Trajectories of nursing hours over the course of hospitalization and estimated additional nurse staffing requirements to reduce the length of stay.

PURPOSE: The aims of this study are to examine the trajectories of nursing hours per patient day (NHPPD) over the course of hospitalization according to the patient's length of stay (LOS) and to estimate changes in the total nursing hours during hospitalization, average NHPPD, and the number of nurses additionally required when the LOS was reduced by 1 day. DESIGN: This retrospective longitudinal study analyzed patient data collected from a tertiary university hospital located in Seoul, South Korea. The study sample included 11,316 inpatients who were discharged between September 1 and October 31, 2022. METHODS: NHPPD over the course of each patient's hospitalization was estimated using the total score of the Korean Patient Classification System-1 (KPCS-1), which nurses evaluated and recorded every day from admission to discharge. The NHPPD trajectories were examined using linear mixed models to analyze repeated KPCS-1 measurements and control for the effects of patient characteristics. The changes in the average NHPPD when LOS was reduced by 1 day were estimated using maximum and minimum estimations. The impact of a 1-day reduction in LOS on staffing requirements was calculated as the number of nurses additionally required to work each shift and to be hired. FINDINGS: The average LOS was 5.6 days, and the short (1-6 days) and medium (7-14 days) LOS groups accounted for 78.9% and 14.3% of patients, respectively. The NHPPD trajectories showed a "rise-peak-decline" pattern. Patients in the short LOS group received the most NHPPD on day 1 (day of admission) or day 2, whereas the NHPPD for patients in the medium LOS group peaked on days 3-6. After peaking, the NHPPD tended to decrease toward the end of hospitalization, with the least NHPPD on the day of discharge, followed by the day before discharge. When LOS was reduced by 1 day, the average NHPPD was estimated to increase by 7.7-50.0% in the maximum estimation, and 0.9-12.5% in the minimum estimation. In response to a 1-day reduction, 1.10-7.44 nurses were additionally required to care for 100 patients each shift and 5.28-35.70 additional nurses needed to be hired in the maximum estimation. In the minimum estimation, these values were 0.13-1.85 additional nurses per shift and 0.65-8.90 additional nurses to be hired, respectively. CONCLUSIONS: Since NHPPD exhibited a "rise-peak-decline" trajectory, reducing the LOS by 1 day was estimated to increase the average NHPPD and lead to additional staffing requirements. The additional nurse requirement for a 1-day reduction was not constant; instead, it increased with each day subtracted from an already shorter LOS. CLINICAL RELEVANCE: Sufficient nurse staffing is necessary to provide increased NHPPD as a result of shortened LOS. Changes in the LOS should be considered when determining nurse staffing requirements.

Synthesis of carboxymethyl chitosan-guar gum-poly(vinylpyrrolidone) ternary blended hydrogels with antibacterial/anticancer efficacy and drug delivery applications.

Biopolymers have the utmost significance in biomedical applications and blending synthetic polymers has shown favorable characteristics versus individual counterparts. The utilization of the blends can be restricted through the use of toxic chemical agents such as initiators or crosslinkers. In this regard, a chemical agent-free ionizing irradiation is a beneficial alternative for preparing the hydrogels for biomedical applications. In this study, carboxymethyl chitosan (CM-CS), guar gum (GG), and poly(vinylpyrrolidone) (PVP) based ternary blends (TB) were crosslinked using various doses of ionizing irradiation to fabricate hydrogels. The prepared hydrogels were characterized for physicochemical properties, swelling analysis, biological assays, and drug delivery applications. Swelling analysis in distilled water revealed that the hydrogels exhibit excellent swelling characteristics. An in vitro cytocompatibility assay showed that the hydrogels have greater than 90% cell viability for the human epithelial cell line and a decreasing cell viability trend for the human alveolar adenocarcinoma cell line. In addition, the prepared hydrogels possessed excellent antibacterial characteristics against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). Finally, the release studies of anti-inflammatory Quercus acutissima (QA) loaded hydrogels exhibited more than 80% release in phosphate-buffered saline (pH = 7.4). These findings suggest that TB hydrogels can be used as suitable carrier media for different release systems and biomedical applications.

