45 research outputs found
Beta1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and signaling responses in cardiomyocytes
Ī²1-adrenergic receptors (Ī²1ARs) mediate catecholamine actions in
cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent
/growth-regulatory pathways. Structural studies of the Ī²1AR define ligand-
binding sites in the transmembrane helices and effector docking sites at the
intracellular surface of the Ī²1AR, but the extracellular N-terminus, which is
a target for post-translational modifications, typically is ignored. This
study identifies Ī²1AR N-terminal O-glycosylation at Ser37/Ser41 as a mechanism
that prevents Ī²1AR N-terminal cleavage. We used an adenoviral overexpression
strategy to show that both full-length/glycosylated Ī²1ARs and N-terminally
truncated glycosylation-defective Ī²1ARs couple to cAMP and ERK-MAPK signaling
pathways in cardiomyocytes. However, a glycosylation defect that results in
N-terminal truncation stabilizes Ī²1ARs in a conformation that is biased toward
the cAMP pathway. The identification of O-glycosylation and N-terminal
cleavage as novel structural determinants of Ī²1AR responsiveness in
cardiomyocytes could be exploited for therapeutic advantage
A novel mosaic mutation in in a Korean patient with hypophosphatemic rickets
X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea
Determining the Facile Routes for Oxygen Evolution Reaction by In Situ Probing of Li-O-2 Cells with Conformal Li2O2 Films
An ongoing challenge with lithium-oxygen (Li-O-2) batteries is in deciphering the oxygen evolution reaction (OER) process related to the slow decomposition of the insulating lithium peroxide (Li2O2). Herein, we shed light on the behavior of Li2O2 oxidation by exploiting various in situ imaging, gas analysis, and electrochemical methods. At the low potentials 3.2-3.7 V (vs Li/Li+), OER is exclusive to the thinner parts of the Li2O2 deposits, which leads to O-2 gas evolution, followed by the concomitant release of superoxide species. At higher potentials, OER initiates at the sidewalls of the thicker Li2O2. The succeeding lateral decomposition of Li2O2 indicates the preferential Li+ and charge transport occurring at the sidewalls of Li2O2. To ameliorate the OER rate, we also investigate an alternative approach of rerouting charge carriers by using soluble redox mediators. Our in situ probes provide insights into the favorable charge-transport routes that can aid in promoting Li2O2 decomposition.11Nsciescopu
A Preterm Infant with Feeding Aspiration Diagnosed with BOR Syndrome, Confirmed Case by Whole-Genome Sequencing and Structural Variant Calling
Branchiootorenal (BOR) syndrome is a rare autosomal dominant inherited disease with a prevalence of approximately 1 in 40,000 newborns. This disease is characterized by hearing loss, preauricular pits, branchial fistulas or cysts, and renal dysplasia. We discovered a case of BOR syndrome in a premature 2-week-old female infant with a gestational age of 32 weeks and two days. She and her family had major symptoms and a family history of BOR. BOR syndrome was confirmed by whole-genome sequencing and structural variant calling, which revealed an EYA1 exon 5ā6 deletion. The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea
Conservative Management of Patent Ductus Arteriosus Is Feasible in the Peri-Viable Infants at 22ā25 Gestational Weeks
The purpose of this study was to determine the natural course of hemodynamically significant (HS) patent ductus arteriosus (PDA) with conservative management and whether the presence or prolonged duration of HS PDA affected mortality/morbidities in infants at 22ā25 weeks estimated gestational age (EGA). We retrospectively reviewed the medical records of 77 infants born at 22ā25 weeks EGA, stratified into 22ā23 weeks (n = 21) and 24ā25 weeks EGA (n = 56). HS PDA was present in 77%, 76%, and 77%, and open ductus at discharge was 12%, 13%, and 12% in the total and at 22ā23 and 24ā25 weeks EGA infants, respectively. For backup rescue treatment, 7% and 5% of the infants received oral ibuprofen and device closure, respectively. A mortality rate of 9% was found in the HS PDA (+) infants, significantly lower than the 28% in HS PDA (ā) infants. There are no significant differences in morbidities. In multivariate analyses, the presence and/or prolonged duration of HS PDA was not associated with increased mortality or morbidity. Spontaneous closure of HS PDA was achieved through conservative management in the peri-viable infants at 22ā25 weeks EGA
The Acceptance and Use of Digital Technologies for Self-Reporting Medication Safety Events After Care Transitions to Home in Patients With Cancer: Survey Study
BackgroundActively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patientsā various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patientsā just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patientsā transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood.
ObjectiveWe aim to assess oncology patientsā perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance.
MethodsA cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participantsā perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participantsā technology acceptance through bivariate correlation analyses and multiple logistic regressions.
ResultsParticipants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78).
