Postnasal drip and chronic cough in patients with chronic rhinitis treated with temperature-controlled radiofrequency neurolysis.
To evaluate the contribution of postnasal drip (PND) and chronic cough (CC) to symptoms of patients with chronic rhinitis treated with temperature-controlled radiofrequency (TCRF) neurolysis of the posterior nasal nerve (PNN), and correlate PND and CC scores with components of the reflective total nasal symptom score (rTNSS). Pooled data from three prospective studies: two single-arm studies and the index active treatment arm of a randomized controlled trial. Adult patients with baseline rTNSS ≥6 were treated with TCRF neurolysis at nonoverlapping regions of the PNN. PND and CC symptoms were evaluated on a 0 (none) to 3 (severe) scale. Data from 228 patients (57.9% women, 42.1% men) were included. The mean baseline rTNSS was 8.1 (95% confidence interval [CI], 7.8-8.3), which decreased to 3.2 (95% CI, 2.9-3.5) at 6 months. At baseline, 97.4% of patients had PND and 80.3% had CC. Median baseline PND and CC symptom scores were 3 (interquartile range [IQR], 2-3) and 2 (IQR, 1-2), respectively. At 6 months, this decreased to 1 (IQR, 0-2) and 0 (IQR, 0-1), respectively, showing significant improvement from baseline (both p < 0.001). Spearman correlation coefficients with components of rTNSS (rhinorrhea, congestion, itching, sneezing) were 0.16 to 0.22 for CC and 0.19 to 0.46 for PND, indicating only a weak to moderate correlation. PND and CC contribute to the symptomatology of chronic rhinitis and are significantly improved after TCRF neurolysis of the PNN. The inclusion of PND and CC symptoms in a chronic rhinitis assessment instrument could provide important additional information for the characterization of the disease state and outcomes after any therapeutic treatment.


MotifPrototyper: a Bayesian profile model for motif families.
In this article, we address the problem of modeling generic features of structurally but not textually related DNA motifs, that is, motifs whose consensus sequences are entirely different but nevertheless share "metasequence features" reflecting similarities in the DNA-binding domains of their associated protein recognizers. We present MotifPrototyper, a profile Bayesian model that can capture structural properties typical of particular families of motifs. Each family corresponds to transcription regulatory proteins with similar types of structural signatures in their DNA-binding domains. We show how to train MotifPrototypers from biologically identified motifs categorized according to the TRANSFAC categorization of transcription factors and present empirical results of motif classification, motif parameter estimation, and de novo motif detection by using the learned profile models.


Liver resection for hepatocellular carcinoma using a microwave tissue coagulator: Experience of 1118 cases.
To present our extensive experience of hepatectomy for hepatocellular carcinoma using a microwave tissue coagulator to demonstrate the effectiveness of this device. A total of 1118 cases (1990-2013) were reviewed, with an emphasis on intraoperative blood loss, postoperative bile leakage and fluid/abscess formation, and adaptability to anatomical resection and hepatectomy with hilar dissection. The median intraoperative blood loss was 250 mL; postoperative bile leakage and fluid/abscess formation were seen in 3.0% and 3.3% of cases, respectively. Anatomical resection was performed in 275 cases, including 103 cases of hilar dissection that required application of microwave coagulation near the hepatic hilum. There was no clinically relevant biliary tract stricture or any vascular problems due to heat injury. Regarding the influence of cirrhosis on intraoperative blood loss, no significant difference was seen between cirrhotic and non-cirrhotic patients (P = 0.38), although cirrhotic patients tended to have smaller tumors and underwent less invasive operations. This study demonstrated outcomes of an extensive experience of hepatectomy using heat coagulative necrosis by microwave tissue coagulator.


Immunohistochemical analysis of contact sensitivity reactions in the guinea-pig using novel monoclonal antibodies: the influence of topical cyclosporin A.
When applied topically to guinea-pig skin from the time of epicutaneous antigen challenge, cyclosporin A (CsA) in ethanol:olive oil (1:2) significantly reduced contact sensitivity reactions to dinitrofluorobenzene (DNFB). This immunosuppressive effect was no longer apparent when initial drug administration was delayed for several hours, or when a non-immunosuppressive cyclosporin derivative was applied. Attenuation of skin reactions was accompanied by significant reductions in T cells recognized by putative pan T cell (CT7) and T cytotoxic/suppressor cell (CT6) monoclonal antibodies, whilst there were also concomitant decreases in basophil infiltration. There was no reduction in epidermal Langerhans cells or in infiltrating mononuclear cells recognized by MSGp9 (mainly dendritic cells) in CsA-treated reaction sites. There was no apparent reduction in Ia antigen expression (staining with MSGp8) on intralesional inflammatory cells with CsA treatment. Whilst demonstrating the efficacy of topical CsA in contact sensitivity, our findings suggest that more than one mechanism may be operative in the suppression of these cutaneous inflammatory reactions.


Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.
Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.


[Automation of extraction in the determination of blood triglyceride].
A complete automation of the determination of triglycerides is described which replaces the manual extraction and the final determination with an autoanalyzer chain, based on the method of Royer et al. For the automation of triglyceride extraction, we have modified the sampler, by incorporating a magnetic stirrer under the sample table. The sample table has two rows of holes. The sera, which are taken from the inner row and diluted with sulphuric acid, are reacted quantitatively with the extraction reagent in the beakers of the outer row, which contain a magnetic follower. After stirring, the upper phase is quantitatively removed and the determination is started. The problem of phasing the individual steps of the analysis is thus solved.


What factors contribute to differences in the practice of peritoneal dialysis between Asian countries and the West?
To study variations in the practice of peritoneal dialysis within Asia and between Asia and the West, relevant information was collected through questionnaires from nephrologists in several Asian countries and by a literature search. Data indicate that economy significantly affects dialysis treatment rates. Peritoneal dialysis was often underutilized. The effect of Kt/V on survival was less obvious compared to the West in countries where peritoneal dialysis patient survival rates were high. More cost-effective dialysis regimes should be developed to increase dialysis treatment rates.


Plasma homocysteine concentrations in the acute phase after central retinal vein occlusion in a Chinese population.
To explore the relationship between total plasma homocysteine (tHcy) concentration and central retinal vein occlusion (CRVO) in the acute phase in a Chinese population. This was a matched case-control study, and participants were recruited between January 2008 and April 2012. The cohort included 68 consecutive patients with CRVO and 68 controls, matched for age and gender, aged 50 years and over. The total plasma homocysteine, vitamin B12 and folate levels and the presence of C677T MTHFR polymorphisms were analyzed in all patients and controls. Fasting venous blood samples were collected within three days after CRVO. There were no significant differences (p = 0.134) in mean plasma tHcy between CRVO patients (10.73 ± 3.21 µmol/l) and controls (9.99 ± 2.57 µmol/l), nor were there any statistically significant differences when subjects were categorized by ischemic and nonischemic CRVO. However, six patients (27.3%) in the ischemic group and three patients (6.5%) in the nonischemic group were found to have hyperhomocysteinemia (p = 0.018). There were no statistically significant differences in serum folate (p = 0.503) or vitamin B12 levels (p = 0.419) between CRVO patients (folate, 5.97 ± 2.06 ng/ml; vitamin B12, 411 ± 122 pg/ml) and controls (folate, 6.18 ± 1.42 ng/ml; vitamin B12, 427 ± 115 pg/ml). The prevalence of the homozygous genotype of the MTHFR C677T mutation was not significantly different in patients than in controls. We found no association between tHcy in the acute phase after CRVO and CRVO occurrence in a Chinese population, but hyperhomocysteinemia were associated with the development of CRVO.


Is it useful to add an anticholinergic treatment to beta 2-adrenergic medication in acute asthma attack?
The aim of our study was to determine whether the combination of an anticholinergic treatment with a beta 2-adrenergic medication is a more effective treatment for acute asthma attack than the two treatments individually. The association of salbutamol-ipratropium was compared to treatment with salbutamol and ipratropium alone. It was a prospective double-blind study in children with acute asthma attack, participating as outpatients. Their clinical history and characteristics of bronchial obstruction were recorded on a standard form. Afterwards, they were included in one of the three following study groups: group one, 100 micrograms/inh salbutamol; group two, 20 micrograms/inh ipratropium; group three, 100 micrograms/inh of salbutamol plus 20 micrograms/inh ipratropium. There were 40 patients in each group, with Tal score +/- 5 and PEF < 80% of the predicted value. They were evaluated at the beginning (0 min), and at 15, 30, 45, 60, 80, 100 and 120 min. Each patient was treated with two inhalations of the study medication and was then evaluated for variations in Tal score. The mean age was 7.3 years; Tal score was 5.6, 5.6 and 6.0 at 0 min (p > 0.05). Decrease in Tal score after 15 min meant p < 0.01 for salbutamol-ipratropium and salbutamol vs. ipratropium. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and at 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol. PEF at 0 min was 70.9%, 71.3% and 68.6% (p > 0.05) increasing after 15 min. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and p < 0.01 vs. ipratropium. At 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. A total 4.7 doses of salbutamol were needed to improve the asthma attack, 5.3 of ipratropium and 3.7 of salbutamol-ipratropium, with p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. We conclude that the combination of salbutamol and ipratropium is more effective than each medication alone in treating acute asthma attacks in pediatric patients.


