Notes

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The toxicity of peroxynitrite, ONOO-, is directed by carbon dioxide via the formation of the corresponding adduct, ONOOCO2-. Entity ONOOCO2- is believed to be a highly unstable compound that primarily decomposes to nitrate and carbon dioxide, but it also undergoes fractional homolysis to generate carbonate radical anion, CO3•-, and nitrogen dioxide, NO2•, in a so-called solvent (radical) cage reaction. Recently, Koppenol et al. reviewed their proposal that ONOOCO2- is a relatively long-lived intermediate, arguing that "the solvent cage as proposed is physically not realistic". To further address whether ONOOCO2- could be a long-lived species, bond dissociation enthalpies (BDE) were calculated by the composite reference method (SMD)W1BD. Anion ONOOCO2- can exist in two conformers, s-cis-gauche and s-trans-gauche with predicted gas-phase O-O BDEs of about 10.8 and 9.5 kcal mol-1, respectively. Therefore, both conformers should have very short lifetimes. The (SMD)W1BD method was also used to evaluate the thermodynamic parameters of interest, revealing that the homolytic decomposition of ONOOCO2- is the most reasonable pathway. Moreover, previously reported experimental chemically induced dynamic nuclear polarization data also support the intermediacy of the radical cage and the formation of products CO2 and NO3- at a total yield of about 70%. Because the solvent radical cage concept for the decay of ONOO- in the presence of CO2 is supported by a variety of spectrometric methods as well as by quantum chemical calculations at high levels of theory, it provides strong evidence against the "out-of-cage" construct. For clarification of the nature of the transient UV/vis absorption(s) between 600 and 700 nm, as observed by Koppenol et al., several experimental approaches are suggested.
To identify the rates and types of postoperative complications in patients with and without Graves' disease undergoing total thyroidectomy using the National Surgical Quality Improvement Program (NSQIP) database.

Retrospective cohort study.

All hospitals participating in NSQIP from 2007 to 2017.

Thyroidectomy data were abstracted from the NSQIP database from 2007 to 2017 using related
codes. Exclusion criteria included diagnosis of malignancy and partial thyroidectomy. Patients with a diagnosis of Graves' disease were compared against the control group, which consisted of other nononcologic diagnoses. Statistical analysis including matched pair analysis was performed.

Unmatched data demonstrated that patients with Graves' disease who underwent total thyroidectomy (n = 5495) had a higher rate of readmission (odds ratio [OR], 1.41; 95% CI, 1.16-1.73) and rate of reoperation (OR, 2.29; 95% CI, 1.88-2.79) in comparison to control patients (n = 24,213). They also had a higher rate of postoperative comd to select patients who meet criteria for surgery.
Tetralogy of Fallot is one of the most frequent cyanotic heart diseases in our country, occupying the second place reported by the national health program 2007- 2012 and its prevalence is around 11%. Patients undergoing correction for tetralogy of Fallot are considered patients with a prolonged ischemic time and a high risk of presenting low cardiac output syndrome.

To compare levosimendan with milrinone to prevent low cardiac output syndrome in patients undergoing tetralogy of Fallot correction.

Randomized controlled open, prospective, longitudinal and comparative clinical trial. The sample size consisted of 19 patients, with a 95% confidence level. Group 1 levosimendan 0.1 mcg/kg/min from anesthetic induction. Group 2 conventional management with milrinone 0.5 mcg/kg/min.

When comparing the final measurements, it can be observed that the mean arterial pressure of the intervention group (levosimendan) was statistically significant (p = 0.04), both in the intraoperative measurement and in the final measurement. Genipin supplier When comparing uresis, we found that the intervention group had a greater amount of uresis (p = 0.03). Regarding lactate, both in the intraoperative measurement (p = 0.002) and in the final measurement (p = 0.02), a lower amount was found in the intervention group.

