[Serrated adenomas of the colon: Clinical, morphological, and molecular genetic characteristics].
to investigate the clinical, morphological, and molecular genetic characteristics of serrated adenomas of the colon. The study included 82 colon adenomas from 63 patients aged 29 to 81 years, who underwent colonoscopy with biopsy or polypectomy. The mean age of men was 63.3 years; that of women was 56.8 years. Comprehensive clinical, morphological, immunohistochemical, and molecular genetic examinations were made. The histological examination showed that sessile serrated adenomas (SSA) of the colon were most common (46.4%), while hyperplastic polyp (HP) and traditional serrated adenoma (TSA) were found less often and with the same frequency (26.8%). The most typical location of SSA was the right colon; that of TSA was the left one. HP was detected equally on both sides of the colon. The immunohistochemical examination of the subtypes revealed no significant differences in the expression of markers. An analytical panel of antibodies against Desmin, Podoplanin (D2-40), CK20, CD34, Ki-67, Muc2, CEA, and CDX2 was used when identifying dysplasia areas, suspecting malignancy with invasion into the muscular layer of the mucous membrane and when determining the possible presence of emboli in blood and lymph vessels. BRAF gene mutation was identified in half of SSA cases; genetic BRAF mutation was observed in 41.7% of HP cases; genetic KRAS mutation was seen in 16.6%. The patients with TSA showed KRAS and BRAF mutations in 58.4 and 8.3% of cases, respectively. Mutations of these genes were absent. The study revealed that the subtypes of serrated adenomas substantially differ by sex, age, localization, and molecular genetic characteristics.


Long-term efficacy of hydroxyapatite-coated cylindrical implants.
A two-site clinical study of hydroxyapatite-coated cylindrical titanium alloy implants was undertaken to evaluate their efficacy. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic examinations and annual comprehensive patient visits. Implant failure criteria included mobility, peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain on palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life table methodology. From the 316 implants restored in 154 patients, 11 implants in 8 patients failed before prosthetic attachment, for a surgical success rate of 96.4 percent. Four implants failed during an observation period extending up to 85 months after completion of prosthetic treatment. The Cutler-Ederer life table success rate after 6 years was 97.8 percent. No significant adverse events were reported during the observation period. Results of this investigation suggest that hydroxyapatite-coated cylindrical titanium alloy implants are an effective treatment modality.


Proteases in cyst fluid from human gross cyst breast disease.
Cyst fluid from women with gross cystic breast disease was found to contain protease activity when assayed against [14C]albumin. At least six different proteases were detected when the fluid was fractionated by a combination of S-300 Sephacel, hydroxylapatite, and DEAE-Sephacel chromatographic techniques. The distribution of the proteases appeared to be related to the ionic composition of the fluids. A major protease component, found in both high Na and high K fluids, was isolated. It showed chymotryptic cleavage characteristics against the beta-chain of insulin. It was partially inhibited by alpha 2-macroglobulin, N-tosyl-L-phenylalanine chloromethyl ketone, and benzamidine but not by leupeptin, pepstatin, N-tosyl-L-lysine chloromethyl ketone, or alpha 1-protease inhibitor. The protease has an apparent molecular weight of 110,000 with Mr 24,000 subunits. This protease may be identical or closely associated with Haagensen's GCDFP-24 progesterone binding protein which was isolated in a similar manner. An imbalance between protease and protease inhibitors in cyst fluid may account for gross cyst formation and may be involved in the tumorigenic process. The accumulation of poorly diffusible peptide fragments, as a result of protease activity, would increase the oncotic pressure leading to enlargement of the cyst cavity as water enters to reestablish osmotic equilibrium.


POEMS syndrome with venous sinus thrombosis and visual failure: a case report.
POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome is a multisystem disorder associated with plasma cell dyscrasia. Other clinical signs include clubbing of the fingers, edema, papilledema etc. Although papilledema and increased intracranial pressure are common features, their causes or pathophysiology have been uncertain. The authors report here a 16-year-old Thai patient with these features who also suffered from venous sinus thrombosis and visual failure which have never been reported before. The former is considered to be one of the possible causes of the intracranial hypertension and visual failure. MRI of the brain and optic nerve revealed enhancement and swelling of the optic nerve sheaths and optic discs. MRV findings were compatible with chronic veno-occlusive disease. Bone marrow aspiration and biopsy demonstrated an increase of aggregates of intermediate and mature plasma cells. The CSF pressure was markedly elevated. His clinical condition continued to deteriorate and he expired 3 years and 5 months from the onset of his illness. Although, overproduction of vascular endothelial growth factor has been reported and is being considered to be the possible cause of vascular hyperpermeability, the chronic venous sinus thrombosis may play an important role in the pathogenesis of intracranial hypertension and visual failure.


Night vision goggles, human factors aspects--a questionnaire survey of helicopter aircrew.
Night vision goggles have become an essential component of military aviation. They provide superior visual capability over unaided night vision, but there are several inherent limitations associated with human factors and systems limitations. This study used a questionnaire survey of Army helicopter aircrew to investigate the incidence of human factors problems which continued after NVG use, with particular reference to visual problems and neck discomfort. It also looked at hardware interaction problems, such as cockpit lighting, and other aspects of NVG use, such as training and aircrew concerns. The issues are described and analysed, and areas of concern, which may have bearings on operational effectiveness and/or safety, have been highlighted.


Deciphering the physician-older patient interaction.
The purpose of this article is to provide a commentary on non-verbal communication in the physician-older patient interaction. A literature review of physician-older patient communication yielded several published studies on this topic. Nonverbal behaviors were rarely examined in this body of literature even though the need to adopt a more "biopsychosocial" model of care was mentioned in several of the articles. The nonverbal communication literature was also reviewed to determine whether aging had been a variable of interest with regard to encoding (sending) and decoding communication (receiving) skills. To date there have been very few studies that have investigated the role of nonverbal communication in the physician-older patient interaction. Selected encoding and decoding characteristics for both physicians and patients are discussed with the context of the aging process. In lieu of direct evidence linking nonverbal behavior and physician-older patient communication, possible implications are offered for the following characteristics: expression of emotion, pain expression, gestures, gaze, touch, hearing, and vocal affect. Three relevant outcomes (satisfaction with care, quality of life, and health status) are also discussed within the nonverbal behavior-aging framework. The connection between nonverbal behavior and how physicians and older patients interact with one another has not been rigorously examined. Identifying and improving nonverbal communication will likely enhance the verbal exchange in the medical encounter and may improve the older patient's quality of care.


Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study.
Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration-time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs). Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00-1.14) for the AUC; 1.06 (0.98-1.16) for Cmax and 1.03 (0.92-1.16) for C12h. Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov).


Association between health literacy and hypertension management in a Chinese community: a retrospective cohort study.
Low health literacy is associated with poor clinical outcomes. The relationship between literacy and blood pressure (BP) has been inconsistent. We investigated the determinants of health literacy and the potential relationship between health literacy and hypertension management. We conducted a retrospective cohort trial of 360 hypertensive patients. Scale measurements, physical examination, and laboratory tests were performed based on a standard protocol. To determine factors associated with health literacy, multiple logistic regression analysis was performed and the discriminatory power of the scale score for hypertension control was assessed by the area under the receiver operating curve. After adjusting for potential confounders, our findings show that the level of education, home blood pressure measurement, regular medication, and systolic blood pressure are significantly associated with health literacy. Moreover, patients with high health literacy have better hypertension control, a lower risk of ischemic cardiovascular disease (ICVD), lower brachial ankle pulse wave velocity values, and better health-related quality of life. In addition, our study also demonstrates that we can identify the health literacy level of hypertensive patients using the Chinese Health Literacy Scale for Hypertension. At a cut-off value of 13.5, we predict that patients will achieve long-term hypertension control. Adequate health literacy is a contributing factor to better blood pressure (BP) control and better perceived quality of life in hypertensive patients. Low health literacy increases the 10-year risk of ICVD and incidence of artery stiffness in hypertensive patients. Improving health literacy should be considered an important part of the management of hypertension.


[Enhanced expression of EPHX2 gene in the kidney of the hypertensive ISIAH rats].
Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. EETs mediate vasodilation of rat preglomerular microvessels and activate ion channels. Ephx2 is coding for the soluble epoxide hydrolase (sEH) which catalyze the degradation of EETs. Renal cortex and renal medulla were tested for Ephx2 mRNA level in hypertensive ISIAH and normotensive WAG rats at rest and emotional stress conditions. The microarray analysis and real-time PCR were used to assess the transcriptional activity of Ephx2. Enhanced transcriptional activity of Ephx2 in both renal structures of ISIAH rats was found at rest and stress conditions. The emotional stress caused elevation of Ephx2 mRNA level in renal medulla of ISIAH rats and opposite response--a decrease in Ephx2 expression in the renal medulla and cortex of WAG rats.The results suggest Ephx2 participation in the control of the vascular tone changes in kidney promoting the hypertensive state in the ISIAH rats.


Serological status of Canadian cattle for brucellosis, anaplasmosis, and bluetongue in 2007-2008.
A national bovine serological survey was conducted to confirm that the prevalence of brucellosis, bluetongue, and anaplasmosis does not exceed 0.02% (95% confidence) in live cattle in Canada. Sampling consisted of a systematic random sample of 15 482 adult cattle slaughtered in federally inspected abattoirs, stratified by province. Samples were tested to detect antibodies for brucellosis, bluetongue, and anaplasmosis. All samples were negative for brucellosis. Three samples were seroreactors to bluetongue, 2 of which originated from the Okanagan Valley in British Columbia and 1 from Ontario, which after follow-up, was considered an atypical result. A total of 244 samples were seroreactors to Anaplasma and follow-up identified infection in Saskatchewan, Manitoba, and Quebec. In conclusion, the Canadian cattle population remains free of brucellosis and free of bluetongue outside the Okanagan Valley. Canada is no longer free of anaplasmosis and will be unable to claim freedom until eradication measures are completed.


Antioxidant and antiproliferative activities of heterofucans from the seaweed Sargassum filipendula.
Fucan is a term used to denominate a type of polysaccharide which contains substantial percentages of l-fucose and sulfate ester groups. We obtained five heterofucans from Sargassum filipendula by proteolytic digestion followed by sequential acetone precipitation. These heterofucans are composed mainly of fucose, glucose, glucuronic acid, galactose and sulfate. These fucans did not show anticoagulant activity in PT and aPTT tests. Their antioxidant activity was evaluated using the follow tests; total antioxidant capacity, scavenging hydroxyl and superoxide radicals, reducing power and ferrous ion [Fe(II)] chelating. All heterofucans displayed considerable activity, especially SF-1.0v which showed the most significant antioxidant potential with 90.7 ascorbic acid equivalents in a total antioxidant capacity test and similar activity when compared with vitamin C in a reducing power assay. The fucan antiproliferative activity was performed with HeLa, PC3 and HepG2 cells using MTT test. In all tested conditions the heterofucans exhibited a dose-dependent effect. The strongest inhibition was observed in HeLa cells, where SF-1.0 and SF-1.5 exhibited considerable activity with an IC50 value of 15.69 and 13.83 μM, respectively. These results clearly indicate the beneficial effect of S. filipendula polysaccharides as antiproliferative and antioxidant. Further purification steps and additional studies on structural features as well as in vivo experiments are needed to test the viability of their use as therapeutic agents.


Application of a Z-Shaped Umbilical Incision and a Saline-Cooled Radiofrequency Device to Single-Incision Laparoscopic Surgery for a Huge Liver Cyst: Report of a Case.
When compared with other diseases, few authors have reported on single-incision laparoscopic surgery (SILS) for liver cysts. We herein describe our experience with SILS for a huge liver cyst with the application of an umbilical Z-shaped incision using a gel port and a high-density monopolar saline-cooled radiofrequency device with a successful outcome. An 80-old-year woman was diagnosed with a huge liver cyst with abdominal pain. She underwent percutaneous drainage of the liver cyst and injection of both absolute ethanol and an antimicrobial agent into the liver cyst at the previous hospital. Because of re-expansion of the liver cyst and symptom recurrence, we performed SILS for the liver cyst. An umbilical Z-shaped incision was made for gel port placement. After aspiration of the cystic fluid and dissection of the thin cystic wall by laparoscopic coagulating shears, the thick cystic wall was divided using an endoscopic linear stapler to avoid bleeding and bile leakage. After wide fenestration, a high-density monopolar saline-cooled radiofrequency device was applied for the ablation of the remnant membrane of the cystic wall. All maneuvers could be performed only through the gel port. The patient was discharged 4 days after surgery and was satisfied with the cosmetic results. This case shows that the application of an umbilical Z-shaped incision using a gel port and a high-density monopolar saline-cooled radiofrequency device is useful for the accomplishment of SILS for a huge liver cyst.


Stability of the multi-finger prehension synergy studied with transcranial magnetic stimulation.
We used transcranial magnetic stimulation (TMS) to explore the stability of the three constituents of the multi-finger prehension synergy. Patterns of co-variation between mechanical variables produced by individual digits were used as indices of the prehension synergy. We tested hypotheses that TMS would violate these patterns and that different components of the prehension synergy would take different times to restore. Subjects held an instrumented handle with one of the three external load and one of the seven external torques statically in the air. Single-pulse TMS was applied unexpectedly over the hand projection in the contralateral hemisphere. The normal forces showed a quick TMS-induced increase that was proportional to the background force magnitude. This was also true for the tangential forces produced by the thumb, middle, and ring fingers but not by the index and little fingers. The total moment of force changed proportionally to its background value with predominance of supination responses. During the quick force response to TMS, patterns of digit force co-variation stabilizing the total tangential force and total moment of force were violated. Two stages of synergy restoration were identified taking approximately 0.3 and 1.5 s. These times differed among the three synergy components. The results support the idea of a prehension synergy as a neural mechanism that facilitates conjoint changes in forces produced by individual digits with the purpose to stabilize the hand action on the hand-held object. The data also support applicability of the principle of superposition to the human hand action.


Photocytotoxicity of a new Rh2(II,II) complex: increase in cytotoxicity upon irradiation similar to that of PDT agent hematoporphyrin.
A new type of heteroleptic dirhodium complex cis-[Rh(2)(mu-O2CCH3)2-(bpy)(dppz)]2+ (3) was synthesized and its potential as a photodynamic therapy (PDT) agent was investigated. Although 27% hypochromicity of the absorption of 3 in the near-UV and visible regions is observed in the presence of duplex DNA, relative viscosity measurements reveal that the complex does not intercalate between the DNA bases. The DNA photocleavage with visible light by 3 proceeds via both oxygen dependent and independent mechanisms, and it is more efficient than that of related complexes. The increase in the cytotoxicity of 3 towards human skin cells is similar to that of hematoporphyrin, a key ingredient in a PDT drug currently in use. This feature makes this complex a useful candidate for further PDT studies.


Human peripheral blood xenografts in the SCID mouse: characterization of immunologic reconstitution.
Immune reconstitutions (hu-PBL-SCID mice) resulting from adoptive transfer of human peripheral blood mononuclear cells into 1800 C.B-17 scid-/scid-mice were characterized. Over 90% of reconstitutions were successful as evidenced by human immunoglobulin production. Variability was noted with donor, cell number, and cell type. Human cells (T lymphocytes, few B cells) could be recovered by 5 days after engraftment. High levels of soluble CD8 and interleukin-2 receptors were detected in sera of hu-PBL-SCID mice. Cells recovered from 17 mice proliferated in response to antigens to which the donor had been primed; responses to nonboosted antigen also increased in some animals. After reconstitution, lymphocytes were found in the spleen and lymph nodes without full restoration of normal architecture. The hu-PBL-SCID mouse shows promise as a model system for a variety of immunologic studies. The inherent variation in the system must be minimized for appropriate use of the model.


Structural analysis of SNARE motifs from sea perch, Lateolabrax japonicus by computerized approaches.
Three cDNA sequences encoding four SNARE (N-ethylmaleimide-sensitive fusion protein attachment protein receptors) motifs were cloned from sea perch, and the deduced peptide sequences were analyzed for structural prediction by using 14 different web servers and softwares. The "ionic layer" structure, the three dimensional extension and conformational characters of the SNARE 7S core complex by using bioinformatics approaches were compared respectively with those from mammalian X-ray crystallographic investigations. The result suggested that the formation and stabilization of fish SNARE core complex might be driven by hydrophobic association, hydrogen bond among R group of core amino acids and electrostatic attraction at molecular level. This revealed that the SNARE proteins interaction of the fish may share the same molecular mechanism with that of mammal, indicating the universality and solidity of SNARE core complex theory. This work is also an attempt to get the protein 3D structural information which appears to be similar to that obtained through X-ray crystallography, only by using computerized approaches.


Calibration of higher eigenmodes of cantilevers.
A method is presented for calibrating the higher eigenmodes (resonant modes) of atomic force microscopy cantilevers that can be performed prior to any tip-sample interaction. The method leverages recent efforts in accurately calibrating the first eigenmode by providing the higher-mode stiffness as a ratio to the first mode stiffness. A one-time calibration routine must be performed for every cantilever type to determine a power-law relationship between stiffness and frequency, which is then stored for future use on similar cantilevers. Then, future calibrations only require a measurement of the ratio of resonant frequencies and the stiffness of the first mode. This method is verified through stiffness measurements using three independent approaches: interferometric measurement, AC approach-curve calibration, and finite element analysis simulation. Power-law values for calibrating higher-mode stiffnesses are reported for several cantilever models. Once the higher-mode stiffnesses are known, the amplitude of each mode can also be calibrated from the thermal spectrum by application of the equipartition theorem.


Dual enzyme mimicry exhibited by ITO nanocubes and their application in spectrophotometric and electrochemical sensing.
The dual enzyme mimicry (peroxidase/catalase-like activities) exhibited by ITO nanocubes (ITO NCs) was investigated by spectrophotometric and electrochemical methods. The peroxidase mimic was successfully applied for the electrochemical detection of H2O2 and spectrophotometric biosensing of glucose. Further, the detection could be extended to the detection of glucose in real samples.


