Distinct morphologies of arterial waveforms reveal preload-, contractility-, and afterload-deficient hemodynamic instability: An in silico simulation study.
Hemodynamic instability is frequently present in critically ill patients, primarily caused by a decreased preload, contractility, and/or afterload. We hypothesized that peripheral arterial blood pressure waveforms allow to differentiate between these underlying causes. In this in-silico experimental study, a computational cardiovascular model was used to simulate hemodynamic instability by decreasing blood volume, left ventricular contractility or systemic vascular resistance, and additionally adaptive and compensatory mechanisms. From the arterial pressure waveforms, 45 features describing the morphology were discerned and a sensitivity analysis and principal component analysis were performed, to quantitatively investigate their discriminative power. During hemodynamic instability, the arterial waveform morphology changed distinctively, for example, the slope of the systolic upstroke having a sensitivity of 2.02 for reduced preload, 0.80 for reduced contractility, and -0.02 for reduced afterload. It was possible to differentiate between the three underlying causes based on the derived features, as demonstrated by the first two principal components explaining 99% of the variance in waveforms. The features with a high correlation coefficient (>0.25) to these principal components are describing the systolic up- and downstroke, and the anacrotic and dicrotic notches of the waveforms. In this study, characteristic peripheral arterial waveform morphologies were identified that allow differentiation between deficits in preload, contractility, and afterload causing hemodynamic instability. These findings are confined to an in silico simulation and warrant further experimental and clinical research in order to prove clinical usability in daily practice.


An integrative study of Necremnus Thomson (Hymenoptera: Eulophidae) associated with invasive pests in Europe and North America: taxonomic and ecological implications.
The species of Necremnus attacking two invasive pests of tomato and canola in Europe and North America, respectively, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), have been revised using an integrative taxonomy approach. Molecular data from the mitochondrial cytochrome oxidase c subunit I and the nuclear D2 expansion region of the 28S ribosomal subunit and internal transcribed spacer 2, the discovery of new morphological features, and study of type material resulted in the delineation of three species groups, the Necremnus artynes, Necremnus cosconius, and Necremnus tidius groups, the discovery of four new species, and the resurrection of three taxa from synonymy. Lectotypes have been designated for 13 species originally described in Eulophus by Walker. Although Necremnus has not been revised, an illustrated key is given to differentiate 23 recognized European species. The key, type images, and treatments of the three species groups will enable more accurate identification of the valid species of Necremnus in the future. They will also benefit biological control practitioners of pest species. The ecological consequences of the new taxonomic concepts are discussed.


Inconsistent screening for lead endangers vulnerable children: policy lessons from South Bend and Saint Joseph County, Indiana, USA.
Lead exposure is a major health hazard affecting children and their growth and is a concern in many urban areas around the world. One such city in the United States (US), South Bend Indiana, gained attention for its high levels of lead in blood and relatively low testing rates for children. We assessed current lead screening practices in South Bend and the surrounding St. Joseph County (SJC). The 2005-2015 lead screening data included 18,526 unique children. Lead screening rates ranged from 4.7 to 16.7%. More than 75% of children had 'elevated blood lead levels' (EBLL) ≥ 1 micrograms per deciliter (µg/Dl) and 9.7% had an EBLL ≥ 5 μg/dL. Over 65% of the census tracts in SJC had mean EBLL ≥ 5 μg/dL, suggesting widespread risk. Inconsistent lead screening rates, coupled with environmental and societal risk factors, put children in SJC at greater risk for harmful lead exposure than children living in states with provisions for universal screening. Indiana and other states should adhere to the US Centers for Disease Control's guideline and use universal lead testing to protect vulnerable populations.


Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats.
The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D(2) receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D(2) antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n = 17) or were ethanol-naive (n = 24). Stable intake of 15% (v/v) ethanol (>/=0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 microl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 microM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. In ethanol-drinking rats, 100 and 200 microM SUL increased extracellular NAc DA levels to approximately 200% of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 microM SUL increased extracellular NAc DA levels significantly more (450% of basal; p < 0.05) than in the ethanol-drinking group. The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D(2) autoreceptors in the NAc of P rats.


A Candidate Magnetic Sense Organ in the Yellowfin Tuna, Thunnus albacares.
Single-domain magnetite crystals have been isolated and characterized from tissue located in a sinus within the dermethmoid bone of the skull of the yellowfin tuna, Thunnus albacares. Their chemical composition, narrow size distribution, and distinctive crystal morphology indicate that these crystals are biochemical precipitates. Experiments on the interaction between particles reveal the organization of the particles in situ and suggest a possible form for candidate magnetoreceptor organelles. The consistent localization of such particles with similar arrangement within the dermethmoids of this and other pelagic fishes suggests that the ethmoid region is a possible location for a vertebrate magnetic sense organ.


Refined fetal abdominal growth assessment in normal pregnancy: Part I. Abdominal anteroposterior diameter.
The assessment of the adequacy of fetal growth by parameters other than the abdominal anteroposterior diameter (AAPD) of the fetus has been studied extensively. However the designs of these studies and the statistical methods used appears to deserve some criticism, based on present knowledge. Noncross-sectional cases selection, uncertainty of the fetal normality and inadequacy in statistical method, mostly ignored the changing property of each standard deviation (SD) of each gestational age (GA) which was proposed by Altman et. al. in 1993, are the three most common flaws in previous publishes. We tried to use AAPD with a strict study design as well as a reasonable statistical method to evaluate the fetal growth. This study was performed in the Division of Maternal Fetal Medicine, National Cheng Kung University Hospital, Taiwan. The prenatal sonographic data of the fetuses were collected prospectively based on the following criteria: (1) accurate dating by knowing the maternal last menstration period (LMP) and early ultrasonography of the fetuses, (2) singleton pregnancy, (3) no fetal structural or chromosomal abnormality confirmed by prenatal ultrasonography and postnatal examination, (4) GA at birth was between 37 and 41 weeks' gestation, (5) no birth asphyxia, (6) appropriate birth body weight, and (7) no maternal medical disease or obstetrical complication which might predictably interfere with fetal growth. The collected data were analyzed by polynomial regression test and the best-fit equation for prediction of fetal growth was selected. The standard deviation (SD) of each GA was modeled before constructing the fetal growth centile charts by Altman's method. A total of 2077 cross-sectional sonographic data meeting the above criteria were collected for statistical analysis. The best-fit equation for the prediction of fetal GA by AAPD is GA = 20.8539 - 3.36743 x AAPD + 0.86927 x (AAPD)2 - 0.03789 x (AAPD)3 +/- k x [1.2533 x (0.36772 + 0.10938 x AAPD)], (r = 0.97287, p < 0.0001). The best-fit equation for prediction of fetal AAPD by GA is AAPD = -2.49495 + 0.38247 x GA - 1.07071 x 0.001 x (GA)2 +/- k x [1.2533 x (0.01760 + 0.01372 x GA)], r = 0.97122, p < 0.0001. The SD of AAPD for each complete GA was not the same. The fetal growth centile charts in the study are presented in this article. The SD of each complete GA changed with each specific GA. The GA of the fetus can be assessed accurately by measuring the AAPD alone. The utilization of these growth centile charts for evaluation of fetal growth is recommended.


Functionality, satisfaction, and global impression of change with ubrogepant for the acute treatment of migraine in triptan insufficient responders: a post hoc analysis of the ACHIEVE I and ACHIEVE II randomized trials.
Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016.


Investigations on the frequency of norovirus contamination of ready-to-eat food items in Istanbul, Turkey, by using real-time reverse transcription PCR.
Investigation of norovirus (NoV) contamination of food items is important because many outbreaks occur after consumption of contaminated shellfish, vegetables, fruits, and water. The frequency of NoV contamination in food items has not previously been investigated in Turkey. The aim of this study was to investigate the frequency of human NoV genogroups (G) I and II in ready-to-eat tomatoes, parsley, green onion, lettuce, mixed salads, and cracked wheat balls. RNA was extracted with the RNeasy Mini Kit, and a real-time reverse transcription (RT) PCR assay was performed using primers specific for NoV GI and GII. Among the 525 samples analyzed, NoV GII was detected in 1 green onion sample and 1 tomato sample by both SYBR Green and TaqMan real-time RT-PCR assays; no GI virus was detected. The Enterobactericaeae and Escherichia coli levels in the NoV-positive green onion were 6.56 and 1.28 log CFU/g, and those in the tomato were 5.55 and 1.30 log CFU/g, respectively. No significant difference in the bacterial levels was found between the NoV-positive and NoV-negative samples. This study is the first in which NoV GII was found in ready-to-eat food collected from Istanbul, Turkey; thus, these foods may be considered a risk to human health. Epidemiological studies and measures to prevent NoV infection should be considered.


Pulmonary leiomyosarcoma--report of three cases.
Three cases of pulmonary leiomyosarcoma were presented. The characteristic clinical features were described with review of literature. In comparison with bronchogenic carcinoma, the leiomyosarcoma has some characteristics: 1) On chest X-ray, it usually appears as a sharply demarcated, even density round mass, growing rapidly within the lung, it rarely accompanies with hilar or mediastinal lymph node metastasis. 2) The preoperative cytological or pathological diagnosis is difficult either by sputum smear or by bronchoscopic biopsy or by fine needle percutaneous aspiration biopsy. 3) Pathological differential diagnosis of leiomyosarcoma of lung from anaplastic lung cancer is difficult. In conclusion, the primary pulmonary leiomyosarcoma is a rare malignant tumor, detecting the present illness seriously, paying attention to the chest X-ray films characterize, early surgical resection is the only way to get diagnosis and effective treatment method.


Role of coronary angiography in myxoma patients: a 14-year experience in one medical center.
Cardiac myxoma is the most common form of primary heart tumor and often treated with surgical resection without a preoperative angiographic examination for fear of potential risk of sudden death. During the last 14 years, 24 of 38 patients with myxoma underwent coronary angiography. Coronary artery disease (CAD) and other abnormalities were found in 5. Our findings indicated that CAD is not uncommon among the myxoma patients, and coronary angiography should be performed preoperatively in all cases.


Deep Learning Segmentation of Lower Extremities Radiographs for an Automatic Leg Length Discrepancy Measurement.
Leg length measurement is relevant for the early diagnostic and treatment of discrepancies as they are related with orthopedic and biomechanical changes. Simple radiology constitutes the gold standard on which radiologists perform manual lower limb measurements. It is a simple task but represents an inefficient use of their time, expertise and knowledge that could be spent in more complex labors. In this study, a pipeline for semantic bone segmentation in lower extremities radiographs is proposed. It uses a deep learning U-net model and performs an automatic measurement without consuming physicians' time. A total of 20 radiographs were used to test the methodology proposed obtaining a high overlap between manual and automatic masks with a Dice coefficient value of 0.963. The obtained Spearman's rank correlation coefficient between manual and automatic leg length measurements is statistically different from cero except for the angle of the left mechanical axis. Furthermore, there is no case in which the proposed automatic method makes an absolute error greater than 2 cm in the quantification of leg length discrepancies, being this value the degree of discrepancy from which medical treatment is required.Clinical Relevance- Leg length discrepancy measurements from X-ray images is of vital importance for proper treatment planning. This is a laborious task for radiologists that can be accelerated using deep learning techniques.


Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC).
This study aims at describing the natural history and outcome of small duct primary sclerosing cholangitis (PSC). Thirty-two patients with small duct PSC were studied. The average time taken for diagnosis was 69 (1-168) months. The median follow-up time was 63 (1-194) months. All patients including one who underwent liver transplantation because of end-stage liver disease and hepatocellular carcinoma were alive at follow-up. None developed cholangiocarcinoma. In 27 patients repeated cholangiographic examinations were done after a median time of 72 (12-192) months from first ERCP. Four developed features of large duct PSC. Small duct PSC rarely progresses to large bile duct PSC and it seems to have a benign course in most patients and no development of cholangiocarcinoma was found.


Pathogenicity of the fungus, Verticillium lecanii, to the green peach aphid, Myzus persicae (Hom.: Aphididae).
Pathogenicity of the hyphomycete, Verticillium lecanii (DAOM 198499), was investigated to aphid, Myzus persicae under laboratory conditions. Analysis of lethal effect of six various concentrations 0, 10(4), 10(5), 10(6), 10(7) and 10(8) conidia/ml of V. lecanii against third nymphal stage of M. persicae, indicated significant mortality on aphids. Mean comparisons showed that there was significant difference between treatments. Three days after treatment, aphid mortality observed and after 12 days minimal mortality was 17.77 in control and maximum was 100 percent related to 10(7) and 10(8) conidia/ml. LC50 and LT50 values were estimated by probit analysis and life test. LC50 value for aphid mortality was 1.4 x 10(4) conidia/ml, LT50 values for concentrations 10(4), 10(6), 10(6), 10(7) and 10(8) conidla/ml was 10, 10, 9, 8 and 6 days, respectively. In this experiment, net reproduction rate of aphid's (R0) decreased significantly when concentration increased. These observations showed that V. lecanii (DAOM 198499) can be an active biological agent against aphids.


Finasteride-induced prostatic involution by apoptosis in dogs with benign prostatic hypertrophy.
To determine the effect of finasteride on programmed cell death (apoptosis) of prostatic cells during prostatic involution in dogs with benign prostatic hypertrophy (BPH). 9 dogs with BPH. Dogs were randomly assigned to treatment or control groups. Treatment dogs (n = 5) were administered finasteride (0.1 to 0.5 mg/kg, PO, q 24 h) for 16 weeks, whereas the 4 control dogs were administered an inert compound. Prostatic cells from the prostatic fluid portion of the ejaculate of treatment and control dogs were obtained before and 1, 2, 3, 4, 8, and 16 weeks after initiation of treatment. Cells were concentrated by use of centrifugation. Prostatic cells were examined for indications of apoptosis by use of a terminal deoxyribonucleotidyl transferase-mediated deoxyuracil triphosphate nick-end labeling technique. After receiving the inert compound for 16 weeks, the 4 control dogs were administered finasteride for 16 weeks, and evaluations were repeated. Percentage of apoptotic prostatic cells in ejaculated prostatic fluid of treatment dogs increased significantly (from 9% before treatment to 33, 31, 26, and 27% after 1, 2, 3, and 8 weeks of treatment, respectively). There was no significant change in percentage of apoptotic prostatic cells in the ejaculated prostatic fluid of control dogs. Finasteride-induced prostatic involution appears to be via apoptosis in dogs with BPH. Finasteride treatment of dogs with BPH causes prostatic involution by apoptosis rather than necrosis.


Preparation and in vitro evaluation of strontium-doped calcium silicate/gypsum bioactive bone cement.
The combination of two or more bioactive components with different biodegradability could cooperatively improve the physicochemical and biological performances of the biomaterials. Here we explore the use of α-calcium sulfate hemihydrate (α-CSH) and calcium silicate with and without strontium doping (Sr-CSi, CSi) to fabricate new bioactive cements with appropriate biodegradability as bone implants. The cements were fabricated by adding different amounts (0-35 wt%) of Sr-CSi (or CSi) into the α-CSH-based pastes at a liquid-to-solid ratio of 0.4. The addition of Sr-CSi into α-CSH cements not only led to a pH rise in the immersion medium, but also changed the surface reactivity of cements, making them more bioactive and therefore promoting apatite mineralization in simulated body fluid (SBF). The impact of additives on long-term in vitro degradation was evaluated by soaking the cements in Tris buffer, SBF, and α-minimal essential medium (α-MEM) for a period of five weeks. An addition of 20% Sr-CSi to α-CSH cement retarded the weight loss of the samples to 36% (in Tris buffer), 43% (in SBF) and 54% (in α-MEM) as compared with the pure α-CSH cement. However, the addition of CSi resulted in a slightly faster degradation in comparison with Sr-CSi in these media. Finally, the in vitro cell-ion dissolution products interaction study using human fetal osteoblast cells demonstrated that the addition of Sr-CSi improved cell viability and proliferation. These results indicate that tailorable bioactivity and biodegradation behavior can be achieved in gypsum cement by adding Sr-CSi, and such biocements will be of benefit for enhancing bone defect repair.


Spatial electrocardiography.
Spatial electrocardiography can express the spatial characteristics of electromotive forces of the heart quantiatively. The pattern of the sequential changes of these spatial characteristics of the cardiac vectors also provides important diagnostic informations. Accordingly, spatial electrocardiography is considered to be useful in clinical cardiology in association with conventional electrocardiography and vectorcardiography.


[The use of the new biological adhesive preparation fibrin polymer in thyroid surgery].
A study made in 18 patients with nodular euthyroiditis and toxic goiter proved high efficacy of a new preparation "Fibrin Polymer" ("Bioadhesive") based on a combined action of human fibrinogen and thrombin. Employment of the above preparation makes for maintaining intraoperative hemostasis, reducing postoperative wound serous and haemorrhagic and lymphatic secretion, joining lips of skin wound to improve cosmetic results of the operation. A novel modality is proposed for low-invasive treatment of cystic forms of nodular goiter based on obliteration of the cyst with the aid of the preparation "Fibrin Polymer" administered by puncturing the cyst following aspiration of its contents. Of the eight treated patients, 1 had a recurrence, 2 subjects had more than 2-fold diminution in cyst size, 5 patients recovered 12 months following the treatment. The preparation "Fibrin Polymer" should, we believe, come to be widely used in thyroid surgery.


[Post-traumatic pulsating exophthalmus coexisting with congenital carotid-cavernous fistula].
Pulsating exophthalmus develops most frequently in the course of penetrating or bitemporal head trauma. Idiopathic form is even more rare. Orbit venous system over-loading with pathological arterial blood infiltration is the cause of pulsating exophthalmus. A patient with congenital carotid-cavernous fistula (right eyeball enlargement and noise), suffering from head trauma after road accident has been presented. Carotid-cavernous fistula was diagnosed and than treated casually by endovascular closure of the infiltration between internal carotid artery and cavernous sinus. After 5-month treatment regression of the noise and exophthalmus was observed.