Naturally manufactured biochar materials based sensor electrode for the electrochemical detection of polystyrene microplastics.

In recent times, microplastics have become a disturbance to both aquatic and terrestrial ecosystems and the ingestion of these particles can have severe consequences for wildlife, aquatic organisms, and even humans. In this study, two types of biochars were manufactured through the carbonization of naturally found starfish (SF-1) and aloevera (AL-1). The produced biochars were utilized as sensing electrode materials for the electrochemical detection of ∼100 nm polystyrene microplastics (PS). SF-1 and AL-1 based biochars were thoroughly analyzed in terms of morphology, structure, and composition. The detection of microplastics over biochar based electrodes was carried out by electrochemical studies. From electrochemical results, SF-1 based electrode exhibited the detection efficiency of ∼0.2562 µA/µM∙cm2 with detection limit of ∼0.44 nM whereas, a high detection efficiency of ∼3.263 µA/µM∙cm2 was shown by AL-1 based electrode and detection limit of ∼0.52 nM for PS (100 nm) microplastics. Process contributed to enhancing the sensitivity of AL-1 based electrode might associate to the presence of metal-carbon framework over biochar's surfaces. The AL-1 biochar electrode demonstrated excellent repeatability and detection stability for PS microplastics, suggesting the promising potential of AL-1 biochar for electrochemical microplastics detection.

Intermolecular interactions in clusters of ethylammonium nitrate and 1-amino-1,2,3-triazole.

The intermolecular interaction energies, including hydrogen bonds (H-bonds), of clusters of the ionic liquid ethylammonium nitrate (EAN) and 1-amino-1,2,3-triazole (1-AT) based deep eutectic propellants (DeEP) are examined. 1-AT is introduced as a neutral hydrogen bond donor (HBD) to EAN in order to form a eutectic mixture. The effective fragment potential (EFP) is used to examine the bonding interactions in the DeEP clusters. The resolution of the Identity (RI) approximated second order Møller-Plesset perturbation theory (RI-MP2) and coupled cluster theory (RI-CCSD(T)) are used to validate the EFP results. The EFP method predicts that there are significant polarization and charge transfer effects in the EAN:1-AT complexes, along with Coulombic, dispersion and exchange repulsion interactions. The EFP interaction energies are in good agreement with the RI-MP2 and RI-CCSD(T) results. The quasi-atomic orbital (QUAO) bonding and kinetic bond order (KBO) analyses are additionally used to develop a conceptual and semi-quantitative understanding of the H-bonding interactions as a function of the size of the system. The QUAO and KBO analyses suggest that the H-bonds in the examined clusters follow the characteristic hydrogen bonding three-center four electron interactions. The strongest H-bonding interactions between the (EAN)1:(1-AT)n and (EAN)2:(1-AT)n (n = 1-5) complexes are observed internally within EAN; that is, between the ethylammonium cation [EA]+ and the nitrate anion ([NO3]-). The weakest H-bonding interactions occur between [NO3]- and 1-AT. Consequently, the average strengths of the H-bonds within a given (EAN)x:(1-AT)n complex decrease as more 1-AT molecules are introduced into the EAN monomer and EAN dimer. The QUAO bonding analysis suggests that 1-AT in (EAN)x:(1-AT)n can act as both a HBD and a hydrogen bond acceptor simultaneously. It is observed that two 1-AT molecules can form H-bonds to each other. Although the KBOs that correspond to H-bonding interactions in [EA]+:1-AT, [NO3]-:1-AT and between two 1-AT molecules are weaker than the H-bonds in EAN, those weak H-bond networks with 1-AT could be important to form a stable DeEP.

Impact assessment of a primary care physician counseling program for youth population.