Tensor fasciae latae perforator flap: minimizing donor-site morbidity in the treatment of trochanteric pressure sores.
To report a new technique with less morbidity for coverage of trochanteric defects, an anatomical and clinical study was performed. Twenty-four fresh cadavers were dissected. The following parameters were measured: origin, location, number, and length of the perforating vessels. In addition, a clinical study was performed on 21 patients with trochanteric pressure sores. The anatomical study of 24 fresh cadavers revealed the constant presence of perforator pedicles anterior to the greater trochanter, which provides an adequate arc of rotation arc for flap harvest without sacrificing the underlying muscles. The mean length of the pedicles was 9.59 +/- 2.16 cm. This flap is nourished by perforator vessels arising from the ascending branch of the lateral circumflex femoral artery, which arises from the deep femoral artery and runs through the intermuscular septum, tensor fasciae latae, and rectus femoralis muscles. In this study, flaps were raised based on perforators located preoperatively using a unidirectional Doppler probe. Good results were obtained with primary closure of the donor site, with only two donor-site dehiscences. This flap is an alternative to myocutaneous flaps, as it preserves local musculature without functional sequelae in patients who walk. It also preserves the local musculature in the event of recurrence, as is usually seen in paralytic patients with pressure sores.


Neuromodulation for the treatment of refractory interstitial cystitis.
Interstitial cystitis (IC) is a symptom complex of urinary urgency, frequency and pelvic pain. Multimodality behavioral and phamacologic treatment is often effective in treating IC. Unfortunately, some patients with IC are refractory to standard treatments. Neuromodulation has been shown to be effective in treating voiding dysfunction. Small studies have demonstrated improvement in pelvic pain and IC symptoms during temporary sacral nerve stimulation. This current study demonstrates that patients refractory to traditional therapies for IC can respond well to sacral nerve stimulation and maintain improvement in symptoms after permanent implantation of a neurogenerator. The technique used to place the neurostimulator can impact on the degree of the response and the complication rate. Sacral neurostimulation continues to evolve and should be in the armamentarium available to treat voiding dysfunction.


Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans.
In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea.


Effectiveness of a proteoliposome-based vaccine against salmonid rickettsial septicaemia in Oncorhynchus mykiss.
Salmonid rickettsial septicaemia (SRS) is a contagious disease caused by Piscirickettsia salmonis, an intracellular bacterium. SRS causes an estimated economic loss of $700 million USD to the Chilean industry annually. Vaccination and antibiotic therapy are the primary prophylactic and control measures used against SRS. Unfortunately, commercially available SRS vaccines have not been shown to have a significant effect on reducing mortality. Most vaccines contain whole inactivated bacteria which results in decreased efficacy due to the limited ability of the vaccine to evoke a cellular mediated immune response that can eliminate the pathogen or infected cells. In addition, SRS vaccine efficacy has been evaluated primarily with Salmo salar (Atlantic salmon). Vaccine studies using Oncorhynchus mykiss (rainbow trout) are scarce, despite SRS being the leading cause of infectious death for this species. In this study, we evaluate an injectable vaccine based on P. salmonis proteoliposome; describing the vaccine security profile, capacity to induce specific anti-P. salmonis IgM and gene expression of immune markers related to T CD8 cell-mediated immunity. Efficacy was determined by experimental challenge with P. salmonis intraperitoneally. Our findings indicate that a P. salmonis proteoliposome-based vaccine is able to protect O. mykiss against challenge with a P. salmonis Chilean isolate and causes a specific antibody response. The transcriptional profile suggests that the vaccine is capable of inducing cellular immunity. This study provides new insights into O. mykiss protection and the immune response induced by a P. salmonis proteoliposome-based vaccine.


Restriction isotyping of human apolipoprotein A-IV: rapid typing of known isoforms and detection of a new isoform that deletes a conserved repeat.
Genetic polymorphisms of apolipoprotein A-IV (apoA-IV) have been detected by isoelectric focusing of serum proteins. Because genetic variation in apoA-IV has significant effects on lipid risk factors, we used restriction enzyme isoform genotyping (restriction isotyping) to determine apoA-IV isoform genotypes at the DNA level for a large population (n = 509). In contrast to isoelectric focusing methods, restriction isotyping relies on nucleotide differences, enabling unambiguous typing of known isoforms and detection of new alleles that mimic other isoforms with shared charge properties. To determine genotypes for the common A-IV-1 isoform (Gln at aa position 360) and A-IV-2 isoform (360His), we used a mismatched primer for polymerase chain reaction (PCR) to introduce a restriction site (PvuII) that distinguishes each isoform. Using a portion of the same PCR reaction, we used HinfI to distinguish isoforms with Thr at position 347 (347Thr) versus Ser (347Ser). In surveys for these common genotypes, we detected heterozygotes for an allele with an insertion of 12 bp. Nucleotide sequencing showed that this allele is identical to the A-IV-0 isoform that inserts a hydrophilic repeat (Glu Gln Gln Gln) in a conserved region near the carboxy terminus. In addition, we discovered a new allele with a 12 bp deletion that removes a repeat (Glu Gln Gln Gln) from the same region. Nucleotide sequencing showed that this allele removes an acidic charge relative to A-IV-1, so we have named this isoform A-IV-2*. This isoform has not been discovered at the protein level, perhaps due to shared charge properties with A-IV-2 isoforms.


Devosia marina sp. nov., isolated from deep seawater of the South China Sea, and reclassification of Devosia subaequoris as a later heterotypic synonym of Devosia soli.
A Gram-stain-negative, aerobic, rod-shaped and motile bacterial strain, designated L53-10-65T, was isolated from deep seawater of the South China Sea. Strain L53-10-65T was found to grow at 4-41 °C (optimum, 28 °C), at pH 5.0-9.0 (pH 7.0-8.0) and in 0-7 % (w/v) NaCl (2 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain L53-10-65T fell within the genus Devosia, with the highest similarity to Devosia indica IO390501T (98.4 %), followed by 'Devosia lucknowensis' L15T (97.7 %) and Devosia riboflavina IFO 13584T (96.8 %). The digital DNA-DNA hybridization (dDDH) values between strain L53-10-65T and the three relatives above were 43.7, 21.5 and 20.9 %, respectively; the average nucleotide identity (ANI) values were 91.3, 78.4 and 76.8 %, respectively. These values were below the 70 % dDDH and 95-96 % ANI thresholds for bacterial species delineation. The major cellular fatty acids of strain L53-10-65T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C18 : 1 ω7c 11-methyl and C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The respiratory quinone was identified as Q-10. The DNA G+C content of strain L53-10-65T was 61.3 mol%. Based on the results of phylogenetic analysis and distinctive phenotypic characteristics, strain L53-10-65T is concluded to represent a novel species of the genus Devosia, for which the name Devosia marina sp. nov. is proposed. The type strain of the species is L53-10-65T (=MCCC 1A05139T=KCTC 72888T). Moreover, we propose that Devosia subaequoris is a later heterotypic synonym of Devosia soli based on the present results.


Pathogenicity and virulence of Burkholderia pseudomallei.
The soil saprophyte, Burkholderia pseudomallei, is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to B. pseudomallei by either inhalation or inoculation can lead to severe disease. B. pseudomallei rapidly shifts from an environmental organism to an aggressive intracellular pathogen capable of rapidly spreading around the body. The expression of multiple virulence factors at every stage of intracellular infection allows for rapid progression of infection. Following invasion or phagocytosis, B. pseudomallei resists host-cell killing mechanisms in the phagosome, followed by escape using the type III secretion system. Several secreted virulence factors manipulate the host cell, while bacterial cells undergo a shift in energy metabolism allowing for overwhelming intracellular replication. Polymerisation of host cell actin into "actin tails" propels B. pseudomallei to the membranes of host cells where the type VI secretion system fuses host cells into multinucleated giant cells (MNGCs) to facilitate cell-to-cell dissemination. This review describes the various mechanisms used by B. pseudomallei to survive within cells.


The medline UK filter: development and validation of a geographic search filter to retrieve research about the UK from OVID medline.
A validated geographic search filter for the retrieval of research about the United Kingdom (UK) from bibliographic databases had not previously been published. To develop and validate a geographic search filter to retrieve research about the UK from OVID medline with high recall and precision. Three gold standard sets of references were generated using the relative recall method. The sets contained references to studies about the UK which had informed National Institute for Health and Care Excellence (NICE) guidance. The first and second sets were used to develop and refine the medline UK filter. The third set was used to validate the filter. Recall, precision and number-needed-to-read (NNR) were calculated using a case study. The validated medline UK filter demonstrated 87.6% relative recall against the third gold standard set. In the case study, the medline UK filter demonstrated 100% recall, 11.4% precision and a NNR of nine. A validated geographic search filter to retrieve research about the UK with high recall and precision has been developed. The medline UK filter can be applied to systematic literature searches in OVID medline for topics with a UK focus.


