Genetic interaction between Patched1 and Sox10 in enteric nervous system development

The enteric nervous system (ENS) is derived from neural crest cells (NCCs). Once these NCCs reach the foregut, they are recognized as enteric NCCs(ENCCs) which subsequently colonize the gastrointestinal track. The proliferation, migration and neuronal versusglial differentiation of ENCCs are tightly controlled by multiple signaling pathways and transcription factors. Impaired ENS development may result in various human congenital disorders such as Hirschsprung disease(HSCR). Hedgehog (Hh) signaling is a key element in ENS development. Patched-1 (Ptch1) is a negatively regulated receptor for Hh. Binding to Hh or deletion of Ptch1releases its inhibitory function and activates the Hh signaling cascade. Our group has previously revealedPTCH1as a susceptibility gene for HSCR. In particular, NCC-specific deletionofPtch1in mice led to premature glial differentiation and depletion of proliferative ENCC pool, but the molecular mechanisms are still not very clear. Sox10, a member of SRY-related HMG-box family transcription factor, is implicated in these two processes of ENS development. It prompted us to hypothesis that Ptch1 may interact with Sox10 to control ENCC proliferation and glial lineage differentiation. In this study, I generated compound mouse mutants to i) investigate the potential functional interaction between Ptch1 and Sox10 in ENCC differentiation and proliferation, and ii) examine the link between the perturbed NCC differentiation and aberrant proliferation of ENS progenitors, to determine how interruption of these processes may lead to intestinal hypoganglionosis of Ptch1mutants. I found that persistent Hh activation through deletionofPtch1causes a differentiation bias toward glial lineage. Ptch1mutants consistently contained more Sox10expressing glial committed ENCCs and exhibited premature gliogenesis. To test whether elevated Sox10expressing cells contribute in the ENS phenotypes of Ptch1 mutants, 〖Sox10〗^(NGFP/+); Ptch1 compound mutants were generated, where one copy of Sox10 was deleted. Immunohistochemical analysis revealed that 〖Sox10〗^(NGFP/+) mutants exhibitpremature neurogenesis as reported previously, while the proliferation and glial differentiation of ENCCs are not affected.On the other hand, in the compound mutants, heterozygous deletion of Sox10 markedly rescued premature gliogenesis caused by deletion of Ptch1. These data suggest that Ptch1 regulates gliogenesis of ENCCs through maintaining Sox10 expression. To delineate how premature glial differentiation of ENCCs leads to hypoganglionosis, I further investigated whether the differentiation defect perturbs the proliferation capacities of ENCCs. Correction of glial differentiation defect in Ptch1 mutant by heterogeneous deletion of Sox10 could significantly restore the pool size of the proliferative ENCCs of the compound mutant. This observation implies that proliferation defects in Ptch1 mutant represents a secondary consequence of premature gliogenesis, highlighting the close link between these two developmental processes. In summary, the current study provides evidence that Sox10 works coordinately with Ptch1 to mediate ENS development. Loss of Ptch1 favors glial differentiation and formation ofSox10 expressing glial progenitors, leading to intestinal hypoganglionosis as seen in Hirschsprung’s disease.published_or_final_versionSurgeryMasterMaster of Philosoph

Aggregation and DNA intercalation properties of Di(isocyano) rhodium(I) Diimine complexes

A series of di(isocyano) rhodium(I) diimine complexes has been synthesized and characterized. Owing to the aggregation affinity of these complexes, they were found to exhibit thermochromism. To provide further insights into the aggregation affinity of these complexes, the enthalpy (δH) and entropy (δS) changes of dimerizations of some of the complexes have been determined. In addition, the DNA intercalation properties of these complexes have also been investigated by the DNA unwinding assay

A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

BACKGROUND:Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS:One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS:High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS

Online information seeking by patients with bipolar disorder: results from an international multisite survey: Erratum in Int J Bipolar Disord. 2017 Dec;5(1):18. doi: 10.1186/s40345-017-0082-8

International audienceBackground: Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information.Methods: A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data.Results: 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor.Conclusion: Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites

Erratum to: Online information seeking by patients with bipolar disorder: results from an international multisite survey

Additional file 1. Questionnaire: Information seeking in bipolar disorder

Online Information Seeking by Patients with Bipolar Disorder: Results from an International Multisite Survey

Background Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites

Online information seeking by patients with bipolar disorder: results from an international multisite survey

Abstract Background Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites