Supramolecular Interactions-Assisted Polymorphism and Unique Mechanofluorochromism in 9,10-Bis((E)-4-(trifluoromethyl)styryl)anthracene.

A fluorinated distyrylanthracene (DSA) derivative, 9, 10-bis((E)-4-(trifluoromethyl)styryl)anthracene abbreviated as 4FDSA with two crystalline polymorphs (4FDSA-G (green emission) and 4FDSA-O (orange emission)), showing remarkable aggregation-induced enhanced emission and mechanofluorochromic characteristics, was developed. One of the polymorphs in its crystalline arrangement exhibits the hardly seen F…F interactions. It questions the conventional belief of the non-polarisable nature of fluorine atoms in forming the halogen bond. The twisted molecular conformation facilitated by the various supramolecular interactions resulted in the formation of another intensely emissive bluer nanocrystal (4FDSA-NC) at aggregating conditions. Even though, the both polymorphs show distinct tricolor luminescence switching on the action of mechanical force, fumigation of ground crystals with solvent vapor resulted in the formation of a more thermodynamically favorable 4FDSA-NC form. The work demonstrates the effect of supramolecular interactions assisted conformational changes in tuning the unique mechanofluorochromic characteristics of the polymorphic crystals.

Fermented milk retains beneficial effects on skeletal muscle protein anabolism after processing by centrifugation and supernatant removal.

Lactobacillus-fermented milk can stimulate anabolic effects in skeletal muscle. Fermented milk containing Lactobacillus produces aqueous molecules, such as free AA and lactate. This study aimed to investigate how processing fermented milk by centrifugation and removal of supernatant affects AA absorption and postprandial skeletal muscle protein synthesis (MPS) when mice are fed fermented milk. We gavaged male Sprague-Dawley rats with skim milk (S), fermented milk (F), or processed fermented milk (P), and examined the total AA content in portal vein blood (reflecting AA absorption) and plantaris muscle MPS at 30, 60, and 90 min following administration. Relative to fasted rats, at 30 min the total AA concentration in portal vein blood from rats in the P groups was significantly higher, followed by F and S, respectively. The MPS rates were higher for the F or P groups compared with the S group. Phosphorylation levels of p70S6 kinase in the P and F groups were significantly higher than those for the S group 30 min after administration, although the level of Akt phosphorylation was similar among the groups. These results suggested that fermentation improves AA absorption that in turn enhances postprandial MPS via Akt-independent mechanisms, and that processed fermented milk retains these favorable effects on MPS.

Top Ten Tips Palliative Care Clinicians Should Know about Implementing a Team Wellness Program.

Palliative care (PC) providers often face challenging and emotional cases while operating in the structures that are not ideally resourced. This combination can lead to burnout and further jeopardize resources from turnover, morale, and decreased productivity. Although many wellness efforts have focused on building personal resilience skills for individuals, programmatic approaches to improve a culture wellness are equally important in supporting clinical teams. This article brings together the perspectives of PC leaders with expertise in wellness to collate practical pearls for interventions that impact the culture of well-being in their organizations. In this article, we use a "Top 10" format to highlight the interventions that PC leaders can implement to support the well-being of clinical staff and promote program sustainability.

Effects of Low-Dose Dairy Protein Plus Micronutrient Supplementation during Resistance Exercise on Muscle Mass and Physical Performance in Older Adults: A Randomized, Controlled Trial.

OBJECTIVES: To investigate whether supplementation with low-dose dairy protein plus micronutrients augments the effects of resistance exercise (RE) on muscle mass and physical performance compared with RE alone among older adults. DESIGN: Randomized controlled trial. SETTING: Tokyo, Japan. PARTICIPANTS: Eighty-two community-dwelling older adults (mean age, 73.5 years) were randomly allocated to an RE plus dairy protein and micronutrient supplementation group or an RE only group (n = 41 each). INTERVENTION: The RE plus supplementation group participants ingested supplements with dairy protein (10.5 g/day) and micronutrients (8.0 mg zinc, 12 µg vitamin B12, 200 µg folic acid, 200 IU vitamin D, and others/day). Both groups performed the same twice-weekly RE program for 12 weeks. MEASUREMENTS: Whole-body, appendicular, and leg lean soft-tissue mass (WBLM, ALM, and LLM, respectively) with dual-energy X-ray absorptiometry, physical performance, biochemical characteristics, nutritional intake, and physical activity were measured before and after the intervention. Data were analyzed by using linear mixed-effects models. RESULTS: The groups exhibited similar significant improvements in maximum gait speed, Timed Up-and-Go, and 5-repetition and 30-s chair stand tests. As compared with RE only, RE plus supplementation significantly increased WBLM (0.63 kg, 95% confidence interval [CI]: 0.31-0.95), ALM (0.37 kg, 95% CI: 0.16-0.58), LLM (0.27 kg, 95% CI: 0.10-0.46), and serum concentrations of 25-hydroxyvitamin D (4.7 ng/mL, 95% CI: 1.6-7.9), vitamin B12 (72.4 pg/mL, 95% CI: 12.9-131.9), and folic acid (12.9 ng/mL, 95% CI: 10.3-15.5) (all P < 0.05 for group-by-time interactions). Changes over time in physical activity and nutritional intake excluding the supplemented nutrients were similar between groups. CONCLUSION: Low-dose dairy protein plus micronutrient supplementation during RE significantly increased muscle mass in older adults but did not further improve physical performance.

Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, inhibits the growth of squamous cell carcinoma (SCC) cells in vitro and in vivo by down-regulating expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) and FGF-2.

Heparin-binding protein 17 (HBp17)/fibroblast growth factor-binding protein-1 (FGFBP-1) was first purified from medium conditioned by A431 cells for its capacity to bind to fibroblast growth factors 1 and 2 (FGF-1 and -2). Among FGF family members, FGF-2 is a potent mitogen for various cell types, including vascular endothelial cells, fibroblasts, and cancer cells such as oral squamous cell carcinoma (OSCC) cells. Besides being well known in bone metabolism, the active form of vitamin D3, i.e., 1α,25(OH)2D3 (1,25D3), was reported to have protective effects for heart disease and cancer. Previously, we reported that 1,25D3 inhibited HBp17/FGFBP-1 expression in OSCC cell lines through NF-κB inhibition (IκBα activation) and resulted in the inactivation of FGF-2. In this study, we examined the potential anti-tumor effect of ED-71, an analog of 1α,25(OH)2D3, for squamous cell carcinoma cells in vitro and in vivo. The cell lines used were OSCC cell lines (NA-HO-1-n-1 and UE-HO-1-u-1), established from oral cancer patients in our laboratory, and an epidermoid carcinoma/SCC cell line (A431). The growth assay in serum-free culture revealed that ED-71 inhibited the growth of the cancer cell lines in a dose-dependent manner. In addition, ED-71 suppressed HBp17/FGFBP-1 expression by inhibiting the NF-κB pathway as did 1,25D3. Furthermore, a luciferase reporter assay revealed that the promoter activity of HBp17/FGFBP-1 (region between -217 and +61) was down-regulated by ED-71. Oral administration of ED-71 significantly inhibited the growth of A431-derived tumors in athymic nude mice. Immunohistochemical analysis revealed that the expression of HBp17/FGFBP-1, FGF-2, CD31, and Ki-67 in the tumors of ED71-treated group was down-regulated in comparison to control. These results suggest that ED-71 possesses potential anti-tumor activity for SCCs both in vitro and in vivo. This compound may act directly on the tumor cells or on endothelial cells by modulating the tumor microenvironment.

Effect of nCPAP therapy on heart rate in patients with obstructive sleep apnoea-hypopnoea.

BACKGROUND: Elevated heart rate (HR) is a risk factor for cardiovascular disease. The effects of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) on HR are controversial. AIM: To investigate the effect of nasal continuous positive airway pressure (nCPAP) therapy on HR in OSAHS patients. METHODS: Sixty-two OSAHS patients underwent 24-h electrocardiographic recording, both before and 3 or 4 days after instigation of nCPAP. RESULTS: After nCPAP was started, HR significantly decreased (mean +/- SD 71.8 +/- 10.6 vs. 67.5 +/- 9.4 bpm, p < 0.0001), both in the daytime (0600-2200 h, 76.3 +/- 12.2 vs. 72.2 +/- 10.2 bpm, p < 0.0001) and at night-time (2200-0600 h, 64.5 +/- 9.1 vs. 60.0 +/- 8.9 bpm, p < 0.0001). HR was significantly reduced in both periods in the 44 patients with hypertension and/or diabetes mellitus, but only during the night-time in the 18 with neither condition. Before nCPAP treatment, HR was positively correlated with percentage time of arterial O2 saturation <90% during sleep (p = 0.008) and with the apnoea-hypopnoea index during sleep (p = 0.003). In 15 patients undergoing HR for 2 days before starting nCPAP, the mean HRs for the two periods were similar (p = 0.95). DISCUSSION: nCPAP therapy appears to decrease HR in OSAHS patients, and may thereby reduce their risk of cardiovascular disease.

Molecular cloning and sequencing of cDNAs encoding homologues of human Ku70 and Ku80 autoantigen from Xenopus and their expression in various Xenopus tissues.

We isolated cDNA clones encoding Ku70 and Ku80 homologues of Xenopus laevis from a cDNA library prepared from Xenopus oocytes. The nucleotide sequences of these Ku70 and Ku80 homologues have coding sequences of 1833 bp and a 611 aa protein, and 2178 bp and a 726 aa protein, respectively. The amino acid sequences deduced from the open reading frame of the Ku70 and Ku80 cDNA clones were highly homologous to those from Ku genes previously isolated, such as human (ca. 65% and ca. 62% identity, respectively) and mouse (ca. 65% and ca. 60%), and show a certain degree of homology to Drosophila (ca. 27% with Ku70), Caenorhabditis elegans (ca. 20% with Ku80) and Saccharomyces cerevisiae (ca. 23% and ca. 19%). Our detailed comparison of the predicted amino acid sequences among these species revealed the highly conserved octa-peptide LPFXXDIR common to both Xenopus Ku70 and Ku80 homologues in the region showing the high homology throughout the species tested. A Northern analysis using specific cDNA probes showed that Ku poly(A)+ mRNAs are expressed at high levels in Xenopus adult oocyte and testis.

The Bean Seed Storage Protein [beta]-Phaseolin Is Synthesized, Processed, and Accumulated in the Vacuolar Type-II Protein Bodies of Transgenic Rice Endosperm.

The seed storage protein [beta]-phaseolin of the common bean (Phaseolus vulgaris L.) was expressed in the endosperm of transgenic rice (Oryza sativa L.) plants. The 5.1- or 1.8-kb promoter fragment of the rice seed storage protein glutelin Gt1 gene was fused transcriptionally to either the genomic or cDNA coding sequence of the [beta]-phaseolin gene. The highest quantity of phaseolin estimated by enzyme-linked immunosorbent assay was 4.0% of the total endosperm protein in the transgenic rice seeds. The phaseolin trait was segregated as a single dominant trait with a positive gene dosage effect and was stably inherited through three successive generations. Both phaseolin genomic and cDNA coding sequences were used to synthesize four isoforms of mature phaseolin protein with apparent molecular masses of 51, 48, 47, and 45 kD. Enzyme deglycosylation experiments indicated that the 51-kD form contains high-mannose N-glycans; the 48- and 47-kD forms have further modified N-glycans; and the 45-kD form is a nonglycosylated protein. Immunolabeling studies using light and electron microscopy demonstrated that phaseolin accumulates primarily in the vacuolar type-II protein bodies located at the periphery of the endosperm near the aleurone layer. We discuss the implications of these results on nutritional improvement of rice grains.

Structure and differential response to abscisic acid of two promoters for the cytosolic copper/zinc-superoxide dismutase genes, SodCc1 and SodCc2, in rice protoplasts.

We determined the 5'-flanking sequences of two nuclear genes (SodCc1 and SodCc2) encoding cytosolic copper/zinc-superoxide dismutase in rice (Oryza sativa L.). Utilizing transient beta-glucuronidase (GUS) reporter assays, functional promoter-GUS analysis was performed in rice protoplasts exposed to the phytohormone abscisic acid (ABA) or the antioxidant sulfhydryl reagent, dithiothreitol (DTT). Transcriptional activities from both SodCc-GUS fusions were stimulated by DTT, which induces the promoter activity of the tobacco SodCc gene [Proc. Natl. Acad. Sci. USA 90 (1993) 3108-3112]. ABA had no effect on SodCcl-GUS expression but specifically induced the gene expression of the SodCc2-GUS fusion. The simultaneous application of ABA and gibberellin A3, however, abolished the enhancing effect of ABA. These results indicated that two rice SodCc promoters differentially respond to externally supplied ABA and that one of the regulatory factors for plant SodCc expression is ABA in addition to cellular redox-modulating antioxidants.

Structure-taste correlation of L-aspartyl dipeptides using SIMCA method.

One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. The classification rates were calculated to be 87% and 81% for sweet and bitter peptides, respectively. The SIMCA method has also suggested that two factors, shape and size, of the C-terminal amino acid moiety R in the dipeptides are extremely important to model their taste qualities.

Does extensive dissection of lymph nodes improve the results of surgical treatment of gastric cancer?

The results of surgical treatment of patients with advanced gastric cancer were analyzed retrospectively in terms of the extent of dissection of lymph nodes. The postoperative 5-year survival rate was 50.3% for 160 patients who had undergone potentially curative surgery with dissection of group 1, 2, and 3 lymph nodes (R3), compared with 48.8% for 185 patients with dissection of group 1 and 2 lymph nodes (R2). There was no difference in terms of survival between the two groups of patients. Of 160 patients receiving R3, 19 (11.9%) were found to be positive for metastasis to group 3 lymph nodes, and only 5 survived for more than 5 years after surgery (postoperative 5-year survival rate of 26.3%). In four of these five patients, metastases in the group 3 lymph nodes were confined to nodes in the hepatoduodenal ligament. Thus, it appears that in dissection of the deepest nodes, lymph nodes in the hepatoduodenal ligament are the most important to remove in the surgical treatment of advanced gastric cancer.

Pure red cell aplasia during carbamazepine monotherapy.

A 7-year-old girl developed pure red cell aplasia during carbamazepine (CBZ) monotherapy for epilepsy. She developed generalized clonic convulsions at the age of 7 years and 8 months. Treatment with CBZ was begun. Two months later she was admitted to our hospital because of severe anemia. Bone marrow examination revealed the almost complete absence of erythroblasts, with normal myelopoiesis and megakaryocytopoiesis, indicating pure red cell aplasia. Following the discontinuation of CBZ, she developed brisk reticulocytosis within 1 week and her hemoglobin level rose to a normal one within 1 month. Although the hematological toxicity of CBZ is well documented, isolated cessation of red cell production is uncommon. A patient who is undergoing treatment with CBZ should be carefully monitored, especially for serious adverse reactions including pure red cell aplasia.

Cerebral blood flow changes in orthostatic dysregulation fainters.

The changes in blood flow of both the internal carotid and the vertebral artery during orthostatic test with or without fainting attack were studied in 25 healthy children and 30 patients with orthostatic dysregulation (OD). In healthy children and non-fainted OD patients, no change in blood flow occurred in either the internal carotid artery or the vertebral artery during orthostatic test. On the other hand, a significant decrease in blood flow of the internal carotid artery and/or the vertebral artery occurred during fainting of OD patients. These data suggest that three mechanisms might be involved in fainting of OD patients; a decrease in blood flow of the internal carotid artery, the vertebral artery and a decrease in blood flow of both these arteries.

Antiepileptic effects of clobazam in children.

Many benzodiazepines used as anticonvulsants have nitrogen radicals in positions 1 and 4. Clobazam has nitrogen radicals in positions 1 and 5. We studied the antiepileptic effect of clobazam in 36 patients with intractable epilepsies in childhood. Their ages were 1 year 1 month to 16 years 5 months (mean 8 years). The mean initial dose was 0.33 mg/kg of daily doses and increased up to 0.71 mg/kg. Nine cases (primary generalized epilepsy 2/2, secondary generalized epilepsy 7/29) were completely free from seizures, and another 9 (secondary generalized epilepsy 8/29, partial epilepsy 1/5) experienced a decrease of 50% or more in seizure frequency. Seizure frequency did not change in 16, and increased in the other 2 (secondary generalized epilepsy 2/29). The antiepileptic effects were observed on the first day to 10th day after clobazam treatment. There were recurrences of seizures in 4 out of 9 patients with complete control of seizures, 1 month alter in 3 and 10 months later in one. Mean serum clobazam level of 7 improved cases was 73 ng/ml and that of 3 cases with no response was 94 ng/ml. Although mild clinical side effects such as drowsiness were observed transiently in 17 cases, no abnormality was found in laboratory investigations performed.

Internal carotid blood flow velocity in children with cerebral palsy by Doppler Ultrasound method.

Cerebral blood flow assessed noninvasively by Doppler ultrasound technique in 30 children with cerebral palsy. The average maximal blood velocity (A/L) and end-diastolic blood velocity (d) of internal carotid artery were measured before and during brief digital compression of contralateral common carotid artery. Both A/L and d values in children with cerebral palsy were significantly lower than those observed in normal healthy children. In 13 children with spastic hemiplegia, no significant difference in either A/L or d was seen between the non-affected side and affected side both before and during brief digital compression. This data suggests that mean cerebral blood flow decreases in our children with cerebral palsy, and that no lateralization of the decrease in hemispheric cerebral circulation in hemiplegic children may explain by supposing the existence of generalized bilateral brain damage in those subjects.

Nonconvulsive status epilepticus in a child with congenital bilateral perisylvian syndrome.

A 9-year-old male with congenital bilateral perisylvian syndrome is described. He had pseudobulbar palsy, mental retardation, and intractable epilepsy. Computed tomography and magnetic resonance images of the brain demonstrated bilateral perisylvian malformations and a diffuse pachygyric appearance. At 8 years of age, he had episodes of excessive drooling, fluctuating impairment of consciousness, unsteady sitting, and frequent head drop that lasted several days. The electroencephalogram demonstrated continuous diffuse slow spike and waves. These findings suggested atypical absence status epilepticus. Intravenous administration of diazepam resulted in transient improvement of clinical and electroencephalographic findings. Status epilepticus recurred within several minutes after diazepam administration. Although no patient has been reported to have a history of status epilepticus among those affected by this syndrome, it seems that atypical absence status can occur more frequently than expected, as seen in Lennox-Gastaut syndrome. After recognition and confirmation of nonconvulsive status epilepticus, immediate treatment must be attempted.

Mutations in the human homologue of the Drosophila segment polarity gene patched in oral squamous cell carcinoma cell lines.

In the present study, we have analyzed tumor deoxyribonucleic acid from oral squamous cell carcinoma (OSCC) cells for patched mutations using an exon-by-exon single strand conformation polymorphism assay and direct sequencing. We found two missense mutations which affected the conserved residue in the transmembrane domains of the gene product and in the intracellular loop at the C-terminal residue implicated in regulating the smoothened molecule. In addition, we demonstrated that the N-terminal fragment of sonic hedgehog (Shh-N) stimulates the growth of normal epithelial cells, the OSCC cell line, NA, and the salivary gland adenocarcinoma cell lines, HSG and HSY, which have no detectable mutation in patched. On the other hand, Shh has no effect on human SCC cells (UE, KA, KO, NI, A431 cells) that have mutations in patched. These results strongly suggest that an Shh-patched signaling is involved in the cell growth of oral epithelial cells and in the tumorigenesis of OSCCs.

Role of anions on heavy metal sorption of a cellulose modified with poly(glycidyl methacrylate) and polyethyleneimine.

The influence of anions on the equilibrium and kinetic uptake of heavy metals from an aqueous solution by a novel nitrogen-type chelating adsorbent was evaluated. Equilibrium experiments revealed that stoichiometric amounts of metals and anions are adsorbed by the resin. Kinetic studies showed that during the initial stage of adsorption, the anions are adsorbed by the adsorbent prior to the metal ions. This occurred almost simultaneously with an increase in solution pH. At equilibrium, the pH returned towards its initial value. The concentration of anion also fluctuated during the entire equilibration process. Following these observations, mechanisms governing the role of anions on enhancing capacity and rate of metal uptake of this type of chelating adsorbent type were established.

Seroepidemiological study of toxoplasmosis in two different geographical areas in Nepal.

A total of 302 serum samples collected from Chitawan (159) and Mustang (143) districts of Nepal were included in this study. Anti-toxoplasma antibody was detected using micro-latex agglutination (MLA) and ELISA methods. An overall positive rate was found to be 57.9%. The positive rate in Chitawan was significantly higher (64.1%) (less than 1,000 m altitude) compared to that in Mustang (51.0%) (more than 3,000 m altitude) (p < 0.05). Females in Chitawan showed significantly higher positive rate (71.2%) compared to males (56.9%) (p < 0.05). On the contrary, though insignificantly, males showed higher positive rate (57.9%) compared to that of females (43.3%) in Mustang. Almost equal positive rate was observed among males in both study area. Females in Chitawan showed significantly higher (71.2%) positive rate compared to their counterparts in Mustang (43.3%) (p < 0.001). A slight increase in positive rate with age was observed in Chitawan while in Mustang a decreasing trend was noticed. Ethnically though statistically not significant, Indo-Aryans showed a higher positive rate (69.2%) compared to the positive rate shown by Tibeto-Burmans (63.1%) in Chitawan while the reverse was true in Mustang (Tibeto-Burmans: 53.8% and Indo-Aryans: 38.4%). Interestingly, 2.9% and 1.3% of MLA positive samples showed toxoplasma IgM antibody. None of the IgM positive samples were positive for toxoplasmic antigens.

Toxoplasma antibody prevalence in Nepalese pregnant women and women with bad obstetric history.

Sera from randomly selected 345 pregnant Nepalese women aged 16-36 years and 13 women with bad obstetric history (BOH) were tested for the presence of Toxoplasma antibodies using microlatex agglutination (MLA) and ELISA methods. The overall prevalence was 55.4% (191/345). Prevalence was slightly higher (59.0%) in older age-group (27-36 years) compared with younger age-group (16-26 years) (52.2%). No significant difference in antibody prevalence in women belonging to two different ethnic-groups (Tibeto-Burmans 57.8%, Indo-Aryans 52.7%) was observed (p>0.05). MLA antibody titer ranged from 1:16 to 1:2,048. Over three-fourth of the women showed either high (1:510 or over) or low (1:16 or 1:32) antibody titer. Three percent (6/191) of MLA antibody positive subjects had Toxoplasma IgM antibodies by IgM-ELISA. All six IgM antibody positive pregnant women had MLA antibody titer of over 1:510. Of the total 13 women with BOH, 5 (38.5%) had Toxoplasma antibodies of which 2 (40.0%) were positive for Toxoplasma-IgM antibodies.