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Gold ultrathin nanorods (Au UNRs) are anisotropic nanostructures constructed by attaching gold nanoclusters in one dimension. Au UNRs exhibit localized surface plasmon resonance (LSPR) only in the longitudinal direction because their diameter is smaller than the Fermi wavelength of an electron (<2 nm). In this study, we found that the LSPR wavelength of oleylamine-stabilized Au UNRs is blue-shifted simply by mixing with Ag(I). High-resolution elemental mapping and X-ray photoelectron spectroscopy of the resulting UNRs indicate that a Ag monatomic layer is formed on the Au UNR surface by the antigalvanic reduction of Ag(I). This process allowed us to synthesize a series of Au@Ag core-shell UNRs with LSPR wavelengths in the range of 1.2-2.0 μm.

Background: Designing competency-based education (CBE) programmes is a priority in global nursing education for better nursing care for the population. In the Democratic Republic of the Congo (DRC), object-based education (OBE) remains mainstream in pre-service nursing education programmes. Recently, the Ministry of Health developed a self-assessment tool and quantitatively compared the clinical competency of CBE- and OBE-trained nurses. This study aimed to qualitatively triangulate the results of self-evaluation by exploring perception of supervisors, incumbent CBE-, and OBE-trained nurses in comparison with the competence of the two types of nurses, and to identify influential factors or barriers to their competence in clinical settings., Methods: A qualitative descriptive approach with conventional content analysis was applied. Twenty interviews with clinical supervisors who oversaw both CBE- and OBE-trained nurses, 22 focus group discussions (FGDs) with CBE-trained nurses, and 21 FGDs with OBA-trained nurses currently working in health facilities were conducted. Participants of the FGDs were selected from the participants of the DRC self-assessment competency comparison study where there was no statistically significance between CBE- and OBE-trained nurses in the demographic characteristics. Data were analysed in terms of the competencies identified by the Ministry of Health., Results: The supervisors recognised that the CBE-trained nurses had stronger competencies in professional communication, making decisions about health problems, and engaging in professional development, but were weak in clinical skills. This study identified challenges for supervisors in assuring standardised care in health facilities with OBE- and CBE-trained nurses, as well as barriers for CBE-trained nurses as a minority in the workplace in demonstrating their competencies., Conclusions: The study results support the Ministry of Health's policy to expand CBE in pre-service education programmes but reveal that its slow implementation impedes full utilisation of the acquired competencies at health facilities. Implementation could be accelerated by strengthening cooperation among the Ministry of Health's three human resource departments, and developing and implementing a well-planned, legally binding, long-term CBE reform strategy, including an approach to the Continuing Professional Development system., (© 2024. The Author(s).)

Acromegaly is a chronic systemic disease characterized by facial and peripheral changes caused by soft tissue overgrowth and is associated with multiple comorbidities. Despite available surgical and medical therapies, suitable treatments for acromegaly are still lacking. Efficient drug development requires an understanding of the exposure-response (E-R) relationship based on nonclinical and early clinical studies. We aimed to establish a platform to facilitate the development of novel drugs to treat acromegaly. We evaluated the E-R relationship of the growth hormone (GH)-inhibitory effect of the somatostatin analog octreotide under growth hormone-releasing hormone + arginine stimulation in healthy participants and compared the results with historical data for patients with acromegaly. This randomized five-way crossover study included two placebo and three active-treatment periods with different doses of octreotide acetate. GH secretion in the two placebo periods was comparable, which confirmed the reproducibility of the response with no carryover effect. GH secretion was inhibited by low-, medium-, and high-dose octreotide acetate in a dose-dependent manner. We also examined the E-R relationship in monkeys as a preclinical drug evaluation study and in rats as a more convenient and simple system for screening candidate drugs. The E-R relationships and EC 50 values were similar among animals, healthy participants, and patients with acromegaly, which suggests that GH stimulation studies in early research and development allowed simulation of the drug response in patients with acromegaly. SIGNIFICANCE STATEMENT: This study demonstrated similar exposure-response relationships in terms of the growth hormone-inhibitory effect of octreotide after growth hormone-releasing hormone stimulation among healthy participants, monkeys, and rats. The research methods and analyses utilized in this study will be useful for simulating the dosages and therapeutic effects of drugs for acromegaly and will facilitate the research and development of novel therapeutic agents with similar modes of action., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Somatostatin receptors are members of G-protein coupled receptor superfamily. Receptors can be classified into five subtypes, SSTR1 to 5. The highly potent and orally active SSTR2 agonist 7, which had been identified by our group, was found out to have toxicological liabilities such as hERG inhibition and phospholipidosis (PLD). We investigated the relationship between in silico physicochemical properties and hERG and PLD, and explored well-balanced agonists to identify amide 19 and benzimidazole 30. As a result of this exploration, we found out that the value of (cLogP) [2] + (pKa) [2] needs to be less than 110 to mitigate the liabilities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acromegaly is a disease caused by the oversecretion of growth hormone. It is currently treated by intravenous injection with cyclic peptide drugs that activate somatostatin receptor subtype 2 (SSTR2). Here, novel nonpeptidic, small-molecule, and orally active SSTR2 agonists were identified from a hit compound ( 13 ). Pharmacophore studies enabled scaffold hopping to obtain a unique 3,4,5-trisubstituted pyridine motif. Further optimization conferred potent SSTR2 agonistic activity and metabolic stability. Several compounds were evaluated and these showed good oral pharmacokinetic profiles in rats, and one representative compound ( 25 ) showed highly potent inhibition of growth hormone secretion induced by growth hormone-releasing hormone in rats. Based on these results, 25 was identified as a promising lead for further optimization. A structure-activity relationship (SAR) study and the metabolic stability data for this compound are also described.

