Comparing Variations in Advance Directives Timing among Older Adults with End-Stage Renal Disease versus Cancer.

Background: Having an advance directive (AD) is associated with better care at end of life and better quality of death. However, AD completion rates among End-Stage Renal Disease patients are lower than among cancer patients. ESRD patients commonly experience cognitive impairment, reducing their ability to make their own care choices as their disease progresses. Thus, having an AD earlier in the disease trajectory is important. Little is known about differences in AD completion timing among ESRD and cancer patients. Therefore, the purpose of this study was to (1) investigate difference in AD completion and timing between ESRD and cancer patients; and, (2) identify factors associated with the early and late AD completion. Setting and Participants: A retrospective cohort study was conducted. Data was drawn from the Health and Retirement Study, a United States representative longitudinal survey of older adults, using exit interviews conducted from 2006 to 2016 among 1886 proxy reporters of deceased participants with ESRD or cancer. Results: ESRD patients had lower rates of AD completion compared to those with cancer. Higher education and being older were negatively associated with late AD completion in the last 3 months of life. Additionally, decedents with a diagnosis of ESRD, older age, and with higher education had higher odds of completing ADs one year or more before death. Discussions/Conclusions: While ESRD patient were less likely to have ADs, those that had ADS were more likely than cancer patients to develop ADs earlier in the disease trajectory. Further studies are needed to determine effective strategies to increase the AD completion rate among patients with ESRD.

Identifying Paths Forward: Expanding Palliative Care to Low-Income Patients in California.

Multiple studies demonstrate most consumers do not know about palliative care. And, since January 2018, California's Medi-Cal Managed Care patients have been eligible for palliative care services under Senate Bill 1004 (SB 1004). Yet, the uptake of palliative care services was underwhelming. The purpose of this study was to explore patient-centered barriers to palliative care. We recruited 27 adult Medicaid managed care patients from community-based sites in Los Angeles and conducted semi-structured qualitative interviews. Each participant was asked questions to elicit their knowledge about, and perspectives on, palliative care as well as their preferred communication approaches for receiving a referral to palliative care. The interviews were audio-recorded and transcribed verbatim. We used a grounded theory approach to guide our analysis of primary themes. Our findings indicated that the barriers to palliative care referrals among this population included lack of knowledge about palliative care and available services; the reliance on, and trust in, primary care physicians for information; language and cultural barriers; housing instability; and patient believing they are neither old enough nor sick enough to need palliative care. These findings emphasize the critical role primary care physicians play in advocating for low-income patients and the necessity for culturally sensitive education about palliative care. Promoting knowledge and understanding of palliative care among both primary care physicians and consumers is critical to ensuring access to care.

Olfactory Outcomes After Middle Turbinate Resection in Endoscopic Transsphenoidal Surgery: A Prospective Randomized Study.

OBJECTIVE: Endoscopic endonasal transsphenoidal surgery is safe and effective for sellar and parasellar tumor removal. Partial middle turbinate (MT) resection is sometimes performed to optimize the surgical field and facilitate postoperative care. Disturbances in olfaction are concerning because of the lack of randomized studies in this field. STUDY DESIGN: Prospective randomized trial. SETTING: Single academic medical center. METHODS: We resected the lower halves of bilateral MTs in the resected group and laterally fractured bilateral MTs in the preserved group. Olfactory outcomes and sinonasal conditions were assessed by using the validated Taiwan Smell Identification Test and Lund-Kennedy Endoscopy Score, respectively. Forty-nine patients were enrolled in the final analysis, of whom 23 underwent partial MT resection. RESULTS: The average Taiwan Smell Identification Test result was 36.9 one month after surgery, with a significant change of -4.4 ± 3.1 (mean ± SD; P < .01) from baseline. The impact was not significant at 3 months (-2.1 ± 2.6, P = .13) or 6 months (0.3 ± 2.0, P = .79). Between the MT resection and preservation groups, there were no significant differences at postoperative 1 month (P = .60), 3 months (P = .86), and 6 months (P > .99). Lund-Kennedy Endoscopy Score was still higher at 3 months (P = .006) after surgery but returned to the preoperative level at 6 months (P = .63). CONCLUSIONS: Endoscopic endonasal transsphenoidal surgery may affect olfaction at 1 month after surgery, and olfactory function is expected to return after 3 months. Partial MT resection did not result in additional olfactory loss. It is safe to perform partial MT resection during surgery without compromising the olfactory outcomes.

Fructobacillus apis sp. nov., isolated from the gut of honeybee (Apis mellifera).

A Gram-positive, facultatively anaerobic, catalase-negative, fructose-dependent strain (W13T) was isolated from the gut of honeybee (Apis mellifera). Phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain W13T represents a distinct line of descent within the genus Fructobacillus, with the closest neighbours being Fructobacillus broussonetiae BCRC 81240T (98.9 % sequence similarity) and Fructobacillus durionis DSM 19113T (96.8 % sequence similarity). Comparative sequencing of the additional phylogenetic markers rpoC and recA confirmed the 16S rRNA gene tree topology. The complete genome of strain W13T consisted of 1 292 712 bp with a G+C content of 48.3 mol%. Pairwise comparisons of the average nucleotide identity values and digital DNA-DNA hybridization values between the genomes of W13T and its close phylogenetic neighbours, F. broussonetiae BCRC 81240T and F. durionis DSM 19113T, resulted in 76.2-84.1 % and 20.2-27.6 %, respectively. The main cellular fatty acids of strain W13T were C16 : 0, C18 : 1 ω9c and C18 : 1 ω7c. Thus, we propose a novel species within the genus Fructobacillus, with the name Fructobacillus apis sp. nov. and the type strain is W13T (= NBRC 115637T=BCRC 81365T).

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.

Simvastatin Possesses Antitumor and Differentiation-Promoting Properties That Affect Stromal Cells in Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCTB) is a locally aggressive destructive bone lesion. The management of pulmonary metastasis and local recurrence after the surgical treatment of GCTB remains a challenge. Pathologically, stromal cells in GCTB are known as primary neoplastic cells and are recognized as incompletely differentiated preosteoblasts. Therefore, inducing GCTB stromal cells to differentiate into cells with a mature osteoblastic phenotype may stop tumor growth and recurrence. In this study, we aimed to investigate how simvastatin, a clinically approved and commonly used statin that has been known to promote the maturation of cells of the osteogenic lineage, affects GCTB stromal cells. We found that simvastatin effectively inhibited cell viability by suppressing proliferation and by inducing apoptosis in GCTB stromal cells. Moreover, simvastatin treatment upregulated the expression of genes related to osteogenic maturation, such as runt-related transcription factor 2, osteopontin, and osteocalcin, and increased the mineralization of the extracellular matrix in GCTB stromal cells. Ingenuity pathway analysis was used to discover that the vitamin D receptor pathway was involved in the simvastatin-induced osteogenic differentiation of GCTB stromal cells by upregulating the 1,25-dihydroxyvitamin D metabolism. Taken together, this in vitro study demonstrates the antitumor and differentiation-promoting effects of simvastatin on GCTB stromal cells and suggests the possibility of using simvastatin as an adjuvant therapy for GCTB. These findings support further clinical investigation of the efficacy of using simvastatin as an adjuvant therapy for GCTB to reduce recurrence and distant metastasis after surgical treatment. © 2019 Orthopedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:297-310, 2020.

Critical Factors in Human Antizymes that Determine the Differential Binding, Inhibition, and Degradation of Human Ornithine Decarboxylase.

Antizyme (AZ) is a protein that negatively regulates ornithine decarboxylase (ODC). AZ achieves this inhibition by binding to ODC to produce AZ-ODC heterodimers, abolishing enzyme activity and targeting ODC for degradation by the 26S proteasome. In this study, we focused on the biomolecular interactions between the C-terminal domain of AZ (AZ95-228) and ODC to identify the functional elements of AZ that are essential for binding, inhibiting and degrading ODC, and we also identified the crucial factors governing the differential binding and inhibition ability of AZ isoforms toward ODC. Based on the ODC inhibition and AZ-ODC binding studies, we demonstrated that amino acid residues reside within the α1 helix, ß5 and ß6 strands, and connecting loop between ß6 and α2 (residues 142-178), which is the posterior part of AZ95-228, play crucial roles in ODC binding and inhibition. We also identified the essential elements determining the ODC-degradative activity of AZ; amino acid residues within the anterior part of AZ95-228 (residues 120-145) play crucial roles in AZ-mediated ODC degradation. Finally, we identified the crucial factors that govern the differential binding and inhibition of AZ isoforms toward ODC. Mutagenesis studies of AZ1 and AZ3 and their binding and inhibition revealed that the divergence of amino acid residues 124, 150, 166, 171, and 179 results in the differential abilities of AZ1 and AZ3 in the binding and inhibition of ODC.

Chemo-, regio-, and enantioselective synthesis of allylic nitrones via rhodium-catalyzed addition of oximes to allenes.

The first chemo-, regio-, and enantioselective rhodium-catalyzed addition of oximes to allenes is reported. Using a Rh(i)/Josiphos catalyst system under mild conditions, the construction of allylic C-N bonds instead of C-O bonds was achieved. This method permits the atom-economic synthesis of branched allylic nitrones in good to quantitative yields with excellent enantioselectivities.

Mechanical stretch induces hair regeneration through the alternative activation of macrophages.

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.

Differential effects of postoperative oral corticosteroid on eosinophilic vs. non-eosinophilic CRSwNP subtypes.

PURPOSE: The efficacy of postoperative oral corticosteroids on surgical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients following endoscopic sinus surgery (ESS) remains controversial. This study evaluated the potential benefits of postoperative oral corticosteroids on surgical outcomes in CRSwNP patients and investigated the differential effects on eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). MATERIALS AND METHODS: Patients with bilateral CRSwNP who underwent ESS were enrolled and randomized to receive either oral prednisolone (30 mg/day) or placebo for 2 weeks after surgery. Visual analog scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22) scores were chosen as the subjective outcomes, evaluated at preoperative baseline and 1, 3, and 6 months postoperatively. Lund-Kennedy Endoscopic Scores (LKESs) were used as the objective outcome, evaluated at preoperative baseline and at 2 weeks and 2, 3, and 6 months postoperatively. RESULTS: In total, 100 patients with bilateral CRSwNP were enrolled, of whom only 82 completed the 6-month follow-up. The subjective outcomes showed no significant difference at each follow-up points. Of the objective outcomes, the corticosteroid group reporting a trend of improvement in LKESs at 6 months postoperatively (p = 0.05). After stratification by tissue eosinophils, only patients with NECRSwNP (<10 eosinophils/HPF) demonstrated a significant improvement in LKESs at 3 months postoperatively (p = 0.03). CONCLUSIONS: Postoperative oral corticosteroids did not provide additional improvements in VAS and SNOT-22 scores; nevertheless, a trend of LKES improvement was noted at 6 months postoperatively. After stratification by tissue eosinophils, this effect was significant only among NECRSwNP patients at 3 months follow-up.

A Paper-Based Piezoelectric Accelerometer.

This paper presents the design and testing of a one-axis piezoelectric accelerometer made from cellulose paper and piezoelectric zinc oxide nanowires (ZnO NWs) hydrothermally grown on paper. The accelerometer adopts a cantilever-based configuration with two parallel cantilever beams attached with a paper proof mass. A piece of U-shaped, ZnO-NW-coated paper is attached on top of the parallel beams, serving as the strain sensing element for acceleration measurement. The electric charges produced from the ZnO-NW-coated paper are converted into a voltage output using a custom-made charge amplifier circuit. The device fabrication only involves cutting of paper and hydrothermal growth of ZnO NWs, and does not require the access to expensive and sophisticated equipment. The performance of the devices with different weight growth percentages of the ZnO NWs was characterized.

Amylolysis is predominated by cell-surface-bound hydrolase during anaerobic fermentation under mesophilic conditions.

While knowing the amylolysis mechanism is important to effectively decompose corn starch fed into an anaerobic digestor, the objective of this study was to detect the activities and locations of α-amylase in a continuous reactor and batch cultures. In the continuous reactor operated at 35 °C, the greatest cell-bound α-amylase activity was found to be 4.7 CU mL-1 at hydraulic retention time (HRT) = 9 h, while the greatest volumetric hydrogen production rate (rH2) was observed at HRT = 3 h as 61 mmol L-1 day-1. In the batch tests, the cell-bound α-amylase activities increased when the carbohydrate concentration decreased, and no significant reducing sugar accumulation was found in the serum bottles. By examining the specific hydrogen production rate (qH2) against different corn starch concentrations, the half-saturation constant (KSta) and the maximum qH2 were regressed to be 0.47 g L-1 and 6 mmol g-VSS-1 d-1, respectively. The electronic microscopic images showed that the microbes could colonize on the starch granules without the disturbance of any floc-like materials. Conclusively, by excluding the methanogens and floc matrix, the secreted α-amylases are predominately bound on the cell surfaces and enabled the microbial cells favorably attach on large substrates for hydrolysis under the mesophilic condition.

Rhodium-catalyzed addition of sulfonyl hydrazides to allenes: regioselective synthesis of branched allylic sulfones.

A rhodium-catalyzed regioselective addition of sulfonyl hydrazides to allenes is reported. With Rh(i)/DPEphos/benzoic acid as the catalyst system, branched allylic sulfones can be obtained, in good to excellent yields and regioselectivities.

The impact of chronic carrier of hepatitis B virus on liver function in a 7-day ultramarathon race.

BACKGROUND: Several changes in physiological characteristics occur during long-distance and 24-hour ultramarathons, including hyponatremia, skeletal muscle breakdown, plasma volume changes, iron depletion, anemia, and possible hepatic damage. The purpose of this study was to investigate the impact of hepatitis B virus (HBV) carrier status on liver function during multi-day races. METHODS: This prospective study recruited 10 Taiwanese runners who were scheduled to participate in the 7-day 2008 Athens Ultramarathon Festival Race, and three of them were chronic carriers of HBV. Blood samples were collected before, during, and 3 days after the race, including alkaline phosphatase (ALP), albumin (ALB), total protein (TP) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-BIL) RESULTS: Ten Taiwanese runners (40% female; average age 52.3 ± 7.9 years) who all planned to run in the race were recruited. Three runners were chronic carriers of HBV (HBV carrier), and all participants were anti-HCV antibody-negative and anti-hepatitis A virus (HAV) IgG-positive. There were no significant time-by-group effects on ALP, ALB, and TP levels, but the change over time effects were significant (p < 0.001, p = 0.001 and p = 0.010, respectively). ALT, AST, and T-BIL increased significantly to markedly higher levels in the HBV carrier group compared to the non-carrier group (group effect p = 0.009, p = 0.004, and p = 0.05, respectively), and the time-by-group interaction was also significant for these liver function markers (p < 0.001, p < 0.001, and p = 0.001, respectively). CONCLUSION: Compared to their counterparts, runners who are HBV carriers had significantly greater increases in levels of ALT, AST, and T-BIL during a 7-day ultramarathon, indicating that the liver function of carriers is more highly impacted in these races.

Asymmetric synthesis of allylic amines via hydroamination of allenes with benzophenone imine.

Rhodium-catalyzed highly regio- and enantioselective hydroamination of allenes is reported. Exclusive branched selectivities and excellent enantioselectivities were achieved applying a rhodium(i)/Josiphos catalyst. This method permits the practical synthesis of valuable α-chiral allylic amines using benzophenone imine as ammonia carrier.

Photocyclization and Photoaddition Reactions of Arylphenols via Intermediate Quinone Methides.

A series of five benzannelated derivatives of 2-phenylphenol were prepared, and their photochemistry was investigated. Two of these (3-phenyl-2-naphthol, 10, and 1-phenyl-2-naphthol, 11) were photoinert. For 2-(1-naphthyl)phenol (12) and 1-(1-naphthyl)-2-naphthol (13), ESPT took place to either the 2'-position or the 7'-position of the naphthalene ring to give quinone methides (QMs) that underwent either reverse proton transfer (RPT) or electrocyclic ring closure to give dihydrobenzoxanthenes. The intermediate QMs for 12 and 13 were detected and characterized by laser flash photolysis. For 2-(9-phenanthryl)phenol (14), ESPT took place either to the 5'-position to give a QM that underwent quantitative electrocyclic ring closure to give the corresponding benzoxanthene or to the 10'-position to give a QM that underwent RPT. If the solution contained methanol, the QM produced on ESPT to the 10'-position in 14 could be trapped as the photoaddition product. The compounds studied in this work demonstrate three possible reactions of QMs produced following ESPT to aromatic carbon atoms: (1) reverse proton transfer (RPT) to regenerate starting material; (2) addition of hydroxylic solvents to give the photoaddition product; and (3) electrocyclic ring closure to give benzoxanthene derivatives.

Structural basis of antizyme-mediated regulation of polyamine homeostasis.

Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az1 binding. The structural basis of the Az1-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az1 complexed with either ODC or AzIN. Structural analysis revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az1-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN may effectively compete with ODC for Az1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.

Synthesis of Bicyclic Isoxazoles and Isoxazolines via Intramolecular Nitrile Oxide Cycloaddition.

An efficient and straight forward procedure for the syntheses of bicyclic isoxazole/isoxazoline derivatives from the corresponding dimethyl-2-(2-nitro-1-aryl/alkyl)-2-(prop-2-yn-1yl)malonates or dimethyl 2-allyl-2-(2-nitro-1-aryl/alkyl ethyl)malonate is described. High yields and simple operations are important features of this methodology.