Rigid, Variable-View Endoscope in Neurosurgery: First Intraoperative Experience.
The endoscope became a highly valued visualization tool in neurosurgery. However, technical limitations caused by the rigidity of current standard endoscopes significantly decrease ergonomy in transcranial neurosurgery. Further technological developments will aid enlarging the surgical applicability. To evaluate the intraoperative features of a rigid variable-view endoscope in neurosurgery. We assessed a 4 mm rigid rod lens endoscope (EndoCAMeleon, Karl Storz, Tuttlingen, Germany) in the intraoperative setting. The device offers a variable angle of view from 15° to 90° in one plane. The endoscope was used in 3 cases (aneurysm clipping, vestibular schwannoma surgery, endoscopic third ventriculostomy) for inspection. Direct insertion of the device through the craniotomy/burr hole with the lowest angled view (15°) was always possible. Neurovascular structures crossing the access route could be visualized and avoided. This allowed a targeted positioning of the endoscope's tip in the operating field. Once the target point was reached, viewing direction was changed in one plane from 15° to 90° according to anatomic demands. As the endoscope's tip does not move while the lens is rotated, surrounding neurovascular structures are not at risk to be injured. However, turning of the lens-controlling wheel in proximity to delicate structures may be inconvenient. The rigid, variable-view endoscope has the potential to become an appreciated visualization tool in neuroendoscopy. The steerable lens enables a tremendous expansion of the visual field, resulting in higher efficiency for surgeons and increased safety for patients.


Chemotaxis in Borrelia burgdorferi.
Borrelia burgdorferi is a motile spirochete which has been identified as the causative microorganism in Lyme disease. The physiological functions which govern the motility of this organism have not been elucidated. In this study, we found that motility of B. burgdorferi required an environment similar to interstitial fluid (e.g., pH 7.6 and 0.15 M NaCl). Several methods were used to detect and measure chemotaxis of B. burgdorferi. A number of chemical compounds and mixtures were surveyed for the ability to induce positive and negative chemotaxis of B. burgdorferi. Rabbit serum was found to be an attractant for B. burgdorferi, while ethanol and butanol were found to be repellents. Unlike some free-living spirochetes (e.g., Spirochaeta aurantia), B. burgdorferi did not exhibit any observable chemotaxis to common sugars or amino acids. A method was developed to produce spirochete cells with a self-entangled end. These cells enabled us to study the rotation of a single flagellar bundle in response to chemoattractants or repellents. The study shows that the frequency and duration for pausing of flagella are important for chemotaxis of B. burgdorferi.


Semiquantitative Screening of THC Analogues by Silica Gel TLC with an Ag(I) Retention Zone and Chromogenic Smartphone Detection.
With the ever-evolving cannabis industry, low-cost and high-throughput analytical methods for cannabinoids are urgently needed. Normally, (potentially) psychoactive cannabinoids, typically represented by Δ9-tetrahydrocannabinol (Δ9-THC), and nonpsychoactive cannabinoids with therapeutic benefits, typically represented by cannabidiol (CBD), are the target analytes. Structurally, the former (tetrahydrocannabinolic acid (THCA), cannabinol (CBN), and THC) have one olefinic double bond and the latter (cannabidiolic acid (CBDA), cannabigerol (CBG), and CBD) have two, which results in different affinities toward Ag(I) ions. Thus, a silica gel thin-layer chromatography (TLC) plate with the lower third impregnated with Ag(I) ions enabled within minutes a digital chromatographic separation of strongly retained CBD analogues and poorly retained THC analogues. The resolution (Rs) between the closest two spots from the two groups was 4.7, which is almost 8 times higher than the resolution on unmodified TLC. After applying Fast Blue BB as a chromogenic reagent, smartphone-based color analysis enabled semiquantification of the total percentage of THC analogues (with a limit of detection (LOD) of 11 ng for THC, 54 ng for CBN, and 50 ng for THCA when the loaded volume is 1.0 μL). The method was validated by analyzing mixed cannabis extracts and cannabis extracts. The results correlated with those of high-performance liquid chromatography with ultraviolet detection (HPLC-UV) (R2 = 0.97), but the TLC approach had the advantages of multi-minute analysis time, high throughput, low solvent consumption, portability, and ease of interpretation. In a desiccator, Ag(I)-TLC plates can be stored for at least 3 months. Therefore, this method would allow rapid distinction between high and low THC varieties of cannabis, with the potential for on-site applicability.


Levels of Aggression among Turkish Adolescents and Factors Leading to Aggression.
Aggression, an increasing problem among adolescents, is a potential threat to public health as it can lead to violence. Determining the factors causing aggression plays an important role in taking measures to reduce violence. This study aimed at determining the level of aggression among adolescents and at identifying the factors associated with high levels of aggression. This cross-sectional study was conducted with 2,409 Turkish adolescents. Data were collected with the Socio-demographic Questionnaire, Aggression Scale, Perceived Social Support Scale, and Communication Skills Attitude Scale. Data were analyzed using descriptive statistics, the chi-square test, t-test, and logistic regression. The participants' mean aggression score was 91.83 ± 24.05, and 24.0% of the adolescents' aggression levels rated high. According to the logistic regression model, aggression was 1.26 times higher among males, 1.92 times higher among those who perceived their mental health as poor, 1.58 times higher among those with suicidal ideation, 1.29 times higher among those who did not get prepared for university entrance exams, and 1.62 times higher among those who perceived their school performance as poor. Perceived family social support was a protective factor against high aggression. Approximately one out of every four adolescents in the two Turkish high schools where the study was conducted was determined to display high levels of aggression. Therefore, in order to reduce aggression among adolescents, programs such as coping management and coping with anger should be applied by nurses. Programs should include not only students but also families.


Social Development of Adults with Autism Spectrum Disorder During Dog-Assisted Therapy: A Detailed Observational Analysis.
Social communication and self-esteem are often affected in adults with autism spectrum disorder. Implementation and evaluation of interventions targeting social skills are challenged due to specific characteristics of autism. Intensive, valid evaluation of social skills programs is needed. In this explorative multiple case study, we examined effects and working mechanisms of dog-assisted therapy on social communication and self-esteem, by analyzing detailed observations with Monte Carlo permutation tests (testing against 10,000 random samples) and using self- and other-reports in N=6 high-functioning adults with ASD. Results showed significant positive effects on secure body posture. There was an indication of improved self-esteem and more spontaneous touching of the dog, while no convincing increase was found for verbal initiatives. Cross-correlation analyses revealed that touching the therapy dog may be an important determinant to elicit social development in Animal Assisted Therapy (AAT). Considering preliminary results, we recommend exploring underlying mechanisms more thoroughly with real-time observations, accounting for possible gender-effects.


Ambient air pollutants and hospital visits for pneumonia: a case-crossover study in Qingdao, China.
Pneumonia is one of the principal reasons for incidence and death in the world. The former research mainly concentrated on specific sources of patients. Besides, due to the heterogeneity among regions, there are inconsistencies in the outcome of these surveys. To explore the relationship between atmospheric pollution and hospital visits for pneumonia under the climate and pollution conditions in Qingdao, we carried out this study. The medical records of pneumonia patients were gathered from the affiliated hospital of Qingdao University during Jan 1st, 2014, and Dec 31st,2018. Daily concentrations of PM2.5, PM10, SO2, NO2, as well as CO, were collected from the national air quality monitoring stations in Qingdao. Case-crossover study design and conditional logistic regression model were used to estimate the associations. Daily temperature, relative humidity, and atmospheric pressure were adjusted as the covariates in all models. A principal component analysis was used to solve the multicollinearity between atmospheric pollutants and investigate the relationship between various air pollutants and pneumonia occurs. In the single pollutant model, with interquartile range increment of the density of PM2.5, PM10, NO2 and SO2 at the lag2 days, the odds ratio of hospital visits for pneumonia patients increased by 6.4% (95%CI, 2.3-10.7%), 7.7% (95%CI, 3.2-12.4%), 6.7% (95%CI, 1.0-12.7%), and 7.2% (95%CI, 1.1-13.5%). Stratified analysis showed that pollutants were more significant in the cold period. Besides, the impact of atmospheric particulates on different ages mainly occurs in the young child (0 to 3-year-old). The odds ratio was 1.042 (95%CI, 1.012-1.072) when the principal components of atmospheric pollutants were included in the conditional logistic model. Our study found a significant relationship between short-term uncovering to PM2.5, PM10, NO2, SO2, and hospital visits for pneumonia in Qingdao. The effect of atmospheric pollutants mainly arose in a cold period. The particulate matter might be the principal reason in inducing hospital visits for pneumonia.


The human dorsal action control system develops in the absence of vision.
The primate dorsal pathway has been proposed to compute vision for action. Although recent findings suggest that dorsal pathway structures contribute to somatosensory action control as well, it is yet not clear whether or not the development of dorsal pathway functions depends on early visual experience. Using functional magnetic resonance imaging, we investigated the pattern of cortical activation in congenitally blind and matched blindfolded sighted adults while performing kinesthetically guided hand movements. Congenitally blind adults activated similar dorsal pathway structures as sighted controls. Group-specific activations were found in the extrastriate cortex and the auditory cortex for congenitally blind humans and in the precuneus and the presupplementary motor area for sighted humans. Dorsal pathway activity was in addition observed for working memory maintenance of kinesthetic movement information in both groups. Thus, the results suggest that dorsal pathway functions develop in the absence of vision. This favors the idea of a general mechanism of movement control that operates regardless of the sensory input modality. Group differences in cortical activation patterns imply different movement control strategies as a function of visual experience.