Purpose: To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex., Methods: The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats., Results: TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions., Conclusions: These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

We characterized TRK-130 (N-[(5R,6R,14S)-17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-yl]phthalimide; naltalimide), an opioid ligand, to clarify the therapeutic potential for overactive bladder (OAB). In radioligand-binding assays with cells expressing human µ-opioid receptors (MORs), δ-opioid receptors (DORs), or κ-opioid receptors (KORs), TRK-130 showed high selectivity for MORs (Ki for MORs, DORs, and KORs = 0.268, 121, and 8.97 nM, respectively). In a functional assay (cAMP accumulation) with cells expressing each human opioid receptor subtype, TRK-130 showed potent but partial agonistic activity for MORs [EC50 (Emax) for MORs, DORs, and KORs = 2.39 nM (66.1%), 26.1 nM (71.0%), and 9.51 nM (62.6%), respectively]. In isovolumetric rhythmic bladder contractions (RBCs) in anesthetized guinea pigs, TRK-130 dose-dependently prolonged the shutdown time (the duration of complete cessation of the bladder contractions) (ED30 = 0.0034 mg/kg i.v.) without affecting amplitude of RBCs. Furthermore, TRK-130 ameliorated formalin-induced frequent urination at doses of higher than 0.01 mg/kg p.o. in guinea pigs under the freely moving condition. Meanwhile, TRK-130 showed only a negligible effect on the gastrointestinal transit at doses of up to 10 mg/kg s.c. in mice. These results indicate that TRK-130 is a potent and selective human MOR partial agonist without undesirable opioid adverse effects such as constipation and enhances the storage function by suppressing the afferent limb of the micturition reflex pathway, suggesting that TRK-130 would be a new therapeutic agent for OAB., (Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.)

In Cambodia, the number of nurses is insufficient and details of nursing services are unknown and undocumented. This research explored who provides nursing service activities in Cambodia. The study was conducted at nine hospitals in Cambodia. Findings indicate that non-invasive medical care such as vital signs taking was designated to nurses. In performing more complex medical interventions, nurses shared the tasks with medical doctors. Conversely, simpler nursing tasks, including maintaining bedside environment/hygiene and supporting patient activities, tasks were shared by nurses with patients' family. This study elucidated an optimal personnel mix and task shared between nurses, doctors and patients' families. There are important implications for nursing legislation related to streamlining the production of nurses to provide an adequate and qualified nursing service in Cambodia., (© 2014 Wiley Publishing Asia Pty Ltd.)