ConclusionsIn general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care
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Microanatomical changes and biomolecular expression at the PDLāentheses during experimental tooth movement
The novel aspect of this study was to contextualize the co-localization of biomolecular expression in widened and narrowed periodontal ligament (PDL)-space within a mechanically activated periodontal complex. The PDL is unique as it is the only ligament with both innervation and vascularization. Maxillary molars in 6-week-old male C57BL/6 mice (N = 5) were experimentally translated for 2 weeks using an elastic spacer. Contralateral teeth were used as controls. Mechanical testing of the periodontal complex of a mouse in situ and imaging using X-ray micro-computed tomography (micro-XCT) illustrated deformations within blood vessels (BV) of the PDL. PDL-bone and PDL-cementum entheses at the widened and narrowed PDL-spaces following experimental tooth movement (ETM) illustrated osterix (OSX), bone sialoprotein (BSP), cluster of differentiation 146 (CD146), and protein gene product 9.5 (PGP9.5), indicating active remodeling at these sites. PGP9.5 positive nerve bundles (NBs) were co-localized with multinucleated cells (MCs), Howship's resorption lacunae, and CD146 positive BVs. Association between nerves and MC was complemented by visualizing the proximity of osmium tetroxide stained NBs with the ultrastructure of MCs by performing scanning transmission electron microscopy. Spatial association of NB with BV, and NB with MC, provided insights into the plausible co-activation of NBs to initiate osteoclastic activity. Resorption of mineral occurred as an attempt to restore PDL-space of the load-bearing complex, specifically at the PDL-entheses. Mapping of anatomy-specific structural elements and their association with regenerative molecules by correlating light and electron micrographs provided insights into the use of these extracellular matrix molecules as plausible targets for pharmacological interventions related to tooth movement. Within the realm of tissue regeneration, modulation of load can reverse naturally occurring mineral formation to experimentally induced resorption, and naturally occurring mineral resorption to experimentally induced formation at the enthesial sites to permit tooth translation
Unexpected Li<sub>2</sub>O<sub>2</sub> Film Growth on Carbon Nanotube Electrodes with CeO<sub>2</sub> Nanoparticles in LiāO<sub>2</sub> Batteries
In lithiumāoxygen
(LiāO<sub>2</sub>) batteries, it is believed that lithium peroxide
(Li<sub>2</sub>O<sub>2</sub>) electrochemically forms thin films with
thicknesses less than 10 nm resulting in capacity restrictions due
to limitations in charge transport. Here we show unexpected Li<sub>2</sub>O<sub>2</sub> film growth with thicknesses of ā¼60 nm
on a three-dimensional carbon nanotube (CNT) electrode incorporated
with cerium dioxide (ceria) nanoparticles (CeO<sub>2</sub> NPs). The
CeO<sub>2</sub> NPs favor Li<sub>2</sub>O<sub>2</sub> surface nucleation
owing to their strong binding toward reactive oxygen species (e.g.,
O<sub>2</sub> and LiO<sub>2</sub>). The subsequent film growth results
in thicknesses of ā¼40 nm (at cutoff potential of 2.2 V vs Li/Li<sup>+</sup>), which further increases up to ā¼60 nm with the addition
of trace amounts of H<sub>2</sub>O that enhances the solution free
energy. This suggests the involvement of solvated superoxide species
(LiO<sub>2</sub>(sol)) that precipitates on the existing Li<sub>2</sub>O<sub>2</sub> films to form thicker films via disproportionation.
By comparing toroidal Li<sub>2</sub>O<sub>2</sub> formed solely from
LiO<sub>2</sub>(sol), the thick Li<sub>2</sub>O<sub>2</sub> films
formed from surface-mediated nucleation/thin-film growth following
by LiO<sub>2</sub>(sol) deposition provides the benefits of higher
reversibility and rapid surface decomposition during recharge
Benchmarking metal and metal oxide promoters for oxygen evolution reaction in Li-O2 cells
Determining the Facile Routes for Oxygen Evolution Reaction by <i>In Situ</i> Probing of LiāO<sub>2</sub> Cells with Conformal Li<sub>2</sub>O<sub>2</sub> Films
An
ongoing challenge with lithiumāoxygen (LiāO<sub>2</sub>) batteries is in deciphering the oxygen evolution reaction
(OER) process related to the slow decomposition of the insulating
lithium peroxide (Li<sub>2</sub>O<sub>2</sub>). Herein, we shed light
on the behavior of Li<sub>2</sub>O<sub>2</sub> oxidation by exploiting
various <i>in situ</i> imaging, gas analysis, and electrochemical
methods. At the low potentials 3.2ā3.7 V (vs Li/Li<sup>+</sup>), OER is exclusive to the thinner parts of the Li<sub>2</sub>O<sub>2</sub> deposits, which leads to O<sub>2</sub> gas evolution, followed
by the concomitant release of superoxide species. At higher potentials,
OER initiates at the sidewalls of the thicker Li<sub>2</sub>O<sub>2</sub>. The succeeding lateral decomposition of Li<sub>2</sub>O<sub>2</sub> indicates the preferential Li<sup>+</sup> and charge transport
occurring at the sidewalls of Li<sub>2</sub>O<sub>2</sub>. To ameliorate
the OER rate, we also investigate an alternative approach of rerouting
charge carriers by using soluble redox mediators. Our <i>in situ</i> probes provide insights into the favorable charge-transport routes
that can aid in promoting Li<sub>2</sub>O<sub>2</sub> decomposition