Tissue-specific roles of mitochondrial unfolded protein response during obesity.

Obesity is a worldwide multifactorial disease caused by an imbalance in energy metabolism, increasing adiposity, weight gain, and promoting related diseases such as diabetes, cardiovascular diseases, neurodegeneration, and cancer. Recent findings have reported that metabolic stress related to obesity induces a mitochondrial stress response called mitochondrial unfolded protein response (UPRmt), a quality control pathway that occurs in a nuclear DNA-mitochondria crosstalk, causing transduction of chaperones and proteases under stress conditions. The duality of UPRmt signaling, with both beneficial and detrimental effects, acts in different contexts depending on the tissue, cell type, and physiological states, affecting the mitochondrial function and efficiency and the metabolism homeostasis during obesity, which remains not fully clarified. Therefore, this review discusses the most recent findings regarding UPRmt signaling during obesity, bringing an overview of UPRmt across different metabolic tissues.

FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation.

Exocrine acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor receptors (FGFR) are essential for early development of multiple organs, including SG. However, the role of FGFR signaling in specific populations later in development and during acinar differentiation are unknown. Here, we use scRNAseq and conditional deletion of murine FGFRs in vivo to identify essential roles for FGFRs in craniofacial, early SG development and progenitor function during duct homeostasis. Importantly, we also discover that FGFR2 via MAPK signaling is critical for seromucous acinar differentiation and secretory gene expression, while FGFR1 is dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activates the FGFR2-dependent seromucous transcriptional program. Here, we propose a model where MEC-derived FGF7 drives seromucous acinar differentiation, providing a rationale for targeting FGFR2 signaling in regenerative therapies to restore acinar function.

The role of targeted temperature management in 30-day hospital readmissions in cardiac arrest survivors: A national population-based study.

Background: Targeted temperature management (TTM) implementation following resuscitation from cardiac arrest is controversial. Although prior studies have shown that TTM improves neurological outcomes and mortality, less is known about the rates or causes of readmission in cardiac arrest survivors within 30 days. We aimed to determine whether the implementation of TTM improves all-cause 30-day unplanned readmission rates in cardiac arrest survivors. Methods: Using the Nationwide Readmissions Database, we identified 353,379 adult cardiac arrest index hospitalizations and discharges using the International Classification of Diseases, 9th and 10th codes. The primary outcome was 30-day all-cause unplanned readmissions following cardiac arrest discharge. Secondary outcomes included 30-day readmission rates and reasons, including impacts on other organ systems. Results: Of 353,379 discharges for cardiac arrest with 30-day readmission, 9,898 (2.80%) received TTM during index hospitalization. TTM implementation was associated with lower 30-day all-cause unplanned readmission rates versus non-recipients (6.30% vs. 9.30%, p < 0.001). During index hospitalization, receiving TTM was also associated with higher rates of AKI (41.12% vs. 37.62%, p < 0.001) and AHF (20.13% vs. 17.30%, p < 0.001). We identified an association between lower rates of 30-day readmission for AKI (18.34% vs. 27.48%, p < 0.05) and trend toward lower AHF readmissions (11.32% vs. 17.97%, p = 0.05) among TTM recipients. Conclusions: Our study highlights a possible negative association between TTM and unplanned 30-day readmission in cardiac arrest survivors, thereby potentially reducing the impact and burden of increased short-term readmission in these patients. Future randomized studies are warranted to optimize TTM use during post-arrest care.

FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation.

Exocrine secretory acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor receptors (FGFR) are essential for early development of multiple organs, including SG. However, the role of FGFR signaling in specific epithelial SG populations later in development and during acinar differentiation are unknown. Here, we predicted FGFR dependence in specific populations using scRNAseq data and conditional mouse models to delete FGFRs in vivo. We identifed essential roles for FGFRs in craniofacial and early SG development, as well as progenitor function during duct homeostasis. Importantly, we discovered that FGFR2b was critical for seromucous and serous acinar cell differentiation and secretory gene expression (Bpifa2 and Lpo) via MAPK signaling, while FGFR1b was dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activated the FGFR2b-dependent seromucous transcriptional program. We propose a model where MEC-derived FGF7 drives seromucous acinar differentiaton, providing a rationale for targeting FGFR2b signaling in regenerative therapies to restore acinar function.