The results in favor of the use of levosimendan were reported, demonstrating the prevention of low cardiac output syndrome.
The results in favor of the use of levosimendan were reported, demonstrating the prevention of low cardiac output syndrome.
Asymptomatic subjects, the lack of diagnostic tests and, in countries like Mexico, the epidemiological surveillance method does not allow to establish the real number of infections in the COVID-19 pandemic. Frontline health personnel, as well as other groups related to priority activities are considered of high risk. We included administrative workers in contact with health personnel in the hospital units of the Mexican Institute for Social Security (IMSS, according to its initials in Spanish).

To identify the seroprevalence of antibodies to SARS-CoV-2 in IMSS' administrative staff who does not treat patients.

76 volunteer participating individuals were incluided; IgG antibodies against the SARS-CoV-2 nucleoprotein were measured. A questionnaire was administered to the participants in order to identify possible risk factors.

76 participants were included (39 men, 51.7%), with a median age of 42 years. 29 out of 76 subjects (38.2%), whose median age was 38 years (range 18-69 years); 15 men (51.7%), and 14 women (48.3%). A higher percentage of positive subjects under 45 years of age (n = 20, 84.2%) was observed than those aged 45 or over (n = 9, 25%), with an OR of 3 (95% CI 1.13-7.96, p = 0.03). No statistically significant difference was found regarding the type of comorbidity.

The prevalence identified shows an important circulation of the virus in the administrative staff.
The prevalence identified shows an important circulation of the virus in the administrative staff.Disrupted liver regeneration following hepatectomy represents an "undruggable" clinical challenge associated with poor patient outcomes. Yes-associated protein (YAP), a transcriptional coactivator that is repressed by the Hippo pathway, is instrumental in liver regeneration. We have previously described an alternative, Hippo-independent mechanism of YAP activation mediated by downregulation of protein tyrosine phosphatase nonreceptor type 11 (PTPN11, also known as SHP2) inhibition. Herein, we examined the effects of YAP activation with a selective SHP1/SHP2 inhibitor, NSC-87877, on liver regeneration in murine partial hepatectomy models. In our studies, NSC-87877 led to accelerated hepatocyte proliferation, improved liver regeneration, and decreased markers of injury following partial hepatectomy. The effects of NSC-87877 were lost in mice with hepatocyte-specific Yap/Taz deletion, and this demonstrated dependence on these molecules for the enhanced regenerative response. Furthermore, administration of NSC-87877 to murine models of nonalcoholic steatohepatitis was associated with improved survival and decreased markers of injury after hepatectomy. Evaluation of transcriptomic changes in the context of NSC-87877 administration revealed reduction in fibrotic signaling and augmentation of cell cycle signaling. Cytoprotective changes included downregulation of Nr4a1, an apoptosis inducer. Collectively, the data suggest that SHP2 inhibition induces a pro-proliferative and cytoprotective enhancement of liver regeneration dependent on YAP.Striated preferentially expressed protein kinase (SPEG), a myosin light chain kinase, is mutated in centronuclear myopathy (CNM) and/or dilated cardiomyopathy. No precise therapies are available for this disorder, and gene replacement therapy is not a feasible option due to the large size of SPEG. We evaluated the potential of dynamin-2 (DNM2) reduction as a potential therapeutic strategy because it has been shown to revert muscle phenotypes in mouse models of CNM caused by MTM1, DNM2, and BIN1 mutations. We determined that SPEG-β interacted with DNM2, and SPEG deficiency caused an increase in DNM2 levels. The DNM2 reduction strategy in Speg-KO mice was associated with an increase in life span, body weight, and motor performance. Additionally, it normalized the distribution of triadic proteins, triad ultrastructure, and triad number and restored phosphatidylinositol-3-phosphate levels in SPEG-deficient skeletal muscles. Although DNM2 reduction rescued the myopathy phenotype, it did not improve cardiac dysfunction, indicating a differential tissue-specific function. Combining DNM2 reduction with other strategies may be needed to target both the cardiac and skeletal defects associated with SPEG deficiency. DNM2 reduction should be explored as a therapeutic strategy against other genetic myopathies (and dystrophies) associated with a high level of DNM2.Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia.The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgaris vAU), and a second, North American, short-read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species-specific transcript mapping and gene annotation revealed good gene-level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions.
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