A Systematic Review and Meta-Analysis of Randomized Controlled Trials on Supine vs. Nonsupine Endotracheal Intubation.
This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the safety and efficacy of supine vs. nonsupine positions during intubation. Based on the literature from inception to October 2020, 13 studies with nonemergent intubation in supine and nonsupine positions were chosen using PRISMA and MOOSE protocols. Pooled estimates were calculated using random-effects models with 95% confidence interval (CI). The primary outcome was a successful intubation, attempt, and duration of intubation. The secondary outcome was adverse events (trauma and hypoxia). Bias was evaluated qualitatively, by visual analysis, and quantitatively through the Egger test. The final analysis included 13 clinical trials with 1,916 patients. The pooled success rates in the supine vs. lateral positions were 99.21% and 98.82%. The supine vs. semierect positions were 99.21% and 98.82%. The 1st attempt success rate in the supine vs. lateral position was 85.35% and 88.56% compared to 91.38% and 90.76% for the supine vs. semierect position. The rate of total adverse events in the supine position was 3.73% vs. 6.74% in the lateral position, and the rate of total adverse events in the supine position was 0.44% vs. 0.93% in semierect position. Low to substantial heterogeneity was noted in our analysis. Discussion. There is no significant difference between total successful intubations and success from 1st intubation attempt between supine and nonsupine positions. However, there are slightly higher rates of adverse events in nonsupine position. Addition of more recent studies on supine vs. nonsupine intubations would improve this study. Given these findings, it is important to develop more studies regarding different intubation positions and techniques with the aim of improving efficacy and decreasing adverse outcomes. Other. This review is not registered in a public database. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Primary cutaneous follicle-center lymphoma.
We present a 64-year-old man with a three-year history of pruritic, pink papules and nodules of the face who was found to have a clonal lymphoproliferative B-cell disease that was characterized by a clonal IGH rearrangement. Although morphologic features present in the biopsy specimen were consistent with a reactive process, additional clinicopathologic correlation (anatomic presentation of lesions on the face, the absence of t(14:18) translocation, and bcl-2 and MUM1 expression) reinforced suspicion of a cutaneous B-cell lymphoma. Systemic work-up with CT/PET and a bone marrow biopsy ultimately excluded systemic disease and primary cutaneous follicle-center lymphoma (PCFCL) was a strong diagnostic consideration. The patient was treated with systemic rituximab with a partial resolution of the facial lesions. The case demonstrates both clinical and pathologic challenges to the diagnosis of primary cutaneous B-cell lymphoma (PCBCL). Furthermore, despite a newly refined classification system, the case also specifically highlights the persistent requirement for flexible clinical reasoning and pathologic correlation. Such reasoning is necessary to generate individualized strategies for diagnosis and treatment when cutaneous B-cell lymphoma is suspected.


Growth and haematological response of indigenous Venda chickens aged 8 to 13 weeks to varying dietary lysine to energy ratios.
The effect of feeding varying dietary lysine to energy levels on growth and haematological values of indigenous Venda chickens aged 8 - 13 weeks was evaluated. Four hundred and twenty Venda chickens (BW 362 ± 10 g) were allocated to four dietary treatments in a completely randomized design. Each treatment was replicated seven times, and each replicate had fifteen chickens. Four maize-soya beans-based diets were formulated. Each diet had similar CP (150 g/kg DM) and lysine (8 g lysine/kg DM) but varying energy levels (11, 12, 13 and 14 MJ ME/kg DM). The birds were reared in a deep litter house; feed and water were provided ad libitum. Data on growth and haematological values were collected and analysed using one-way analysis of variance. Duncan's test for multiple comparisons was used to test the significant difference between treatment means (p < 0.05). A quadratic equation was used to determine dietary lysine to energy ratios for optimum parameters which were significant difference. Results showed that dietary energy level influenced (p < 0.05) feed intake, feed conversion ratio, live weight, haemoglobin and pack cell volume values of chickens. Dry matter digestibility, metabolizable energy and nitrogen retention not influenced by dietary lysine to energy ratio. Also, white blood cell, red blood cell, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration in female Venda chickens aged 91 days were not influenced by dietary lysine to energy ratio. It is concluded that dietary lysine to energy ratios of 0.672, 0.646, 0.639 and 0.649 optimized feed intake, growth rate, FCR and live weight in indigenous female Venda chickens fed diets containing 8 g of lysine/kg DM, 150 g of CP/kg DM and 11 MJ of ME/kg DM. This has implications in diet formulation for indigenous female Venda chickens.


Home-Based Intervention Program to Reduce Food Insecurity in Elderly Populations Using a TV App: Study Protocol of the Randomized Controlled Trial Saúde.Come Senior.
The limited or uncertain access to adequate food in elderly people includes not only economic restrictions but also inability of food utilization due to functional or cognitive impairment, health problems, and illiteracy. The aim of this work is to present the protocol of the randomized controlled trial Saúde.Come Senior, an educational and motivational television (TV)-based intervention to promote healthy lifestyles and decrease food insecurity in elderly people. A randomized controlled study will be conducted in subjects aged 60 years and older with food insecurity, identified at 17 primary care centers in the Lisboa e Vale do Tejo health region in Lisbon, Portugal. The primary outcome will be the changes in participants' food insecurity score (evaluated by the Household Food Insecurity Scale) at 3 months. Change in other outcomes will be assessed (dietary habits, nutritional status, physical activity, health status, and clinical outcomes). Subjects will be followed over 6 months; the intervention will last 3 months. Data collection will be performed at 3 different time points (baseline, end of intervention at 3 months, and follow-up at 6 months). The intervention is based on an interactive TV app with an educational and motivational program specifically developed for the elderly that has weekly themes and includes daily content in video format: (1) nutrition and diet tips for healthy eating, (2) healthy, easy to cook and low-cost recipes, and (3) physical exercise programs. Furthermore, brief reminders on health behaviors will also be broadcasted through the TV app. The total duration of the study will be 6 months. The intervention is considered to be effective and meaningful if 50% of the individuals in the experimental group have a decrease of 1 point in the food insecurity score, all the remaining being unchanged. We expect to include and randomize 282 (141 experimental and 141 control) elderly with food insecurity. We will recruit a total of 1,128 subjects considering that 50% of the target individuals are food insecure (based on INFOFAMÍLIA Survey) (567) and about 50% of those will adhere to the study (282). The randomized controlled trial with the 12-week home-based intervention with a comprehensive program on healthy eating and physical activity delivery is planned to start recruiting participants at the end of 2017. This study will assess the efficacy of this innovative tool (Saúde.Come Senior) for disseminating relevant health information, modifying behaviors, and decreasing food insecurity in an easy, low-cost, and massive way.


Evaluation of multicentre clinical trial data using adaptations of the Mosteller-Tukey procedure.
Two procedures, based on proposals discussed by Mosteller and Tukey, are described for obtaining a combined estimate of the difference between two treatment means and its confidence interval from multicentre clinical trial data. Both procedures provide estimates in the possible presence of heteroscedasticity. The first procedure is designated the primary analysis for efficacy assessment. It omits treatment-by-centre interaction from the error term for treatment, unless there is substantial evidence of qualitative interaction (Ciminera et al.) or other special circumstances. The second procedure is the primary analysis whenever there is substantial evidence of qualitative interaction, and can be used whenever there are other reasons to make an analysis allowing for interaction.


Topography Measurements Using High Mass Resolution Time-of-Flight Secondary Ion Mass Spectrometry: Application to Banknotes.
An unconventional approach using the time-of-flight secondary ion mass spectrometry (TOF-SIMS) technique to determine the height topography at the microscale is detailed in this work with an application to cotton paper banknotes. The study was conducted by determining the effect of all related factors and parameters on the height measurement by taking the simplest model made from two Post-it sheets. For each sample, the difference in the TOF of the same secondary ion coming from two different heights was successfully attributed to the step height of the studied areas' topography, which was measured using classic methods. The measurement was independent of the orientation of the topography with regard to the primary ion beam and the electron beam azimuth. Moreover, the adjustment of the extraction gap with different layers has no effect on such measurements. However, a range of the analyzer acceptance energy values could be considered to achieve the expected outcomes only if the different analyzers' component energies are also changing accordingly. Heights between 20 and 180 μm were successfully measured using this new method. An added benefit to this method over other height measurement methods is the ability to discern areas with different chemical compositions, which eventually may help aid understanding of the sample in question.


Correlates of facility delivery for rural HIV-positive pregnant women enrolled in the MoMent Nigeria prospective cohort study.
Low rates of maternal healthcare service utilization, including facility delivery, may impede progress in the prevention of mother-to-child transmission of HIV (PMTCT) and in reducing maternal and infant mortality. The MoMent (Mother Mentor) study investigated the impact of structured peer support on early infant diagnosis presentation and postpartum maternal retention in PMTCT care in rural Nigeria. This paper describes baseline characteristics and correlates of facility delivery among MoMent study participants. HIV-positive pregnant women were recruited at 20 rural Primary Healthcare Centers matched by antenatal care clinic volume, client HIV prevalence, and PMTCT service staffing. Baseline and delivery data were collected by participant interviews and medical record abstraction. Multivariate logistic regression with generalized estimating equation analysis was used to evaluate for correlates of facility delivery including exposure to structured (closely supervised Mentor Mother, intervention) vs unstructured (routine, control) peer support. Of 497 women enrolled, 352 (71%) were between 21 and 30 years old, 319 (64%) were Christian, 245 (49%) had received secondary or higher education, 402 (81%) were multigravidae and 299 (60%) newly HIV-diagnosed. Delivery data was available for 445 (90%) participants, and 276 (62%) of these women delivered at a health facility. Facility delivery did not differ by type of peer support; however, it was positively associated with secondary or greater education (aOR 1.9, CI 1.1-3.2) and Christian affiliation (OR 1.4, CI 1.0-2.0) and negatively associated with primigravidity (OR 0.5; 0.3-0.9) and new HIV diagnosis (OR 0.6, CI 0.4-0.9). Primary-level or lesser-educated HIV-infected pregnant women and those newly-diagnosed and primigravid should be prioritized for interventions to improve facility delivery rates and ultimately, healthy outcomes. Incremental gains in facility delivery from structured peer support appear limited, however the impact of duration of pre-delivery support needs further investigation. Religious influences on facility delivery and on general maternal healthcare service utilization need to be further explored. ClinicalTrials.gov number NCT01936753 , registered September 2013.


