Chromatin Laser Imaging Reveals Abnormal Nuclear Changes for Early Cancer Detection

We developed and applied rapid scanning laser-emission microscopy to detect abnormal changes in cell nuclei for early diagnosis of cancer and cancer precursors. Regulation of chromatins is essential for genetic development and normal cell functions, while abnormal nuclear changes may lead to many diseases, in particular, cancer. The capability to detect abnormal changes in apparently normal tissues at a stage earlier than tumor development is critical for cancer prevention. Here we report using LEM to analyze colonic tissues from mice at-risk for colon cancer by detecting prepolyp nuclear abnormality. By imaging the lasing emissions from chromatins, we discovered that, despite the absence of observable lesions, polyps, or tumors under stereoscope, high-fat mice exhibited significantly lower lasing thresholds than low-fat mice. The low lasing threshold is, in fact, very similar to that of adenomas and is caused by abnormal cell proliferation and chromatin deregulation that can potentially lead to cancer. Our findings suggest that conventional methods, such as colonoscopy, may be insufficient to reveal hidden or early tumors under development. We envision that this work will provide new insights into LEM for early tumor detection in clinical diagnosis and fundamental biological and biomedical research of chromatin changes at the biomolecular level of cancer development

Effect of adjunctive ranitidine for antipsychotic-induced weight gain: A systematic review of randomized placebo-controlled trials

This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, nonrandomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m2) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective an

Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability

Predicting the HMA-LMA status in marine sponges by machine learning

The dichotomy between high microbial abundance (HMA) and low microbial abundance (LMA) sponges has been observed in sponge-microbe symbiosis, although the extent of this pattern remains poorly unknown. We characterized the differences between the microbiomes of HMA (n=19) and LMA (n=17) sponges (575 specimens) present in the Sponge Microbiome Project. HMA sponges were associated with richer and more diverse microbiomes than LMA sponges, as indicated by the comparison of alpha diversity metrics. Microbial community structures differed between HMA and LMA sponges considering Operational Taxonomic Units (OTU) abundances and across microbial taxonomic levels, from phylum to species. The largest proportion of microbiome variation was explained by the host identity. Several phyla, classes, and OTUs were found differentially abundant in either group, which were considered “HMA indicators” and “LMA indicators”. Machine learning algorithms (classifiers) were trained to predict the HMA-LMA status of sponges. Among nine different classifiers, higher performances were achieved by Random Forest trained with phylum and class abundances. Random Forest with optimized parameters predicted the HMA-LMA status of additional 135 sponge species (1,232 specimens) without a priori knowledge. These sponges were grouped in four clusters, from which the largest two were composed of species consistently predicted as HMA (n=44) and LMA (n=74). In summary, our analyses shown distinct features of the microbial communities associated with HMA and LMA sponges. The prediction of the HMA-LMA status based on the microbiome profiles of sponges demonstrates the application of machine learning to explore patterns of host-associated microbial communities

Ultra-fast Au(III)-mediated Arylation of Cysteine

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to pM concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleo-tides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to the range of reac-tivities that are largely unmatched by classical organic chemistry tools

Predictors of motivation for type 2 diabetes mellitus self management of patients in primary care in Singapore

Background: Diabetes is among the top 10 causes of death in Singapore, which has the second-highest proportion of diabetics among all developed nations. Diabetic patients’ self-management is often driven by their perceptions about their own chronic condition. This study explored specific aspects of patients’ (1) cognitive appraisal, (2) emotional distress and (3) a motivational measure in relation to their diabetic condition and attitude toward self-management. Methods: Seventy adult participants (41 female and 29 male) with type-2 diabetes were recruited in this cross-sectional study from patients who sought psychological consultation at polyclinics. The questionnaires administered were (1) Brief Illness Perception Questionnaire, (2) Diabetes Distress Scale, (3) Generalised Anxiety Disorder-7, (4) Insomnia Severity Index, (5) Patient Health Questionnaire-9, (6) Readiness-to-Change Ruler and (7) Sheehan Disability Scale. Results: Multiple regression analysis showed that severity of insomnia symptoms (β = -.26 , p < .05), emotional distress of diabetes (β = -.48 , p < .05), interpersonal distress of diabetes (β = -.35 , p < .05), total distress of diabetes (β = .58 , p < .05), and perception of personal control over diabetes (β = .-.30, p < .05) were significantly associated with reported motivation for engaging in diabetes self-management (R2 = .26, F(5, 62) = 4.26, p < 0.01). Conclusion: Insomnia, emotional distress and perception of personal control over diabetes significantly predicted patients’ reported motivation for diabetes self-management. It may be more productive for clinicians to focus their interventions on these particular aspects of diabetic patients’ experience in promoting self-management behaviour. Future studies may involve (1) the measurement of actual self-management behaviour beyond participants’ report of their motivation to engage in such desirable behavior and (2) qualitative approaches for understanding subjective dimensions of “insomnia,” “distress” and “personal control” in relation to diabetes self-management