Pcdh19 mediates olfactory sensory neuron coalescence during postnatal stages and regeneration.

The mouse olfactory system regenerates constantly throughout life. While genes critical for the initial projection of olfactory sensory neurons (OSNs) to the olfactory bulb have been identified, what genes are important for maintaining the olfactory map during regeneration are still unknown. Here we show a mutation in Protocadherin 19 (Pcdh19), a cell adhesion molecule and member of the cadherin superfamily, leads to defects in OSN coalescence during regeneration. Surprisingly, lateral glomeruli were more affected and males in particular showed a more severe phenotype. Single cell analysis unexpectedly showed OSNs expressing the MOR28 odorant receptor could be subdivided into two major clusters. We showed that at least one protocadherin is differentially expressed between OSNs coalescing on the medial and lateral glomeruli. Moreover, females expressed a slightly different complement of genes from males. These features may explain the differential effects of mutating Pcdh19 on medial and lateral glomeruli in males and females.

Clinical Features and Duration of Viral Shedding in Individuals With SARS-CoV-2 Omicron Variant Infection.

We analyzed the duration of infectivity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant by viral culture of respiratory samples collected daily from isolated patients with SARS-CoV-2 infection. The culture positivity rate of the Omicron variant was higher than that of the Delta variant within 8 days after symptom onset.

Polymer Thin Film-Induced Tumor Spheroids Acquire Cancer Stem Cell-like Properties.

: Although cancer stem cells (CSC) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of diverse, patient-derived CSC. Here, we present a functional polymer thin film (PTF) platform that promotes conversion of cancer cells to highly tumorigenic three-dimensional (3D) spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular tumor spheroids within 24 hours with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed a significant increase in the expression of CSC-associated genes and acquired increased drug resistance compared with two-dimensional monolayer-cultured controls. These spheroids also exhibited enhanced xenograft tumor-forming ability and metastatic capacity in nude mice. By enabling the generation of tumorigenic spheroids from diverse cancer cells, the surface platform described here harbors the potential to contribute to CSC-related basic research and drug development. SIGNIFICANCE: A new cell culture technology enables highly tumorigenic 3D spheroids to be easily generated from various cancer cell sources in the common laboratory.

The P-mJOA: A Patient-derived, Self-reported Outcome Instrument for Evaluating Cervical Myelopathy: Comparison with the mJOA.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: The objective of this study is to evaluate and validate a patient-derived version of the modified Japanese Orthopaedic Association (the "P-mJOA") that a patient can complete along with other patient-derived outcome measures. SUMMARY OF BACKGROUND DATA: The modified Japanese Orthopaedic Association (mJOA) is a validated instrument widely used in the assessment of cervical myelopathy; however, it is not a patient-derived outcome. If available and reliable, a patient-derived version of the mJOA (P-mJOA) could facilitate research because the data would be immediately available upon patient completion and also remove any potential physician bias. Currently, there is no patient-derived myelopathy survey with the widespread acceptance of the mJOA. METHODS: The P-mJOA was created by very slightly modifying the verbiage of the mJOA to make it possible for a patient to complete the instrument while maintaining the questionnaire's core structure. A total of 100 consecutive consenting patients with cervical myelopathy were enrolled. After the patient completed the P-mJOA, the mJOA was scored by a physician blinded to the P-mJOA result. RESULTS: The P-mJOA and the mJOA had identical mean scores of 14.7 (mean difference±SD: 0.0±1.5; P=0.89). Several measures of reliability demonstrated agreement between the 2 surveys, including strong agreement with the intraclass correlation coefficient and Spearman ρ (both 0.83) and moderate to substantial agreement with weighted κ values (0.55 to 0.66). In addition, 67% of patients preferred to fill out the P-mJOA themselves, suggesting low patient burden. CONCLUSIONS: The P-mJOA provided identical mean scores to the mJOA in assessing myelopathy with moderate to strong agreement. Comprised of the same 4 questions as the mJOA but slightly reworded for patient comprehension, the P-mJOA also demonstrated low patient burden in completing the survey. We believe the P-mJOA is a promising tool in cervical myelopathy research with the benefits of a patient-derived outcome measure and low patient burden. LEVEL OF EVIDENCE: Level II.

Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density.

Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg(-1), higher than that of conventional tubular sodium-nickel chloride batteries (280 °C), is obtained for planar sodium-nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.

Liquid-metal electrode to enable ultra-low temperature sodium-beta alumina batteries for renewable energy storage.

Commercial sodium-sulphur or sodium-metal halide batteries typically need an operating temperature of 300-350 °C, and one of the reasons is poor wettability of liquid sodium on the surface of beta alumina. Here we report an alloying strategy that can markedly improve the wetting, which allows the batteries to be operated at much lower temperatures. Our combined experimental and computational studies suggest that addition of caesium to sodium can markedly enhance the wettability. Single cells with Na-Cs alloy anodes exhibit great improvement in cycling life over those with pure sodium anodes at 175 and 150 °C. The cells show good performance even at as low as 95 °C. These results demonstrate that sodium-beta alumina batteries can be operated at much lower temperatures with successfully solving the wetting issue. This work also suggests a strategy to use liquid metals in advanced batteries that can avoid the intrinsic safety issues associated with dendrite formation.