Arginase-1 is More Specific Than Hepatocyte Paraffin 1 for Differentiating Hepatocellular Carcinomas With Cytoplasmic Clearing from Nonhepatocellular Clear Cell Tumors in Liver Biopsies.
Arginase-1 (Arg1) and hepatocyte paraffin antigen 1 (HepPar1) are specific and sensitive markers of hepatocellular differentiation. HepPar1 is a granular cytoplasmic immunostain that may be negative in hepatocellular carcinoma (HCC) with cytoplasmic clearing. Arg1 shows uniform cytoplasmic positivity and frequent nuclear positivity. This study was undertaken to determine the staining pattern of Arg1 in HCC with cytoplasmic clearing and compare its use to HepPar1. Fifteen resected HCCs with cytoplasmic clearing and 31 biopsies of clear cell liver tumors (14 HCCs and 17 nonhepatocellular tumors) were identified. Resections were stained with Arg1 to characterize the pattern, intensity, and extent of Arg1 positivity. Biopsies were stained with Arg1 (n=31) and HepPar1 (n=28). In all, 13/15 resected and 11/14 biopsied HCCs with cytoplasmic clearing showed nuclear positivity for Arg1. Both Arg1 and HepPar1 stained significantly more HCCs than nonhepatocellular tumors (13/14 and 11/12, respectively, with P <0.0001 and P =0.0018, respectively). However, HepPar1 stained significantly more nonhepatocellular tumors (5/12) than Arg1 (0/17, P =0.0445). Arg1 frequently displayed nuclear positivity, and interobserver agreement was better for Arg1 ( K =0.93 vs. 0.79). Overall, Arg1 is more specific than HepPar1 for differentiating HCC with cytoplasmic clearing from nonhepatocellular clear cell tumors in the liver. Its staining characteristics, including nuclear positivity, make it easier to interpret in combination with morphology, improving interobserver variability, and it stains significantly fewer mimics than HepPar1.


Interprofessional collaboration with service users in the development of cancer services: the Cancer Partnership Project.
Patient and Public Involvement (PPI) is a cornerstone of UK National Health Service (NHS) policy. The Cancer Partnership Project (CPP) is the leading national PPI initiative in cancer care. The CPP espouses a "partnership" model, with a "Partnership Group" - collaborative service improvement groups formed of NHS staff and service users - in each of 34 cancer networks in England. These groups aim to enable service users to influence local cancer service development and thereby improve the effectiveness of services. We interviewed 59 cancer service users and NHS staff in a reflective evaluation of CPP. Groups were active and visible in 30 networks, their main activities being: providing an accessible source of consumer opinion; prolific networking and representation; patient information and communication projects; and lobbying for service improvements. The groups exhibited some significant tensions. The motivations of professional staff varied markedly, and "obligatory" involvement as part of a person's job was counter-productive when not coupled with a "personal" belief in the value of PPI. Other controversial areas were the disclosure by patients' of personal health and treatment experiences, and emotional attachment to the group. It was concluded that partnership groups represent a useful PPI model, but more attention generally should be paid to the complexities of PPI and timescales required for meaningful cultural change.


Rare functional genetic variants in COL7A1, COL6A5, COL1A2 and COL5A2 frequently occur in Chiari Malformation Type 1.
Chiari Malformation Type 1 (CM-1) is characterized by herniation of the cerebellar tonsils below the foramen magnum and the presence of headaches and other neurologic symptoms. Cranial bone constriction is suspected to be the most common biologic mechanism leading to CM-1. However, other mechanisms may also contribute, particularly in the presence of connective tissue disorders (CTDs), such as Ehlers Danlos Syndrome (EDS). Accumulating data suggest CM-1 with connective tissue disorders (CTD+) may have a different patho-mechanism and different genetic risk factors than CM-1 without CTDs (CTD-). To identify CM-1 genetic risk variants, we performed whole exome sequencing on a single large, multiplex family from Spain and targeted sequencing on a cohort of 186 unrelated adult, Caucasian females with CM-1. Targeted sequencing captured the coding regions of 21 CM-1 and EDS candidate genes, including two genes identified in the Spanish family. Using gene burden analysis, we compared the frequency of rare, functional variants detected in CM-1 cases versus publically available ethnically-matched controls from gnomAD. A secondary analysis compared the presence of rare variants in these genes between CTD+ and CTD- CM-1 cases. In the Spanish family, rare variants co-segregated with CM-1 in COL6A5, ADGRB3 and DST. A variant in COL7A1 was present in affected and unaffected family members. In the targeted sequencing analysis, rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls. In total, 47% of CM-1 cases presented with rare variants in at least one of the four significant collagen genes and 10% of cases harbored variants in multiple significant collagen genes. Moreover, 26% of CM-1 cases presented with rare variants in the COL6A5 gene. We also identified two genes (COL7A1, COL3A1) for which the burden of rare variants differed significantly between CTD+ and CTD- CM-1 cases. A higher percentage of CTD+ patients had variants in COL7A1 compared to CTD+ patients, while CTD+ patients had fewer rare variants in COL3A1 than did CTD- patients. In summary, rare variants in several collagen genes are particularly frequent in CM-1 cases and those in COL6A5 co-segregated with CM-1 in a Spanish multiplex family. COL6A5 has been previously associated with musculoskeletal phenotypes, but this is the first association with CM-1. Our findings underscore the contribution of rare genetic variants in collagen genes to CM-1, and suggest that CM-1 in the presence and absence of CTD symptoms is driven by different genes.


Hypothenar Hammer Syndrome Presenting as Critical Limb Ischemia in a 41-year-Old Caucasian Female; A Case Report.
Traumatic injuries to the hand are commonly encountered in the adult population. Arterial occlusion from digital emboli due to thrombosis is a less frequently observed etiology. An example is hypothenar hammer syndrome, which usually arises following a mechanical injury. We report a case of hypothenar hammer syndrome in a 41-year-old Caucasian female following a blunt injury from exercise. She presented to our facility with complaints of intermittent severe pain in her left hand with discoloration of her fourth and fifth digits. Her symptoms began following an intense upper body strength exercise session and recurred intermittently over the following four to six weeks. MRI of the left hand showed no bony fractures or soft tissue injury. She was commenced on aspirin and Xarelto and subsequently had an arteriogram revealing thrombosis in the distal left ulnar artery. She ultimately had surgical resection of the thrombosed artery with repair using a venous graft which led to the resolution of her symptoms. Xarelto was discontinued after surgery, but she remains on Aspirin.


Numeracy, adult education, and vulnerable adults: a critical view of a neglected field.
This survey paper examines selected issues related to the intersection of three broad scholarly areas: numeracy, adult education, and vulnerability. Numeracy encompasses the ways in which people cope with the mathematical, quantitative, and statistical demands of adult life, and is viewed as an important outcome of schooling and as a foundational skill for all adults. The focus on vulnerability stems from the realization that concerns of policy makers and educators alike often center on populations seen as vulnerable. The paper is organized in five sections. After a brief introduction, Section 2 examines adult numeracy, focusing on five numeracy domains (health, financial, digital, civic, and workplace numeracy), literacy-numeracy linkages, functional and critical aspects of numeracy, and the centrality of numeracy practices, and notes sources of vulnerability for each of these. Section 3 sketches formal, non-formal and informal contexts in which adults learn or develop their numeracy, and examines factors that may be potential sources of vulnerability, including systemic factors and dispositional and affect factors. Section 4 reflects more broadly on the concept of vulnerability, introduces selected aspects of the papers published in this issue of ZDM Mathematics Education, and points to findings regarding adult learners who may be deemed vulnerable. The closing section summarizes conclusions and research directions regarding the intersection of the three core domains. Overall, the paper points to emerging research needs and educational challenges that are relevant to scholars, practitioners, and policy makers interested in developing the numeracy of adults as well as in the mathematics education of younger learners.


The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA.
The NXF1:NXT1 complex (also known as TAP:p15) is a general mRNA nuclear export factor that is conserved from yeast to humans. NXF1 is a modular protein constructed from four domains (RRM, LRR, NTF2-like and UBA domains). It is currently unclear how NXF1:NXT1 binds transcripts and whether there is higher organization of the NXF1 domains. We report here the 3.4 Å resolution crystal structure of the first three domains of human NXF1 together with NXT1 that has two copies of the complex in the asymmetric unit arranged to form an intimate domain-swapped dimer. In this dimer, the linkers between the NXF1 LRR and NTF2-like domains interact with NXT1, generating a 2-fold symmetric platform in which the RNA-binding RRM, LRR and NTF2-like domains are arranged on one face. In addition to bulk transcripts, NXF1:NXT1 also facilitates the export of unspliced retroviral genomic RNA from simple type-D retroviruses such as SRV-1 that contain a constitutive transport element (CTE), a cis-acting 2-fold symmetric RNA stem-loop motif. Complementary structural, biochemical and cellular techniques indicated that the formation of a symmetric RNA binding platform generated by dimerization of NXF1:NXT1 facilitates the recognition of CTE-RNA and promotes its nuclear export.


[Usefulness and predictive value of PSA density, adjusted by transition zone volume, in men with PSA levels between 2 and 4 ng/ml].
To assess the diagnostic significance of prostate-specific antigen (PSA), density (PSAD) accuracy, and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.0 and 4.0 ng/ml. Between 2000 and 2010, 138 men with PSA levels between 2 and 4.0 ng/ml underwent transrectal ultrasonography (TRUS) and 12-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml. The detection rate of prostate cancer was 23,8% (32/134). The percentage of patients with extracapsular disease was 28.1% (10/32) and primary Gleason grade 4 or 5 was obtained in 8/32 (25%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.0 to 4.0 ng/ml.


Domestic violence and sexually transmitted diseases: the experience of prenatal care patients.
The authors analyzed interview responses of patients at a prenatal care clinic to explore whether women who had been victims of sexual and physical abuse were more likely than non-victimized women to have experienced a sexually transmitted disease (STD). A consecutive sample of 774 prenatal patients of a large health department in North Carolina were interviewed concerning a variety of health issues, including violence and STDs. Logistic regression analysis was used to model the women's STD status as a function of their experiences of sexual and physical abuse, controlling for several potentially confounding factors. Thirty percent of the women reported having experienced at least one STD, with the most common infections being chlamydia and gonorrhea. Twenty-eight percent of the women reported having been victims of abuse; 16% reported physical abuse only, while 12% reported both physical and sexual abuse. The majority of violence was domestic in nature, perpetrated by the victims' husbands, boyfriends, male friends, and relatives. After controlling for confounding variables, the authors found that women who reported both physical and sexual abuse were significantly more likely to have experienced STDs than non-victims (odds ratio [OR] = 2.25; 95% confidence interval [CI] 1.37, 3.69). The logistic regression analysis also showed a relationship of borderline statistical significance between non-sexual physical abuse and STDs. Health care providers should routinely screen patients for both abuse and STDs, and they should assist identified women in accessing appropriate health, social, and legal services.


Application of nonnegative matrix factorization to improve profile-profile alignment features for fold recognition and remote homolog detection.
Nonnegative matrix factorization (NMF) is a feature extraction method that has the property of intuitive part-based representation of the original features. This unique ability makes NMF a potentially promising method for biological sequence analysis. Here, we apply NMF to fold recognition and remote homolog detection problems. Recent studies have shown that combining support vector machines (SVM) with profile-profile alignments improves performance of fold recognition and remote homolog detection remarkably. However, it is not clear which parts of sequences are essential for the performance improvement. The performance of fold recognition and remote homolog detection using NMF features is compared to that of the unmodified profile-profile alignment (PPA) features by estimating Receiver Operating Characteristic (ROC) scores. The overall performance is noticeably improved. For fold recognition at the fold level, SVM with NMF features recognize 30% of homolog proteins at > 0.99 ROC scores, while original PPA feature, HHsearch, and PSI-BLAST recognize almost none. For detecting remote homologs that are related at the superfamily level, NMF features also achieve higher performance than the original PPA features. At > 0.90 ROC50 scores, 25% of proteins with NMF features correctly detects remotely related proteins, whereas using original PPA features only 1% of proteins detect remote homologs. In addition, we investigate the effect of number of positive training examples and the number of basis vectors on performance improvement. We also analyze the ability of NMF to extract essential features by comparing NMF basis vectors with functionally important sites and structurally conserved regions of proteins. The results show that NMF basis vectors have significant overlap with functional sites from PROSITE and with structurally conserved regions from the multiple structural alignments generated by MUSTANG. The correlation between NMF basis vectors and biologically essential parts of proteins supports our conjecture that NMF basis vectors can explicitly represent important sites of proteins. The present work demonstrates that applying NMF to profile-profile alignments can reveal essential features of proteins and that these features significantly improve the performance of fold recognition and remote homolog detection.


Pathophysiology as a basis for understanding symptom complexes and therapeutic targets.
Sensorimotor disorders of the stomach, small intestine and colon have a limited repertoire of clinical manifestations, and there is the potential for more than one mechanism to lead to symptoms. In many recent clinical trial programs of novel agents in neurogastroenterology, the emphasis has been primarily on symptom assessment of broad groups of patients identified by the Rome criteria. Drugs of potential value have fallen by the wayside with this approach. We propose the current paradigm is partly to blame; physiological testing should provide the basis for identifying more homogeneous populations and therapeutic targets within functional bowel disease, and this applies to the upper and lower gut. Here we summarize the evidence that certain biomarkers can, in a limited fashion, be used to predict the success of an experimental medicine in common disorders of gastrointestinal function, including the irritable bowel syndrome and functional dyspepsia. Although the current evidence is limited and is most convincingly demonstrated with examples of transit measurements (for loperamide, alosetron, tegaserod and piboserod), we perceive this paradigm that studies using validated and responsive biomarkers have an important role to play in drug development.


Accelerating GW Calculations of Point Defects with the Defect-Patched Screening Approximation.
The GW approximation has been widely accepted as an ab initio tool for calculating defect levels with the many-electron effect included. However, the GW simulation cost increases dramatically with the system size, and unfortunately, large supercells are often required to model low-density defects that are experimentally relevant. In this work, we propose to accelerate GW calculations of point defects by reducing the simulation cost of many-electron screening, which is the primary computational bottleneck. The random-phase approximation of many-electron screening is divided into two parts: one is the intrinsic screening, calculated using a unit cell of pristine structures, and the other is the defect-induced screening, calculated using the supercell within a small energy window. Depending on specific defects, one may only need to consider the intrinsic screening or include the defect contribution. This approach avoids the summation of many conduction states of supercells and significantly reduces the simulation cost. We have applied it to calculate various point defects, including neutral and charged defects in two-dimensional and bulk systems with small or large bandgaps. The results are consistent with those from the direct GW simulations. This defect-patched screening approach not only clarifies the roles of defects in many-electron screening but also paves the way to fast screen defect structures/materials for novel applications, including single-photon sources, quantum qubits, and quantum sensors.


Double-negative (CD27-IgD-) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations.
The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A+CD27-IgD-. These CD27-IgD- (double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue. A total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A+ B cells subsets were classified as either naïve (CD27-IgD+), affinity-matured (CD27+IgD-), early memory/germinal center cells (CD27+IgD+) or double-negative B cells (CD27-IgD-). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation. We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman's coefficient of - 0.76. This study is the first to observe the presence of CD27-IgD- double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.


Statistical optimization of arsenic removal from synthetic water by electrocoagulation system and its application with real arsenic-polluted groundwater.
Arsenic presence in the water has become one of the most concerning environmental problems. Electrocoagulation is a technology that offers several advantages over conventional treatments such as chemical coagulation. In the present work, an electrocoagulation system was optimized for arsenic removal at initial concentrations of 100 µg/L using response surface methodology. The effects of studied parameters were determined by a 23 factorial design, whereas treatment time had a positive effect and current intensity had a negative effect on arsenic removal efficiency. With a p-value of 0.1629 and a confidence of level 99%, the type of electrode material did not have a significant effect on arsenic removal. Efficiency over 90% was reached at optimal operating conditions of 0.2 A of current intensity, and 7 min of treatment time using iron as the electrode material. However, the time necessary to accomplish with OMS arsenic guideline of 10 µg/L increased from 7 to 30 min when real arsenic-contaminated groundwater with an initial concentration of 80.2 ± 3.24 µg/L was used. The design of a pilot-scale electrocoagulation reactor was determined with the capacity to meet the water requirement of a 6417 population community in Sonora, Mexico. To provide the 1.0 L/s required, an electrocoagulation reactor with a working volume of 1.79 m3, a total electrode effective surface of 701 m2, operating at a current intensity of 180 A and an operating cost of 0.0208 US$/day was proposed. Based on these results, electrocoagulation can be considered an efficient technology to treat arsenic-contaminated water and meet the drinking water quality standards.


[A diagnostic problem: hearing disorder in childhood].
Hearing losses of different etiology can impair the individual development during the entire childhood. Especially moderate hearing losses are difficult to diagnose because they rather present as speech or learning disorders. From the paedaudiologist's view methods are printed out for an early detection of hearing loss during childhood.


Lyme disease: epidemiologic characteristics of an outbreak in Westchester County, NY.
Epidemiological and clinical characteristics of 210 cases of Lyme disease in Westchester County, New York, reported during 1982 and 1983 are described. Most cases occurred during summer months in individuals under age 40 (male: female ratio 1:2 to 1). Symptoms included skin rash (75 per cent), joint pain or swelling (50 per cent), Bell's palsy (11 per cent), and aseptic meningitis (3 per cent). With greater public and medical awareness of this tick-borne disease, Lyme disease is being recognized with increasing frequency characteristic of an emerging epidemic in Westchester County.


The "Gift wrap" technique - a method that simplifies the placement of fascia lata in the reconstruction of the skull base following endoscopic endonasal surgery: A technical note.
With the advancement of endoscopic endonasal surgery in the treatment of anterior skull base (ASB) pathologies, extended, watertight reconstructions are needed to prevent cerebrospinal fluid (CSF) leakage. This often involves the use of multilayers closure, with free fascia lata (FL) graft frequently used as an in- and/or outlay. However, positioning the FL properly can be challenging and time-consuming, particularly on wider defects. In this technical note, we present an easier and faster way to position FL using a silicone sheet. FL graft is harvested using a standard technique. The required dimensions are evaluated depending on the extent of the dural defect taking in consideration that FL graft should exceed the edges of the dural defect especially laterally. It is then wrapped around a semi rigid pattern (Silastic sheet) and secured with several monofilament 5/0 sutures. The "package" is transferred through the endonasal corridor to the defect. The sutures are divided and taken out; the fascia is unfolded, and its edges are inserted into the subdural space without any twisting or folding of the flap. Finally, the silicone sheet is withdrawn from the nasal cavity, leaving the FL well stretched in perfect position. We illustrate this technique in the management of a large anterior skull base chondrosarcoma, which necessitated significant bone and dural resection. The "Gift wrap" technique offers an alternative approach for positioning the FL, which is less time-consuming compared to the traditional technique. Moreover, it enables improved placement of the FL, enhancing its efficacy.


Molecularly imprinted nanoparticle-based assay (MINA) for microcystin-LR detection in water.
Microcystins (MCs) are highly toxic peptides produced by cyanobacteria during algal blooms. Microcystin-leucine-arginine (MC-LR) is the most toxic and common MC variant with major effects on human and animal health upon exposure. MC-LR detection has become critical to ensure water safety, therefore robust and reliable analytical methods are needed. This work reports the development of a simple and optimized Molecularly Imprinted Nanoparticle-Based Assay (MINA) for MC-LR detection in water. Molecularly Imprinted Nanoparticles (MINs) were prepared by solid-phase polymerization on glass beads conjugated to MC-LR through (3-aminopropyl) triethoxysilane (APTES) via amide bonding. APTES-modified glass beads were obtained under optimized conditions to maximize the density of surface amino groups available for MC-LR conjugation. Two quinary mixtures of acrylic monomers differing in charge, polarity, and functionality were selected from molecular docking calculations and used to obtain MINs for MC-LR recognition using N,N'-methylene-bis-acrylamide (BIS) as the crosslinking agent. MINs were immobilized by physical adsorption onto 96-well polystyrene microplate and evaluated as per their rebinding capacity toward the analyte by using a covalent conjugate between MC-LR and the enzyme horseradish peroxidase (HRP). Experimental conditions for the MINs immobilization protocol, HRP-MC-LR concentration, and composition of the blocking solution were set to maximize the colorimetric response of the MINs compared to non-treated wells. Optimized conditions were then applied to conduct competitive MINAs with the HRP-MC-LR conjugate and the free analyte, which confirmed the preferential binding of MC-LR to the immobilized MINs for analyte concentrations ranging from 1 × 10-5 nmol L-1 to 100 nmol L-1. The best competitive MINA showed a limit of detection of 2.49 × 10-4 nmol L-1 and coefficients of variation less than 10% (n = 6), which are auspicious for the use of MINs as analytical tools for MC-LR detection below the permissible limits issued by WHO for safe water consumption (1.00 nmol L-1). This assay also proved to be selective to the analyte in cross-reactivity studies with two analogous microcystins (MC-RR and MC-YR). Analyses of lagoon and drinking water samples enriched with MC-LR revealed strong matrix effects that reduce the MINA response to the analyte, thus suggesting the need for sample pretreatment methods in future development in this subject.


Adjusting anticoagulation to prosthesis thrombogenicity and patient risk factors. Recommendations for the Medtronic Hall valve.
In order to determine optimum anticoagulation levels for the Medtronic Hall valve, the effect of low anticoagulation (mean International Normalized Ratio [INR] 2.5, 1979-1984) and moderate anticoagulation (mean INR 3.0, 1985-1989) was determined in 345 patients (183 low, 162 moderate) undergoing isolated mitral valve replacement (MVR) and 241 patients (91 low, 150 moderate) undergoing isolated aortic valve replacement (AVR). There were no cases of valve thrombosis. Embolic events and bleeding events were graded in severity and multiple decrement event-free survival calculated according to valve site and anticoagulation level: MVR low, MVR moderate, AVR low, and AVR moderate. In the MVR low group, 80% were free of all events and 93% free of serious events at 3 years compared with 89% and 98%, respectively, in the MVR moderate group. The AVR low group experienced a very small incidence of embolic events (one only) and no bleeding events. The AVR moderate group suffered more bleeding and more embolic events and at 3 years only 87% were event-free compared with 99% in the AVR low group. In both AVR groups, all embolic events were associated with one or more known stroke risk factors. Patients under 70, in sinus rhythm who were normotensive and were nonsmokers suffered no embolic events irrespective of their anticoagulation level. We conclude that the optimum INR for the average Medtronic Hall patient is 3.0 after MVR and 2.5 after AVR but some adjustments may be required in relation to stroke risk factor analysis.


The monophyly of Susisuchidae (Crocodyliformes) and its phylogenetic placement in Neosuchia.
Eusuchian crocodyliforms, which include all living crocodylians, have historically been characterized by two anatomical specializations: a ball-in-socket vertebral joint and an extensive secondary hard palate with a pterygoid-bound internal choana. The Early Cretaceous neosuchian clade Susisuchidae is typically regarded as phylogenetically near Eusuchia. The putative susisuchid Isisfordia duncani was initially described as a transitional form exhibiting incipient versions of these eusuchian traits. Here we examine aspects of the morphology of Isisfordia and comment on the morphology of its putative sister taxon Susisuchus. Our reexamination supports the notion of Isisfordia possessing transitional vertebral morphology but we present a new interpretation of its palate construction that shows it to be more plesiomorphic than previously thought. The secondary choana of Isisfordia is not pterygoid bound. Instead, long palatines expand distally lapping under the pterygoid to form the anterior border of the choana as is common among many advanced neosuchians. Incorporation of these observations into an expanded phylogenetic dataset of neosuchian crocodyliforms results in a new phylogenetic hypothesis for Susisuchidae. Isisfordia and Susisuchus form a monophyletic Susisuchidae that sits near the base of Neosuchia, and is not the sister taxon of Eusuchia.


National survey of Korean dentists' knowledge and opinions: dental caries etiology and prevention.
Dentists have the potential to influence what their patients know and do regarding dental caries prevention. The practices of dentists and what they tell their patients are influenced, in part, by their own knowledge and opinions. The purposes of this study were to determine the level of knowledge and opinions about caries etiology and prevention among Korean dentists and to describe related factors. A pretested, 27-item questionnaire was mailed to 2,047 dentists, selected by a stratified random sampling allocated proportionately. A postcard reminder was sent to all dentists after one week. Nonrespondents were sent additional complete mailings after three, seven, and nine weeks. The response rate was 83 percent (n = 1,700 dentists). Analysis of six factors thought to be related to knowledge about caries etiology and prevention showed that recent graduates and dentists who worked in public health centers were likely to be more knowledgeable about caries etiology and prevention than their counterparts (P < .05). In regression analysis of perceived effectiveness of caries-preventive procedures for children, recent graduates, males, and dentists who worked in public health centers tended to rate caries-preventive procedures more effective than other dentists (P < .05). Dentists who had experience with school-based preventive programs and dentists in rural areas were likely to rate caries-preventive procedures for adults more effective than other dentists (P < .05). Overall, results of this study suggest that the majority of dentists do not know current information concerning etiology and prevention of dental caries, mechanisms of action of fluoride, and effectiveness of preventive procedures for children and adults. Efforts to enhance the level of knowledge and practices of Korean dentists about caries prevention should focus on strategies to educate older graduates and female dentists, especially those in private practice.


Direct observation of phosphate inhibiting the force-generating capacity of a miniensemble of Myosin molecules.
Elevated levels of phosphate (Pi) reduce isometric force, providing support for the notion that the release of Pi from myosin is closely associated with the generation of muscular force. Pi is thought to rebind to actomyosin in an ADP-bound state and reverse the force-generating steps, including the rotation of the lever arm (i.e., the powerstroke). Despite extensive study, this mechanism remains controversial, in part because it fails to explain the effects of Pi on isometric ATPase and unloaded shortening velocity. To gain new insight into this process, we determined the effect of Pi on the force-generating capacity of a small ensemble of myosin (∼12 myosin heads) using a three-bead laser trap assay. In the absence of Pi, myosin pulled the actin filament out of the laser trap an average distance of 54 ± 4 nm, translating into an average peak force of 1.2 pN. By contrast, in the presence of 30 mM Pi, myosin generated only enough force to displace the actin filament by 13 ± 1 nm, generating just 0.2 pN of force. The elevated Pi also caused a >65% reduction in binding-event lifetime, suggesting that Pi induces premature detachment from a strongly bound state. Definitive evidence of a Pi-induced powerstroke reversal was not observed, therefore we determined if a branched kinetic model in which Pi induces detachment from a strongly bound, postpowerstroke state could explain these observations. The model was able to accurately reproduce not only the data presented here, but also the effects of Pi on both isometric ATPase in muscle fibers and actin filament velocity in a motility assay. The ability of the model to capture the findings presented here as well as previous findings suggests that Pi-induced inhibition of force may proceed along a kinetic pathway different from that of force generation.


