A sensitive and versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch.
In the present study, a versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch has been developed. An aptamer probe is designed to hybridize with the methylene blue (MB)-modified DNA capture probe immobilized on the gold electrode to form rigid triple-helix DNA, impeding the efficient electron transfer of MB to the electrode and resulting in the decreased oxidation peak current of MB. However, upon introduction of the perfectly matched target, for example, human α-thrombin (Tmb), the interaction between Tmb and the aptamer probe leads to the dissociation of the triple-helix DNA structure and thereby liberates the MB-modified end of the capture probe, allowing the MB to collide with the electrode surface and resulting in an increase of the oxidation peak currents of MB. Therefore, the sensitive signal-on detection of Tmb is realized, and the detection limit of Tmb is 0.12 nM. The proposed approach also demonstrates excellent regenerability, reproducibility and stability. Additionally, it also has the advantages of simplicity in design and easy operation. The success in the present biosensor provides a promising alternative to the electrochemical detection of a variety of analytes and may have potential applications in point-of-care testing and clinical diagnosis.


Distinguishing the Structures of High-Pressure Hydrides with Nuclear Magnetic Resonance Spectroscopy.
The structural characterization of high-pressure hydrides has encountered many difficulties mainly due to the weak X-ray scattering of hydrogen. Herein, we investigate the prospect of detecting the H3S and LaH10 structures with nuclear magnetic resonance (NMR) spectroscopy. Our calculations demonstrate that the different candidate structures of H3S (or LaH10) exhibit significant differences in the electric field gradient (EFG) tensor of the 33S (or 139La) sites, indicating that the NMR spectroscopy can well capture the structural differences, even the small changes in the atomic position, and hence can be used to effectively probe the structures and the phase transitions of H3S and LaH10. Our results clarify the relationship between the structures and the EFG tensor parameters and provide a potential means to detect the structures of high-pressure hydrides.


Comparison of four phaC genes from Haloferax mediterranei and their function in different PHBV copolymer biosyntheses in Haloarcula hispanica.
The halophilic archaeon Haloferax mediterranei is able to accumulate large amounts of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with high molar fraction of 3-hydroxyvalerate (3HV) from unrelated carbon sources. A Polyhydroxyalkanoate (PHA) synthase composed of two subunits, PhaCHme and PhaEHme, has been identified in this strain, and shown to account for the PHBV biosynthesis. With the aid of the genome sequence of Hfx. mediterranei CGMCC 1.2087, three additional phaC genes (designated phaC1, phaC2, and phaC3) were identified, which encoded putative PhaCs. Like PhaCHme (54.8 kDa), PhaC1 (49.7 kDa) and PhaC3 (62.5 kDa) possessed the conserved motifs of type III PHA synthase, which was not observed in PhaC2 (40.4 kDa). Furthermore, the longer C terminus found in the other three PhaCs was also absent in PhaC2. Reverse transcription PCR (RT-PCR) revealed that, among the four genes, only phaCHme was transcribed under PHA-accumulating conditions in the wild-type strain. However, heterologous coexpression of phaEHme with each phaC gene in Haloarcula hispanica PHB-1 showed that all PhaCs, except PhaC2, could lead to PHBV accumulation with various 3HV fractions. The three kinds of copolymers were characterized using gel-permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Their thermal properties changed with the variations in monomer composition as well as the different molecular weights (Mw), thus might meet various application requirements. We discover three cryptic phaC genes in Hfx. mediterranei, and demonstrate that genetic engineering of these newly identified phaC genes has biotechnological potential for PHBV production with tailor-made material properties.


Ropinirole-induced symptomatic sinus node dysfunction.
Restless legs syndrome is a neurological disorder that can be treated with ropinirole. We report the case of a patient who presented with syncope during treatment with ropinirole due to prolonged sinus pauses. The treatment was discontinued and the patient remained asymptomatic. Ropinirole may induce symptomatic sinus pauses in patients without organic sinus node dysfunction.


Towards a new understanding of provider continuity.
Provider continuity is in need of an expanded definition that is not exclusively clinician centered. Currently, provider continuity is defined by visits over time to the same clinician. Many patients and informal caregivers, however, are co-providers of health care, not merely consumers. As a result, provider continuity will not happen if there is a lack of consistency in who attends with or for the patient during successive visits. Such fragmentation may weaken knowledge of the patient and information exchange. Consequently, there is a need to redefine provider continuity to mean that the same attendees visit the same clinician(s), service, or facility as an uninterrupted succession of events. More than semantic quibbling, the proposed reconceptualization challenges the foundation of family medicine in terms of the values and language by which the discipline defines itself in clinician-centered ways. The change required has implications for practice and research.


Development and Evaluation of MCC-SiO2/CMC-SiO2 Conjugates as Tablet Super-Disintegrants.
In the present study, microcrystallinecellulose-colloidal silicon dioxide (MCC-SiO2) and carboxymethylcellulose-colloidal silicon dioxide (CMC-SiO2) conjugates have been investigated as superdisintegrants in fast dissolving tablets (FDTs). MCC-SiO2 and CMC-SiO2 conjugates were prepared and micromeritic studies, FTIR, SEM and XRD methods were utilized for characterizing the powdered conjugates. The conjugates were used for the preparation of domperidone FDTs by direct compression and the wetting time, water absorption ratio, disintegration time and in vitro drug release were evaluated. Effective pore radius of MCC-SiO2 and CMC-SiO2 conjugates for 1:1, 1:2.5 and 1:5 was found to be 13.35 ± 0.31 µm, 15.66 ± 0.17 µm and 18.38 ± 0.44 µm, and 16.81 ± 0.24 µm, 20.12 ± 0.39 µm and 26.37 ± 0.24 µm, respectively, compared to 12.21 ± 0.23 µm for MCC and 13.65 ± 0.21 µm for CMC. The results of effective pore radius indicate the wicking capability as well as the disintegration potential of MCC-SiO2 and CMC-SiO2 conjugates over pure MCC and CMC. The results of wetting time, water absorption ratio and disintegration time for MCC-SiO2 conjugates were found to be in the range of 19 ± 1.21 to 30 ± 1.33 s, 42 ± 0.28 to 49 ± 0.47% and 15 ± 2 to 40 ± 1 s, and for CMC-SiO2 conjugates were found to be in the range of 21 ± 1.13 to 40 ± 1.17 s, 42 ± 0.94 to 49 ± 0.57% and 12 ± 2 to 20 ± 3 s, respectively. Conjugation of MCC and CMC with SiO2 led to the formation of a complex with remarkable tablet superdisintegrant potential that could be used in preparing fast disintegrating tablets.


Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian cancer.
The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide. Twenty-five newly diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment. Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8. This regimen was well tolerated, as abdominal pain and hematological toxicities were minor, while neurotoxicity grade I/II was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients had no evidence of disease. At a median follow-up of 30 months patients with residual disease after surgery (n = 10) had a median progression-free survival (PSF) of 13 months; for the optimally debulked group (n = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from the peritoneal cavity and plasma followed first-order kinetics and was not influenced by adding carboplatin with cyclophosphamide. This regimen was well tolerated, with minimal hematologic or neurotoxicity, and allowed the application of a triple-drug schedule without compromising dose intensity. To judge its efficacy, comparison with a standard iv paclitaxel-based schedule should be performed in a formal phase III study.


[Bartter syndrome--case report].
The authors present the case of 4-month-old girl, who was admitted to our hospital with hypokalemia, metabolic alkalosis, hyperaldosteronism, hyperreninism with normal blood pressure and high urine concentration of PGE2. All the clinical and biochemical features have led to the diagnosis of Bartter syndrome. Treatment consisted of 15% KCI, spironolacton and indometacin.


Hydrogen-bonding-induced shifts of the excitation energies in nucleic acid bases: an interplay between electrostatic and electron density overlap effects.
The theoretically calculated dimerization-induced shifts of the lowest excitation energies in two model systems, adenine-thymine and guanine-cytosine base pairs, are analyzed. The applied formalism is based on first principles and allows one to study the influence of the microscopic environment of a given molecule on its ground- [Wesolowski, T. A.; Warshel, A. J. Phys. Chem. 1993, 97, 8050] and excited-state [Casida, M. E.; Wesolowski, T. A. Int. J. Quantum Chem. 2004, 96, 577] properties. The assessment of the relative importance of such effects as (a) Coulomb interactions, (b) orbital interactions, (c) electronic polarization of the environment, and (d) electron density overlap effects is straightforward in this formalism. In the applied formalism, electron density overlap effects can be further decomposed into the exchange-correlation component which provides a small attractive contribution and the repulsive kinetic energy-dependent component. It is shown that the shifts can be attributed to the electrostatic interactions and the repulsive overlap-dependent term in the embedding potential. The electronic polarization of the environment plays a significant role (up to 30% of the total shift) only in transitions involving the orbitals localized on hydrogen bond donor groups. For all analyzed shifts, the contribution of the intermolecular orbital interactions is negligible. The analysis of this work provides strong evidence supporting the use of the widely applied embedding-molecule strategy in computational studies of chromophores in a condensed phase even in such cases where only one end of the hydrogen bond is included in the quantum mechanical part.


Furofuran Lignan Glucosides with Estrogen-Inhibitory Properties from the Bangladeshi Medicinal Plant Terminalia citrina.
Extracts from the leaves of the Bangladeshi medicinal plant Terminalia citrina were prepared, and 13 new furofuran lignan glucosides, terminalosides A-K (1-4, 6-12), 2-epiterminaloside D (5), and 6-epiterminaloside K (13), were characterized using various spectroscopic techniques. Twelve of the isolates were found to contain rare tetraoxygenated aryl groups in their structures. Analysis of the NMR chemical shifts for the oxymethine signals in the furofuran ring suggested a pragmatic approach to determining the relative configuration of these compounds. The ECD and NOESY spectroscopic data obtained allowed for the deduction of the absolute configurations and conformations of the compounds. The isolates were tested for their estrogenic/antiestrogenic activity using the MCF-7 and T47D estrogen-responsive human breast cancer cell lines. Terminalosides B (2) and G (8) exhibited inhibitory effects for both cell lines, and estradiol-enhanced cell proliferation was suppressed by 90% at concentrations lower than 10 μM. Terminaloside E (6) showed inhibitory activity against the T47D cell line, whereas terminalosides C (3), F (7), and I (10) and 6-epiterminaloside K (13) displayed antiestrogenic activity against MCF-7 cells.


Identification of Pelvic Congestion Syndrome Using Transvaginal Ultrasonography. A Useful Tool.
The gold standard for the diagnosis of pelvic congestion syndrome (PCS) is venography (VG), although transvaginal ultrasound (TVU) might be a noninvasive, nonionizing alternative. Our aim is to determine whether TVU is an accurate and comparable diagnostic tool for PCS. An observational prospective study including 67 patients was carried out. A TVU was performed on patients, measuring pelvic venous vessels parameters. Subsequentially, a VG was performed, and results were compared for the test calibration of TVU. Out of the 67 patients included, only 51 completed the study and were distributed in two groups according to VG results: 39 patients belonging to the PCS group and 12 to the normal group. PCS patients had a larger venous plexus diameter (15.1 mm vs. 12 mm; p = 0.009) and higher rates of crossing veins in the myometrium (74.35% vs. 33.3%; p = 0.009), reverse or altered flow during Valsalva (58.9% vs. 25%; p = 0.04), and largest pelvic vein ≥ 8 mm (92.3% vs. 25%). The sensitivity and specificity of TVU were 92.3% (95% CI: 78.03-97.99%) and 75% (95% CI: 42.84-93.31%), respectively. In conclusion, transvaginal ultrasonography, with the described methodology, appears to be a promising tool for the diagnosis of PCS, with acceptable sensitivity and specificity.


Older people and their care partners' experiences of living with mental health needs: a focus on collaboration and cooperation.
To explore how older people living at home with mental health needs and their care partners experienced the practices of collaboration within and between services. Many healthcare strategies for community mental health services for older people espouse a person-centred approach or principles that are similar in focus. This study reports on the first stage of a three-year action research project that focused on improving mental health services for older people and their care partners living at home. Data were collected through individual interviews. Twenty people were interviewed. Data were analysed continuously and in parallel with data collection for the identification of themes. We focus on two particular themes, 'acknowledgement, recognition and respect' and 'the prestige hierarchy of mental illness in older people'. We highlight how older people and their care partners experience discontinuities in their everyday interactions with nurses and care workers and that this impacts on their experience of person-centred care. Older people with mental health needs and their care partners need high levels of energy to express their needs and have them met in a way that reflects principles of partnership working. Nurses and care workers need to consider how 'tasks' can be used as a vehicle for creating emotional connections with service users. Service managers and leaders need to consider the implications of discontinuities in care on service user, care partner, nurses and care workers experiences.


Anti-osteoarthritic activity of Bungarus fasciatus venom fraction BF-F47 involving molecular markers in the rats.
A heat stable protein BF-F47 was purified from the crude venom of Bungarus fasciatus by CM cellulose ion exchange chromatography and HPLC. Osteoarthritis (OA) was developed in male albino Wistar rats by collagenase injection. BF-F47 treatment significantly restored urinary hydroxyproline and glucosamine in OA rats. Serum acid phosphatase, alkaline phosphatase, creatinine and serum molecular markers TNF-α, IL-1β, IL-17, cytokine induced neutrophil chemoattractant-1, matrix metalloproteinase-1, cathepsin-K, osteocalcin and PGE2 were also significantly altered. BF-F47 showed partial restoration of osteoarthritis joints. Thus, BF-F47 induced anti-osteoarthritic activity in Wistar rats acted through molecular markers of arthritis and inflammation.


Function and upright time following limb salvage, amputation, and rotationplasty for pediatric sarcoma of bone.
We wished to determine the relative physical and psychosocial merits of limb-sparing reconstruction, above-knee amputation, and rotationplasty in survivors of childhood and adolescent lower extremity bone sarcoma. In comparing minimum 5-year disease-free survivors, we found that outcome was somewhat dependent on the measuring tool administered. A superior score of statistical significance on the system of evaluation of the Musculoskeletal Tumour Society and a trend toward higher Toronto Extremity Salvage Scores were found among patients with a limb-sparing reconstruction compared with those with an above-knee amputation. Short-Form 36 results and the amount of time spent in the upright position (uptime), as assessed with a remote activity monitor, were similar between these groups. Uptime was highest in patients who had undergone rotationplasty, although statistical assessment of this group was not feasible. Psychosocial outcome was similar between all groups. This information may be useful in discussing reconstruction with patients and their families.


Evaluation of anterior third of superior sagittal sinus in normal population: Identifying the subgroup with dominant drainage.
The ligation and transection of anterior third of superior sagittal sinus (AT-SSS) is an important step to approach anterior skull base lesions. Some clinical studies have shown frontal lobe venous infarct following such surgical procedures questioning the safety of its ligation. We have studied the variations in venous drainage patterns to AT-SSS in the normal population using postcontrast magnetic resonance venogram (MRV). A novel scoring system to recognize the subgroup with dominant venous drainage from frontal lobes has been described. In this study, 60 three-dimensional contrast-enhanced (CE) MRVs were obtained from those cases being evaluated for a headache not harboring any intracranial mass lesion. The AT-SSS with all its draining veins was studied in detail. Morphology of individual veins such as length, caliber, tributaries, and angulation with AT-SSS was studied, and a numerical value of 0 or 1 was assigned for each of the above parameters. Summing up these scores derived from the individual cortical veins quantified the drainage of AT-SSS. There are 3-4 veins on either side draining to AT-SSS. Barely, 3% of the veins had > 3 tributaries. Only 6.6% of veins had a caliber >3 mm, and 16.5% drained at acute angles to AT-SSS. About 26% of the veins did cross at least half of the lateral frontal lobe. We found in 26 individuals the AT-SSS score was 0-2, in 22 it was 3-5 and, in only in 12 (20%) the score was 6 or more (dominant drainage). There are anatomical variations in venous drainage of frontal lobes into AT-SSS. Those with dominant drainage are likely to develop venous congestion and complications if sacrificed. It is possible to identify these individuals on the basis of venous drainage pattern as shown in CE-MRV.


Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating.
Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression, paracoccidioidomycosis is an important disease for dermatologists, who must be up-to-date about it. This article focuses on recent epidemiological data and discusses the new insights coming from molecular studies, as well as those related to clinical, diagnostic and therapeutic aspects. In the latter section, we give particular attention to the guideline on paracoccidioidomycosis organized by specialists in this subject.


Monoclonal antibody against human sperm acrosome inhibits sperm penetration of zona-free hamster eggs.
Human spermatozoa were exposed to a monoclonal antibody (C11H), which recognizes sperm acrosin. The antibody was presented to the sperm during capacitation and/or insemination, and its effect on penetration was tested using zona-free hamster eggs. An inhibitory effect on penetration was observed when the antibody was present during insemination but not when it was included only in the capacitation medium. As judged by immunofluorescence microscopy, most of the sperm bound to the egg surface were devoid of acrosomal staining. Some of the bound sperm were stained at their equatorial segments. Sperm that had penetrated the ooplasm did not exhibit immunofluorescence.


Theory-Practice Gap: The Knowledge and Perception of Nigerian Nurses.
The theory-practice gap can be described as a lack of ability to relate the knowledge acquired in academics and research work with practice. This study aims to assess the knowledge and the perception of Nigerian nurses on the theory-practice gap in Nursing. This cross-sectional correlational study was carried out with a sample of 196 nurses who were working in the Federal Medical Centre Keffi and Aminu Kano Teaching hospital in Kano, all from the northern part of Nigeria, from April to June 2019. The participants were selected using a convenient sampling technique, where a self-administered questionnaire was utilized to collect the data and analysis was undertaken using SPSS. The results of this study showed that 83.80% of respondents had good knowledge and 89.10% of the respondents had good perceptions. The levels of knowledge were significantly different in correlation with the educational level of respondents (χ2 = 13.88, df = 6, p = 0.022), which was determined using a Fischer exact test. Also, the level of perception was significantly different when considering the nature of work participants undertook (X2 = 7.65, df = 2, p = 0.022). Given the participants' awareness and perceptions in this study, it is clear that they are well informed of the theory-practice gap. This is a call for all professionals at an individual and organizational level to work, as it will translate into gap minimization, thereby increasing the quality of health care delivery as nurses constitute the largest part of the health care team in Nigeria.


A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation.
Transferring collagen-pulsed, bone marrow-derived dendritic cells (DCs) into congenic DBA/1 recipient mice produced arthritis in joints adjacent to the site of DC transfer and could be inhibited by treatment with TNF antagonists. Disease was Ag specific, as transfer of control, unpulsed DCs, or DCs pulsed with OVA did not produce arthritis. In contrast to other experimental arthritis models, DC-induced arthritis localized to the site of injection and did not spontaneously generalize to uninvolved joints, despite the demonstration of circulating collagen-reactive T cells. Similarly, transfer of T cells primed by collagen/DCs was not sufficient to produce arthritis in recipient mice. In collagen/DC-primed mice however, disease could be induced in uninvolved joints by local administration of noncollagen-pulsed DCs and this could be reduced through TNF inhibition. Similarly, injection of collagen/DC-primed mice with low-dose TNF also resulted in local induction of arthritis, as did administration of TNF to mice receiving T cells from collagen/DC but not OVA/DC-primed mice. Thus, we have demonstrated for the first time that administration of collagen-pulsed mature DCs is sufficient for the induction of arthritis. Furthermore, this disease process is mediated through both adaptive and innate effects of DCs; first, priming of autoreactive T cells and, second, induction of local inflammation via mediators such as TNF.


Spatial demographic trends and patterns in the Warsaw urban region.
The relationship between the age and sex structure of the Warsaw urban region of Poland and the population dynamics of this area is analyzed. "The process of spatial population development in the Warsaw urban region is of a cyclical nature. Starting from 1948-1950, the changes in the proportions of the population increase between the core and the remaining parts of the region oscillated over time. These trends can be interpreted with reference to the basic components of population change--natural increase and net migration, as well as policy-related factors."


Chlamydia trachomatis infection mimicking testicular malignancy in a young man.
A young man with a low risk history for sexually transmitted diseases presented with an apparently longstanding, previously asymptomatic scrotal mass, highly suggestive of testicular malignancy on palpation. Ultrasound sited the lesion in the epididymis. Although there was no evidence of urethritis, chlamydia polymerase chain reaction testing was positive. Tumour markers were negative. Complete clinical and radiological response was achieved after a long course of doxycycline treatment, without surgical exploration of the scrotum, confirming the diagnosis of chlamydial epididymitis.


Papillary collecting tubule responsiveness to vasoactive hormones in spontaneously hypertensive rats.
Renal papillary collecting tubule (RPCT) hormone responsiveness was compared between cultured RPCT cells from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Unstimulated cells from 4-week-old SHR produced less prostaglandin E2 (PGE2) and cyclic (c)AMP than comparable cells from WKY, while cells from both stains synthesized similar amounts of PGE2 after stimulation with arachidonate, A23187 or bradykinin and similar amounts of cAMP after stimulation with vasopressin or PGE2. There was no difference in basal or stimulated levels of cyclic (c)GMP between the strains. In RPCT cells from 16-week-old rats, basal levels of cAMP, cGMP and PGE2 were significantly lower than those from 4-week-old rats, but they did not differ between the strains. These results suggest that RPCT cells of SHR and WKY at the post-weaning period may differ in the metabolism of PGE2 and cAMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.


Orthodontic and orthognathic management of a complex mandibular asymmetry.
The application of a combined surgical-orthodontic procedure for the treatment of major facial deformities (eg, asymmetries) and associated malocclusions has become an increasingly prevalent treatment modality over the past few decades. Development of sound conjoint treatment principles made possible the correction of skeletal and dental dysplasias that were unyielding to either surgical or orthodontic treatment alone. The presence and severity of dentofacial asymmetries has been the subject of many commentaries and investigations. Treatment of facial asymmetry has always been a challenge with respect to the cause and the rationale behind the corrective procedures adopted. This case report describes a 23-year-old male patient whose chief complaint was attributed solely to the clinically discernible facial asymmetry. A combined orthodontic and surgical approach was done to correct both the dental and skeletal asymmetry. The reasons for selecting this treatment protocol and the 5-year postretention stability of the final results obtained are highlighted in this report.


Osteomyelitis at two noncontiguous sites caused by Mycobacterium marinum in an immunocompetent host: case report and literature review.
Nontuberculous mycobacteria are rare causes of skin, soft tissue, and musculoskeletal infections. Mycobacterium marinum remains one of the most commonly encountered mycobacterial species in humans, causing superficial cutaneous as well as deep infections. We are reporting a case of M. marinum osteomyelitis involving two primary noncontiguous sites in an immunocompetent host, which was successfully treated with surgical drainage and antibiotic therapy.


Molecular mechanism of NFAT family proteins for differential regulation of the IL-2 and TNF-alpha promoters.
Nuclear factor of activated T cells (NFAT) is a family of transcription factors that regulates activation-induced transcription of many immunologically important genes. Although all NFAT family proteins contain a highly conserved DNA-binding domain and also bind cooperatively with AP-1 proteins to the interleukin-2 (IL-2) promoter NFAT site, each member shows characteristic site preferences to other promoters. Previously, we have shown that NFATc.beta, an isoform of NFATc, is different from NFATp in both DNA binding and transactivation of the TNF-alpha promoter. To further characterize target gene specificity of NFATc and NFATp, we generated deletion mutants as well as mutants swapping the C-terminal region of their DNA binding domains, and analyzed their DNA-binding specificity to different target sites. Our results show that the C-terminal one third of DNA binding domain confers different binding specificity of NFATc and NFATp to an NFAT site in the TNF-alpha promoters. Transient expression of the mutant NFAT proteins also demonstrates that transcriptional activation of the target promoters is consistent with the DNA binding specificity of the mutant NFATs. These results strongly suggest that a binding site preference and availability of different NFAT proteins may program the temporal expression of distinct cytokine genes. Importantly, the C-terminal region of the DNA binding domain plays an important role in determining the binding site preferences at least of NFATp and NFATc members.


Ultraviolet-Stimulated KHCO(3) Efflux from Rose Cells: Regulation of Cytoplasmic pH.
Suspension-cultured cells of Rosa damascena that have been irradiated with ultraviolet light (254 nanometers, 2.1 x 10(4) joules per square meter) rapidly lose K(+) and HCO(3) (-) ions to the medium. If the HCO(3) (-) is derived from respiratory CO(2) inside the cell, then loss of HCO(3) (-) should be accompanied by an acidification of the cytoplasm. Estimates of the pH of control and ultraviolet-irradiated cells by (31)P-nuclear magnetic resonance spectroscopy indicated that, following irradiation, the pH of both cytoplasm and vacuole dropped by 0.2 to 0.3 units. This change was not as great as was predicted from the observed HCO(3) (-) loss. Analysis of nitrogenous compounds in the cell suggested that reduction of nitrate and synthesis of gamma-aminobutyric acid absorbed some of the protons formed by the synthesis and dissociation of bicarbonate.


Oxidative stress induced by fluoroquinolones on treatment for complicated urinary tract infections in Indian patients.
The aim of the study is to examine the oxidative stress in patients on fluoroquinolones (ciprofloxacin, levofloxacin, gatifloxacin) therapy for complicated urinary tract infections and to correlate with plasma concentrations at different time intervals. Superoxide dismutase (SOD), glutathione, plasma antioxidant status and lipid peroxides were evaluated in 52 patients on different dosage regimens up to 5 days. There is significant and gradual elevation of lipid peroxide levels in patients on ciprofloxacin (3.6 ± 0.34 nmol/ml to 6.2 ± 0.94 nmol/ml) and levofloxacin (3.5 ± 0.84 nmol/ml to 5.1 ± 0.28 nmol/ml) dosage regimen but not with gatifloxacin (3.5 ± 0.84 nmol/ml to 3.74 ± 0.17 nmol.ml). There was substantial depletion in both SOD and glutathione levels particularly with ciprofloxacin. On the 5(th) day of treatment, plasma antioxidant status decreased by 77.6% %, 50.5%, 7.56% for ciprofloxacin, levofloxacin and gatifloxacin respectively. In conclusion ciprofloxacin and levofloxacin induce more reactive oxygen species that lead to cell damage than gatifloxacin irrespective of their concentrations in patient population.


EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression.
The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50-100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.


Inter-laboratory validation of a rapid assay for the detection and quantification of Legionella spp. in water samples.
To compare the standard culture method with a new, rapid test (ScanVIT-Legionella™) using fluorescently labelled gene probes for the detection and enumeration of Legionella spp. The new technique was validated through experiments conducted on both artificially and naturally contaminated water and through an inter-laboratory comparison. All samples were processed by the ScanVIT test according to the manufacturer's instructions and by a culture method (ISO 11731). ScanVIT detected significantly more positive samples, although concentrations were similar and a strong positive correlation between the two methods was observed (r = 0.888, P < 0.001). The new test was more accurate in identifying the co-presence of Legionella pneumophila and Leg. non-pneumophila. ScanVIT showed a slightly higher Legionella recovery from water samples artificially contaminated with Leg. pneumophila alone or together with Pseudomonas aeruginosa. Lastly, the inter-laboratory comparison revealed that the ScanVIT test exhibits a lower variability than the traditional culture test (mean coefficient of variation 8.7 vs 16.1%). The results confirmed that the ScanVIT largely overlaps the reference method and offers advantages in terms of sensitivity, quantitative reliability and reduced assay time. The proposed method may represent a useful validated alternative to traditional culture for the rapid detection and quantification of Legionella spp. in water.


Community-Based Health Insurance Enrollment and Child Health Service Utilization in Northwest Ethiopia: A Cross-Sectional Case Comparison Study.
Utilization of primary healthcare services in the rural communities of Ethiopia is very low. The Ethiopian government has introduced community-based health insurance (CBHI) to improve the health service utilization of the rural community. Thus, this study was conducted to examine the association between CBHI enrollment and child health service utilization in northwest Ethiopia. A cross-sectional case comparison study among CBHI enrolled and unenrolled households was conducted. A total of 226 sick children from 2008 surveyed households were included in the study. Bivariate-probit regression analysis was employed to account the endogenous nature of insurance enrollment and child health services utilization. The results showed that the overall sick child healthcare visit in the CBHI enrolled group was about 0.44 (44%) point more compared to those unenrolled households. CBHI enrolled households in the poorest wealth group have a higher probability of visiting healthcare facilities for their sick children (coefficient: 0.13, SD: 0.07, 95% CI: -0.01, 0.27), whereas CBHI enrolled households with older age household head have a lower probability of visiting healthcare facilities for their sick children (coefficient: -0.16, SD: 0.08, 95% CI: -0.32, 0.01). A promising positive effect on sick children's health services utilization among CBHI enrolled was noticed. Moreover, households in the poorest wealth status and older age head affect the use of sick children's healthcare services among those CBHI enrolled. Therefore, policy measures to expand benefit packages and supply-side interventions are essential to enhance the effects of CBHI on different health service utilization.


The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders.
Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells which has proven to be effective in the therapy of CD-20 positive lymphomas. Its B-cell cytotoxic action has also been exploited in many non-malignant autoimmune disorders in which it has been used with the aim of interfering with the production of pathologic antibodies. The present knowledge regarding the use of rituximab in antibody-associated disorders of hemostasis (i.e. idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, acquired hemophilia A, congenital hemophilia with inhibitors, acquired inhibitors against coagulation factors) is presented briefly in this review. The results suggest that rituximab can be useful in the treatment of disorders of hemostasis associated with inhibitor formation. Although collectively the number of patients treated is now quite substantial, most of the data are drawn from isolated case reports or descriptions of small, uncontrolled series. Large, prospective, randomized trials are, therefore, needed to confirm the positive, preliminary results.