Purpose: Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to pirfenidone therapy., Materials and Methods: Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs., Results: The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the pirfenidone group and 74.6 ± 16.6% in controls (p=NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the pirfenidone group than the control in both of visual score (p=0.006) and computer analysis (p<0.001). The decline in VC correlated significantly with the increase in fibrotic lesion (p<0.001)., Conclusion: CT can be used to assess pirfenidone-induced slowing of progression of pulmonary fibrosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Miliary brain metastasis is a rarity and refers to the presence of numerous small tumors in a perivascular distribution without intraparenchymal invasion and focal edema. Although the presence of epidermal growth factor receptor (EGFR) mutation and good response to gefitinib have been reported in non-small cell lung cancer (NSCLC) patients with miliary brain metastases, the influence of the EGFR mutations on the radiographic features remains unclear., Patients and Methods: All NSCLC patients with synchronous brain metastases detected at the time of a new diagnosis of NSCLC from March 2005 through May 2011 were divided according to EGFR mutation status. The number of brain tumors, size of the largest brain tumors, and size of peritumoral brain edema were compared among the groups., Results: Fifty-seven patients who met the criteria were divided into three groups: wild-type EGFR group (31 patients), exon 19 deletion group (18 patients), and exon 21 point mutation group (8 patients). The exon 19 deletion group had more multiple and smaller brain tumors with smaller peritumoral brain edema than did the wild-type group (P = 0.024, P = 0.0016, and P = 0.0036, respectively). The exon 21 point mutation group showed no significant difference in any of the radiographic values when compared with the wild-type group., Conclusion: Our results indicate that NSCLC patients with the exon 19 deletion have such a peculiar pattern of brain metastases as multiple small metastases with small brain edema. This metastatic pattern may be similar to that of miliary brain metastases. Because it is unclear whether or not severe neurologic symptoms develop during their clinical courses like miliary brain metastases, regular evaluation with brain magnetic resonance imaging (MRI) should be considered, regardless of the presence of neurologic symptoms. Accumulation of knowledge about specific pattern of brain metastasis will help approach to "individual" management., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: We recently developed an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue. This study was undertaken to use that model to investigate the role of prostaglandin E2 (PGE2) and its receptor subtypes in the development of pannus growth and osteoclast activity in rheumatoid arthritis (RA)., Methods: Inflammatory cells that infiltrated pannus from patients with RA were collected without enzyme digestion and designated synovial tissue-derived inflammatory cells. Their single-cell suspensions were cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by the development of resorption pits in calcium phosphate-coated slides., Results: Primary culture of the synovial tissue-derived inflammatory cells resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during which tumor necrosis factor α, PGE2, macrophage colony-stimulating factor, and matrix metalloproteinase 9 were produced in the supernatant. This aberrant overgrowth was inhibited by antirheumatic drugs including methotrexate and infliximab. On calcium phosphate-coated slides, synovial tissue-derived inflammatory cells showed numerous resorption pits. In the presence of inhibitors of endogenous prostanoid production such as indomethacin and NS398, exogenous PGE1 and EP4-specific agonists significantly inhibited all these activities of synovial tissue-derived inflammatory cells in a dose-dependent manner. Addition of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of these cells' activities. EP2-specific agonist had a partial effect, while EP1- and EP3-specific agonists had no significant effects., Conclusion: These results suggest that endogenous PGE2 produced in rheumatoid synovium negatively regulates aberrant synovial overgrowth and the development of osteoclast activity via EP4., (Copyright © 2011 by the American College of Rheumatology.)

We report a patient with extensive lipomatosis involving both the ileum and mesentery. Axial computed tomographic images showed that diffuse and multiple intramural masses of fat densities compressed the ileum interior and abundant mesenteric fat compressed the retroperitoneum. Coronal magnetic resonance images showed thumbprinting of fluid containing ileum caused by fat-intensity masses.

Using rat peritoneal neutrophils, the complete nucleotide sequence of rat macrophage inflammatory protein-2 (MIP-2) mRNA including 5'untranslated region (UTR) and 3'UTR was determined (GenBank Accession number, AB060092). It was found that the MIP-2 mRNA has a 70 bp 5'UTR, a 303 bp coding region and a 728 bp 3'UTR which contains adenylate/uridylate (AU)-rich areas defined as AU-rich elements (AREs). Site-directed mutagenesis studies using the tetracycline-sensitive transactivator protein-expressing rat basophilic leukemia cells (RBL-2H3-TO cells) revealed that MIP-2 mRNA mutants which lack the 3'UTR are more stable than MIP-2-wild-type (wt) mRNA. A MIP-2 mRNA mutant in which some mutations were introduced to the ARE was also stable. The stability of MIP-2 mRNA was low in untreated RBL-2H3-TO cells, but it increased in the antigen-stimulated immunoglobulin E (IgE)-sensitized cells. The antigen-induced MIP-2 mRNA stabilization was counteracted by the highly specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the MAPK/ERK kinase (MEK-1) inhibitor PD98059. These findings indicate that ARE is the cis-element which mediates the rapid decay of MIP-2 mRNA, and the antigen stimulation stabilizes MIP-2 mRNA and the p38 MAPK and p44/42 MAPK pathways are involved in the antigen-induced stabilization of MIP-2 mRNA., (Copyright 2003 Wiley-Liss, Inc.)