[Study on trans-differentiation of adult human myoblasts into neural precursor cells and its implantation in rats].
To investigate the feasibility of inducing adult human myoblasts into neural precursor cells. The myoblasts were isolated with mixed digestive enzyme from minced human temporal muscle samples, cultured and purified clonally. The 3rd passage cells were incubated with serum free medium including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). Morphological change was investigated during incubation period. Immunofluorescence cytochemistry and RT-PCR analysis were used to assess cell differentiation and trans differentiation. After the induction, cells became non-adherent aggregates as neurospheres. The myoblast-derived neurospheres was immuno-positive for nestin. In differentiation condition, they looked like neurons and glial cells and expressed neuronal (microtubule associated protein 2, MAP-2), astrocytic (Glial fibrillary acidic protein, GFAP) and oligodendrocytic (Galactocerebroside, Galc) markers by immunocytochemistry. The result by RT-PCR was coincident with immunocytochemistry. The myoblast-derived neurospheres expressed MAP-2 and GFAP after they were transplanted into the brain of rats with cerebral ischemia. Adult human myoblasts can be inducted to trans-differentiate into neural precursor cells.


Divergent Dynamic Kinetic Resolution of a Racemic Mixture of Four Stereoisomers via N-Heterocyclic Carbene Organocatalysis.
Racemic mixtures of four stereoisomers are easily formed via many fundamental organic transformations, but the direct utilities of these mixtures have been less studied and remain large challenges to date. In this work, we introduce a new method, i.e., divergent dynamic kinetic resolution, to achieve the separation of racemic mixtures of four stereoisomers. The hypothesis was proved by using a N-heterocyclic carbene-catalyzed benzoin reaction, which afforded two separable diastereomeric products bearing three consecutive stereocenters with good to excellent enantioselectivties. We believe that this resolution protocol will find applications in more transformations.


Noninvasive methods to identify early vascular access dysfunction.
A functional vascular access is of critical importance to the hemodialysis patient, the patient's healthcare providers, and the hemodialysis treatment center. A poorly functioning or thrombosed vascular access can lead to increased morbidity, hospitalization, length of stay, and cost. This article reviews the increasing evidence supporting surveillance of arteriovenous (AV) hemodialysis access and the various strategies and techniques available for detection of a failing access.


Hypothalamic Menin regulates systemic aging and cognitive decline.
Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.


Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells.
Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1-agonist and anticancer activities. These experiments led to the identification of 9-epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain potency against apoptosis-resistant cancer cells as well as those displaying the multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal-Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.


Postoperative morbidity and mortality after surgical resection of small bowel neuroendocrine neoplasms: A systematic review and meta-analysis.
Although small bowel resection is generally considered a low risk gastrointestinal procedure, this might not be true for small bowel neuroendocrine neoplasms (SB-NEN) as a result of potential central mesenteric involvement. We aimed to determine the reported morbidity and mortality after resection of SB-NEN in the literature and assess the effect of hospital volume on postoperative morbidity and mortality. A systematic review was performed by searching MEDLINE and Embase in March 2021. All studies reporting morbidity and/or mortality after SB-NEN resection were included. Pooled proportions of overall morbidity (Clavien-Dindo I-IV), severe morbidity (Clavien-Dindo III-IV), 30-day mortality, 90-day mortality and in-hospital mortality were calculated, as well as the association with hospital volume (high volume defined as the fourth quartile). Thirteen studies were included, with a total of 1087 patients. Pooled proportions revealed an overall morbidity of 13% (95% confidence interval [CI] = 7%-24%, I2 = 90%), severe morbidity of 7% (95% CI = 4%-14%, I2 = 70%), 30-day mortality of 2% (95% CI = 1%-3%, I2 = 0%), 90-day mortality of2% (95% CI = 2%-4%, I2 = 35%) and in-hospital mortality of 1% (95% CI = 0%-2%, I2 = 0%). An annual hospital volume of nine or more resections was associated with lower overall and severe morbidity compared to lower volume: 10% vs 15% and 4% vs 9%, respectively. Thirty-day mortality was similar (2% vs 1%) and 90-day mortality was higher in high-volume hospitals: 4% vs 1%. This systematic review with meta-analyses showed severe morbidity of 7% and low mortality rates after resection of SB-NEN. The currently available literature suggests a certain impact of hospital volume on postoperative outcomes, although heterogeneity among the included studies constrains interpretation.


Should suspected early gallbladder cancer be treated laparoscopically?
Early gallbladder cancer (EGC), defined as T1 and T2 disease, is frequently curable when completely excised without bile spillage. The objective of the present study was to determine what effect initial laparoscopic cholecystectomy has on outcome in patients with EGC. Of 89 patients referred to our institution with gallbladder cancer over an 11-year period, 26 had undergone initial laparoscopic cholecystectomy. Sixteen of the 26 patients had T1 or T2 disease and are the subjects of this report. These patients were reviewed retrospectively to assess preoperative diagnosis, intraoperative bile spillage, and outcome (recurrence and survival). In addition, the Western literature was reviewed to determine the impact of initial laparoscopic cholecystectomy on recurrence and survival of patients with EGC. Six patients had a preoperative ultrasound consistent with a mass in the gallbladder wall. Seven (44%) had documented bile spillage during the laparoscopic cholecystectomy. T stage based on the laparoscopic cholecystectomy was T1 (n = 1) and T2 (n = 15). Twelve patients underwent reexploration of whom seven underwent further radical excision (gallbladder liver bed resection and extensive lymphadenectomy). After a mean follow-up of 20.1 months (range 4 to 39 months), 69% of patients have had a recurrence or died. Three patients had a port-site recurrence. Five (71%) of seven patients with bile spillage at laparoscopic cholecystectomy have had a recurrence or died of disease. A review of the Western literature on EGC initially removed by laparoscopic cholecystectomy (including the present series) yielded 21 patients with T1 and 42 patients with T2 disease. One-year Kaplan-Meier survival (T1 = 89%, T2 = 71%) and 3-year Kaplan-Meier survival (T1 = 47%, T2 = 40%) of these patients is worse than prior reports for open cholecystectomy. An initial laparoscopic cholecystectomy with its potential for bile spillage can convert potentially curable EGC to incurable disease. Patients with preoperative findings suspicious for gallbladder cancer should undergo open exploration with intent to perform a radical cancer operation as a primary procedure if the diagnosis is confirmed intraoperatively.


Relations between the motor and cognitive dimensions of preschool girls and boys.
The aim of this study was to compare relations between latent motor dimensions and cognitive abilities of preschool boys and girls (N=665, age: 5 to 6 years). The psychological part of the testing was implemented with the Test Razkol. For the assessment of motor abilities 28 tests were given. The associations of motor and cognitive variables were estimated by multiple regression analysis, which showed positive and significant associations between the latent motor variables and the cognitive variable for both boys and girls. On both sexes, the motor dimensions with the strongest associations with the cognitive abilities are those of coordination and the speed of movement. Despite some differences between boys and girls, they still have a lot in common since the most important latent motor dimensions prevailing in the connection between motor and cognitive dimensions are similar.


Thyroid carcinoma with spinal cord compression.
Characteristics of cases of spinal cord compression from metastatic thyroid carcinoma show that this rare complication is not necessarily a preterminal event. It seems to have some propensity to occur during withdrawal of thyroid suppressive therapy in preparation for radioactive iodine treatment.


Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an increase in urinary oxalate excretion.
Unabsorbed fat and bile acids may react with calcium in the intestinal lumen, limiting the amount of free calcium binding with oxalate and thereby raising intestinal oxalate absorption leading to hyperoxaluria. The aim of the present study was to determine whether orlistat (Xenical), a gastrointestinal lipase inhibitor, might increase urinary oxalate in an experimental rat model. Thirty-nine male adult Wistar rats were fed a standard diet alone (controls) or supplemented with either 2% sodium oxalate (NaOx) or 3.2 mL of soy oil, or with both (NaOx + soy oil) for 4 weeks (diet period). Orlistat (16 mg/day) was added to the diet from the 5th to the 8th week (diet + orlistat period). Urinary oxalate (uOx), calcium (uCa), magnesium (uMg), and citrate (uCit) were determined and the ion-activity product of calcium oxalate [AP (CaOx) index(rat)] was estimated. Compared to baseline uOx significantly increased after diet + orlistat in controls (0.64 +/- 0.1 mg/24 hours vs. 0.56 +/-0.1 mg/24 hours), soy oil (0.80 +/- 0.3 mg/24 hours vs. 0.49 +/-0.2 mg/24 hours), and NaOx (2.48 +/- 0.8 mg/24 hours vs. 0.57 +/- 0.2 mg/24 hours), but the most marked increase occurred in NaOx + soy oil (3.87 +/- 0.7 mg/24 hours vs. 0.47 +/- 0.1 mg/24 hours). All groups except controls presented a significant reduction in uCa and uMg. Orlistat induced a significant increase in AP (CaOx) index(rat) compared, respectively, to baseline and to the diet period in NaOx (4.52 +/- 2.34 mg/24 hours vs. 0.94 +/- 0.86 and 1.53 +/- 0.93 mg/24 hours) and NaOx + soy oil (6.49 +/- 4.03 mg/24 hours vs. 0.54 +/- 0.17 and 1.76 +/- 1.32 mg/24 hours). These data suggest that the use of lipase inhibitors, especially under a diet rich in oxalate alone or associated with fat, leads to a significant and marked increase in urinary oxalate and a slight reduction in uCa and uMg that, taken together, resulted in an increase in AP (CaOx) index(rat), elevating the risk of stone formation.


[Complex treatment of chronic cystitis in women].
Evaluation of the efficacy and safety of Phytolysin in complex treatment of female patients with chronic cystitis. 40 women with chronic cystitis were examined from January 2016 to March 2016. Depending on the treatment, all patients were divided into two groups of 20 people. Main group of patients was treated with Fosfomycin (Monural) and Phytolysin. Control group of patients received monotherapy with fosfomycin. The results were assessed at 1 and 2 months after initiation of therapy. Rapid normalization of the status and laboratory parameters, improvement of dynamics of the endoscopic view was observed in main group of patients. The complex of biologically active substances contained in Phytolysin has antimicrobial, anti-inflammatory, antispasmodic, and immunomodulatory effects, promotes the normalization of urodynamics of lower urinary tract, reduces the risk of relapse of chronic recurrent cystitis. Thus, Phytolysin can be recommended as a component of complex therapy of exacerbations of chronic cystitis, as well as a drug for prevention of the disease in disease-free periods.


