict treatment responses and disease progression in non-small cell lung cancer patients.

The effect of EDTA with and without ultrasonics on removal of the smear layer.

This study evaluated in vitro effectiveness of 17% EDTA with and without ultrasonics on smear layer removal. One hundred and five extracted premolars randomly divided into seven groups were instrumented with different final irrigating protocols: group A (Sal3US), saline for 3 minutes with ultrasonics; groups B (Na3) and C (Na3US), 1% sodium hypochlorite for 3 minutes without and with ultrasonics, respectively; groups D (ED3) and E (ED3US), 17% EDTA for 3 minutes without and with ultrasonics, respectively; and groups F (ED1) and G (ED1US), 17% EDTA for 1 minute without and with ultrasonics, respectively. Specimens were examined under scanning electron microscope and scored for smear layer and debris removal. Statistical analysis showed that groups with EDTA and ultrasonic irrigation, groups E (ED3US) and G (ED1US), had significantly more specimens with complete smear layer and debris removal. There was no significant difference between groups E (ED3US) and G (ED1US). A 1-minute application of combined use of EDTA and ultrasonics is efficient for smear layer and debris removal in the apical region of the root canal.