Localization of Fungal Components in the Pea-Fusarium Interaction Detected Immunochemically with Anti-chitosan and Anti-fungal Cell Wall Antisera.
Antisera specific for purified cell walls of Fusarium solani f. sp. pisi and phaseoli and of shrimp shell chitosan were utilized as immunochemical probes to determine the location of fungal components in the pea-Fusarium interaction.Within 15 minutes after inoculation, fungal cell wall components appear to enter the plant cell and to accumulate inside the plant cell wall as fungal growth on the plant tissue is inhibited. The accumulation patterns of chitosan and all components containing hexosamine polymers resembled those of the fungal wall components.Chitosan is present on, and is released from, the outer surface of the fungal spore. Within 15 minutes after applying [(3)H]chitosan to the surface of the plant tissue, the label is readily detectable within the plant cytoplasm and conspicuously detectable within the plant nucleus. It is proposed that the potential for transport of chitosan between the spores of Fusarium solani and pea cells, in addition to its potential to inhibit fungal growth and elicit disease resistance responses, suggests chitosan has a major regulatory role in this host-parasite interaction.


Copper use and accumulation in catfish culture in the Mekong Delta, Vietnam.
Aquaculture of Pangasius hypophthalmus (striped catfish) in Vietnam reached 1.1 million tonnes in 2011 and catfish fillets are exported worldwide. The intensive cultures of catfish mainly in earth ponds have made it necessary to apply CuSO4 and other chemicals to control external parasites and other pathogens. However, accumulation of Cu in aquaculture ponds may pose a hazard to growth of fish or to the aquatic environment. The aim of this study was to determine accumulation of Cu in sediment, water and fish in a catfish pond with a history of repeated treatment with CuSO4 in the Mekong Delta, Vietnam. Copper concentrations in pond sediment were in the interval 21.3-45.7 mg kg(-1) dw and did not exceed the Vietnamese values for soil to be used for agricultural production (70 mg kg(-1) dw.). During three samplings the total mean concentration of Cu in pond water (4 μg L(-1)) did not exceed the LC50-value (70 μg L(-1)) for catfish and the mean dissolved concentration of Cu (0.986 μg L(-1)) did not seem to constitute a risk for the stability of the aquatic ecosystem. No significant variation in Cu concentrations between sampling sites in the pond and depth of sediment profile were determined. The accumulation of Cu in catfish was highest in the liver compared to the skin, gills and muscle tissue. With the current practice of removing pond sludge three to four times during a production cycle little if any Cu seems to accumulate in catfish ponds despite repeated anti-parasite treatments with CuSO4. Further studies are needed to assess the eco-toxicity and impact on agricultural production when pond sediment is discharged into aquatic recipients and used as soil fertilizer.


Data-mining the FlyAtlas online resource to identify core functional motifs across transporting epithelia.
Comparative analysis of tissue-specific transcriptomes is a powerful technique to uncover tissue functions. Our FlyAtlas.org provides authoritative gene expression levels for multiple tissues of Drosophila melanogaster (1). Although the main use of such resources is single gene lookup, there is the potential for powerful meta-analysis to address questions that could not easily be framed otherwise. Here, we illustrate the power of data-mining of FlyAtlas data by comparing epithelial transcriptomes to identify a core set of highly-expressed genes, across the four major epithelial tissues (salivary glands, Malpighian tubules, midgut and hindgut) of both adults and larvae. Parallel hypothesis-led and hypothesis-free approaches were adopted to identify core genes that underpin insect epithelial function. In the former, gene lists were created from transport processes identified in the literature, and their expression profiles mapped from the flyatlas.org online dataset. In the latter, gene enrichment lists were prepared for each epithelium, and genes (both transport related and unrelated) consistently enriched in transporting epithelia identified. A key set of transport genes, comprising V-ATPases, cation exchangers, aquaporins, potassium and chloride channels, and carbonic anhydrase, was found to be highly enriched across the epithelial tissues, compared with the whole fly. Additionally, a further set of genes that had not been predicted to have epithelial roles, were co-expressed with the core transporters, extending our view of what makes a transporting epithelium work. Further insights were obtained by studying the genes uniquely overexpressed in each epithelium; for example, the salivary gland expresses lipases, the midgut organic solute transporters, the tubules specialize for purine metabolism and the hindgut overexpresses still unknown genes. Taken together, these data provide a unique insight into epithelial function in this key model insect, and a framework for comparison with other species. They also provide a methodology for function-led datamining of FlyAtlas.org and other multi-tissue expression datasets.


Scalable Synthesis of Nano-Sized Bi for Separator Modifying in 5V-Class Lithium Metal Batteries and Potassium Ion Batteries Anodes.
With the advantages of high theoretical-specific capacity and lowest working potential, lithium metal anode is considered as the most promising anode for next-generation batteries. Here, a scalable dealloying method is developed to prepare nano-sized bismuth (Bi). It is found that the Bi-modification can not only enhance the wettability of the commercial polyethylene separator but also suppresses the lithium dendrite growth. With the nano-sized Bi modified separator, 5V-class lithium metal batteries with commercial carbonate-based electrolyte show a 91% capacity retention ratio after 800 cycles. First-principle calculations prove that lithium atoms tend to deposit smoothly on the Bi surface. Moreover, for potassium ion batteries, nano-sized Bi shows a stable cycling performance and high capacity. The results may be useful for the development of high-energy and high-safety batteries.


Antioxidant machinery differs between melanic and light nestlings of two polymorphic raptors.
Colour polymorphism results from the expression of multiallelic genes generating phenotypes with very distinctive colourations. Most colour polymorphisms are due to differences in the type or amount of melanins present in each morph, which also differ in several behavioural, morphometric and physiological attributes. Melanin-based colour morphs could also differ in the levels of glutathione (GSH), a key intracellular antioxidant, because of the role of this molecule in melanogenesis. As GSH inhibits the synthesis of eumelanin (i.e. the darkest melanin form), individuals of darker morphs are expected to have lower GSH levels than those of lighter morphs. We tested this prediction in nestlings of two polymorphic raptors, the booted eagle Hieraaetus pennatus and the Eleonora's falcon Falco eleonorae, both of which occur in two morphs differing in the extent of eumelanic plumage. As expected, melanic booted eagle nestlings had lower blood GSH levels than light morph eagle nestlings. In the Eleonora's falcon, however, melanic nestlings only had lower GSH levels after controlling for the levels of other antioxidants. We also found that melanic female eagle nestlings had higher levels of antioxidants other than GSH and were in better body condition than light female eagle nestlings. These findings suggest an adaptive response of melanic nestlings to compensate for reduced GSH levels. Nevertheless, these associations were not found in falcons, indicating species-specific particularities in antioxidant machinery. Our results are consistent with previous work revealing the importance of GSH on the expression of melanic characters that show continuous variation, and suggest that this pathway also applies to discrete colour morphs. We suggest that the need to maintain low GSH levels for eumelanogenesis in dark morph individuals may represent a physiological constraint that helps regulate the evolution and maintenance of polymorphisms.


Intracule functional models. IV. Basis set effects.
We have calculated position and dot intracules for a series of atomic and molecular systems, starting from an unrestricted Hartree-Fock wave function, expanded using the STO-3G, 6-31G, 6-311G, 6-311++G, 6-311++G(d,p), 6-311++G(3d,3p), and 6-311++G(3df,3pd) basis sets as well as the nonpolarized part of Dunning's cc-pV5Z basis. We find that the basis set effects on the intracules are small and that correlation energies from the dot intracule ansatz are remarkably insensitive to the basis set quality. Mean absolute errors in correlation energies across the G1 data set agree to within 2 mE(h) for all basis sets tested.


Intimate partner violence constrains timely utilisation of antenatal care services among Armenian women: Results from a nationally representative sample.
Well-timed utilisation of antenatal care (ANC) services during pregnancy emphatically impact pregnancy outcomes. Intimate Partner Violence (IPV) predominance during pregnancy is exceptionally noticeable in Armenia, yet we have restricted information on the association between IPV and ANC attendance. The aim of this study was to determine the association between IPV and utilisation of adequate ANC services among Armenian women. A nationally representative sample survey from 2015 to 2016 Armenia Demographic and Health Survey was considered for this study. A total of 6116 women were interviewed. To estimate the association between outcome and explanatory variable, Pearson's Chi-square test followed by bivariate logistic regression analysis were performed. About 58% of participants, more than 35 years old has encountered IPV. Women with advanced education (54.7%) attended ANC services between 0 and 3 months. It was found that only the richer women are two times more likely to visit ANC services above four times than other groups and its association with IPV claimed that richer women are more likely to face IPV. Moreover, women who are residing with alcoholic husbands/partners are two times more likely to suffer from partner abuse (P < 0.001). The impact of IPV on accessibility and timely utilisation of ANC services in Armenia cannot be overlooked as IPV is causing risk in healthy delivery and the country's overall productivity in a broader perception.


Hydrochloric acid corrosion induced bifunctional free-standing NiFe hydroxide nanosheets towards high-performance alkaline seawater splitting.
We report a facile route to fabricate free-standing NiFe hydroxides by corrosion engineering as high-performance bifunctional electrocatalysts for seawater splitting. Compared with H2SO4 and HNO3, HCl can promote the dissolution of Ni2+ from NiFe foam and the in situ formation of active NiFe hydroxides due to the strong interaction between Cl- and metal. In situ Raman spectroscopic characterization reveals that HCl corrosion induced NiFe hydroxides (HCl-c-NiFe) can generate oxygen evolution reaction (OER) active NiOOH species at a low potential of 1.4 V vs. reversible hydrogen electrode (RHE) and exhibits equally respectable activity for the hydrogen evolution reaction (HER). During a 1000 h test in an alkaline electrolyte or a 300 h test in an alkaline seawater electrolyte within a two-electrode system at 100 mA cm-2, the cell exhibits outstanding stability and high Cl- tolerance with a low working voltage of 1.62 V, outperforming benchmark Pt/IrO2 and most of the reported bifunctional catalysts.


Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.
Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an additional signaling role for APOA5 in high-fat diet (HFD)-induced obesity. Wild-type (WT) and Apoa5(-/-) mice fed a chow diet showed no difference in body weight or 24-h food intake (Apoa5(-/-), 4.5±0.6 g; WT, 4.2±0.5 g), while Apoa5(-/-) mice fed an HFD ate more in 24 h (Apoa5(-/-), 2.8±0.4 g; WT, 2.5±0.3 g, P<0.05) and became more obese than WT mice. Also, intravenous injection of APOA5-loaded VLDL-like particles lowered food intake (VLDL control, 0.26±0.04 g; VLDL+APOA5, 0.11±0.07 g, P<0.01). In addition, the HFD-induced hyperphagia of Apoa5(-/-) mice was prevented by adenovirus-mediated hepatic overexpression of APOA5. Finally, intracerebroventricular injection of APOA5 reduced food intake compared to injection of the same mouse with artificial cerebral spinal fluid (0.40±0.11 g; APOA5, 0.23±0.08 g, P<0.01). These data indicate that the increased HFD-induced obesity of Apoa5(-/-) mice as compared to WT mice is at least partly explained by hyperphagia and that APOA5 plays a role in the central regulation of food intake.


Is suicidal ideation associated with puberty?
Chronological age, rather than puberty, was associated with suicidal ideation in both sexes in a sample of 1,060 children and adolescents aged nine to fourteen years who were referred to a child psychiatry service in Perth, Western Australia.


Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions.
Contrast nephropathy (CIN) increases adverse clinical outcomes. We examine risks and clinical predictors of CIN in patients undergoing percutaneous coronary intervention (PCI) and effectiveness of prophylactic therapy. A cohort of 8,798 patients who underwent PCI from May 2000 to April 2008 was enrolled. We divided patients into 3 groups. A: STEMI patient undergoing primary PCI; B: UA/NSTEMI patients undergoing early PCI; C: Patients without MI undergoing elective PCI. Pre-PCI saline hydration was given to group B and C if baseline glomerular filtration rate (GFR) <60 ml/min/1.73 m². Mean age was 57.4 years; 35.9% was diabetics. Incidence of CIN were 12.0%, 9.2%, and 4.5%, in group A, B and C (P = <0.0005). CIN correlated with higher mortality (15.5% vs. 1.3%, P < 0.0005) at 1 month. The important predictors of CIN were age >70, female gender, anemia, low systolic BP < 100 mmHg, high creatinine kinase level, abnormal LVEF, baseline renal impairment, MI and insulin dependent diabetes. Incidence of CIN in patients with GFR >60 were 8.2%, 9.2%, and 4.3% in group A, B, and C respectively (p < 0.0005). Incidence of CIN in patients with GFR = 30-60 were 19.1%, 4.5%, and 2.4% (p < 0.0005) and in patients with GFR < 30 were 34.4%, 40.0%, and 25.9% (p = 0.510). Pre-hydration prophylaxis was effective in preventing CIN in mild renal impaired patients (GFR 30-60) but are less so in more severely renal impaired patients (GFR < 30). STEMI patients undergoing primary PCI regardless of baseline GFR were at high risk. Accelerated prophylactic regime can be considered in this cohort.


[Determination of inorganic anions and gluconate by two-dimensional ion chromatography].
A new two-dimensional ion chromatography method was developed to parallelly analyze two different types of samples with the application of valve switching technology-suppressed conductivity and pulsed amperometric analysis system, for concurrent determination of chloride, nitrite, sulfate, nitrate four inorganic anions and gluconate. The first dimensional chromatography was using Ionpac AG18+Ionpac AS18 anion analysis columns with a suppressed conductivity detector for the separation and detection of Cl-, NO2-, SO4(2-) and NO3-. Respectively, the elution was 5 and 20 mmol/L NaOH at an isocratic flow rate of 1.0 mL/min and sample injection volume of 25 μL. The second dimensional chromatography was utilizing two guard columns, CarboPac PA1 and CarboPac PA20, with 90 mmol/L NaOH solution for the isocratic eluent of 0.8 mL/min. Gluconate was enriched by an AG15 column and switched into the pulsed amperometric detector. The results showed that: each inorganic anion in 0. 1-5.0 mg/L and gluconate in 0.085 6-4.282 5 mg/L had a good linear relationship (R2 ≥ 0.994 5). The RSDs of the peak areas were between 1.05%-1.94%. The limits of detection were 0.61-2.17 μg/L for the anions and 24.24 μg/L for the gluconate. The recoveries were between 90.3% - 102.8%. The two detection modes parallelly have good separation efficiency, detection accuracy and the precision of the separation and are suitable for the analysis of complex samples.


Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment.
Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.


The validity of the temporal parameters of the daily rhythm of melatonin levels as an indicator of morningness.
The present study tested the assumption that the temporal parameters of melatonin synthesis indicate the individual circadian phase position better than the minimum of rectal temperature. Thirty-four men and 17 women (16-32 yr, 14 morning, 14 neither, 23 evening types) completed a constant routine (24-26 h bedrest, <30 lux, 18-20 degrees C, hourly isocaloric diet). Salivary melatonin level was determined hourly, rectal temperature and heart rate were continuously recorded throughout. The minima of rectal temperature and heart rate as well as the temporal parameters of melatonin synthesis occurred earlier in morning than in evening types and were significantly related to the subjective circadian phase as determined by the morningness-eveningness questionnaire. The level of significance and the resolving power was greater for the melatonin parameters and for the minimum of heart rate than for the minimum of rectal temperature. The temporal differences between the opposite diurnal types were larger and the correlation coefficients with morningness were higher in men than in women. The temporal parameters of melatonin synthesis are valid indicators of the individual circadian phase. As morningness is closely related to the ability to cope with shiftwork, the determination of the melatonin profile might be a valuable element of the criteria when assigning a person to shiftwork.


Biological Anchorage and Canine Orthodontic Movement Rate with a New Technique for Micro-Osteoperforations.
The differential management of anchorage and the acceleration of tooth movement are some of the current greatest challenges for orthodontists. Diverse techniques and devices to reinforce anchorage and increase the rate of tooth movement have been proposed. Whether micro-osteoperforations (MOPs) can be used for both purposes is currently investigated. To propose and describe a new technique for biological anchorage, which involves six MOPs performed every four weeks, and to present its results in a clinical case of upper premolar extraction. Intervention. In a dental class II patient who met the selection criteria, three MOPs both on the buccal and palatine sides on the intervention side were performed on the extraction area following the protocol described. No MOPs were performed on the control side. The allocation of the intervention was randomised. The MOPs were performed three times at an interval of four weeks. A 0.019 × 0.025-inch stainless steel wire was activated with calibrated NiTi springs. The three-dimensional movement of the first molars and upper canines was evaluated. In addition, the comfort, periodontal status, and canine root resorption of the patient were evaluated. Clinical and radiographic results suggest that the MOPs had a positive effect in reducing the loss of biological anchorage of the posterior sector and in the rate of canine tooth movement, without damaging changes in the soft and hard tissues. The proposed protocol involving six MOPs every four weeks improved the behaviour of biological anchorage and increased distalization on the intervention side in this clinical case.


The contribution of a Ca(2+)-activated Cl(-) conductance to amino-acid-induced inward current responses of ciliated olfactory neurons of the rainbow trout.
To determine whether amino-acid-induced inward currents of ciliated olfactory receptor neurons (ORNs) in rainbow trout (Oncorhynchus mykiss) include a Ca(2+)-activated Cl(-) conductance, we first studied changes in reversal potential and the current/voltage relationships of the responses of ORNs to an amino acid mixture (l-alanine, l-arginine, l-glutamate and l-norvaline; all 10 mmol l(-)(1)) with different concentrations of Na(+) and Cl(-) in the perfusion and recording pipette solutions. We also examined the effects of six different Cl(-) channel blockers on the responses of ORNs using a conventional whole-cell voltage-clamp technique. The amino acid mixture and one blocker were applied focally to the cilia of ORNs using a double-barrelled micropipette and a pressure ejection system. The expected shifts in reversal potential, indicating the contribution of the Ca(2+)-activated Cl(-) conductance, occurred in both positive and negative directions depending on the external and internal Na(+) and Cl(-) concentrations. Niflumic acid, flufenamic acid, NPPB [5-nitro-2-(3-phenylpropylamino)-benzonate] and DCDPC (3', 5-dichlorodiphenylamine-2-carboxylate), at 0.5 mmol l(-)(1), reversibly blocked both the amino-acid-induced inward currents and the background activity in most ORNs. The effectiveness of these blocking agents varied from 77 to 91 % for ORNs perfused externally with standard Ringer's solution. SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate), at 5.0 mmol l(-)(1), irreversibly inhibited the physiological response (100 % inhibition), whereas DIDS (4,4'-diisothiocyanatostilbene-2, 2'-disulphonate), at 5.0 mmol l(-)(1), had the smallest effect (45 %) of the inhibitors tested. The dose of niflumic acid inducing 50 % inhibition (IC(50)), determined specifically for the current component of the Ca(2+)-activated Cl(-) channels, was 70 micromol l(-)(1). Our results suggest that these blockers are not specific for Ca(2+)-activated Cl(-) channels and that the density of these channels varies between individual ORNs. Our results also show that the Ca(2+)-activated Cl(-) conductance plays an important role in olfactory transduction and allows fishes to adapt to various ionic environments.


