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The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI −0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI −0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. PROSPERO CRD42022360433. • Investigates the indirect impact of the pandemic on T2DM patients without infection. • Meta-analysis shows that hemoglobin A1c and body mass index changed insignificantly. • Meta-analysis shows that triglyceride and total cholesterol might worsen. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.02.009 Byline: Claire A. Canning (a)(b), Lily Lee (a), Carol Irving (b)(c), Ivor Mason (b), C. Michael Jones (a) Keywords: Isthmus; Fgf8; Wnt; Maintenance; Rhombomere 1; Chick Abstract: Fibroblast growth factor 8 (FGF8) is expressed at the mid-hindbrain boundary and is an important signal emanating from the isthmic organizer. Wnt1 is expressed in the caudal midbrain juxtaposed to Fgf8 expression and has been implicated in its regulation. In this study, we examine the requirement for continuous Wnt signaling in the maintenance of Fgf8 expression at the isthmus. We demonstrate that prior to HH10, ongoing Wnt signaling is required to maintain the normal pattern of isthmic Fgf8 expression in ovo. Similarly, in explant assays, sustained Wnt signaling is essential to maintain Fgf8 expression in rhombomere 1. The mechanism by which Wnt signaling regulates isthmic Fgf8 expression is likely to be a maintenance response rather than an inductive effect. Finally, we show that Wnt maintenance of Fgf8 expression is dependent upon positive feedback by FGF signaling itself, and that rhombomere 1 does not receive instructive cues from the posterior hindbrain. In summary, these findings establish that a sustained reciprocal interaction between Wnt and FGF signaling is essential to maintain isthmic identity. Author Affiliation: (a) Centre for Molecular Medicine, 61 Biopolis Drive, Singapore 138673, Singapore (b) MRC Centre for Developmental Neurobiology, Kings College London, London, SE1 1UL, UK (c) Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, UK Article History: Received 12 September 2006; Revised 16 January 2007; Accepted 12 February 2007

• Smart grids are modelled as hybrid multiple-to-multiple interdependent graphs. • Sequential node attacks trigger cascading dynamics according to the FDIA strategy. • A new method is introduced to determine the critical vulnerable nodes. • Three node types and their locations affect the topological vulnerabilities. Smart grids integrate power system engineering with information and communication technology to form a complex system. In this study, a framework is proposed to model the smart grid as interdependent complex networks and investigate the topology vulnerabilities subject to targeted attacks. As a serious targeted cyber-physical threat, the load redistribution attack is a type of false data injection attack. Adversaries can intentionally intercept communication traffic flows or cooperatively manipulate data transmitted over the communication network to mislead the control centre to perform incorrect actions, thereby tripping off lines or breakers, and even triggering cascading failures. Based on the intelligent attack mechanism, a new approach is introduced to identify sequential attack targets according to the node importance, which can in turn collapse the entire power system. Based on the particular characteristics of power systems, the components require achieving a power balance through the redistribution or shedding of loads in each attack. Compared to random removal and block removal, the effectiveness of the proposed strategy was validated on the IEEE 39-bus and the actual provincial backbone network. From the analysis of the experimental results, we find that the topology vulnerability is closely related to the critical node types and locations. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome measures (PROMs) are being used increasingly to determine the success of total knee arthroplasty (TKA). Our goal is to investigate whether advanced age is associated with lower PROM scores.Methods: We used our hospital's TKA registry to examine the relationship between age and PROMs in all patients 50-90 years of age who underwent unilateral or simultaneous bilateral primary TKA between 2007 and 2011 with a primary diagnosis of osteoarthritis. All 5 domains of the Knee Injury and Arthritis Outcomes Score (KOOS) and the Lower Extremity Activity Scale (LEAS) at baseline, 2 years, and 5 years were collected. The association between age and PROM score was assessed by piecewise linear regression using generalized estimating equations, adjusting for demographics, comorbidity, and baseline score.Results: Significant nonlinear relationships among age, KOOS subdomains, and LEAS were found. The placement of the age spline knot was at 70 years for KOOS Symptom and 68 years for KOOS Pain, KOOS Activities of Daily Living (ADL), and LEAS. The KOOS Symptom domain showed a significant worsening between 2-year and 5-year follow-up (P < .05) as patients got older.Conclusion: We found an age-related decline in KOOS Pain, KOOS Symptom, KOOS ADL, and LEAS scores. The best fitting spline knots were at 68 (KOOS Pain, KOOS ADL, and LEAS) and 70 years (KOOS Symptoms), respectively. This demonstrates that there is a critical age at which functional decline begins regardless of the quality of the TKA surgery. Our findings will help surgeons accurately guide patient expectations after TKA based on age.Level Of Evidence: Level II, prognostic study. [ABSTRACT FROM AUTHOR]