Gallbladder cancer.
Gallbladder cancer (GC) is a relatively rare but highly lethal neoplasm. We review the epidemiology, etiology, pathology, symptoms, diagnosis, staging, treatment, and prognosis of GC. A Pubmed database search between 1971 and February 2007 was performed. All abstracts were reviewed and articles with GC obtained; further references were extracted by hand-searching the bibliography. The database search was done in the English language. The accurate etiology of GC remains unclear, while the symptoms associated with primary GC are not specific. Treatment with radical cholecystectomy is curative but possible in only 10% to 30% of patients. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated, where feasible, for all disease except T1a. Patients with advanced disease should receive palliative treatment. Laparoscopic cholecystectomy is contraindicated in the presence of GC. Prognosis generally is extremely poor. Improvements in the outcome of surgical resection have caused this approach to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.


Ultrasound examination in diffuse liver disease. Clinical significance of enlarged lymph nodes in the hepato-duodenal ligament.
Seventy-three patients with pathologic liver function tests were examined using ultrasound one day prior to liver biopsy. The ultrasound findings were compared with the histologic findings. In 23 patients enlarged lymph nodes were found in the hepatoduodenal ligament and 21 of these had active immune-mediated liver disease. Of the remaining 2 patients one had ulcerative colitis (and fatty liver) and one chronic cholecystitis (and haemosiderosis). Of the 33 patients with biopsy-proven active immune-mediated liver disease 21 had pathologic lymph nodes in the hepato-duodenal ligament at ultrasound. It was not possible to identify the ligament in 8 patients and in the remaining 4 no pathologic lymph nodes could be found. Twenty-one of these patients had normal liver echoes on ultrasound, 5 exhibited increased echogenicity and 5 had heterogeneous echogenicity. In a further 2 patients both increased echogenicity and heterogeneous parenchyma were found. Ultrasound examination of the liver parenchyma alone would thus lead to 21 of the 33 patients being classified as normal and a further 5 being classified as having fatty changes of the liver. Only 7 would be regarded as having significant liver pathology. However, if demonstration at ultrasound of pathologic lymph nodes in the hepato-duodenal ligament is regarded as being consistent with significant hepatic pathology a further 15 patients could be added to these 7 patients, giving a total of 22 out of 33 patients (67%) identified as having significant liver pathology using ultrasound alone. The reliability of ultrasound in the diagnosis of immune-mediated liver disease can thus be improved considerably by actively searching for lymph nodes in the hepato-duodenal ligament.


Quantifying the Separation Between the Retinal Pigment Epithelium and Bruch's Membrane using Optical Coherence Tomography in Patients with Inherited Macular Degeneration.
To describe and quantify Bruch's membrane (BM) and retinal pigment epithelium (RPE) separation using spectral-domain (SD) optical coherence tomography (OCT) in patients affected by inherited macular degenerations associated with BM thickening. Patients with molecularly confirmed Sorsby fundus dystrophy (SFD), dominant drusen (DD), and late-onset retinal degeneration (L-ORD) were included in this retrospective study. Each disease was classed as early stage if subjects were asymptomatic, intermediate stage if they had nyctalopia alone, and late stage if they described loss of central vision. The main outcome was measurement of BM-RPE separation on SD-OCT. The BM-RPE separation measurements were compared against those in normal age-matched controls. Seventeen patients with SFD, 22 with DD, and eight with L-ORD were included. BM-RPE separation on SD-OCT demonstrated a high test-retest and interobserver reproducibility (intraclass correlation coefficients >0.9). BM-RPE separation was not identified in normal subjects. In SFD, there was greater BM-RPE separation in late-stage disease compared with intermediate-stage patients both at subfoveal (P < 0.05) and juxtafoveal (P < 0.01) locations. In DD, there was increased BM-RPE separation in late-stage disease compared with early stage at subfoveal (P < 0.001) and juxtafoveal (P < 0.05) topographies. There was no significant difference in BM-RPE separation between disease stages in L-ORD. BM-RPE separation is a novel, quantifiable phenotype in the three monogenic macular dystrophies studied, and may be an optical correlate of the histopathological thickening in BM that is known to occur. BM-RPE separation, as measured by OCT, varies with stage of disease in SFD and DD, but not in L-ORD. SFD, DD, and L-ORD are associated with BM thickening. In this group of patients, OCT assessment of macular structure identifies a separation of the usually single, hyperreflective line thought to represent BM and the overlying RPE. This separation is a novel and quantifiable feature of disease staging in SFD and DD.


Modern Management Practices and Hospital Admissions.
We investigate whether the modern management practices and publicly reported performance measures are associated with choice of hospital for patients with acute myocardial infarction (AMI). We define and measure management practices at approximately half of US cardiac care units using a novel survey approach. A patient's choice of a hospital is modeled as a function of the hospital's performance on publicly reported quality measures and the quality of its management. The estimates, based on a grouped conditional logit specification, reveal that higher management scores and better performance on publicly reported quality measures are positively associated with hospital choice. Management practices appear to have a direct correlation with admissions for AMI--potentially through reputational effects--and indirect association, through better performance on publicly reported measures. Overall, a one standard deviation change in management practice scores is associated with an 8% increase in AMI admissions.


An analysis of transformed clones obtained by coinfections with hr-t and ts-a mutants of polyoma virus.
Clones of stably transformed rat cells from the F-111 (Fisher rat embryo) and NRK (normal rat kidney) cell lines have been obtained by complementation using pairs of nontransforming polyoma mutants of the hr-t and ts-a classes. A total of 78 clones were isolated and studied, 21 from the NRK line, and 57 from the F-111 line. These "complementation transformed clones" were then examined for the presence and expression of each of the parental mutant viruses. The expression of viral T (tumor) antigens was analyzed by immunoprecipitation. Every one of 54 clones examined express the 22K (small) and 56K (middle) T antigens which are the products of the hr-t viral gene. This indicates a requirement for the presence of a wild-type hr-t allele contributed by the ts-a mutant parent. Ten clones lack detectable large T antigen, while four show thermolabile large T antigen. These results support the conclusion that middle and small but not large T antigen(s) are essential for the maintenance of the transformed phenotype. Most of the 57 F-111 clones are virogenic when fused to mouse cells under permissive conditions and yield both mutant types. Surprisingly, wild-type recombinants have been recovered from 40 of the F-111 clones. Three clones show evidence of retention of only the ts-a mutant genome. Virus cannot be rescued from the majority of the 21 NRK clones. The few clones which are virogenic, however, yield both hr-t and ts-a mutants. Integration patterns of several clones analyzed by Southern blotting confirm the expectations based on viral T antigen(s) and virus rescue analyses. Hr-t mutant genomes, though not required for the maintenance of the transformed state, are frequently retained in complementation transformed clones. Tandem integration of the two parental mutants is clearly demonstrated in one clone and implicated in the other eight out of nine virogenic F-111 complementation transformed clones examined. This observation provides the basis of a model for the generation of wild-type recombinants following fusion of F-111 clones.


Effects of different sterilization techniques and varying anodized TiO₂ nanotube dimensions on bacteria growth.
Infection of titanium (Ti)-based orthopedic implants is a growing problem due to the ability of bacteria to develop a resistance to today's antibiotics. As an attempt to develop a new strategy to combat bacteria functions, Ti was anodized in the present study to possess different diameters of nanotubes. It is reported here for the first time that Ti anodized to possess 20 nm tubes then followed by heat treatment to remove fluorine deposited from the HF anodization electrolyte solution significantly reduced both S. aureus and S. epidermidis growth compared to unanodized Ti controls. It was further found that the sterilization method used for both anodized nanotubular Ti and conventional Ti played an important role in the degree of bacteria growth on these substrates. Overall, UV light and ethanol sterilized samples decreased bacteria growth, while autoclaving resulted in the highest amount of bacteria growth. In summary, this study indicated that through a simple and inexpensive process, Ti can be anodized to possess 20 nm tubes that no matter how sterilized (UV light, ethanol soaking, or autoclaving) reduces bacteria growth and, thus, shows great promise as an antibacterial implant material.