[Progressive multifocal leukoencephalopathy in a patient with multiple myeloma].
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease in the central nervous system. It is caused by reactivation of John Cunningham-virus and has a grave prognosis. PML occurs most frequently in HIV-patients, but can also be seen in patients with iatrogenic immunodeficiency. Here, we present a patient with multiple myeloma and cardiac amyloidosis who developed PML after receiving treatment with several chemotherapeutics. This case report underlines the importance of bearing PML in mind when immunocompromised patients develop diffuse neurological symptoms.


Lack of circadian change of concentration of C-type natriuretic peptide in rabbit aqueous humor.
To determine whether there is a circadian change of the concentration of C-type natriuretic peptide (CNP) in rabbit aqueous humor. Forty-one male white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All groups consisted of four animals but two had more animals to increase the power of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested by Pearson's correlation. The mean of two eyes was considered for analysis. Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test and COSINOR analysis. There were no significant differences between the 6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and dark), the C-type natriuretic peptide concentration of the light group was lower, 2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but did not reach a significant difference (t test; p = 0.23). COSINOR analysis was not statistically significant (R% = 7.72 p = 0.209). These data demonstrate that the concentration of CNP in aqueous humor did not show a statistically significant circadian change in rabbits entrained to a 12 h light: 12 h dark lighting schedule.


c-FMS chromatin structure and expression in normal and leukaemic myelopoiesis.
The macrophage colony-stimulating factor receptor is encoded by the c-FMS gene, and it has been suggested that altered regulation of c-FMS expression may contribute to leukaemic transformation. c-FMS is expressed in pluripotent haemopoietic precursor cells and is subsequently upregulated during monocytic differentiation, but downregulated during granulopoiesis. We have examined transcription factor occupancy and aspects of chromatin structure of the critical c-FMS regulatory element located within the second intron (FIRE - fms intonic regulatory element) during normal and leukaemic myelopoiesis. Granulocytic differentiation from normal and leukaemic precursors is accompanied by loss of transcription factors at FIRE and downregulated c-FMS expression. The presence of AML1-ETO in leukaemic cells does not prevent this disassembly. In nonleukaemic cells, granulocytic differentiation is accompanied by reversal to a chromatin fine structure characteristic of c-FMS-nonexpressing cells. In addition, we show that low-level expression of the gene in leukaemic blast cells and granulocytes does not associate with increased CpG methylation across the c-FMS locus.


The Biological Basis for Nonunions.
Fracture nonunion is a failure of the biological processes of fracture-healing. Critical cellular events in fracture-healing include the inflammatory response, differentiation and proliferation of progenitor cells, formation of fibrocartilage callus, angiogenesis and subsequent mineralization of the callus, vascular union (restoration of normal medullary circulation), and conversion of woven bone to lamellar bone. All critical events are closely regulated and coordinated by numerous cytokines and growth factors, which are expressed in complex spatial and temporal patterns throughout the repair process. At all phases of fracture-healing, poor cellular and metabolic capacity (e.g., chronic disease), excessive instability, and poor vascularity inhibit cellular responses and healing. Many biological treatments to prevent or treat nonunions are emerging in clinical use, including stem-cell and bone-marrow-aspirate preparations, various progenitor cells and growth factors (e.g., recombinant human bone morphogenetic proteins), and gene therapy.


Spectrum and dynamics of optical frequency combs generated with monolithic whispering gallery mode resonators.
Optical frequency comb generation in whispering gallery mode resonators has been demonstrated in several experiments. The spectra of the combs exhibit a wide variety of complex profiles that are not fully understood. We report a detailed study on frequency comb generation in whispering gallery mode resonators including a complete stability analysis and numerical simulations. We show that the interaction of dispersion and nonlinearity is the key in determining the stability of the comb, the complex characteristics of its spectral profile, and its frequency span. The results will be important for understanding the essential physical processes leading to efficient comb generation.


Kinetics of T cell response in the testes and CNS during experimental autoimmune encephalomyelitis: Simultaneous blood-brain and -testis barrier permeability?
Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are regarded as autoimmune diseases of the central nervous system (CNS). The CNS, testes, and eyes are immune privileged sites. It was initially presumed that ocular involvement in EAE and infertility in MS are neural-mediated. However, inflammatory molecules have been detected in the eyes of animals affected by EAE. It prompted us to investigate if the testes may also be targeted by immune response during EAE. kinetics of T cell response was investigated in the CNS and testes in EAE at different clinical scores. IFN-γ, IL-4, IL-17, and FoxP3 mRNA expressions were considered as representatives of Th1, Th2, Th17, and Treg, respectively. In CNS, IL-17 and IFN-γ were initially up-regulated and attenuated at the late phase of the disease. IL-4 and FoxP3 were markedly down-regulated, but IL-4 was then up-regulated at the late phase of the disease. In the testes, IFN-γ and IL-17 were diminished but increased at the late phase of the disease. FoxP3 was gradually increased from the initial step to the peak of the disease. IL-17/ IFN-γ showed a similar pattern between the CNS and testes. However, FoxP3 and IL-4 expression appeared to have different timing patterns in the CNS and testes. Given the permeability in blood-retina/brain/CSF barrier by complete Freund's adjuvant, the pattern of T cells may be changed in the testes during EAE as a consequence of the blood-testis barrier permeability. More research is required to explore the connection between immune privileged organs.


Assessment of chemical skin-sensitizing potency by an in vitro assay based on human dendritic cells.
The skin-sensitizing potential of chemicals is an important concern for public health and thus a significant end point in the hazard identification process. To determine skin-sensitizing capacity, large research efforts focus on the development of assays, which do not require animals. As such, an in vitro test has previously been developed based on the differential expression of CREM and CCR2 transcripts in CD34(+) progenitor-derived dendritic cells (CD34-DC), which allows to classify chemicals as skin (non-)sensitizing. However, skin sensitization is not an all-or-none phenomenon, and up to now, the assessment of relative potency can only be derived using the in vivo local lymph node assay (LLNA). In our study, we analyzed the feasibility to predict the sensitizing potency, i.e., the LLNA EC3 values, of 15 skin sensitizers using in vitro data from the CD34-DC-based assay. Hereto, we extended the in vitro-generated gene expression data set by an additional source of information, the concentration of the compound that causes 20% cell damage (IC20) in CD34-DC. We statistically confirmed that this IC20 is linearly independent from the gene expression changes but that it does correlate with LLNA EC3 values. In a further analysis, we applied a robust linear regression with both IC20 and expression changes of CREM and CCR2 as explanatory variables. For 13 out of 15 compounds, a high linear correlation was established between the in vitro model and the LLNA EC3 values over a range of four orders of magnitude, i.e., from weak to extreme sensitizers.


Interleukin-38: A crucial player in periodontitis.
The objective of this study was to compare the levels of gingival crevicular fluid (GCF), salivary, and serum matrix metalloproteinase-9, interleukin (IL)-17, IL-36γ, and IL-38 in individuals with healthy periodontium, gingivitis, and periodontitis and to evaluate their correlations with clinical periodontal parameters. Ninety systemically healthy and nonsmoking volunteers divided into a healthy (H) group (n = 30), a gingivitis (G) group (n = 30), and a periodontitis (P) group (n = 30) were included in this study. Clinical periodontal parameters of volunteers were recorded, and GCF, unstimulated saliva, and serum samples were collected. Data analysis was done with enzyme-linked immunosorbent assays. The Kruskal-Wallis test and Bonferroni correction were used for multiple comparisons and post hoc statistical analyses. The group H had significantly lower clinical parameters than the group P (p < 0.001). GCF and salivary IL-36γ and IL-38 levels were significantly higher in the group P than in the H and G groups (p < 0.05). Positive correlations between biochemical findings and clinical periodontal parameters were observed. IL-36γ and IL-38 levels in GCF, saliva, and serum correlate with clinical periodontal parameters and may play a role in determining the activity of periodontitis.


Functional characterization of an endosome-disruptive peptide and its application in cytosolic delivery of immunoliposome-entrapped proteins.
Antibody-directed liposomes (immunoliposomes) are frequently used for targeted drug delivery. However, delivery of large biotherapeutic molecules (i.e. peptides, proteins, or nucleic acids) with immunoliposomes is often hampered by an inefficient cytosolic release of entrapped macromolecules after target cell binding and subsequent endocytosis of immunoliposomes. To enhance cytosolic drug delivery from immunoliposomes present inside endosomes, a pH-dependent fusogenic peptide (diINF-7) resembling the NH(2)-terminal domain of influenza virus hemagglutinin HA-2 subunit was used. Functional characterization of this dimeric peptide showed its ability to induce fusion between liposome membranes and leakage of liposome-entrapped compounds when exposed to low pH. In a second series of experiments, diINF-7 peptides were encapsulated in immunoliposomes to enhance the endosomal escape of diphtheria toxin A chain (DTA), which inhibits protein synthesis when delivered into the cytosol of target cells. Immunoliposomes targeted to the internalizing epidermal growth factor receptor on the surface of ovarian carcinoma cells (OVCAR-3) and containing encapsulated DTA did not show any cytotoxicity toward OVCAR-3 cells. Cytotoxicity was only observed when diINF-7 peptides and DTA were co-encapsulated in the immunoliposomes. Thus, diINF-7 peptides entrapped inside liposomes can greatly enhance cytosolic delivery of liposomal macromolecules by pH-dependent destabilization of endosomal membranes after cellular uptake of liposomes.


[Multidisciplinary therapy for 3 patients with lymph node recurrence after curative gastrectomy].
We report multidisciplinary treatment of 3 patients with lymph node recurrence after curative gastrectomy. Case 1: A 71- year-old woman had a history of distal gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Para-aortic lymph node metastasis was observed 36 months after surgery. Complete response( CR) was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 2: A 51-year-old man had a history of total gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Right cervical lymph node metastasis was observed 48 months after surgery. CR was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 3: A 68-year-old man had a history of distal gastrectomy with D2 lymphadenectomy followed by neoadjuvant chemotherapy for the treatment of advanced gastric cancer. CR was achieved after sequential treatment with irinotecan( CPT-11) plus cisplatin( CDDP), radiation, and 5-fluorouraci(l 5-FU) plus Leucovorin therapy for lymph node recurrence near the head of the pancreas. These cases suggest that the combination of systemic chemotherapy and local radiation therapy might be effective for the treatment of lymph node recurrence in patients with gastric cancer.


Protective Effect of Troxerutin on Nickel-Induced Testicular Toxicity in Wistar Rats.
Nickel (Ni)-induced oxidative damage is a serious problem that leads to reproductive system failure through testicular damage. The present investigation was carried out to determine the effect of troxerutin (Txn) on testicular toxicity induced by Ni in experimental rat testes. The oral administration of Txn (100 mg/kg body weight [bw]) showed a significant (p < 0.01) increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), reduced glutathione, ascorbate, total sulphydryl groups, and testis-organ weight. Subsequently, the administration of Txn also significantly reduced the accumulation of Ni, lipid peroxidation products, and protein carbonyl levels in Txn-treated animals. Testicular protection in the experimental animals by Txn is further substantiated by a remarkable reduction of Ni, which was revealed through testicular tissue histopathology. These studies suggest that Txn could prevent oxidative damage and testicular toxicity induced by Ni in experimental animals.


Diagnostic content validity of nursing diagnoses.
A random sample of 600 registered professional nurses in New York State were asked to rate the relevance of The North American Nursing Diagnosis Association's list of defining characteristics for the six most frequently used nursing diagnostic categories on Likert-type scales. The diagnostic categories were Alteration in Comfort: Pain; Anxiety; Impaired Physical Mobility; Impaired Skin Integrity: Actual; Self-Care Deficit; and Knowledge Deficit. Based on 148 usable responses, the results indicated critical and supporting characteristics and total content validity scores for each of six diagnostic categories. The only defining characteristic that did not attain at least supporting status was "Regretful" for the diagnosis of anxiety.


New techniques for the prenatal diagnosis of hemoglobinopathies.
Two new techniques have been devised for the prenatal diagnosis of hemoglobinopathies performed on fetal blood samples. Isoelectric focusing (IEF) of hemoglobins was compared to the classical chromatography of labelled globin chains for 51 fetal blood samples, 40 being obtained for prenatal diagnosis of hemoglobinopathies, in Paris. In all cases the two methods provided identical results. Adult hemoglobin was quantitatively evaluated. In addition blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta thalassemia did not exhibited measureable amounts of Hb A by IEF. The fetal blood must be free of maternal contamination. If present maternal red blood cells can be completely eliminated by selective lysis using the 0RSKOV reaction. A chromatography of hemoglobins on Biorex 70 has been devised very recently to overcome the two limitations of IEF: First the contamination of fetal blood samples by maternal cells, and second the impossibility to evaluate Hb A when present in proportion below 1%. The chromatography of hemoglobins on Biorex 70 is performed in 75 minutes with 0.1 mg of hemoglobin present in membrane free hemolysate. The optical density recording allows to evaluate .5% of Hb A and to detect .1% of Hb A. In addition, the radioactivity profile of the chromatography can be determined. It has to be used in case of maternal contamination.


The Role of Inflammation in β-cell Dedifferentiation.
Chronic inflammation impairs insulin secretion and sensitivity. β-cell dedifferentiation has recently been proposed as a mechanism underlying β-cell failure in T2D. Yet the effect of inflammation on β-cell identity in T2D has not been studied. Therefore, we investigated whether pro-inflammatory cytokines induce β-cell dedifferentiation and whether anti-inflammatory treatments improve insulin secretion via β-cell redifferentiation. We observed that IL-1β, IL-6 and TNFα promote β-cell dedifferentiation in cultured human and mouse islets, with IL-1β being the most potent one of them. In particular, β-cell identity maintaining transcription factor Foxo1 was downregulated upon IL-1β exposure. In vivo, anti-IL-1β, anti-TNFα or NF-kB inhibiting sodium salicylate treatment improved insulin secretion of isolated islets. However, only TNFα antagonism partially prevented the loss of β-cell identity gene expression. Finally, the combination of IL-1β and TNFα antagonism improved insulin secretion of ex vivo isolated islets in a synergistic manner. Thus, while inflammation triggered β-cell dedifferentiation and dysfunction in vitro, this mechanism seems to be only partly responsible for the observed in vivo improvements in insulin secretion.


Screening of crucial long non-coding RNAs in oral epithelial dysplasia by serial analysis of gene expression.
Oral epithelial dysplasia (OED) is a premalignant lesion of the oral mucosa. Considering the poor 5-year survival rate of oral cancer, further investigation is needed in order to determine the pathogenesis of OED. In the present study, serial analysis of gene expression (SAGE) data from patients with OED were compared to normal controls to identify differentially expressed genes (DEGs). SAGE data were obtained from the Gene Expression Omnibus, and included samples from patients with mild, moderate, or severe dysplasia. The DEGs were identified using the edgeR software package and functional-enrichment analysis was performed with the DAVID (https://david.ncifcrf.gov/) software program. The co-expression network was constructed using the CoExpress software and target genes of long non-coding RNAs (lncRNAs) were predicted according to the proximity between the lncRNAs and mRNAs in the genome. A total of 517 DEGs were identified, including 409 mRNAs and 108 lncRNAs. Functional-enrichment analysis showed that mRNAs and lncRNAs involved in epithelial cell differentiation, epithelium development, and epidermal cell differentiation were significantly enriched in the DEGs. Thirty-eight potential regulatory relationships were unveiled between lncRNAs and mRNAs, and two subnetworks were discovered by analyzing the topological properties of the co-expression network. In conclusion, we have identified key mRNAs and lncRNAs in OED, and these findings may aid in understanding the pathogenesis of OED and advance potential future treatments.


Enterotoxin production in natural isolates of Bacillaceae outside the Bacillus cereus group.
Thirty-nine Bacillus strains obtained from a variety of environmental and food sources were screened by PCR for the presence of five gene targets (hblC, hblD, hblA, nheA, and nheB) in two enterotoxin operons (HBL and NHE) traditionally harbored by Bacillus cereus. Seven isolates exhibited a positive signal for at least three of the five possible targets, including Bacillus amyloliquefaciens, B. cereus, Bacillus circulans, Bacillus lentimorbis, Bacillus pasteurii, and Bacillus thuringiensis subsp. kurstaki. PCR amplicons were confirmed by restriction enzyme digest patterns compared to a positive control strain. Enterotoxin gene expression of each strain grown in a model food system (skim milk) was monitored by gene-specific reverse transcription-PCR and confirmed with the Oxoid RPLA and Tecra BDE commercial kits. Lecithinase production was noted on egg yolk-polymyxin B agar for all strains except B. lentimorbis, whereas discontinuous beta hemolysis was exhibited by all seven isolates grown on 5% sheep blood agar plates. The results of this study confirm the presence of enterotoxin genes in natural isolates of Bacillus spp. outside the B. cereus group and the ability of these strains to produce toxins in a model food system under aerated conditions at 32 degrees C.


Laparoscopic proctocolectomy with ileal j-pouch anal anastomosis in children.
We aimed to evaluate postoperative fecal incontinence scales of children who underwent laparoscopic proctocolectomy and ileal J-pouch anastomosis for familial adenomateous polyposis (FAP) and inflammatory bowel disease (IBD). Fecal incontinence scores were collected at 3 months post-surgery. A retrospective chart review was also performed to obtain the demographic data and operative technical details. The postoperative Wexner Fecal Incontinence Score was 0 in 9 of 11 patients and satisfactory in the remaining two. None of the children had a major complication. Even though the presented study does not have any comparable data, it seems that laparoscopic total proctocolectomy with ileal J-pouch anal anastomosis (TP IPAA) might be the best choice of surgery because it provides good continence with low complication rates.


Smoke-free homes and attitudes towards banning smoking in vehicles carrying children in Spain (2016).
To describe the voluntary adoption of smoke-free homes and social attitudes in Spain towards banning smoking in vehicles in which children are present. Cross-sectional study of a representative sample of the adult Spanish population age range, 18-75 years (n=1036). The field work was conducted via a computer-assisted telephone survey in March and April 2016. Survey respondents answered questions about smoking rules at home and attitudes towards a smoking ban in cars with or without children. Home smoking rules were defined as complete (smoking not allowed anywhere in the house), partial (smoking allowed in some areas inside the house) or absent (smoking allowed everywhere). Most (83.0%) of the surveyed population had some type of smoking restriction in place at home (45.6% complete and 37.5% partial). There were significant differences between groups according to age group (the highest prevalence was 86.1% from 66 to 75 years and the lowest prevalence was 77.8% from 46 to 65 years) and smoking status (the highest prevalence was 89.4% in people who had never been smokers and the lowest prevalence was 75.0% in current smokers) with regards to the prevalence of smoke-free homes (p<0.05), with partial bans more prevalent in smoking households (49.0%). Most (61.6%) of the population favored banning smoking in cars, and 90.1% supported a ban in cars carrying minors. Attitudes towards smoking regulation in cars (with or without children) varied significantly by age group (the highest prevalence was 81.9% from 66 to 75 years and the lowest prevalence was 54.5% from 18 to 45 years) and smoking status (the highest prevalence was 71.4% in people who had never been smokers and the lowest prevalence was 46.0% in current smokers). However, no significant differences were found with regard to attitudes towards smoking regulation in cars carrying children, regardless of sex, age, social class, or smoking status. Approximately half of the adult population in Spain have implemented a complete smoke-free rule at home. More than 9 out of 10 adults favor regulating smoking in cars in the presence of minors. These findings support the expansion of smoke-free regulations to include private vehicles, particularly when minors are in the car.


[Metallosis: A Rare Cause of Autoimmune Hemolytic Anemia].
Hemolytic anemia may be associated with multiple etiologies, including toxic substances, such as metals, which is a rare cause. 55-year-old male, who underwent a total arthroplasty of the right hip (uncemented prostheses with ceramic-ceramic articulation with an acetabular component consisting of a dome composed of an alloy of titanium, aluminum and vanadium into which fitted a ceramic 'insert'). Approximately 4 years after surgery the patient complained of noise originating from the prosthesis which occurred on movement. A surgical revision was performed and showed the presence of dark thick intracapsular fluid, fracture of the ceramic acetabular 'insert' and signs of wear of the acetabular metal dome. Extensive washing was carried out and the fractured ceramic 'insert' was replaced for a polyethylene 'insert'. Two months later he was referred to the Emergency Room due to worsening of his general health, floating in the right hip and mucocutaneous jaundice. Laboratory tests suggested autoimmune hemolytic anemia. Arthrocentesis was performed and a large volume of metal fluid was drained off. The CT scan showed a large heterogeneous pelvic cystic collection seeded with prosthesis fragments, suggestive of metallosis. Hemolytic anemia was explained as toxicity of the particles and metal ions caused by the wear of the prosthesis. The patient was started on a high-dose steroid treatment. Afterwards, when he was stable, prosthesis components replacement and drainage of pelvic debris fluid were carried out. After the fracture of the ceramic 'insert' the ceramic head began to articulate directly with the metallic acetabular component, causing noise and wear with release of particles and ions. This caused a cystic pelvic abscess, which went unnoticed on the first surgical revision. Surgical debridement lead to the cystic collection extending into the adjacent tissues and the systemic circulation, triggering serious systemic effects, such as autoimmune hemolytic anemia. The potential toxicity of each of the metal elements of this prosthesis is unknown, and there are still no available laboratory tests for its detection. Metallosis is a rare cause of autoimmune hemolytic anemia.


[The prognostic value of thyroid stimulating antibodies after antithyroid drug treatment of Graves' disease].
Thyroid stimulating antibodies (TsAb) and thyrotropin releasing hormone (TRH) test were used as the indices for predicting relapse and remission in 58 patients. The variation of TsAb activities was observed before and after antithyroid drug (ATD) treatment. The findings showed that TsAb activities of untreated patients were significantly higher than those of patients treated by ATD, and TsAb activities were weak or negative after ATD treatment. When TsAb was positive or TRH test was abnormal at the time of cessation of ATD therapy, nearly 93% patients relapsed. Further analyses of relapsed patients indicated that there was no correlation between the two indicators, and the TsAb positive rate (84%) was significantly higher than the rate of abnormal TRH test (45%). The average ATD treatment duration in relapsed patients was shorter than that in remission patients. It is concluded that TsAb is more useful than TRH test when they are used for predicting the prognosis of Graves' disease. The duration of ATD treatment could affect relapse or remission. The immunosuppression effect of ATD was also identified.


Capsaicin-induced gastric hyperemia and protection are NO- dependent.
Topical treatment of gastric mucosa with capsaicin (cap) increases gastric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypothesis that this hyperemia related "cytoprotection" is mediated by nitric oxide. Male Sprague-Dawley rats were anesthetized and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into four groups. All groups received a 5-min topical saline exposure. Groups 1 and 2 received iv saline or nitro-L-arginine methyl ester (L-NAME, 25 mg/kg iv), a specific nitric oxide inhibitor, 5 min prior to baseline treatment, followed by a 15-min preinjury period of saline and a 15-min injury period of 10 mM acidified taurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 microM) was used during the preinjury period. GMBF was measured with a laser Doppler flowmeter (ml/min/100 g tissue). Injury was assessed grossly (grade 0-3), histologically (grade 0-3), and by measuring DNA content of a 5-min N-acetylcysteine wash (DNAE). Baseline GMBF of 30 +/- 1.5 significantly decreased to 15 +/- 1.2 in group 1 versus group 2 (P < 0.05). When topical ATC was used GMBF increased to 59 +/- 4.9 and 25 +/- 2.8, respectively. Injury by grade and DNAE was not significantly different between these groups. GMBF during cap exposure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Graded histologic and gross injuries were significantly worse in group 4 compared to group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Optical homodyne PSK demonstration of 1.5 photons per bit at 156 Mbps with rate-(1/2) turbo coding.
We report the first demonstration of a near quantum-limited optical homodyne PSK receiver combined with powerful forward-error-correction coding, achieving 1.5 photons/bit sensitivity, within 4.5 dB of the Shannon limit. Phase-locking was achieved at 1.55 microm using an analog dither-based optical phase-locked loop with an external phase modulator. Analysis for this configuration with arbitrary loop damping is given showing a performance advantage for the overdamped case.


A challenge and an opportunity for medical regulators--considering the public's interests in cases using ADR to resolve disputes about physicians' practices: a Canadian analysis.
Disputes between patients or their families and the patient's treating physician are not uncommon. While many of these disputes are resolved by the disputants alone or informally with others, many are resolved through formal adjudication processes of court litigation or through processes of medical regulators. Alternative dispute resolution (ADR) options either within the courts or within regulatory bodies are becoming more popular as decision-makers realize the benefits to using these options in appropriate cases. ADR offers both opportunities for advancing our appropriate dealings of these disputes and challenges in terms of ensuring that the public's interests are met. This article examines the public's interests in cases using mediation to resolve disputes about physician's practices from a Canadian perspective. The article concludes with recommendations to protect the public interests and to respect the rights of disputants.


Influence of the Microstructure and Silver Content on Degradation, Cytocompatibility, and Antibacterial Properties of Magnesium-Silver Alloys In Vitro.
Implantation is a frequent procedure in orthopedic surgery, particularly in the aging population. However, it possesses the risk of infection and biofilm formation at the surgical site. This can cause unnecessary suffering to patients and burden on the healthcare system. Pure Mg, as a promising metal for biodegradable orthopedic implants, exhibits some antibacterial effects due to the alkaline pH produced during degradation. However, this antibacterial effect may not be sufficient in a dynamic environment, for example, the human body. The aim of this study was to increase the antibacterial properties under harsh and dynamic conditions by alloying silver metal with pure Mg as much as possible. Meanwhile, the Mg-Ag alloys should not show obvious cytotoxicity to human primary osteoblasts. Therefore, we studied the influence of the microstructure and the silver content on the degradation behavior, cytocompatibility, and antibacterial properties of Mg-Ag alloys in vitro. The results indicated that a higher silver content can increase the degradation rate of Mg-Ag alloys. However, the degradation rate could be reduced by eliminating the precipitates in the Mg-Ag alloys via T4 treatment. By controlling the microstructure and increasing the silver content, Mg-Ag alloys obtained good antibacterial properties in harsh and dynamic conditions but had almost equivalent cytocompatibility to human primary osteoblasts as pure Mg.


Preservation of Microalgae, Lignocellulosic Biomass Blends by Ensiling to Enable Consistent Year-Round Feedstock Supply for Thermochemical Conversion to Biofuels.
Seasonal variation in microalgae productivity is a significant barrier to economical production of algae biofuels and chemicals. Summer production can be 3-5 times higher than in the winter resulting in uneven feedstock supplies at algae biorefineries. A portion of the summer production must be preserved for conversion in the winter in order to maintain a biorefinery running at capacity. Ensiling, a preservation process that utilizes lactic acid fermentation to limit microbial degradation, has been demonstrated to successfully stabilize algae biomass (20% solids) and algae-lignocellulosic blends (40% algae-60% lignocellulosic biomass, dry basis) for over 6 months, resulting in fuel production cost savings with fewer emissions. Preservation of algae as blends could be beneficial to biorefineries that utilize thermochemical approaches to fuel production as co-processing of algae and lignocellulosic biomass has been observed to enhance biocrude yield and improve oil quality. This study conducts a resource assessment of biomass residues in the southern United States to identify materials available during peak algae productivity and in sufficient quantity to meet the algae storage needs of an algae biofuel industry. Eight feedstocks met the quantity threshold but only three, distillers grains, haylage, and yard waste, were also available in season. Storage experiments utilizing both freshwater and marine strains of microalgae - Scenedesmus acutus, Chlorella vulgaris, Chlorella zofingiensis, Nannochloropsis gaditana, and Porphyridium purpureum - and yard waste were conducted for 30 days. Storage losses were less than 10% in all but one case, and the pH of all but one blend was reduced to less than 4.7, indicating that yard waste is a suitable feedstock for blending with algae prior to storage. To better understand whether the benefits to conversion realized by processing blends might be affected by storage, elemental analysis and bomb calorimetry of pre- and post-storage algae-yard waste blends were conducted to characterize changes occurring during storage. Storing algae biomass as blends with lignocellulosic biomass could be an effective method of mitigating seasonal variability in algae biomass production while retaining the synergistic effect of co-processing algae blends in thermochemical conversion.


Liver resection for intrahepatic stones.
Long-term outcome is good for a selected group of patients with hepatolithiasis treated with liver resection. Liver resection should also be offered to patients with complex hepatolithiasis such as bilateral stones or those with strictures. Retrospective study. Regional hospital. A total of 174 patients with hepatolithiasis (201 procedures) treated between January 1, 1989, and September 30, 2003. Liver resection (52 procedures) or removal of stones primarily by percutaneous choledochoscopy (149 procedures). Recurrence of cholangitis. Most patients in the liver resection group had stones localized to the left side. The overall success rate in this group was 98.0% (49 of 50 patients, excluding 2 patients found to have cholangiocarcinoma). The chance of biliary sepsis at 5 years after resection was 13.3%. The overall success rate of stone removal primarily by percutaneous choledochoscopy was 70.5%. The bilaterality of stones, the presence of stricture, and the presence of atrophy were found to be significant risk factors for a poor long-term outcome after stone removal alone. The chance of biliary sepsis at 5 years was 26.4% and 43.2% for those without and with stricture, respectively. The long-term outcome after liver resection for hepatolithiasis was excellent for a selected group of patients. Poor outcomes were recorded for patients whose intrahepatic stones were removed primarily by percutaneous choledochoscopy, especially those with strictures. The indication for liver resection for hepatolithiasis should be extended to patients with strictures and those with bilateral stones. A combination of different treatment modalities is necessary to improve the outcome of these patients.


Invitro Anti-mycotic Activity of Hydro Alcoholic Extracts of Some Indian Medicinal Plants against Fluconazole Resistant Candida albicans.
Candidiasis is one of the most common opportunistic infections caused by Candida albicans. Fluconazole is the drug of choice for prevention and management of this condition. However, the emergence of fluconazole resistant candidal strains has become a major concern. Many herbs like fenugreek, cinnamon, papaya, oregano, garlic are rich in phytochemical constituents known to express antimycotic activity. With the available information, the present research study was carried out to assess the invitro anti-mycotic activity of hydro alcoholic extracts of Trigonella foenum-graecum seeds, Cinnamomum verum bark and Carica papaya leaves and seeds against fluconazole resistant Candida albicans. Hydro alcoholic extracts of Trigonella foenum-graecum (seeds), Cinnamomum verum (bark), Carica papaya CO.2 strain (male and female leaves) and Carica papaya CO.2 strain (seeds) were prepared by maceration. The anti-mycotic activity of the prepared extracts against Candida albicans was assessed by agar well diffusion method. Three independent experiments were performed in triplicates and the mean and standard deviation were calculated. Minimum inhibitory concentration was determined. The results of the present study revealed that all the extracts exhibited anti-mycotic activity in a dose dependent manner and minimum inhibitory concentration of all the extracts was found to be 15.62 μg/ml. The results of the present study shed light on the fact that plant extracts could be used not only as an alternate drug for management of fluconazole resistant candidiasis but also explored further for oral cancer prevention as a therapeutic adjunct.


Dual Inhibition of NOX2 and Receptor Tyrosine Kinase by BJ-1301 Enhances Anticancer Therapy Efficacy via Suppression of Autocrine-Stimulatory Factors in Lung Cancer.
NADPH oxidase-derived reactive oxygen species (ROS) potentiate receptor tyrosine kinase (RTK) signaling, resulting in enhanced angiogenesis and tumor growth. In this study, we report that BJ-1301, a hybrid of pyridinol and alpha-tocopherol, exerts anticancer effects by dual inhibition of NADPH oxidase and RTK activities in endothelial and lung cancer cells. BJ-1301 suppresses ROS production by blocking translocation of NADPH oxidase cytosolic subunits to the cell membrane, thereby inhibiting activation. The potency of RTK inhibition by BJ-1301 was lower than that of sunitinib (a multi-RTK inhibitor), but the inhibition of downstream signaling pathways (e.g., ROS generation) and subsequent biological changes (e.g., NOX2 induction) by BJ-1301 was superior. Consistently, BJ-1301 inhibited cisplatin-resistant lung cancer cell proliferation more than sunitinib did. In xenograft chick or mouse tumor models, BJ-1301 inhibited lung tumor growth, to an extent greater than that of sunitinib or cisplatin. Treatments with BJ-1301 induced regression of tumor growth, potentially due to downregulation of autocrine-stimulatory ligands for RTKs, such as TGFα and stem cell factor, in tumor tissues. Taken together, the current study demonstrates that BJ-1301 is a promising anticancer drug for the treatment of lung cancer. Mol Cancer Ther; 16(10); 2144-56. ©2017 AACR.


Structural Changes of the Macula on Optical Coherence Tomography after Vitrectomy for Proliferative Diabetic Retinopathy.
This study aimed to evaluate the relationship between macular structural changes and visual prognosis after pars plana vitrectomy (PPV) for proliferative diabetic retinopathy. The study included 60 eyes that had undergone PPV. Macular optical coherence tomography (OCT) findings were classified into 5 groups preoperatively and 10 groups postoperatively. Best-corrected visual acuity (BCVA) were analyzed according to pre- and postoperative OCT. From the preoperative OCT, normal fovea with/without traction, normal fovea with preretinal hemorrhage, and tractional retinal detachment involving fovea showed an increase in BCVA after PPV (all p < 0.05). Normal fovea, epiretinal membrane and macular thickening were common after surgery. Normal fovea, epiretinal membrane and edema outside of the fovea showed good visual prognosis (BCVA >20/50). Subfoveal fibrosis, macular hole, loss of foveal depression, and serous foveal detachment showed poor visual prognosis (BCVA <20/100). Macular structural changes were various after PPV, and visual prognosis correlated with these changes.


Metformin induces glucose uptake in human preadipocyte-derived adipocytes from various fat depots.
To evaluate the effect of metformin on basal and insulin-induced glucose uptake in subcutaneous and visceral preadipocyte-derived adipocytes from obese and non-obese patients, preadipocytes were obtained from subcutaneous and visceral fat depots during abdominal surgery. Differentiation efficiency was evaluated by measurement of intracellular triglyceride accumulation. Preadipocyte-derived adipocytes were treated with metformin (1 mM) for 24 h with or without the addition of insulin (100 nM) for 20 min and glucose uptake was measured. In cells from each donor, intracellular triglyceride accumulation was more abundant in subcutaneous preadipocyte-derived adipocytes than in visceral preadipocyte-derived adipocytes (p < 0.001). Insulin stimulated glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. basal). In visceral preadipocyte-derived adipocytes, insulin did not increase basal glucose uptake. In subcutaneous preadipocyte-derived adipocytes from non-obese and obese patients, metformin alone increased glucose uptake to 2.7 +/- 0.2 (p < 0.001) and 2.1 +/- 0.1 fold (p < 0.001) respectively. Metformin increased glucose uptake in visceral preadipocyte-derived adipocytes from non-obese (1.7 +/- 0.1 fold vs. basal, p < 0.001) and obese (2.0 +/- 0.2 fold vs. basal, p < 0.001) patients. Combined treatment with metformin and insulin increased glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. insulin alone). In preadipocyte-derived adipocytes glucose uptake is induced by metformin independent of the fat depot origin of the preadipocytes (subcutaneous or visceral) and the obesity state of the patients (non-obese or obese). In adipocytes, metformin seems to induce glucose uptake independent of insulin suggesting an alternative mechanism of action of this drug.


Exercise intensity and muscle hypertrophy in blood flow-restricted limbs and non-restricted muscles: a brief review.
Although evidence for high-intensity resistance training-induced muscle hypertrophy has accumulated over the last several decades, the basic concept of the training can be traced back to ancient Greece: Milo of Croton lifted a bull-calf daily until it was fully grown, which would be known today as progressive overload. Now, in the 21st century, different types of training are being tested and studied, such as low-intensity exercise combined with arterial as well as venous blood flow restriction (BFR) to/from the working muscles. Because BFR training requires the use of a cuff that is placed at the proximal ends of the arms and/or legs, the BFR is only applicable to limb muscles. Consequently, most previous BFR training studies have focused on the physiological adaptations of BFR limb muscles. Muscle adaptations in non-BFR muscles of the hip and trunk are lesser known. Recent studies that have reported both limb and trunk muscle adaptations following BFR exercise training suggest that low-intensity (20-30% of 1RM) resistance training combined with BFR elicits muscle hypertrophy in both BFR limb and non-BFR muscles. However, the combination of leg muscle BFR with walk training elicits muscle hypertrophy only in the BFR leg muscles. In contrast to resistance exercise with BFR, the exercise intensity may be too low during BFR walk training to cause muscle hypertrophy in the non-BFR gluteus maximus and other trunk muscles. Other mechanisms including hypoxia, local and systemic growth factors and muscle cell swelling may also potentially affect the hypertrophic response of non-BFR muscles to BFR resistance exercise.


Genetic secrets: social issues of medical screening in a genetic age.
In the 1990s, as the multi-billion-dollar Human Genome Project makes more and more genetic information available, we would do well to look closely at the social context of power dynamics, control, and economic interests within which that information will be used. Let us consider four specific questions. How does social stratification by race, ethnicity, gender, and social class affect the use of genetic information in the workplace? In what ways are perspectives on genetic testing socially located? What can fetal exclusion policies teach us about how genetic information might be used to identify high-risk individuals? What social and political challenges are posed by new information about genetic abnormalities, and how might that information be distributed fairly?


The risk of mental health disorders among U.S. military personnel infected with human immunodeficiency virus, active component, U.S. Armed Forces, 2000-2011.
Mental health disorders (MHD) are reportedly more common among soldiers and airmen with HIV than their seronegative counterparts. This report documents the incidence rates of MHD among HIV-positive members of all service branches and compares the rates to those of two HIV-unexposed control groups: an HSV2-infected group and a group without documented HIV or HSV2 infections. Approximately 56 percent of HIV-infected service members received an incident diagnosis of a MHD six months or more after the initial detection of their infections. Cumulative incidence rates in nearly all MHD categories of interest were highest in the HIV group, intermediate in the HSV2 group and lowest in the referent group. The disorders more frequently diagnosed among HIV-infected service members compared to their uninfected counterparts were psychosis/schizophrenia, substance dependence, substance abuse, bipolar disorder, suicide ideation and depression. The findings are consistent with previous studies and reiterate the importance of long-term and comprehensive clinical monitoring of individuals diagnosed with HIV-1 infections.


Dynamical transition of protein-hydration water.
Thin layers of water on biomolecular and other nanostructured surfaces can be supercooled to temperatures not accessible with bulk water. Chen et al. [Proc. Natl. Acad. Sci. U.S.A. 103, 9012 (2006)]10.1073/pnas.0602474103 suggested that anomalies near 220 K observed by quasielastic neutron scattering can be explained by a hidden critical point of bulk water. Based on more sensitive measurements of water on perdeuterated phycocyanin, using the new neutron backscattering spectrometer SPHERES, and an improved data analysis, we present results that show no sign of such a fragile-to-strong transition. The inflection of the elastic intensity at 220 K has a dynamic origin that is compatible with a calorimetric glass transition at 170 K. The temperature dependence of the relaxation times is highly sensitive to data evaluation; it can be brought into perfect agreement with the results of other techniques, without any anomaly.


Evaluating single-cell variability in proteasomal decay.
Gene expression is a stochastic process that leads to variability in mRNA and protein abundances even within an isogenic population of cells grown in the same environment. This variation, often called gene-expression noise, has typically been attributed to transcriptional and translational processes while ignoring the contributions of protein decay variability across cells. Here we estimate the single-cell protein decay rates of two degron GFPs in Saccharomyces cerevisiae using time-lapse microscopy. We find substantial cell-to-cell variability in the decay rates of the degron GFPs. We evaluate cellular features that explain the variability in the proteasomal decay and find that the amount of 20s catalytic beta subunit of the proteasome marginally explains the observed variability in the degron GFP half-lives. We propose alternate hypotheses that might explain the observed variability in the decay of the two degron GFPs. Overall, our study highlights the importance of studying the kinetics of the decay process at single-cell resolution and that decay rates vary at the single-cell level, and that the decay process is stochastic. A complex model of decay dynamics must be included when modeling stochastic gene expression to estimate gene expression noise.


Helical Polybissilsesquioxane Bundles Prepared Using a Self-Templating Approach.
Polybissilsesquioxanes with single-handed helical morphologies attracted much attention during the last decade, which could be applied as asymmetric catalysts and chiral stationary phases. Herein, a pair of chiral biphenylene-bridged bissilsesquioxanes were synthesized. They self-assembled into helical bundles in ethanol, behavior that was confirmed in field emission scanning electron microscopy images. Circular dichroism analysis indicated that the biphenylene groups twisted in a single-handed fashion. Single-handed helical polybissilsesquioxane bundles were prepared via polycondensation of the bissilsesquioxanes, using a self-templating approach. Because of the shrinkage that occurred during polycondensation, the helical pitches of the bundles were shorter than those of their corresponding organic self-assemblies. The wide-angle X-ray diffraction pattern indicated that there were no π-π interactions among the diphenylene groups. The circular dichroism spectra indicated that the chirality was successfully transferred from the bissilsesquioxane self-assemblies to the polybissilsesquioxane. The polybissilsesquioxanes displayed a capacity for the adsorption of nitrobenzene and had potential application for enantioseparation.


Two Episodes of Transfusion-related Acute Lung Injury (TRALI) Occurring within a Short Period.
Transfusion-related acute lung injury (TRALI) is a non-hemolytic adverse reaction that occurs ≤6 hours after receiving a transfusion. A 72-year-old man with leukemia developed severe hypoxemia after platelet transfusions on two occasions within a 4-day period. During the first episode, the transfused platelet preparation was positive for anti-human-leukocyte antigen antibodies. The pathogenesis of TRALI includes an antibody-mediated mechanism and a non-antibody-mediated mechanism, in which various factors combine to activate pulmonary neutrophils. In our case, it is considered that the patient's neutrophils reached the activation threshold for the development of TRALI after the accumulation of various factors besides anti-leukocyte antibodies.


The Potential Impact of COVID-19 Virus on the Heart and the Circulatory System.
Heart attacks, arrhythmias, and cardiomyopathy are all linked to the 2019 coronavirus disease (COVID-19), which has been identified as a risk factor for cardiovascular disease. Nothing can be held accountable in the current state of affairs. Undiagnosed chronic systolic heart failure (CSHF) develops when the heart's second half of the cardiac cycle does not function properly. As a result, the heart's blood pumping function is interrupted. Stress-induced cardiomyopathy may be caused by a variety of factors inside the body (SICM). Cytokine storm and microvascular dysfunction are among the issues. There is inflammation in the heart muscle, which may lead to stress-induced cardiomyopathy. A major part of our study is going to be devoted to understanding the effects of coronavirus on the cardiovascular system and blood vessels. A lot of time and effort has been put into figuring out the health effects of radiation exposure. The heart and circulatory system are shown to be affected by the coronavirus in this research. COVID-19 is shown to influence persons with heart disease, heart failure, arrhythmias, microvascular angiopathy, and cardiac damage in this study.


Progressive inactivation of the expression of an erythroid transcriptional factor in GM- and G-CSF-dependent myeloid cell lines.
The transcriptional binding protein NFE-1 (also called GF-1 and Ery-f1) is thought to play a necessary, but not sufficient, role in the regulation of differentiation-related gene expression in a subset of hematopoietic lineages (erythroid, megakaryocytic, and basophil-mast cell). In order to clarify the mechanism which underlies the lineage-specificity of the NFE-1 expression, as well as the relationship between the expression of this factor and growth factor responsiveness, we have evaluated the capacity of erythropoietin (Epo)-, granulomonocytic (GM)-colony stimulating factor (CSF)-, and granulocyte (G)-CSF-dependent subclones derived from the interleukin 3 (IL-3)-dependent cell line 32D, to express 1) NFE-1 mRNA, 2) NFE-1-related nuclear proteins, and 3) chloramphenicol acetyl transferase (CAT) activity when transfected with a CAT gene under the control of NFE-1 cognate sequences. NFE-1 mRNA was found to be expressed not only in cells with mast cell (IL-3-dependent 32D) and erythroid (Epo-dependent 32D Epo1) phenotypes, but also in cells with predominantly granulocyte/macrophage properties, such as the GM-CSF- (early myelomonocytic) and G-CSF- (myelocytic) dependent subclones of 32D. However, a gradient of expression, correlating with the lineage, the stage of differentiation, and the growth factor responsiveness of the cell lines, was found among the different subclones: Epo greater than or equal to IL-3 greater than GM-CSF greater than G-CSF. Binding experiments demonstrated NFE-1 activity in all cell lines except the G-CSF-dependent line. Function of the NFE-1 protein was assessed by the expression of the CAT gene linked to the SV40 promoter and a mutant (-175 T----C) HPFH gamma-globin promoter. High level CAT expression was seen only in the Epo1 cells although low level expression was also seen in the parent 32D. These results demonstrate that the specificity of the expression of NFE-1 for the erythroid--megakaryocytic--mast cell lineages is obtained by progressive inactivation of its expression in alternative lineages.


Non-adiabatic coupling in the potential energy surfaces of SO2 molecule.
To investigate the potential energy surfaces and the coupling between the adiabatic states of SO2 molecules, it is necessary to consider the non-adiabatic coupling terms (NACTs), where the Born-Oppenheimer approximation breaks down. In this work, we analyze the conical intersections between 1 1A1 and 1 1B2 states (the A' states in Cs symmetry) and 1 1A2 and 1 1B1 states (the A'' states in Cs symmetry) using NACTs and adiabatic-to-diabatic transformation (ADT) angles. Our results confirm reasonable interaction between 1 1A1 and 1 1B2 states and strong interaction between 1 1A2 and 1 1B1 states.


Construction of 3-D Cellular Multi-Layers with Extracellular Matrix Assembly Using Magnetic Nanoparticles.
Construction of 3-dimensional (3-D) engineered tissue is increasingly being investigated for use in drug discovery and regenerative medicine. Here, we developed multi-layered 3-D cellular assembly by using magnetic nanoparticles (MNP) isolated from Magnetospirillum sp. AMB-1 magnetotactic bacteria. Magnetized human dermal fibroblasts (HDFBs) were prepared by treatment with the MNP, induced to form 3-D assembly under a magnetic field. Analyses including LIVE/DEAD assay, transmission electron microscopy revealed that the MNP were internalized via clathrin-mediated endocytosis without cytotoxicity. The magnetized HDFBs could build 3-D structure as a function of seeding density. When the highest seeding density (5 × 105 cells/mm2 was used, the thickness of assembly was 41.90 ± 1.69 μm, with approximately 9.3 ± 1.6 cell layers being formed. Immunofluorescence staining confirmed homogeneous distribution of ECM and junction proteins throughout the 3-D assembly. Real-time PCR analysis showed decrease in expression levels of collagen types I and IV but increase in that of connexin 43 in the 3-D assembly compared with the 2-D culture. Finally, we demonstrated that the discernible layers can be formed hierarchically by serial assembly. In conclusion, our study showed that a multi-layered structure can be easily prepared using magnetically-assisted cellular assembly with highlighting cell-cell and cell-ECM communication.


Structures and Electronic Properties of (KI)n(-/0) (n = 1-4) and K(KI)n(-/0) (n = 1-3) Clusters: Photoelectron Spectroscopy, Isomer-Depletion, and ab Initio Calculations.
The (KI)n(-) (n = 1-4) and K(KI)n(-) (n = 1-3) clusters were studied by negative ion photoelectron spectroscopy and ab initio calculations. Comparison between the theoretical vertical detachment energies and the experimental values revealed that multiple isomers may coexist in the experiments. The existence of two isomers for K(KI)(-) and K(KI)2(-) were confirmed directly by isomer-depletion experiments, in which the low adiabatic detachment energy isomers were depleted by a 1064 nm laser beam before the anions were photodetached by a 532 nm laser beam. Our results show that the most stable structures of the K(KI)(-), (KI)2(-), and K(KI)2(-) anions are chain structures, while those of their neutral counterparts are planar. Three-dimensional structures start to appear at n = 3 for (KI)n(-/0) and K(KI)n(-/0). In the K(KI)n(-) cluster anions, the excess electron is localized on the extra K atom and forms an electron pair with the existing s electron of the K atom; the resulting negatively charged K prefers to interact with the other positively charged K atoms rather than with the I atoms. Both the anionic and neutral (KI)4 clusters have cuboid structures, which may be regarded as the smallest structural motif of KI crystal.


Evaluation of Immune Infiltration Based on Image Plus Helps Predict the Prognosis of Stage III Gastric Cancer Patients with Significantly Different Outcomes in Northeastern China.
Gastric cancer (GC) might have significantly different outcomes within the same AJCC/UICC-TNM stage. The purpose of this study is to help predict the different prognosis through the pattern of immune cell infiltration. We retrospectively analyzed 2605 patients who underwent radical gastrectomy in the Harbin Medical University Cancer Hospital between 2002 and 2013. For stage III with significantly different survival probability, we analyzed the relationship between immune cell surface antigen and survival in TCGA dataset. Furthermore, 200 cases in stage III GC with different survival outcomes were randomly selected for immunohistochemical verification. Image Plus software was used to evaluate the area of immune cell infiltration. We found that patients in stage III had significantly different outcomes. Bioinformatics analysis showed that there was a significant negative correlation between the expression of immune cell surface antigen and prognosis. In order to investigate whether immune infiltration can distinguish GC patients in stage III with differences in prognosis, we verified by immunohistochemistry that CD4+ T cells, CD20+ B cells, and CD177+ neutrophils infiltrated more in group B with better prognosis; CD8+ T cells, CD68+ macrophages, and CD117+ mast cells infiltrated more in group A with poor prognosis. CD117+ mast cells have the same trend of predicting significance for prognosis in the RNA and protein levels. In conclusion, patients with GC in northeastern China have significant prognostic differences only in stage III. CD117+ mast cells may be important evaluation factors in further studies of Immunoscore.


Evidence in Orthodontics related to qualitative research.
Research in Orthodontics has historically followed the positivist model based on the direct relationship of cause and effect between diseases and their specific etiological factors. Despite the objectivity and the great potential of statistical procedures, quantitative methods have progressively been sharing space with other models that can encompass the multiplicity of factors that affect the health-disease process, which until such time was reduced to its biological dimension. This study aims, through an integrative review, to identify orthodontics articles published over a 10-year period that have used, exclusively or not, some method of qualitative research, and analyze the main aspects of their content. A survey was performed on Pubmed, Medline, Scopus, and Lilacs databases from 2007 to 2016 with a focus on the applicability of the qualitative methodology in orthodontic research. The 27 articles selected showed a trend to increase in publications, with the most recent four years concentrating almost 60% of them. Most studies were from Europe, particularly the UK, and the more frequent study objectives were related to the perception of people about the reasons for orthodontic treatment, about the aesthetic and psychosocial impact of malocclusion or orthodontic treatment, and the implications of these factors for their quality of life. Because of its potential to explore behaviours and socio-cultural attitudes sustained in subjectivity, qualitative research offers new possibilities for orthodontic studies and can be used in an exclusive or complementary way in relation to quantitative methods.


High-sensitivity Raman scattering substrate based on Au/La(0.7)Sr(0.3)MnO(3) periodic arrays.
We have developed Au/La(0.7)Sr(0.3)MnO(3) (Au/LSMO) periodic arrays with tunable surface plasmon properties that can be used as novel surface-enhanced Raman scattering (SERS) substrates. The periodic arrays are created by electron beam lithography of LSMO resist and metal film deposition. The LSMO electron beam resist is unique in that it exhibits either positive or negative resist behaviors depending on the electron beam dosage. Interestingly, surface plasmon behavior of the arrays can be controlled by just changing the electron beam dosage when presented with a fixed design pattern. Scanning confocal microscopy and spectral microreflectometry have been adapted to directly demonstrate this unique behavior. Furthermore, we show that our novel Au/LSMO array can be used as a high-sensitivity Raman scattering substrate. To illustrate this working principle, the Au/LSMO periodic array is applied to enhance the Raman scattering of a thin film containing 0.1 wt % poly-3-hexylthiophene (P3HT) in poly(methyl methacrylate) (PMMA). By controlling the geometry of the patterned substrate that exhibits gold surface plasmon near the excitation wavelength, we can enhance the intensity of Raman scattering of P3HT at 1350 cm(-1) up to 4 orders of magnitude as compared with previously generated planar Au substrates.


Modelling health expenditure at the household level in Greece.
Health expenditure data are known to be afflicted by restricted range, zero values, skewness and kurtosis. Several methods for modelling such data have been suggested in the literature to cope with these problems. This paper compares the performance of several alternative estimators, including two-part models and generalised linear models. The dependent variable is household expenditure on health care in Greece, a country where out-of-pocket health expenditure is higher than anywhere else in the European Union, whether as a proportion of GDP, as a share of all health spending, or in per capita terms. To facilitate comparison of model performance, household health expenditure is examined in two different specifications: expenditure on all health care (where zero values are rare) and expenditure on hospital services alone (where zero values are common). In the case of expenditure on all health care, three of the estimators performed almost equally well in terms of three alternative model performance indicators: a modified two-part model with non-linear least squares in the second part, a constant-variance generalised linear model and a variance-proportional-to-mean generalised linear model. In the case of expenditure on hospital services, the constant-variance generalised linear model out-performed the rest. The findings suggest that no estimator is best under all circumstances, while most alternative estimators are likely to produce relatively similar results. The paper concludes by discussing implications for further research.


Graphene-encapsulated hollow Fe₃O₄ nanoparticle aggregates as a high-performance anode material for lithium ion batteries.
Graphene-encapsulated ordered aggregates of Fe(3)O(4) nanoparticles with nearly spherical geometry and hollow interior were synthesized by a simple self-assembly process. The open interior structure adapts well to the volume change in repetitive Li(+) insertion and extraction reactions; and the encapsulating graphene connects the Fe(3)O(4) nanoparticles electrically. The structure and morphology of the graphene-Fe(3)O(4) composite were confirmed by X-ray diffraction, scanning electron microscopy, and high-resolution transmission microscopy. The electrochemical performance of the composite for reversible Li(+) storage was evaluated by cyclic voltammetry and constant current charging and discharging. The results showed a high and nearly unvarying specific capacity for 50 cycles. Furthermore, even after 90 cycles of charge and discharge at different current densities, about 92% of the initial capacity at 100 mA g(-1) was still recoverable, indicating excellent cycle stability. The graphene-Fe(3)O(4) composite is therefore a capable Li(+) host with high capacity that can be cycled at high rates with good cycle life. The unique combination of graphene encapsulation and a hollow porous structure definitely contributed to this versatile electrochemical performance.


[Medical rehabilitation of patients with pneumonia associated with the new COVID-19 coronavirus infection].
Effective medical rehabilitation of patients with pneumonia caused by the new SARS-CoV-2 coronavirus is critical for the recovery and optimization of emergency and specialty care outcomes. In this regard, it is relevant to develop a scientifically based medical rehabilitation program for patients with the coronavirus infectious disease COVID-19, whose composition and structure includes methods and tools that have proven effectiveness. To develop evidence-based approaches to medical rehabilitation for patients with pneumonia associated with the new COVID-19 coronavirus infection. The clinical effects and suggested mechanisms of action of rehabilitation technologies in patients with pneumonia, including those associated with the new COVID-19 coronavirus infection, are considered in Detail. The most studied of the physical methods that have a proven effect are physical exercises, breathing exercises, the complex effect of factors of resort therapy, hydrotherapy, which affect the main clinical manifestations of the underlying disease, astheno-neurotic syndrome and increasing immunity. Clinical recommendations for medical rehabilitation are proposed and its promising methods are considered. Regular generalization and analysis of high-quality randomized controlled clinical trials to evaluate various physical methods of treatment of patients with pneumonia associated with the new COVID-19 coronavirus infection is Necessary, which serve as a basis for the development of future valid clinical recommendations. Timely and adequate specialized medical rehabilitation care is critical to maintaining the health, reducing disability and mortality of patients with pneumonia associated with the new COVID-19 coronavirus infection.


Toward the Allelopathy of Peganum sp. and Related Chemical Constituents in Agriculture.
The genus Peganum constitutes one of the perennial groups of plants of semi-arid regions across the world. It produces diverse classes of metabolites with claimed valuable pharmacological applications. Despite the key chemical and biological properties of the genus, its allelopathy or that of one of its species has not been reviewed yet. Thus, the present survey aims to report the agricultural applications of extracts, fractions, and compounds from the genus Peganum. This work was based on the available literature related to both the Peganum genus and agriculture, which were generated from available high-impact scientific engines. The plants in this genus contain a large group of secondary metabolites including phenolic compounds, terpenes, and N-containing compounds. Alkaloids, as the main components of the extracts from plants in the genus, were identified as the major active principles. The toxicity of Peganum isolates against plants and related pest organisms was also reviewed. Extract preparations from species of Peganum were listed among insecticidal and herbicidal allelochemicals used for crop protection. The review also tried to contextualize natural products in agriculture. Peganum plant extracts and fractions have showed significant potential in weed and crops management, soil health, and biopesticide production.


Phosphatidylcholine activation of bacterial phosphatidylinositol-specific phospholipase C toward PI vesicles.
The effect of different phospholipids on the kinetic behavior of phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis toward PI vesicles has been investigated. Cosonicated PC/PI vesicles displayed enhanced hydrolysis of PI when less than 0. 20 mole fraction PC was incorporated into the vesicle; higher mole fractions of PC led to a decrease from the maximum activity mimicking surface dilution of substrate. Since the PC could affect PI-PLC binding to vesicles, the effect of separate PC vesicles on enzymatic hydrolysis of PI vesicles was examined. Separate phosphatidylcholine vesicles were found to activate PI-PLC-catalyzed cleavage of PI vesicles up to 7-fold. The activation was completely abolished when the PC vesicle was composed of cross-linked molecules. In the absence of enzyme, fluorescence resonance energy transfer studies did not detect any fusion between PI and PC vesicles if the total lipid concentration was below 2 mM. Higher total lipid concentrations (>20 mM) increased PC transfer between PC and PI vesicles, producing a PI vesicle population with small amounts of PC in the outer monolayer. This suggested that the activation of PI-PLC toward PI vesicles reflects the time scale of transfer of PC from PC vesicles to PI vesicles. Cosonicated PC/PI vesicles provide a measure of enzyme activity versus mole fraction of PC that can be used to estimate the extent of vesicle exchange or fusion between separate vesicle pools. The effects of other phospholipid vesicles on PI-PLC hydrolysis of PI were also examined; zwitterionic lipids were activators while anionic phospholipids inhibited activity. The results indicated that PC molecules in the PI interface allosterically bind to PI-PLC and help anchor enzyme in a more active conformation to the PI interface.


Can gadolinium compete with La-Fe-Co-Si in a thermomagnetic generator?
A thermomagnetic generator is a promising technology to harvest low-grade waste heat and convert it into electricity. To make this technology competitive with other technologies for energy harvesting near room temperature, the optimum thermomagnetic material is required. Here we compare the performance of a state of the art thermomagnetic generator using gadolinium and La-Fe-Co-Si as thermomagnetic material, which exhibit strong differences in thermal conductivity and type of magnetic transition. gadolinium is the established benchmark material for magnetocaloric cooling, which follows the reverse energy conversion process as compared to thermomagnetic energy harvesting. Surprisingly, La-Fe-Co-Si outperforms gadolinium in terms of voltage and power output. Our analysis reveals the differences in thermal conductivity are less important than the particular shape of the magnetization curve. In gadolinium an unsymmetrical magnetization curve is responsible for an uncompensated magnetic flux, which results in magnetic stray fields. These stray fields represent an energy barrier in the thermodynamic cycle and reduce the output of the generator. Our detailed experiments and simulations of both, thermomagnetic materials and generator, clearly reveal the importance to minimize magnetic stray fields. This is only possible when using materials with a symmetrical magnetization curve, such as La-Fe-Co-Si.


Electron transfer in a genetically modified bacterial reaction center containing a heterodimer.
Time-resolved optical measurements encompassing the femtoseconds to seconds time scales have been used to investigate Rhodobacter capsulatus reaction centers (RCs) in which the histidine residue at position 200 on the M polypeptide has been changed to a leucine by site-directed mutagenesis. The HisM200----Leu RC, which has a heterodimer consisting of a bacteriochlorophyll and a bacteriopheophytin, is capable of the primary photochemistry observed in wild-type Rb. capsulatus RCs, but with an overall quantum yield reduced by about half. The lower yield resides in the initial electron transfer reaction and may be associated in part with substantial charge transfer character of the excited heterodimer. These and other comparisons between Rb. capsulatus wild-type and HisM200----Leu RCs have important implications for our understanding of the mechanism of electron transfer in the RC and the efficiency of the charge separation process.


A logical starting point for developing priorities for lizard and snake ecotoxicology: a review of available data.
Reptiles, specifically lizards and snakes, usually are excluded from environmental contamination studies and ecological risk assessments. This brief summary of available lizard and snake environmental contaminant data is presented to assist in the development of priorities for lizard and snake ecotoxicology. Most contaminant studies were not conducted recently, list animals found dead or dying after pesticide application, report residue concentrations after pesticide exposure, compare contaminant concentrations in animals from different areas, compare residue concentrations found in different tissues and organs, or compare changes in concentrations over time. The biological significance of the contaminant concentrations is rarely studied. A few recent studies, especially those conducted on modern pesticides, link the contaminant effects with exposure concentrations. Nondestructive sampling techniques for determining organic and inorganic contaminant concentrations in lizards and snakes recently have been developed. Studies that relate exposure, concentration, and effects of all types of environmental contaminants on lizards and snakes are needed. Because most lizards eat insects, studies on the exposure, effects, and accumulation of insecticides in lizards, and their predators, should be a top priority. Because all snakes are upper-trophic-level carnivores, studies on the accumulation and effects of contaminants that are known to bioaccumulate or biomagnify up the food chain should be the top priority.


The effects of milk intake and whole-body vibration exercise on bone mineral density in elderly women in nursing homes.
[Purpose] This study was designed to investigate the effects of lactose-free milk intake and whole-body vibration exercises on bone density in elderly female nursing home residents who had difficulty exercising outdoors and had not consumed milk. [Subjects and Methods] Twenty seven elderly women aged 70 or older from 3 nursing homes located in Incheon, Korea participated in the study. The experimental group (n=13) carried out whole-body vibration exercises and drank lactose-free milk, while the control group (n=14) continued to live their ordinary nursing home lives. Weight, BMI, T-scores, and Z-scores were compared between the experimental and control groups after 12 weeks. [Results] The comparison of changes in weight and BMI in the control group before and after the 12-week experiment found no statistically significant differences. However, bone mineral density was significantly different, with the T-score significantly decreasing from -2.99 to -3.48 and the Z-score decreasing from -1.87 to -2.58. The other comparisons of physical changes in the control group before and after the 12-week experiment found no statistical significance. [Conclusion] The results indicate that regular consumption of lactose-free milk and performing whole-body vibration exercises can delay the progression of bone density loss in older adults in nursing homes; adequate exercise and calcium intake could eventually help prevent fractures.


Liquid-structure forces and electrostatic modulation of biomolecular interactions in solution.
Molecular interactions in solution are controlled by the bulk medium and by the forces originating in the structured region of the solvent close to the solutes. In this paper, a model of electrostatic and liquid-structure forces for dynamics simulations of biomolecules is presented. The model introduces information on the microscopic nature of the liquid in the vicinity of polar and charged groups and the associated non-pairwise character of the forces, thus improving upon conventional continuum representations. The solvent is treated as a polar and polarizable medium, with dielectric properties described by an inhomogeneous version of the Onsager theory. This treatment leads to an effective position-dependent dielectric permittivity that incorporates saturation effects of the electric field and the spatial variation of the liquid density. The non-pairwise additivity of the liquid-structure forces is represented by centers of force located at specific points in the liquid phase. These out-of-the-solute centers are positioned at the peaks of liquid density and exert local, external forces on the atoms of the solute. The density is calculated from a barometric law, using a Lennard-Jones-type solute-liquid effective interaction potential. The conceptual aspects of the model and its exact numerical solutions are discussed for single alkali and halide ions and for ion-pair interactions. The practical aspects of the model and the simplifications introduced for efficient computation of forces in molecular solutes are discussed in the context of polar and charged amino acid dimers. The model reproduces the contact and solvent-separated minima and the desolvation barriers of intermolecular potentials of mean force of amino acid dimers, as observed in atomistic dynamics simulations. Possible refinements based on an improved treatment of molecular correlations are discussed.


Potent antagonists of somatostatin: synthesis and biology.
The search for synthetic analogues of somatostatin (SRIF) which exhibit selective affinities for the five known receptor subtypes (sst1-5) has generated a large number of potent agonist analogues. Many of these agonists display good subtype selectivities and affinities for the subtypes 2, 3, and 5, with very few selective for sst1 or sst4. Until the recent report by Bass and co-workers (Mol. Pharmacol. 1996, 50, 709-715; erratum, Mol. Pharmacol. 1997, 51, 170), no true antagonists had been discovered, let alone any displaying differential receptor subtype selectivity. In this present study, we explore the effect of this putative L5,D6 antagonist motif on various series of somatostatin agonist analogues, both linear and cyclic. It was found that many D5,L6 agonists could be converted into competitive antagonists by applying this motif, the most potent of which was H-Nal-cyclo[DCys-Pal-DTrp-Lys-Val-Cys]-Nal-NH2 (32). This antagonist was selective for hsst2 with an affinity of 75 nM and an IC50 of 15.1 nM against SRIF-14 in a rat in vitro antagonist bioassay. Receptor-selective somatostatin antagonists should provide valuable tools for characterizing the many important physiological functions of this neuropeptide.


Optical modulation based on tunable light absorption and amplification in metasurfaces coupled with gain medium.
While previous tunable metasurfaces were based mainly on tuning of dielectric permittivity or losses in associated tunable elements, here we propose gain-assisted tunable metasurfaces as optical modulators with high ON-OFF ratio. They consist of a dye-doped film placed within metal-insulator-metal (MIM) cavities. Plasmonic modes with enhanced electric field significantly enhance both absorption and emission of light by dye molecules. As a result, it is possible to achieve the perfect absorption in MIM cavities with zero reflection, as well as to compensate losses thus achieving unit reflection. As a result, the achievable ON/OFF ratio is more than 100.


A genome-wide association study of frailty identifies significant genetic correlation with neuropsychiatric, cardiovascular, and inflammation pathways.
Frailty is an aging-related clinical phenotype defined as a state in which there is an increase in a person's vulnerability for dependency and/or mortality when exposed to a stressor. While underlying mechanisms leading to the occurrence of frailty are complex, the importance of genetic factors has not been fully investigated. We conducted a large-scale genome-wide association study (GWAS) of frailty, as defined by the five criteria (weight loss, exhaustion, physical activity, walking speed, and grip strength) captured in the Fried Frailty Score (FFS), in 386,565 European descent participants enrolled in the UK Biobank (mean age 57 [SD 8] years, 208,481 [54%] females). We identified 37 independent, novel loci associated with the FFS (p < 5 × 10-8), including seven loci without prior described associations with other traits. The variants associated with FFS were significantly enriched in brain tissues as well as aging-related pathways. Our post-GWAS bioinformatic analyses revealed significant genetic correlations between FFS and cardiovascular-, neurological-, and inflammation-related diseases/traits, and subsequent Mendelian Randomization analyses identified causal associations with chronic pain, obesity, diabetes, education-related traits, joint disorders, and depressive/neurological, metabolic, and respiratory diseases. The GWAS signals were replicated in the Health and Retirement Study (HRS, n = 9,720, mean age 73 [SD 7], 5,582 [57%] females), where the polygenic risk score built from UKB GWAS was significantly associated with the FFS in HRS individuals (OR per SD of the score 1.27, 95% CI 1.22-1.31, p = 1.3 × 10-11). These results provide new insight into the biology of frailty by comprehensively evaluating its genetic architecture.


Microbes in heavy metal remediation.
Heavy metal contamination due to natural and anthropogenic sources is a global environmental concern. Release of heavy metal without proper treatment poses a significant threat to public health because of its persistence, biomagnification and accumulation in food chain. Non-biodegradability and sludge production are the two major constraints of metal treatment. Microbial metal bioremediation is an efficient strategy due to its low cost, high efficiency and ecofriendly nature. Recent advances have been made in understanding metal--microbe interaction and their application for metal accumulation/detoxification. This article summarizes the potentials of microbes in metal remediation.


Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques.
Human metapneumovirus (HMPV) is an important cause of acute respiratory tract disease for which the development of vaccine candidates is warranted. We have previously described the generation of an iscom matrix-adjuvanted HMPV fusion protein subunit vaccine (Fsol) and a live-attenuated vaccine (HMPVM11). Here, we evaluate the immunogenicity and efficacy of these vaccines in cynomolgus macaques. Immunization with Fsol induced HMPV F-specific antibody responses, virus neutralizing antibody titers, and cellular immune responses, but the induced humoral immune response waned rapidly over time. HMPVM11 was strongly attenuated and displayed limited immunogenicity, although immunization with this virus primed for a good secondary HMPV-specific lymphoproliferative response after challenge infection. The duration of virus shedding in HMPVM11-immunized animals was reduced compared to sham-immunized animals. Both vaccines induced HMPV-specific immune responses, but the rapid waning of immunity is a challenging obstacle for vaccine development.