Abstract: 2-(2-Chloro-6-fluorophenyl)acetamides having 2,2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (K i =0.9–33.9nM). 2-(5-Chloro-pyridin-2-yl)-2,2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (K i =0.7nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced the affinity for thrombin significantly. The aminopyridine P1s also provided an increase in potency. [Copyright &y& Elsevier]

Abstract: Venous thromboembolism (VTE) continues to be one of the most important, and highly controversial, topics in orthopaedics. While many surgeons have discussed the incidence and treatment of this potentially life-threatening complication, little has been published about the clinical outcomes of patients who receive treatment and recover from these conditions. We evaluated the clinical outcomes of patients who suffered non-fatal VTE and compared them to a matched cohort with no complications after total knee arthroplasty using our institution’s joint arthroplasty registry. At two years, the patient-reported clinical outcomes were equivalent between the groups. While VTE remains an important consideration in total knee arthroplasty, it is helpful for surgeons to know that patient outcomes are not negatively affected after appropriate treatment of these complications. [Copyright &y& Elsevier]

A fully functional model of hair reconstitution remains elusive because of the complexity of cellular organization and the number of molecular interactions that must be approximated. In this issue, Havlickova et al. (2009) report a significant contribution to hair engineering with their human folliculoid microsphere assay.Journal of Investigative Dermatology (2009) 129, 815–817. doi:10.1038/jid.2008.434 [ABSTRACT FROM AUTHOR]

Highlights: [•] Mannosylation has strong anti-amyloidogenic effect as GalNAc glycosylation. [•] Galactosylation retards the amyloidogenesis of the prion peptide. [•] Peptide modification might be able to affect the resulting amyloid structure. [ABSTRACT FROM AUTHOR]

Summary: The prosurvival protein BCL-2 is frequently overexpressed in estrogen receptor (ER)-positive breast cancer. We have generated ER-positive primary breast tumor xenografts that recapitulate the primary tumors and demonstrate that the BH3 mimetic ABT-737 markedly improves tumor response to the antiestrogen tamoxifen. Despite abundant BCL-XL expression, similar efficacy was observed with the BCL-2 selective inhibitor ABT-199, revealing that BCL-2 is a crucial target. Unexpectedly, BH3 mimetics were found to counteract the side effect of tamoxifen-induced endometrial hyperplasia. Moreover, BH3 mimetics synergized with phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors in eliciting apoptosis. Importantly, these two classes of inhibitor further enhanced tumor response in combination therapy with tamoxifen. Collectively, our findings provide a rationale for the clinical evaluation of BH3 mimetics in therapy for breast cancer. [Copyright &y& Elsevier]

Abstract: 2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14, which is a potent thrombin inhibitor (K i =1.2nM) that exhibits robust efficacy in canine anticoagulation and thrombosis models upon oral administration. [Copyright &y& Elsevier]

Introduction: Because of the rapidly increasing use of electronic cigarettes (e-cigarettes), this study aimed to investigate the individual characteristics and state-level prevalence of U.S. adults who have switched to e-cigarettes from traditional cigarettes.Methods: Data from the 2012-2013 and 2013-2014 National Adult Tobacco Surveys were analyzed in 2016. Relative percent change in switching was estimated, and the state-specific prevalence of adults who switched to e-cigarettes from traditional cigarettes was calculated and mapped. Multivariate logistic regression was conducted to examine how switching varied by sociodemographic subgroups and region.Results: Overall, the number of individuals who switched from traditional cigarettes to e-cigarettes increased by approximately 100% over the 1-year interval. Significant increases were found among a number of sociodemographics and regions. Multivariate logistic regression analyses showed that young adults and those living in the South and West were more likely to switch to e-cigarettes, compared to former smokers who did not switch. Compared with current dual users, those with higher education and those who were not single were more likely to switch to e-cigarettes. The state with the highest prevalence of switching was New Mexico (7.3%), whereas Connecticut had the lowest prevalence (0.8 %) among former smokers.Conclusions: There is an increase in the progression from traditional cigarette use to e-cigarette use. Further research is warranted to determine whether this change continues and facilitates cigarette smoking cessation as a possible public health benefit and opportunity to save lives rather than constitutes a potential threat to public health. [ABSTRACT FROM AUTHOR]

Background: There is considerable geographic variation in gestational diabetes mellitus (GDM) rates. We used data from two Canadian provinces, British Columbia (BC) and Alberta (AB), to determine the impact of ethnicity on GDM prevalence and neonatal outcomes.Research Design and Methods: All deliveries between 04/01/2004 and 03/31/2010 in AB (n=249,796) and BC (n=248,217) were analyzed. We calculated GDM prevalence among Chinese, South-Asian, and the general population (predominantly Caucasian) women.Results: Overall GDM prevalence was 4.8% (n=12,036) in AB and 7.2% (n=17,912) in BC. In both provinces, the prevalence of GDM was significantly higher in Chinese (AB:11%; BC:13.5%) and South Asian women (AB:8.4%;BC:13.9%) compared to the general population (AB:4.2%; BC: 5.8%). Chinese women were significantly older (AB:32.7; BC:33.0years) compared to the general population (AB:29.1; BC:30.1years). The odds of GDM relative to the general-population were 2-fold higher for South Asians in both provinces and almost 3-fold higher for Chinese in BC. Among GDM cases, compared to the general population, Chinese and South Asian infants were less likely to be LGA, more likely to be SGA, and had similar neonatal mortality rates.Conclusions: Compared to the general population, GDM prevalence is higher in Chinese and South Asian Canadians. Increased maternal age is a major contributor to higher prevalence of GDM in Chinese women. GDM rates were higher in both ethnic and general population women in BC compared to AB, suggesting that in addition to differences in ethnic distribution, differences in diagnostic practices are likely contributing to observed geographic differences in GDM prevalence. [ABSTRACT FROM AUTHOR]

The increasing frequency and duration of extreme heat events prompts questions regarding mitigation proposals and evaluation of current strategies such as cooling centers. Cooling centers may be formally designated or informally used spaces such as indoor shopping centers that the public use as a refuge from heat. Smartphone location data show how a sample of the population moves during the day, what behavioral adjustments they apply in response to heat events, if cooling centers are being used, what factors correlate with use, and whether centers are serving vulnerable populations. We compared spatial patterns of smartphone locations in Los Angeles County between paired extreme heat days and control days (n = 12) in summer 2017. Cooling centers were used 1.1–1.7 times longer during heat events, depending on type, with formal cooling centers used longer. Informal centers, however, were used more (90% of visits). Distance to nearest public transit stop was inversely related to the number of center visits. Vulnerable communities, as measured by the Social Vulnerability Index (SoVI), used centers located in neighborhoods with higher vulnerability scores more. Use of smartphone data to assess activity space of individuals has substantial potential for evaluating mitigation strategies in the face of increasing extreme heat events. • Mobile phone users' activity space data provides an assessment of cooling center use as a heat mitigation strategy. • Comparison of data from hot versus control days shows longer visits in cooling centers of Los Angeles County on hot days. • Cooling center visitors are from neighborhoods with higher proportions of elderly, Asian, and Hispanic residents. • Informal commercial spaces like shopping centers are used more frequently as a heat refuge than formal cooling centers. • Residents of vulnerable neighborhoods visit centers more on hot days, but their visits drop as their distance increases. [ABSTRACT FROM AUTHOR]

Nucleotide excision repair is a versatile repair pathway that counteracts the deleterious effects of various DNA lesions. In nucleotide excision repair, there is a transcription-coupled repair (TCR) pathway that focuses on DNA damage that blocks RNA polymerase IIo in transcription elongation. XAB2 (XPA- binding protein 2), containing tetratricopeptide repeats, has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A protein (XPA). Moreover, XAB2 has been shown to interact with Cockayne syndrome group A and B proteins (CSA and CSB) and RNA polymerase II, as well as XPA, and is involved in TCR and transcription. Here we purified XAB2 as a multimeric protein complex consisting of hAquarius, XAB2, hPRP19, CCDC16, hISY1, and PPIE, which are involved in pre-mRNA splicing. Knockdown of XAB2 with small interfering RNA in HeLa cells resulted in a hypersensitivity to killing by UV light and a decreased recovery of RNA synthesis after UV irradiation and regular RNA synthesis. Enhanced interaction of XAB2 with RNA polymerase IIo or XPA was observed in cells treated with DNA-damaging agents, indicating DNA damage-responsive activity of the XAB2 complex. These results indicated that the XAB2 complex is a multifunctional factor involved in pre-mRNA splicing, transcription, and TCR. [ABSTRACT FROM AUTHOR]