The dual benefits of synchronized mating signals in a Japanese treefrog: attracting mates and manipulating predators.
In dense mating aggregations, such as leks and choruses, acoustic signals produced by competing male conspecifics often overlap in time. When signals overlap at a fine temporal scale the ability of females to discriminate between individual signals is reduced. Yet, despite this cost, males of some species deliberately overlap their signals with those of conspecifics, synchronizing signal production in the chorus. Here, we investigate two hypotheses of synchronized mating signals in a Japanese treefrog (Buergeria japonica): (1) increased female attraction to the chorus (the beacon effect hypothesis) and (2) reduced attraction of eavesdropping predators (the eavesdropper avoidance hypothesis). Our results from playback experiments on female frogs and eavesdropping micropredators (midges and mosquitoes) support both hypotheses. Signal transmission and female phonotaxis experiments suggest that away from the chorus, synchronized calls are more attractive to females than unsynchronized calls. At the chorus, however, eavesdroppers are less attracted to calls that closely follow an initial call, while female attraction to individual signals is not affected. Therefore, synchronized signalling likely benefits male B. japonica by both increasing attraction of females to the chorus and reducing eavesdropper attacks. These findings highlight how multiple selective pressures likely promoted the evolution and maintenance of this behaviour. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


[Patients with diagnostic challenging intestinal involvement of the endometriosis].
A considerable proportion of women with endometriosis have intestinal involvement of the endometriosis. Intestinal endometriosis (IE) often results in abdominal pain and thus mimics the symptoms of other bowel diseases, including colon cancer. As a consequence, some women with IE are initially referred to general surgery and treated under suspicion of colon cancer. This case report demonstrates the diagnostic challenges and describes the key symptoms of IE. Women with key symptoms should be referred to a gynaecological department for transvaginal ultrasonography. The optimal surgical treatment for IE is laparoscopically assisted bowel resection.


Protection against pertussis by Takeda's acellular pertussis vaccine: household contact studies in Kawasaki City, Japan.
To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 27 siblings (62.9%) not immunized with pertussis vaccine. On the other hand, 26 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.8%). The present study revealed an efficacy rate of 93.9% for Takeda's acellular pertussis vaccine.


Sowing seeds: transperineal implantation.
Prostate cancer, the second leading cause of male deaths in the United States, has increased by 126% since 1987 (Stephenson, 1998). Early diagnosis is attributed to public awareness and technologic advances. Multiple options for definitive treatment with equally positive outcomes dramatically influence the patient's decision-making process. One popular option for these patients is transperineal implantation of radioactive seeds into the prostate.


Longitudinal proximity effects in superconducting transition-edge sensors.
We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T{c} of the TES is current dependent and at fixed current scales as 1/L{2}. We have also found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 microm, 1450 times the mean-free path.


Tumor Suppressor Lzap Suppresses Wnt/β-Catenin Signaling to Promote Zebrafish Embryonic Ventral Cell Fates via the Suppression of Inhibitory Phosphorylation of Glycogen Synthase Kinase 3.
Wnt/β-catenin signaling controls various cell fates in metazoan development, and its dysregulation is often associated with cancer formation. However, regulations of this signaling pathway are not completely understood. Here, we report that Lzap, a tumor suppressor, controls nuclear translocation of β-catenin. In zebrafish embryos disruption of lzap increases the expression of chordin (chd), which encodes a bone morphogenetic protein (BMP) antagonist that is localized in prospective dorsal cells and promotes dorsal fates. Consistently, lzap-deficient embryos with attenuated BMP signaling are dorsalized, which can be rescued by overexpression of zebrafish lzap or bmp2b or human LZAP. The expansion of chd expression in embryos lacking lzap is due to the accumulation of nuclear β-catenin in ventral cells, in which β-catenin is usually degraded. Furthermore, the activity of GSK3, a master regulator of β-catenin degradation, is suppressed in lzap-deficient embryos via inhibitory phosphorylation. Finally, we also report that a similar regulatory axis is also likely to be present in a human tongue carcinoma cell line, SAS. Our results reveal that Lzap is a novel regulator of GSK3 for the maintenance of ventral cell properties and may prevent carcinogenesis via the regulation of β-catenin degradation.


Evaluation of the risk of aflatoxin contamination in fresh medicinal plants.
Based on experimental results of aflatoxin analysis as well as information from literature, this contribution discusses the likelihood of aflatoxin contamination in fresh medicinal plants. As cultivation and collection of medicinal plants in accordance with Good Agricultural and Collection Practice (GACP) and the local climatic conditions minimise aflatoxin contamination and, as fresh raw material is normally processed immediately, aflatoxin contamination of fresh medicinal plants from Central European countries is extremely unlikely. As a result of the risk-based approach to aflatoxin testing, 3 options are proposed depending on the origin of the material and the plant parts used: no testing, skip lot testing or routine testing.


A Multiple Logistic Regression Model Based on Gamma-Glutamyl Transferase as a Biomarker for Early Prediction of Drug-Induced Liver Injury in Vietnamese Patients.
The discovery of new biomarkers and the causality of drug-induced liver injury (DILI) is a major focus in modern medicine. Alcoholism is considered a risk factor for DILI. However, the extraction and assessment of alcohol history are difficult due to noncooperation by patients and intermittent management. Therefore, we conducted a case-control study of 1277 patients diagnosed with DILI according to the Roussel Uclaf Causality Assessment Method scale to evaluate gamma-glutamyl transferase (GGT) as a biomarker for predicting DILI in Vietnamese patients, where the proportion of alcoholism is quite high. Further, we built and validated a logistic regression model to predict the risk of DILI in hospitalized patients. The risk of DILI increased by 10% for 1 UI/L higher levels of GGT before prescription (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.01). A history of alcoholism was not a risk factor for DILI occurrence (OR, 1.83; 95%CI, 0.99-3.04; P = .057). A logistic regression model was successfully built and validated based on age; sex; initial levels of alanine aminotransferase, alkaline phosphatate, GGT, likelihood score of the suspected drug, and history of liver disease; the area under the receiver operating characteristic curve of the model was 0.883 (95%CI, 0.868-0.897). Our results thus suggest the necessity of exercising caution when prescribing to patients without a history of alcoholism but having high GGT levels. This model can be applied clinically to assess the risk of DILI before prescribing to reduce the risk of DILI in the patient.


Complex mixtures of air pollutants: characterizing the cancer risk of polycyclic organic matter.
Complex mixtures of polycyclic organic matter (POM) are used to illustrate the scientific problems and issues associated with characterizing the comparative risk of related complex mixtures. The complexity of mixtures in which the active components are not well characterized present special challenges, which include identifying the critical components of mixtures, their sources, and the appropriate biomarker(s) of exposure and dose; developing the appropriate experimental models for dose-response assessment; species extrapolation; and developing a scientific basis for predicting from one mixture to another. Strategies for addressing these issues include bioassay-directed chemical characterization of bioactive components of complex mixtures, apportionment methods to determine the source of biological activity and risk, DNA adduct methods to determine tissue exposure and target dose of mixtures, and comparative approaches to determining the relative similarity, potency, and risk of complex mixtures. Epidemiological data are available for humans exposed to POM from coke ovens, coal roofing tar, coal smoke, aluminum smelters, and cigarette smoke. These emissions are characterized and compared to POM from automotive emissions (diesel and gasoline), woodstove emissions, residential oil furnace emissions, and ambient air particles. The tumor potency and estimated cancer risks for these POM mixtures ranges over nearly three orders of magnitude.


Mice with Tak1 deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development.
Cleft palate represents one of the most common congenital birth defects in humans. TGFβ signaling, which is mediated by Smad-dependent and Smad-independent pathways, plays a crucial role in regulating craniofacial development and patterning, particularly in palate development. However, it remains largely unknown whether the Smad-independent pathway contributes to TGFβ signaling function during palatogenesis. In this study, we investigated the function of TGFβ activated kinase 1 (Tak1), a key regulator of Smad-independent TGFβ signaling in palate development. We show that Tak1 protein is expressed in both the epithelium and mesenchyme of the developing palatal shelves. Whereas deletion of Tak1 in the palatal epithelium or mesenchyme did not give rise to a cleft palate defect, inactivation of Tak1 in the neural crest lineage using the Wnt1-Cre transgenic allele resulted in failed palate elevation and subsequently the cleft palate formation. The failure in palate elevation in Wnt1-Cre;Tak1(F/F) mice results from a malformed tongue and micrognathia, resembling human Pierre Robin sequence cleft of the secondary palate. We found that the abnormal tongue development is associated with Fgf10 overexpression in the neural crest-derived tongue tissue. The failed palate elevation and cleft palate were recapitulated in an Fgf10-overexpressing mouse model. The repressive effect of the Tak1-mediated noncanonical TGFβ signaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting.


Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations.
Advances in molecular biology and recombinant DNA technology have led to the development of cytokines as therapeutic agents for a variety of disease states. The pharmacokinetic analysis of cytokines involves the understanding of analytical methods capable of detecting these agents in biological fluids and recognition of several factors which may have an impact on the cytokine concentration-time curves. Enzyme-linked immunosorbent assays (ELISA) have become the most common method of detection and commercial kits are available for a wide variety of cytokines. Monoclonal antibody products are sensitive, have minimal cross-reactivity and are relatively inexpensive when compared with high performance liquid chromatography (HPLC). However, the primary limitation of these assays is their inability to measure biologically active protein. Conversely, bioassays do measure a biological event (i.e. proliferation or cytotoxicity) but are generally not used for cytokine analysis because of their high cost, long assay completion time, lack of specificity, poor sensitivity and influence of environmental conditions on the outcome. The pharmacokinetic profile of recombinant cytokines is influenced by a number of variables: endogenous production, circulating soluble receptors and cell-associated receptors, immunocompetence and antibody production against the cytokine all may influence the disposition of the agent. Thus, pharmacokinetic modelling of cytokines may involve complex models capable of characterising these nonlinear processes and resulting effects. The route of administration is an important variable since cytokines administered by subcutaneous injection may be partially metabolised by proteases present in the subcutaneous tissue. Other methods to simplify cytokine delivery are being actively investigated and include formulations for inhalation, topical and oral administration. A variety of cytokines (including interferon-alpha, interleukin-6 and tumour necrosis factor) are capable of inhibiting cytochrome P450 hepatic enzymes and, therefore, possess the potential to cause drug-cytokine interactions. Inhibition has been demonstrated in several in vitro systems and animal models, although clinical data are currently limited. An increased understanding of the many factors which can alter the analysis and pharmacokinetics of cytokines is essential to the design of optimal dosage regimens.


Adverse events in hospitals: the patient's point of view.
The publication of the report "To err is human: building a safer system" by the Institute of Medicine incited a profuse research addressing improvements in healthcare safety. However, there is still little acknowledgement of the key role of the patient in preventing adverse events of medical care. The aim of this review is to analyse and compare studies about patient's perception and opinion about care safety in hospitals. We searched 10 databases (EMBASE, MEDLINE, PsychINFO, SCOPUS, Science Citation Index Expanded, Social Science Citation, IME, Sociological Abstracts, LILACS and The Cochrane Library) to identify articles and reports on patient's safety perception published between 1989 and 2006. From the 699 articles, 18 were selected: eight determined the frequency of experiences related to adverse events and the safety perception reported by patients, seven focused on the impact of the adverse events regarding the communication to the patient, and three included patient's opinions about the management and disclosure of adverse events and proposals to prevent them. The incidence of adverse events reported by patients was similar to that estimated by other procedures. The patient's concept of adverse events was different from that of the physician. The quality of communication from the physician influenced the patient's perception of adverse events, and the majority wanted adverse events to be disclosed. Patients emphasised emotional consequences of the adverse events. The majority supported system modifications to prevent adverse events and to sanction the physicians when an adverse event occurs.


The complete remission concept.
The presence of esophageal lesions and gastroesophageal reflux disease (GERD) symptoms do not coincide in some patients: some individuals suffer from the symptoms of GERD but have no evidence of GERD at endoscopy; while conversely, some with endoscopic evidence of GERD do not experience symptoms. In order to combine both healing of esophageal lesions and the presence of symptoms when measuring treatment efficacy, the concept of complete remission has been redefined to include both parameters. Until recently, an effective means of measuring GERD symptoms and response to therapy had been lacking. The symptomatic reflux questionnaire ReQuest(TM) was therefore developed; it is a validated, self-administered, hierarchical, dimension-oriented scale to assess response of a broad range of symptoms to treatment. It measures the frequency and intensity of seven symptom dimensions: acid complaints; upper abdominal complaints; lower abdominal complaints; nausea; sleep disturbances; other complaints; and general well-being (intensity only). ReQuest(TM) has recently been combined with an adaptation of the Los Angeles classification for endoscopic measurement of GERD, thus linking the assessment of symptom relief and healing of esophageal lesions. The new ReQuest(TM)/ LA-classification enables the detailed clinical characterization of GERD patients at any stage and accurate assessment of treatment outcome by a single global measure.


[International outcomes from attempts to implement a clinical decision support system in gastroenterology].
This study aimed at describing the recent experience acquired with the implementation and use of clinical decision support system in gastroenterology in order to determine the level of development, tests used and advantages that such a system can offer to the medical practice. A search in the PubMed, LILACS and ISI Web of Knowledge databases for studies in decision-making support systems in gastroenterology including original papers produced from 2005 to 2010 was performed. A total of 104 scientific papers were retrieved initially. These were analyzed using inclusion and exclusion criteria, thus yielding nine studies for further analysis. The clinical decision support system analyzed in the present study showed a great variety of clinical problems regarding the investigation of a disease and the determination of a diagnosis. Eighty-nine per cent of the studies showed experimental models for clinical decision support system development. Seventy-eight per cent of the studies described the outcomes obtained with artificial intelligence technique. Two studies compared the clinical decision support system performance with that of a doctor, and only one research work described a controlled study evidencing improvements in the medical practice. The studies analyzed showed evidence of potential benefits that clinical decision support system can bring to the clinical practice. However, further controlled studies performed in medical day-to-day conditions and environment should be performed in order to provide more clear evidence of the usefulness of clinical decision support system in the medical practice.


Corticosteroid-responsive pulmonary toxicity associated with fludarabine monophosphate: a case report.
Fludarabine monophosphate is an effective drug for the treatment of lymphoid malignancies. Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. Chest X-ray revealed bilateral pneumofibrotic changes and chest CT showed bilateral diffuse interstitial changes with fibrotic alterations. No evidence of infectious agents was noted. The patient had a reduced carbon monoxide transfer factor (45%). Her symptoms and radiographic findings resolved following treatment with prednisolone. The literature contains several cases of fludarabine-associated interstitial pulmonary toxicity that responded to steroid therapy. Fludarabine-induced pulmonary toxicity is reversible with cessation of the drug and administration of glucocorticosteroids. None declared.


Regenerative Rehabilitation for Stroke Recovery by Inducing Synergistic Effects of Cell Therapy and Neurorehabilitation on Motor Function: A Narrative Review of Pre-Clinical Studies.
Neurological diseases severely affect the quality of life of patients. Although existing treatments including rehabilitative therapy aim to facilitate the recovery of motor function, achieving complete recovery remains a challenge. In recent years, regenerative therapy has been considered as a potential candidate that could yield complete functional recovery. However, to achieve desirable results, integration of transplanted cells into neural networks and generation of appropriate microenvironments are essential. Furthermore, considering the nascent state of research in this area, we must understand certain aspects about regenerative therapy, including specific effects, nature of interaction when administered in combination with rehabilitative therapy (regenerative rehabilitation), and optimal conditions. Herein, we review the current status of research in the field of regenerative therapy, discuss the findings that could hold the key to resolving the challenges associated with regenerative rehabilitation, and outline the challenges to be addressed with future studies. The current state of research emphasizes the importance of determining the independent effect of regenerative and rehabilitative therapies before exploring their combined effects. Furthermore, the current review highlights the progression in the treatment perspective from a state of compensation of lost function to that of a possibility of complete functional recovery.


The symptoms and recognition of post-traumatic stress reactions.
The three most common clinical sequelae of trauma have been outlined above. However, the vast majority of cases will produce a normal reaction, which would not fulfil any of the diagnostic criteria. Overall, therefore, clinically significant traumatic responses are rare in the military environment, and for the most part short lived. For the conditions that are not self-limited, there are effective treatment options available which will be outlined later in this series.


Determinants of insulin resistance in infants at age 1 year: impact of gestational diabetes mellitus.
The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM. In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR). HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039). In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.


Pneumoencephaly following lumbar puncture in association with an ethmoidal osteoma and porencephalic cyst.
A 50-year-old woman developed pneumoencephaly following a CSF examination for evaluation of dysequilibrium. Previous investigations had demonstrated a number of high signal T2 lesions on MRI of the brain. In addition, there was what was thought to be an asymptomatic cystic lesion in the left frontal lobe communicating with the lateral ventricle. After the lumbar puncture she developed extensive pneumoencephaly with pressure dilatation of the ventricular system. There was CSF rhinorrhoea. Further CT scans showed an osteoma in the ethmoidal air sinus with protrusion into the cystic area. This was the site of both the CSF leak and air entry. Caution must be taken when considering a CSF examination in the presence of either a presumed asymptomatic porencephalic cyst or ethmoid osteoma.


A biological sequence comparison algorithm using quantum computers.
Genetic information is encoded as linear sequences of nucleotides, represented by letters ranging from thousands to billions. Differences between sequences are identified through comparative approaches like sequence analysis, where variations can occur at the individual nucleotide level or collectively due to various phenomena such as recombination or deletion. Detecting these sequence differences is vital for understanding biology and medicine, but the complexity and size of genomic data require substantial classical computing power. Inspired by human visual perception and pixel representation on quantum computers, we leverage these techniques to implement pairwise sequence analysis. Our method utilizes the Flexible Representation of Quantum Images (FRQI) framework, enabling comparisons at a fine granularity to single letters or amino acids within gene sequences. This novel approach enhances accuracy and resolution, surpassing traditional methods by capturing subtle genetic variations with precision. In summary, our approach offers algorithmic advantages, including reduced time complexity, improved space efficiency, and accurate sequence comparisons. The novelty lies in applying the FRQI algorithm to compare quantum images in genome sequencing, allowing for examination at the individual letter or amino acid level. This breakthrough holds promise for advancing biological data analysis and enables a more comprehensive understanding of genetic information.


[ASSESSMENT OF NOSOLOGICAL STRUCTURE ASSOCIATED WITH ANEMIC SYNDROME].
The anemic syndrome at the stage of primary health care delivery on an outpatient basis is a risk factor for an unfavorable outcome in patients with chronic somatic diseases, primarily cardiovascular and oncological pathologies. In order to understand the true prevalence of anemia among outpatients it is necessary to improve the registration of patients with this disease. Aim: to analyze the features of managing patients with anemia in the primary health care system using a computerized patient monitoring system. The study included 1498 patients aged 18 to 80 who were under dispensary observation by family physicians. For the analysis of the medical records, a computer program developed by the authors "Monitoring system for patients with anemic syndrome" was used. The structure of morbidity in two selected areas of the outpatient department in the context of the main classes of diseases of ICD-10 is analyzed. According to the analysis of the medical records carried out using the program developed by us, anemia was recorded in 208 patients (13.89%), while in the analysis using the computer register according to the WHO criteria, 500 people had anemic syndrome (33.38%), which indicates the underdiagnosis of this pathological condition and the need to direct the efforts of healthcare organizers to the early revealing of patients with anemia.


Calcaneal fractures: what the surgeon needs to know.
The calcaneus is an uncommonly fractured bone that plays a critical role in foot biomechanics, weight-bearing, and the ability to wear a shoe. The radiologist acts as a consultant during screening, operative planning, and follow-up imaging of these often complex injuries. Effective communication between radiologist and surgeon requires an understanding of calcaneal anatomy, goals of surgical reduction, and factors that affect patient management and outcomes. In the following pictorial review we will discuss radiologic screening/classification/characterization and their correlation with surgical management and patient morbidity.


Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug-Metabolizing Enzymes as a Response to Redox Alteration.
The lumen of the endoplasmic reticulum (ER) provides an oxidizing environment to aid in the formation of disulfide bonds, which is tightly regulated by both antioxidant proteins and small molecules. On the cytoplasmic side of the ER, cytochrome P450 (P450) proteins have been identified as a superfamily of enzymes that are important in the formation of endogenous chemicals as well as in the detoxication of xenobiotics. Our previous report described oxidative inhibition of P450 Family 4 enzymes via oxidation of the heme-thiolate cysteine to a sulfenic acid (-SOH) (Albertolle, M. E. et al. (2017) J. Biol. Chem. 292, 11230-11242). Further proteomic analyses of murine kidney and liver microsomes led to the finding that a number of other drug-metabolizing enzymes located in the ER are also redox-regulated in this manner. We expanded our analysis of sulfenylated enzymes to human liver and kidney microsomes. Evaluation of the sulfenylation, catalytic activity, and spectral properties of P450s 1A2, 2C8, 2D6, and 3A4 led to the identification of two classes of redox sensitivity in P450 enzymes: heme-thiolate-sensitive and thiol-insensitive. These findings provide evidence for a mammalian P450 regulatory mechanism, which may also be relevant to other drug-metabolizing enzymes. (Data are available via ProteomeXchange with identifier PXD007913.).


[Role of preoperative ultrasonography in evaluating early cervical metastasis in patients with differentiated thyroid carcinoma].
To evaluate the role of preoperative ultrasonography in detecting early cervical lymph node metastasis in differentiated thyroid carcinoma. Data were reviewed retrospectively from medical records between July 2003 and July 2005, in which patients were divided into 2 groups: group A (study group): 51 (55 sides) patients of differentiated thyroid carcinoma patients with impalpable node but with ultrasonic positive nodal metastasis; group B (control group): 57 (64 sides) patients with preoperative palpable cervical lymph nodes. All patients had been undergone modified neck dissection. The preoperative ultrasonographic results and the preoperative pathologic finding had been compared in group A. In 51 patients (55 sides of preoperative positive ultrasonography 49 sides had been demonstrated cervical lymph nodes metastasis pathologically. The sensitivity of ultrasonography was 89.1%. Ultrasonography detected cervical lymph node believed to be uninvolved by physical examination in 41.2% of patients. 65.5% of the cervical lymph metastasis was multilevel and the most frequent involvement site was middle neck and the involvement rate was 70.9% in ultrasonography. 75.5% of the cervical lymph metastasis was multilevel and the most frequent involvement site was level Ill (65.3%) in pathologic finding. Preoperative ultrasonograpy is a mainstay in detecting cervical lymph nodes metastasis in thyroid cancer patients. It can detect the early cervical lymph node metastasis and localize the position of the cervical metastasis. All the thyroid cancer patients should undergo preoperative ultrasonography and the extent of the neck dissection relies on the preoperative ultrasonic finding of the neck.


Enhanced salt tolerance of euryhaline tadpoles depends on increased Na+, K+-ATPase expression after salinity acclimation.
Understanding physiological responses and osmoregulatory mechanisms for dealing with salinity stress is essential to clarify how amphibians living in coastal areas adapt to fluctuating salinity levels. Euryhaline species are rare among reported tadpole species inhabiting saline habitats, and few studies addressed the osmoregulatory mechanisms. We quantified the effects of salinity acclimation on survival, osmolality, water content, ion concentration, and gill Na+, K+-ATPase (NKA) expression of euryhaline tadpoles of Fejervarya cancrivora, to examine time-course changes of osmoregulatory responses of tadpoles subjected to salinity stress and how osmoregulatory mechanisms were involved in the process. Acclimation to 10 ppt for 24 h increased tadpole survival of F. cancrivora in 15 ppt, and it activated osmoregulatory mechanisms such as increase in NKA expression, which enabled them to maintain a stable osmolality below that of the surrounding media, to reach lower sodium and chloride concentrations of body fluid, and to modulate dehydration at higher salinities. The minimum required acclimation period is shorter than that reported previously on this species and non-euryhaline tadpoles. This study highlights that these physiological mechanisms are ecologically relevant and critical for tadpoles living in coastal brackish waters, improving their survival in coastal microhabitats with highly variable salinity levels.


[The clinical case of successful combined treatment of refractory arterial hypertension. Case report].
In recent years, there has been an increase of patients with arterial hypertension, one of the variants of which is refractory arterial hypertension. This unfavorable clinical variant of the course of hypertension worries clinicians, due to the higher risk of developing cardiovascular complications, realizing the need for a better control of blood pressure. The presented clinical case demonstrates the successful combined treatment of refractory hypertension using antihypertensive therapy and renal denervation.


Effects of hypophysectomy and metyrapone on the catecholamine content and volumes of adrenaline- and noradrenaline-storing cells in the rat adrenal medulla.
Using morphometric analysis and high-pressure liquid chromatography with electrochemical detection of catecholamines the volumes of adrenaline-storing (A) and noradrenaline-storing (NA) cells and the adrenaline and noradrenaline contents of adrenal glands of normal and age-matched hypophysectomized rats were determined and compared. Some hypophysectomized rats were also administered 150 mg metyrapone/kg daily for a 4-week period. Hypophysectomy resulted in an increase in noradrenaline storage in adrenal glands. This was more marked in hypophysectomized animals not treated with metyrapone even though the combination of metyrapone and hypophysectomy resulted in a reduction of blood corticosterone concentration to only approximately 6% normal. There was no evidence of a change in proportion of A and NA cells in the adrenal medulla of hypophysectomized rats or hypophysectomized animals treated with metyrapone and it is concluded that the changes in amine concentrations and proportions observed reflect an increase in the storage of noradrenaline in A cells as a consequence of less efficient methylation of noradrenaline after hypophysectomy. The findings also showed that the left adrenal gland and medulla was usually slightly larger and had a greater catecholamine content and slightly higher proportion of NA cells than the right adrenal gland. During the period of the experiment (animals aged 6-15 weeks) there was an increase in the concentration of both adrenaline and noradrenaline in the normal adrenal glands. In normal Sprague-Dawley rats weighing 140 and 400 g the adrenal medulla accounted for some 5% of adrenal volume; this increased to 13% after hypophysectomy; A and NA cells together accounted for 50-60% of the volume of adrenal medulla.


Short-term climate change influence on surface water quality impacts from agricultural activities.
Climate change is a global phenomenon that directly affects agriculture by altering crop yield, nutritional quality, pests, and plant diseases. The North Aegean Basin located in Turkey has considerable agricultural importance due to its fertile soils. Agricultural activities have increased significantly and uncontrollably in the last decade, resulting in dramatic changes in nitrate and phosphorus levels in surface water within the watershed. Changes in climatic conditions have the potential to impact the quantity and quality of water resources. Best management practices (BMPs) are presently utilized as a planning tool to enhance the quality of water resources. To develop policies in this regard, it is necessary to evaluate the effectiveness of BMPs. To this end, this study aims to investigate the potential effect of climate change on the surface water quality of the North Aegean Basin. For the period between 2010 and 2030, global climate data retrieved from Concentration Pathway (RCP) scenarios 4.5 and 8.5 and regionally downscaled were used to feed the Soil and Water Assessment Tool (SWAT) model. The various potential BMP scenarios were developed and simulated in the hydrological model by considering the effects of climate change. The RCP4.5 scenario reduced the precipitation by 15.11%, while the RCP8.5 scenario reduced the precipitation by 10.97%. Decreased precipitation also affected the runoff and the nutrient loads and concentrations. As a result of the RCP4.5 simulation, TP and TN concentrations increased by 24.42% and 58.45%, respectively, in the IST_KEN014 station. Improvements were observed in TN and TP concentrations with the effect of applied BMP simulations. Also, the results revealed that the applied BMP scenarios may contribute to considerable reductions in nutrient loads. Considering the RCP4.5 scenario, BMPs reduced TN loads in the basin by 2.42-10.97%, while reducing TP loads by around 3.60-16.81%. Considering the RCP8.5 scenario, the BMPs reduced the TN loads in the basin between 2.21 and 10.04%, while they reduced the TP loads between 3.57 and 16.67%.


Is continuous venovenous hemofiltration effective against severe acute pancreatitis?
Our aim was to investigate the efficacy of continuous venovenous hemofiltration (CVVH) in treating severe acute pancreatitis (SAP). A literature search was performed using PubMed (1992-present), and all studies investigating the efficacy of CVVH in treating SAP were included. Four comparative studies and seven case series comprising a total of 354 patients were included. The overall mortality rate of patients receiving CVVH was 20% (55/275). A decreased mortality rate and decreased serum cytokine levels were reported in the CVVH groups in only two studies. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of CVVH varied among the studies, and the impact of these parameters on the efficacy of CVVH was poorly reported. High-volume CVVH, when started early, was demonstrated to be more effective in eliminating cytokines in only one study. After the application of CVVH, the patient conditions started to improve between the 6th and 72nd hours. In conclusion, no solid clinical evidence has proven the efficacy of CVVH in treating SAP. High-volume CVVH that is started early and sustained for at least 72 h may be adopted to investigate the efficacy of CVVH for treating SAP.


Gradientless temperature-driven rotating motor from a double-walled carbon nanotube.
Rotation of the inner tube in a double-walled carbon nanotube (DWCNT) system with a fixed outer tube is investigated and found to be inducible by a relatively high uniform temperature (say, 300 K). We also found the mechanism of a gradientless temperature-driven rotating motor lies in the inner tube losing its geometric symmetry in a high-temperature field. This mechanism can be taken as a guide for designing a motor from such a bi-tube system. Using a computational molecular dynamics (CMD) approach and the adaptive intermolecular reactive empirical bond order (AIREBO) potential, the dynamic behavior of a bi-tube system subjected to uniformly distributed temperature is studied. In particular, the effects of environmental temperature, boundary conditions of the outer tube, and intertube gap on the dynamic behavior of the bi-tube system are investigated. Numerical examples show that a bi-tube system with the inner tube having 0.335 nm of interlayer gap produces the highest rotational speed.


Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates.
Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.1.351 (beta or β) variant. Reciprocal ID 50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the β variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost β-specific reciprocal ID 50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the β variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations. mRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.


The Direct-Indirect Technique for Composite Restorations Revisited.
In the direct-indirect composite technique, composite is applied to a nonretentive tooth preparation (eg, a noncarious cervical lesion or a veneer/inlay/onlay preparation) without any bonding agent, sculpted to a primary anatomic form, and light-cured. The partially polymerized restoration is then removed from the preparation and finished and tempered extraorally chairside. The finished inlay is bonded to the preparation using a resin-based luting agent. Advantages of this technique include enhanced physical and mechanical properties afforded by the extraoral chairside tempering process because of increased monomer conversion, and greater operator control over the final marginal adaptation, surface finishing and polishing, and anatomy of the restoration, given that these elements are defined outside of the patient's mouth. The direct-indirect approach also affords enhanced gingival health and patient comfort. This article presents a clinical case in which the direct-indirect composite technique was used to restore three noncarious cervical lesions on the same quadrant on an adult patient. Clinical steps and tips for success are offered. The authors also present scanning electron microscope and atomic force microscope images showing the excellent marginal fit obtained with the direct-indirect composite technique.


Efficacy of living donor liver transplantation for patients with methylmalonic acidemia.
Application of liver transplantation to methylmalonic acidemia (MMAemia) is controversial because MMAemia is caused by a systemic defect of methylmalonyl-CoA mutase. The clinical courses of seven pediatric patients with MMAemia undergoing living donor liver transplantation (LDLT) were reviewed. Serum and urinary methylmalonic acid (MMA) levels were found to be significantly decreased after LDLT, whereas serum and urinary MMA levels did not return to normal in any patient. One patient died of sepsis 44 days after LDLT. The other six patients are currently doing well. All patients had preoperative history of acute metabolic decompensation and/or metabolic stroke. However, no episode of acute metabolic decompensation or metabolic stroke was observed postoperatively in any surviving patients. In the preoperative period, all patients showed lethargy and cognitive deficit, both of which were eradicated after LDLT in all surviving patients. Preoperatively, all patients were subjected to dietary protein intake restriction and tube feeding, and were administered several metabolism-correcting medications. The metabolism-correcting medications being administered remained mostly unchanged after LDLT, whereas protein restriction was liberalized and tube feeding became unnecessary in all surviving patients. In addition, physical and neurodevelopmental growth delay remained in all surviving patients during the observation period, which ranged from 4 to 21 months with a median of 10.5 months.


Assessment of TLR3 and MDA5-Mediated Immune Responses Using Knockout Quail Fibroblast Cells.
Toll-like receptor 3 (TLR3) and melanoma differentiation-associated gene 5 (MDA5) are double-stranded RNA (dsRNA)-recognizing receptors that mediate innate immune responses to virus infection. However, the roles played by these receptors in the pathogenesis of avian viruses are poorly understood. In this study, we generated TLR3 and MDA5 single knockout (SKO) and TLR3-MDA5 double knockout (DKO) quail fibroblast cells and examined dsRNA receptor-mediated innate immune responses in vitro. The knockout cells were then stimulated with a synthetic dsRNA ligand polyinosinic:polycytidylic acid [poly(I:C)] or influenza A virus. Endosomal stimulation of TLR3 by adding poly(I:C) in cell culture media or cytoplasmic stimulation of MDA5 by transfecting poly(I:C) resulted in significant increases of TLR3, MDA5, interferon (IFN) β, and interleukin 8 gene expression levels in wild type (WT) cells. Endosomal poly(I:C) treatment induced a higher level expression of most of the genes tested in MDA5 SKO cells compared with WT cells, but not in TLR3 SKO and DKO cells. Cytoplasmic transfection of poly(I:C) led to significant upregulation of all four genes in WT, TLR3 SKO, and MDA5 SKO cells at 8 hr posttransfection and negligible gene expression changes in TLR3-MDA5 DKO cells. Upon infection with a strain of influenza virus with compromised IFN antagonistic capability, WT cells produced the highest amount of biologically active type I IFN followed by TLR3 SKO and MDA5 SKO cells. DKO cells did not produce detectable amounts of type I IFN. However, the IFN did not induce an antiviral state fast enough to block virus replication, even in WT cells under the experimental conditions employed. In summary, our data demonstrate that TLR3 and MDA5 are the key functional dsRNA receptors in quail and imply their coordinated roles in the induction of innate immune responses upon virus infection.


Perfluorinated alkyl substances: Sewage treatment and implications for receiving waters.
This study comprises a detailed analysis of data for perfluorooctanesulfonic acid (PFOS), and perfluorooctanoic acid (PFOA) for over 600 wastewater treatment works effluents (WwTW) as well as samples upstream and downstream of each discharge of effluent into its receiving water. This has allowed an investigation of not only the effectiveness of removal of the perfluoroalkyl substances (PFAS) compounds during wastewater treatment but also implications for compliance with the environmental quality standard (EQS) set for PFOS under the Water Framework Directive. It is shown that effluents contain concentrations of PFOS that exceed the annual average EQS by a factor between 1.1-fold and 40-fold. The corresponding factors for PFOA are between 2-fold and 22-fold. The presence of high concentrations upstream, means that between a quarter and a third of individual effluents are found to reduce the concentration of fluorocarbons in the river downstream of the discharge point. The elevated concentrations upstream of the studied wastewater treatment works suggest inputs of these perfluoro compounds into the aquatic environment are ubiquitous and therefore difficult to address from simply setting permit conditions for individual WwTW. The freshwater EQS set for PFOS is based on several worst-case accumulation coefficients and large safety factors, which, when combined, result in a sub ng/L EQS. Consequently, the use of the biota derived quality standard may be a more realistic measure of environmental risk. It may be prudent, to assess the effectiveness of controls implemented in the last few years before considering widespread end-of-pipe treatment.


Microbial diversity and activity through a permafrost/ground ice core profile from the Canadian high Arctic.
Culture-dependent and culture-independent methods were used in an investigation of the microbial diversity in a permafrost/massive ground ice core from the Canadian high Arctic. Denaturing gradient gel electrophoresis as well as Bacteria and Archaea 16S rRNA gene clone libraries showed differences in the composition of the microbial communities in the distinct core horizons. Microbial diversity was similar in the active layer (surface) soil, permafrost table and permafrost horizons while the ground ice microbial community showed low diversity. Bacteria and Archaea sequences related to the Actinobacteria (54%) and Crenarchaeota (100%) respectively were predominant in the active layer while the majority of sequences in the permafrost were related to the Proteobacteria (57%) and Euryarchaeota (76%). The most abundant phyla in the ground ice clone libraries were the Firmicutes (59%) and Crenarchaeota (82%). Isolates from the permafrost were both less abundant and diverse than in the active layer soil, while no culturable cells were recovered from the ground ice. Mineralization of [1-(14)C] acetic acid and [2-(14)C] glucose was used to detect microbial activity in the different horizons in the core. Mineralization was detected at near ambient permafrost temperatures (-15 degrees C), indicating that permafrost may harbour an active microbial population, while the low microbial diversity, abundance and activity in ground ice suggests a less hospitable microbial habitat.


[Study of correlations between antibiotics prescriptions and guidelines in a neonatal intensive care unit].
The increasing use of wide spectrum antibiotics has been reported to be associated with a greater prevalence of multi-resistant bacteria. The aims of this study were to survey the use of antibiotics and to evaluate the correlations between patterns of prescription of antibiotics and prescription guidelines in a neonatal intensive care unit. In this 6-month study, all newborns admitted to the NICU and treated with antibiotics were included. Data regarding criteria of antibiotic prescription, length of treatment, and criteria of withdrawing treatment were collected. The correlation between prescriptions and guidelines was evaluated a posteriori by a non-prescriber physician. One hundred and sixteen newborns were included, of whom nine had received antibiotics on more than one occasion. Mean gestational age was 33.5 weeks. In 82% of cases, the reason for hospitalisation was respiratory distress syndrome. Patients received systemic antibiotics for primary infection (78%), nosocomial infection (17%) and postsurgical prophylaxis (5%). Suspected foeto-maternal infections (SFMI) were the dominant features of primary infection (96%). In 49% of cases, suspected infection was not proven and justified withdrawal of treatment within 3 days. Sixty percent of nosocomial infections occurred in newborns with gestational ages of less than 28 weeks. Bacterial criteria were decision-making factors only in nosocomial infections. An absence of observance of guidelines occurred in 9% of treated newborns, and in most cases involved excessive length of treatment. These results show: (1) the majority of antibiotic prescriptions were for not proven SMFI; (2) a low rate of nosocomial infections; (3) the predominance of nosocomial infections in premature newborns; (4) less than 10% of non-observance of guidelines. It appears necessary to develop more precise guidelines to limit antibiotic use and to evaluate them regularly.


Trans-scleral diode laser cyclophotocoagulation for refractory glaucoma after high-risk penetrating keratoplasty.
To analyze the intraocular pressure reduction, number of anti-glaucoma medications needed, and post-operative complications of trans-scleral diode laser cyclophotocoagulation (DCPC) in patients with high-risk penetrating keratoplasty (PKP) and secondary refractory glaucoma. Prospective interventional, longitudinal, non-comparative series of cases, including 16 eyes of 15 patient's post-PKP on maximal anti-glaucoma medical therapy with intraocular pressures above 22 mmHg. All patients received 18 shots, 360° peri-limbal (avoiding the long posterior ciliary nerves and arteries at 3 and 9 o'clock positions) of trans-scleral DCPC (2000 mW, time: 2.0 s/shot). There was a 55.5 % reduction (total of 14.0 mmHg) of the mean pre-operative IOP (31.5 mmHg) after the first diode laser application (p = 0.0020). Re-treatment was required in 31.2 % of eyes over a mean period of 10.7 months. In these five eyes, the mean pre-operative IOP was 40.4 mmHg, which decreased to 15.0 mmHg post-therapy, and a mean IOP reduction of 25.4 mmHg (p = 0.0218). There was a 51.0 % reduction in the mean number of medications used after the first, and a 57.1 % reduction after a second laser application. The incidence of failure (IOP ≥ 22 mmHg or need of additional medical therapy) from initial intervention to loss of follow-up was 1.3 % per person-month. DCPC effectively reduces the intraocular pressure and the number of anti-glaucoma medications with few complications in patients after high-risk PKP and secondary glaucoma. Only, one-third of the eyes needed a second intervention to control the intraocular pressure. Post-DCPC complications were limited to phthisis bulbi and endothelial dysfunction, one eye each. Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct.


Combined octreotide and insulin therapy in acromegaly.
To describe an unusual treatment strategy for certain patients with both acromegaly and insulin-requiring diabetes. We present a case history of a man with a pituitary adenoma and diabetes mellitus and chronicle his response to various treatment modalities. Acromegaly, a disease state with excess growth hormone (GH) and insulin-like growth factor-I, is associated with carbohydrate intolerance. Octreotide, a somatostatin analogue, is used in the treatment of acromegaly to lower GH levels. Despite effective lowering of GH levels, certain patients with acromegaly have persistent or even worsening carbohydrate intolerance and may require insulin therapy. Such a regimen would necessitate five or more injections per day. We describe a 51-year-old man who was diagnosed with a GH-producing pituitary adenoma in 1987. Despite transsphenoidal resection, frontal craniotomy, and radiation therapy, symptoms and increased levels of GH persisted. The patient was diagnosed with diabetes mellitus in August 1989 and treated with glipizide. Because of persistently increased GH levels, he was treated with octreotide. His glycohemoglobin level increased to 21% despite use of maximal doses of glipizide. The patient refused insulin therapy because of his objection to numerous daily injections. Despite adjustments in diet and exercise, glycemic control remained poor. As a trial, we thus attempted combining octreotide and regular insulin in the same syringe and administering the medications in a single subcutaneous injection. No precipitate formation was evident, and he had no adverse effects. Glucose control improved, and the glycohemoglobin level was lower but still elevated. GH levels remained at less than 5 ng/mL. His symptoms of acromegaly were unchanged, but his overall attitude and energy level improved. The efficacy of the individual components of this treatment was demonstrated in the combination of insulin and octreotide. The combined administration of insulin and octreotide has limited application in patients with acromegaly and insulin-requiring diabetes mellitus.


Using media in rural clerkships.
To enhance the educational value of rural clerkships for health professions students, the Biomedical Communications Division of the University of Nebraska Medical Center explored ways of providing instructional media to off-campus training sites. Faculty and community hospitals in rural areas were surveyed to identify appropriate topics. Videocassettes and slide-tape packages were previewed, evaluated, and purchased when acceptable. The packages were stored at Biomedical Communications. Off-campus faculty and students were encouraged to order media for use during preceptorships, but few took advantage of the opportunity. The greatest use of media occurred when packages were made available on-campus and students were encouraged to view them before or after rural clerkships.


Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas.
Epidermal growth factor receptor (EGFR) is an important therapeutic target and a poor prognosis factor in head and neck squamous cell carcinoma (HNSCC). The aim of the study was to analyze EGFR expression and KRAS and EGFR mutational status and to correlate it with treatment response to anti-EGFR therapy combined with radiotherapy in 29 patients with advanced head and neck squamous cell carcinomas (HNSCC).EGFR gene expression normalized to GAPDH and EGFR variant type III (EGFRvIII) was detected in tumor tissue using real time reverse transcription -PCR. The mutational status of the EGFR and KRAS genes was investigated by real time PCR with sequence specific primers.Gene expression median values were 3.1x10(8) GAPDH gene copies per µg of RNA, and 8x10(6) EGFR gene copies per µg of RNA. The median EGFR/GADPH ratio reached 0.14. Patients, who achieved complete response after Cetuximab combined with radiotherapy, had significantly higher expression of the EGFR gene in tumors than patients with partial remission or patient without treatment response. An EGFRvIII mutation was found in 20.7 % of patients and no association was found between this mutation and treatment response. 27 patients (93.1 %) had an EGFR gene wild type tumor, and deletion in exon 19 was found in two patients with a poor clinical outcome. Most of the patients (82.8%) had a KRAS wild type tumor; a p.Gly12Cys was found in three patients and a p.Gly12Val mutation in one. Presence of a p.Gly12Val mutation in the KRAS gene was associated with an absence of response to treatment. Our data suggest that KRAS mutation (p.Gly12Val) and somatic EGFR mutation located in exon 19 may contribute to the limited clinical response to therapy with cetuximab + radiotherapy. Higher EGFR gene expression serves as an independent indicator of good clinical response to EGFR-targeted therapy + radiotherapy.


Evolved Gas Analysis-Mass Spectrometry to Identify the Earliest Organic Binder in Aegean Style Wall Paintings.
An organic binder was identified in the painted fragments from the Canaanite palace of Tel Kabri, Israel. Recently dated to the late 18th century B.C.E. by 14 C, Tel Kabri is the most ancient of the Eastern Mediterranean sites in which Aegean style paintings have been found. The application of pigments was suspected to be using an organic binding medium, particularly for the Egyptian Blue pigment. Samples of blue paint were examined using evolved gas analysis-mass spectrometry (EGA-MS) in order to overcome the analytical challenges imposed by highly degraded aged proteinaceous materials. Egg was identified as the binder based on the presence of hexadecanonitrile and octadecanonitrile, confirming the use of a secco painting technique. Lysozyme C from Gallus gallus was detected by proteomics analysis, confirming the presence of egg. To our knowledge, this is the earliest use of egg as a binder in Aegean style wall paintings.


Error-Based Observer of a Charge Couple Device Tracking Loop for Fast Steering Mirror.
The charge couple device (CCD) tracking loop of a fast steering mirror (FSM) is usually used to stabilize line of sight (LOS). High closed-loop bandwidth facilitates good performance. However, low-rate sample and time delay of the CCD greatly limit the high control bandwidth. This paper proposes an error-based observer (EBO) to improve the low-frequency performance of the CCD tracking system. The basic idea is by combining LOS error from the CCD and the controller output to produce the high-gain observer, forwarding into the originally closed-loop control system. This proposed EBO can improve the system both in target tracking and disturbance suppression due to LOS error from the CCD's sensing of the two signals. From a practical engineering view, the closed-loop stability and robustness of the EBO system are investigated on the condition of gain margin and phase margin of the open-loop transfer function. Two simulations of CCD experiments are provided to verify the benefits of the proposed algorithm.


AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic β-cells.
5'-AMP-activated protein kinase (AMPK) and its pharmacological modulators have been targeted for treating type 2 diabetes. Extracellular uridine 5'-diphosphate (UDP) activates P2Y6 receptors (P2Y6Rs) in pancreatic β-cells to release insulin and reduce apoptosis, which would benefit diabetes. Here, we studied the role of P2Y6R in activation of AMPK in MIN6 mouse pancreatic β-cells and insulin secretion. Treatment with a potent P2Y6R dinucleotide agonist MRS2957 (500nM) activated AMPK, which was blocked by P2Y6R-selective antagonist MRS2578. Also, MRS2957 induced phosphorylation of acetyl-coenzyme A carboxylase (ACC), a marker of AMPK activity. Calcium chelator BAPTA-AM, calmodulin-dependent protein kinase kinase (CaMKK) inhibitor STO-069 and IP3 receptor antagonist 2-APB attenuated P2Y6R-mediated AMPK phosphorylation revealing involvement of intracellular Ca(2+) pathways. P2Y6R agonist induced insulin secretion at high glucose, which was reduced by AMPK siRNA. Thus, P2Y6R has a crucial role in β-cell function, suggesting its potential as a therapeutic target in diabetes.


Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke Prevention Study.
Microangiopathy-related cerebral damage (MARCD) includes white matter abnormalities and lacunar infarctions and represents a common MRI observation in subjects above 50 years of age. The risk factors of such brain abnormalities are not fully determined. The goal of this study was to determine whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the occurrence of MARCD. Brain MRI (1.5 T) was performed in 280 individuals (ages 50 to 75 years) without neuropsychiatric disease randomly selected from the official register of residents of the city of Graz, Austria. All study participants underwent apoE genotyping, carotid Doppler sonography, electrocardiography, echocardiography, and a complete blood chemistry panel. MARCD was defined as evidence of early confluent and confluent white matter hyperintensities or lacunes. Carotid atherosclerosis was graded on a five-point scale ranging from not present (0) to complete occlusion (5). MARCD occurred in 61 individuals (21%). The distribution of apoE genotypes differed significantly between subjects with and without MARCD (P = .036). Subjects with such findings more commonly had the epsilon 2/epsilon 3 genotype (24.6% versus 10%) at similar frequencies of genotypes containing the epsilon 4 allele. The epsilon 2/epsilon 3 genotype was associated with lower levels of total cholesterol (P = .0009), LDL cholesterol (P = .00001), and apolipoprotein B (P = .00001). Also, there was a nonsignificant trend toward less cardiac disease. Other major vascular risk factors and carotid abnormalities were similar among the various genotypes. Multiple logistic regression analysis created a model of significant MARCD predictors, including age (odds ratio [OR], 1.1 per year), hypertension (OR, 3.4), and the apoE epsilon 2/epsilon 3 genotype (OR, 3.0). These data suggest an association between the apoE epsilon 2/epsilon 3 genotype and MARCD despite favorable effects on the lipid profile and cardiac disease.


Research with human subjects.
Ackerman reviews three recent books on moral issues in human research: Who Goes First? The Story of Self-Experimentation in Medicine, by Lawrence K. Altman (Random House; 1987); The Patient as Partner: A Theory of Human-Experimentation Ethics, by Robert M. Veatch (Indiana University Press; 1987); and Ethics and Regulation of Clinical Research, 2d ed., by Robert J. Levine (Urban & Schwarzenberg; 1986).


Determining Recommendations for Improvement of Communication Skills Training in Dental Education: A Scoping Review.
Professional communication skills have a significant impact on dental patient satisfaction and health outcomes. Communication skills training has been shown to improve the communication skills of dental students. Therefore, strengthening communication skills training in dental education shows promise for improving dental patient satisfaction and outcomes. The aim of this study was to facilitate the development of dental communication skills training through a scoping review with compilation of a list of considerations, design of an example curriculum, and consideration of barriers and facilitators to adoption of such training. A search to identify studies of communication skills training interventions and programs was conducted. Search queries were run in three databases using both text strings and controlled terms (MeSH), yielding 1,833 unique articles. Of these, 35 were full-text reviewed, and 17 were included in the final synthesis. Considerations presented in the articles were compiled into 15 considerations. These considerations were grouped into four themes: the value of communication skills training, the role of instructors, the importance of accounting for diversity, and the structure of communication skills training. An example curriculum reflective of these considerations is presented, and consideration of potential barriers and facilitators to implementation are discussed. Application and evaluation of these considerations are recommended in order to support and inform future communication skills training development.


BLOOD PRESSURE CHANGES DURING HUMAN SLEEP.
Systolic blood pressure measurements were made on normal human subjects throughout entire nights of natural sleep and were correlated with cyclical changes in electroencephalographic patterns. During the recurrent rapid-eye-movement phase of sleep mean blood pressure levels were found to be generally higher, and the minute-to-minute variability of level was much greater than during the remainder of sleep.


Individual differences in the visual attention of human infants: further evidence for separate sensitization and habituation processes.
How many and what kinds of processes mediate infant visual attention? Are they influenced by stimulus "complexity?" Analyses were performed on visual fixation data from ninety 4-month-old infants; the time each infant spent looking at a black and white checkerboard pattern containing either 4 x 4, 12 x 12, or 20 x 20 checks per picture was measured for eight 10-s trials, with 10-s interstimulus intervals (Kaplan & Werner, 1986). Correlational and factor analyses revealed one significant source of individual variability (or factor) in the 4 x 4 data, and two significant sources in the 12 x 12 and 20 x 20 data. One factor gained strength over progressive trials and accounted for decreases in looking time. A second factor gained strength over the first few trials, then lost strength over the remaining trials, and accounted for initial increments in looking time. The two factors are consistent with a dual-process model of infant response dynamics; the first may represent habituation, a decremental process, and the second may represent sensitization, an incremental process that is activated by "complex" stimuli.


Oral health, temporomandibular disorder, and masticatory performance in patients with Charcot-Marie-Tooth type 2.
The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD) and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2). The average number of decayed, missing, and filled teeth (DMFT) for both groups, control (CG) and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P = 0.227). The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P = 0.899). The prevalence of self-reported TMD was 33.3% and 38.9% (P = 0.718) in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG) and 22.2% (CMT2), without significant difference between groups (P = 0.162). The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7%) and temporalis (CG = 19.0%; GCMT2 = 33.3%) muscle pain. The geometric mean diameter (GMD) was not significantly different between groups (CG = 4369; CMT2 = 4627, P = 0.157). We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance.


Abdominal aortic aneurysm: pictorial review of common appearances and complications.
Abdominal aortic aneurysms (AAAs) are defined as focal dilatations of the abdominal aorta that are 50% greater than the proximal normal segment or when it is more than 3 cm in maximum diameter. The early diagnosis and treatment is very important to prevent catastrophic complications. Due to its ability to assess the peri-aortic soft tissue and the exact extension of aneurysm, as well as its excellent vascular opacification and multiplanar reconstruction capabilities, computed tomography angiography (CTA) has become an integral part of the evaluation of AAA and has virtually replaced conventional angiography for the evaluation of AAA. Knowledge of the characteristic imaging features of AAA is essential for the prompt diagnosis of life-threatening complications. In this pictorial essay, we will discuss the CTA findings in AAA and its complications including rupture, infection, aorto-enteric fistula and aorto-caval fistula.


Sexually transmitted infections among pregnant women attending antenatal clinics in Mongolia: potential impact on the Mongolian HIV epidemic.
We conducted Mongolia's first nation-wide cross-sectional survey of sexually transmitted infections (STIs) among pregnant women attending prenatal care. Among our 2000 participants, 386 (19.3%) were infected with Chlamydia trachomatis, 133 (6.7%) with Trichomonas vaginalis, 121 (6.1%) with Neisseria gonorrhoeae, and 128 (6.4%) were seropositive for Treponemal antibodies. None of our participants were seropositive for HIV infection. Additionally, 605 (30.3%) of the women had at least one STI, 133 (6.7%) had a double infection, and 15 (0.8%) had a triple infection. Our results suggest that STIs are a serious problem in Mongolia. Pregnant women represent a lower-risk general population; these high STI rates suggest that at this nascent stage, the identification, treatment, and prevention of STIs as risk factors for HIV transmission are crucial in the prevention of the emerging Mongolian HIV epidemic.


Analysis of internal defects in all-ceramic crowns using micro-focus X-ray computed tomography.
The purpose of this study was to examine all-ceramic crowns for internal defects using micro-focus X-ray computed tomography (microCT). Mono-ceramic CAD/CAM crowns, ceramic-core CAD/CAM crowns, and heat-pressed ceramic crowns were used as specimens. The microCT images of the specimens were obtained and analyzed using a 3D volume rendering software. Mono-ceramic CAD/CAM crowns contained almost no pores, while ceramic-core CAD/CAM crowns contained pores only in the porcelain veneer area. Heat-pressed ceramic crowns had lots of pores in the cusps and the area around them. Results of this study indicated that internal pores in all-ceramic crowns could be observed non-destructively using microCT, and that CAD/CAM all-ceramic crowns contained fewer pores than crowns fabricated using manual techniques.


Phase evolution of the two-dimensional Kondo lattice model near half-filling.
Within a mean-field approximation, the ground state and finite temperature phase diagrams of the two-dimensional Kondo lattice model have been carefully studied as functions of the Kondo coupling J and the conduction electron concentration [Formula: see text]. In addition to the conventional hybridization between local moments and itinerant electrons, a staggered hybridization is proposed to characterize the interplay between the antiferromagnetism and the Kondo screening effect. As a result, a heavy fermion antiferromagnetic phase is obtained and separated from the pure antiferromagnetic ordered phase by a first-order Lifshitz phase transition, while a continuous phase transition exists between the heavy fermion antiferromagnetic phase and the Kondo paramagnetic phase. We have developed an efficient theory to calculate these phase boundaries. As [Formula: see text] decreases from the half-filling, the region of the heavy fermion antiferromagnetic phase shrinks and finally disappears at a critical point [Formula: see text], leaving a first-order critical line between the pure antiferromagnetic phase and the Kondo paramagnetic phase for [Formula: see text]. At half-filling limit, a finite temperature phase diagram is also determined on the Kondo coupling and temperature (J-T) plane. Notably, as the temperature is increased, the region of the heavy fermion antiferromagnetic phase is reduced continuously, and finally converges to a single point, together with the pure antiferromagnetic phase and the Kondo paramagnetic phase. The phase diagrams with such triple point may account for the observed phase transitions in related heavy fermion materials.


