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UnlabelledHow the integrity of laminar structures in the postnatal brain is maintained impacts neuronal functions. Ndel1, the mammalian homolog of NuDE from the filamentous fungus Aspergillus nidulans, is an atypical microtubule (MT)-associated protein that was initially investigated in the contexts of neurogenesis and neuronal migration. Constitutive knock-out mice for Ndel1 are embryonic lethal, thereby necessitating the creation a conditional knock-out to probe the roles of Ndel1 in postnatal brains. Here we report that CA1 pyramidal neurons from mice postnatally lacking Ndel1 (Ndel1 conditional knock-out) exhibit fragmented MTs, dendritic/synaptic pathologies, are intrinsically hyperexcitable and undergo dispersion independently of neuronal migration defect. Secondary to the pyramidal cell changes is the decreased inhibitory drive onto pyramidal cells from interneurons. Levels of the glycoprotein Reelin that regulates MTs, neuronal plasticity, and cell compaction are significantly reduced in hippocampus of mutant mice. Strikingly, a single injection of Reelin into the hippocampus of Ndel1 conditional knock-out mice ameliorates ultrastructural, cellular, morphological, and anatomical CA1 defects. Thus, Ndel1 and Reelin contribute to maintain postnatal CA1 integrity.Significance statementThe significance of this study rests in the elucidation of a role for Nde1l and Reelin in postnatal CA1 integrity using a new conditional knock-out mouse model for the cytoskeletal protein Ndel1, one that circumvents the defects associated with neuronal migration and embryonic lethality. Our study serves as a basis for understanding the mechanisms underlying postnatal hippocampal maintenance and function, and the significance of decreased levels of Ndel1 and Reelin observed in patients with neurological disorders.

Lactic acid bacteria (LAB) are recognized as food-grade safe microorganisms and have many beneficial effects. LAB could maintain the host intestinal homeostasis and regulate intestinal microbial community to exert antibacterial effects. In this study, Lactiplantibacillus plantarum (L. plantarum, Lp01) strain isolated from pig intestine was orally administered to C57BL/6 mice, and mice were then infected with Salmonella typhimurium (ATCC14028). The protective effects of L. plantarum were evaluated by monitoring body weight loss, survival rates, bacterial loads in tissue, colon histopathology analysis, and cytokine secretion. 16S rRNA gene sequencing was also utilized to detect the dynamics of the blind gut microbial community in mice. We found that L. plantarum could significantly reduce the body weight loss and improve the survival rates. The survival rate in the L. P-Sty group was up to 67.5%, which was much higher than that in the STY group (25%). Counting of bacterial loads displayed that the colony-forming unit (CFU) of S. typhimurium in the spleen (p < 0.05) and the liver (p < 0.05) from L. P-Sty group both decreased, compared with STY group. Intestinal histopathology showed that it alleviated the intestinal injury caused by Salmonella, inhibited the secretion of pro-inflammatory cytokines, and promoted anti-inflammatory cytokines (p < 0. 01). In addition, L. plantarum also significantly ameliorated the intestinal gut microbiome disturbance caused by Salmonella. It displayed an obvious increase of beneficial bacteria including Lactobacillus and Bacteroidetes and reduction of pathogenic bacteria like Proteobacteria. In conclusion, L. plantarum could regulate microbial community to inhibit Salmonella typhimurium infection. [ABSTRACT FROM AUTHOR]

Background: Facial filler is emerging as a nonsurgical alternative for addressing static asymmetry in facial paralysis (FP). Objectives: To elucidate the patient experience for facial filler and to facilitate preprocedure counseling and education. Materials and Methods: Patients receiving hyaluronic acid filler for FP at a tertiary academic medical center were prospectively recruited. Primary outcomes included patient-reported pain, facial symmetry (on a visual analog scale), and the results of quality-of-life surveys (FACE-Q satisfaction with facial appearance [SFA], FACE-Q psychosocial distress [PSD], Patient Health Questionnaire-9 [PHQ-9], and Euro Quality of Life 5-Dimension [EQ5D]) preprocedure and at 1 and 14 days postprocedure. Results: Twenty patients (90% women, average age 55 ± 11) completed the study. Sites of filler included the cheek, lower lip, nasolabial fold, chin, and temple regions. Patients reported minimal pain at postprocedure days (PPDs) 1 and 14. Patient-perceived symmetry scores improved significantly ( p  < 0.0001), as did FACE-Q SFA and FACE-Q PSD scores ( p  < 0.0001, <0.0001) when comparing preprocedure with PPD 14. Depression, assessed by PHQ-9, and the anxiety/depression domain of EQ5D, decreased after treatment ( p  = 0.016, 0.014) but no change was observed in the other domains of EQ5D. Conclusion: Facial filler for FP can be performed with minimal morbidity (pain, impact on daily routine, and complications) and leads to improvements across multiple psychosocial domains.

Importance: Hypocalcemia is a common complication of total thyroidectomy., Objectives: To identify factors associated with hypocalcemia after total thyroidectomy and to explore the association between hypocalcemia, magnesium disorders, and costs of care., Design, Setting, and Participants: A retrospective cross-sectional analysis was performed using data from the MarketScan Commercial Claim and Encounters database on 126 766 commercially insured patients younger than 65 years undergoing total thyroidectomy between January 1, 2010, and December 31, 2012. Statistical analysis was performed from January 1, 2016, to May 30, 2019., Main Outcomes and Measures: Short- and long-term hypocalcemia and the costs of care were examined using multivariable regression modeling., Results: Among the 126 766 patients in the study (81.6% women; mean age, 46.5 years [range, 18-64 years]), postoperative hypocalcemia was present in 19.1% of patients in the initial 30-day postoperative period and in 4.4% of patients at 1 year. Magnesium disorders were present in 2.1% of patients at the time of surgery. Short- and long-term hypocalcemia were significantly more likely in women (short-term: odds ratio [OR], 1.39 [95% CI, 1.29-1.50]; long-term: OR, 1.69 [95% CI, 1.52-1.89]), those younger than 40 years (short-term: OR for ages 40-64 years, 0.83 [95% CI, 0.78-0.87]; long-term: OR for ages 40-64 years, 0.73 [95% CI, 0.67-0.79]), those with a diagnosis of thyroiditis (short-term: OR, 1.48 [95% CI, 1.16-1.89]; long-term: OR, 1.60 [95% CI, 1.13-2.26]) or cancer (short-term: OR, 1.32 [95% CI, 1.05-1.67]; long-term: OR, 1.17 [95% CI, 0.83-1.63]), vitamin D deficiency (short-term: OR, 1.96 [95% CI, 1.74-2.21]; long-term: OR, 3.72 [95% CI, 3.30-4.18]), concurrent lateral neck dissection (short-term: OR, 1.51 [95% CI, 1.37-1.66]; long-term: OR, 1.95 [95% CI, 1.69-2.26]), concurrent central neck dissection (short-term: OR, 1.15 [95% CI, 1.07-1.24]; long-term: OR, 1.25 [95% CI, 1.12-1.40]), intraoperative parathyroid (short-term: OR, 1.58 [95% CI, 1.46-1.71]; and long-term: OR, 2.05 [95% CI, 1.82-2.31]) or recurrent laryngeal nerve injury (short-term: OR, 1.49 [95% CI, 1.27-1.74]; long-term: OR, 2.04 [95% CI, 1.64-2.54]), and magnesium disorders (short-term: OR, 8.40 [95% CI, 7.21-9.79]; long-term: OR, 25.23 [95% CI, 19.80-32.17]). Compared with the initial postoperative period, the odds of hypocalcemia decreased by 90.0% (OR, 0.10 [95% CI, 0.09-0.11]) at 6 months and 93.0% (OR, 0.07 [95% CI, 0.06-0.08]) at 1 year. After controlling for all other variables, magnesium disorders were associated with the highest odds of short- and long-term postoperative hypocalcemia. Hypocalcemia ($3392) and magnesium disorders ($14 314) were associated with increased mean incremental 1-year costs of care., Conclusions and Relevance: Hypocalcemia is common after total thyroidectomy but resolves in most patients by 1 year. Magnesium disorders are significantly independently associated with short- and long-term hypocalcemia and are associated with greater costs of care. These data suggest a potentially modifiable target to reduce the incidence and cost of long-term hypocalcemia at patient and systemic levels.