Gene regulation by glucocorticoid in ENaC-mediated Na⁺ transport by middle ear epithelial cells.

OBJECTIVES/HYPOTHESIS: The epithelial sodium channel (ENaC) is a Na(+) transport channel located in the apical membrane of the human middle ear epithelium. Although ENaC-mediated sodium transport has been reported to be upregulated by dexamethasone in human middle ear epithelium, there has been no study of the downstream pathways for increased ENaC expression mediated by glucocorticoids in this tissue. We investigated the effect of dexamethasone on the expression of ENaC and glucocorticoid regulatory genes for ENaC expression in human middle ear epithelial cells (HMEECs). STUDY DESIGN: In vitro investigation. METHODS: Real-time RT-PCR and Western blot analysis were used to determine the expression level of ENaC and its regulatory genes in HMEECs. RESULTS: The transcript and protein expression of the α-, ß-, and γ-ENaC subunits were all upregulated by dexamethasone (100 nM) in HMEECs. Dexamethasone treatment also increased the transcript expression of serum/glucocorticoid-regulated kinase1 (SGK1) and neural precursor cell-expressed developmentally downregulated (Nedd) 4-2, and decreased the transcript expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). ENaC transcript expression was not changed after mifepristone (a glucocorticoid antagonist, 100 nM) + dexamethasone treatment when compared to the control, but increased after spironolactone (a mineralocorticoid antagonist, 100 nM) + dexamethasone treatment. CONCLUSIONS: These findings indicate that dexamethasone increases the transcript and protein expression of the α-, ß-, and γ-ENaC subunits via the GR-SGK1-Nedd4-2 pathway and provides insight into the molecular mechanism of the increased sodium transport mediated by ENaC with steroid treatment in HMEECs. LEVEL OF EVIDENCE: N/A.

Prevalence and management of pain by different age groups of Korean cancer patients.

The aims of this study were to evaluate the differences in cancer prevalence and pain management between young and elderly patients. The patients were grouped into 3 groups. The prevalence of cancer pain was 50.0% in those younger than 65 years, 55.9% in those aged between 65 and 75, and 58.3% in those older than 75 years. The prevalence of cancer pain was higher for patients in advanced stages and with poor performance status. Using logistic regression analysis, we found that performance status has a significant correlation with cancer pain. Severe cancer pain occurred in 8.0% of the patient and was most prevalent in the advanced stage. Side effects of analgesics were observed in 24.5%. Cancer pain correlates with performance status and cancer stage but not significantly with age.

Curcuminoids in neurodegenerative diseases.

Neurodegeneration is a term used to describe progressive deterioration of structure and/or function of neurons that affects different parts of the central nervous system and leads to eventual death. Neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Down's syndrome (DS), multiple sclerosis (MS), glaucoma, age-related macular degeneration (AMD), and diabetic encephalopathy (DE). Although the initial events that trigger these disorders may be different from each other, they share similar biochemical reactions that lead to neurodegeneration. Curcuminoids, polyphenol compounds from turmeric (Curcuma longa), possess diverse biological properties that modulate debilitating biochemical processes involved in AD that include attenuation of mitochondrial dysfunction-induced oxidative stress and inflammatory responses to inflammatory cytokines, COX-2, and iNOS. Curcuminoids also bind to ß-amyloid (Aß) plaques to inhibit amyloid accumulation and aggregation in the brain, in addition to inhibiting the toxic Aß oligomer formation and oligomer-dependent Aß toxicity. These properties can be further elaborated to DS, glaucoma and AMD. Curcuminoids also prevent α-synuclein aggregation in PD; attenuate ROS-induced COX-2 expression in ALS; ameliorate the symptoms of MS, DE and traumatic brain injury, in addition to neurodamages caused by heavy metal poisoning. These results demonstrate curcuminoids may be potentially effective therapeutic means to treat neurodegenerative diseases. A bulk of patents discloses methods to improve bioavailability of curcuminoids for therapeutic development. This review provides a comprehensive description on the current progress on curcuminoids against neurodegenerative diseases.

Peri-implant soft tissue level secondary to a connective tissue graft in conjunction with immediate implant placement: a 2-year follow-up report of 11 consecutive cases.

The purpose of this case series was to evaluate secondary soft tissue level changes of a single-stage surgical protocol combining immediate implant placement and connective tissue grafting in maxillary incisors associated with gingival recession defects. Ten patients underwent the proposed combined treatment consisting of 11 single-tooth implant restorations. Peri-implant soft tissue level and the width of keratinized gingiva were evaluated at baseline, the time of implant restoration connection, and 2 years postrestoration. All parameters used to assess esthetic outcomes showed improvements. The proposed clinical procedure can be considered an alternative approach to achieving an ideal esthetic anterior restoration.