Molecular Detection of Anaplasma phagocytophilum from Larvae of Haemaphysalis longicornis in Ibaraki, Japan.
We collected 1,084 ticks by flagging vegetation in Tsukuba and Moriya (Ibaraki, Japan), where several cases of canine granulocytic anaplasmosis were reported. The DNA of the collected ticks was molecularly examined for infection with the family Anaplasmataceae. Twenty-six positive samples of Anaplasmataceae-specific PCR of partial 16S rRNA gene were subjected to semi-nested PCR, covering the divergent regions, the gene, and sequence analysis. Anaplasma phagocytophilum was detected in 3 pools of Haemaphysalis longicornis larvae and A. bovis from a H. flava male. Sequences of both amplicons had high homologies to those from dogs in our previous studies in Ibaraki. These results suggest that Haemaphysalis ticks are candidate vectors of A. phagocytophilum and A. bovis in Ibaraki, Japan.


Prinzmetal's angina pectoris with normal coronary arteriograms.
Four cases of variant angina pectoris with normal findings on coronary arteriogram were experienced. The facts may show that the existence of serious arteriosclerotic lesions in a major branch of coronary artery as pointed out by Prinzmetal is at least not essential for the occurrence of anginal attack in the present disease. But the finding that age and sex distribution of variant angina was nearly the same as that of effort angina seems to still indicate the possibility that arteriosclerotic lesion somehow participates in the mechanism of occurrence of the present disease.


Dosimetry for radiocolloid therapy of cystic craniopharyngiomas.
The dosimetry for radiocolloid therapy of cystic craniopharyngiomas is investigated. Analytical calculations based on the Loevinger and the Berger formulas for electrons and photons, respectively, are compared with Monte Carlo simulations. The role of the material of which the colloid introduced inside the craniopharyngioma is made of as well as that forming the cyst wall is analyzed. It is found that the analytical approaches provide a very good description of the simulated data in the conditions where they can be applied (i.e., in the case of a uniform and infinite homogeneous medium). However, the consideration of the different materials and interfaces produces a strong reduction of the dose delivered to the cyst wall in relation to that predicted by the Loevinger and the Berger formulas.


A Summary of the First HIV Microbiome Workshop 2015.
The role of microbiota in the pathogenesis of HIV infection has become the subject of intense research in recent years. A rapidly growing amount of data suggest that microbial dysbiosis-in the gut or the genital tract-can influence HIV transmission and/or disease progression; however, a deeper understanding of the mechanisms involved is lacking. To better understand the relationship between the microbiome and HIV infection, investigators from a wide variety of disciplines, including those working in basic and clinical HIV studies, cardiovascular disease, reproductive health, and bioinformatics, gathered at the first International Workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment, at NIH on 7 and 8 April, 2015.


Mixed Nut Consumption May Improve Cardiovascular Disease Risk Factors in Overweight and Obese Adults.
Emerging research indicates that nuts are a source of health-promoting compounds demonstrating cardioprotective benefits. However, most studies have assessed the effect of single nuts rather than a nut mixture. The objective of this study was, therefore, to examine the effect of mixed-nut consumption on cardiovascular disease (CVD) risk factors in overweight and obese adults. In a randomized, parallel-arm, controlled trial, 48 participants consumed isocaloric (250 kcal) amounts of pretzels or mixed-nuts. Body weight (BW) (p = 0.024), BMI (p = 0.043), and insulin levels (p = 0.032) were significantly lower in the nut group compared to the pretzel group. Mixed-nut consumption also significantly reduced glucose (p = 0.04) and insulin (p = 0.032) levels after 4 and 8 weeks compared to baseline, respectively. Lactate dehydrogenase of the nut group was significantly lower than the pretzel group (p = 0.002). No significant differences were detected between groups for triglycerides, LDL-C, and HDL-C. However, pretzel consumption increased triglycerides (p = 0.048) from 4 weeks to 8 weeks. Moreover, LDL-C increased (p = 0.038) while HDL-C transiently decreased (p = 0.044) from baseline to 4 weeks. No significant lipid changes were detected within the nut group. Our results suggest that supplementing the diet with mixed-nuts could improve CVD risk factors by improving BW and glucose regulation in comparison to a common carbohydrate-rich snack without promoting the negative effects on lipids detected with pretzels.


HADC8 Inhibitor WK2-16 Therapeutically Targets Lipopolysaccharide-Induced Mouse Model of Neuroinflammation and Microglial Activation.
Glial activation and neuroinflammatory processes play important roles in the pathogenesis of brain abscess and neurodegenerative diseases. Activated glial cells can secrete various proinflammatory cytokines and neurotoxic mediators, which contribute to the exacerbation of neuronal cell death. The inhibition of glial activation has been shown to alleviate neurodegenerative conditions. The present study was to investigate the specific HDAC8 inhibitor WK2-16, especially its effects on the neuroinflammatory responses through glial inactivation. WK2-16 significantly reduced the gelatinolytic activity of MMP-9, and expression of COX-2/iNOS proteins in striatal lipopolysaccharide (LPS)-induced neuroinflammation in C57BL/6 mice. The treatment of WK2-16 markedly improved neurobehavioral deficits. Immunofluorescent staining revealed that WK2-16 reduced LPS-stimulated astrogliosis and microglial activation in situ. Consistently, cellular studies revealed that WK2-16 significantly suppressed LPS-induced mouse microglia BV-2 cell proliferation. WK2-16 was proven to concentration-dependently induce the levels of acetylated SMC3 in microglial BV-2 cells. It also reduced the expression of COX-2/iNOS proteins and TNF-α production in LPS-activated microglial BV-2 cells. The signaling studies demonstrated that WK2-16 markedly inhibited LPS-activated STAT-1/-3 and Akt activation, but not NF-κB or MAPK signaling. In summary, the HADC8 inhibitor WK2-16 exhibited neuroprotective effects through its anti-neuroinflammation and glial inactivation properties, especially in microglia in vitro and in vivo.


Factors related to acute hydrocephalus after subarachnoid hemorrhage.
To evaluate the influence of the amount and distribution of blood on acute ventricular enlargement in subarachnoid hemorrhage (SAH). In a retrospective study, non-contrast computed tomography (CT) images of 180 patients with aneurysmal SAH were analysed by two neuroradiologists. The amount and distribution of the hemorrhage were scored, and prospective hydrocephalus was identified on the basis of acute CT images by calculating the cella media index, by measuring the width of the third ventricle, and by visual impression. Statistical analysis was done using the logistic regression model, analysis of variance, and chi-square test. The incidence of acute hydrocephalus was higher among the patients with blood distributed in the anterior, lateral, and basal regions (70.8%) than among the patients who did not have blood distributed in all three areas (P=0.010). The proportion of acute hydrocephalus differed depending on the type of hemorrhage (P<0.001). Intraventricular hemorrhage was the most consistent predictive factor in the logistic regression model, while the other predictive factors included the total blood amount score and the volume of intracerebral hemorrhage. A positive correlation was found between acute hydrocephalus and the amount of subarachnoid and, more importantly, intraventricular blood. This is consistent with the literature and confirms the current pathophysiologic concepts that the acute hydrocephalus following SAH is an obstructive form of hydrocephalus.


Altered expression and modulation of the two-pore-domain (K2P) mechanogated potassium channel TREK-1 in overactive human detrusor.
Detrusor overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. The mechanisms of bladder smooth muscle compliance upon the wall stretch are poorly understood. We previously reported that the function of normal detrusor is regulated by TREK-1, a member of the mechanogated subfamily of two-pore-domain potassium (K2P) channels. In the present study, we aimed to identify the changes in expression and function of TREK-1 channels under pathological conditions associated with DO, evaluate the potential relationship between TREK-1 channels and cytoskeletal proteins in the human bladder, and test the possibility of modulation of TREK-1 channel expression by small RNAs. Expression of TREK-1 channels in DO specimens was 2.7-fold decreased compared with control bladders and was associated with a significant reduction of the recorded TREK-1 currents. Isolated DO muscle strips failed to relax when exposed to a TREK-1 channel opener. Immunocytochemical labeling revealed close association of TREK-1 channels with cell cytoskeletal proteins and caveolins, with caveolae microdomains being severely disrupted in DO specimens. Small activating RNA (saRNA) tested in vitro provided evidence that expression of TREK-1 protein could be partially upregulated. Our data confirmed a significant downregulation of TREK-1 expression in human DO specimens and provided evidence of close association between the channel, cell cytoskeleton, and caveolins. Upregulation of TREK-1 expression by saRNA could be a future step for the development of in vivo pharmacological and genetic approaches to treat DO in humans.


Chronic pancreatitis: the diagnostic significance of pancreatic size and echo amplitude.
Pancreatic size and pancreatic echo amplitude were examined to determine their value for distinguishing chronic pancreatitis from normal. Using patients with cystic fibrosis as a model for chronic pancreatitis, a prospective study was performed comparing 16 patients with this disease and 16 normals. Absolute measurements of the pancreatic body and the ratio of pancreatic size to vertebral body size were determined. Pancreatic echo amplitude was both measured clinically from the B-scan and evaluated in a blind review by seven observers. The pancreases of cystic fibrosis could be distinguished on the basis of echo amplitude with sensitivity and specificity of 94 per cent and 100 per cent for direct B-scan echo amplitude measurements and 74 per cent and 88 per cent for reviewers. Pancreatic size was of no value as a distinguishing characteristic, probably because as the diseased pancreas increases in echo amplitude by fat and fibrous tissue replacement, it blends imperceptibly with the peripancreatic soft tissues. Measurement of pancreatic size in chronic pancreatitis is therefore inaccurate and probably overestimated.