Metformin represses glucose starvation induced autophagic response in microvascular endothelial cells and promotes cell death.
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose. Mouse MECs (MMECs) were glucose-starved for up to 48h in the absence or presence of metformin (50μM and 2mM) and the status of ER stress, autophagic, cell survival and apoptotic markers were assessed. Activation of ER stress and autophagy was observed in glucose starved MECs as evidenced by the significant increase in the levels of ER stress and autophagic markers while accumulation of LC3B stained punctae in the MECs confirmed autophagic activation. Treatment with 2mM metformin, independent of AMPK, significantly reversed glucose starvation induced ER stress and autophagy in MECs, but, at 24h, did not decrease cell viability; however, at 48h, persistent ER stress and metformin associated inhibition of autophagy decreased cell viability, caused cell cycle arrest in G2/M and increased the number of cells in the sub-G0/G1 phase of cell cycle. Treatment with metformin reduced phosphorylation of Akt and mTOR and inhibited downstream targets of mTOR. Our findings support the argument that treatment with metformin when used in combination with glycolytic inhibitors will inhibit pro-survival autophagy and promote cell death and potentially prove to be the basis for an effective anti-cancer strategy.


Prejunctional beta 1-adrenoceptors inhibit cholinergic transmission in canine bronchi.
The aim of the present study was to determine in canine bronchi the effects produced by norepinephrine (released from adrenergic nerve terminals) on cholinergic neurotransmission. Electrical stimulation of canine bronchi activates cholinergic and adrenergic nerve fibers. The adrenergic neuronal blocker, bretylium tosylate, inhibited the increase in [3H]norepinephrine overflow evoked by electrical stimulation but did not prevent that caused by the indirect sympathomimetic tyramine. During blockade of the exocytotic release of norepinephrine with bretylium, the pharmacological displacement of the sympathetic neurotransmitter by tyramine significantly decreased the contractions evoked by electrical stimulation but did not affect contractions caused by exogenous acetylcholine. Metoprolol, a beta 1-adrenergic antagonist, abolished and propranolol significantly reduced the effect of tyramine during electrical stimulation. alpha 2-Adrenergic blockade, beta 2-adrenergic blockade, or removal of the epithelium did not significantly affect the response to tyramine. These results suggest that norepinephrine when released from sympathetic nerve endings can activate prejunctional inhibitory beta 1-adrenoceptors to depress cholinergic neurotransmission in the bronchial wall.


Sequence-Dependent Self-Assembly of Chiral Polyimides.
Sequence-defined chiral polyimides comprising identical asymmetric diamine monomers arranged in different directions along the main chain were designed and prepared. These new sequence-defined polymers exhibit sequence-dependent self-assembly behaviors and responses to ibuprofen enantiomers, as revealed by their chiroptical spectra and gelation properties. For the first time, the self-assembly of polymers and their interactions with guest molecules have been successfully controlled by means of the directional arrangement of the monomers in their polymer backbones.


Effects of Angiotensin-Converting Enzyme Inhibition and Alpha 1-Adrenergic Receptor Blockade on Inflammation and Hemostasis in Human Hypertension.
Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.


Preparing Nurse Managers for Authentic Leadership: A Pilot Leadership Development Program.
This study examined the impact of a pilot leadership development program on nurse managers' (NMs') use of authentic leadership behaviors. Nurse managers often receive little or no formal training. Literature suggests formal leadership development programs can enhance their leadership competency. A leadership development program was designed and pilot tested to determine effectiveness in enhancing authentic leadership competency. A cross-sectional study used a convenience sample of 16 NMs who participated in the pilot program. Measurable increases in authentic leadership behaviors were demonstrated in both the self-assessments (mean scores increased in 3 of 4 subscales) and RN direct report assessments (mean scores increased in all 4 subscales), with statistical significance achieved in 1 self-awareness behavior. The pilot program demonstrated merit as a tool to enhance NMs' authentic leadership behaviors. Managers perceived greater self-awareness, and direct reports perceived positive change in managers' use of authentic leadership behaviors.


Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles.
Respiratory syncytial virus (RSV) has been identified as a main cause of hospitalisation in infants and children. To date, the current therapeutic arsenal is limited to ribavirin and palivizumab with variable efficacy. In this work, starting from a number of in-house series of previously described anti-RSV agents based on the benzimidazole scaffold, with the aim at gaining a better understanding of the related chemical features involved in potency and safety profiles, we applied a computational study including two focussed comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results allowed us to derive useful suggestions for the design of derivatives and also to set up statistical models predicting the potency and selectivity index (SI = CC50/EC50) of any new analogue prior to synthesis. Accordingly, here, we discuss preliminary results obtained through the applied exhaustive QSAR analyses, leading to design and synthesise more effective anti-RSV agents.


Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.
Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression.


Proposal to modify Rules 27 and 30(3)(b) of the International Code of Nomenclature of Prokaryotes.
We propose to modify Rules 27 and 30(3)(b) of the International Code of Nomenclature of Prokaryotes so that the formal description of new taxa (the 'protologue') will include a statement about the nomenclatural type, so that this information will be linked to the name of the taxon, the derivation (etymology) of the name, and the properties of the taxon.


Views on health information sharing and privacy from primary care practices using electronic medical records.
To determine how patients and physicians balance the perceived benefits and harms of sharing electronic health data for patient care and for secondary purposes. Before-after survey of patients and providers in practices using electronic medical records (EMRs) enrolled in a clinical trial in Ontario, Canada. Outcomes were measured using the Health Information Privacy Questionnaire (HIPQ) at baseline and end of study. Thirteen questions in 4 general domains investigated attitudes towards the privacy of EMRs, outsider's use of patient's health information, the sharing of patient's information within the health care system, and the overall perception of benefits versus harms of computerization in health care. 511 patients (mean age 60.3 years, 49.6% female) and 46 physicians (mean age 47.2 years, 37.0% female) participated. Most (>90%) supported the computerized sharing of the patient's health records among their health care professionals and to provide clinical advice. Fewer agreed that the patient's de-identified information should be shared outside of the health care circle (<70%). Only a minority of either group supported the notion that computerized records can be keep more private than paper records (38-50%). Overall, a majority (58% patients, 70% physicians) believed that the benefits of computerization were greater than the risks of confidentiality loss. This was especially true for patients who were frequent computer users. While these primary care physicians and their patients valued the clinical features of EMRs, a substantial minority have concerns about the secondary use of de-identified information.


New Galantamine Derivatives with Inhibitory Effect on Acetylcholinesterase Activity.
Inhibitors of acetylcholinesterase (AChE) are used to treat many disorders, among which are neurodegenerative upsets, like Alzheimer's disease (AD). One of the limited licensed AChE inhibitors (AChEIs) used as drugs is the natural compound galantamine (Gal). As Gal is a toxic compound, here we expose data about its four derivatives in hybrid peptide-norgalantamine molecules, which have shown 100 times lower toxicity. Four newly synthesized galantamine derivatives have been involved in docking analysis made by Molegro Virtual Docker. Biological assessments were performed on ICR male mice. The change in short and long-term memory performance was evaluated by passive avoidance test. AChE activity and levels of main oxidative stress parameters: lipid peroxidation, total glutathione (GSH), enzyme activities of catalase (CAT), superoxide dismutase, and glutathione peroxidase were measured in brain homogenates. Our experimental data revealed that the new hybrid molecules did not impair memory performance in healthy mice. Two of the compounds demonstrated better than Gal AChE inhibitory activity in the brain. None of them changed the level of lipid peroxidation products, one of the compounds increased GSH levels, and all of them increased CAT enzyme activity. The new galantamine-peptide hybrids demonstrated a potential for inhibition of AChE and antioxidant activity and deserve further attention.


Synthesis of polar head group homologs of all-trans-cyclopentano-phosphatidylcholine, phosphatidyl-N,N-dimethylethanolamine, and phosphatidylethanolamine.
The polar head group region of a conformationally restricted analog of phosphatidic acid (diacylglycero-phosphate) has been systematically modified to give analogs of phosphatidylcholine, phosphatidylethanolamine, and phosphatidyl-N,N-dimethylethanolamine. These analogs differ from their natural counterpart in both the backbone region and in the polar head region, respectively, as follows: the diacylglyceryl moiety has been replaced by an all-trans diacylcyclopentane-1,2,3-triol moiety and the phosphorus-nitrogen separation has been increased incrementally from two to nine methylene units. The synthesis of these homologous series involved phosphorylation of (1,3/2)-2,3-dipalmitoylcyclopentane-1,2,3-triol with each of a series of homologous bromoalkylphosphoric acid dichlorides, which were themselves obtained by phosphorus oxychloride treatment of the homologous bromoalkanols. The resulting bromoalkyl esters of 2,3-dipalmitoylcyclopentane-1,2,3-triol-1-phosphoric acid were reacted with trimethylamine, dimethylamine, or ammonia to give the cyclopentano-phosphatidylcholines, cyclopentano-N,N-dimethylethanolamines, and cyclopentano-phosphatidylethanolamine, respectively. All the compounds were obtained as stable microcrystalline solids. The yields of cyclopentano-phosphatidylethanolamines and of cyclopentano-N,N-dimethylethanolamines were reduced by the formation of compounds which analyzed as monoacyl (lyso) derivatives.


The correlations of psychological status, quality of life, self-esteem, social support and body image disturbance in Chinese patients with Systemic Lupus Erythematosus.
This study aimed (i) to complement existing research by focusing on body image disturbance issues in Chinese Systemic Lupus Erythematosus (SLE) patients; (ii) to investigate how Chinese patients make sense of disease diagnosis and perceived cultural influences within the context of their SLE. A total of 118 SLE patients underwent standardized laboratory examinations and completed several questionnaires. Independent sample t-test, Mann-Whitney U-test, Chi-square test, and multivariate analysis using backward stepwise logistic regression model were used to analyze these data. We found 18.3% SLE patients had BID, which were significantly higher than the control group (.8%). SLE patients are more concerned about their physical changes caused by disease. There were significant correlations among personal health insurance, complication of diabetes, appearance of new rash, depression, anxiety, self-esteem and BID in patients with SLE. Meanwhile, logistic regression analysis revealed that appearance of new rash and high anxiety were significantly associated with BID in SLE patients. In conclusion, it is beneficial to pay attention to the physical and mental health of patients with rheumatic disease from the perspective of body image, to understand their needs and to provide effective and effective service for them.


[Risk factors for alcoholic psychosis in patients with eating disorders].
The aim of the study was to reveal risk factors for development of alcoholic psychosis in patients with eating disorders. Ten inpatients with anorexia nervosa and bulimia nervosa abusing alcohol for 1-4 years have been examined. Delirium tremens was diagnosed in 5 patients in the first few days of staying in the hospital, other 5 patients were included in the control group. Factors precipitating delirium tremens were low body mass index, water-electrolytic imbalance, severe dehydration caused by vomiting and hypoglycemia. A careful choice of doses of psychotropic drugs taking into account concomitant somatic-endocrine disturbances, the degree of electrolytic imbalance and thorough alcoholic anamnesis is important at the earlier stage of treatment.


[Epiperiostal, percutaneous plate osteosynthesis. A new minimally invasive technique with reference to "biological osteosynthesis"].
Conservation of bone perfusion, protection of the soft tissue envelope and reduction of systemic stress by strengthening the host defence mechanism are general and essential aspects of a biological osteosynthesis. The minimal invasive operating techniques with the use of technical aids and tricks form the necessary presupposition for successful bone healing with a low complication rate. For an epiperiosteal, percutaneous plate osteosynthesis, the technique using a sliding tip and a manipulation handle is demonstrated.


Association of obesity with serum leptin, adiponectin, and serotonin and gut microflora in beagle dogs.
Serotonin (5-hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity. To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity. Fourteen healthy Beagle dogs were used in this study. Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF-5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system. Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, P = .025). Adiponectin and 5-hydroytryptamine of cerebrospinal fluid (CSF-5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, P = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group. Decreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram-negative might be related with chronic inflammation status in obese dogs.


Presence and function of dopamine D1 receptors in the rat ventral tegmental area.
In the recent years there is a growing number of reports suggesting that dopamine D1 receptors are involved in the phenomenon of sensitization. In this article we are reviewing the data suggesting the crucial role of dopamine D1 receptors, localized in the rat ventral tegmental area in this phenomenon.


Measurement of leukemia inhibitory factor in biological fluids by radioimmunoassay.
Leukemia inhibitory factor (LIF) exhibits multiple biological activities in various tissues, and we have shown that LIF activates POMC gene transcription in response to immune signals. As higher serum levels of LIF have been reported in septicemia, we measured LIF values in biological fluids by RIA. Immunoreactive LIF was detected in 303 of 428 human serum samples. Circulating LIF detection rates were 69% in acute inflammatory diseases, 83% in chronic inflammatory diseases, 61% in noninflammatory diseases, and 90% in cancer patients. Serum concentrations of human LIF was higher in patients with inflammatory disease than in noninflammatory disease (0.80 +/- 0.10 vs. 0.53 +/- 0.02 ng/mL; P < 0.05) or in cancer patients (0.44 +/- 0.06; P < 0.05). Higher serum human LIF levels were found in septicemia (0.78 +/- 0.14 ng/mL), pneumonia (0.80 +/- 0.10 ng/mL), acute bronchitis (0.88 +/- 0.09 ng/mL), other infections (1.01 +/- 0.17 ng/mL), and systemic lupus erythematosus (SLE; 0.79 +/- 0.06 ng/mL). In 7 septicemia patients, Gram-negative infection was associated with higher LIF levels (1.06 +/- 0.16 ng/mL) than was Gram-positive infection (0.58 +/- 0.14 ng/mL). In patients with acute inflammatory disease, serum LIF levels decreased within several days after hospitalization. To test circulating mouse (m) LIF changes in response to inflammatory stress, lipopolysaccharide (LPS) was injected ip to mice. LPS increased serum mLIF values concordantly with ACTH levels. After i.p. injection of 80 microg LPS, serum mLIF increased by 144% (P < 0.05), 173% (P < 0.05), and 134% at 30, 90, and 120 min respectively. In vitro, however, LPS did not increase ACTH and mLIF secretion from dispersed mouse primary pituitary cells. These results suggest that LIF is an important participant in the pathogenesis of the acute inflammatory response. The elevated serum LIF levels observed in inflammation do not appear to originate from the pituitary.


Substituent and solvent effects on the electrochemical properties and intervalence transfer in asymmetric mixed-valent complexes consisting of cyclometalated ruthenium and ferrocene.
Four heterodimetallic complexes [Ru(Fcdpb)(L)](PF6) (Fcdpb=2-deprotonated form of 1,3-di(2-pyridyl)-5-ferrocenylbenzene; L=2,6-bis-(N-methylbenzimidazolyl)-pyridine (Mebip), 2,2':6',2''-terpyridine (tpy), 4-nitro-2,2':6',2''-terpyridine (NO2tpy), and trimethyl-4,4',4''-tricarboxylate-2,2':6',2''-terpyridine (Me3tctpy)) have been prepared. The electrochemical and spectroelectrochemical properties of these complexes have been examined in CH2Cl2, CH3NO2, CH3CN, and acetone. These complexes display two consecutive redox couples owing to the stepwise oxidation of the ferrocene (Fc) and ruthenium units, respectively. The potential difference, ΔE(1/2)(E(1/2)(Ru(II/III))-E(1/2)(Fc(0/+))), decreased slightly with increasing solvent donocity. The mixed-valent states of these complexes have been generated by electrolysis and the resulting intervalence charge-transfer (IVCT) bands have been analyzed by Hush theory. Good linear relationships exist between the energy of the IVCT band, E(op), and ΔE(1/2) of four mixed-valent complexes in a given solvent.


Efficient broadband polarization retarder via shortcuts to adiabaticity.
The use of two-level atomic systems in quantum optics allows for the design of highly efficient and broadband achromatic retarders through the application of adiabatic passage and composite pulse techniques. In this work, we propose shortcuts to adiabaticity to improve broadband polarization retarders with shorter lengths. We achieve this by inversely engineering the relative refractive indices and further optimizing them with respect to the perturbation of input wavelength. Our results are compared with adiabatic and composite protocols, demonstrating that our method provides the advantage of integrating efficiency and robustness.


Effects of photobiomodulation therapy (PBMT) on the management of pain intensity and disability in plantar fasciitis: systematic review and meta-analysis.
To review the effects of photobiomodulation therapy (PBMT) on pain intensity and disability in people with plantar fasciitis (PF) when compared with control conditions, other interventions, and adjunct therapies. Systematic searches were conducted in five database randomized controlled trials (RCT). We only included randomized controlled trials (RCTs) in adults with PF that compared PBMT to placebo, as well as RCTs that compared PBMT to other interventions; and as an adjunct to other therapies. The methodological quality and certainty were assessed through PEDro Scale and GRADE approach, respectively. The data of comparison were pooled and a meta-analysis was conducted when possible. Nineteen RCTs involving 1089 participants were included in this review. PBMT alone (MD = - 22.02 [- 35.21 to - 8.83]) or with exercise (MD = - 21.84 [- 26.14 to - 17.54]) improved pain intensity in short-term treatment. PBMT was superior to (extracorporeal shock wave therapy) EWST for relief of pain (MD = - 20.94 [- 32.74 to - 9.13]). In the follow-up, PBMT plus exercise had a superior to exercise therapy alone (MD = - 18.42 [- 26.48 to - 10.36]). PBMT may be superior to (ultrasound therapeutic) UST in medium- and long-term follow-ups for disability, but can be not clinically relevant. There is uncertainty that PBMT is capable of promoting improvement in disability. PBMT when used with adjuvant therapy does not enhance outcomes of interest. PBMT improves pain intensity with or without exercise. PBMT has been shown to be superior to ESWT for pain relief, but not superior to other interventions for pain intensity and disability. The evidence does not support PBMT as an adjunct to other electrotherapeutic modalities.


The NTN2L gene encoding a novel human netrin maps to the autosomal dominant polycystic kidney disease region on chromosome 16p13.3.
The netrins define a family of chemotropic factors that have been shown to play a central role in axon guidance. We identified two exon traps encoding netrin-like sequences during the assembly of a transcriptional map for the genomic interval surrounding the polycystic kidney disease type 1 and tuberous sclerosis type 2 genes. We describe the characterization of a novel human netrin-2-like gene, designated NTN2L, and its transcript. The genomic interval containing the NTN2L gene was sequenced, and the coding region was predicted based on computer analysis. The structure of the NTN2L gene has been confirmed utilizing nested RT-PCR. The NTN2L gene is predicted to encode a 580-amino-acid protein having homology to the chicken and Drosophila netrins and to Caenorhabditis elegans UNC-6. The NTN2L gene has a restricted pattern of expression; its transcript is undetectable by Northern analysis in all tissues examined, but can be recovered from spinal cord RNA by RT-PCR. This report represents the first description and characterization of a human netrin.


Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells.
Nanoparticles (NPs) containing cationic monovalent lipids such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTMA), have been widely used for the delivery of nucleic acid such as small-interfering RNA and polypeptide to cells as cancer therapies and vaccine development. Several previous reports have suggested that cationic liposomes induce reactive oxygen species (ROS) and ROS-mediated toxicity in cells. Here, we systematically investigated the effects of DOTAP- or DOTMA-containing NPs without any cargo on the human carcinoma cells, HepG2. Treatment with NPs containing DOTAP or DOTMA increased the production of cellular ROS, such as H2O2 and lipid peroxidation, in HepG2 cells and concomitantly decreased cell viability. These effects were dependent on the lipid concentration, surface density of cationic lipids, and particle size of NPs. However, neutral NPs consisting of 1,2-dioleoyl-3-phosphocholine did not elicit the effective ROS generation or cell death regardless of the lipid concentration and particle size. The present study suggests that DOTAP- and DOTMA-NPs are able to induce cancer cell death through production of ROS in the absence of any therapeutic cancer reagents. These results also provide a rational background for the design of delivery systems using cationic lipid-based NP formulations.


Mycophenolic acid suppresses granulopoiesis by inhibition of interleukin-17 production.
Mycophenolic acid is a commonly used immunosuppressant after organ transplantation and in autoimmune diseases; however, myelosuppression is a major complication despite its largely favorable side-effect profile. Mycophenolic acid targets inosine monophosphate dehydrogenase, which is essential for T-cell proliferation. The T-cell cytokine interleukin-17 (IL-17 or IL-17A) and its receptor maintain normal neutrophilic granulocyte numbers in mice by induction of granulocyte-colony-stimulating factor. To test whether mycophenolic acid induces neutropenia by inhibiting IL-17-producing T cells, we treated C57Bl/6 mice with mycophenolate-mofetil (the orally available pro-drug) and found a dose-dependent decrease in blood neutrophils. This myelosuppressive effect was completely abolished in mice that lack the IL-17 receptor. Mycophenolic acid delayed myeloid recovery after bone marrow transplantation and decreased the percentage of IL-17-producing T cells in the spleen and thymus, and inhibited IL-17 production in human and mouse T cells in vitro. Injection of IL-17 during mycophenolic acid treatment overcame the suppression of the circulating neutrophil levels. Our study shows that mycophenolic acid suppresses neutrophil production by inhibiting IL-17 expression, suggesting that measurement of this interleukin might be useful in estimating the risk of neutropenia in clinical settings.


Toll-like receptors as targets for allergen immunotherapy.
Toll-like receptors (TLRs) are novel and promising targets for allergen immunotherapy. Bench studies suggest that TLR agonists reduce Th2 responses and ameliorate airway hyper-responsiveness. In addition, clinical trials are at initial phases to evaluate the safety and efficacy of TLR agonists for the allergen immunotherapy of patients with allergic rhinitis and asthma. (Figure is included in full-text article.) To date, two allergy vaccine-containing TLR agonists have been investigated in clinical trials; Pollinex Quattro and AIC. The former contains monophosphoryl lipid, a TLR4 agonist and the latter contains, CpG motifs activating the TLR9 cascade. Preseasonal subcutaneous injection of both of these allergy vaccines has been safe and efficacious in control of nasal symptoms of patients with allergic rhinitis. CRX-675 (a TLR4 agonist), AZD8848 (a TLR7 agonist), VTX-1463 (a TLR8 agonist) and 1018 ISS and QbG10 (TLR9 agonists) are currently in clinical development for allergic rhinitis and asthma. TLR agonists herald promising results for allergen immunotherapy of patients with allergic rhinitis and asthma. Future research should be directed at utilizing these agents for immunotherapy of food allergy (for instance, peanut allergy) as well.


Anhydrolide macrolides. 2. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbazate erythromycin A analogues.
A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.


The hemostatic profile of cold-stored whole blood from non-greyhound and greyhound dogs over 42 days.
To compare the hemostatic characteristics of cold-stored whole blood (CSWB) from non-greyhound dogs (NGD) and greyhound dogs (GD) over 42 days of storage, notably, platelet closure time (PCT) (NGD only), manual platelet count (PLT) (GD only), ellagic acid (INTEM) and tissue factor activated (EXTEM) rotational thromboelastometry, prothrombin (PT) and activated partial thromboplastin time (aPTT), fibrinogen concentration (FIB), and the activities of factors (F) FII, FV, FVII, FVIII, FIX, FX, FXIII antigen (FXIII:Ag), and von Willebrand factor antigen (vWF:Ag). Whole blood from 10 NGD and 10 GD, was refrigerated in CPD blood bags at 4°C for 42 days. Blood was analyzed before refrigeration (day 0) and at day 1 (d1), 3, 5, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, and 42. Multivariate linear mixed effects models were created to evaluate coagulation parameters over time and compare NGD and GD. Data are summarized as estimated marginal means with 95% confidence intervals. Significance was set at P < 0.05. The PCT for all NGD CSWB was above the device limit by d7. The PLT for GD CSWB did not change during storage. The mean alpha-angle for INTEM and EXTEM decreased to <50% of baseline at d38 and d31 for NGD, and d31 and d17 for GD CSWB. The mean maximum clot firmness (MCF) for INTEM and EXTEM reduced to <50% of baseline at d42 and d28 for both GD and NGD. PT and aPTT for NGD and GD increased over time. For NGD CSWB, the mean FVIII and vWF:Ag activities decreased to <50% of baseline at d7 and d28, respectively, and FIB reached 0.982 g/dL by d24. For GD CSWB, FVIII, FXIII:Ag and FV activities decreased to <50% of baseline by d3, d38, and d38, respectively, and FIB was 0.982 g/dL at baseline. Alpha-angle and MCF for both INTEM and EXTEM, and activities for FII, FV, FIX, FXIII:Ag were significantly lower, and vWF:Ag was significantly higher overall in GD CSWB compared with NGD. A significant difference in the pattern of change over time was detected between NGD and GD in EXTEM alpha-angle, INTEM and EXTEM MCF, FII, and FVIII activities. The in vitro viscoelastic parameters of GD and NGD CSWB declines over 42 days, but numerous hemostatic parameters (INTEM and EXTEM alpha-angle and MCF, activity of FII, FV, FV, FVII, FIX, FX, FXIII:Ag, vWF:Ag, and FIB) remain within 50% of baseline for more than 14 days. CSWB from GD compared to NGD has reduced hemostatic activity overall, but a similar pattern of decline for most parameters over time.


Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids.
Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (omega3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were measured before and after intervention (mean+/-SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2 U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28), levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/-7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/-0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.


[The questionnaire on paternal engagement of separated fathers].
The present contribution presents psychometric findings of a newly developed questionnaire on paternal engagement after parental separation based on a sample of 225 separated or divorced fathers living in the German part of Switzerland. Factor analyses led to the following five dimensions: educational responsibility, cognitive and social support, quality of the emotional relationship, temporal availability, and leisure activities. Internal consistency coefficients (Cronbach's Alpha) ranged from .86 to .91. The dimensions reflect significant differences of paternal engagement regarding child custody, living arrangements of the mother, and parental cooperation. These findings clearly indicate that paternal engagement after separation should be considered in a differentiated multidimensional way.


Lifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency.
We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9.


Cloning of human T cells specific for measles virus haemagglutinin and nucleocapsid.
T cell lines specific for measles virus (MV) were generated from blood of two DR1/DR2 heterozygous healthy donors with a history of past measles infection. The antigenic specificity of 66 T cell clones derived from the lines was studied in a blastogenic assay using whole measles virus and two purified virus components, haemagglutinin and nucleocapsid. Thirty-nine of the clones were specific for one of the two purified antigens. None of the seven synthetic peptides covering 20% of the MV haemagglutinin amino acid sequence stimulated T cell clones with haemagglutinin specificity. Responsiveness of the majority of the clones were restricted by HLA-D/DR antigens, although two clones were isolated that responded only to MV antigens presented by autologous cells. Ten of 11 clones recognizing the nucleocapsid antigen were DR1-restricted, while the haemagglutinin antigen and whole measles virions were recognized more often in association with the DR2 antigen. These results indicate that much of the MV-specific memory T cell response is specific for the haemagglutinin and nucleocapsid virus antigens, with the DR antigen being the main restriction element involved.


Navigating adalimumab biosimilars: an expert opinion.
The patent expiry of Humira® in 2018 opened up the current European market to eight adalimumab biosimilars - (in alphabetical order) Amgevita®, Amsparity®, Hulio®, Hukyndra®, Hyrimoz®, Idacio®, Imraldi® and Yuflyma® - for the treatment of various immune and inflammatory conditions. Amjevita, Hadlima®, Hyrimoz and Yuflyma have recently become available in the USA, with others expected to reach this market in 2023 as the US patent protection for Humira ends. Although adalimumab biosimilars demonstrate efficacy, safety and immunogenicity similar to the originator, they may differ in product excipient(s) and preservatives, along with their device type(s). Physicians may find it both difficult and time consuming to navigate their way among the array of available adalimumab biosimilars when they need to make a treatment decision. This article explores the characteristics of various adalimumab biosimilars to help clinicians navigate the various options available across Europe and the USA. In addition to drug selection, effective patient-physician communication is needed to nurture realistic patient expectations and minimise potential nocebo effects when prescribing biosimilars.


New Scalable and Efficient Online Pairwise Learning Algorithm.
Pairwise learning is an important machine-learning topic with many practical applications. An online algorithm is the first choice for processing streaming data and is preferred for handling large-scale pairwise learning problems. However, existing online pairwise learning algorithms are not scalable and efficient enough for large-scale high-dimensional data, because they were designed based on singly stochastic gradients. To address this challenging problem, in this article, we propose a dynamic doubly stochastic gradient algorithm (D2SG) for online pairwise learning. Especially, only the time and space complexities of O (d) are needed for incorporating a new sample, where d is the dimensionality of data. This means that our D2SG is much faster and more scalable than the existing online pairwise learning algorithms while the statistical accuracy can be guaranteed through our rigorous theoretical analysis under standard assumptions. The experimental results on a variety of real-world datasets not only confirm the theoretical result of our new D2SG algorithm, but also show that D2SG has better efficiency and scalability than the existing online pairwise learning algorithms.


Optimizing the recovery efficiency of Finnish oil combating vessels in the Gulf of Finland using Bayesian Networks.
Oil transport has greatly increased in the Gulf of Finland over the years, and risks of an oil accident occurring have risen. Thus, an effective oil combating strategy is needed. We developed a Bayesian Network (BN) to examine the recovery efficiency and optimal disposition of the Finnish oil combating vessels in the Gulf of Finland (GoF), Eastern Baltic Sea. Four alternative home harbors, five accident points, and ten oil combating vessels were included in the model to find the optimal disposition policy that would maximize the recovery efficiency. With this composition, the placement of the oil combating vessels seems not to have a significant effect on the recovery efficiency. The process seems to be strongly controlled by certain random factors independent of human action, e.g. wave height and stranding time of the oil. Therefore, the success of oil combating is rather uncertain, so it is also important to develop activities that aim for preventing accidents. We found that the model developed is suitable for this type of multidecision optimization. The methodology, results, and practices are further discussed.


Diabetic macular edema in proliferative stage treated with anti-vascular endothelial growth factor agent and triamcinolone acetonide by laser-based strategies.
To appraise the effect of treatment for diabetic macular edema (DME) in proliferative stage with sufficient panrentinal photocoagulation (PRP) therapy and intravitreal injections (IV) Conbercept and posterior subtenon's triamcinolone acetonide (STTA) sequential therapy. This prospective clinical randomized controlled trial of cross-over design was conducted in three phases. The participants included cases of DME in proliferative stage. They were divided into two groups and treated with PRP before enrollment. Group A were treated with IV-Conbercept 0.5 mg for one month in the 1st phase. Group B were treated with STTA 40 mg (twice per two weeks). The interventions were exchanged in the second phase (2mo) between the two groups. In the third phase (3-6mo) no other treatment was given. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by OCT and complications were compared. After phase I: in Group A, BCVA improved from 0.201±0.17 to 0.37±0.24 (F=5.88, P=0.004). CMT changed from 449±155.10 to 304.1±84.70 µm (F=14.9, P<0.01). In Group B, BCVA changed from 0.195±0.19 to 0.26±0.20 (F=0.76, P=0.41) while CMT changed from 463.82±152.92 to 366.00±115.40 µm (F=3.70, P<0.03). The improvement of BCVA was better in Group A (P<0.05). After phase II: in Group A, BCVA raised to 0.47±0.27 (F=0.26, P<0.01), CMT reduced to 260.67±62.97 µm (F=-188.3, P<0.01); in Group B, BCVA raised to 0.51±0.26 (F=0.31, P<0.01), CMT reduced to 261.93±50.15 µm (F=-201.9, P<0.01). But there were no difference between two groups (P>0.05). After phase III: in Group A, BCVA maintained 0.42±0.25 (F=0.22, P=0.001), CMT maintained 267.8±58.34 µm, (F=-0.27, P<0.01); in Group B, BCVA was 0.47±0.25 (F=-0.27, P<0.01), CMT was 272.71±49.16 µm (F=-191.1, P<0.01). No serious complications happened in all phases. PRP+Conbercept is better than PRP+STTA in DME with proliferative stage but PRP+Conbercept+STTA sequential therapy may be a wiser choice for persistent effectiveness on anatomical as well as functional status.


Sporadic Multifocal Venous Malformations of the Head and Neck.
Objective. To report a case of unusually widespread sporadic venous malformations of the head and neck associated with normal D-dimer levels and, due to the protean clinical manifestations and increased risk of coagulopathy of these lesions, to review their diagnosis and clinical management. Case Report. A 25-year-old man presented with a one-year history of intermittent right-sided neck swelling and tongue swelling. Physical exam revealed additional lesions present throughout the head and neck. There was no family history suggestive of heritable vascular malformations. Radiographic imaging demonstrated 15 lesions located in various tissue layers consistent with venous malformations. A coagulation screen showed a normal prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer level, and fibrinogen level. It was determined that the patient was not at increased risk for intraoperative coagulopathy and preoperative heparin administration would not be necessary. The patient's buccal and tongue lesions were subsequently excised with no complications. The patient also underwent sclerotherapy evaluation for his neck mass. Conclusion. This case describes a unique presentation of sporadic multifocal venous malformations. It also emphasizes the importance of prompt diagnosis and workup when multiple venous malformations are present to prevent morbidity during surgical excision secondary to intravascular coagulopathy.


Adult stem cell treatment of scleroderma.
Provides an update of hematopoietic stem cell transplantation for systemic sclerosis from phase I/II studies and prospective randomized phase III trials, and introduces the concept of mesenchymal stem cells as potential therapy for autoimmune disease. Around 170 transplanted systemic sclerosis patients are registered in Europe. Most received autologous, peripheral blood derived hematopoietic stem cell transplantation. Treatment-related mortality has fallen to 2.5% in the controlled trials compared with 12.5% in the first report in 2002. Over one-third of patients have experienced sustained remission. Two prospective randomized phase III studies are active: the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial in Europe and the Scleroderma Cyclophosphamide Or Transplant (SCOT) trial in the USA. Both have similar selection criteria, endpoint and control arms, but the SCOT trial uses radiation and less cyclophosphamide. So far, no unexpected toxicity has occurred. Reports produced in the past 12 months show reduction of skin collagen and reversal of microvascular remodelling, years after transplant. Bone marrow-derived mesenchymal stem cells from systemic sclerosis patients show in-vitro immunomodulatory properties equal to healthy controls. Hematopoietic stem cell transplantation is currently being tested in prospective randomized controlled trials and appears to 'reset' autoimmunity in systemic sclerosis. Mesenchymal stem cells may have an immunomodulatory role in autoimmune disease.


Self-assembled polynuclear clusters derived from some flexible polydentate dihydrazide ligands.
Polynuclear manganese(II), cobalt(II)/(III), iron(II)/(III) and nickel(II) complexes of a group of flexible polydentate dihydrazone ligands, based on pyridine-2,6-dipicolinic (A), oxalic (B) and malonic (C) subunits are described. Structural details are reported for the linear dinuclear complexes [Ni2(2poap)2(H2O)2](NO3)4 . 2CH3OH . 2.5H2O (1), [Mn2(pttp)(NO3)2(CH3OH)2(H2O)2](NO3)2 . H2O (2) and [Mn2(mapttp)2(NO3)2(H2O)2](NO3)2 . 10H2O (3), a square tetranuclear complex [Co4(pttp)4]Br6 . 9H2O (4), a tetranuclear tetrahedral complex [Ni4(pttp)6](BF4)6F2 . 14H2O (7), and a mixed spin state tetranuclear Ni(II) complex [(2pyoap)2Ni4(CH3OH)4] . 1.5CH3OH (10), with a diamond-like arrangement of metal ions. The paramagnetic metal centers are well separated in each case, leading to weak antiferromagnetic coupling or non-existent spin exchange.


Synthesis and cytotoxic evaluation of C-9 oxidized podophyllotoxin derivatives.
A series of podophyllotoxin and podophyllic aldehyde derivatives, lacking the lactone ring and oxidized at C-9 position, has been prepared. The functionalities considered at C-9 were carboxylic acids and several derivatives such as esters, amides, nitriles or anhydrides. The synthesized compounds were cytotoxic at the micromolar level, though less potent and selective than the parent compounds, revealing the influence of the C-9 electrophilic character on the potency and selectivity of these cyclolignans.


The impact of accuracy motivation on interpretation, comparison, and correction processes: accuracy x knowledge accessibility effects.
Four studies provide evidence for the notion that there may be boundaries to the extent to which accuracy motivation may help perceivers to escape the influence of fortuitously activated information. Specifically, although accuracy motivations may eliminate assimilative accessibility effects, they are less likely to eliminate contrastive accessibility effects. It was found that the occurrence of different types of contrast effects (comparison and correction) was not significantly affected by participants' accuracy motivations. Furthermore, it was found that the mechanisms instigated by accuracy motivations differ from those ignited by correction instructions: Accuracy motivations attenuate assimilation effects because perceivers add target interpretations to the one suggested by primed information. Conversely, it was found that correction instructions yield contrast and prompt respondents to remove the priming event's influence from their reaction to the target.


Alcoholism: a pharmacogenetic disorder.
Alcoholism is an extremely common psychosocial behavioral disorder for which genetic factors may play an important role. Statistical analysis of special kinds of family studies that separate inherited factors from the common family environment point strongly to genetic predisposition. This paper presents data and speculations on the genetically determined differences among population subgroups and individuals in the acute effects of ethanol ingestion, the metabolism of ethanol, the process of tolerance, physical dependence and addictability, premorbid personality features and serious complications of alcoholism in the liver and brain of the alcoholic and in the offspring of alcoholic mothers.


Exenatide-loaded microsphere/thermosensitive hydrogel long-acting delivery system with high drug bioactivity.
A series of mixed hydrogels of PLGA-PEG-PLGA and PCLA-PEG-PCLA were synthesized, and investigated in terms of their critical micelle concentration, stability and thermosensitive properties. Also, some mixed hydrogel was selected to prepare Depot-gel-in-Ms-in-Matrix-gel system for the treatment of type 2 diabetes mellitus. Briefly, Exenatide (EXT) loaded hydrogels was encapsulated in PLGA microspheres (Ms) and further encapsulated into blank hydrogel. The mechanism of Exenatide release involved drug diffusion, hydrogel diffusion, PLGA erosion and mixed hydrogel erosion. The results showed that EXT release in vitro was at a sustained rate for 46days, because it is controlled by the inner-deport-gel, the Ms matrix and the outer-Matrix-gel successively. No burst release or platform was observed due to the interception function and control function of the outer-Matrix-gel. The biological activity of EXT was protected, because the hydrophilic EXT molecules tend to distribute in the hydrophilic domain of the mixed hydrogel. In vivo, a single injection of Depot-gel-in-Ms-in-Matrix-gel allowed mice to maintain a stable blood glucose concentration and well-controlled body weight for 20days. In addition, results of oral glucose tolerance test and Hematoxylin-Eosin staining demonstrated that triple-barrier Depot-gel-in-Ms-in-Matrix-gel was a promising hydrophilic protein/polypeptide-loaded long-acting system with high drug bioactivity.


Protective effects of the pericellular matrix of chondrocyte on articular cartilage against the development of osteoarthritis.
Understanding the pathogenesis of osteoarthritis (OA) provides invaluable information in the search of therapeutic targets for the development of disease-modifying OA drugs. Emerging results from investigations demonstrate that the pericellular matrix of chondrocytes plays important roles in protecting articular cartilages from being degraded. Thus, maintaining the structural integrity of the pericellular matrix may be an effective approach to prevent the development of osteoarthritic joints. In this review article, we discuss the consequences of lacking one or more components of the pericellular matrix, and biological effects of the destruction of the pericellular matrix in the development of OA. We believe that more attention should be directed towards the pericellular matrix for the identification of novel biomarkers and therapeutic targets for the prevention and treatment of OA.


Chronic ascites in late onset systemic lupus erythematosus with antiphospholipid antibodies.
Because doctors are reluctant to diagnose systemic lupus erythematosus (SLE) in elderly patients, the initial diagnosis in this age group is usually tardy. Furthermore, the presenting manifestations in these patients are commonly atypical. We describe a 72-year-old woman in whom chronic ascites with antiphospholipid antibodies was the initial predominant manifestation of subsequently fatal SLE. Only 13 cases of chronic lupus ascites have been reported in the English and French literature. Our patient represents the first case reported in an elderly person.


Scapulothoracic dissociation: a rare variant: a case report.
Scapulothoracic dissociation is a rare injury involving separation of scapula from the thorax along with the upper extremity. Majority of the patients have concomitant neurovascular injury and the prognosis is uniformly poor in such cases. We present a case of scapulothoracic dissociation with comminuted fracture of scapula and acromioclavicular joint disruption without neurovascular deficit. There were associated avulsion fractures of the spinous processes of vertebrae (T3-T5). Such presentation is rare in an already rare scapulothoracic dissociation injury. A discussion regarding the probable mechanism of injury, management and prognosis is presented. scapulothoracic dissociation, scapula fracture, brachial plexus injury, vascular injury.


Electrochemistry, spectroelectrochemistry, chloride binding, and O2 catalytic reactions of free-base porphyrin-cobalt corrole dyads.
Three face-to-face linked porphyrin-corrole dyads were investigated as to their electrochemistry, spectroelectrochemistry, and chloride-binding properties in dichloromethane or benzonitrile. The same three compounds were also investigated as to their ability to catalyze the electroreduction of dioxygen in aqueous 1 M HClO4 or HCl when adsorbed on a graphite electrode. The characterized compounds are represented as (PCY)H2Co, where P = a porphyrin dianion; C = a corrole trianion; and Y = a biphenylenyl, 9,9-dimethylxanthenyl, or anthracenyl spacer, which links the two macrocycles in a face-to-face arrangement. An axial binding of one or two Cl- ligands to the cobalt center of the corrole is observed for singly and doubly oxidized (PCY)H2Co, with the exact stoichiometry of the reaction depending upon the spacer size and the concentration of Cl- added to solution. No Cl- binding occurs for the neutral or reduced forms of the dyad, which contrasts with what is seen for the monocorrole, (Me4Ph5Cor)Co, where a single Cl- ligand is added to the Co(III) corrole in PhCN. The Co(III) form of the corrole in (PCY)H2Co also appears to be the catalytically active species in the electroreduction of dioxygen, which occurs at potentials associated with the Co(IV)/Co(III) reaction, that is, 0.35 V in 1 M HClO4 as compared to 0.31-0.42 V for the same three dyads in PhCN and 0.1 M TBAP. The potential for the catalytic electroreduction of O2 in HCl shifts negatively by 60 to 70 mV as compared to E(1/2) values in 1 M HClO4, consistent with the binding of Cl- to the Co(IV) form of the corrole and its rapid dissociation after electroreduction to Co(III) at the electrode surface.


Palliative surgery for intestinal obstruction due to recurrent ovarian cancer.
Intestinal Obstruction is a frequent complication after operation for Ovarian Cancer. This study was done to see the outcome of palliative surgery for Intestinal Obstruction due to recurrent ovarian Cancer. We retrospectively evaluated the records of all the patients who presented with intestinal obstruction after operations for Ovarian Cancer in all the three Surgical Units of Ayub Teaching Hospital Abbottabad from March 1998 to April, 2009. Demographic data, type of management, morbidity, mortality, hospital stay, surgical procedure, symptomatic relief, return of bowel function and outcome were analyzed. There were 56 patients with symptoms of partial or complete intestinal obstruction. Conservative treatment was successful in 22 (39%) patients. Laparotomy was done in 30 (53.5%) patients. The cause of intestinal obstruction was adhesions 8 (26.6%), local recurrence 10 (33.3%) and diffuse carcinomatosis in 12 (40%) patients. Palliative surgery was done in 20 (66.6%) patients while 8 (26.6%) had adhesionolysis only. 9 (30%) patients had resection and anastomosis, 7 (23.3%) had bypass surgery, 3 (10%) had colostomy and one (3%) had Hartmann procedure. Postoperative complications occurred in 26 (86.6%) patients. 12 (40 %) patients died after surgery. Mean hospital stay was 18 (9-42) days. Palliative surgery was successful in 8 (26.65%). Majority of patients with Intestinal obstruction after operation for Ovarian Cancer can be managed conservatively. Palliative surgery is associated with high mortality and morbidity but it should be done in patients not responding to conservative measures.


The stability of an sir epidemic model with time delays.
In this paper, an SIR epidemic model for the spread of an infectious disease transmitted by direct contact among humans and vectors (mosquitoes ) which have an incubation time to become infectious is formulated. It is shown that a disease-free equilibrium point is globally stable if no endemic equilibrium point exists. Further, the endemic equilibrium point (if it exists) is globally stable with respect to a "weak delay". Some known results are generalized.


Enhancement of the Immune Function by Titanium Dioxide Nanorods and Their Application in Cancer Immunotherapy.
With the rapid development of nanotherapy, concerns surrounding the possible use of nanomaterials-mediated immunomodulation are growing. Thus, evaluating the effects of novel materials for potential application in nanotherapy is essential. Herein, we studied the effects of TiO2-nanorods (NRs) on the immune function and their potential application in immunotherapy. TiO2-NRs exerted specific immunomodulatory effects on the main immune cells. Cytokines TNF-α and IL-2, which play a key role in antitumor processes, were upregulated more significantly than other cytokines (IL-4, IL-5, IFN-γ) in the main immune cells. The cells group treated with a high dose of TiO2-NRs (50 mg/L) for 12 h produced a higher TNF-α content of 530.4 pg/mL relative to that (238.2 pg/mL) treated with saline solution only. The TNF-α content increased to 2.2- and 4.9-fold for macrophages and lymphocytes, respectively. Also, we conclude that TiO2-NRs exposure may trigger T cell proliferation and bias toward Th1 immune response and cause a long-lasting activation of lymphocytes involved in adaptive immunity rather than an innate immunity in BALB/c mice. Furthermore, we explored the potential application of TiO2-NRs in immunotherapy. At a given dose of 1 mg/kg, the inhibition rate by TiO2-NRs (26.7%) was much higher than that by DOX (13.3%).


Three-Dimensional Dendritic Structures of NiCoMo as Efficient Electrocatalysts for the Hydrogen Evolution Reaction.
First-row (3d) transition-metal catalysts, such as bimetallic Ni-Co, represent an emerging class of electrocatalysts for HER, but they usually suffer from a large overpotential significantly above thermodynamic demands. Here, we doped NiCo catalyst with non3d metals molybdenum (Mo) for improvement in catalyzing the hydrogen evolution reaction. The ternary catalyst was readily obtained by a one-pot process via the sequential electrodeposition of Ni, Co, and Mo precursors on titanium (Ti) support. By tailing the deposition conditions, we fabricated NiCoMo catalysts with three-dimensional dendritic structures, exhibiting large amounts of electrochemically active sites. To attain the benchmark HER current density of -10 mA cm-2, an overpotential of ∼132 mV is required in 0.1 M KOH for the Mo-doped NiCo (5 atom % Mo in bath), and they produced the decreasing in Tafel slope of ∼108 mV decade-1 exceeding those of binary NiCo alloy catalysts and other contents of Mo doping. In a synergistic effect, dopant incorporation of Mo element may provide near-optimal adsorption energies for HER intermediates promoting the process of water dissociation and hydrogen intermediates production and binding into molecular hydrogen.


The role of the functional independence measure score in predicting the home discharge of inpatients with cerebrovascular diseases in convalescent rehabilitation wards.
[Purpose] To clarify the cutoff point of the Functional Independence Measure tool for predicting home discharge of patients in convalescent rehabilitation wards. [Participants and Methods] This retrospective observational study analyzed the data of 91 inpatients with cerebrovascular disease who received rehabilitation treatment at a convalescent rehabilitation ward. We categorized the participants into two groups: the home-discharged group and the non-home discharged group. We divided the outcome parameters in the two groups into different categories and compared them using the Mann-Whitney U test. To identify the relevant cutoff points in a clinical setting, we applied the receiver operating characteristic curve. [Results] In patients with cerebrovascular disease, the Functional Independence Measure motor, cognitive, and total scores were significantly higher in the home-discharged group than in the non-home discharged group. We statistically calculated the Functional Independence Measure motor score cutoff point that can predict home discharge, and the predicted Functional Independence Measure motor score at the time of hospitalization was 53.5-60.0 points. [Conclusion] It is important to start rehabilitation at an early stage and increase the amount of training to increase the likelihood of returning home.


[Initial experience with peroperative autotransfusion in spinal surgery].
The authors describe combinations of anaesthesiological methods which enabled them during extensive spondylosurgical operations in 66 patients to reduce the consumption of homologous blood during operation to 90 ml, on the first day after operation to 300 ml and on the second day after operation to 120 ml. In six patients they used preoperative collection of the patient's own blood, in 45 patients acute normovolaemic haemodilution, in all patients controlled hypotension with sodium nitroprusside to a mean arterial pressure of 8-9 kPa and peroperative collection of blood by means of an autotransfusion apparatus Dideco Stat with a standard programme and yield higher than 50%. During and after peroperative collection they did not record any complications. Lower haemoglobin and haematocrit values and a reduced number of erythrocytes, lower than the lower normal range, during and after operation did not threaten the postoperative course in these patients. The authors draw, however, attention to the rise of the number of leucocytes immediately after operation to 19.7 x 10(9). 1(-1) which is due to their shift into the final product. Solution of this phenomenon which can produce ARDS is according to the authors the use of a programme different from the standard one.


Mild Cognitive Impairment is Associated with Poorer Everyday Decision Making.
Older adults are faced with many unique and highly consequential decisions such as those related to finances, healthcare, and everyday functioning (e.g., driving cessation). Given the significant impact of these decisions on independence, wellbeing, and safety, an understanding of how cognitive impairment may impact decision making in older age is important. To examine the impact of mild cognitive impairment (MCI) on responses to a modified version of the Short Portable Assessment of Capacity for Everyday Decision making (SPACED). Participants were community-dwelling, actively driving older adults (N = 301; M age = 77.1 years, SD = 5.1; 69.4% with a college degree or higher; 51.2% female; 95.3% White) enrolled in the Advancing Understanding of Transportation Options (AUTO) study. A generalized linear model adjusted for age, education, sex, randomization group, cognitive assessment method, and study site was used to examine the relationship between MCI status and decision making. MCI status was associated with poorer decision making; participants with MCI missed an average of 2.17 times more points on the SPACED than those without MCI (adjusted mean ratio: 2.17, 95% CI: 1.02, 4.61, p = 0.044). This finding supports the idea that older adults with MCI exhibit poorer decision-making abilities than cognitively normal older adults. It also suggests that older adults with MCI may exhibit poorer decision making across a wide range of decision contexts.


The use of patient-reported outcome measures to classify type 1 and 2 systemic lupus erythematosus activity.
We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity. Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0-3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification. The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group. Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.


Childhood cruelty to animals, firesetting, and enuresis as correlates of competence to stand trial.
The present study investigated the incidence of the childhood symptoms of cruelty to animals, firesetting , and enuresis in the case reports of 1935 offenders evaluated at a court psychiatric clinic. The presence of all or part of this triad of symptoms was more common in those found competent to stand trial than in those found incompetent. However, no association was found between the presence of the triad of symptoms in those charged with violent crimes and those charged with nonviolent crimes.


A national survey of attitudes toward intimate partner violence among married women in Kazakhstan, Kyrgyzstan, and Tajikistan: Implications for health prevention and intervention.
Attitudes toward intimate partner violence (IPV) can affect the prevalence of IPV, response of victims' to IPV (e.g., whether to seek help), and the response of professionals (e.g., police, social workers, health care professionals) to IPV. Knowledge about IPV-related attitudes is essential for developing effective social work and violence-related programs. Using data from the 2005-2006 Multiple Indicator Cluster Surveys, this study examines attitudes toward IPV and socio-demographic predictors of these attitudes among married women in Kazakhstan, Kyrgyzstan, and Tajikistan. Women were asked whether they approved of a husband beating his wife: if she goes out without telling him, neglects their children, argues, refuses to have sex, and burns food. The prevalence of IPV acceptance for at least one of the five reasons varied from 12.3% in Kazakhstan to 45.3% in Kyrgyzstan and 74.5% in Tajikistan. Women who were less educated, members of Asian ethnic groups, resided in middle-class urban areas, and lived in specific regions were more likely to accept IPV. Few age differences that emerged indicated that young women were more approving of IPV. Proactive efforts are needed to confront attitudes about gender roles and IPV in Tajikistan and Kyrgyzstan.


Kinetic studies on the inhibition of Proteus vulgaris beta-lactamase by imipenem.
Imipenem was found to inhibit Proteus vulgaris beta-lactamase in a progressive manner. Kinetic experiments confirmed that the inactivated enzyme was not completely recovered after intact imipenem had been exhausted.


Delayed recurrence of atypical pulmonary carcinoid cluster: a rare occurrence.
Carcinoid is one of the most common tumors of the gastrointestinal tract followed by the tracheobronchial tree. Bronchial carcinoid compromises 20% of total carcinoid and accounts for 1-5% of pulmonary malignancies. Carcinoid can be typical or atypical, with atypical carcinoid compromises 10% of the carcinoid tumors. Carcinoid usually presents as peripheral lung lesion or solitary endobronchial abnormality. Rarely it can present as multiple endobronchial lesion. We hereby present a rare case of an elderly gentleman who had undergone resection of right middle and lower lobe of lung for atypical carcinoid. Seven years later he presented with cough. CT scan of chest revealed right hilar mass. Flexible bronchoscopy revealed numerous endobronchial polypoid lesions in the tracheobronchial tree. Recurrent atypical carcinoid was then confirmed on biopsy.


Plasma concentrations after bath treatment and oral administration of trioxsalen.
An analytical method comprising homogenous extraction and determination by gas chromatography mass spectrometry has been developed for the quantitation of trioxsalen in plasma. The limit of sensitivity of the method has been 2 ng/ml of trioxsalen. The method was used to monitor concentrations of trioxsalen in plasma after a 40 mg oral dose or after trioxsalen bath treatment. The concentrations in plasma after oral administration did not exceed 3 ng/ml, while in 2 patients after bath treatment trioxsalen could be determined (2-3 ng/ml). The low plasma concentrations found throw light on the poor UV-sensitizing properties found after oral trioxsalen therapy.


Roles of APOL1 G1 and G2 variants in sickle cell disease patients: kidney is the main target.
In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30·4 (24·3-36·4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease (P = 0·003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0·001). Further, these genotypes were associated in an age-dependent manner with lower estimated glomerular filtration rate (eGFR, P = 0·008), proteinuria (P = 0·009) and albuminuria (P < 0·001) but not with other SCD complications. Compared to APOL1 G1/wild type (WT), the APOL1 G2/WT genotype was associated with a lower eGFR (P = 0·04) in an age-dependent manner, suggesting that the G2/WT patients are likely to have worse kidney prognosis. Other genes variants analysed were not associated with SCN or other SCD complications. Our data indicate that APOL1 screening should be considered for the management of SCD patients, including those of non-African-American origin, as those with homozygous or double heterozygous variants are clearly at higher risk of SCN.


Poly(ethylene) glycol hydrogel based on oxa-Michael reaction: Precursor synthesis and hydrogel formation.
This paper reported a facile strategy for the one-pot synthesis of vinyl sulfone (VS) group terminated hydrogel precursors [poly(ethylene) glycol (PEG)-VS] and PEG hydrogels via catalytic oxa-Michael reaction. Nine potential catalysts were investigated for the reaction between PEG and divinyl sulfone, among which 4-dimethylaminopyridine (DMAP) prevailed for its high catalytic activity. DMAP produced PEG-VS with a conversion of more than 90% in 2 h under a solvent-free condition at room temperature, which significantly simplifies the synthesis of PEG-VS. The preparation of PEG hydrogels was realized by adding glycerol as a crosslinker, and the physical and the mechanical properties were easily controlled by changing the crosslinker concentration as well as the PEG chain length. This strategy can also be applied to other polyhydroxy compounds as crosslinkers, and thus, a library of hydrogels with designed structures and desired properties could be prepared. The PEG hydrogels showed good antifouling properties, low cytotoxicity, and ability to release drugs at a tunable rate, indicating versatile potential bioapplications.


Medical students' academic emotions: the role of perceived learning environment.
Research shows that there is a relationship between students' perceptions of classroom and learning environment and their cognitive, affective, emotional and behavioral outcomes, so, in this study the relationship between medical students' perception of learning environment and academic emotions was examined. The research method used was descriptive-correlative. The statistical population consisted of medical students of Shiraz University of Medical Sciences. Stratified sampling method was used to select 342 participants. They completed self-report questionnaires of Dundee Ready Educational Environment Measure (DREEM) and Achievement Emotions Questionnaire (AEQ). All descriptive statistics, Pearson's correlations and simultaneous multiple regression were performed using SPSS 14 software. Simultaneous multiple regression of the students' perceived learning environment on their academic achievement emotions showed that the perceived learning environment predicts the students' academic emotions.


Factorial modeling of differential distractor functioning in multiple-choice items.
A factorial procedure for investigating differential distractor functioning in multiple-choice items is proposed. The procedure adopts the formulation of general linear models and treats grouping factors as independent variables and item parameters across the grouping factors as a dependent variable. Specifically, each distractor in a multiple-choice item is modeled with a distinct distractibility parameter. The distractibility parameters across groups are partitioned into a grand mean distractibility and sets of parameters representing main effects of the individual grouping factors, and interaction effects among them. Results of a simulation study show that the parameters of the proposed modeling were recovered very well. Ten four-choice items in the English test of the 1997 Taiwan Joint College Entrance Examination with seven thousands of examinees in two grouping factors were analyzed.


Biodecolorization of textile azo dye using Bacillus sp. strain CH12 isolated from alkaline lake.
Textile azo dye decolorizing bacteria were isolated from alkaline Lakes Abaya and Chamo using Reactive Red 239 (RR239) dye. Through subsequent screening process, strain CH12 was selected to investigate the effects of nutrient supplement, DO, pH, temperature, dye concentration and types on decolorization. Based on 16S rRNA gene sequence analysis, strain CH12 was identified as Bacillus sp. Decolorization efficiencies were significantly enhanced with carbon (≥98%) and organic nitrogen (∼100%) supplements. Complete decolorization was also observed under anoxic and anaerobic conditions, and at the temperature of 30 °C and the pH of 10. However, the azo dye decolorization efficiency of strain CH12 was significantly reduced when NaNO3 (1-8%) was supplemented or under aerobic culturing condition (≤6%), indicating that RR239 was less preferred electron acceptor. Overall, strain CH12 can be a promising candidate for decolorization applications due to its potential to effectively decolorize higher RR239 concentrations (50-250 mg/L) and six additional dyes.


A ten-inch manipulator (TIM) based fast-electron spectrometer with multiple viewing angles (OU-ESM).
The measurement of angularly resolved energy distributions of mega-electron-volt electrons is important for gaining a better understanding of the interaction of ultra-intense laser pulses with plasma, especially for fast-ignition laser-fusion research. It is also crucial when evaluating the production of suprathermal (several 10-keV) electrons through laser-plasma instabilities in conventional hot-spot-ignition and shock-ignition research. For these purposes, we developed a 10-in. manipulator-based multichannel electron spectrometer-the Osaka University electron spectrometer (OU-ESM)-that combines angular resolution with high-energy resolution. The OU-ESM consists of five small electron spectrometers set at every 5°, with an energy range from ∼40 keV to ∼40 MeV. A low-magnetic-field option provides a higher spectral resolution for an energy range of up to ∼5 MeV. We successfully obtained angularly resolved electron spectra for various experiments on the OMEGA and OMEGA EP laser systems.


Treating atherosclerosis with regulatory T cells.
Regulatory T cells (Tregs) play an important role in the regulation of T-cell-mediated immune responses through suppression of T-cell proliferation and secretion of inhibitory cytokines, such as interleukin-10 and transforming growth factor-β. Impaired Treg numbers and function have been associated with numerous diseases, and an imbalance between proinflammatory/proatherogenic cells and Tregs promotes atherosclerotic disease. Restoration of this balance by inducing Tregs has great therapeutic potential to prevent cardiovascular disease. In addition to suppressing differentiation and function of effector T cells, Tregs have been shown to induce anti-inflammatory macrophages, inhibit foam cell formation and to influence cholesterol metabolism. Furthermore, Tregs suppress immune responses of endothelial cells and innate lymphoid cells. In this review, we focus on the recent knowledge on Treg subsets, their activity and function in atherosclerosis, and discuss promising strategies to use Tregs as a therapeutic tool to prevent cardiovascular disease.


Detection of Vibrio cholerae with monoclonal antibodies specific for serovar O1 lipopolysaccharide.
Six hybridoma cell lines, each of which produced a monoclonal antibody (MAb) against Vibrio cholerae O1 lipopolysaccharide (LPS), were established. Each MAb was active serologically by both enzyme-linked immunosorbent assay (ELISA) and the slide agglutination test. In the ELISA, each MAb was tested against 7 O1 and 9 non-O1 LPS preparations. Three MAbs reacted with both Inaba and Ogawa serovars (A antigen), two MAbs reacted with the Ogawa serovars only (B antigen), and one MAb reacted with the Inaba serovars only (C antigen). Each MAb was also tested in the ELISA against whole-cell preparations of 37 O1 and 52 non-O1 V. cholerae serovars, 20 heterologous Vibrio species, and 37 heterologous bacterial species. The MAbs reacted with V. cholerae O1 cells only, except for one anti-A antigen MAb which reacted weakly with five V. cholerae non-O1 serovars and Serratia marcescens. Each anti-A antigen MAb was labeled with fluorescein isothiocyanate (FITC) and tested by direct immunofluorescence against selected O1 and non-O1 serovars. Each MAb-FITC conjugate, when tested alone, exhibited O1-specific fluorescence; however, mixtures of the MAb-FITC dramatically enhanced fluorescence intensity on O1 cells. This finding was also visualized by immunoelectron microscopy on both thin-sectioned and negatively stained O1 cells by using an anti-mouse immunoglobulin-colloidal gold conjugate. These results suggest that the A antigen can be described by more than one epitope and that a superior serotyping reagent can be prepared from a defined mixture of MAbs.


Updated Data on Linkage to Human Immunodeficiency Virus Care and Antiretroviral Treatment Among Men Who Have Sex With Men-20 Cities, United States.
We examined differences in prevalence of linkage to care and antiretroviral (ARV) treatment among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) between 2008 and 2014 in National HIV Behavioral Surveillance. Prevalence of linkage to care increased from 79% in 2008 to 87% in 2014 (prevalence ratio [PR], 1.05; 95% confidence interval [CI], 1.03-1.07). ARV treatment increased from 69% in 2008 to 88% in 2014 (adjusted PR, 1.15; 95% CI, 1.12-1.18). Despite these increases, a large disparity in ARV treatment between white and black MSM remains. Increased resources are needed to support immediate referrals for ARV treatment for all MSM newly diagnosed with HIV.


Noncontact Electrical Permittivity Mapping and pH-Sensitive Films for Osseointegrated Prosthesis and Infection Monitoring.
The objective of this paper is to develop a noncontact, noninvasive system for detecting and monitoring subcutaneous infection occurring at the tissue and osseointegrated prosthesis interface. It is known that the local pH of tissue can change due to infection. Therefore, the sensing system integrates two parts, namely, pH-sensitive thin films that can be coated onto prosthesis surfaces prior to them being implanted and an electrical capacitance tomography (ECT) algorithm that can reconstruct the spatial permittivity distribution of a region of space in a noncontact fashion. First, a thin film pH sensor was fabricated by spray coating, and tests confirmed that the film exhibited changes in its permittivity due to pH. Second, the ECT forward and inverse problems were implemented. Third, an aluminum rod was employed as a representative phantom of an osseointegrated prosthesis and then spray coated with the pH sensor. Finally, the film-coated phantom was immersed in different pH buffers, dried, and subjected to ECT interrogation and spatial permittivity reconstruction. The results validated that ECT was able to detect and localize permittivity variations correlated to pH changes.


The centromere: epigenetic control of chromosome segregation during mitosis.
A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.


Bilateral migration of open-cell design carotid stents in the early post-procedure period: a rare complication.
We describe migration of bilateral carotid stents in a 63-year-old man shortly after stenting. Carotid stent migration was found four days post-procedure on the right side and one day post-procedure on the left side on angiography and duplex ultrasound, respectively. This is the first reported case of bilateral carotid artery stenting complicated by bilateral proximal migration of open-cell design stents in the early post-procedure period.


Hepatitis C and Risk of Nonhepatic Malignancies.
Epidemiologic studies show an increased risk of mortality among hepatitis C virus (HCV)-infected individuals compared with uninfected individuals from hepatic and nonhepatic causes. This article reviews the biologic plausibility of and epidemiologic evidence for the association between HCV and five extrahepatic malignancies: cholangiocarcinoma (CCA), pancreatic adenocarcinoma, papillary thyroid cancer, oral squamous cell cancer, and renal/kidney cancer. There is sufficient evidence to suggest that HCV is associated with intrahepatic CCA. The evidence for the link between HCV and pancreatic adenocarcinoma, oral squamous cell cancer, and renal/kidney cancer is compelling but requires further study. Based on available studies, there is no significant association between HCV, extrahepatic CCA, and papillary thyroid cancer.


Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial.
Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL·24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL·24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg·24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.


Coordination complexes of NbX5 (X = F, Cl) with (N,O)- and (O,O)-donor ligands and the first X-ray characterization of a neutral NbF5 adduct.
A variety of fairly air-stable complexes were prepared by straightforward reactions of NbX5 (X = F, Cl) with a series of potential bidentate (N,O)- and (O,O)-donor ligands in CH2Cl2. NbF5 reacted with equimolar amounts of 2-[(2,6-diisopropylphenyl)iminomethyl]phenol (dpimpH) and 2-benzoyl-6-hydroxy-6-phenylpentafulvene (bhpfH) to afford the mononuclear complexes NbF5[κ(1)(O)-OC6H4CH=NHC6H3(CHMe2)2], 2, and NbF5[κ(1)(O)-bhpfH], 7, respectively. The 1:1 reactions of NbF5 with salicylaldehyde oxime (saoH2) and 2-phenylaminoethanol gave the hexafluoroniobato salts [NbF4{κ(1)(O)-ON(H)=CHC6H4OH}2][NbF6], 3, and [NbF4{κ(1)(O)-OCH2CH2NH2Ph}2][NbF6], 6, respectively. The syntheses of 2, 3 and 6 are accompanied by oxygen to nitrogen intramolecular H migration, leading to the formation of metal-alkoxide moieties. The parallel chemistry of NbCl5 is characterised by HCl release. The 1:1 reactions with dpimpH, saoH2 and bhpfH yielded, respectively, the ionic complex [NbCl2{κ(1)(N):κ(1)(O)-dpimp}2][NbCl6], 4a, the neutral-dinuclear Nb2Cl7[κ(1)(O)-saoH][κ(2)(O)-sao], 5, and the mononuclear NbCl4[κ(2)(O)-bhpf], 8. The tantalum species [TaCl2{κ(1)(N):κ(1)(O)-dpimp}2][TaCl6], 4b, was prepared from TaCl5/dpimpH. The new products 2-8 were fully characterized by analytical and spectroscopic techniques. Moreover the solid state structures of 2 and 8 were ascertained by X-ray diffraction studies; the structure of 2 exhibits an intramolecular bifurcated N-H···(O,F) hydrogen bond. DFT calculations were carried out in order to predict the lowest energy structures in the distinct cases, showing generally good agreement with the experimental data.


A case of a malignant mixed tumor in the vagina.
Malignant mixed tumors in the vagina are extremely rare. We experienced a case of a malignant mixed tumor (synovioid variant). Surgical treatment was performed, followed by 3 courses of chemotherapy. Up to the present time, 4 years after the first treatment, no signs of recurrence have been observed.


Bacterial extracellular polysaccharides.
The synthesis of extracellular polysaccharides has been recognized in certain bacterial cultures since the 1880s. It is now apparent that a wide range of bacteria produce these polymers and an equally wide range of chemical structures are possible. Their surface location, together with the range of available monosaccharide combinations, noncarbohydrate substituents, and linkage types, make extracellular polysaccharides excellent agents of diversity. As a result, much effort has been directed towards elucidating their structure in pathogenic bacteria and in enteric organisms in particular. Commercial applications of microbial polysaccharides have now broadened the scope of structural information. Most recently, technological advances in molecular biology have created the possibility of manipulating desired polymer characteristics, and with these advances, our knowledge of the mechanisms of synthesis and regulation of cell surface polysaccharides has improved. Ultimately more information regarding the function of extracellular polysaccharides in natural environments may result.


The role of Aβ in Alzheimer's Disease as an Evolutionary Outcome of Optimized Innate Immune Defense.
Alzheimer's Disease is a progressive manifestation of aging associated with accumulated Amyloid β. It remains frustratingly unclear why this protein accumulates and how it contributes to Alzheimer's Disease pathology. In one recent hypothesis, Amyloid β is suggested to function as an antimicrobial peptide in innate immune defense within the brain, where Amyloid β gains toxicity when it becomes abundant. This essay proposes an evolutionary explanation for why Amyloid β expression is regulated at an optimum based on its function as a defense and how this leads to disease. Among its potential physiological functions, Amyloid β confers benefits to reduce direct pathogen damage while this simultaneously entails cellular cost of defense. Optimal Amyloid β expression occurs when the gain in fitness from an incremental increase is balanced by the marginal cost of this increase. It proposes that natural selection acting upon the young favored systems to maintain Amyloid β at an optimal level through mechanisms that induce the defense and repress its expression. With age, the force of natural selection declines and permits mechanisms of negative feedback repression to degenerate. Consequently, Amyloid β is expressed beyond its optimum. Age also elevates cumulative pathogen exposure, reduces pathogen barriers and reactivates latent pathogens. The net effect is elevated, chronic induction of Amyloid β in the brain. The model recommends attention to innate immune negative regulation in the brain to discover ways to restore these functions toward a youthful state in the elderly.


A sewage disposal failure as a cause of ascariasis and giardiasis epidemic in a family.
In monitoring the incidence of intestinal parasites in children and employees of a nursery the authors examined 31 children with 8 (25.81%) and 16 employees with 3 (18.75%) positive results. The authors wanted to examine also the family members of 8 positive children and 3 positive employees but except from the cleaner's family, (Ascaris lumburicoides, Enterobius vermicularis and Entamoeba coli) nobody accepted the offer. All 8 members of a large family except for Patient 1 (a cleaner) and her grandson were without clinical and laboratory findings. They constitute 3 independent families who lived in 1st category flats. On August 31 there was an extensive sewage disposal failure in the ground floor flat of Family II and the flat was flooded by sewage. All family members worked solidarily on cleaning and also the members of Family IV who are friends of Family II. As shown by clinical symptoms of 'virosis', during the pre-patent period and after an outbreak within 73-78 days, laboratory findings of the family members demonstrated a severe family infection equal to a epidemic of intestinal parasitosis. Ascaris lumbricoides was diagnosed in 8 family members (61.54%) and Giardia intestinalis in 7 family members (53.85%) involved in cleaning. Enterobius vermicularis was found in 2 and Etamoeba coli in 1 family member. In monitored persons, in extreme hygienic conditions during the failure and later, a mass contraction arose on the basis of infection. The fact, that family epidemic arose subsequently, proved, in contrast to sporadic findings in children and adults, a 6.4 and 3.3 times higher incidence of Ascaris lumbricoides and a 5.6 and 8.6 times higher incidence of Giardia intestinalis. The authors discus the reasons of incidence and also preventive measures in population. (Tab. 3, Ref. 29.).


Stenting the vertical ductus arteriosus via axillary artery access using "wire-target" technique.
To retrospectively review the outcome of stent placement in neonates with a vertical ductus, present a technique of ductal stenting via the axillary artery and compare it to ductal stening via the femoral venous access. Nineteen patients with duct-dependent pulmonary circulations through a vertical ductus arteriosus were treated with stent implantation. Those patients were retrospectively included in the study. In the first nine of these cases, stent delivery was done transvenously. In the latter ten cases, we favored the axillary artery access to the transvenous approach for stenting the vertical ductus arteriosus. Wire-target technique was used to attain access to axillary artery. PDA stenting was successful in six out of nine cases in whom the procedure was done anterogradely via the femoral vein and in all cases in whom the procedure was done via axillary artery (P = .047). Wire-target technique was used successfully in all ten cases in whom the procedure was done via axillary artery. Fluoroscopy time and total procedure time were significantly shorter in patients in whom the procedure was done via axillary artery (P < .001) CONCLUSIONS: Stenting of a vertical ductus arteriosus via the axillary artery using wire-target technique is feasible and safe in selected patients.