A quantitative method for simultaneous determination of 5-methoxy-N,N-diisopropyltryptamine and its metabolites in urine using liquid chromatography-electrospray ionization-tandem mass spectrometry.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a designer hallucinogen derived from tryptamine and is reportedly abused and involved in criminal activities. For the detection of 5-MeO-DIPT use, a liquid chromatography-tandem mass spectrometric method for 5-MeO-DIPT and its metabolites, 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N,N-isopropyltryptamine (5-MeO-IPT) was developed and validated in rat urine. The urine samples were pretreated by protein precipitation with acetonitrile and introduced into a BDS HYPERSIL C(18) column (50 × 2.0 mm, 5 µm) for chromatographic separation. Mobile phases consisted of methanol, water, and 1% formic acid, and gradient elution was used at a flow rate of 0.2 mL/min. For the MS detection, multiple-reaction monitoring analysis was adopted. The linear range was 0.01-10 µg/mL, and the lower limit of quantification was 10 ng/mL for all analytes. The intra- and interday accuracies and precisions met the criteria (<15%). The developed method was successfully applied to the drug-treated rat urine.

Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing.

Tooth infections or injuries involving dental pulp are treated routinely by root canal therapy. Endodontically treated teeth are devitalized, susceptible to re-infections, fractures, and subsequent tooth loss. Here, we report regeneration of dental-pulp-like tissue by cell homing and without cell transplantation. Upon in vivo implantation of endodontically treated real-size, native human teeth in mouse dorsum for the tested 3 weeks, delivery of basic fibroblast growth factor and/or vascular endothelial growth factor (bFGF and/or VEGF) yielded re-cellularized and revascularized connective tissue that integrated to native dentinal wall in root canals. Further, combined delivery of bFGF, VEGF, or platelet-derived growth factor (PDGF) with a basal set of nerve growth factor (NGF) and bone morphogenetic protein-7 (BMP7) generated cellularized and vascularized tissues positive of VEGF antibody staining and apparent neo-dentin formation over the surface of native dentinal wall in some, but not all, endodontically treated teeth. Newly formed dental pulp tissue appeared dense with disconnected cells surrounded by extracellular matrix. Erythrocyte-filled blood vessels were present with endothelial-like cell lining. Reconstructed, multiple microscopic images showed complete fill of dental-pulp-like tissue in the entire root canal from root apex to pulp chamber with tissue integration to dentinal wall upon delivery of bFGF, VEGF, or PDGF with a basal set of NGF and BMP7. Quantitative ELISA showed that combinatory delivery of bFGF, VEGF, or PDGF with basal NGF and BMP7 elaborated von Willerbrand factor, dentin sialoprotein, and NGF. These findings represent the first demonstration of regenerated dental-pulp-like tissue in endodontically treated root canals of real-size, native human teeth. The present chemotaxis-based approach has potent cell homing effects for re-cellularization and revascularization in endodontically treated root canals in vivo, although in an ectopic model. Regeneration of dental pulp by cell homing, rather than cell delivery, may accelerate clinical translation.

Bone reaction to bovine hydroxyapatite for maxillary sinus floor augmentation: histologic results in humans.

This study was designed to examine the sequential progress of healing, at two different time intervals, following delayed sinus augmentation using bovine hydroxyapatite (BHA) as the sole grafting material. Fourteen pairs of bone biopsies were taken from 10 patients after 6 and 12 months of healing, respectively. The biopsy specimens were examined histologically and histomorphometrically. The bone that was formed following sinus augmentation with BHA increased and matured over time up to 12 months after grafting; meanwhile, no overt signs of resorption of BHA were visible within the study period.

Identification of differentially expressed proteins in imatinib mesylate-resistant chronic myelogenous cells.

Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a 1 microM imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.

A 3-year longitudinal evaluation of subpedicle free connective tissue graft for gingival recession coverage.

BACKGROUND: The purpose of this study was to longitudinally evaluate, over a 3-year period, the reduction of gingival recession through use of a subepithelial free connective tissue graft placed under a coronally advanced partial-thickness pedicle flap. METHODS: Twenty-one buccal recession defects (mean 3.67 mm; range 3 to 4.5 mm; Miller Class I, II, and III) in 15 patients were treated using this technique. Amount of gingival recession (GR), clinical attachment loss (CAL), and width of keratinized gingiva (WKG) were followed for 3 years after surgery. The measurements were performed at presurgery, and 1, 3, 6, 12, 18, 24, and 36 months postsurgery. RESULTS: GR decreased from 3.67 +/- 0.58 mm at baseline to 0.33 +/- 0.43 mm at 36 months, representing a reduction of 3.33 mm, corresponding to 91.28% mean root coverage. CAL was significantly decreased at 36 months from 5.26 +/- 0.77 mm to 2.14 +/- 0.57 mm. At 36 months, 3.12 mm of attachment gain was obtained. WKG significantly increased after 36 months (1.95 mm). GR, CAL, and WKG had the most positive outcomes at 12 months and were maintained at stable levels throughout the 36-month observation period. CONCLUSIONS: These results indicate that the connective tissue graft with a partial thickness coronal advancement pedicle is a predictable method for root coverage and, provided that optimal maintenance care is provided, the clinical outcomes gained by this technique can be well maintained.