Prediction of Lysine Malonylation Sites Based on Pseudo Amino Acid.
Protein malonylation is a newly discovered post-translational modification. Malonylation is known to closely be associated with type 2 diabetes and to play its regulatory role in fatty acid oxidation and the associated genetic disease. Identifying protein malonylations might lay a solid foundation to explore malonylation function. Due to the limitations of experimental techniques, it is a great challenge to fast and accurately identify malonylation sites. We proposed a computational method to predict malonylation sites and to analyze malonylation pattern. We firstly extracted protein segments so that the lysine is at the center of each segment. Then, each segment was encoded by the pseudo amino acid compositions. The support vector machine classifier trained by a training dataset was built to distinguish malonylation sites from non-malonylation ones. The leave-one-out test on the training dataset reached the accuracy of 0.7733, and the independent test on the testing dataset got 0.8889. Furthermore, the classifier also successfully identified 144 of 160 putative malonylation sites. Analyses on the differences between malonylation and non-malonylation segments implicated that lysine malonylation should follow a specific pattern, e.g. lysine with its neighbors being Glycine and Alanine might be more likely to be malonylated. Therefore, the proposed method is expected to be a promising tool to identify malonylation sites.


"Beyond saving lives": Current perspectives of interventional radiology in trauma.
Interventional radiology (IR) has become an integral part in the management of traumatic injuries. There is an ever-increasing role of IR in traumatic injuries of solid abdominal organs, pelvic and peripheral arteries to control active bleeding by therapeutic embolization or vascular reconstruction using stent grafts. Traditionally, these endovascular treatments have been offered to hemodynamically stable patients. However, in recent times endovascular approach has become preferable to surgery even in hemodynamically unstable patients with injury of surgically difficult-to-access sites. With shifting trends towards non operative management coupled with availability of the current state-of-the-art equipments, hardware and technical expertise, IR has gained an impeccable role in trauma management. However, due to lack of awareness and widespread acceptance, IR continues to remain an ocean of unexplored potentialities.


An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.
Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis.


Hepatotoxic effect of subacute vincristine administration activates necrosis and intrinsic apoptosis in rats: protective roles of broccoli and Indian mustard.
This study investigated the hepatotoxic effect of long-term vincristine (VCR) administration in rats and to assess if an individual or combined therapy with Indian mustard and broccoli afforded protection. Signs of hepatotoxicity, including altered liver architecture and higher serum levels of ALT and AST, were seen in VCR-treated rats. Concomitantly, the impaired antioxidant potential and higher mRNA levels of IL-12 and IL-4, which are markers of apoptosis, were seen in rat livers. VCR treatment induced hepatocyte apoptosis, shown by the up-regulation of mRNA and protein levels of 53, increased protein levels of cleaved caspase-3 and Bax, and reduced levels of intracellular ATP and BCl-2mRNA and protein. Although individual administration of mustard or broccoli partially ameliorated all these responses, the combined therapy of both extracts resulted in the maximum improvement. Thus, the long-term administration of VCR is hepatotoxic and induces apoptosis; however, the combined therapy of both extracts mitigated these effects.


Effects of CGA-N12 on the membrane structure of Candida tropicalis cells.
The antimicrobial peptide CGA-N12 (NH2-ALQGAKERAHQQ-COOH) is an active peptide derived from chromogranin A (CGA) and consists of the 65th to 76th amino acids of the N-terminus. The results of our previous studies showed that CGA-N12 exerts anti-Candida activity by inducing apoptosis without destroying the integrity of cell membranes. In this study, the effect of CGA-N12 on the cell membrane structure of Candida tropicalis was investigated. CGA-N12 resulted in the dissipation of the membrane potential, the increase in membrane fluidity, and the outflow of potassium ions in C. tropicalis without significantly changing the ergosterol level. Fluorescence quenching was applied to evaluate the membrane channel characteristics induced by CGA-N12 through detection of the following: membrane permeability of hydrated Cl- (ϕ ≈ 0.66 nm) using the membrane-impermeable halogen anion-selective fluorescent dye lucigenin, passage of the membrane-impermeable dye carboxyfluorescein (CF) (ϕ ≈ 1 nm) through the membrane, and membrane permeation of H3O+ based on the membrane non-permeable pH-sensitive fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt (HPTS). In conclusion, CGA-N12 can induce the formation of non-selective ion channels <1 nm in diameter in the membranes of C. tropicalis, resulting in the leakage of potassium ions, chloride ions, and protons, among others, leading to dissipation of the membrane potential. As a result, the fluidity of membranes is increased without destroying the synthesis of ergosterol is not affected.


Molecular dynamics study of alkyl benzene sulfonate at air/water interface: effect of inorganic salts.
Molecular dynamics simulations have been performed to investigate the effect of inorganic salts on the structural and dynamic properties of alkyl benzene sulfonate monolayer formed at the air/water interface. The alkyl benzene sulfonates are two surfactant isomers in the family of sodium hexadecane benzene sulfonates defined by 1C16 and 5C16, indicating a benzene sulfonate group attached to the first and fifth carbon atom in hexadecane backbone. It has been observed that both benzene ring groups and headgroups (-SO(3)(-)) are hydrated due to their polar nature. Water molecules can form stable hydrogen bonds with headgroups of surfactants, and the counterions (Na(+), Mg(2+), or Ca(2+)) are distributed close to the air/water interface. The stronger electrostatic repulsion drives the 1C16 monolayer arranged in disorder in comparison with 5C16, and the presence of inorganic salts may screen electrostatic repulsions between headgroups and decrease the thickness of the interfacial water layer, which follows the series Ca(2+) > Mg(2+) > Na(+). The order of inorganic salt tolerance of two surfactants is 5C16 > 1C16. The counterions may penetrate into the hydration shell of the surfactant headgroups and restrict the mobility of the water molecules situated in this area.


Diagnosis of intestinal amebiasis using salivary IgA antibody detection.
Attempts were made to use soluble antigen extract of strain HK-9 of Entamoeba histolytica to detect salivary IgA antibodies in intestinal amebiasis patients by using ELISA. Total salivary samples of 109 individuals were divided into four groups. Group I comprised 32 patients whose stools were positive only for E. histolytica cysts and/or trophozoites. Group II comprised 12 individuals whose stools were positive for E. histolytica and other intestinal parasites. Group III comprised 36 individuals whose stools were negative for E. histolytica but contained other intestinal parasites such as E. coli, E. nana, Blastocystis hominis, Trichomonas hominis, Giardia lamblia, Opisthorchis viverrini, and hookworm. Group IV comprised 29 healthy individuals whose stools were free from any intestinal parasitic infections. Based on the mean optical density, OD + 2SD of the results from 29 parasitologically negative healthy individuals, the cut-off OD value for salivary IgA antibodies was 1.265. Therefore, the assays were positive in 14 out of 32 (43.75%) of group I and 2 out of 12 (16.6%) of group II. The assays were positive in 16 out of 36 (44.44%) for group III whereas 2 out of 29 (6.90%) for group IV were positive. The overall sensitivity and specificity of the assays were 36% and 72%, respectively. The false positive rate was 28% and the false negative rate was 64%. The predictive values of positive and negative results were 47% and 63%, respectively. The diagnostic accuracy of ELISA for the presence of salivary IgA antibodies was 58%.


T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients.
Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.


Management and Outcomes of Spontaneous Cerebrospinal Fluid Otorrhoea.
Objective: A cohort of patients with spontaneous cerebrospinal fluid (sCSF) otorrhoea. To report surgical outcome and discuss a treatment protocol. Materials and Methods: Between 2012 and 2018 all patients presenting with sCSF were collected and data assessment was performed including clinical symptoms (hearing loss, aural fullness, meningitis, recurrent otitis media), preoperative audiometry, CT and MRI scanning. According to the site and size of the dural defect, different surgical approaches were applied. Results: A total of 12 patients (14 operations) were included. Four of these had a history of meningitis. All beta-trace protein testings were positive. These patients were treated with different surgical approaches: middle fossa approach (MCF, seven patients), transmastoid approach (TMA) with bony obliteration of the cavity (three patients), and four patients underwent a subtotal petrosectomy (STP) procedure. Three cases underwent revision surgery (MCF or STP) due to residual disease (CFS leakage). After follow up duration of 13 months (6.5 months SD), no recurrence was observed. No severe adverse events such as cerebrovascular injury, meningitis, wound infection, or headache was observed in the postoperative course. Conclusion: Spontaneous aural cerebrospinal fluid leakage is a rare but manageable pathology with potential severe complications. Appropriate diagnosis, laboratory testing, and imaging is primordial to obtain optimal patient outcome.


