A randomized controlled trial of supervised remotely-delivered attention bias modification for posttraumatic stress disorder.
Many individuals with posttraumatic stress disorder (PTSD) have limited access to first-line treatments, warranting the development of remotely-delivered treatments. Attention bias modification (ABM), targeting perturbed threat-related attentional patterns, shows promise when delivered in-person. However, previous studies found ABM to be ineffective when delivered remotely. Randomized clinical trials usually applied two variations of ABM: ABM away from threat or attention control training (ACT) balancing attention between threat-related and neutral stimuli. We tested remotely-delivered ACT/ABM with tighter supervision and video-based interactions that resemble in-clinic protocols. We expected to replicate the results of in-clinic trials, in which ACT outperformed ABM for PTSD. In this double-blinded, parallel-group randomized controlled trial, 60 patients diagnosed with PTSD were randomized (ABM n = 30; ACT n = 30). Patients performed eight bi-weekly remotely-delivered supervised ABM/ACT sessions. Symptoms were assessed pre- and post-treatment with Clinician-Administered PTSD Scale 5 (CAPS-5) severity score and PTSD diagnosis as the primary outcomes. Current depressive episode, current anxiety-related comorbidity, and time elapsed since the trauma were examined as potential moderators of treatment outcome. Significant decrease in CAPS-5 severity scores and PTSD diagnosis was observed following both ACT and ABM with no between-group difference. Patients without depression or whose trauma occurred more recently had greater symptom reduction in the ACT than the ABM group. Contrary to our expectation, symptoms decreased similarly following ACT and ABM. Moderator analyses suggest advantage for ACT in non-depressed patients and patients whose trauma occurred more recently. Further refinements in remotely-delivered ABM/ACT may be needed.


Lactose-ornithine bolaamphiphiles for efficient gene delivery in vitro.
The development of new nonviral vectors characterized by high transfection efficiency and low cytotoxicity remains an important challenge in the field of gene delivery. Unsymmetrical bolaamphiphiles (bolas) appear as new emerging candidates for this application. In this work, new unsymmetrical bolas, bearing neutral lactonic acid and cationic ornithine residues at the two ends of a hydrophobic spacer, were synthesized and their properties were compared to analogues bearing a gluconic acid residue. The new bolas showed DNA binding and condensation at higher N/P ratios than their gluconic analogues, probably due to their larger neutral head group. Whereas the size of the complexes of the new bolas with DNA (bolaplexes) increased with N/P, as a result of charge neutralization, their formulations with DOPE at high N/P were of small size (ca. 200 nm). These DOPE formulations showed high transfection efficiency in different cell lines (HeLa, COS-7 and HepG2), close to that of jetPEI. Their cytotoxicity was relatively low, which allowed repetitive transfection in vitro. Fluorescence imaging showed that the bolaplexes bind rapidly to cell surface and internalize mainly through endocytosis. This work suggests a new type of efficient nonviral vectors based on bolaamphiphiles.


Meloxicam-induced rhabdomyolysis in the context of an acute ross river viral infection.
Acute rhabdomyolysis is a clinical and laboratory syndrome resulting from the breakdown of skeletal muscle, with the release of intracellular contents into the circulatory system, which can cause potentially lethal complications. Here, we present the case of a patient who developed acute rhabdomyolysis after consumption of meloxicam for jaw pain and experienced generalized myalgias in the context of an acute febrile illness with generalized urticaria. Further investigation indicated elevated muscle enzymes and acute renal failure. Serological analysis revealed that the patient was positive for Ross River virus (RRV) IgM. Genetic studies to detect CYP2C9 polymorphisms were negative. Meloxicam was discontinued. He responded to conservative measures within 2 weeks. Oral aspirin challenge was negative, suggesting a drug-specific effect of meloxicam rather than a class effect. Our case indicates a causative role for meloxicam and/or acute RRV in rhabdomyolysis.


[Early outcome in diabetic patients following coronary artery bypass grafting].
Diabetes is one of the most important risk factors for coronary artery disease. Diabetics often have severe three vessel disease and coronary bypass surgery is in most cases the preferred treatment of choice in these patients. We investigated early surgical complications and outcomes in diabetic patients following isolated CABG in Iceland and compared them to those of non-diabetic patients. A retrospective study of 1626 consecutive CABG patients operated in Iceland 2001-2012. Diabetic patients were 261 (16%) and were compared to 1365 non-diabetics in terms of patient demographics, operative data, and postoperative outcomes. Logistic regression was used to identify risk factors for major complications and 30-day mortality. The groups were similar in terms of age, gender and Euro-SCORE. Diabetic patients had a higher BMI (30 vs. 28 kg/m(2), p<0.001), were more likely to have hypertension (82% vs. 60%, p<0.01) and glomerular filtration rate <60 ml/min/1.73m(2) (22% vs. 15%, p=0.01). The rate of deep sternal wound infections, stroke and perioperative myo-cardial infarction was similar in both goups. Acute kidney injury, classified according to the RIFLE-criteria, was higher in diabetic patients, both in the RISK (14% vs. 9%, p=0.02) and FAILURE category (2% vs. 0.5%, p=0.01). Minor complications, (atrial fibrillation, pneumonia, urinary tract infections and superficial wound infections) were similar in both groups. 30-day mortality was 5.0% vs. 2% for diabetics and non-diabetics patients, respectively (p=0.01). Diabetes was not a significant risk factor for 30-day mortality when adjusted for other risk factors with logistic regression (OR=1.98, 95% CI 0.72-4.95). Diabetic patients that underwent CABG more often suffered acute renal injury but diabetes was not an independent prognostic factor of operative mortality.


