Apps may be an effective component to help control HbA and could be considered as an adjuvant intervention to the standard self-management for patients with type 2 diabetes. Given the reported clinical effect, access, and nominal cost of this technology, it is likely to be effective at the population level. The functionality and use of this technology need to be standardized, but policy and guidance are anticipated to improve diabetes self-management care.

A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed "susceptible exposed infectious recovered" (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6-18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of

In this study we report on the clinical and autoimmune characteristics of severe and critical novel coronavirus pneumonia caused by severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). The clinical, autoimmune, and laboratory characteristics of 21 patients who had laboratory-confirmed severe and critical cases of coronavirus disease 2019 (COVID-19) from the intensive care unit of the Huangshi Central Hospital, Hubei Province, China, were investigated. A total of 21 patients (13 men and 8 women), including 8 (38.1%) severe cases and 13 (61.9%) critical cases, were enrolled. Cough (90.5%) and fever (81.0%) were the dominant symptoms, and most patients (76.2%) had at least one coexisting disorder on admission. The most common characteristics on chest computed tomography were ground-glass opacity (100%) and bilateral patchy shadowing (76.2%). The most common findings on laboratory measurement were lymphocytopenia (85.7%) and elevated levels of C-reactive protein (94.7%) and interleukin-6 (89.5%). The prevalence of anti-52 kDa SSA/Ro antibody, anti-60 kDa SSA/Ro antibody, and antinuclear antibody was 20%, 25%, and 50%, respectively. We also retrospectively analyzed the clinical and laboratory data from 21 severe and critical cases of COVID-19. Autoimmune phenomena exist in COVID-19 subjects, and the present results provide the rationale for a strategy of preventing immune dysfunction and optimal immunosuppressive therapy.

The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease HdhQ111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.HdhQ111) than on a 129 background (129.HdhQ111). Linkage mapping in (B6x129).HdhQ111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.HdhQ111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. HdhQ111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1–MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2–MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions.

SummaryBackgroundThe age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.Methods512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.FindingsDuring a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.InterpretationAmong adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.FundingUK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.

Expansion of CAG/CTG trinucleotide repeats is associated with certain familial neurological disorders, including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism contributes to their expansion. However, the molecular mechanism(s) by which cells remove CAG/CTG hairpins remain unknown. Here, we demonstrate that human cell extracts can catalyze error-free repair of CAG/CTG hairpins in a nick-directed manner. The repair system specifically targets CAG/CTG tracts for incisions in the nicked DNA strand, followed by DNA resynthesis using the continuous strand as a template, thereby ensuring CAG/CTG stability. PCNA is required for the incision step of the hairpin removal, which utilizes distinct endonuclease activities for individual CAG/CTG hairpins depending on their strand locations and/or secondary structures. The implication of these data for understanding the etiology of neurological diseases and trinucleotide repeat instability is discussed.

We conducted a systematic review with meta-analysis of randomized controlled trials that evaluated the effect of diabetes mobile phone applications. A total of 1550 participants from 21 studies were included. For type 1 diabetes, a significant 0.49% reduction in HbA1c was seen (95% CI, 0.04-0.94; I = 84%), with unexplained heterogeneity and a low GRADE of evidence. For type 2 diabetes, using diabetes apps was associated with a mean reduction of 0.57% (95% CI, 0.32-0.82; I = 77%). The results had severe heterogeneity that was explained by the frequency of HCP feedback. In studies with no HCP feedback, low frequency and high frequency HCP feedback, the mean reduction is 0.24% (95% CI, 0.02-0.49; I = 0%), 0.33% (95% CI, 0.07-0.59; I = 47%) and 1.12% (95% CI, 0.91-1.32; I = 0%), respectively, with a high GRADE of evidence. There is evidence that diabetes apps improve glycaemic control in type 1 diabetes patients. A reduction of 0.57% in HbA1c was found in type 2 diabetes patients. However, HCP functionality is important to achieve clinical effectiveness. Future studies are needed to explore the cost-effectiveness of diabetes apps and the optimal intensity of HCP feedback.

Antibiotics are widely used to monitor signalling cascades within a plant cell, for example between the nucleus and chloroplasts, and to study the function of the photosynthetic machinery. In the present study, we attempted to test various antibiotics with respect to their expected modes of function and also to monitor their possible side effects on metabolic processes in mature leaves of pea (Pisum sativum L.). Streptomycin, despite its reported prokaryotic nature, prevented translation not only in the chloroplast, but also in the cytosol. Application of puromycin, an inhibitor of protein synthesis in both the pro- and eukaryotes, resulted in severe photoinhibition of photosystem II upon illumination, yet had no effect on plastid translation, thus implying a severe side effect on plastid metabolism. Prokaryotic-type translation inhibitors lincomycin, spectinomycin and erythromycin blocked translation in the chloroplast without any direct effects on cytoplasmic protein synthesis. More detailed studies with lincomycin, however, revealed a strong modulation of the expression of nuclear-encoded genes by slowing down the transcription rate of photosynthesis-related Lhcb and RbcS genes, and furthermore, lincomycin clearly decreased the phosphorylation level of the LHCII proteins.