Determination of affinity and activity of ligands at the human neuropeptide Y Y4 receptor by flow cytometry and aequorin luminescence.
Fluorescence-labeled neuropeptide Y (NPY) has been used in flow cytometric binding assays for the determination of affinity constants of NPY Y1, Y2, and Y5 receptor ligands. Because the binding of fluorescent NPY is insufficient for competition studies at the human Y4 receptor (hY4R), we replaced Glu-4 in hPP with Lys for the derivatization with cyanine-5. Because cy5-[K(4)]hPP has high affinity (Kd 5.6 nM) to the hY4R, it was used as a probe in a flow cytometric binding assay. Specific binding of cy5-[K(4)]hPP to hY4R was visualized by confocal microscopy. The hY(4)R, the chimeric G protein G(qi5) and mitochondrially targeted apoaequorin were stably coexpressed in CHO cells. Aequorin luminescence was quantified in a microplate reader and by a CCD camera. By application of these methods 3-cyclohexyl-N-[(3-1H-imidazol-4-ylpropylamino)(imino)methyl]propanamide (UR-AK49) was discovered as the first nonpeptidic Y4R antagonist (pKi 4.17), a lead to be optimized in terms of potency and selectivity.


[Not Available].
25 medical historians born between 1800 and 1900 have been selected, mainly by citation frequency, for a study in comparative biography. They originated in Germany, U.S.A., U.K., France, Switzerland, Italy, and Austria. A number of them were active in two countries due to emigration from fascist Europe in the 1930s. All were MDs except for one historian. Most of them showed an interest in the history of medicine early in life, some only between age 40-50. Their motivations were quite varied. Most of them made their living with clinical practice, at least initially. Those ten who attained a chair in the history of medicine did so usually between age 41 and 56. Our selection of medical historians active between 1825 and 1975 is very heterogeneous, much more so than in the final decades of the 20th century.


[Relationship between elderly hip fracture and osteoporosis].
To explore the relationship between elderly hip fracture and osteoporosis. 85 elderly patients with hip fractures were admitted into our hospital from January 2009 to March 2012. Mineral density in bones and the concentration of biochemical markers I collagen such as hydroxy terminal peptide (crosslaps) and deoxypyridinoline (DPD) in urine sample of the patients were measured. Another 60 non-hip fracture patients were selected as controls. Bone mineral density from the non-hip-fractured group appeared significantly higher than the hip-fractured group (P < 0.05), while the concentration of crosslaps and DPD in the urine of patients were significantly higher than the normal control group (P < 0.05), suggesting that the patients suffered from osteoporosis were more prone to hip fracture. Although the hip fracture in the elderly was generally caused by trauma while factors as bone mineral density, concentration of crosslaps and DPD showed that osteoporosis played an important 'internal'role on hip fractures in the elderly. Attention should be paid to the elderly people with symptoms of osteoporosis and early treatment provided, to prevent hip fracture in this population.


Future-proofing the koala: Synergising genomic and environmental data for effective species management.
Climatic and evolutionary processes are inextricably linked to conservation. Avoiding extinction in rapidly changing environments often depends upon a species' capacity to adapt in the face of extreme selective pressures. Here, we employed exon capture and high-throughput next-generation sequencing to investigate the mechanisms underlying population structure and adaptive genetic variation in the koala (Phascolarctos cinereus), an iconic Australian marsupial that represents a unique conservation challenge because it is not uniformly threatened across its range. An examination of 250 specimens representing 91 wild source locations revealed that five major genetic clusters currently exist on a continental scale. The initial divergence of these clusters appears to have been concordant with the Mid-Brunhes Transition (~430 to 300 kya), a major climatic reorganisation that increased the amplitude of Pleistocene glacial-interglacial cycles. While signatures of polygenic selection and environmental adaptation were detected, strong evidence for repeated, climate-associated range contractions and demographic bottleneck events suggests that geographically isolated refugia may have played a more significant role in the survival of the koala through the Pleistocene glaciation than in situ adaptation. Consequently, the conservation of genome-wide genetic variation must be aligned with the protection of core koala habitat to increase the resilience of vulnerable populations to accelerating anthropogenic threats. Finally, we propose that the five major genetic clusters identified in this study should be accounted for in future koala conservation efforts (e.g., guiding translocations), as existing management divisions in the states of Queensland and New South Wales do not reflect historic or contemporary population structure.


Outcomes following combined median sternotomy and ventral midline laparotomy for bicavitary penetrating wooden foreign bodies.
Combined abdominal and thoracic pathology caused by extra-gastrointestinal migration of an ingested wooden foreign body (WFB) is an uncommon but serious injury. Presenting clinical signs are typically nonspecific and, in the absence of observed WFB ingestion, diagnosis is challenging. Treatment requires concurrent abdominal and thoracic surgical exploration to remove the WFB and address injuries caused by its migration. This case series describes perioperative characteristics and outcomes in 4 dogs following combined median sternotomy and ventral midline laparotomy (CMSVML) for bicavitary penetrating WFBs. Key clinical message: Treatment of bicavitary penetrating WFBs with CMSVML provided postoperative outcomes similar to those in previous reports; however, high-grade complications and prolonged hospitalization were commonly encountered.


Growth and migration of gingival epithelial cells on mineralized and partially demineralized root surfaces in an in vitro system.
The capacity of epithelial cells to migrate and grow from gingival explants cultured on mineralized and partially demineralized root surfaces in an in vitro system was assessed. Explants of attached gingiva were obtained from mongrel dogs, cut into rectangular pieces (1 x 2 mm) and cultured either on mineralized or partially demineralized cementum in a defined culture medium containing transferrin, insulin, epidermal growth factor, cortisone, high density lipoprotein and selenium. After seven days of culture, the specimens were prepared for scanning electron microscopic examination. The amount of epithelial outgrowth from each explant was assessed by measuring the distances between the four aspects of the rectangular explant and the furthest epithelial cell located opposite to each of these aspects. The mean value obtained for epithelial outgrowth of explants grown on mineralized cementum was six times higher than that for explants cultured on partially demineralized cementum. These results indicate that partially demineralized cementum does not support epithelial growth and migration in vitro.


Abortion--a philosophical perspective.
The central issue in the abortion debate is the moral status of the conceptus. There are two positions that argue this issue. At one extreme are the views of the pro-life group which argues that human life begins at the moment of conception whilst at the other are views of the pro-choice group that argues in favour of a woman's right to self-determination. Two basic principles come into conflict in this debate, namely the Value of Life and that of Self-determination. In this paper the arguments forwarded by each group in justification of its position are presented. Also discussed is the moderate developmental viewpoint which accepts that the genetic basis of an individual is established at conception. Some development, however, has to occur before the conceptus can be called a person. The fact that an entity is a potential person is a prima facie reason for not destroying it. On the other hand, we need not conclude that a person has a right to life by virtue of that potentiality. Simultaneously we should recognise that the right a potential entity has, may be nullified by the woman's right to self-determination.


Red Blood Cell Transfusion in Preterm Infants: Current Evidence and Controversies.
The current evidence regarding the indication, advantages and risks of red blood cell transfusion (RBCT) for preterm infants is discussed. This is an important area in Neonatology to be examined given that 90% of extremely low birth weight infants receive RBCT and many controversies remain regarding when to transfuse and the risks of RBCT. The various treatment thresholds and guidelines used are presented and we compare the short-term clinical benefits of liberal and restrictive RBCT in preterm infants; the majority of these are equivocal and sadly long-term outcome data is limited. The latest evidence on how anaemia and blood transfusion affect organ perfusion in preterm infants is presented. This is important when trying to establish the optimal trigger threshold for RBCT in preterm infants, especially because the knowledge about the adaptive physiological responses to anaemia in very low birth weight infants and the effects of RBCT at various levels of anaemia is also inadequate. Further research into the physiological adaptive response to anaemia of varying degrees and to RBCT at different levels of anaemia in preterm infants of different gestational and post-natal ages is needed before we can conclusively guide the optimal timing and trigger thresholds for RBCT in preterm infants.


Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells.
Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are still not fully understood. Here, we provide evidence for PRL-3-induced hyperactivation of EGFR and its downstream signaling cascades in multiple human cancer cell lines. Mechanistically, PRL-3-induced activation of EGFR was attributed primarily to transcriptional downregulation of protein tyrosine phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3-induced hyperactivation of EGFR correlated with increased cell growth, promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of these oncogenic attributes upon EGFR-specific inhibition. Of clinical significance, we verified elevated PRL-3 expression as a predictive marker for favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient cohort treated with the clinically approved anti-EGFR antibody cetuximab. The identification of PRL-3-driven EGFR hyperactivation and consequential addiction to EGFR signaling opens new avenues for inhibiting PRL-3-driven cancer progression. We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy.


Sensitivity of alpha-1 adrenoceptor-mediated pressor responses to inhibition by Ca++ entry blockers in the pithed rat: arguments against the role of receptor reserve.
In pithed rats, nifedipine (i.a., -15 min) maximally shifted the alpha-1 adrenoceptor-mediated log dose-pressor response curve to i.v. (-)-phenylephrine 5-fold to the right, doses of 1 and 3 mg/kg being equieffective. Phenoxybenzamine (3-1000 micrograms/kg i.v., -60 min) enhanced the potency of nifedipine, expressed as -log ID50, to inhibit the vasopressor response to (-)-phenylephrine. After treatment with 0.1, 0.3 or 1 mg/kg of phenoxybenzamine a dose of 1 mg/kg of nifedipine was sufficient to virtually eliminate the pressor responses. The potentiating effect of phenoxybenzamine was already present at a low dose of 3 micrograms/kg, which by itself had no influence on the log dose-pressor response curve to (-)-phenylephrine. It was also clearly limited, inasmuch as the -log ID50 values of nifedipine determined after treatment with 0.1, 0.3 and 1 mg/kg of phenoxybenzamine were identical and similar to the value reported for nifedipine against alpha-2 adrenoceptor-mediated vasoconstriction in pithed rats. Infusion of vasopressin to counteract the vasodilatory action of nifedipine did not affect its inhibitory potency compared to the effectiveness quantified under the conditions of reduced baseline diastolic pressure. The data support the conclusions that the resistance of the pressor response to (-)-phenylephrine (and other full alpha-1 adrenoceptor agonists) to inhibition by nifedipine (or other Ca++ channel blockers) is due to the dual nature of the Ca++ utilization in the vasoconstriction to these stimulants, i.e., transmembranous influx of extracellular Ca++ (sensitive to Ca++ channel blockers) and a mobilization of intracellular Ca++ (insensitive to Ca++ channel blockers).(ABSTRACT TRUNCATED AT 250 WORDS)


Testing Variance Components in Linear Mixed Modeling Using Permutation.
Inference of variance components in linear mixed modeling (LMM) provides evidence of heterogeneity between individuals or clusters. When only nonnegative variances are allowed, there is a boundary (i.e., 0) in the variances' parameter space, and regular inference statistical procedures for such a parameter could be problematic. The goal of this article is to introduce a practically feasible permutation method to make inferences about variance components while considering the boundary issue in LMM. The permutation tests with different settings (i.e., constrained vs. unconstrained estimation, specific vs. generalized test, different ways of calculating p values, and different ways of permutation) were examined with both normal data and non-normal data. In addition, the permutation tests were compared to likelihood ratio (LR) tests with a mixture of chi-squared distributions as the reference distribution. We found that the unconstrained permutation test with the one-sided p-value approach performed better than the other permutation tests and is a useful alternative when the LR tests are not applicable. An R function is provided to facilitate the implementation of the permutation tests, and a real data example is used to illustrate the application. We hope our results will help researchers choose appropriate tests when testing variance components in LMM.


Transport mechanism of a glutamate transporter homologue GltPh.
Glutamate transporters are responsible for uptake of the neurotransmitter glutamate in mammalian central nervous systems. Their archaeal homologue GltPh, an aspartate transporter isolated from Pyrococcus horikoshii, has been the focus of extensive studies through crystallography, MD simulations and single-molecule FRET (smFRET). Here, we summarize the recent research progress on GltPh, in the hope of gaining some insights into the transport mechanism of this aspartate transporter.


Family planning clinics--a story of growth and conflict.
During the 1960s, as demand for effective contraceptives increased and women expressed a desire for smaller families, an "odd lot" of groups came together to press for federally supported family planning services for low-income women. The drive culminated in 1970 with the passage of Title X of the Public Health Service Act, which authorized the funds that fed a network of family planning clinics. At the height of the national family planning program, approximately 2,500 agencies were operating clinics at more than 5,000 sites, providing services annually to almost five million patients. As part of the screening for medical methods of birth control, family planning clinics have provided basic physical examinations and related tests to millions of low-income women and teenagers who might not otherwise have had access to those services. Clinics have also been heavily utilized for pregnancy tests, screening for sexually transmitted diseases (STDs), infertility screening and referral for abortion, adoption and sterilization services. Other desired achievements have been more elusive and difficult to document--reductions in the number of high-risk and unintended pregnancies and in poverty rates, for example. The program's role in providing contraceptive services to teenagers and its involvement in the abortion controversy have led to a number of political, legislative and judicial skirmishes with conservatives, Congress and the Reagan administration. Funding for Title X declined during the 1980s and is now surpassed by Medicaid as the largest source of family planning dollars. Diminishing funds at a time when some expenses--for supplies, malpractice insurance and treatment of STDs, for example--are increasing have resulted in fewer clinic sites and other service cutbacks. The suggestion has been made that it is time to eliminate categorical funds for family planning and integrate all services into the general medical care system. Family planning providers say an integrated arrangement would not meet the needs of much of their patient population and would not provide the special attention they feel is needed for successful contraceptive practice among low-income, high-risk women. Instead, they suggest expanding the scope of services in family planning clinics, out of an awareness that the continuing high prevalence of unintended childbearing, among the young and disadvantaged in particular, is part of a larger problem of living in a desolate social environment.


Profound Change in Soil Microbial Assembly Process and Co-occurrence Pattern in Co-inoculation of Bradyrhizobium japonicum 5038 and Bacillus aryabhattai MB35-5 on Soybean.
Rhizosphere microbial communities are vital for plant growth and soil sustainability; however, the composition of rhizobacterial communities, especially the assembly process and co-occurrence pattern among microbiota after the inoculation of some beneficial bacteria, remains considerably unclear. In this study, we investigated the structure of rhizomicrobial communities, their assembly process, and interactions contrasting when Bradyrhizobium japonicum 5038 and Bacillus aryabhattai MB35-5 are co-inoculated or Bradyrhizobium japonicum 5038 mono-inoculated in black and cinnamon soils of soybean fields. The obtained results indicated that the Chao and Shannon indices were all higher in cinnamon soil than that in black soil. In black soil, the co-inoculation increased the Shannon indices of bacteria comparing with that of the mono-inoculation. In cinnamon soil, the co-inoculation decreased the Chao indices of fungi comparing with that of mono-inoculation. Compared with the mono-inoculation, the interactions of microorganisms of co-inoculation in the co-occurrence pattern increased in complexity, and the nodes and edges of co-inoculation increased by 10.94, 40.18 and 4.82, 16.91% for bacteria and fungi, respectively. The co-inoculation of Bradyrhizobium japonicum 5038 and Bacillus aryabhattai MB35-5 increased the contribution of stochastic processes comparing with Bradyrhizobium japonicum 5038 inoculation in the assembly process of soil microorganisms, and owing to the limitation of species diffusion might restrict the direction of pathogenic microorganism movement. These findings support the feasibility of rebuilding the rhizosphere microbial system via specific microbial strain inoculation and provide evidence that the co-inoculation of Bradyrhizobium japonicum 5038 and Bacillus aryabhattai MB35-5 can be adopted as an excellent compound rhizobia agent resource for the sustainable development of agriculture.


The effect of a multimedia interactive tutorial on learning endodontic problem-solving.
New technology may create additional opportunities for learning in dental education. One of these new features is a multimedia approach, courseware combining sound, text, stills and video with interactive learning. A multimedia program was developed to train dental students and dental practitioners in decision making and problem solving in endodontics. This study compared the effects of the multimedia program with a more traditional approach consisting of written information, without interaction. 28, 4th-year dental students at the University of Kentucky in Lexington, KY, USA were randomly assigned to the multimedia or the text-based groups. They were given a written pre-test using 2 cases of dental pain and were instructed to study independently using either the multimedia program (group A) or the written information (group B). No restrictions were imposed on the amount of time to be invested, and the total study time was recorded for each student. 3 weeks after the pre-test, the students completed the post-test. A total of 18 students completed both the pre-test and the post-test and their scores were included in the final data. Statistical analysis of the average scores using paired t-tests revealed no significant difference between the performance of the students in either group, indicating that the multimedia approach to learning endodontic problem solving may successfully replace traditional learning strategies.


Caenorhabditis elegans ATAD-3 modulates mitochondrial iron and heme homeostasis.
ATAD3 (ATPase family AAA domain-containing protein 3) is a mitochondrial protein, which is essential for cell viability and organismal development. ATAD3 has been implicated in several important cellular processes such as apoptosis regulation, respiratory chain function and steroid hormone biosynthesis. Moreover, altered expression of ATAD3 has been associated with several types of cancer. However, the exact mechanisms underlying ATAD3 effects on cellular metabolism remain largely unclear. Here, we demonstrate that Caenorhabditis elegans ATAD-3 is involved in mitochondrial iron and heme homeostasis. Knockdown of atad-3 caused mitochondrial iron- and heme accumulation. This was paralleled by changes in the expression levels of several iron- and heme-regulatory genes as well as an increased heme uptake. In conclusion, our data indicate a regulatory role of C. elegans ATAD-3 in mitochondrial iron and heme metabolism.


Physicochemical characterization of exopolysaccharides produced by Lactobacillus rhamnosus on various carbon sources.
The impact of five carbohydrate sources (glucose, maltose, galactose, sucrose, and lactose) on the chemical composition, structure, morphology, and physicochemical properties, as well as, viscosity of exopolysaccharides (EPSs) produced by Lactobacillus rhamnosus E/N was investigated. GLC-MS analysis and 2DNMR spectroscopy showed that the EPSs had the same primary structure independently of the carbon source used in the growth medium. The following EPS composition was elucidated: four rhamnose, two glucose, and one galactose residue with a pyruvate substituent. Molecular masses (M(w)) were determined by gel permeation chromatography, which revealed differences in M(w) distribution. EPS-Gal, EPS-Suc, and EPS-Lac showed heterogenic fractions of a high and low molecular weight, while EPS-Mal and EPS-Glc contained only a high-molecular-weight fraction. AFM microscopy revealed morphological differences in chain length, thickness, and branching. Differences in the Mw ratio and thickness of the polymer chain were correlated with high viscosity of EPS solutions. Our results indicate that a single bacterial strain, depending on the carbon source in the medium, can produce EPSs of different rheological properties.


Quasispecies composition and evolution of a typical Zika virus clinical isolate from Suriname.
The arthropod-borne Zika virus (ZIKV) is currently causing a major international public health threat in the Americas. This study describes the isolation of ZIKV from the plasma of a 29-year-old female traveler that developed typical symptoms, like rash, fever and headache upon return from Suriname. The complete genome sequence including the 5' and 3' untranslated regions was determined and phylogenetic analysis showed the isolate clustering within the Asian lineage, close to other viruses that have recently been isolated in the Americas. In addition, the viral quasispecies composition was analyzed by single molecule real time sequencing, which suggested a mutation frequency of 1.4 × 10-4 for this ZIKV isolate. Continued passaging of the virus in cell culture led to the selection of variants with mutations in NS1 and the E protein. The latter might influence virus binding to cell surface heparan sulfate.


Peripheral mononuclear cells of haemophiliacs with chronic liver disease are infected with replicating hepatitis C virus.
Most haemophiliacs treated with non-virally inactivated concentrates have been infected with the hepatitis C virus (HCV). 19/21 (90%) patients with HCV antibody were found to have HCV RNA in their serum and in 16 of these it was also detected in peripheral blood mononuclear cells (PBMC). We used specific primers to detect the negative (replicative) strand of this single positively stranded virus. The negative strand was detected in the serum or PBMC of 16 patients indicating active replication outside the liver. The detection of replicating HCV RNA in the cells of HIV negative haemophiliacs could explain at least some of the immunological abnormalities previously reported in these patients and attributed to clotting factor concentrates.


[2 cases of colitis caused by Clostridium difficile during antibiotic therapy].
Defined the most important clinical, endoscopic and pathological aspects of antibiotic-associated colitis, the AA. examine the Clostridium difficile as the etiological agent. The range of examination has been limited to two cases of pseudomembranous colitis, a diagnostic and a therapeutic evaluation is suggested for patients with AAD and PMC. Furthermore the importance of a strictly observance of hospital hygienic rules in the prevention of such pathological cases is strongly stressed.


Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7.
Herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 stimulates lytic infection and the reactivation of quiescent viral genomes. These roles of ICP0 require its RING finger E3 ubiquitin ligase domain, which induces the degradation of several cellular proteins, including components of promyelocytic leukemia nuclear bodies and centromeres. ICP0 also interacts very strongly with the cellular ubiquitin-specific protease USP7 (also known as HAUSP). We have shown previously that ICP0 induces its own ubiquitination and degradation in a RING finger-dependent manner, and that its interaction with USP7 regulates this process. In the course of these studies we found and report here that ICP0 also targets USP7 for ubiquitination and proteasome-dependent degradation. The reciprocal activities of the two proteins reveal an intriguing situation that poses the question of the balance of the two processes during productive HSV-1 infection. Based on a thorough analysis of the properties of an HSV-1 mutant virus that expresses forms of ICP0 that are unable to bind to USP7, we conclude that USP7-mediated stabilization of ICP0 is dominant over ICP0-induced degradation of USP7 during productive HSV-1 infection. We propose that the biological significance of the ICP0-USP7 interaction may be most pronounced in natural infection situations, in which limited amounts of ICP0 are expressed.


Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway.
Anacardic acid, which is commonly seen in plants of Anacardiaceae, is an important composition of cashew, ginkgo leaf and fruit, and it has been suggested in previous research to show antitumor activity. The main aim of the present study was to evaluate the anticancer effects of anacardic acid on cell apoptosis of prostatic cancer and molecular mechanisms of this phenomenon. In this study we found that anacardic acid inhibited cell proliferation, induced apoptosis and caspase-3/9 activities and Bax protein expression of prostatic cancer. Anacardic acid induced the ER stress inducing factors (BiP, CHOP, p-eIF2α), autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression, and suppressed p-Akt and p-mTOR protein expression of prostatic cancer. Si-CHOP was used to inhibit ER stress in prostatic cancer by anacardic acid, which showed that the cell proliferation was increased, apoptosis, and caspase-3/9 activities and Bax protein expression was suppressed, autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression was reduced, and p-Akt and p-mTOR protein expression was promoted. DAPK3 inhibited p-Akt and p-mTOR protein expression, enhanced the anticancer effects of anacardic acid on prostatic cancer through autophagy. For the first time, the present study showed that anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway.


Cardiac pacing in children.
Indications for cardiac pacing in pediatric patients continue to expand. In addition to its traditional use in sinus and atrioventricular nodal disease, applications for cardiac pacing now include treatment of tachyarrhythmias after repair of congenital heart disease, reduction of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and prevention of sudden death in the congenital long QT syndrome. Whereas many benefits have been well documented in adults, they remain anecdotal in children. Programmable features such as rate-response and antitachycardia pacing contribute to pacemaker versatility and facilitate the achievement of normal hemodynamics in children requiring long-term pacing therapy.


Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.
To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life.


Obesity and kidney disease.
Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD). Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.


Ferromagnetic coupling in d(1)-d(3) linear oxido-bridged heterometallic complexes: ground-state models of metal-to-metal charge transfer excited states.
Convenient strategies have been developed to synthesize heterobi/trimetallic oxido complexes containing V(IV)-O-Cr(III), V(IV)-O-Cr(III)-O-Ti(IV) and V(IV)-O-Cr(III)-O-V(IV) cores. These compounds can serve as ground state models for probing the magnetic properties of metal-to-metal charge transfer excited states. Each of these complexes represents the first experimental demonstration of ferromagnetic coupling in a d(1)-d(3) oxido bridged compound, which confirms a long standing theoretical prediction for such a linkage. Structural characterization reveals a similar structure for each of the bi/trimetallic complexes with identical V[double bond, length as m-dash]O bond lengths (∼1.644 Å) and a linear V-O-Cr geometry. The Cr-O distances (1.943-1.964 Å) are significantly influenced by the ligands in the trans axial positions. Ferromagnetic coupling between the V(IV) and Cr(III) of V-O-Cr is measured by temperature-dependent magnetic susceptibility, showing J = +42.5 to +50.7 cm(-1) (H = -2JŜVŜCr). This is further supported by variable temperature X-band EPR. The values of J are found to be consistent with the function J = Ae(βr) (A = 9.221 × 10(8) and β = 8.607 Å(-1)), where r is the Cr-O bond distance. We propose a model that links either ferromagnetic or antiferromagentic exchange coupling with long excited state lifetimes in metal-to-metal charge transfer (MMCT) chromophores.


Effectiveness of two novel anionic and cationic platinum complexes in the treatment of osteosarcoma.
This study aimed to characterize the cellular basis of the platinum cytotoxicity of two novel platinum complexes, 3Pt and 1Pt, in comparison with that of cisplatin. 3Pt comprises anionic phosphate moieties, while 1Pt comprises neutral aromatic ligands. We compared the cytotoxic potency of 3Pt and 1Pt with that of cisplatin in osteosarcoma cell lines and an orthotopic mouse model. The cytotoxic potency of 3Pt was markedly higher than that of cisplatin in all cell lines. Both novel platinum complexes showed a complete lack of cross resistance in cisplatin-resistant cells. Caffeine enhanced the cytotoxic potency of these novel platinum complexes, as observed for cisplatin. Apoptosis after drug administration was observed by DNA ladder formation and an annexin V/PI assay. DNA double-strand breaks were confirmed by phosphorylation of histone H2AX. In vivo, the antitumor activity of 3Pt and 1Pt was superior and similar, respectively, to that of cisplatin. Both novel platinum complexes exerted strong antitumor effects on osteosarcoma in vitro and in vivo. 3Pt may be an effective drug for the treatment of bone cancer because the PO3 moiety has a high affinity to bone, as exhibited by bisphosphonates, and is expected to decrease the incidence of side effects at extraskeletal sites and overcome drug resistance. Cationic 1Pt may also be an effective antitumor drug because of its unique chemical structure and properties. Further investigations to detail the antitumor effects of these ionic Pt complexes on osteosarcoma are warranted.