Psychogenic Polydipsia in a Patient With a Clinical Triad.

Psychogenic Polydipsia (PP) is a condition involving excessive fluid intake causing hyponatremia. While the mechanism is unknown, treating arginine vasopressin (AVP) dysregulation with the class of drugs, vaptans, during acute psychotic episodes has been an effective treatment. These patients may present with a triad of acute psychosis, polydipsia, and electrolyte imbalances suggesting a syndrome of inappropriate antidiuretic hormone. Our patient is a 57-year-old female with a past medical history of schizophrenia who presented with seizures due to severe hyponatremia in the context of excessive water consumption and mild delusions regarding her sister. Her episodes of neural dysfunction started after she stopped taking her antipsychotic medications, making a drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) less likely. However, she had a normal urine osmolality raising suspicion of antidiuretic hormone involvement. The mechanism of hyponatremia in the context of polydipsic schizophrenia is not well established. Some evidence suggests that brain changes may cause AVP dysregulation, which can be exacerbated by acute psychotic episodes. Our case report describes a clinical scenario with the clinical triad of acute psychosis, polydipsia, and electrolyte imbalances suggestive of this mechanism.

Atto 465 Derivative Is a Nuclear Stain with Unique Excitation and Emission Spectra Useful for Multiplex Immunofluorescence Histochemistry.

Multiplex immunofluorescence (mIF) is an effective technique for the maximal visualization of multiple target proteins in situ. This powerful tool is mainly limited by the spectral overlap of the currently available synthetic fluorescent dyes. The fluorescence excitation wavelengths ranging between 405 and 488 nm are rarely used in mIF imaging and serve as a logical additional slot for a fluorescent probe. In the present study, we demonstrate that the addition of 2,3,4,5,6-pentafluoroaniline to Atto 465 NHS ester, creating Atto 465-pentafluoroaniline (Atto 465-p), generates a bright nuclear stain in the violet-blue region of the visible spectrum. This allows the 405 nm excitation and emission, classically used for nuclear counterstains, to be used for the detection of another target protein. This increases the flexibility of the mIF panel and, with appropriate staining and microscopy, enables the quantitative analysis of at least six targets in one tissue section. (J Histochem Cytochem XX: XXX-XXX, XXXX).

Salivary ZG16B expression loss follows exocrine gland dysfunction related to oral chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) targets include the oral mucosa and salivary glands after allogeneic hematopoietic stem cell transplant (HSCT). Without incisional biopsy, no diagnostic test exists to confirm oral cGVHD. Consequently, therapy is often withheld until severe manifestations develop. This proteomic study examined saliva and human salivary gland for a biomarker profile at first onset of oral cGVHD prior to initiation of topical steroid therapy. Whole saliva collected at onset of biopsy-proven oral GVHD was assessed using liquid chromatography-coupled tandem mass spectrometry with identification of 569 proteins, of which 77 significantly changed in abundance. ZG16B, a secretory lectin protein, was reduced 2-fold in oral cGVHD saliva (p <0.05), and significantly decreased in salivary gland secretory cells affected by cGVHD. Single-cell RNA-seq analysis of healthy MSG localized ZG16B expression to two discrete acinar cell populations. Reduced ZG16B expression may indicate specific cGVHD activity and possibly general salivary gland dysfunction.

HPV32-related Heck's disease in a chronic graft-versus-host disease patient with long-term successful KTP laser treatment: A rare case report.

We recently identified and treated a rare case of oral focal epithelial hyperplasia (FEH) in an adult patient with chronic graft-vs-host disease. This is the first report linking KTP laser therapy to successful long-term treatment HPV32 FEH.