Coupling of the expressed cannabinoid CB1 and CB2 receptors to phospholipase C and G protein-coupled inwardly rectifying K+ channels.
Signaling of the cannabinoid CB1 and CB2 receptors through phospholipase C (PLC) and G protein-coupled inwardly rectifying K+ channels (GIRK) was studied after their expression in COS7 cells and Xenopus oocytes. The CB1 or CB2 receptor was co-expressed with alpha subunits of the Galphaq family (Galphaq, Galpha11, Galpha14, Galpha15 and Galpha16) in COS7 cells. Receptor-dependent activation of PLC was observed after co-expressing the CB1 receptor with Galpha14, Galpha15 or Galpha16 but not with Galphaq or Galpha11. Co-expression of Gbeta1 and Ggamma2 abolished the activation, indicating that the activation was mediated by Galpha. PLC activation was not observed when the CB2 receptor was expressed alone or co-expressed with any of the above Galpha subunits. Coupling to GIRK was observed with both CB1 and CB2 receptors after expression in Xenopus oocytes. Significantly larger currents were induced when the receptor was co-expressed with both GIRK1 and GIRK4 than with either GIRK alone. Co-expression of Galpha transducin with the receptor significantly reduced the K+ currents, indicating that GIRK activation was mediated by Gbetagamma but not by Galpha. These findings suggest two new signaling pathways for the cannabinoid receptors.


Effect of changes in pelvic tilt on range of motion to impingement and radiographic parameters of acetabular morphologic characteristics.
The current understanding of the effect of dynamic changes in pelvic tilt on the functional acetabular orientation and occurrence of femoroacetabular impingement (FAI) is limited. To determine the effect of changes in pelvic tilt on (1) terminal hip range of motion and (2) measurements of acetabular version as assessed on 2- and 3-dimensional imaging. Controlled laboratory study. Preoperative pelvic computed tomographic scans of 48 patients (50 hips) who underwent arthroscopic surgery for the treatment of FAI were analyzed. The mean age of the study population was 25.7 years (range, 14-56 years), and 56% were male. Three-dimensional models of the hips were created, allowing manipulation of the pelvic tilt and simulation of hip range of motion to osseous contact. Acetabular version was measured and the presence of the crossover sign, prominent ischial spine sign, and posterior wall sign was recorded on simulated plain radiographs. Measurements of range of motion to bony impingement during (1) hip flexion, (2) internal rotation in 90° of flexion, and (3) internal rotation in 90° of flexion and 15° adduction were performed, and the location of bony contact between the proximal femur and acetabular rim was defined. These measurements were calculated for -10° (posterior), 0° (native), and +10° (anterior) pelvic orientations. In native tilt, mean cranial acetabular version was 3.3°, while central version averaged 16.2°. Anterior pelvic tilt (10° change) resulted in significant retroversion, with mean decreases in cranial and central version of 5.9° and 5.8°, respectively (P < .0001 for both). Additionally, this resulted in a significantly increased proportion of positive crossover, posterior wall, and prominent ischial spine signs (P < .001 for all). Anterior pelvic tilt (10° change) resulted in a decrease in internal rotation in 90° of flexion of 5.9° (P < .0001) and internal rotation in 90° of flexion and 15° adduction of 8.5° (P < .0001), with a shift in the location of osseous impingement more anteriorly. Posterior pelvic tilt (10° change) resulted in an increase in internal rotation in 90° of flexion of 5.1° (P < .0001) and internal rotation in 90° of flexion and 15° adduction of 7.4° (P < .0001), with a superolateral shift in the location of osseous impingement. Dynamic changes in pelvic tilt significantly influence the functional orientation of the acetabulum and must be considered. Dynamic anterior pelvic tilt is predicted to result in earlier occurrence of FAI in the arc of motion, whereas dynamic posterior pelvic tilt results in later occurrence of FAI, which may have implications regarding nonsurgical treatments for FAI.


Lessons from community based management of floodplain fisheries in Bangladesh.
Inland (floodplain) fisheries remain the most important contributor to fish production in Bangladesh. They have in the past been administered to generate government revenue without due concern for sustainability or equity. Community Based Fisheries Management (CBFM) is a possible solution and was tested in 19 waterbodies (rivers and beels) during 1996-2000. The outcomes so far are assessed with respect to social, institutional, and physical context, and the interactions that arose in establishing CBFM. The lessons drawn are that: it was essential that communities obtained rights over the fisheries, strong facilitation was necessary, taking up visible resource management actions greatly helped, success was more likely in homogeneous communities, external threats were a strong limiting factor, clear boundaries and small fisheries were not so critical, and new institutions could be built with as much ease (or difficulty) as modifying existing ones. Effective well-defined partnerships of NGOs and government were not easy to establish but were sufficiently beneficial that in several locations new community institutions for fisheries management were established. This is a slow process, the sustainability of local management institutions is not yet established, although they continued during an interim period without funding, further phased support is planned to strengthen these organizations and to generate evidence of impacts and momentum to influence wider fisheries policy in and beyond Bangladesh.


Deep brain stimulation for obsessive-compulsive disorder: a systematic review and meta-analysis.
Deep brain stimulation (DBS) is increasingly being applied to psychiatric conditions such as obsessive-compulsive disorder (OCD), major depression and anorexia nervosa. Double-blind, randomized controlled trials (RCTs) of active versus sham treatment have been limited to small numbers. We therefore undertook a systematic review and meta-analysis of the effectiveness of DBS in psychiatric conditions to maximize study power. We conducted a systematic literature search for double-blind, RCTs of active versus sham treatment using Pubmed/Medline and EMBASE up to April 2013. Where possible, we combined results from studies in a meta-analysis. We assessed differences in final values between the active and sham treatments for parallel-group studies and compared changes from baseline score for cross-over designs. Inclusion criteria were met by five studies, all of which were of OCD. Forty-four subjects provided data for the meta-analysis. The main outcome was a reduction in obsessive symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS). Patients on active, as opposed to sham, treatment had a significantly lower mean score [mean difference (MD) -8.93, 95% confidence interval (CI) -13.35 to -5.76, p < 0.001], representing partial remission. However, one-third of patients experienced significant adverse effects (n = 16). There were no differences between the two groups in terms of other outcomes. DBS may show promise for treatment-resistant OCD but there are insufficient randomized controlled data for other psychiatric conditions. DBS remains an experimental treatment in adults for severe, medically refractory conditions until further data are available.


Bacteroides ureolyticus (NTU) medium for the selective recovery of Bacteroides gracilis.
Bacteroides gracilis is a gram-negative anaerobic bacillus which requires formate and fumarate for growth; it has been implicated in periodontal disease and serious infections of the head and neck. In this study, Bacteroides ureolyticus (NTU) medium was tested for its ability to allow the growth of B. gracilis and other formate-fumarate requiring gram-negative anaerobes and to enable the recovery of these organisms from clinical specimens. All reference strains grew on NTU medium with the exception of Wolinella recta and formate-fumarate requiring organisms were isolated from 18 of 20 samples of subgingival dental plaque from patients with chronic periodontitis. B. gracilis was the commonest species isolated (14 of the 29 isolates); B. ureolyticus was not found.


Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial.
Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration. To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS). Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours. The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation. There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26). Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality. clinicaltrials.gov Identifier: NCT00091507.


Iatrogenic facial nerve injury: the role of facial nerve monitoring.
Intraoperative facial nerve monitoring has emerged as a powerful tool for facilitation of surgery involving the facial nerve. This tool must be properly applied and maintained, however, in order to avoid untoward results and to maximize its potential benefits. Facial nerve monitoring is best suited for prevention of iatrogenic injury. Once injury has become established, its value may be severely limited, especially for moderate to severe injury, in which visual assessment of injury is still the most effective means to determine the need for repair. The most valuable derivative of facial nerve monitoring is enhanced awareness of the edge of the facial nerve contour. This allows strategic alterations in surgical technique for improved facial nerve functional preservation. Although facial nerve monitoring appears to have already had a favorable influence on facial nerve preservation, further improvement seems likely over time through an ongoing process of trial and error.


Can Medullary Thyroid Carcinoma Arise in Thyroglossal Duct Cysts? A Search for Parafollicular C-cells in 41 Resected Cases.
Thyroglossal duct cysts (TGDCs) are present in ~7% of adults and develop from the midline migratory tract between the foramen cecum and anatomic location of the thyroid. Thyroid tissue can be identified in 2/3 of TGDCs, and up to 1% develop associated malignancy, 90% of which are papillary thyroid carcinoma. Cases of follicular and anaplastic carcinoma have been documented, but there are no reports of medullary thyroid carcinoma arising in a TGDC. This is presumably due to the distinct embryologic origin of parafollicular C-cells, from which medullary carcinoma arises. The goal of this study is to determine whether parafollicular C-cells are present in TGDCs. H&E sections from 41 TGDC cases were examined for thyroid tissue, thyroglossal duct remnants, ultimobranchial remnants, and parafollicular C-cells. Immunohistochemistry was performed for TTF-1 and calcitonin. Eighty three percent (34/41) of cases contained thyroid tissue on H&E and by TTF-1. No cases (0/41) had ultimobranchial remnants or parafollicular C-cells on H&E or with calcitonin. One case of papillary carcinoma in a TGDC was identified. These cases illustrate that although TGDCs often contain thyroid tissue, parafollicular C-cells are absent. Therefore, unlike other thyroid neoplasms, there is no evidence to support the possibility of medullary carcinoma arising in a TGDC.


Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth. In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction. Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity. MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches.