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While animal bodies are typically bilaterally symmetric on the outside, the internal organs nearly always show an invariant left-right (LR) asymmetry. In comparison, snails are both internally and externally LR asymmetric, outwardly obvious in the shell coiling direction, or chirality. Although some species of snail are naturally variable for chirality, sinistral individuals occur very rarely in most species. The developmental and genetic basis of these rare mirror-imaged individuals remains mysterious. To resolve this issue, the finding of a 'one in a million' sinistral garden snail called 'Jeremy' was used to recruit citizen scientists to find further sinistral snails. These snails were then bred together to understand whether their occurrence is due an inherited condition. The combined evidence shows that rare sinistral garden snails are not usually produced due to a major effect maternal Mendelian locus. Instead, they are likely mainly produced by a developmental accident. This finding has relevance to understanding the common factors that define cellular and organismal LR asymmetry, and the origin of rare reversed individuals in other animal groups that exhibit nearly invariant LR asymmetry.Breastfeeding behaviours can significantly change mothers' physiological and psychological states. The hormone oxytocin may mediate breastfeeding and mothers' emotion recognition. This study examined the effects of endogenous oxytocin fluctuation via breastfeeding on emotion recognition in 51 primiparous mothers. Saliva oxytocin was assessed before and after the manipulation (breastfeeding or holding an infant), and emotion recognition tasks were conducted. Among mothers who breastfed daily, mothers with more increased levels of oxytocin after breastfeeding showed more reduced negative recognition and enhanced positive recognition of adult facial expressions. These oxytocin functions accompanying breastfeeding may support continued nurturing behaviours and also affect the general social cognition of other adults beyond any specific effect on infants.Annual influenza epidemics are associated with high morbidity and mortality worldwide, with vaccinations being the main preventive intervention; however, the compliance rate of health care employees remains low. Study aims were to examine vaccination rates among physicians and nurses in surgical and medicine wards, compare between medium and large tertiary hospitals, and identify factors associated with increased vaccination rates. Structured questionnaires were distributed. A total of 238/339 (70.2%) were vaccinated. In multivariate analysis, respiratory illness during precedent winter (odds ratio [OR] 3.146, P = .007), working in a medium hospital (OR 2.4, P = .003), and an attending resident with an infectious diseases subspecialty (OR 20.473, P = .007) were associated with a higher vaccination rate. Institutional email or portal messages were associated with decreased vaccination rates (OR = 0.259, P = .007). The leading reason for vaccination was "to stay healthy" (73.5%). Recruiting experts in the field, providing up-to-date information, and increasing management's involvement could encourage vaccination among health care employees.In this report, we describe two patients with systemic lupus erythematosus (SLE) who manifested with posterior segment flare-up approximately three months after cessation of hydroxychloroquine (HCQ). They were stable systemically with no history of hypertension or nephropathy at the time of referral. Our first patient presented with bilateral retinal vein occlusion, while evidence of choroidal involvement such as vascular leakage and wedge-shaped filling delay was present in indocyanine green angiography of both patients. HCQ is well known to have a role in the treatment of SLE for its immunomodulatory and antithrombotic effects. Although reports of systemic flare-up of SLE following HCQ cessation exist in the literature, this is the first report of ocular flare-up in such settings.Objective Rituximab (RTX) has important usage in rheumatoid arthritis and vasculitis. There remains a need for more, better, and safer treatments for patients with lupus nephritis (LN). RTX has been trialed in such patients without definitive conclusions about its effectiveness. As a role for RTX has not been clearly established for LN, we carried out a systematic review and analysis. Methods We identified 31 studies of RTX for class I-VI LN, and assessed complete renal response (CRR) and partial renal response (PRR) using criteria including serum creatinine, proteinuria, and urinary sediment. Due to differences in the pediatric presentation of the disease, studies focusing on pediatric patients were excluded. Results One randomized controlled trial (RCT) showed superiority of RTX+cyclophosphamide (CYC) versus CYC alone (64% vs. 21% CRR and 19% vs. 36% PRR). Six prospective and retrospective studies utilizing RTX monotherapy found 66% CRR or PRR in all patients. Eleven studies that investigated RTX in combinabelimumab, CYC, and MMF groups, with pulse-dose steroids during induction followed by maintenance steroids and MMF. The CRR and PRR would be assessed at 12 and 24 months. This or a similar study might clarify RTX's role in the treatment of LN.Background There are no data on the influence of disease severity and cardiac autonomic tone on ventricular repolarization and dispersion in 24-hour Holter monitoring in systemic lupus erythematosus (SLE). Methods Consecutive 92 SLE and 51 healthy subjects were studied. Degrasyn The standard 12-lead electrocardiography (ECG), Holter monitoring with heart rate turbulence (HRT) and QT, Tp-e and Tp-e/QT ratio assessment (including corrected values) were performed. Subjects with conditions causing repolarization abnormalities or insufficient number of beats suitable for QT evaluation were excluded (17 SLE and 8 controls). Results Finally, 75 SLE and 43 sex- and age-matched controls were included to the study. In SLE patients, the median disease severity score (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)) was 3.0. The mean values of QTc, cTp-e and cTp-e/QTc were significantly higher in SLE patients than in controls. QTc ≥ 460 ms was observed in 18.7% of patients using standard ECG and in 58.7% using Holter monitoring. With Holter monitoring, patients with SLICC/ACR-DI >3.0 presented longer QTc than those with SLICC/ACR-DI ≤3.0 (418±15 vs. 409 ± 16, p = 0.04), while cTp-e and cTp-e/QTc values were similar. Patients with abnormal HRT presented longer cTp-e and higher cTp-e/QTc than those with normal HRT (92 ± 52 vs. 71 ± 16 ms, p = 0.04; 0.244 ± 0.126 vs. 0.187 ± 0.035, p = 0.03), while QTc values were similar. No differences in QT and Tp-e parameters were observed according to disease duration. Conclusion In SLE patients, Holter monitoring revealed QTc prolongation more frequently than standard ECG. Longer QTc values were observed in patients with more advanced disease, while increased cTp-e and cTp-e/QTc were related to cardiac autonomic dysfunction expressed by abnormal HRT.Diacylglycerol kinase (DGK) plays a pivotal role in intracellular signaling pathways in mammals. Activated G protein-coupled receptor activates phospholipase C (PLC) through heterotrimeric G protein, following which PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP3). DGK catalyzes DG phosphorylation to produce phosphatidic acid. DG and phosphatidic acid function as second messengers and their intracellular concentrations are regulated by DGK; therefore, DGK plays an important role in regulating many biological processes. There are ten DGK isozymes, of which DGKη is classified as a type II DGK. Reports have shown that DGKη is associated with several diseases; for example, it is highly expressed in the hippocampus and cerebellum and is a key element in bipolar disorder. Although a DGKη-specific monoclonal antibody (mAb) is necessary to reveal the association between the expression of DGKη and diseases, an anti-DGKη mAb for immunohistochemistry has not yet been established. In this study, we established a specific anti-human DGKη (hDGKη) mAb, DhMab-4 (mouse IgG2b, kappa). DhMab-4 strongly stained Purkinje cells of human cerebellum in immunohistochemistry analysis. For epitope mapping of DhMab-4, we produced deletion or point mutants of hDGKη and performed western blotting to determine the binding epitope of DhMab-4. DhMab-4 reacted with dN745 mutant but not with dN750 mutant, indicating that the N-terminus of the DhMab-4 epitope is located between amino acids 745 and 750. More detailed analysis using point mutants demonstrated that five mutants, that is, D747A, P748A, F749A, G750A, and T752A, were not detected by DhMab-4. These results indicate that Asp747, Pro748, Phe749, Gly750, and Thr752 are important for DhMab-4 binding to hDGKη.We describe three children who developed an osteosarcoma after receiving treatment for acute lymphoblastic leukemia, which included an allogeneic bone marrow transplant (BMT). We discuss the therapeutic options. None of the patients responded to conventional chemotherapy, but one patient given regorafenib showed a temporary response. We conclude that osteosarcoma after BMT has an aggressive course and it is worth further investigating multikinase inhibitors in this setting.Mexico recently voted to implement front-of-pack warning labels on food and beverage products deemed high in calories, sugar, saturated fat, trans fat, and sodium, and those containing non-caloric sweeteners. Research shows that warning labels allow consumers to quickly identify healthy and unhealthy products. Supporters claim these labels can help people make healthier decisions and combat growing rates of obesity and diet-related diseases. Warning labels will replace the Guideline Daily Amount (GDA) nutrition labels, which were implemented in 2014 against the guidance of public health leaders who argued the GDA was hard to understand and ineffective at conveying health risks. Conflicting interests between public health, government, and food industry slowed efforts to adopt a new nutrition label. Actions by academia and civil society to change the GDA were met with common strategies used to interfere in public health policies. However, in 2019, several factors came together to create favorable conditions for the approval of warning labels. The new leftist government's public promises to fight corruption fit well with labeling advocates' calls for transparency. Civil society and academia developed a highly coordinated response thanks to international funding, which propelled extensive marketing campaigns around the country and supported research efforts. These actions helped make the topic visible and place it strategically in the political and public agendas. Despite this legislative victory, the opposition has been strong and there are struggles ahead. Only time will reveal how effectively the law is implemented and to what extent it is upheld and defended.The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is a widely used genome-editing tool with great clinical potential. However, its application is limited because of low editing efficiency of some target sequences and off-target effects. As this system contains only the Cas9 protein and a single-guide RNA (sgRNA; engineered from crRNA and tracrRNA), the structure and function of these components should be studied in detail to address the current clinical needs. Consequently, we investigated the structural and sequence features of the core hairpin (the first stem loop of sgRNA) of SpCas9 sgRNA. We showed that the core hairpin structure of sgRNA is essential for SpCas9/sgRNA-mediated DNA cleavage and that the internal loop structure in the core hairpin plays a vital role in target DNA cleavage. We observed that the root stem structure within the core hairpin preferentially forms Watson-Crick base pairs and should be of a specific length to maintain an appropriate spatial conformation for Cas9 binding.
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