Caprini Scores, Risk Stratification, and Rivaroxaban in Plastic Surgery: Time to Reconsider Our Strategy.
Limited data are available regarding the pathophysiology of venous thromboembolism in plastic surgery patients. In an effort to identify patients at greater risk, some investigators promote individual risk assessment using Caprini scores. However, these scores do not correlate with relative risk values. Affected patients cannot be reliably predicted (97% false positive rate). Caprini scores make many body contouring patients candidates for chemoprophylaxis, an intervention that introduces risks related to anticoagulation. Caprini has financial conflicts with several companies that manufacture products such as enoxaparin, commonly used for chemoprophylaxis. Rivaroxaban, taken orally, has been used by some plastic surgeons as an alternative to enoxaparin injections. However, this medication is not United States Food and Drug Administration approved for venous thromboembolism prophylaxis in plastic surgery patients, and a reversal agent is unavailable. This article challenges the prevailing wisdom regarding individual risk stratification and chemoprophylaxis. Alternative methods to reduce risk for all patients include safer anesthesia methods and Doppler ultrasound surveillance. Clinical findings alone are unreliable in diagnosing deep venous thromboses. Only by using a reliable diagnostic tool such as Doppler ultrasound are we able to learn more about the natural history of this problem in our patients. Such knowledge is likely to better inform our treatment recommendations.


lncRNA IL-17RA-1 Attenuates LPS-Induced Sepsis via miR-7847-3p/PRKCG-Mediated MAPK Signaling Pathway.
Sepsis represents a syndrome of systemic inflammatory response, which is mostly a result of infection with various pathogenic microorganisms, characterized by an uncontrolled infection response of the organism leading to life-threatening organ dysfunction. Long noncoding RNA (lncRNA), as competing endogenous RNA, can affect the binding of microRNA (miRNA) to mRNA, thus influencing the development of sepsis. In this study, based on transcriptome data from GEO database, we screened differentially expressed lncRNAs and constructed lncRNA-miRNA-mRNA network. And pathway IL-17RA-1/miR-7847-3p/protein kinase C gamma (PRKCG) coexpression network was successfully sorted out. The effect of this network on LPS-induced sepsis model in THP-1 cells was also verified by CCK-8, scratch, ELISA, Western blot, and qRT-PCR assays. Corresponding binding sites of miR-7847-3p to IL-17RA-1 and miR-7847-3p to PRKCG were verified using dual luciferase gene reporter assays, respectively. Compared with control, si-IL-17RA-1 significantly inhibited the cell viability and migration ability of THP-1, and levels of proinflammatory factors IL-6, IL-1β, and TNF-α secreted were markedly decreased, and the expression of IL-17RA-1, PRKCG, p-MEKK1, and p-JNK were markedly reduced. In addition, IL-17RA-1 could target binding to miR-7847-3p and inhibit its expression, and miR-7847-3p could also bind to PRKCG. Our experiments demonstrate that IL17-RA-1 attenuates the sepsis response through the miR-7847-3p/MAPK pathway, and this competing endogenous RNA (ceRNA) network may be a potential approach to predict and combat sepsis.


[Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review)].
The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.


Pathologic assessment of tumor-associated macrophages and their histologic localization in invasive breast carcinoma.
Tumor-associated macrophages (TAMs) are important in regulating cross-talk between tumor cells and tumor microenvironment. TAMs are involved in multiple steps of tumor progression and invasion. This study aimed to compare CD163 expression with the widely used CD68 pan-macrophage marker in invasive breast carcinoma. Furthermore, it focused on assessing the significance of TAMs localization in relation to clinicopathological parameters. CD68 and CD163 immunohistochemical expressions within TAMs infiltrating both tumor nest (TN) and tumor stroma (TS) were evaluated in 60 specimens with invasive breast carcinoma. High CD68-positive stromal TAMs was significantly related to larger tumor, nodal metastasis and vascular invasion (p = 0.003, 0.037, 0.032, respectively), whereas high CD163-positive stromal TAMs was significantly related to larger tumors, nodal metastasis, stage III tumors, vascular invasion, estrogen receptor (ER) negativity, and triple-negative subtype (p = 0.023, < 0.001, 0.001, 0.022, 0.002, 0.017, respectively). On multivariate analysis, high CD68-positive TAMs infiltrating TS was significantly associated with larger tumor and positive nodal metastasis (p = 0.006 and 0.016, respectively), whereas high CD163 TAMs density within TS was significantly associated with positive vascular invasion, nodal metastasis, and molecular subtypes (p = 0.003, 0.001, and 0.009, respectively). TAMs within tumor stroma and tumor nest have different levels of association with poor prognostic parameters. So, it is of great importance to consider the histologic localization of TAMs in addition to the degree of TAMs infiltration.


IL-22 Up-Regulates β-Defensin-2 Expression in Human Alveolar Epithelium via STAT3 but Not NF-κB Signaling Pathway.
Human β-defensin-2(HBD-2) is one of the two major vertebrate antimicrobial peptide families (α and β), which is highly expressed by proinflammatory induction in the lung and exhibit broad-spectrum antimicrobial activity. We observed that IL-22 receptors high expressed on the membrane of A549 cells; HBD-2 mRNA was expressed in a time- and concentration-dependent manners in A549 cells when treated with IL-22; further studies demonstrated that HBD-2 expression was attenuated by AG490, but to JSH-23, inhibitors of p-STAT3 DNA binding and NF-κB/p65 subunit nuclear translocation, respectively. These results support that IL-22-mediated signalling pathway of HBD-2 gene expression involved STAT3 but not NF-κB in human alveolar epithelium. These findings provide a new insight into how IL-22 may play an important link between innate and adaptive immunity, thereby anti-infection locally in the alveolar epithelium.


GENETICS OF RESISTANCE OF SALIX SERICEA TO A DIVERSE COMMUNITY OF HERBIVORES.
We measured resistance of Salix sericea, the silky willow, to a diverse assemblage of 12 herbivores. We investigated the potential for multispecies coevolution among these herbivores by measuring genetic correlations between pairs of herbivores interacting within the component community. After measuring herbivore attack on half-sib families of potted S. sericea during three years, we found significant narrow-sense heritabilities of resistance to Phyllonorycter salicifoliella and Phyllocnistis sp. in 1991. Thus, there is the potential for selection on resistance to these two herbivores. Despite the many significant phenotypic correlations between herbivore abundances within a year, most genetic correlations between herbivore abundances within a year were not significant. The genetic and phenotypic correlation structure varied from year to year in this three-year study. Thus, it appears that there is the potential for evolution of resistance to the two herbivores for which we found significant heritabilities, but multispecies coevolution seems unlikely.


Facile urea-assisted precursor pre-treatment to fabricate porous g-C3N4 nanosheets for remarkably enhanced visible-light-driven hydrogen evolution.
Hydrogen generation photocatalyzed by low-cost graphite carbon nitride (g-C3N4) is a fascinating and effective route to solve energy crisis, but is mainly limited by the few reactive sites, low carrier separation efficiency and mediocre visible-light utilization. In this work, these limitations were tackled through a facile eco-friendly precursor pretreatment by tuning bulk g-C3N4 into porous structure. This pretreatment restricted agglomeration in the subsequent condensation and created more porous channels for charge carrier transfer and more surface active sites for reaction. The modified g-C3N4 has larger surface area, broader visible-light response, enhanced electron migration capacity and prolonged lifetime of photogenerated carriers. These well-amended g-C3N4 nanosheets possess an average hydrogen evolution rate 5.7 times that of bulk g-C3N4. This work affords a facile, eco-friendly and scalable strategy to design or synthesize other porous materials.


Localized Liquid-Phase Synthesis of Porous SnO2 Nanotubes on MEMS Platform for Low-Power, High Performance Gas Sensors.
We have developed highly sensitive, low-power gas sensors through the novel integration method of porous SnO2 nanotubes (NTs) on a micro-electro-mechanical-systems (MEMS) platform. As a template material, ZnO nanowires (NWs) were directly synthesized on beam-shaped, suspended microheaters through an in situ localized hydrothermal reaction induced by local thermal energy around the Joule-heated area. Also, the liquid-phase deposition process enabled the formation of a porous SnO2 thin film on the surface of ZnO NWs and simultaneous etching of the ZnO core, eventually to generate porous SnO2 NTs. Because of the localized synthesis of SnO2 NTs on the suspended microheater, very low power for the gas sensor operation (<6 mW) has been realized. Moreover, the sensing performance (e.g., sensitivity and response time) of synthesized SnO2 NTs was dramatically enhanced compared to that of ZnO NWs. In addition, the sensing performance was further improved by forming SnO2-ZnO hybrid nanostructures due to the heterojunction effect.


Effect of the cooling suit method applied to individuals with multiple sclerosis on fatigue and activities of daily living.
To determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis. Fatigue is one of the most common symptoms in people with multiple sclerosis and adversely affects their activities of daily living. Studies evaluating fatigue associated with multiple sclerosis have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue. This study used a two sample, control group design. The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups. The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living. The cooling suit worn by individuals with multiple sclerosis was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living. The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many multiple sclerosis patients, thus significantly improving their level of independence in activities of daily living.


Tungsten (VI) oxide reinforced antimony glasses for radiation safety applications: A throughout investigation for determination of radiation shielding properties and transmission factors.
We report the functional assessment of tungsten (VI) oxide on gamma-ray attenuation properties of 60Sb2O3-(40-x)NaPO3-xWO3 antimony glasses. The elemental mass-fractions and glass-densities of each glass sample are specified separately for the MCNPX Monte Carlo code. In addition to fundamental gamma absorption properties, Transmission Factors throughout a broad radioisotope energy range were measured. According to findings, holmium (Ho) incorporation into the glass structure resulted in a net increase of 0.3406 g/cm3, whereas cerium (Ce) addition resulted in a net increase of 0.2047 g/cm3. The 40% WO3 reinforced S7 sample was found to have the greatest LAC value, even though seven glass samples exhibited identical behavior. The S2 sample had the lowest HVL values among the glass groups evaluated in this work, computed in the energy range of 0.015-15 MeV. The lowest EBF and EABF values were reported for 40% WO3 reinforced S7 sample with the highest LAC and density values. According to the findings of this research, WO3 will likely make a significant contribution to the gamma ray absorption properties of antimony glasses, which are employed for optical and structural modification. Therefore, it can be concluded that WO3 may be treated monotonically and can be employed successfully in circumstances where gamma-ray absorption characteristics, optical properties, and structural qualities need to be enhanced.


Esophageal Microbiota and Nutritional Intakes in Patients With Achalasia Before and After Peroral Endoscopic Myotomy.
The composition of the microbiota in the esophagus is only partially understood, especially in patients with achalasia. We aim to investigate the esophageal microbial community and nutritional intakes in patients with achalasia before and after peroral endoscopic myotomies (POEM). Twenty-nine patients were prospectively enrolled from 4 referral institutions across Korea. We collected esophageal samples (mucosal biopsies and retention fluid) and conducted dietary surveys for nutritional intake before and 8 weeks after POEM. The esophageal microbiota was analyzed by 16S rRNA gene sequencing targeting the V3-V4 region. Out of the 105 samples from 29 patients, 99 samples were subjected to microbial bioinformatic analysis after quality control, which excluded samples with no amplification or low-quality sequence data. The overall esophageal microbial compositions of patients with achalasia showed that Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria were the dominant phyla, representing over 95% of the total phyla in all groups. At the genus level, Streptococcus was the most abundant in all groups. The observed operational taxonomic unit number was significantly higher in the retention fluid than in the tissue biopsies. However, the esophageal microbial composition showed no significant changes 8 weeks post POEM. The dietary survey analysis showed that nutritional intake significantly improved post POEM. This study determined the unique esophageal microbial composition of patients with achalasia, and also found that the microbial composition did not significantly change after POEM in the short-term, despite a significant improvement in the nutritional intake.


Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP.
Increases in the second messenger cAMP are associated with receptor-mediated ATP release from erythrocytes. In other signaling pathways, cAMP-specific phosphodiesterases (PDEs) hydrolyze this second messenger and thereby limit its biological actions. Although rabbit and human erythrocytes possess adenylyl cyclase and synthesize cAMP, their PDE activity is poorly characterized. It was reported previously that the prostacyclin analog iloprost stimulated receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the PDEs that hydrolyze erythrocyte cAMP synthesized in response to iloprost were not identified. PDE3 inhibitors were reported to augment increases in cAMP stimulated by prostacyclin analogs in platelets and pulmonary artery smooth muscle cells. Additionally, PDE3 activity was identified in embryonic avian erythrocytes, but the presence of this PDE in mammalian erythrocytes has not been investigated. Here, using Western blot analysis, we determined that PDE3B is a component of rabbit and human erythrocyte membranes. In addition, we report that the preincubation of rabbit and human erythrocytes with the PDE3 inhibitors milrinone and cilostazol potentiates iloprost-induced increases in cAMP. In addition, cilostamide, the parent compound of cilostazol, potentiated iloprost-induced increases in cAMP in human erythrocytes. These findings demonstrate that PDE3B is present in rabbit and human erythrocytes and are consistent with the hypothesis that PDE3 activity regulates cAMP levels associated with a signaling pathway activated by iloprost in these cells.


Zika Virus: Origins, Pathological Action, and Treatment Strategies.
The Zika virus (ZIKV) global epidemic prompted the World Health Organization to declare it a 2016 Public Health Emergency of International Concern. The overwhelming experience over the past several years teaches us that ZIKV and the associated neurological complications represent a long-term world-wide challenge to public health. Although the number of ZIKV cases in the Western Hemisphere has dropped since 2016, the need for basic research and anti-ZIKV drug development remains strong. Re-emerging viruses like ZIKV are an ever-present threat in the 21st century where fast transcontinental travel lends itself to viral epidemics. Here, we first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing-particularly in vivo-drug candidates for ZIKV prophylaxis and therapy ZIKV. Quite remarkably, a short, but intensive, drug-repurposing effort has already resulted in several readily available FDA-approved drugs that are capable of effectively combating the virus in infected adult mouse models and, most importantly, in both preventing maternal-fetal transmission and severe microcephaly in newborns in pregnant mouse models.


The Effect of Surface Confined Gold Nanoparticles in Blocking the Extraction of Nitrate by PVC-Based Polymer Inclusion Membranes Containing Aliquat 336 as the Carrier.
Clusters of gold nanoparticles (AuNPs) formed on the surface of PVC-based polymer inclusion membranes (PIMs) with a liquid phase containing Aliquat 336 as the carrier and in some cases 1-dodecanol or 2-nitrophenol octyl ether as plasticizers were found to inhibit the extraction of nitrate by the PIMs. This observation was based on gradually increasing the mass of AuNPs on the membrane surface and testing the ability of the membrane to extract nitrate after each increase. In this way, it was possible to determine the so-called "critical AuNP masses" at which the studied membranes ceased to extract nitrate. On the basis of these results, it can be hypothesized that the surfaces of these PIMs are not homogeneous with respect to the distribution of their membrane liquid phases, which are present only at certain sites. Extraction takes place only at these sites, and at the "critical AuNP mass" of a PIM, all these extraction sites are blocked and the membrane loses its ability to extract.


Sensory and nonsensory portions of the nucleus "ventralis posterior" thalami of chimpanzee and man.
In man and chimpanzee, the large-celled region in the posteroinferior portion of the lateroventral thalamic mass, commonly called the nucleus ventralis posterior thalami, is separated cytoarchitecturally into two regions. The anterior portion is called the nucleus ventrointermedius (Vim) and the posterior part, the nucleus ventrocaudalis (Vc). In the chimpanzee it was found that most of the fibers from the superior cerebellar peduncle entered Vim on the way to distribution in the anterior half of the lateroventral thalamic mass. Fibers from the posterior spinal column (medial lemniscus) entered the Vc. No overlap was evident in the radiations from the two sources. An unusual human case is presented suporting the sensory function of Vc since a lesion in this nucleus resulted in persistent contralateral paresthesia. On the other side, a discrete lesion in Vim caused no sensory disturbance.


Design of an HF-Band RFID System with Multiple Readers and Passive Tags for Indoor Mobile Robot Self-Localization.
Radio frequency identification (RFID) technology has already been explored for efficient self-localization of indoor mobile robots. A mobile robot equipped with RFID readers detects passive RFID tags installed on the floor in order to locate itself. The Monte-Carlo localization (MCL) method enables the localization of a mobile robot equipped with an RFID system with reasonable accuracy, sufficient robustness and low computational cost. The arrangements of RFID readers and tags and the size of antennas are important design parameters for realizing accurate and robust self-localization using a low-cost RFID system. The design of a likelihood model of RFID tag detection is also crucial for the accurate self-localization. This paper presents a novel design and arrangement of RFID readers and tags for indoor mobile robot self-localization. First, by considering small-sized and large-sized antennas of an RFID reader, we show how the design of the likelihood model affects the accuracy of self-localization. We also design a novel likelihood model by taking into consideration the characteristics of the communication range of an RFID system with a large antenna. Second, we propose a novel arrangement of RFID tags with eight RFID readers, which results in the RFID system configuration requiring much fewer readers and tags while retaining reasonable accuracy of self-localization. We verify the performances of MCL-based self-localization realized using the high-frequency (HF)-band RFID system with eight RFID readers and a lower density of RFID tags installed on the floor based on MCL in simulated and real environments. The results of simulations and real environment experiments demonstrate that our proposed low-cost HF-band RFID system realizes accurate and robust self-localization of an indoor mobile robot.


Episodic angioedema associated with eosinophilia.
We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.


The influence of cardiolipin on phosphatidylglycerol/phosphatidylethanolamine monolayers--studies on ternary films imitating bacterial membranes.
In this work the properties of ternary systems composed of phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs) and cardiolipin (CL) were studied with the Langmuir monolayer technique and Brewster Angle Microscopy. In all the investigated mixed films the PE:PG=3:1, which reflects the proportion of these lipids classes in various Gram Negative bacteria. The content of cardiolipin was varied from 5 to 20%, which is in the range of CL concentration in bacterial membranes. The experiments were performed for POPE/POPG/CL and POPE/DPPG/CL films spread on water subphase and on NaCl solution. It was found that the components of the studied films mix nonideally in the investigated range of the composition, however, the addition of cardiolipin weakens the interactions between the molecules. Thermodynamically unfavorable influence of CL results from the structure of this lipid, which due to sterical reasons disturbs the organization of POPE/PG film. It was also found that the presence of sodium ions in the subphase causes the increase of the area per molecule values and in general weakens the interactions between molecules in ternary films. However, the foregoing effect of NaCl both on binary PE/PG films as well as ternary PE/PG/CL monolayers was stronger on DPPG-containing films. The analysis of the collected data evidenced that the influence of cardiolipin as well as inorganic electrolyte on the properties of the studied films is directly connected with molecular structure of monolayers components.


Consequences of Delayed Dental Extraction in Lesch-Nyhan Disease.
Patients with Lesch-Nyhan disease (LND) often engage in self-injurious biting. This problem requires difficult management choices, sometimes including removal of the teeth. Although many health care professionals are reluctant to remove teeth in a child because of the permanent negative cosmetic consequences of the edentulous state, disfigurement of the face and tongue from self-biting can be worse. We analyzed the records of 5 LND patients who used mouth guards to spare the teeth. Success was variable, and dental extraction ultimately was required in 4 cases. We also reviewed previously published cases on the use of dental devices to spare teeth in LND. Various devices have been recommended, but failure rates are high, and tooth extraction often is still needed. Although dental extraction is not required in all cases, it should not be delayed when biting is severe.


Spiropyran to merocyanine conversion: explicit versus implicit solvent modeling.
A polarizable continnum model study and explicit solvation in water investigated through GPU-accelerated ab initio molecular dynamics followed by quantum-chemical calculations have been applied to the process of spiropyran to merocyanine isomerization of two spiropyran derivatives. It has been found that interaction with only one or two water molecules is sufficient to stabilize the merocyanine with respect to the spiropyran form. It has been shown that the agreement between energies obtained in implicit and explicit solvent models depends on the structure of the system and possible specific interactions (hydrogen bonds). Both solvent models predict similar effects in absorption spectra.


Prophylactic anti-staphylococcal antibiotics for cystic fibrosis.
Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested these hypotheses. Prophylaxis:1. improves clinical status, lung function and survival;2. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis);3. leads to fewer isolates of common pathogens from respiratory secretions;4. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted.Most recent search of Register: 04 September 2014. Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity. The authors assessed studies for eligibility and methodological quality and extracted data. We included four studies, totaling 401 randomised participants aged zero to seven years on enrolment. The two older studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results.Fewer children receiving anti-staphylococcal antibiotic prophylaxis had one or more isolates of Staphylococcus aureus. There was no significant difference between groups in infant or conventional lung function. We found no significant effect on nutrition, hospital admissions, additional courses of antibiotics or adverse effects. There was no significant difference in the number of isolates of Pseudomonas aeruginosa between groups, though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis. Anti-staphylococcal antibiotic prophylaxis leads to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.


The dental health of Indo-Chinese and Australian-born adolescents.
Since 1975, more than 100,000 Indo-Chinese refugees from Vietnam, Kampuchea, and Laos have been resettled in Australia. This dental survey was undertaken to compare the dental health of 104 Australian-born and 126 Indo-Chinese adolescents from a State high school within a high migrant area of Melbourne. The mean DMFT score for the Australian-born group was 3.37 teeth, compared with 6.05 for the Vietnamese group, and 3.10 for the Kampuchean-Laotian group. More restorations and extractions were required by the Vietnamese subjects compared with the Australian-born and Kampuchean-Laotian subjects. Almost all subjects had gingivitis, however the proportion of Indo-Chinese subjects with shallow and deep pockets was greater than that of the Australian-born subjects. The periodontal health of the Kampucheans and Laotians was the most severe of the Indo-Chinese groups. These findings indicate that the Indo-Chinese adolescent refugees represent a high risk group for dental problems within the Australian population.


Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.
Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.


[Status and trends of curative therapeutic procedures in localized prostate cancer].
The first 10-year-treatment results may allow an assessment of various therapeutic methods of localized prostatic carcinoma at which the question of survival rate and the spectrum of complications take as a basis. In localized prostatic carcinoma the individual character of curative therapeutic regimens has been increased. The new UICC classification come up to this development. The radical operation is the standard method in the treatment of curable cancer (T1-T2) with most superior survival rates. A safe intraoperative bladder-urethra anastomosis and the postoperatively possible urethrotomia interna may reduce urinary incontinence and stenosis of the anastomosis. The use of erectile-protective PE-technique should be verified with regard to its radicality. The interstitial radiation therapy using J 125 seeds or Iridium 192 is of superior therapeutic value. Whether the perineal ultrasound-guided implantation of J 125 or Ir 192 are advantageous should be checked by further investigation. A benefit from this method is its safe of potency; it may be used in cancer with low grading and tumor stage, but a close urological-radiological co-operation, a special equipment and radiation protection measures are necessary. Radiation therapy is indicated in older patients with localized tumors (T1-T3), but further reduction of irradiation side-effects and a biological judgement of the tumor by posttherapeutic biopsies be required. Since the prognosis of the prostatic cancer patients is dependent on lymphogenous metastatic spread its determination should be demand prior to localized therapy. In radical prostatectomy the pelvic lymph node dissection is performed simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)


Oscillation mode conversion and energy confinement of acoustically agitated bubbles.
The acoustically agitated bubble oscillation in liquids that is considered to be related to the half-subharmonic acoustic bubble oscillations is discussed in terms of parametric decay instability. At the frequency of about 40 kHz, the half-subharmonic bubble oscillation mode should be a surface bubble oscillation that does not easily emit acoustic waves into water and confines acoustic energy from longitudinal waves. The half-subharmonic bubble oscillation is the dominant mode that leads to parametric decay instability of bubble oscillations.


Integrated microfluidics system using surface acoustic wave and electrowetting on dielectrics technology.
This paper presents integrated microfluidic lab-on-a-chip technology combining surface acoustic wave (SAW) and electro-wetting on dielectric (EWOD). This combination has been designed to provide enhanced microfluidic functionality and the integrated devices have been fabricated using a single mask lithographic process. The integrated technology uses EWOD to guide and precisely position microdroplets which can then be actuated by SAW devices for particle concentration, acoustic streaming, mixing and ejection, as well as for sensing using a shear-horizontal wave SAW device. A SAW induced force has also been employed to enhance the EWOD droplet splitting function.


Vasopressin and central control of the cardiovascular system: A 40-year retrospective.
In the 40 years since vasopressin (AVP) was reported to have a central action with respect to raising blood pressure, the finding has been repeatedly replicated using a variety of complimentary approaches. The role of AVP as a central neurotransmitter involved in control of the cardiovascular system is now textbook material. However, it is evident that brain AVP plays, at best, a minor role in regulation of normal blood pressure. However, it appears to be an important player in a several cardiovascular-associated pathologies, ranging from hypertension to neural changes associated with heart failure. There are many interventions that have been shown to affect neural function, many of which are associated with alterations in behaviour. Possible alterations in neuronal AVP actions relevant to cardiovascular control in the setting of chronic inflammatory disease, early-life stress and inflammation are suggested areas for future research.


Cysteamine or beta-mercaptoethanol added to a defined maturation medium improves blastocyst formation of porcine oocytes after intracytoplasmic sperm injection.
The present study was carried out to investigate the effect of adding 100 microM cysteamine (Cys) or 100 microM beta-mercaptoethanol (beta-ME) to a defined maturation medium on in vitro maturation (IVM), and fertilization and developmental competence of in vitro matured porcine oocytes following intracytoplasmic sperm injection (ICSI). The two control media for IVM culture were modified TCM199 containing 10% (v/v) porcine follicular fluid (pFF) or 0.05% (w/v) polyvinyl alcohol (PVA), and Cys or beta-ME was supplemented to the PVA-control medium. There was no significant difference in the proportions of in vitro matured oocytes among the four treatment groups (94.5-98.4%). The percentages of pronuclear formation (51.0-64.2%) after ICSI were also not significantly different among the four groups. The cleavage rate (72.8%) in the oocytes treated with Cys showed no significant difference compared with those of the two control media containing pFF (72.2%) or PVA (61.5%), but was higher (P<0.05) than that in the oocytes treated with beta-ME (56.3%). However, the rates of blastocyst formation of Cys (36.7%), beta-ME (27.1%) and pFF (31.4%) were higher (P<0.05) than that using the control medium containing PVA (15.6%). The mean cell number of blastocysts ranged from 42 to 52 among the four groups, without significant differences. In conclusion, the addition of Cys or beta-ME to a defined maturation medium enhanced blastocyst formation after ICSI, to a level similar to that achieved by adding pFF.


Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing.
The processing of amyloid precursor protein (APP) to the neurotoxic pro-aggregatory Aβ peptide is controlled by the mechanisms that govern the trafficking and localisation of APP. We hypothesised that genes involved in endosomal protein sorting could play an important role in regulating APP processing and, therefore, analysed ~ 40 novel endosome-to-Golgi retrieval genes previously identified in a genome-wide siRNA screen. We report that phospholipase D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and plays an important role in regulating APP processing. PLD3 co-localises with APP in endosomes and loss of PLD3 function results in reduced endosomal tubules, impaired trafficking of several membrane proteins and reduced association of sortilin-like 1 with APP.


Comparative disposition kinetics of two diastereomeric pairs of cinchona alkaloids in the dog.
The comparative disposition kinetics of quinidine, quinine, cinchonine , and cinchonidine were investigated in five male, mongrel dogs after intravenous bolus injections of a 9.2-mmol/kg dose of each alkaloid base. Blood and plasma specimens were obtained at various times up to 6 h postdose and assayed for quinidine and quinine with a TLC-fluorometric procedure and for cinchonine and cinchonidine by HPLC. The plasma alkaloid concentration-time data were analyzed by weighted, nonlinear least-squares regression analysis to obtain the central compartment volume (Vc), disposition rate constants (alpha and beta), and corresponding half-life values (t1/2). Total body clearance (CL) and apparent volume of distribution (Vd) were estimated by nonparametric analysis. In this study, the highest plasma alkaloid concentrations were reached with quinidine and the lowest concentrations with the quinidine congener, cinchonine . The other congeneric pair, quinine and cinchonidine , exhibited plasma alkaloid concentrations that were comparable and intermediate to those of quinidine and cinchonine . With cinchonine and cinchonidine , the plasma and blood concentration-time curves were virtually superimposable. However, with quinidine and quinine, the plasma alkaloid concentrations of these diastereomers were approximately twice the corresponding blood concentrations. The total body clearance rate of quinidine was significantly slower than quinine and cinchonine clearance. No difference in clearance was observed between cinchonine and cinchonidine . The beta and t1/2 beta for quinidine were significantly smaller and larger, respectively, than the corresponding values obtained with the other alkaloids. No significant differences in alpha or Vc and Vd were found between and within the two diastereomeric pairs of alkaloids. The differences in disposition kinetics observed in this study were attributable to an interaction of stereochemical and 6'-methoxy group substitution effects.


"Tell it as it is'--qualitative methodology and nursing research: understanding the student nurse's world.
The aim of this paper is to demonstrate the utility of qualitative methods for nursing research, to this end a case is made for the use of fieldwork methods. The paper focuses upon a study which was concerned with student nurses' accounts of their experience of being learners of nursing. An overview of the students' construction of their nursing world is given and then the discussion moves to one particular aspect described as "nursing in the dark'. This is a conceptual category which deals with the data pertaining to the student's difficulties concerning what they could say to patients. The reader is thus furnished with a substantive as well as a methodological view of the study. The analysis draws upon the work of Glaser & Strauss, both in the attempt to generate ground theory and by reference to their work concerning awareness contexts.


Osteoporosis treatment: quo vadis? (A brief overview).
What we formerly called osteoporosis includes four conditions with an osteopenia: A) osteopenias usually due to mechanical disuse, where injuries cause fractures, and in limb bones more than the spine; B) osteopenias with such fragile bone that normal activities instead of injuries can cause fractures and/or bone pain, and in the spine more than limb bones; C) a group that combines features of (A) and (B); D) temporary osteopenias while major fractures, burns or other injures heal. If belatedly, we now realize our past failure to view those conditions as separate entities compromised many past studies of the prevalence, diagnosis and ways to prevent and cure each of them. That failure also compromised many past explanations of the nature, pathogenesis and natural course of "osteoporosis", and much of the related research. This caused some confusion as well as controversies about illusory instead of genuine issues. Controlling existing osteoblasts and osteoclasts with drugs has not prevented or cured those conditions. That will require controlling the modeling drifts and remodeling BMUs that create those cells. Modeling can increase bone mass and strength, remodeling can conserve or reduce them, and neither can provide the other's functions. During normal mechanical usage modeling is OFF and remodeling works in its "conservation mode" to keep existing bone. In disuse, modeling stays OFF while remodeling works in its "disuse mode" to remove bone and cause an osteopenia. Most natural nonmechanical agents (Table 1) can help or hinder those mechanical responses, but cannot duplicate or override them. Wrist and hip fractures from falls cause the most serious problems associated with these conditions. Those fractures begin in the cortex of epiphyseal-metaphyseal regions of limb bones. They never begin in trabecular bone and rarely in the shafts of long bones. They never begin in the trabecular bone and rarely in the shafts of long bones. Since a bone's strength depends on its shape and size (architecture) as well as on the amount of bone in it (bone mineral "density" and content), treatments intended to prevent or cure these conditions should strengthen the above cortex, and absorptiometric studies should begin to account for both bone architecture and bone tissue content. "Bone anabolic" agents (parathyroid hormone and some prostaglandins) can make modeling add bone to normal and osteopenic skeletons, but when the treatment stops remodeling begins removing that bone. "Antiremodeling agents" (including estrogen and many bisphosphonates) can make remodeling tend to keep existing bone, but when such treatments stop remodeling usually resumes removing bone. Combining anabolic agents with antiremodeling agents offers an exceptionally promising prospect of effective prevention and cure of the above osteopenias. Practical problems make this approach not yet ready for human use, but it soon could be.


Metformin-associated lactic acidosis and temporary ileostomy: a case report.
Lactic acidosis is a well-known complication of the anti-hyperglycemic biguanide agent metformin, especially in peculiar but not rare clinical conditions. Attempts to reduce the incidence of this adverse reaction have been enforced by national agencies over the years. The Italian Medicines Agency recently released a safety recommendation on prescribing the drug and with regard to the existence of several conditions that contraindicate drug continuation, such as dehydration, infection, hypotension, surgery or hyperosmolar contrast agent infusion, but the recommendation does not mention the increased risk related to stoma. The present case report is, to our knowledge, the first in the literature of metformin-associated lactic acidosis in a patient with a recently created ileostomy and low anterior resection for rectal cancer. A 70-year-old Caucasian man who had undergone low anterior resection with total mesorectal excision and temporary loop ileostomy creation at our institution returned to our department 30 days later because of nausea, vomiting, diffuse abdominal pain and anuria of about 24 hours' duration. During his physical examination, the patient appeared dehydrated and had tachypnea and a reduced level of consciousness. His laboratory tests showed that he had acute kidney injury and severe lactic acidosis. An ileostomy puts patients at high risk for output losses that can lead to dehydration and electrolyte abnormalities. The assessment of the losses through the stoma, especially the ileostomy, should be added to the recommendations issued by pharmacovigilance societies. The present clinical case illustrates the need for clinicians on surgical wards to carefully evaluate patients before resuming metformin therapy and to provide appropriate information at discharge to patients with type 2 diabetes mellitus who have undergone ileostomy. Furthermore, this case report highlights the increasing need for more training of general physicians regarding both surgical and internal medicine problems that may arise in the post-operative course after major surgery in patients with co-morbidities.


Molecular Mechanism of Wide Photoabsorption Spectral Shifts of Color Variants of Human Cellular Retinol Binding Protein II.
Color variants of human cellular retinol binding protein II (hCRBPII) created by protein engineering were recently shown to exhibit anomalously wide photoabsorption spectral shifts over ∼200 nm across the visible region. The remarkable phenomenon provides a unique opportunity to gain insight into the molecular basis of the color tuning of retinal binding proteins for understanding of color vision as well as for engineering of novel color variants of retinal binding photoreceptor proteins employed in optogenetics. Here, we report a theoretical investigation of the molecular mechanism underlying the anomalously wide spectral shifts of the color variants of hCRBPII. Computational modeling of the color variants with hybrid molecular simulations of free energy geometry optimization succeeded in reproducing the experimentally observed wide spectral shifts, and revealed that protein flexibility, through which the active site structure of the protein and bound water molecules is altered by remote mutations, plays a significant role in inducing the large spectral shifts.


Epidemiology and spatial analysis of malaria in the Northern Peruvian Amazon.
A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.


Association of missense mutations in epoxyalkane coenzyme M transferase with adaptation of Mycobacterium sp. strain JS623 to growth on vinyl chloride.
Vinyl chloride (VC) is a toxic groundwater pollutant associated with plastic manufacture and chlorinated solvent use. Aerobic bacteria that grow on VC as a carbon and energy source can evolve in the laboratory from bacteria that grow on ethene, but the genetic changes involved are unknown. We investigated VC adaptation in two variants (JS623-E and JS623-T) of the ethene-oxidizing Mycobacterium strain JS623. Missense mutations in the EtnE gene developed at two positions (W243 and R257) in cultures exposed to VC but not in cultures maintained on ethene. Epoxyalkane-coenzyme M transferase (EaCoMT) activities in cell extracts of JS623-E and JS623-T (150 and 645 nmol/min/mg protein, respectively) were higher than that of wild-type JS623 (74 nmol/min/mg protein), and in both variant cultures epoxyethane no longer accumulated during growth on ethene. The heterologous expression of two variant etnE alleles (W243G [etnE1] and R257L [etnE2]) from strain JS623 in Mycobacterium smegmatis showed that they had 42 to 59% higher activities than the wild type. Recombinant JS623 cultures containing mutant EtnE genes cloned in the vector pMV261 adapted to growth on VC more rapidly than the wild-type JS623 strain, with incubation times of 60 days (wild type), 1 day (pMVetnE1), and 35 days (pMVetnE2). The JS623(pMVetnE) culture did not adapt to VC after more than 60 days of incubation. Adaptation to VC in strain JS623 is consistently associated with two particular missense mutations in the etnE gene that lead to higher EaCoMT activity. This is the first report to pinpoint a genetic change associated with the transition from cometabolic to growth-linked VC oxidation in bacteria.


Investigation of hub genes involved in Turner syndrome using biological informatics methods.
This study aimed to explore candidate genes and their potential interaction mechanism critical to the pathophysiology of Turner syndrome by using the Gene Expression Omnibus database. GSE58435 data set was obtained by querying the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using R and subsequently annotated by Gene Ontology. Functional enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database for annotation, visualization, and integrated discovery. A protein-protein interaction network of different genes was constructed based on the STRING database, in which hub genes were explored through Cytoscape software. The expression of the hub genes was verified by analyzing the gene expression in the GSE46687 data set. A total of 733 differential genes were identified. These differentially expressed genes were significantly enriched in nucleoplasm and nucleus. Their molecular function was concentrated on DNA binding and transcription, coronary artery, and adipose tissue development. According to the annotation of Kyoto Encyclopedia of Genes and Genomes, the identified DEGs were mainly enriched in inflammatory mediator regulation of TRP channels, osteoclast differentiation. A total of 10 hub genes (HIST1H2BA, TRIM71, HIST1H2BB, HIST1H4D, TNF, TP53BP1, CDCA8, EGF, HMG20B, and BCL9) were identified from the constructed protein-protein interaction network. These genes were discovered to be highly expressed in osteoclasts, ovaries, digestive tract, blood, and lymphatic tissues through the online application of human protein atlas. In this study, 733 DEGs and 10 hub genes were identified. They would be new candidate targets in Turner syndrome.


Emergency department initiated treatments for tobacco (EDITT): a pilot study.
Emergency departments (EDs) have strong potential to initiate tobacco interventions with economically disadvantaged populations. We piloted three ED-initiated tobacco interventions and derived parameter estimates for future trials. The study enrolled adult patients being treated in an urban ED who were daily smokers. Exclusion criteria included severe illness or pain, isolation (for contagion), altered mental status, an insurmountable language barrier, temporary residence, and lack of telephone access. Subjects in the Bedside + Booster group received motivational counseling by a trained counselor at the bedside, up to three telephone sessions post-visit, and a self-help guide. Subjects in the Faxed Referral group had their personal contact information faxed to the hospital's tobacco dependence clinic, whereupon they received identical treatment as the Bedside + Booster group, but all sessions occurred over the telephone (i.e., no bedside counseling). The Standard Referral group received the self-help guide and a referral to the hospital's tobacco dependence clinic. We used a 2:2:1 randomization schedule to maximize our experience with the motivational interventions. Outcomes were assessed at 1 and 3 months. We enrolled 90 subjects. Of the 36 subjects assigned to the Bedside + Booster condition, 31 (87%) completed bedside counseling and at least one booster session, while 22 (61%) completed the maximum four sessions. Of the 37 subjects assigned to the Faxed Referral group, 28 (76%) completed at least one telephone session, while 19 (51%) completed the maximum four sessions. Quit attempts over the 3 months ranged from 18% (Standard Referral) to 57% (Faxed Referral). Seven-day abstinence was attained by 8% (Bedside + Booster), 14% (Faxed Referral), and 6% (Standard Referral) at 3 months. Motivational cessation counseling can be feasibly initiated during the ED encounter with minimal medical staff involvement. Adequately powered trials are needed to study ED-initiated interventions that include post-visit follow-up.


[Studies of protein clearance in detecting early renal involvement of lupus erythematosus].
By means of protein clearance investigations the differentiation of the damage degree of the kidneys is to be described in a certain extent also with lupus nephritis. The in 1982 stated proteinuria elimination of 0.5 g/24 hour as a criterion for a renal participation could be the cause for the often relatively late stated kidney participation in the LE. The determination of selective and nonselective excreted proteins in connection with the detection of the double strain-DNS antibodies might be more proper to indicate a kidney participation.


Direct analysis of aromatic hydrocarbons in purified mineral oils for foods and cosmetics applications using gas chromatography with vacuum ultraviolet detection.
Highly purified mineral oils are used in several pharmaceutical, foods and cosmetics applications. A fast and simple method was developed for the analysis of the total level of residual mineral oil aromatic hydrocarbons (MOAH) in these oils and in the intermediate oils that were sampled during the purification process. The method is based on gas chromatography with vacuum ultraviolet detection (GC-VUV) and relies on the spectral differences between the aliphatic and aromatic compounds in the sample. Because the detector provides a good selectivity for aromatics, direct quantification of the MOAH content is possible without the need for a laborious preseparation of the mineral oil. The method was successfully applied for the direct analysis of the MOAH levels of 18 different mineral oil samples. The aromatics contents obtained by GC-VUV were similar to those obtained using two conventional methods (NPLC-GC-FID and SPE-GC-FID), with no statistically significant difference. The detector response was linear over the concentration range tested (0.5-20 mg/mL) and the repeatability (RSD value) was less than 8%, which is better than the typical values for the conventional methods (up to 15% RSD). The minimum MOAH level that can be determined with this method is approximately 0.13%, making the GC-VUV method sufficiently sensitive for the analysis of all but the highest purity mineral oils.


Transbronchial needle aspiration in diagnosing intrathoracic tuberculous lymphadenitis.
To assess the role of transbronchial needle aspiration (TBNA) in diagnosing intrathoracic tuberculous lymphadenitis (TB-LA). In a tertiary referral center for thoracic medicine and surgery, using a CT scan as a guide, transbronchial aspirates were obtained with a 19-gauge flexible histology needle in consecutively enrolled patients with sputum smears negative for acid-fast bacilli, and with isolated mediastinal or hilar adenopathy suspicious for tuberculosis (TB). Of 84 eligible patients who were all found to be HIV-negative, 63 (75%) cases of TB were diagnosed by TBNA (histology, 48 patients [76%]; cytology, 9 patients [14%]; and bacteriologic studies, 21 patients [33%; smear, 8 patients; culture, 17 patients]). TBNA was used to diagnose sarcoidosis in two patients, angioimmunoblastic lymphadenopathy in one patient, and Hodgkin lymphoma in one patient. In the 17 TBNA-negative patients, the results of transthoracic needle aspiration were positive in 12 patients (TB, nine patients; lung cancer, two patients; sarcoidosis, one patient), the results of mediastinoscopy were positive in three patients (TB, two patients; Hodgkin lymphoma, one patient), and the results of thoracotomy were positive in two patients (TB, two patients). Thus, 76 patients had TB, and all responded to anti-TB treatment. TB was corroborated by culture or histology of another specimen obtained from subsequently developed lesions in 40 patients (53%) during anti-TB treatment or posttreatment follow-up. TBNA was immediately diagnostic in 59 patients (78%), and exclusively in 52 patients (68%), among all bronchoscopic procedures and prebronchoscopic sputum studies. Sensitivity, specificity, positive and negative predictive values, and accuracy of TBNA for TB were 83%, 100%, 100%, 38%, and 85%, respectively. The only complication, self-limiting hemorrhage of < 30 mL volume, occurred in 65 patients (77%), with a volume of < 5 mL in 59 patients (70%). TBNA is efficient and safe in the bacteriologic and pathologic diagnosis of intrathoracic TB-LA in HIV-negative and sputum smear-negative patients.


Modeling the Actin.myosin ATPase Cross-Bridge Cycle for Skeletal and Cardiac Muscle Myosin Isoforms.
Modeling the complete actin.myosin ATPase cycle has always been limited by the lack of experimental data concerning key steps of the cycle, because these steps can only be defined at very low ionic strength. Here, using human β-cardiac myosin-S1, we combine published data from transient and steady-state kinetics to model a minimal eight-state ATPase cycle. The model illustrates the occupancy of each intermediate around the cycle and how the occupancy is altered by changes in actin concentration for [actin] = 1-20Km. The cycle can be used to predict the maximal velocity of contraction (by motility assay or sarcomeric shortening) at different actin concentrations (which is consistent with experimental velocity data) and predict the effect of a 5 pN load on a single motor. The same exercise was repeated for human α-cardiac myosin S1 and rabbit fast skeletal muscle S1. The data illustrates how the motor domain properties can alter the ATPase cycle and hence the occupancy of the key states in the cycle. These in turn alter the predicted mechanical response of the myosin independent of other factors present in a sarcomere, such as filament stiffness and regulatory proteins. We also explore the potential of this modeling approach for the study of mutations in human β-cardiac myosin using the hypertrophic myopathy mutation R453C. Our modeling, using the transient kinetic data, predicts mechanical properties of the motor that are compatible with the single-molecule study. The modeling approach may therefore be of wide use for predicting the properties of myosin mutations.


Pteropine orthoreovirus: An important emerging virus causing infectious disease in the tropics?
Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that has spilled over from bats to humans. Though initially found only in bats, further case studies have found viable virus in ill patients. PubMed was queried with the keywords of Nelson Bay orthoreovirus OR Pteropine orthoreovirus OR Melaka orthoreovirus OR Kampar orthoreovirus, and returned 17 hits. Based on prevalence studies, the presence of PRV has been reported in Malaysia and Vietnam, both developing countries. Other case reports also provide further evidence of the presence of PRV in the Southeast Asian region. Despite the absence of PRV in their home countries, travellers from Hong Kong and Japan to Indonesia have returned to their countries ill with this virus, indicating that local communities in Indonesia might be affected by this virus. This work aims to bring to light this emerging zoonotic respiratory virus circulating among developing countries in Southeast Asia. To improve the understanding of PRV of the medical and scientific community in the Southeast Asian region, this work introduces the general features of PRV, reports of imported PRV, prevalence, and clinical features of PRV. Gaps in knowledge about PRV have also been identified in this work, and we hope that future studies can be undertaken to improve our understanding of this virus.


The toxic effects and possible mechanisms of Brusatol on mouse oocytes.
Brusatol is a natural quassinoid that shows a potential therapeutic use in cancer models by the inhibition of Nuclear factor erythroid 2-related factor 2 (Nrf2) and is capable of inducing a variety of biological effects. The effects of Brusatol on oocyte meiosis has not been addressed. In this study, we investigated the impact of Brusatol treatment on mouse oocyte maturation and its possible mechanism. Our data demonstrated that Brusatol treatment disrupted oocyte maturation and spindle/chromosome organization by modulating Nrf2-Cyclin B1 pathway, as the influence of Brusatol was compensated by the addition of Nrf2 activation plasmid, and the mRNA and protein levels of Cyclin B1 were severely reduced in oocytes following Nrf2 decline. In summary, our data support a model that Brusatol, through the inhibition of Nrf2, modulate Cyclin B1 levels, consequently disturbing proper spindle assembly and chromosome condensation in meiotic oocytes.


Mass spectrometry imaging of fingerprint sweat on nanostructured silicon.
Desorption ionisation on porous silicon mass spectrometry imaging (DIOS-MSI) was used on fingerprints to map the distribution of exogenous and endogenous molecules present in sweat. Our attention was focused on the proof-of-principle to detect illicit drugs and their metabolites to exemplify the technique's potential in the area of forensic and workplace testing.


Mechanistic comparison of current pharmacological treatments and novel phytochemicals to target amyloid peptides in Alzheimer's and neurodegenerative diseases.
The formation of β amyloid plaques is one of the pathological hallmarks of Alzheimer's disease (AD). The process of accumulation of extracellular deposits of amyloid plaques occurs by the abnormal proteolysis of amyloid precursor protein, resulting in the formation of β amyloid peptides which further aggregates and results in the formation of oligomers, protofibrils, fibrils, and plaques. The complexity in understanding the aggregation process has provided avenues for identifying potential targets against amyloid toxicity in the treatment of AD. The therapeutic approach mainly focuses on reducing the toxicity by halting the β amyloid fibril formation. Besides conventional medicine, several naturally available compounds were shown to reduce the toxicity of amyloid plaques in the current scenario. This review provides a comprehensive account on recent updates of FDA-approved and naturally available compounds against toxicity of amyloid peptides and plaques both in vitro and in vivo.


Establishing a regional contact & service centre for public health care: the case in central macedonia, Greece.
Regional Healthcare System Authorities (RHSAs) run under the Ministry of Health and Welfare in Greece, aim is to improve the level of quality that health care organizations offer as well as to control the expenditure of health care services provided by the health care organizations. In this article we present the considerations taken during the establishment of the first Regional Contact & Service Center for Public Health in Greece in two of the RHSAs. In this respect, the current piece of work provides an up-to-date experience in establishing and setting the RCSC in its organizational context, an outline of its conceptual model and design, an outlook of the first quarterly results of its use, and a discussion of its potential impact.


Comparison of fibreoptic-guided intubation through ILMA versus intubation through LMA-CTrach.
We compared the time taken to intubate the trachea of a manikin by fibreoptic-guided intubation through an intubating laryngeal mask airway (ILMA-FOS) with intubation through a laryngeal mask airway CTrach (LMA-CTrach). Forty-two anaesthetists participated in this randomised crossover study. Although the insertion time was similar, the time taken to intubate the trachea was significantly shorter with the LMA-CTrach as compared with the ILMA-FOS, with a mean time (SD) for ILMA-FOS and CTrach 84 (32) and 53 (21) s, respectively (p < 0.001). The mean difference in the total time between the two techniques was 31 s, with a 95% confidence interval of 22 to 39 s. Thirty (71%) anaesthetists preferred LMA-CTrach as compared with ILMA-FOS (p = 0.008). We conclude that LMA-CTrach is a suitable alternative to fibreoptic-guided intubation through ILMA for the management of unanticipated failed intubation.


Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer.
Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic chemotherapy regimens alone or in concurrent combination with an antiangiogenic drug, pazopanib. Clones of the SKOV-3 human ovarian carcinoma cell line expressing a secretable beta-subunit of human choriogonadotropic (beta-hCG) protein and firefly luciferase were generated and evaluated for growth after orthotopic (i.p.) injection into severe combined immunodeficient mice; a highly aggressive clone, SKOV-3-13, was selected for further study. Mice were treated beginning 10 to 14 days after injection of cells when evidence of carcinomatosis-like disease in the peritoneum was established as assessed by imaging analysis. Chemotherapy drugs tested for initial experiments included oral cyclophosphamide, injected irinotecan or paclitaxel alone or in doublet combinations with cyclophosphamide; the results indicated that metronomic cyclophosphamide had no antitumor activity whereas metronomic irinotecan had potent activity. We therefore tested an oral topoisomerase-1 inhibitor, oral topotecan, at optimal biological dose of 1 mg/kg/d. Metronomic oral topotecan showed excellent antitumor activity, the extent of which was significantly enhanced by concurrent pazopanib, which itself had only modest activity, with 100% survival values of the drug combination after six months of continuous therapy. In conclusion, oral topotecan may be an ideal agent to consider for clinical trial assessment of metronomic chemotherapy for ovarian cancer, especially when combined with an antiangiogenic drug targeting the vascular endothelial growth factor pathway, such as pazopanib. Mol Cancer Ther; 9(4); 996-1006. (c)2010 AACR.


A Case Series of Bee Sting Keratopathy With Different Outcomes in Malaysia.
We report three patients with corneal bee sting at our tertiary care center in a three-year period starting from 2014 to 2016. All patients sustained a bee sting injury to the cornea. All patients received early preoperative topical antibiotics, topical cycloplegic and intensive topical steroids. However, the timing of the initial presentation, the duration, and the location of the retained stinger differed in each case leading to different postsurgical outcomes.


Visual impairment and traits of autism in children.
Visual impairment present from birth or from an early childhood may lead to psychosocial and emotional disorders. 11-40% of children in the group with visual impairment show traits of autism. The aim of this paper was to present the selected examples of how visual impairment in children is related to the occurrence of autism and to describe the available tools for diagnosing autism in children with visual impairment. So far the relation between visual impairment in children and autism has not been sufficiently confirmed. Psychiatric and psychological diagnosis of children with visual impairment has some difficulties in differentiating between "blindism" and traits typical for autism resulting from a lack of standardized diagnostic tools used to diagnosing children with visual impairment. Another difficulty in diagnosing autism in children with visual impairment is the coexistence of other disabilities in case of most children with vision impairment. Additionally, apart from difficulties in diagnosing autistic disorders in children with eye dysfunctions there is also a question of what tools should be used in therapy and rehabilitation of patients.


Effects of propranolol and diltiazem on the rate of high-energy phosphate metabolism in reperfused rat hearts--31P-NMR saturation transfer study.
The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux (Pi-->ATP) were studied in isolated perfused rat hearts by the saturation transfer method using 31P-NMR. The effects of propranolol and diltiazem on phosphate metabolism were also studied. After a 40 min preischemic period, the hearts were subjected to a 15 min period of ischemia, followed by 60 min of reperfusion. Propranolol (0.4-1.2 microM) or diltiazem (3.0-6.0 microM) was infused for 30 min before ischemia and reinfused after reperfusion for 60 min. The flux (PCr-->ATP)/PRP ratio at reperfusion did not differ from that at preischemia. This value was also not affected by propranolol or diltiazem treatment. However, the flux (Pi-->ATP)/PRP ratio at reperfusion was significantly less than that at preischemia. Moreover, this value was significantly improved by propranolol or diltiazem treatment. This study demonstrates that 1) flux (PCr-->ATP) has a good correlation with cardiac performance, 2) stunned myocardium needs less ATP turnover for survival of its depressed contractile activity, and 3) flux (Pi-->ATP) can limit recovery of postischemic performance. Protective effects of propranolol and diltiazem are exerted on the flux (Pi-->ATP), i.e. ATP derived from glycolytic flux, in the reperfused heart.


Biocompatible lipid-based liquid crystals and emulsions.
Due to its potential relevance as a fully biocompatible formulation useful in cosmetic, food, and pharmaceutical applications, the glycerol trioleate/sodium oleate/water ternary system was investigated via optical microscopy and NMR methods. The ternary diagram is dominated by monophasic and biphasic regions where a lamellar phase coexists with different isotropic phases. A broad emulsion region, characterized by small oil droplets dispersed within the lamellar phase, extends from the center toward the water corner of the diagram. Information on the inner structure of these emulsion-like samples is supplied by modeling water and oil NMR self-diffusion data. Sizing of oil droplets was provided at different storage times. A highly polydisperse log-normal distribution was observed. The presence of the liquid crystalline phase is called into play for the negligible differences found in the droplets size distribution upon samples aging. Indeed, samples within this region stored at 25 degrees C did not show phase separation after several months from their preparation.


Modulated crystal structure of InMo4O6.
The (3 + 1)-dimensional modulated crystal structure of the metal-rich cluster compound InMo4O6 was solved and refined from single-crystal data in the superspace group P4/mbm(00γ)00ss [q = 0, 0, 0.1536 (4); a = 9.6664 (9), c = 2.8645 (3) Å; R1(all) = 0.046, wR(all) = 0.076]. The crystal structure is closely related to the NaMo4O6 structure type. It is built from rods of Mo6 clusters condensed via trans edges. These form channels parallel to [001], in which In6 and In7 oligomers alternate. Weak diffuse planes parallel to (001)* interconnect the satellite reflections; they occur due to two-dimensional rod disorder of the In oligomer chains.


No supernovae associated with two long-duration gamma-ray bursts.
It is now accepted that long-duration gamma-ray bursts (GRBs) are produced during the collapse of a massive star. The standard 'collapsar' model predicts that a broad-lined and luminous type Ic core-collapse supernova accompanies every long-duration GRB. This association has been confirmed in observations of several nearby GRBs. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11) were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration and show that the bursts originated in actively star-forming regions. The absence of a supernova to such deep limits is qualitatively different from all previous nearby long-duration GRBs and suggests a new phenomenological type of massive stellar death.


Protein status of infants with phenylketonuria undergoing nutrition management.
The objectives of this study were to determine if Phenex-1, amino-acid modified medical food with iron maintained normal indices of protein status in infants with phenylketonuria (PKU) and to investigate factors that influence plasma amino acid concentrations. A study was conducted for six months in 35 infants with classical PKU diagnosed in the neonatal period. Diet diaries and plasma amino acid concentrations were obtained monthly. Blood for analysis of plasma albumin, blood urea nitrogen (BUN), retinol binding protein (RBP) and transthyretin was obtained at one, three and six months of study. Mean (+/-SEM) total daily intake of medical food and nutrients was 79+/-4 g; 17.3+/-0.6 g protein, 660+/-18 kcal, 255+/-10 mg phenylalanine (Phe), and 1423+/-56 mg tyrosine (Tyr). Mean concentrations of plasma amino acids, except cystine (during entire study), glycine (first month) and Phe were in the normal range. Mean concentrations of plasma Phe were in the treatment range (120 to 360 micromol/L). Plasma concentrations of arginine, methionine, Phe, tryptophan, Tyr, and valine were positively correlated with intakes at various months of study. Concentrations of aspartic and glutamic acids, Phe, and Tyr were positively correlated and 17 amino acids were negatively correlated with the interval between feeding and blood draw. At six months of study, concentration of plasma albumin was 4.1+/-0.1 g/dL, RBP was 3.74+/-0.2 mg/dL, transthyretin was 17.9+/-0.9 mg/dL, and urea nitrogen was 11.9+/-0.5 mg/dL. During study, all mean plasma indices of protein status were in normal reference ranges. Phenex-1 supports normal mean plasma amino acid, albumin, RBP, transthyretin, and BUN concentrations when fed in adequate amounts.


Identification of a Novel HIV Type 1 CRF01_AE/B'/C Recombinant Isolate in Sichuan, China.
We report in this study a novel HIV-1 unique recombinant virus (XC2014EU01) isolated from an HIV-positive man who infected through heterosexual sex in Sichuan, China. The near full-length genome analyses showed that XC2014EU01 harbored one subtype B segment in pol region and two subtype C segments in gag-pol region in a CRF01_AE backbone. The unique mosaic structure was distinctly different from the other CRF01_AE/B'/C recombinant forms reported. Phylogenetic tree analyses revealed that the subtype B region originated from a Thailand subtype B' lineage, the subtype C regions were from an India C lineage, and the backbone was from CRF01_AE. XC2014EU01 was still identified as CCR5-tropic, and plasma of XC2014EU01 infected person had the media neutralizing activity. The emergence of XC2014EU01 may increase the complexity of the HIV-1 epidemic among high-risk populations and the difficulty of vaccine research and development.


Prophylactic external fixation and extensive bone debridement for chronic osteomyelitis.
There is universal agreement that treatment of osteomyelitis should consist of debridement, obliteration of dead space, tissue coverage and antibiotic therapy, with debridement as the most important factor for therapeutic success. Four patients, 27 to 72 years old, with chronic osteomyelitis after a fracture of the femur (two), or of the tibia (two), were included in this study. The patients had already undergone 5 to 15 (mean: 9) surgical procedures. The same surgical technique was used in all of them: sinuses were carefully excised down to the bone, and necrotic bone was aggressively resected until normal bleeding was seen. A prophylactic circular external fixation frame, built on one proximal and one distal ring connected to the bone by thin wires and half pins, was used to protect and support the limbs, significantly weakened by radical debridement. Bone grafting or distraction osteogenesis was not necessary. All wounds healed without complications, and the infection did not recur. The average follow-up period was 43 months (range: 38 to 54).


The aetiology of chronic vulval pain and entry dyspareunia: a retrospective review of 525 cases.
There are few published data about the incidence of diagnoses or treatment outcomes, for chronic vulval pain. To document diagnoses and treatment outcomes in a cohort of chronic vulval pain presentations. A retrospective case review of the patient database of a private vulval clinic between January 2011 and March 2015. Five hundred and twenty-five out of 3360 patients (15.6%) met the criterion of vulval pain alone. Mean age was 47.1 years (range 17-86). Average duration of symptoms was 60 months (range 3-432). Overall, 277/525 (52.7%) patients had satisfactory responses to appropriate treatment and 90/525 (17%) had partial improvement. A dermatosis was identified in 322/525 (61.3%) patients and of these, 211/322 (65.5%) had satisfactory responses to appropriate dermatological treatment. In the remaining 203/525 (38.7%) the skin was normal. These patients were questioned around the possibility of a neuromuscular cause for their pain, including pre-existing dysfunction, trauma or previous operations involving the spine, hips or lower limbs. There were 181/203 (89%) patients considered to have a neuromuscular cause for their pain and considered suitable for physiotherapy and/or neuromodulating medications. Of these patients, 63/182 (34.6%) had satisfactory responses to this treatment. One hundred and sixty-six out of 525 (31.6%) described vulval pain only during sexual intercourse. There was no statistically significant difference between different diagnoses and responses to treatment between patients reporting dyspareunia only and those sexually active women who did not experience dysparenunia (29/525, 5.5%). The majority of this cohort with chronic vulval pain had a dermatological disease with a smaller proportion caused by neuromuscular dysfunction. Both groups are potentially treatable.


Switching DNA-binding specificity by unnatural amino acid substitution.
The specificity of protein-nucleic acid recognition is believed to originate largely from hydrogen bonding between protein polar atoms, primarily side-chain and polar atoms of nucleic acid bases. One way to design new nucleic acid binding proteins of novel specificity is by structure-guided alterations of the hydrogen bonding patterns of a nucleic acid-protein complex. We have used cI repressor of bacteriophage lambda as a model system. In the lambda-repressor-DNA complex, the epsilon-NH(2) group (hydrogen bond donor) of lysine-4 of lambda-repressor forms hydrogen bonds with the amide carbonyl atom of asparagine-55 (acceptor) and the O6 (acceptor) of CG6 of operator site O(L)1. Substitution of lysine-4 (two donors) by iso-steric S-(2-hydroxyethyl)-cysteine (one donor and one acceptor), by site-directed mutagenesis and chemical modification, leads to switch of binding specificity of lambda-repressor from C:G to T:A at position 6 of O(L)1. This suggests that unnatural amino acid substitutions could be a simple way of generating nucleic acid binding proteins of altered specificity.


Different outcome of invasive cervical cancer associated with high-risk versus intermediate-risk HPV genotype.
Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety-six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High-risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p = 0.009), tumour size (p = 0.01) and HPV status (p = 0.02) were associated with disease-free survival (median follow-up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31, 33, 35, 39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p = 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes.


Center for International Blood and Marrow Transplant Research chronic graft-versus-host disease risk score predicts mortality in an independent validation cohort.
We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P < .01). NRM and overall survival at 5 years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG3, respectively (all P < .01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for overall survival and NRM in a contemporary transplantation population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enroll patients in clinical trials.


THE SELECTION BARRIER BETWEEN POPULATIONS SUBJECT TO STABILIZING SELECTION.
The introgression of genes carried by a small group of immigrants is studied. The recipient and the donor populations differ at several autosomal loci subject to weak selection, and two allelic forms of each gene are considered. Fitness variation is determined by additive allelic effects, by dominance effects, and by two-locus additive-by-additive epistatic interaction of the effects of the alleles. The fate of the group of immigrants is quantified by the selection barrier that describes the cumulative mean fitness of the hybrids and hybrid descendants relative to the fitness of the resident population. The monomorphic and the polymorphic loci of the recipient population contribute differently to the selection barrier. If the genetic difference between recipient and donor population is small, then the contribution of the monomorphic loci is dominated by a positive term dependent on the difference in gene frequencies. The contribution of the polymorphic loci depends only on the difference of the leading order in the pairwise linkage disequilibria between the two populations. This contribution may be positive or negative; and, thus, polymorphic loci may either contribute to the barrier or inflate the introgression.


MAO inhibitor therapy in trichotillomania associated with depression: case report.
Trichotillomania may sometimes be an atypical variant of depressive illness. A case is reported in which the MAO inhibitor isocarboxazid was successfully used to treat both depression and associated trichotillomania. The symptoms recurred upon discontinuation of the drug and were ameliorated by reintroduction of isocarboxazid .


Hereditary Persistence of Alpha-Fetoprotein Is Associated with the -119G>A Polymorphism in AFP Gene.
Alpha-fetoprotein (AFP) is a glycoprotein that is produced by the liver and yolk sac during fetal development. Its levels are usually raised in malignant conditions. Hereditary persistence of AFP (HPAFP) is a rare benign condition with elevated levels of AFP. It is inherited in a dominant mode with complete penetrance and is usually not associated with any clinical disability. We report two individuals with elevated levels of AFP harboring the -119G>A polymorphism in the AFP gene. A genetic screening to rule out variants in the AFP gene is advised in cases with unexplained persistent AFP levels to avoid inappropriate treatment and surgical options.


Infantile myofibromatosis with a solitary lesion in the skull--case report.
The term "infantile myofibromatosis" was coined in 1981 to describe a rare type of soft-tissue tumor in infants. Solitary lesions are usual, but extremely rare in the skull. An infantile case involving a lesion in the left parietal bone is described. The patient was a 6-month-old girl admitted with a mass measuring 2 x 2 cm in the left parietal region. Skull x-rays showed an osteolytic lesion with a sclerotic margin in the parietal bone. Computed tomographic (CT) scans revealed a low-density mass with homogeneous enhancement. The tumor adhered to the dura and had destroyed the left parietal bone. Histological examination disclosed spindle-shaped cells arranged in short bundles and abundant vasculature. Phosphotungstic acid hematoxylin staining revealed longitudinal fibrils resembling myofibroblasts. This is the first report in which CT findings are described in a case of infantile myofibromatosis with a solitary lesion occurring in the skull.


HEMA but not TEGDMA induces autophagy in human gingival fibroblasts.
Polymerized resin-based materials are successfully used in restorative dentistry. Despite their growing popularity, one drawback is the release of monomers from the polymerized matrix due to an incomplete polymerization or degradation processes. Released monomers are responsible for several adverse effects in the surrounding biological tissues, inducing high levels of oxidative stress. Reactive oxygen species are important signaling molecules that regulate many signal-trasduction pathways and play critical roles in cell survival, death, and immune defenses. Reactive oxygen species were recently shown to activate autophagy as a mechanism of cell survival and cell death. Although the toxicity induced by dental resin monomers is widely studied, the cellular mechanisms underlying these phenomena are still unknown. The aim of the study was to investigate the behavior of human gingival cells exposed to 2-hydroxy-ethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) to better elucidate the mechanisms of cell survival and cell death induced by resin monomers. Primary culture of human gingival cells were exposed to 3 mmol/L of HEMA or 3 mmol/L of TEGDMA for 24, 48, and 72 h. Morphological investigations were performed by transmission electron microscopy to analyze the ultrastructure of cells exposed to the monomers. The expression of protein markers for apoptosis (caspase - 3 and PARP) and autophagy (beclin - 1 and LC3B I/II) were analyzed by western blot to investigate the influence of dental resin monomers on mechanisms underlying cell death. Results showed that HEMA treatment clearly induced autophagy followed by apoptosis while the lack of any sign of autophagy activation is observed in HGFs exposed to TEGDMA. These data indicate that cells respond to monomer-induced stress by the differential induction of adaptive mechanisms to maintain cellular homeostasis.


Behavioural health consultants in integrated primary care teams: a model for future care.
Significant challenges exist within primary care services in the United Kingdom (UK). These include meeting current demand, financial pressures, an aging population and an increase in multi-morbidity. Psychological services also struggle to meet waiting time targets and to ensure increased access to psychological therapies. Innovative ways of delivering effective primary care and psychological services are needed to improve health outcomes. In this article we argue that integrated care models that incorporate behavioural health care are part of the solution, which has seldom been argued in relation to UK primary care. Integrated care involves structural and systemic changes to the delivery of services, including the co-location of multi-disciplinary primary care teams. Evidence from models of integrated primary care in the United States of America (USA) and other higher-income countries suggest that embedding continuity of care and collaborative practice within integrated care teams can be effective in improving health outcomes. The Behavioural Health Consultant (BHC) role is integral to this, working psychologically to support the team to improve collaborative working, and supporting patients to make changes to improve their health across management of long-term conditions, prevention and mental wellbeing. Patients' needs for higher-intensity interventions to enable changes in behaviour and self-management are, therefore, more fully met within primary care. The role also increases accessibility of psychological services, delivers earlier interventions and reduces stigma, since psychological staff are seen as part of the core primary care service. Although the UK has trialled a range of approaches to integrated care, these fall short of the highest level of integration. A single short pilot of integrated care in the UK showed positive results. Larger pilots with robust evaluation, as well as research trials are required. There are clearly challenges in adopting such an approach, especially for staff who must adapt to working more collaboratively with each other and patients. Strong leadership is needed to assist in this, particularly to support organisations to adopt the shift in values and attitudes towards collaborative working. Integrated primary care services that embed behavioural health as part of a multi-disciplinary team may be part of the solution to significant modern day health challenges. However, developing this model is unlikely to be straight-forward given current primary care structures and ways of working. The discussion, developed in this article, adds to our understanding of what the BHC role might consist off and how integrated care may be supported by such behavioural health expertise. Further work is needed to develop this model in the UK, and to evaluate its impact on health outcomes and health care utilisation, and test robustly through research trials.


Development of an early diagnostic system using fuzzy theory for postoperative infections in patients with gastric cancer.
Early prediction of infection following surgery for gastric cancer may permit earlier intervention. The aim was to develop an early diagnostic system for postoperative infection. Clinical and laboratory data were analyzed in 180 patients who had surgery for gastric cancer at the Wakayama Medical University Hospital (January 1992 to December 1994). Of these, 60 patients developed a postoperative infection. A predictive system was then devised using fuzzy theory and evaluated in a second set of 137 patients who underwent surgery for gastric cancer at Wakayama Medical University and 10 other associated hospitals (August 1995 to January 1997). The system identified seven parameters grouped into six rules and entered into a fuzzy logic system to predict either infection or non-infection. (1) Blood loss, and extent of resection; (2) the febrile pattern during days 2 to 4; (3) differential leukocyte count on day 4; (4) C-reactive protein level on day 4; (5) time sequential vectors during days 1-4 for the band cell neutrophil count, and (6) leukocyte count. The sensitivity was 86% (24/28), the specificity was 90% (98/109), the negative predictive value was 96% (98/102), the positive predictive value was 69% (24/35) and the overall accuracy was 80% (122/137). Fuzzy theory can provide early prediction of postoperative infection using standard clinical and biochemical parameters. The clinical utility of this system needs to be determined in future studies.


Odour identification impairment is a trait but not a disease-specific marker for bipolar disorders: Comparisons of bipolar disorder with different episodes, major depressive disorder and schizophrenia.
Olfactory deficits have been reported in bipolar disorder, but this finding is controversial. This study investigated whether olfactory deficit can serve as a specific marker for bipolar disorder by comparing olfactory function in different mood episodes of bipolar disorder. We also compared olfactory function in bipolar disorder and other mental disorders - namely, major depressive disorder and schizophrenia. The study consisted of two experiments. Experiment 1 enrolled 175 bipolar disorder patients (70 depressed subgroup, 70 manic subgroup and 35 euthymic subgroup) and 47 controls. Experiment 2 enrolled the participants from Experiment 1, along with 85 major depressive disorder and 90 schizophrenia patients. The Sniffin' Sticks test was used to evaluate odour identification ability and odour threshold (as a measure of odour sensitivity). The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to assess depressive symptoms in all subjects and manic symptoms in bipolar disorder patients, respectively. We also used the Positive and Negative Syndrome Scale to assess clinical symptoms in schizophrenia patients. All three bipolar disorder patient subgroups (depressed, manic and euthymic subgroup) showed reduced odour identification ability compared to controls; however, only patients in the acute phase of a mood episode (depressed, and manic subgroup) showed impaired odour sensitivity. Clinical symptoms were negatively correlated with odour sensitivity but not odour identification ability. Bipolar disorder and major depressive disorder patients showed less odour identification and sensitivity impairment than schizophrenia patients. Odour sensitivity is a potential dopaminergic marker for distinguishing between bipolar disorder patients in acute phase vs remission, while odour identification is a trait but a nonspecific marker of bipolar disorder.