This study aimed to investigate the impact of implementing a primary care physician (PCP) counseling program for the youth population with healthcare needs. This quasi-experimental study used a nonequivalent control group pretest-posttest design, and was conducted at Salim Health Innovation Clinic in Seoul between February and October 2019 comprising 46 participating youths (intervention group) and 48 nonparticipating youths (control group). After 6 months of implementation, drinking (alcohol use control) decreased significantly in the intervention group (0.84 points). There was a significant difference in the anxiety level with a decrease of 2.86 and 0.65 points in the intervention and control groups (P = .011) respectively. There was also a significant difference in the health responsibility domain (P = .04). Moreover, a significant difference in self-efficacy level was found with a mean increase of 0.18 and 0.16 points in the intervention and control groups (P = .001), respectively. The youth population is more prone to neglect self-care due to poor physical and mental health status and no hope for the future because of a lack of jobs and rising housing prices. The program reinforces health-promoting behavior for managing stress and practicing eating high-quality meals, regular exercise, and regular health screening, which can help implement continuous and effective healthcare.

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: ß-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Using magnetic resonance imaging to measure the depth of acupotomy points in the lumbar spine: A retrospective study.

BACKGROUND: The acupotomy is an acupuncture device recently used to stimulate lumbar vertebrae such as transverse processes (TPs) and facet joints (FJs). However, there are many organs, nerves, and blood vessels, which can lead to side effects if the needle misses the treatment target. Therefore, information regarding appropriate insertion depths, which is currently lacking, could facilitate its safe use. We retrospectively investigated the depth from the skin to the TP and FJ of the lumbar vertebrae, using magnetic resonance imaging (MRI). METHODS: This retrospective chart review was conducted at a single medical centre in Korea. From 55,129 patient records, 158 subjects were selected. Perpendicular depth from the skin to the left and right TPs and FJs was measured using T1-weighted sagittal plane MRI. Depth differences between the left and right sides were evaluated using the paired t-test and analysis of covariance (body mass index [BMI] as a covariate). The influence of BMI on depth at each location was evaluated by simple linear regression analysis. RESULTS: The mean age was 43.2 years and mean BMI was 23.6 kg/m2. The depth from skin to the TPs or FJs was unaffected by age, sex, or side. Mean depths (cm) were as follows: (TPs) L1 = 4.5, L2 = 4.9, L3 = 5.3, L4 = 5.7, L5 = 5.9; (FJs) L12 = 3.8, L23 = 4.0, L34 = 4.4, L45 = 4.6, L5S1 = 4.6. Depth was highly correlated with BMI at each location. CONCLUSION: The depth of TPs and FJs adjusted for BMI can safely and effectively be used for treatment via various invasive interventions, including acupotomy treatment, in the lumbar region.

NaV1.6 and NaV1.7 channels are major endogenous voltage-gated sodium channels in ND7/23 cells.

ND7/23 cells are gaining traction as a host model to express peripheral sodium channels such as NaV1.8 and NaV1.9 that have been difficult to express in widely utilized heterologous cells, like CHO and HEK293. Use of ND7/23 as a model cell to characterize the properties of sodium channels requires clear understanding of the endogenous ion channels. To define the nature of the background sodium currents in ND7/23 cells, we aimed to comprehensively profile the voltage-gated sodium channel subunits by endpoint and quantitative reverse transcription-PCR and by whole-cell patch clamp electrophysiology. We found that untransfected ND7/23 cells express endogenous peak sodium currents that average -2.12nA (n = 15) and with kinetics typical of fast sodium currents having activation and inactivation completed within few milliseconds. Furthermore, sodium currents were reduced to virtually nil upon exposure to 100nM tetrodotoxin, indicating that ND7/23 cells have essentially null background for tetrodotoxin-resistant (TTX-R) currents. qRT-PCR profiling indicated a major expression of TTX-sensitive (TTX-S) NaV1.6 and NaV1.7 at similar levels and very low expression of TTX-R NaV1.9 transcripts. There was no expression of TTX-R NaV1.8 in ND7/23 cells. There was low expression of NaV1.1, NaV1.2, NaV1.3 and no expression of cardiac or skeletal muscle sodium channels. As for the sodium channel auxiliary subunits, ß1 and ß3 subunits were expressed, but not the ß2 and ß4 subunits that covalently associate with the α-subunits. In addition, our results also showed that only the mouse forms of NaV1.6, NaV1.7 and NaV1.9 sodium channels were expressed in ND7/23 cells that was originally generated as a hybridoma of rat embryonic DRG and mouse neuroblastoma cell-line. By molecular profiling of auxiliary ß- and principal α-subunits of the voltage gated sodium channel complex, our results define the background sodium channels expressed in ND7/23 cells, and confirm their utility for detailed functional studies of emerging pain channelopathies ascribed to mutations of the TTX-R sodium channels of sensory neurons.

Ionic liquids from a fragmented perspective.

The efficacy of using fragmentation methods, such as the effective fragment potential, the fragment molecular orbital and the effective fragment molecular orbital methods is discussed. The advantages and current limitations of these methods are considered, potential improvements are suggested, and a prognosis for the future is provided.

Crystal Structure of Histidine Triad Nucleotide-Binding Protein from the Pathogenic Fungus Candida albicans.

Histidine triad nucleotide-binding protein (HINT) is a member of the histidine triad (HIT) superfamily, which has hydrolase activity owing to a histidine triad motif. The HIT superfamily can be divided to five classes with functions in galactose metabolism, DNA repair, and tumor suppression. HINTs are highly conserved from archaea to humans and function as tumor suppressors, translation regulators, and neuropathy inhibitors. Although the structures of HINT proteins from various species have been reported, limited structural information is available for fungal species. Here, to elucidate the structural features and functional diversity of HINTs, we determined the crystal structure of HINT from the pathogenic fungus Candida albicans (CaHINT) in complex with zinc ions at a resolution of 2.5 Å. Based on structural comparisons, the monomer of CaHINT overlaid best with HINT protein from the protozoal species Leishmania major. Additionally, structural comparisons with human HINT revealed an additional helix at the C-terminus of CaHINT. Interestingly, the extended C-terminal helix interacted with the N-terminal loop (α1-ß1) and with the α3 helix, which appeared to stabilize the dimerization of CaHINT. In the C-terminal region, structural and sequence comparisons showed strong relationships among 19 diverse species from archea to humans, suggesting early separation in the course of evolution. Further studies are required to address the functional significance of variations in the C-terminal region. This structural analysis of CaHINT provided important insights into the molecular aspects of evolution within the HIT superfamily.

Crystal structure of Arabidopsis thaliana RabA1a.

RabGTPase is a member of the Ras superfamily of small GTPases, which share a GTP-binding pocket containing highly conserved motifs that promote GTP hydrolysis. In Arabidopsis, the RabA group, which corresponds to the Rab11 group in animals, functions in the recycling of endosomes that control docking and fusion during vesicle transport. However, their molecular mechanisms remain unknown. In this study, we determined the crystal structures of the GDP-bound inactive form and both GppNHp- and GTP-bound active forms of RabA1a, at resolutions of 2.8, 2.6, and 2.6 Å, respectively. A bound sulfate ion in the active site of the GDP-bound structure stabilized Switch II by bridging the interaction between a magnesium ion and Arg74. Comparisons of the two states of RabA1a with Rab11 proteins revealed clear differences in the Switch I and II loops. These results suggested that conformational change of the Switch regions of RabA1a, derived by GTP or GDP binding, could maintain subcellular membrane traffic through the specific interaction of effector molecules.

Identification of LEM-14 inhibitor of the oncoprotein NSD2.

The NSD family (NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1) are histone lysine methyltransferases (HMTases) essential for chromatin regulation. The NSDs are oncoproteins, drivers of a number of tumors and are considered important drug-targets but the lack of potent and selective inhibitors hampers further therapeutic development and limits exploration of their biology. In particular, MMSET/NSD2 selective inhibition is being pursued for therapeutic interventions against multiple myeloma (MM) cases, especially in multiple myeloma t(4;14)(p16.3;q32) translocation that is associated with a significantly worse prognosis than other MM subgroups. Multiple myeloma is the second most common hematological malignancy, after non-Hodgkin lymphoma and remains an incurable malignancy. Here we report the discovery of LEM-14, an NSD2 specific inhibitor with an in vitro IC50 of 132 µM and that is inactive against the closely related NSD1 and NSD3. LEM-14-1189, a LEM-14 derivative, differentially inhibits the NSDs with in vitro IC50 of 418 µM (NSD1), IC50 of 111 µM (NSD2) and IC50 of 60 µM (NSD3). We propose LEM-14 and derivative LEM-14-1189 as tools for studying the biology of the NSDs and constitute meaningful steps toward potent NSDs therapeutic inhibitors.

Defense sequestration associated with narrowing of diet and ontogenetic change to aposematic colours in the spotted lanternfly.

Bright colours in distasteful prey warn off predators, but processes associated with ontogenetic acquisition of warning colours and distasteful compounds have been studied in only a few organisms. Here, we study spotted lanternflies (Lycorma delicatula; Fulgoridae) that change to red colouration when they narrow their host plant preferences to primarily the tree of heaven (Ailanthus altissima; Simaroubaceae), which is chemically defended by quassinoids. In experiments, we showed that birds taste-avoided lanternflies collected on Ailanthus but not those collected on the secondary hosts. Birds also taste-avoided seeds infused with ailanthone, the main quassinoid sequestered from Ailanthus by lanternflies as shown through mass spectrometry analyses. Hence, the narrowing of host preferences by lanternflies synchronizes the timing of change to red colour with the acquisition of quassinoid defenses. A schematic graphical population-level model of these processes is provided. This is the first report of quassinoid sequestration by insects and the first evidence that Simaroubaceae plants provide defensive chemicals to insects. This is the first report of a fulgoroid insect sequestering identified chemical defenses. The results highlight the importance of the pan-tropical taxon Fulgoridae for evolutionary biology of complex aposematic strategies and for understanding the links between timing of defense sequestration, timing of host plant preference shifts, and timing of colour change.

Enantioselective Synthesis of a Novel Thiazoline Core as a Potent Peroxisome Proliferator-Activated Receptor δ Agonist.

The convergent and enantioselective synthesis of a highly potent human peroxisome proliferator-activated receptor delta agonist is presented. More specifically, the thiazoline structure, which constitutes the biosynthetically distinctive core structure of pulicatin (a secondary metabolite of symbiotic bacteria), was synthesized from a commercially available and inexpensive chiral pool of l-threonine.

Benchmarking the Effective Fragment Potential Dispersion Correction on the S22 Test Set.

The usual modeling of dispersion interactions in density functional theory (DFT) is often limited by the use of empirically fitted parameters. In this study, the accuracies of the popular empirical dispersion corrections and the first-principles derived effective fragment potential (EFP) dispersion correction are compared by computing the DFT-D and HF-D equilibria interaction energies and intermolecular distances of the S22 test set dimers. Functionals based on the local density approximation (LDA) and generalized gradient approximation (GGA), as well as hybrid functionals, are compared for the DFT-D calculations using coupled cluster CCSD(T) at the complete basis set (CBS) limit as the reference method. In general, the HF-D(EFP) method provides accurate equilibrium dimerization energies and intermolecular distances for hydrogen-bonded systems compared to the CCSD(T)/CBS reference data without using any empirical parameters. For dispersion-dominant and mixed systems, the structures and interaction energies obtained with the B3LYP-D(EFP) method are similar to or better than those obtained with the other DFT-D and HF-D methods. Overall, the first-principles derived -D(EFP) correction presents a robust alternative to the empirical -D corrections when used with the B3LYP functional for dispersion-dominant and mixed systems or with Hartree-Fock for hydrogen-bonded systems.

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up.

BACKGROUND: Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. METHODS: This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. RESULTS: Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). CONCLUSION: Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

18F-FDG PET/CT surveillance for the detection of recurrence in patients with head and neck cancer.

BACKGROUND: Posttreatment detection of recurrence may lead to salvage treatment and prognostic prediction in patients with head and neck squamous cell carcinoma (HNSCC). We evaluated the diagnostic and prognostic values of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) after definitive treatment of HNSCC. METHODS: This prospective study included 278 consecutive patients who underwent curative surgery (n = 143, 51.4%) or definitive radiotherapy/chemoradiotherapy (n = 135, 48.6%) for previously untreated HNSCC. The patients were regularly followed up and evaluated by 18F-FDG PET/CT, head and neck CT/magnetic resonance imaging (MRI), and chest CT at regular intervals after treatment. The imaging interpretations were compared with the histological results for recurrence. Receiver operating characteristics curves analysis, McNemar's test and logistic regression using generalised estimating equations were used to compare the diagnostic accuracy of 18F-FDG PET/CT and standard imaging of CT/MRI or chest CT, and a Cox proportional hazards model was used to assess the prognostic value of PET/CT. RESULTS: During a median follow-up of 44 months (range, 24-62 months), 73 patients (26.3%) had recurrence or persistent diseases. The area under curves for 18F-FDG PET/CT and CT/MRI were 0.975 (0.964-0.992) and 0.789 (0.713-0.874), respectively (P < 0.001). 18F-FDG PET/CT detected 65 of 66 recurrences (98.5%) not suggested by physical examination and endoscopy. Positive findings on 18F-FDG PET/CT scans were independent predictors of poorer cancer-specific and overall survival outcomes (P < 0.01). CONCLUSIONS: Posttreatment 18F-FDG PET/CT surveillance helps to properly detect recurrence and to predict the survival following treatment of HNSCC.

Discovery of 2-((R)-4-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-methylpiperazin-1-yl)-N-((1R,2s,3S,5S,7S)-5-hydroxyadamantan-2-yl)pyrimidine-4-carboxamide (SKI2852): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of 11ß-Hydroxysteroid Dehydrogenase Type 1 (11ß-HSD1).

A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound 9. The combination of the replacement of a pyridine ring of 9 with a pyrimidine ring and the introduction of an additional fluorine substituent at the 2-position of the phenyl ring resulted in the discovery of a potent, selective, and orally bioavailable inhibitor, 18a (SKI2852), which demonstrated no CYP and PXR liabilities, excellent PK profiles across species, and highly potent and sustainable PD activity. Repeated oral administration of 18a significantly reduced blood glucose and HbA1c levels and improved the lipid profiles in ob/ob mice. Moreover, the HbA1c-lowering effect of metformin was synergistically enhanced in combination with 18a.

Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists.

We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERRγ but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERRγ over the ERRα, -ß, and ERα. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b-treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b possess advantageous druglike properties and can be used to potentially treat various ERRγ-related disorders.

An Introduction to a Head and Neck Cancer-Specific Frailty Index and Its Clinical Implications in Elderly Patients: A Prospective Observational Study Focusing on Respiratory and Swallowing Functions.

INTRODUCTION: Frailty refers to a decreased physiologic reserve in geriatric patients and its importance in terms of treatment planning and outcome prediction has been emphasized in oncologic practices for older patients with cancer. We investigated the clinical implications of a head and neck cancer (HNC)-specific frailty index suggested by prospective clinical and functional evaluations of HNC patients. MATERIALS AND METHODS: We analyzed data on 165 elderly patients with HNC who were prospectively enrolled in our hospital from 2010 to 2013. Pretreatment functional evaluations were performed according to all comprehensive geriatric assessment (CGA) domains. We additionally evaluated the patients' respiratory and swallowing functions using pulmonary function tests, voice handicap index (VHI), MD Anderson Dysphagia Inventory (MDADI), and other associated tests. Factors affecting the 2-year morbidity and mortality were also analyzed. RESULTS: Respiratory and swallowing problems were major causes of 2-year morbidity. Pretreatment performance status, VHI ≥8, MDADI <70, dental problems, and chemotherapy were significantly associated with early morbidity and mortality (all p < .05). CGA-assessed frailty was found in 72 patients (43.6%) and was significantly associated with 2-year mortality (p = .027) but not with morbidity (p = .716). The high-risk group according to our new HNC-specific frailty index that included functional evaluations of respiration and swallowing showed significantly higher 2-year morbidity (p = .043) and mortality (p < .001). CONCLUSION: Pretreatment functional disabilities related to respiration and swallowing were significantly associated with early morbidity and mortality. The suggested index would be more useful for assessing frailty in elderly HNC patients. IMPLICATIONS FOR PRACTICE: This study is the first report in terms of suggesting a new frailty index focusing on respiratory and swallowing functions in elderly patients with head and neck cancer. This study shows that functional disabilities associated with respiration and swallowing significantly affected early morbidity and mortality in these elderly patients. The head and neck cancer-specific frailty index described in this report, which includes functional evaluations of respiration and swallowing, significantly predicted both early morbidity and mortality.