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MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2Cheterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the predominantly extrasynaptic (e)NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks, suggesting that treatment of MHS deficits may possibly help other forms of ASD as well.

The article discusses the advantages of using dental operating microscopes as preventive oral care. Topics mentioned include the enhancement of collaboration between hygienists and other clinicians, the importance of improving precision in examining dental structures to identify early signs of diseases, and the evolution of ergonomically-designed dental equipment.

The article highlights the role of guided biofilm therapy in maintaining oral health care. Topics mentioned include some protocols of guided biofilm therapy, the involvement of airflow, perioflow, and piezon, the goal of guided biofilm therapy in changing the experience and perception of patients in dental hygiene services, and the link of guided biofilm therapy with the dental hygiene principles.

The author discusses the sense of community among dental hygienists who have common experiences, challenges, and passion for preventive health care. Topics covered include the dental hygiene profession's push towards innovation and patient care improvement via collaboration, and the value of camaraderie in achieving career happiness and personal fulfillment. Also noted is the profession's alignment with diversity to help address the needs of a diverse patient population.

The article offers information on Curodont Repair Fluoride Plus from vVARDIS.

The article explores the problems caused by the COVID-19 pandemic to dental hygiene education and offers potential solutions to these problems. Topics covered include the challenges brought by the sudden shift to virtual learning, the disadvantages of virtual classes, and the modification to teaching models that academic institutions need to consider to accommodate new learning styles.

The urea cycle disorder drug glycerol phenylbutyrate (Ravicti) is presently one of the most expensive medications in the United States, with annual costs estimated at $800,000 as of 2023. An expedient synthesis of this orphan drug was successfully adapted for the undergraduate organic chemistry laboratory. Activation of 4-phenylbutyric acid with thionyl chloride cleanly affords 4-phenylbutyryl chloride, which is then esterified with glycerol in the presence of N-methylimidazole. Glycerol phenylbutyrate is obtained in high yield and purity following silica gel column chromatography. It is anticipated that this synthesis can be readily implemented in other undergraduate organic chemistry laboratory programs, fostering student interest and engagement by highlighting the relevance of chemistry to the societal issue of drug pricing.

The article examines whether a comprehensive exam is needed by a patient before the hygiene service. Topics discussed include phases of patient care, significance of code of ethics in dentistry, and the importance of collaboration between dentists and hygienists. Also mentioned are state dental practice acts that have provisions or guidelines that emphasize that a comprehensive exam is needed before certain dental procedures can be performed.

Organoids are novel in vitromodels to study intercellular cross talk between the different types of cells in the disease pathophysiology. To better understand the underlying mechanisms driving the progression of primary sclerosing cholangitis (PSC), we developed scaffold-free multicellular three-dimensional cholangiocyte organoids (3D-CHOs) using primary liver cells derived from normal patients and patients with PSC. Human liver samples from healthy donors and patients with PSC were used to isolate primary cholangiocytes [epithelial cell adhesion molecule (EpCam)+/ cytokeratin-19+], liver endothelial cells (CD31+), and hepatic stellate cells (HSCs; CD31−/CD68−/desmin+/vitamin A+). 3D-CHOs were formed using cholangiocytes, HSCs, and liver endothelial cells, and kept viable for up to 1 month. Isolated primary cell lines and 3D-CHOs were further characterized by immunofluorescence, RT-qPCR, and transmission electron microscopy. Transcription profiles for cholangiocytes (SOX9, CFTR, EpCAM, AE, SCT, and SCTR), fibrosis (ACTA2, COL1A1, DESMIN, and TGFβ1), angiogenesis (PECAM, VEGF, CDH5, and vWF), and inflammation (IL-6and TNF-α) confirmed PSC phenotypes of 3D-CHOs. Because cholangiocytes develop a neuroendocrine phenotype and express neuromodulators, confocal immunofluorescence demonstrated that the neurokinin-1 receptor was localized within cytokeratin-19+cholangiocytes and desmin+HSCs. Moreover, 3D-CHOs from patients with PSC confirmed PSC phenotypes with up-regulated neurokinin-1 receptor, tachykinin precursor 1, and down-regulated membrane metalloendopeptidase. Scaffold-free multicellular 3D-CHOs showed superiority as an in vitromodel in mimicking PSC in vivophenotypes compared with two-dimensional cell culture, which can be used in PSC disease-related research.

Although electronic behavioral alerts are placed as an alert flag in the electronic health record to notify staff of previous behavioral and/or violent incidents in emergency departments (EDs), they have the potential to reinforce negative perceptions of patients and contribute to bias. We provide characterization of ED electronic behavioral alerts using electronic health record data across a large, regional health care system.

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and has been associated with a late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.

An experimental AIDS vaccine based on attenuated, recombinant vesicular stomatitis virus (rVSV), when administered by a combination of parenteral and mucosal routes, has proven effective at preventing AIDS in a rhesus macaque model (Rose NF, et al.: Cell 2001;106:539–549). In an effort to determine the optimal route of vaccine administration we evaluated the ability of rVSV-based vaccine vectors expressing HIV-1 Env and SIV Gag proteins, when given either intramuscularly (i.m.) or intranasally (i.n.), to elicit antigen-specific cellular and humoral immune responses, and to protect from a subsequent vaginal challenge with simian–human immunodeficiency virus (SHIV89.6P). Our results demonstrate that macaques vaccinated by the i.n. route developed significantly higher antigen-specific cellular immune responses as determined by MHC class I tetramer staining, IFN-γ ELISPOT, and cytotoxic T cell assays. However, systemic and mucosal humoral immune responses did not vary significantly with the route of vaccine administration. Given the importance of cell-mediated immune responses in slowing AIDS progression, intranasal delivery of a VSV-based AIDS vaccine may be an optimal as well as practical route for vaccination and should be considered in design of clinical trials.

Several letters to the editor are presented related to Christianity which include choices that displease God, the estate of being a childless, and the essay on destructive modern education by Joel Belz.