Exercise intervention protocol in children and young adults with cerebral palsy: the effects of strength, flexibility and gait training on physical performance, neuromuscular mechanisms and cardiometabolic risk factors (EXECP).
Individuals with cerebral palsy (CP) have problems in everyday tasks such as walking and climbing stairs due to a combination of neuromuscular impairments such as spasticity, muscle weakness, reduced joint flexibility and poor coordination. Development of evidence-based interventions are in pivotal role in the development of better targeted rehabilitation of CP, and thus in maintaining their motor function and wellbeing. Our aim is to investigate the efficacy of an individually tailored, multifaceted exercise intervention (EXECP) in children and young adults with CP. EXECP is composed of strength, flexibility and gait training. Furthermore, this study aims to verify the short-term retention of the adaptations three months after the end of the EXECP intervention. Twenty-four children and young adults with spastic CP will be recruited to participate in a 9-month research project with a 3-month training intervention, consisting of two to three 90-min sessions per week. In each session, strength training for the lower limbs and trunk muscles, flexibility training for the lower limbs and inclined treadmill gait training will be performed. We will evaluate muscle strength, joint flexibility, neuromuscular and cardiometabolic parameters. A nonconcurrent multiple baseline design with two pre-tests and two post-tests all interspaced by three months is used. In addition to the CP participants, 24 typically developing age and sex-matched participants will perform the two pre-tests (i.e. no intervention) to provide normative data. This study has a comprehensive approach examining longitudinal effects of wide variety of variables ranging from physical activity and gross motor function to sensorimotor functions of the brain and neuromuscular and cardiometabolic parameters, providing novel information about the adaptation mechanisms in cerebral palsy. To the best of our knowledge, this is the first intervention study providing supervised combined strength, flexibility and gait training for young individuals with CP. ISRCTN69044459, prospectively registered (21/04/2017).


Effectiveness of a multidisciplinary rehabilitation program in elderly patients with hip fractures.
Hip fracture is a significant health challenge to the elderly, with a high risk of complications, long hospital stay, and functional deterioration. The purpose of this study was to evaluate the effectiveness of a multidisciplinary rehabilitation program (MRP) in older patients with hip fractures. A before-and-after quasi-experimental design was used. Data were collected at a large teaching hospital in Taipei. The first 105 consecutive patients admitted received conventional care (control group). The next 50 consecutive patients received physical therapy, nurse-supervised exercise, and discharge planning (intervention group). Subjects were assessed upon admission, on the fourth postoperative day, and on the discharge day. The 155 patients recruited met the following criteria: 60 years of age or older, and hospitalized to receive either closed reduction and internal fixation, or hip arthroplasty. Compared with the control group, the intervention group had a shorter average hospital stay (9.9 vs 11.6 days, p = 0.01), earlier ambulation (5.7 vs 6.5 days postoperatively), and a lower rate of bowel incontinence (4.0% vs 23.8%) and pressure sores (14.0% vs 24.8%) during hospitalization. The intervention group experienced less decline in mobility (relative to pre-fracture status) than the control group. No significant difference was found in other outcome variables between the control and intervention groups. The findings of this study indicate that an MRP involving physical therapy, nurse-supervised exercise, and discharge planning positively affects health outcomes in older patients with hip fractures.


Trocar-site hernia after single-port cholecystectomy: not an exceptional complication?
When compared with standard multiport laparoscopy, the larger fascial incision in single-port surgery (SPS) may imply a potentially increased risk of surgical-site complications, such as herniation. The long-term risk of access-site complications in SPS is still unpredictable. Between July 2009 and May 2011, n=78 patients (n=54 females), with a median age of 42 years (range: 18-85 years), underwent single-port cholecystectomy. The median body mass index was 25.4 kg/m(2) (range: 17-39 kg/m(2)). All surgeries were performed by a single surgeon (K.K.) using a completely reusable single-port access device (X-Cone™; KARL STORZ GmbH, Tuttlingen, Germany), and fascial closure technique was comparable in all patients. The first 50 patients (n=32 females) attended a structured follow-up examination including a meticulous clinical examination and ultrasonography of the access site at a median follow-up time of 17 months (range: 9-23 months). We recorded postoperative complications in 5 of the 50 patients (10%) after single-port cholecystectomy. Four occurred in the early postoperative course and presented as mild wound complications. One of the 50 patients (2%) experienced a symptomatic trocar-site hernia (TSH) 4 months after surgery. No biliary complications (bile leakage, retained stones, etc.) were recorded. Although potentially biased by a relatively small number of patients, our study provides evidence that TSH after single-port cholecystectomy is (i) not less frequent when compared with standard laparoscopy, (ii) not as infrequent as suggested by the current literature, and (iii) not only associated with technical failure or patients' comorbidity.


First impressions count: a controlled investigation of social skill following closed head injury.
This study examined social skills in 14 closed head injured (CHI) patients who were assessed at four months post-injury and compared with 19 orthopaedic control (OC) patients. Social skills deficits were found to be more common in the CHI patients, of whom over half were classified as socially unskilled. CHI patients displayed poorer social skills in the earlier (but not later) part of an extended social interaction, indicating that they make a poor first impression. It is suggested that poor initial impression formation skills may be one reason why CHI patients fail to establish and maintain friendships. Implications of these findings for patient management are discussed. Close others of CHI patients reported higher levels of mood disturbance. Higher levels of close other hostility were associated with social skills deficits in CHI patients.


Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases.
A disseminated and progressive infection, penicilliosis marneffei is the third most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients in certain parts of Southeast Asia. Penicillium marneffei is endemic in Southeast Asia and the southern part of China. Cases have been reported from both Eastern and Western countries. This review discusses the history, epidemiology, mycology, clinical manifestations, diagnosis, and treatment of penicilliosis marneffei, on the basis of 155 cases of the infection. About 80% of the patients are immunocompromised. P. marneffei can infect various organs, particularly the lung, liver, and skin. The most common clinical features include fever, weight loss, and anemia. The organism has been isolated most commonly from skin, blood, and bone marrow. Immunologic identification of fungal isolates can be done with exoantigen tests and immunohistochemical methods. Treatment of disseminated penicilliosis marneffei in HIV-infected patients with parenteral amphotericin B and itraconazole is relatively effective and safe.


Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in Psoriasis.
Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (T(reg)) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. To prove that the Zenon immunofluorescent labeling technique is suitable for the demonstration of co-localization of T-cell markers and in particular to show the distribution of T(reg) in psoriatic skin. In biopsies derived from normal and psoriatic skin, CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+, CD8+ CD45RO+ and CD4+ CD25+ Foxp3+ cells in the dermis and in the epidermis were immunophenotyped, using a quantitative immunofluorescent labeling technique (Zenon), analyzed and compared using image analysis. The immunofluorescent labeling technique was shown to be an easy and reliable tool to demonstrate co-localization of T-cell markers. In psoriasis, all pathogenic T-cell subsets (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+ cells) were significantly increased in the dermis and in the epidermis, as compared to normal skin (all p < 0.05). Using this labeling technique we were able to reveal CD4+ CD25+ Foxp3+ T(reg) in psoriatic dermis, but not in the dermis of normal skin (p < 0.0001). The Zenon immunofluorescence technique in combination with image analysis is suitable for the demonstration of co-localization of T-cell markers in tissue. Increased numbers of pathogenic T cells (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+) were shown in the dermis and epidermis, whereas CD4+ CD25+ Foxp3+ T(reg) were identified in psoriatic skin with a predilection for the upper dermis.


Differentiation-associated switches in protein 4.1 expression. Synthesis of multiple structural isoforms during normal human erythropoiesis.
Erythroid differentiation is accompanied by dramatic alterations in morphology and membrane mechanical properties resulting, in large part, from reorganization of the membrane skeletal protein network. The 80-kD protein 4.1 is an important organizational component of this membrane skeleton. Recently, it has been recognized that multiple structural isoforms of 4.1 are encoded by a single gene via alternative pre-mRNA splicing, and that an upstream ATG can be spliced in and used for translation of high molecular weight 4.1. We are exploring the hypothesis that differentiation-associated switches in protein 4.1 structure play an important role in membrane reorganization. To study changes in 4.1 gene expression during normal human differentiation, we analyzed 4.1 protein and mRNA structure at various developmental stages. Using immunofluorescence microscopy, we observed high molecular weight 4.1 isoforms in preproerythroblasts producing punctate, predominantly cytoplasmic staining with a perinuclear area of intense fluorescence, while mature red cells expressed very little high molecular weight 4.1. Isoforms containing an alternatively expressed 102-nucleotide exon near the COOH terminus were abundant in both preproerythroblasts and mature cells but produced a punctate distribution of fluorescence over the entire preproerythroblast and intense membrane-associated fluorescence in the erythrocyte. Characterization of RNA by polymerase chain reaction and nuclease protection assays revealed a differentiation-associated switch in pre-mRNA splicing in the spectrin-actin binding domain. Since this domain plays a critical role in regulating membrane material properties, we speculate that this switch may be crucial to reorganization of the skeletal network during erythropoiesis. We conclude that 4.1 isoforms are differentially expressed and differentially localized during erythropoiesis, and that this isoform family is likely to have diverse functions during terminal differentiation.


Anti-Asthma Effect of an Active Components Group from Decoction of Pheretima Aspergillum and Its Chemical Composition Characterized by Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry.
The decoction of Pheretima aspergillum is used as a traditional medicine for treatment of asthma in China with a long clinical history. The aim of the study was to investigate the anti-asthma activities of an active components group obtained from the decoction of Pheretima aspergillum in histamine and ovalubumin induced asthma guinea pigs. The experimental asthma model was established with spray of histamine and ovalbumin (OVA) followed by intragastric administration of Pheretima aspergillum extract and fractions. The incubation period of asthma, serum IFN-γ, IL-4, and LTB4 levels were tested and determined. In addition, liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was used to identify the bioactive components in active fraction. The significant increase of asthma incubation period, serum IFN-γ level were observed in the asthma guinea pigs treated with the active components group. The serum IL-4 and LTB4 levels were obviously decreased compared to that of model controls. In addition, twenty oligopeptides were first identified or characterized in the active fraction from the decoction of Pheretima aspergillum. The results indicated that Pheretima aspergillum can inhibit infiltration and diffusion of inflammatory cells in asthma model guinea pigs, and regulate IFN-γ, IL-4, and LTB4 secretions. It is reasonable to assume that the anti-asthma activities of Pheretima aspergillum mainly resulted from these oligopeptides. Also, synergistic effects among their compounds may exist in the anti-asthma activity of Pheretima aspergillum.


An investigation into the association between nutritional status and quality of life in older people admitted to hospital.
Malnutrition is prevalent in acute hospitals and malnourished patients have an increased risk of morbidity and mortality. Studies of malnutrition and quality of life (QoL) are generally limited by both the nutritional and QoL assessment methods employed. The present study aimed to evaluate the relationship between malnutrition, as assessed using a range of nutritional assessment methods, and QoL, as measured by EuroQol-5D-3L and Short-Form (SF)-36 questionnaires. The study comprised a prospective cross-sectional study of malnutrition and QoL in 149 inpatients aged 65-99 years. Exclusion criteria were: terminal illness, active malignancy, lack of capacity to consent and severe communication difficulties. Spearman's rank correlation coefficient was used to test the association between QoL indices and nutritional markers. QoL scores for those scoring above and below thresholds for nutritional risk were compared. Regression models were created to identify nutritional indices contributing to the variability of QoL. There were significant associations between QoL scores and the Mini Nutritional Assessment (MNA)-SF. Clear differences were evident between malnourished and well-nourished patients (on the MNA-SF), those with low and normal arm muscle circumference and those with good and poor physical function. Regression analysis showed that nutritional scores and functional status made independent contributions to the prediction of QoL. The effect on food intake, mobility and psychological stress/acute disease also had a significant influence. Malnutrition risk is linked to a poorer QoL in older people on admission to hospital. Functional status and eating-related factors are major influencers on QoL in this group. These findings reinforce the role of nutrition as a priority with respect to achieving improvements in QoL.


Beneficial Plant-Associated Microorganisms From Semiarid Regions and Seasonally Dry Environments: A Review.
Semiarid regions are apparently low biodiversity environments; however, these environments may host a phylogenetically diverse microbial community associated with plants. Their microbial inhabitants are often recruited to withstand stressful settings and improve plant growth under harsh conditions. Thus, plant-associated microorganisms isolated from semiarid and seasonally dry environments will be detailed in the present review, focusing on plant growth promotion potential and the microbial ability to alleviate plant abiotic stress. Initially, we explored the role of microbes from dry environments around the world, and then, we focused on seasonally dry Brazilian biomes, the Caatinga and the Cerrado. Cultivable bacteria from semiarid and seasonally dry environments have demonstrated great plant growth promotion traits such as plant hormone production, mobilization of insoluble nutrients, and mechanisms related to plant abiotic stress alleviation. Several of these isolates were able to improve plant growth under stressful conditions commonly present in typical semiarid regions, such as high salinity and drought. Additionally, we highlight the potential of plants highly adapted to seasonal climates from the Caatinga and Cerrado biomes as a suitable pool of microbial inoculants to maintain plant growth under abiotic stress conditions. In general, we point out the potential for the exploitation of new microbial inoculants from plants growing in dry environments to ensure a sustainable increase in agricultural productivity in a future climate change scenario.


Validated fluorimetric HPLC analysis of acetaldehyde in hemoglobin fractions separated by cation exchange chromatography: three new peaks associated with acetaldehyde.
Stable hemoglobin-acetaldehyde adducts present in hemoglobin fractions separated by polyaspartic acid cation exchange chromatography were quantified by fluorimetric HPLC. The fluorescent species eluted from the HPLC was confirmed by mass spectrometry to be consistent with the expected product from reaction of acetaldehyde, 1,3-cyclohexanedione (CHD), and ammonium ion. Hemolysate (2.2 mM hemoglobin) was incubated in equivalent volumes of either phosphate-buffered saline or 5 mM acetaldehyde at 37 degrees C for 30 min and washed three times with H2O to remove free acetaldehyde and labile adducts before the injection of 14.7 mg hemoglobin onto the cation exchange column. Fluorimetric HPLC analysis of hemolysate samples either with or without in vitro reaction with acetaldehyde revealed that most acetaldehyde resides in the hemoglobin A0 fraction. The reaction with acetaldehyde in vitro resulted in a significant increase in fast-eluting minor hemoglobin species on cation exchange chromatography concomitant with increased acetaldehyde in the HbA1a+b, HbA1c, and HbA1-AcH fractions. We report three new cation exchange chromatographic peaks after reaction with acetaldehyde: HbA1-AcH-3, HbA1c-1, and HbA0-1. Each new peak was found to associate with a significant quantity of CHD-reactive acetaldehyde. These experiments provide additional evidence that stable adducts form between acetaldehyde and hemoglobin and that these adducts occur in multiple hemoglobin species separated by cation exchange chromatography. Further characterization and structural assignment of these species are warranted in view of their potential utility as markers for ethanol intake.


Role of nitric oxide in poly(I-C)-induced endothelial cell expression of leukocyte adhesion molecules.
Polyinosinic-polycytidylic acid [poly(I-C)] is a synthetic double-stranded RNA (dsRNA) that simulates a viral-infected state in cells. It has been shown that viral infection, as well as poly(I-C), stimulates leukocyte adhesion to endothelial cell (EC) monolayers and that this is mediated through the surface expression of the adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1. We have tested the involvement of nitric oxide (NO) in poly(I-C)-induced monocytic cell adhesion to human vascular EC. Using primary cultured EC for these studies, we confirmed the results from previous reports that these cells have higher basal levels of NO production than passaged cells. Poly(I-C)-induced monocytic cell adhesion to primary EC was concentration-dependently inhibited by 40-74% by the nitric oxide synthase (NOS) inhibitor NG-methyl-L-arginine (L-NMA), as well as three other NOS inhibitors, without significantly affecting interleukin-1 beta-induced adhesion. L-NMA inhibited poly(I-C)-induced surface expression of E-selectin and VCAM-1 by 25 and 45%, respectively, and mRNA levels of E-selectin and VCAM-1 by 62 and 74%, respectively. Primary EC transiently transfected with a plasmid containing an E-selectin promoter-driven luciferase reporter gene showed that L-NMA treatment reduced poly(I-C)-induced E-selectin promoter activity to basal levels. Electrophoretic mobility shift analysis indicated that poly(I-C)-induced nuclear factor-kappa B (NF-kappa B) binding to a radiolabeled oligonucleotide corresponding to the consensus NF-kappa B binding domain of the E-selectin promoter was decreased by L-NMA pretreatment. Hence, NO appears to augment E-selectin gene expression in response to poly(I-C) at the transcriptional level in vascular EC. Collectively, these data support the hypothesis that NO augments poly(I-C)-induced EC activation. These data suggest a novel role for NO as a response mediator in dsRNA-induced leukocyte adhesion to EC.


Carbon-Based Alloy-Type Composite Anode Materials toward Sodium-Ion Batteries.
In the scenario of renewable clean energy gradually replacing fossil energy, grid-scale energy storage systems are urgently necessary, where Na-ion batteries (SIBs) could supply crucial support, due to abundant Na raw materials and a similar electrochemical mechanism to Li-ion batteries. The limited energy density is one of the major challenges hindering the commercialization of SIBs. Alloy-type anodes with high theoretical capacities provide good opportunities to address this issue. However, these anodes suffer from the large volume expansion and inferior conductivity, which induce rapid capacity fading, poor rate properties, and safety issues. Carbon-based alloy-type composites (CAC) have been extensively applied in the effective construction of anodes that improved electrochemical performance, as the carbon component could alleviate the volume change and increase the conductivity. Here, state-of-the-art CAC anode materials applied in SIBs are summarized, including their design principle, characterization, and electrochemical performance. The corresponding alloying mechanism along with its advantages and disadvantages is briefly presented. The crucial roles and working mechanism of the carbon matrix in CAC anodes are discussed in depth. Lastly, the existing challenges and the perspectives are proposed. Such an understanding critically paves the way for tailoring and designing suitable alloy-type anodes toward practical applications.


Left ventricular function and right ventricular pacing for isolated congenital heart block.
BACKGROUND: Right ventricular pacing has been the treatment of choice in patients with congenital complete atrioventricular block (CAVB). However, the effect of chronic right ventricular pacing on left ventricular function in young patients is still controversial. AIM: The aim of the study was to assess the change in left ventricular systolic function in young patients (age ≤20 years) paced for isolated CAVB and to identify possible predictors of left ventricular systolic dysfunction. METHODS: We studied 55 young patients who underwent permanent right ventricular pacemaker implantation for CAVB in the absence of significant structural heart disease. We excluded patients affected by any condition known to affect left ventricular function. Echocardiographic data prior to and after pacemaker implantation were obtained. RESULTS: The mean age at the time of pacemaker implantation was 20 months, range 2.3-72 months. The mean duration of follow-up was 94.86 (range: 2-268 months). Chronic right ventricular pacing affected left ventricular shortening fraction (LVSF) significantly (pre = 37.8 ± 7.8 vs. post = 32.8 ± 5.5%, P = 0.0036). In 14 patients (25.4%), LVSF decreased by at least 7% (group A). The only parameter studied able to significantly discriminate the two groups was a better baseline LVSF in group A (baseline LVSF: 42.1 ± 5.2 vs. 32.2 ± 2.2%, P = 0.019; cut-off value >39%, P <0.0001; area under the curve = 0.887). CONCLUSION: Chronic right ventricular pacing in young patients without significant structural heart disease is responsible for a significant reduction in left ventricular systolic function, especially in patients with a good baseline LVSF. These patients need close follow-up not only for pacing parameters but also for left ventricular functional evaluation.


Photoprotective and antiinflammatory effects of topical glycolic acid.
Concerns about photosensitizing potential of alpha hydroxy acids have been expressed. A previous study, however, reported topical glycolic acid showing the opposite potential, that is, photoprotective. This study was designed to test the antiinflammatory and photoprotective capabilities of glycolic acid. The effects of short-wave ultraviolet light (UVB) on skin treated with glycolic acid were evaluated in two different studies at two different locations. In the first study the antiinflammatory potential of topical glycolic acid was tested on erythematous templates on the backs of human volunteers. Erythema was induced by exposure to three times the minimum erythema dose (MED) of UVB. Glycolic acid cream in an oil-in-water vehicle at 12% partially neutralized with ammonium hydroxide to a pH of 4.2 was applied to the template beginning 4 hours postirradiation four times a day. A second template on the same subject was used as a vehicle control. After 48 hours a marked reduction of erythema was noted when compared with the vehicle control site. In the second study, four test sites were exposed to UVB light in the following manner. Site 1 was a nontreated control site and was used to establish the MED for the subjects being tested; site 2 was also exposed to a MED series but was treated 24 hours postirradiation for 7 days with two glycolic acid-based products (cleanser and oil-free moisture lotion, both containing 8.0% glycolic acid at a pH of 3.25); site 3 was treated first with the two glycolic acid-based formulas for 3 weeks prior to being exposed to UVB light; and site 4 was treated as outlined in site 3, with the inclusion that the site was chemically peeled for 6 minutes (with a 50% glycolic solution at a pH of 2.75) 15 minutes prior to UVB exposure. When UVB-burned skin was treated with glycolic acid daily for 7 days (site 2), a 16% reduction in irritation was observed compared to nontreated skin (site 1), implying that skin healed sooner when treated with glycolic acid. When a comparison of nontreated skin was made to skin treated with glycolic acid for 3 weeks prior to UVB exposure (site 1 vs site 3), a sun protection factor (SPF) of 2.4 was achieved. When a comparison of skin treated for 3 weeks was made to skin treated for 3 weeks and chemically peeled (site 3 vs site 4) the data implied that the chemical peel reduced the SPF value of skin treated with glycolic by approximately 50%, however, an SPF trend of 1.7 was still obtained when compared with untreated skin. CONCLUSIONS. The studies demonstrated that topical glycolic acid provides a photoprotective effect to pretreated skin yielding an SPF of approximately 2.4. In addition, when glycolic acid is applied to irradiated skin, it accelerates resolution of erythema. The data obtained from both studies support the hypothesis that glycolic acids acts as an antioxidant.


Oral status and prosthetic factors related to residual ridge resorption in elderly subjects.
Our earlier studies on edentulous elderly subjects have shown associations of severe resorption in the mandibular residual ridge with female gender and systemic diseases. The aim of this study was to examine whether other factors also were related to residual ridge resorption (RRR). Among 177 edentulous elderly subjects effects on RRR were investigated with regard to history of edentulousness and denture-wearing, the condition of the dentures and soft tissues, dental status of the opposing jaw, and oral hygiene habits. No significant association was found between degree of resorption and duration of edentulousness in either the mandible or the maxilla. RRR was related to denture quality (P < 0.05); however, severe resorption was not. In the maxilla previous use of removable partial dentures was a factor contributing to the resorption (odds ratio (OR), 2.4); flabby ridge was related to the severity of the resorption (OR, 2.4). This study showed local factors related to RRR more often in the maxilla than in the mandible, thus suggesting that severe resorption in the mandible is influenced more by systemic factors than by those investigated in this study.


Childhood Health Outcomes in Term, Large-for-Gestational-Age Babies With Different Postnatal Growth Patterns.
Large-for-gestational-age (LGA) babies have a higher risk of metabolic disease later in life, and their postnatal growth in early childhood may be associated with long-term adverse outcomes. This study aimed to determine childhood health outcomes of term LGA babies with different growth patterns. Data were obtained from the US Collaborative Perinatal Project for the years between 1959 and 1976. The growth trajectories of 3,316 term LGA babies were identified and odds ratios of obesity, growth restriction, low intelligence quotient (IQ), and high blood pressure (HBP) were calculated by logistic regression. Compared with term appropriate-for-gestational-age infants, term LGA babies without catch-down growth had increased risks of obesity (adjusted odds ratio (aOR) = 6.37, 95% confidence interval (CI): 5.24, 7.73) and HBP (aOR = 1.67, 95% CI: 1.37, 2.03). Those with high catch-down growth had higher risks of growth restriction (aOR = 2.21, 95% CI: 1.66, 2.95) and low IQ (aOR = 1.61, 95% CI: 1.04, 2.49). Nevertheless, infants with small catch-down growth had lower risks of obesity (aOR = 0.78, 95% CI: 0.63, 0.95), growth restriction (aOR = 0.28, 95% CI: 0.17, 0.46), low IQ (aOR = 0.66, 95% CI: 0.41, 1.06), and HBP (aOR = 0.89, 95% CI: 0.77, 1.04). According to our data, term LGA infants with small catch-down growth had no increased risks of adverse outcomes.


Clinical observations and medical outcome in 149 cases of arsenate ant killer ingestion.
One hundred forty-nine (149) consecutive cases of arsenate-containing ant killer reported to the Minnesota Regional Poison Center over 4 1/2 months were retrospectively reviewed with a follow-up (1 week to 3 months) completed in 132 (89%) of the population studied. One hundred and forty eight (99%) of the ingestions were accidental. The majority of cases involved children 3 years of age and younger. Only three patients accidentally ingesting the product were symptomatic (mild episodes of vomiting and diarrhea which cleared in all patients within 12 hours). No patient was referred to a medical center for treatment and no patient reached on follow-up reported any additional ill effects as a result of the exposure. In addition to the 149 patients in this series, we describe two representative patients who accidentally ingested similar amounts of sodium arsenate-containing ant killer, resulting in urine arsenic of 3500 micrograms/24 h and 5819 micrograms/24 h. They required no chelation treatment and had no evident sequelae during 4-6 months of medical follow-up. This experience supports poison center directed home management for the majority of single, acute, and accidental ingestions of small quantities (< 5 mL) of arsenate-containing ant killers as a safe alternative to medical center referral and adverse reactions to chelation.


Inhibition of proliferation and of IL-2 production and utilization in lymphocytes by S-oxalylglutathione.
Previously we have shown that S-oxalins (monothiolesters of oxalic acid) are ubiquitous mammalian metabolites whose concentrations decrease when lymphocytes are stimulated to proliferate. The present study was undertaken to further examine the role of S-oxalins in the proliferation process. When added to lymphocytes stimulated with concanavalin A, the S-oxalin, S-oxalylglutathione (GS-Ox), inhibited DNA synthesis by 50% when present at ca. 0.15 mM and virtually 100% at 0.5 mM. The inhibition was reversible. The presence of GS-Ox blocked IL-2 production, but addition of IL-2 did not permit DNA synthesis to proceed. GS-Ox also inhibited proliferation of an IL-2-dependent cell line, BT2. In primary lymphocytes GS-Ox reduced IL-2 receptor expression, but not in an IL-2-dependent blast cell line. Overall RNA synthesis and protein synthesis were not significantly altered by GS-Ox. Levels of the positive transcription factor, NF-kappaB, were decreased after incubation of lymphocytes with GS-Ox, but the amount of a negative transcription factor, NREA, was largely unchanged. The results not only provide further evidence that S-oxalins are small-molecule cell proliferation inhibitors, they also clarify to some extent the specific steps in the activation response modulated by S-oxalins.


Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and C/EBPalpha during oral cancer suppression.
Curcumin is a common food ingredient derived from the plant Curcuma longa and is a potent drug against tumorigenesis. Both insulin-like growth factor binding protein-5 (IGFBP-5) and CCAAT/enhancer-binding protein alpha (C/EBPalpha) are suppressors of head and neck carcinogenesis. We identified curcumin as an inducer of IGFBP-5 expression in multiple types of oral keratinocytes; furthermore, curcumin induces IGFBP-5 promoter activity in SAS oral cancer cells. Promoter deletion mapping identified a region (nt -71 to nt -59 relative to the transcription start site) as containing a C/EBPalpha-binding element that is indispensable for curcumin-mediated IGFBP-5 upregulation. Chromatin immunoprecipitation assays revealed that in vivo binding of C/EBPalpha to this region was remarkably increased in the presence of curcumin. Curcumin increased nuclear C/EBPalpha expression and IGFBP-5 expression through p38 activation and this was abrogated by SB203580 treatment. Furthermore, MKK6 expression activated p38 and C/EBPalpha, increasing IGFBP-5 promoter activity and expression. Finally, curcumin-induced IGFBP-5 expression is associated with the suppression of xenograft tumorigenesis in mice due to oral cancer cells. We conclude that curcumin activates p38, which, in turn, activates the C/EBPalpha transactivator by interacting with binding elements in the IGFBP-5 promoter. The consequential upregulation of C/EBPalpha and IGFBP-5 by curcumin is crucial to the suppression of oral carcinogenesis.


Pharmacokinetic, pharmacodynamic, and electrocardiographic effects of dapoxetine and moxifloxacin compared with placebo in healthy adult male subjects.
Selective serotonin reuptake inhibitors (SSRIs) may be associated with electrocardiographic effects. The electrocardiographic pharmacodynamics of dapoxetine, a short-acting SSRI being developed for the treatment of premature ejaculation, are compared with those of placebo and moxifloxacin (positive control) in 2 single-center, randomized, crossover studies in healthy men. In study 1, subjects receive 2 doses of dapoxetine 120 mg, given 3 hours apart; a single dose of moxifloxacin 400 mg; and 2 doses of placebo, given 3 hours apart. In study 2, subjects receive single doses of dapoxetine 60 mg, dapoxetine 120 mg, moxifloxacin 400 mg, and placebo. Moxifloxacin significantly increases QT and corrects QT intervals (QTc) compared with placebo in both studies (eg, Bazett-corrected QTc of 11.90 milliseconds [95% confidence interval, 2.68 to 21.11] and 5.06 [95% confidence interval, -2.26 to 12.38]). Dapoxetine 60, 120, and 240 mg do not prolong the QT/QTc interval and have no clinically significant electrocardiographic effects. Dapoxetine and moxifloxacin pharmacokinetics are similar to previous reports. Adverse events are generally mild in severity; nausea is the most common. The results demonstrate that dapoxetine does not have electrocardiographic effects at doses of 60, 120, and 240 mg.