Alterations in the circadian rhythm of salivary melatonin begin during middle-age.
To investigate whether free melatonin may be better suited to reveal age-related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take place. A total of 52 healthy volunteers participated in the study consisting of young, middle-aged, old and the oldest groups. In each subject, a total of 12 time-point salivary melatonin samples was taken over 24 hr. Of the 52 data sets, 51 exhibited significant circadian rhythm over 24 hr by using the base cosine function analysis to fit the data. A clear circadian rhythm of salivary melatonin was present in all age groups. The decline in nocturnal peak levels (amplitude) in salivary melatonin was found in old and the oldest subjects. Both the old and the oldest subjects showed an increased daytime (baseline) melatonin levels. The off-set melatonin levels were more than two times higher in the oldest group than that in the other groups indicating a delayed phase of salivary melatonin. Most strikingly, we found that a step-wise decrease in the circadian rhythms of saliva melatonin occurred early in life, around 40 yr of ages. The middle-aged subjects had only 60% of the amplitude of the young subjects. In addition, the middle-aged subjects showed the longest peak levels duration and the lowest daytime melatonin levels. The present study showed that the alterations in the circadian rhythms of salivary melatonin begin during middle-age. Our results showed that salivary melatonin measurement is a reliable, sensitive and easy method to monitor changes in the circadian rhythms of melatonin during the course of aging.


Cross correlations in scaling analyses of phase transitions.
Thermal or finite-size scaling analyses of importance sampling Monte Carlo computer simulations in the vicinity of phase transition points often combine different estimates for the same quantity, such as a critical exponent, with the intent to reduce statistical fluctuations. We point out that the origin of such estimates in the same time series often results in pronounced cross correlations which are usually ignored even in high-precision studies, generically leading to significant underestimation of statistical fluctuations. We suggest to use a simple extension of the conventional analysis taking correlation effects into account, which leads to improved estimators with often substantially reduced statistical fluctuations at almost no extra cost in terms of computation time.


Implications of gene amplification for evolution and management of insecticide resistance.
Simulations were used to compare evolution of insecticide resistance predicted by a conventional two-allele model with predictions from three- and four-allele models that assume resistance is based on gene amplification. Results were similar between models when insecticide concentration was low or moderate. In contrast, when 10% of the population was not exposed to insecticide each generation, high insecticide concentrations slowed resistance development in the two-allele model, but caused rapid development of high levels of resistance in the three- and four-allele models. The presence of a third allele at an initial frequency as low as 10-7 doubled or tripled the rate of resistance development in some cases. Attempts to slow evolution of resistance by overwhelming it with high concentrations of insecticides are not likely to succeed if gene amplification or other mechanisms generate alleles that confer high levels of resistance.


Bisphenol A glucuronidation and absorption in rat intestine.
Bisphenol A, an environmental estrogen, can be leached from plastic tableware and from the coating of food and drink cans, orally exposing human beings to the compound. The present study focuses on the absorption and metabolism of bisphenol A in the rat intestine, as elucidated experimentally by segmented everted intestine. One hour after the application of 2 micromol of bisphenol A to the mucosal fluid, the absorption of bisphenol A was slightly greater in the colon (48.6%) than in the proximal jejunum (37.5%). In the serosal side, unconjugated bisphenol A appeared in small amounts, increasing distally (maximal 1.6 nmol, colon). Large amounts of the bisphenol A glucuronide were then transported into the serosal side, also increasing distally (proximal, 80.4 nmol; distal, 478.4 nmol). The greatest amount of the glucuronide (approximately 573 nmol) was excreted into the mucosal side of the small intestine, whereas in the colon, mucosal excretion was minimal (67.2 nmol). On high-dose application of bisphenol A to the mucosal fluid, the transported unconjugated bisphenol A increased markedly throughout the intestine and colon. These results suggest that bisphenol A in the intestinal lumen is glucuronidated almost exclusively during its passage through the intestinal wall.


Expression and function of the vitamin D receptor in malignant germ cell tumour of the testis.
Testicular germ cell tumours (TGCTs) are the most common malignancy in young men aged 18-35 years. They are clinically and histologically subdivided into seminomas and non-seminomas. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D(3)) is the active form of vitamin D and exerts its actions via a specific intracellular vitamin D receptor (VDR). Several investigations in the recent years have revealed, in addition to a physiological occurrence of the VDR in various tissues, VDR expression in different human malignancies. Furthermore, 1,25(OH)(2)D(3) plays an important role in the regulation of cell proliferation and differentiation. In different normal and malignant cell types, antiproliferative and pro-differentiating effects of 1,25(OH)(2)D(3) are described. We investigated whether TGCT express the VDR, wether differences exist between the histological subtypes and if vitamin D has a function on the proliferation of tumour cells. Furthermore, we investigated the potential function of the vitamin D-regulated genes nuclear receptor co-repressor 1(NCOR1), nuclear receptor co-repressor 2 (NCOR2), thyroid receptor interacting protein 15 (TRIP15), Growth Arrest and DNA Damage (GADD45), MAP kinase-activated protein kinase 2 (MAPKAPK2), Cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1) and Cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1) in the pathogenesis of TGCT. We demonstrate, for the first time, that primary TGCT as well as TGCT cell lines, express VDR mRNA and protein. Vitamin D and VDR may play a role in the pathogenesis of TGCTs. Furthermore, vitamin D inhibits proliferation of TGCT cell-lines, potentially via an increase in expression of GADD45. Our data suggest that vitamin D could play a role in antitumour therapy.


Epidemiology of attempted suicide in Hatay, Turkey.
To determine suicide rates, sociodemographic risk factors, and reasons for suicide attempts. This hospital based, retrospective study consisted of 1613 suicide attempts brought to the emergency services of 8 state hospitals in Hatay, Turkey from January 2007 to December 2009. We obtained the data by retrospective analysis of patient record forms including information on age, gender, education level, marital status, occupation, reason for suicide, method of suicide, presence of previous psychiatric disease in the patient or family, previous suicidal behavior in the patient or family. We obtained current population data of the province from the Turkish State Institute of Statistics. Chi-Square test, and percentage distribution was used for the statistical analysis. The mean age of females (23.9+/-7.9) was lower than males (26.6+/-9.7). The mean annual rate of attempted suicides per 100,000 was 38.14 (16.11 in males, 60.42 in females). The rate decreased as the age increased, and was highest in the 15-24 age group, in women, in non-married patients, and in the individuals with high school education. Self-poisoning with a drug overdose was the most common method, and domestic conflicts were the most common reason. Psychiatric disease history in the family or patient, and suicide attempt in the family were risk factors associated with repeated suicide attempts. The suicide attempt rate was lower than in many western countries, and similar to previous studies in Turkey. The risk of recurrence in suicide attempts is high, and is associated with psychosocial factors.


Quantitative Transthoracic Echocardiography of the Response to Dobutamine in Cardiac Surgery Patients With Low Cardiac Output Syndrome.
To quantify the acute effects of dobutamine in postoperative low cardiac output syndrome (LCOS) using transthoracic echocardiographic, hemodynamic, and blood biomarker monitoring and to assess its association with clinical outcomes. Observational prospective study. Single university hospital. Patients undergoing elective cardiac surgery. None. Echocardiographic parameters, hemodynamic data, and plasma biomarkers were obtained before and early after inotrope initiation. The diagnostic value of transthoracic echocardiographic parameters and their association with clinical outcome were evaluated. Thirty-eight LCOS patients and 12 control patients were included. The left ventricular outflow tract velocity time integral was significantly lower in LCOS patients (11.75 v 19.08 cm; p < 0.001) and showed a marked improvement after dobutamine administration (∼37% increase). Dobutamine improved left and right ventricular function, increased mean arterial pressure and urine output, and lowered lactate levels. The duration of dobutamine support, but not in-hospital mortality, was associated with echocardiographic estimates of cardiac performance early after dobutamine initiation. Early transthoracic echocardiographic assessment and the acute response to inotropic therapy may provide rapid and highly valuable information in the diagnostic workup and risk evaluation of patients with suspected LCOS after cardiac surgery.


Detection of a calcium-activated protein kinase in mougeotia by using synthetic Peptide substrates.
By using a synthetic peptide, KM-14, a protein kinase was detected and partially purified from Mougeotia sp. The peptide contains the sequence of the regulatory light chain of smooth muscle myosin that is phosphorylated by calcium-calmodulin-dependent myosin light chain kinase (MLCK). The Mougeotia kinase was stimulated 40-fold by calcium with half-maximal stimulation occurring at 1.5 micromolar. The enzyme was fractionated from calmodulin and was depleted of calmodulin based on enzyme activator analysis. The calmodulin-depleted enzyme was fully active and calcium dependent, and was not stimulated further by exogenous calmodulin nor by the calcium effectors phosphatidylserine and diacylglycerol. The enzyme phosphorylated intact chicken gizzard myosin light chain as well as the KM-14 substrate. KM-13, a peptide analog of KM-14 with a deletion of a glutamine at position 5, was a poor substrate with a V(max)/K(m) ratio 200-fold lower than KM-14. Thus, similarly to vertebrate MLCK, the Mougeotia enzyme is very sensitive to changes in sequence surrounding the phosphorylation site. Calcium-dependent KM-14 kinase activity also was detected in two other algae, Mesotaenium caldariorum and Spirogyra sp., as well as in pea seedlings. The data suggest that plant and algal tissues possess an enzyme with a substrate specificity similar to MLCK, but unlike MLCK, does not appear to require calmodulin for activity.


Notes from the field: Measles outbreak--Indiana, June-July 2011.
On June 20, 2011, an emergency department (ED) physician reported five epidemiologically linked measles cases to the Indiana State Department of Health. The subsequent investigation identified a total of 14 confirmed cases in northeast Indiana. Of these, 10 were laboratory-confirmed, and four were among household contacts of persons with laboratory-confirmed measles. Of the 14 patients, 13 were unvaccinated persons in the same extended family. The nonfamily member was a child aged 23 months who had received 1 dose of measles, mumps, and rubella vaccine 4 months before illness onset. Four of the 14 patients were males; median age was 11.5 years (range: 15 months-27 years). One patient was a woman in week 32 of pregnancy who was hospitalized for acute pneumonitis.


Intraoperative ultrasound examination of the brain: possible pitfalls in diagnosis and biopsy guidance.
The use of ultrasound during surgical procedures is frequently beneficial for both demonstration and diagnosis of various pathologic conditions. In the neurosurgical suite, localization of subcortical brain tumors is easily accomplished with real-time imaging. The depth and size of the tumor are easily assessed, and the relationship of the lesion to adjacent normal structures ascertained. However, there are pitfalls that may result in diagnostic inaccuracies during the evaluation of abnormalities. These include artifacts, use of inappropriate equipment, and poor technique. These problems are illustrated and discussed.


Pleuritis as a presenting manifestation of rheumatoid arthritis: diagnostic clues in pleural fluid cytology.
Pleural effusion is a recognized but relatively uncommon complication of rheumatoid arthritis and has distinctive cytopathologic features. It may occur before, concurrently with, or after the development of joint manifestations of the disease. Clinical diagnosis of rheumatoid pleuritis may be delayed or overlooked in a patient without obvious evidence of arthritis. Failure to recognize the unique cytologic picture of rheumatoid pleuritis caused a 5-month delay in diagnosis of a rheumatoid pleural effusion in an elderly man whose concurrent arthritic symptoms were not given adequate clinical recognition.


Liver transplantation for hepatocellular carcinoma.
Because hepatocellular carcinoma (HCC) arises in cirrhotic livers and is often multifocal, transplantation seems to be a rational approach. Early results were poor, but current restrictive selection criteria can yield excellent results. Patients with 1 HCC nodule </=5 cm in diameter, or 2-3 nodules </=3cm, receive United Network Organ Sharing priority; nevertheless, dropout from the waiting list is common. Predictors of dropout include multiple tumors and tumors with a diameter >3 cm. Nonsurgical methods are commonly used to prevent tumor progression and thus prevent dropout. Expanding selection criteria results in more patients with HCC being cured at the expense of a higher incidence of recurrence. Molecular/biologic information is beginning to be incorporated into current staging systems in order to better predict HCC recurrence. In considering liver transplantation, the impact of the underlying liver disease is an important consideration; recurrent hepatitis C after transplant lowers patient survival independent of tumor recurrence.


Developmental alteration of endocannabinoid retrograde signaling in the hippocampus.
Endocannabinoids are lipid derivatives that mediate paracrine and juxtacrine signaling between cells. In the hippocampal CA1 region, a retrograde endocannabinoid signal suppresses GABA release by acting on presynaptic cannabinoid receptor-1 (CB1) and can be functionally manifested as depolarization-induced suppression of inhibition (DSI). In the present study, whole cell patch-clamp recordings in hippocampal slices were made to examine DSI in rats from P7-P21. Robust DSI develops in rat hippocampus at postnatal ages greater than two weeks, but only modest DSI is observed in P7-9 rat. DSI in neonatal rats can be enhanced by activation of group I metabotropic glutamate receptors (mGluRs) or muscarinic acetylcholine receptors in those neonatal rats. The DSI is also enhanced by sustained low-frequency (1 Hz) stimulation (5 min). This stimulus-enhanced DSI was prevented in the presence of 6-methyl-2-(phenylethynyl)-pyridine (10 microM), a group I mGluR antagonist. WIN55212-2, a synthetic CB1 agonist, produced a similar level of inhibition of GABAergic synaptic transmission at different postnatal time points. Therefore postsynaptic mechanisms appear to be mainly responsible for developmental changes in DSI, although presynaptic mechanisms cannot be ruled out entirely. We have also obtained evidence that tonic endocannabinoid release suppresses GABAergic transmission in the mature but not the neonatal hippocampus. The differential DSI magnitude at different stages of maturation could alter synaptic plasticity and learning and memory during hippocampal development.


[Primary intracranial yolk sac tumor developing in the frontal lobe from the inside of the sphenoidal ridge].
A case of primary intracranial yolk sac tumor, the first known case growing in the frontal lobe, is compared with similar cases of suprasellar region. The case, 18-year-old female, suffered from headache, vomiting and visual disturbance for one month prior to the hospitalization. Plain CT scan demonstrated suppressed left anterior horn and normal density area in front of it. After injection of contrast medium, the area was enhanced distinctly. The left carotid angiography displayed a hypervascular mass in the suprasellar region and tumor stain was also seen in the capillary phase. Bilateral frontal craniectomy was performed and the tumor was almost totally removed macroscopically. The tumor situated in the left frontal lobe infiltrated into the optic nerve and a part of anterior cerebral artery. Histologically the tumor was diagnosed as yolk sac tumor according to Teilum's classification. There were stellate cells arranged in loose vacuolated network which formed cystic cavities and a complicated network of honeycomb with communicating cavities and extracellular PAS-positive hyaline globules. Glomerular-like structures (Schiller-Duval body) was also seen. Immunoperoxidase study clearly demonstrated the presence of intracytoplasmic alphafetoprotein granules in the tumor tissue. In radioimmunoassay, the level of the serum alphafetoprotein measured was two folds higher than that of the normal range, postoperatively. Although irradiation (local 3000 rads, whole 3000 rads) combined with chemotherapy (ACNU, Futraful), PSK had almost no effect. The effect of other chemotherapy (Cis-platin, VBL, Bleomycin) was indicated by the diminish size of the tumor. Five months after the onset, she was discharged with almost no neurological findings other than left visual loss. Pathological findings and clinical treatments were also discussed in detail.


Neurolymphomatosis: a single-center experience of neuromuscular manifestations, treatments, and outcomes.
Neurolymphomatosis (NL) is a disease characterized by the infiltration of malignant lymphocytes into the peripheral nervous system. We report clinical features, radiographic findings, modes of treatment, and outcomes of patients with NL. We retrospectively investigated patients with NL. We extracted data, including clinical features, magnetic resolution imaging (MRI), 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, cerebrospinal fluid cytology findings, the results of electrodiagnostic studies, as well as patient treatments and outcomes. Ten NL patients were identified. All patients reported pain/paresthesia and weakness in the affected area. The MRI scans were abnormal in eight out of nine patients with an enhancement of the spinal nerve root, plexus, peripheral nerve trunk, and cranial nerve. The FDG PET/CT scans were positive in all patients. Radiculopathy or radiculoplexopathy was the most common electrodiagnostic finding. Neurological improvement was observed in only three patients. The condition of the nine patients who underwent multimodality treatments for cancer eventually deteriorated and the patients died. NL should be considered in the differential diagnosis of any type of neuropathy in patients with lymphoma. Because it could be confused with other neuropathies in lymphoma and various musculoskeletal diseases, a high index of suspicion and familiarity with clinical manifestation of NL are key. FDG PET/CT was the most sensitive diagnostic imaging modality to detect relevant neural invasion. The root within the spinal neural foramen was the most frequently affected neural structure. Early diagnosis of this rare neurologic manifestation of lymphoma may improve treatment outcomes.


Approximating a Giving Up Smoking Dynamic on Adolescent Nicotine Dependence in Fractional Order.
In this work, we consider giving up smoking dynamic on adolescent nicotine dependence. First, we use the Caputo derivative to develop the model in fractional order. Then we apply two different numerical methods to compute accurate approximate solutions of this new model in fractional order and compare their results. In order to do this, we consider the generalized Euler method (GEM) and multi-step generalized differential transform method (MSGDTM). We also show the unique positive solution for this model and present numerical results graphically.


Spontaneous Dissolution of Oxometalates Boosting the Surface Reconstruction of CoMOx (M = Mo, V) to Achieve Efficient Overall Water Splitting in Alkaline Media.
Bimetallic materials have been regarded as promising catalysts for efficient alkaline water splitting. However, the spontaneous reconstruction of the surface structures of the catalysts before catalysis has long been overlooked. Here, we present that in situ dissolution of MoO42- in CoMoO4 boosts spontaneous surface reconstruction in an alkaline medium. Our results reveal that CoMoO4 microrod arrays function as precatalysts that undergo spontaneous surface reconstruction under alkaline conditions, forming a layer of Co3O4/CoMoO4 and CoOOH/CoMoO4 heterostructures. X-ray photoelectron spectroscopy (XPS) combined with in situ Raman spectroscopy reveals that in such activated CoMoO4 (A-CoMoO4), the partial electron transfer from Co to Mo sites helps induce a higher valence state of Co centers and the heterostructure of Co3O4/CoMoO4 may promote the generation of CoOOH, which is very likely the precursor to the active Co4+ species for oxygen evolution reaction (OER) catalysis. During the hydrogen evolution reaction (HER), Co3O4 generated after surface reconstruction can promote the dissociation of water, which is considered the rate-determining step of the alkaline HER. Hence, A-CoMoO4 exhibits superior bifunctional electrocatalytic activities that the overpotentials at a working current density of 10 mA cm-2 for the HER and OER are only 13 and 264 mV, respectively. Inspired by the remarkable bifunctionality, the electrolytic cell employing A-CoMoO4 as both anode and cathode shows an appealing potential of 1.51 V to deliver 10 mA cm-2 for overall water splitting. Similarly, CoVOx also shows the spontaneous surface reconstruction behavior in the alkaline medium, which we propose can be extended to a series of oxometalate catalysts.


The road to success in PPS: guiding care for efficiency and effectiveness. Prospective payment system.
This article features one organization's attempt to interpret and form operational definitions for the initiation of the prospective payment system (PPS) by October 1, 2000. Data collection, initiated with the October 28, 1999, proposed regulations, showed inconsistent use of resources when patient needs were similar based on the initial 20 indicators used to calculate acuity and payment levels in PPS. A decision to use a clinical guidance system with the potential to control outcomes and use rates resulted in the development of a system called Care Guides. These tools help home care staff develop and implement efficient and effective home care plans.


Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver.
Contrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was to investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned PCR products as standards, were performed on total RNA of both cell lines and normal liver to evaluate the transcription of 12 transport genes: SLCO1A2, SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1, SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in the tumoral and nontumoral cell lines. Compared with normal liver, the expression of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable, whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal liver. Transport studies and gene expression analyses indicated that B22956 ion is a good substrate to the liver-specific OATP1B3, reported to be poorly expressed or absent in human liver tumors. Therefore, B22956 may be helpful in detecting hepatic neoplastic lesions by CE-MRI.


The tadpole of Hypsiboas guentheri (Boulenger) (Anura: Hylidae).
Hypsiboas guentheri is a species of treefrog that inhabits the surrounding vegetation of temporary and permanent ponds at the coastal region of Southern Brazil, in the States of Santa Catarina and Rio Grande do Sul (Langone 1997; Frost 2016). It belongs to the H. pulchellus species group (Faivovich et al. 2004, Duellman et al. 2016), this group contains 39 species (Frost 2016), but formal descriptions of tadpoles are missing for 15 of them (Kolenc et al. 2008; Pinheiro et al., 2016). Herein we describe tadpoles of H. guentheri collected in February 2014 in the accumulated water on an underpass for wildlife crossing at the RS-486 highway (29º30'44.8" S 50º06'29.9" W), Itati municipality, Rio Grande do Sul State, Brazil.


Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations.
Retinoblastoma (Rb) is a rare and unique eye cancer that usually develops in the retinas of children less than 5 years old due to mutations in the RB1 gene. About 40% of affected individuals have the heritable form making genetics testing of the RB1 gene important for disease management. This study aims to identify germline mutations in RB1 in a cohort of patients with Rb from northern Vietnam. Genomic DNA was extracted from peripheral blood of 34 patients with Rb (nine unilateral and 25 bilateral cases) and their available parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1 gene were screened for mutations with direct PCR sequencing. Multiplex ligation-dependent probe amplification (MLPA) was applied for patients with negative sequencing results. In the mutation-positive patients, their available parental DNA was analyzed to determine the parental origin of the mutation. Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four unilateral and 21 bilateral cases). Of these mutations, 19 were detected, including seven nonsense, six frameshift, four splice-site (one was identified in two siblings), and one missense, with Sanger sequencing. Three novel frameshift mutations were discovered in one unilateral and two bilateral patients. MLPA detected mutations in the RB1 gene in six bilateral cases, of whom five had a whole gene deletion (three familial cases) and one had a partial gene deletion (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed five mutations originated from the fathers and one was inherited from a mother who was mosaic for the mutation. This study provides a data set of germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma. Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.


Making the surgical beds go around.
A planned surgical admission is a major event for a patient and, when cancelled, not only causes great distress to the patient and relatives but is also a frustrating waste of resources if a fully staffed operating theatre lies idle. At Westmead Hospital, a bed management team was established with the appointment of a Clinical Nurse Consultant as Bed Manager to co-ordinate admissions in conjunction with all staff involved in the processing of surgical patients. Despite a reduced number of available surgical beds, throughput was maintained with a significantly reduced number of cancelled booked cases, which decreased to zero and have remained so since the end of 1995. It has been found that it is possible to achieve a situation where all booked surgical patients can be admitted as planned while still providing for emergency patients. This requires a co-ordinated approach with an emphasis on teamwork led by a dedicated Bed Manager working with medical and nursing staff on surgical wards together with the bookings office, pre-admission clinic, operating theatre and anaesthetics department.


The Cost-Effectiveness of Postal and Telephone Methodologies in Increasing Routine Outcome Measurement Response Rates in CAMHS.
This small evaluation compared the cost effectiveness of different methods of questionnaire administration (General system improvements, postal reminders and telephone reminders) sent as part of the CORC protocol employed by three community CAMHS teams. Return rates and costs of these different methods were recorded and compared with a 3-month baseline (during which questionnaires were distributed using existing systems) and following 3-month intervention period. Comparison of return rates between baseline and intervention periods indicated that administrative improvements and a centralised mailing process increased the return rate of questionnaires by 11%. A further limited increase of 16% was achieved when a postal reminder was added, whilst an additional telephone reminder significantly increased the return rate by 34%. Telephone administration and telephone follow-up to initial postal administration is more expensive overall than postal methods alone; however, the cost per return is substantially less. An initial postal mailing plus telephone reminder is predicted to provide services with more representative data on service effectiveness and acceptability than postal methods alone. The findings of this small scale project are useful in informing the Routine Outcome Measurement (ROM) administration protocol and highlight the importance of resourcing ROM and increasing the quality of the data collected.


Chronic kidney disease-related mineral and bone disorders.
The clinical practice guidelines, their scope, limitations and applicability within the field of mineral and bone disorders have been analyzed. The different available guidelines have been compared and their content has been put into the perspective of the user. The aim has been to review their accuracy and relevance for the key set of mineral and bone disorders, and not to attempt to rewrite them or provide new guidelines based on the authors' feelings and experience.


Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture.
To characterize developmental changes in impulse propagation within atrial musculature, we performed high-speed optical mapping of activation sequence of the developing chick atria using voltage-sensitive dye. The activation maps were correlated with detailed morphological studies using scanning electron microscopy, histology, and whole mount confocal imaging with three-dimensional reconstruction. A preferential pathway appeared during development within the roof of the atria, transmitting the impulse rapidly from the right-sided sinoatrial node to the left atrium. The morphological substrate of this pathway, the bundle of Bachman, apparent from stage 29 onward, was a prominent ridge of pectinate muscles continuous with the terminal crest. Further acceleration of impulse propagation was noted along the ridges formed by the developing pectinate muscles, ramifying from the terminal crest toward the atrioventricular groove. In contrast, when the impulse reached the interatrial septum, slowing was often observed, suggesting that the septum acts as a barrier or sink for electrical current. We conclude that these inhomogeneities in atrial impulse propagation are consistent with existence of a specialized network of fast-conducting tissues. The purpose of these preferential pathways appears to be to assure synchronous atrial activation and contraction rather than rapid impulse conduction between the sinoatrial and atrioventricular nodes.


Poly(3,4-ethylenedioxythiophene) (PEDOT) Derivatives: Innovative Conductive Polymers for Bioelectronics.
Poly(3,4-ethylenedioxythiophene)s are the conducting polymers (CP) with the biggest prospects in the field of bioelectronics due to their combination of characteristics (conductivity, stability, transparency and biocompatibility). The gold standard material is the commercially available poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). However, in order to well connect the two fields of biology and electronics, PEDOT:PSS presents some limitations associated with its low (bio)functionality. In this review, we provide an insight into the synthesis and applications of innovative poly(ethylenedioxythiophene)-type materials for bioelectronics. First, we present a detailed analysis of the different synthetic routes to (bio)functional dioxythiophene monomer/polymer derivatives. Second, we focus on the preparation of PEDOT dispersions using different biopolymers and biomolecules as dopants and stabilizers. To finish, we review the applications of innovative PEDOT-type materials such as biocompatible conducting polymer layers, conducting hydrogels, biosensors, selective detachment of cells, scaffolds for tissue engineering, electrodes for electrophysiology, implantable electrodes, stimulation of neuronal cells or pan-bio electronics.


Reducing the morbidity from extravasation injuries.
Extravasation is defined as the leakage of solutions from the vein. This may cause damage to surrounding tissue during intravenous fluid administration. Extravasation has an incidence of 5% of all cytotoxic drug administrations. In the authors' hospital, a protocol has been set up using the dilution flush-out technique. Extravasation packs containing cannulae, normal saline, hyaluronidase, and instructions on how to manage extravasation injuries, accompanied by an audit sheet to assist follow-up, have been introduced to allow the treatment of extravasation at the ward level in an attempt to reduce morbidity from the injury. Between December 1997 and December 1999, 18 adult patients were identified with extravasation injuries after the administration of cytotoxic medication. Seventeen were treated immediately according to the protocol. One, however, was not. Patients were followed-up for 6 months after injury. The 17 patients treated immediately needed no further surgical intervention, whereas the 1 patient not treated needed a split skin graft to cover the defect. The authors recommend the placement of "extravasation packs" on all wards where cytotoxic drugs are prescribed and that all staff members are familiar with this regime. These steps help to reduce the morbidity of a potentially damaging injury.


Dental status of victims from Batajnica's mass graves.
The aim of this paper is to present the post mortem dental evidence and dental health of the victims interred during 1999 in five grave pits at Batajnica near Belgrade. The investigated sample comprised 32 individuals with only maxillae preserved, 80 with mandible, and 260 individuals with both jaws. We have found high degree of enamel hypoplasia (25.89%), frequent signs of the severe forms of periodontal disease (18.55%), very high percent of antemortem tooth loss (31.48%), and evidence of edentate jaws in an early age of individuals. Amalgam was predominant material for tooth fillings; implants and non-metal ceramic crowns were not found, and three quarters of edentate individuals were found with full prostetic dentures. Despite the detailed postmortem dental analysis, antemortem dental charts were not collected. These individuals were identified by other forensic methods.


Home enteral nutrition in paediatric practice.
Nasogastric feeding at home is increasingly being used to provide nutritional support for children with chronic conditions associated with poor growth. The development of specialized feeding products together with accurate and portable enteral feeding pumps has facilitated this process. Parents manage home nasogastric feeding well but require education and continued support. This is probably best offered by a specialized multidisciplinary nutritional care team.


Imaging Parhyale hawaiensis embryogenesis with frequency domain photoacoustic microscopy: A novel tool in developmental biology.
We present the application of a low-cost frequency domain photoacoustic (FDPA) microscope for the label-free imaging of live developing embryos of the crustacean model organism Parhyale hawaiensis. By modulating the intensity of a continuous wave laser source at 9.5 MHz, we achieve the excitation of monochromatic PA waves, which are detected to provide amplitude and phase recordings. The data are subsequently processed to generate accurate maximum amplitude projection and surface reconstructions, delineating the morphological features of the embryos with high resolution and contrast. The findings of this study pave the way for the broader adoption of inexpensive PA diagnostic techniques in developmental biology, shedding light on various fundamental processes in established and emerging model organisms.


Nonsurgical management of two unusual cases of dens in dente.
The management of two unusual cases of dens invaginatus in a maxillary and a mandibular lateral incisor with a periradicular lesion are reported. The patient presented with pain and localized swelling. Despite the complex anatomy and diagnosis of dens invaginatus, nonsurgical root canal treatment was performed successfully. Furthermore essential clinical considerations and treatment options are suggested. Early diagnosis and management are important to avoid complications.


Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion.
Platelet adhesion to the exposed surface of the extracellular matrix in flowing blood is the first and critical reaction for in vivo thrombus formation. However, the mechanism of this in vivo platelet adhesion has yet to be studied extensively. One of the reasons for this is the lack of a practical assay method for assessing platelet adhesion under flow conditions. We have devised an assay method (the fluorescent adhesion assay) that is based on the technique originally reported by Hubbell and McIntire (Biomaterials 7:354, 1986) with some modifications to make it more amenable for assaying small samples and have developed an analysis method to quantify the extent of platelet adhesion and aggregation from fluorescence images by using a computer-assisted image analysis system. In our assay, platelet adhesion, expressed as the percentage of the area covered by adhered platelets, was found to increase biphasically as a function of time. In the first phase, platelets interacted with the coated collagen, transiently stopping on the surface; we called this reaction the temporary arrest. In the second phase, platelets adhered much more rapidly and permanently on the surface, and this adhesion was dependent on the shear rate; platelets formed aggregates in this phase. We used our assay to analyze the effects of platelet aggregation inhibitors on platelet adhesion. All three examined inhibitors, EDTA (10 mmol/L), antiglycoprotein (GP) IIb/IIIa, and GRGDS peptide (1 mmol/L), inhibited the second phase adhesion in flowing blood. Furthermore, GPVI-deficient platelets also showed defective second-phase adhesion under the same conditions. These results suggested that GPIIb/IIIa activation and GPVI contribute to the reaction inducing the second phase. The second-phase adhesion has been extensively investigated, and the consensus is that this reaction is mainly attributable to the platelet-platelet interaction. In this report, we were able to detect an earlier reaction, the temporary arrest. This temporary arrest would reflect the fast and weak interaction between platelet GPIb/IX and collagen-von Willebrand factor complexes on the collagen-coated surface.


The prefrontal cortex and its relation to behavior.
The prefrontal cortex is critical for temporal organization of behavior. It mediates cross-temporal sensory-motor contingencies, integrating motor action (including speech) with recent sensory information. It performs this role through cooperation of two cognitive functions represented in its dorsolateral areas: short-term memory (STM) and preparatory set. Supporting data have been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency. In a given trial, the animal performs an act contingent on a sensory cue given a few seconds or minutes earlier. During the delay between cue and response, cells in dorsolateral prefrontal cortex show sustained activation. Two cell categories can be identified in tasks in which cue and response are spatially separate. Cells of the first participate in STM: Their activation tends to diminish as the delay progresses; in some, the activation level depends on the particular cue received. Similar cells are found elsewhere in cortex. Cells of the second category seem to take part in preparation of motor response: Their activation tends to increase in anticipation of it and may be attuned to the particular movement the cue calls for. This cell type is rare outside of frontal cortex. The temporally integrative function of the prefrontal cortex is probably based on local interactions between "memory" and "motor-set" cells, as well as on neural associations between prefrontal cortex and posterior cortical areas.


Nanoparticle facilitated extracellular electron transfer in microbial fuel cells.
Microbial fuel cells (MFCs) have been the focus of substantial research interest due to their potential for long-term, renewable electrical power generation via the metabolism of a broad spectrum of organic substrates, although the low power densities have limited their applications to date. Here, we demonstrate the potential to improve the power extraction by exploiting biogenic inorganic nanoparticles to facilitate extracellular electron transfer in MFCs. Simultaneous short-circuit current recording and optical imaging on a nanotechnology-enabled platform showed substantial current increase from Shewanella PV-4 after the formation of cell/iron sulfide nanoparticle aggregates. Detailed characterization of the structure and composition of the cell/nanoparticle interface revealed crystalline iron sulfide nanoparticles in intimate contact with and uniformly coating the cell membrane. In addition, studies designed to address the fundamental mechanisms of charge transport in this hybrid system showed that charge transport only occurred in the presence of live Shewanella, and moreover demonstrated that the enhanced current output can be attributed to improved electron transfer at cell/electrode interface and through the cellular-networks. Our approach of interconnecting and electrically contacting bacterial cells through biogenic nanoparticles represents a unique and promising direction in MFC research and has the potential to not only advance our fundamental knowledge about electron transfer processes in these biological systems but also overcome a key limitation in MFCs by constructing an electrically connected, three-dimensional cell network from the bottom-up.


Regulatory T cells in pregnancy. IV. Genetic characteristics and mode of action of early MLR suppressive T cell subpopulations.
The genetic characteristics, surface markers, and mechanisms of action of early-acting, mitomycin-resistant, MLR suppressor T cells from multiparous mouse spleens were studied in MLR of various strain combinations. The cell activity appears to be genetically restricted at the suppressor/reactive cell level, and the major restriction occurs via the IC subregion. However, C3H.OL recombinant pointed toward a possible minor requirement for S-G subregion syngenicity. The suppressor T cell was characterized as an Ia+, Ly1-, Ly2+ subset. The use of Karush double chambers as well as of supernatants of regulated MLR provided evidence that the suppressor cells act via soluble product(s).


Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development.
Carbohydrate-deficient glycoprotein syndrome (CDGS) type II is a multisystemic congenital disease with severe involvement of the nervous system. Two unrelated CDGS type II patients are shown to have point mutations (one patient having Ser-->Phe and the other having His-->Arg) in the catalytic domain of the gene MGAT2, encoding UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N- acetylglucosaminyltransferase II (GnT II), an enzyme essential for biosynthesis of complex Asn-linked glycans. Both mutations caused both decreased expression of enzyme protein in a baculovirus/insect cell system and inactivation of enzyme activity. Restriction-endonuclease analysis of DNA from 23 blood relatives of one of these patients showed that 13 donors were heterozygotes; the other relatives and 21 unrelated donors were normal homozygotes. All heterozygotes showed a significant reduction (33%-68%) in mononuclear-cell GnT II activity. The data indicate that CDGS type II is an autosomal recessive disease and that complex Asn-linked glycans are essential for normal neurological development.


Effects of Cold Hardening on the Regulation of Polyamine Levels in Wheat (Triticum aestivum L.) and Alfalfa (Medicago sativa L.).
When leaves of wheat (Triticum aestivum L.) are exposed to a cold hardening temperature, a major accumulation of putrescine (6-9 times) takes place. Spermidine accumulates to a lesser extent and, conversely, spermine decreases slightly. These variations are completely reversible when plants are returned to initial growing conditions. A similar response is obtained with crowns. During cold hardening, arginine decarboxylase activity remains near its initial level while a considerable loss of activity is observed in control plants. Ornithine decarboxylase and diamine oxidase activity levels are not substantially modified by the treatment. Alfalfa (Medicago sativa L.) also accumulates putrescine under low temperature stress, indicating that this phenomenon is not typical of cereals. The physiological significance of this accumulation of putrescine is still unexplained but the results obtained suggest the involvement of polyamines in the biochemical processes of cold hardening.


An XANES study on the modification of single-walled carbon nanotubes by nitric acid.
X-ray absorption near-edge structure (XANES) spectroscopy has been applied to identify the modification process of single-walled carbon nanotubes (SWCNTs) treated by nitric acid. The carboxyl groups created by the nitric acid treatment have been found to be formed on both the carbonaceous fragments and the side walls of SWCNTs. The carbonaceous fragments could be removed by a following washing treatment with sodium hydroxide. XANES spectra indicate that carbonaceous fragments are the result of the synthesis process and/or of the nitric acid treatment. Tube walls of SWCNTs are weakly oxidized by the nitric acid treatment although, after removing carbonaceous fragments, a direct oxidation process of SWCNTs is observed. Experimental data address the removal of carbonaceous fragments on SWCNTs as an efficient method for side-wall modification of a SWCNT.


A bioinformatic workflow for in silico secretome prediction with the lignocellulose degrading ascomycete fungus Parascedosporium putredinis NO1.
The increasing availability of microbial genome sequences provides a reservoir of information for the identification of new microbial enzymes. Genes encoding proteins engaged in extracellular processes are of particular interest as these mediate the interactions microbes have with their environments. However, proteomic analysis of secretomes is challenging and often captures intracellular proteins released through cell death and lysis. Secretome prediction workflows from sequence data are commonly used to filter proteins identified through proteomics but are often simplified to a single step and are not evaluated bioinformatically for their effectiveness. Here, a workflow to predict a fungal secretome was designed and applied to the coding regions of the Parascedosporium putredinis NO1 genome. This ascomycete fungus is an exceptional lignocellulose degrader from which a new lignin-degrading enzyme has previously been identified. The 'secretome isolation' workflow is based on two strategies of localisation prediction and secretion prediction each utilising multiple available tools. The workflow produced three final secretomes with increasing levels of stringency. All three secretomes showed increases in functional annotations for extracellular processes and reductions in annotations for intracellular processes. Multiple sequences isolated as part of the secretome lacked any functional annotation and made exciting candidates for novel enzyme discovery.


Differential cytokinin structure-activity relationships in phaseolus.
The activities of eight cytokinins in promoting callus growth were tested in two Phaseolus genotypes, P. vulgaris L. var. Great Northern, and P. lunatus L. var. Kingston. The structural feature which contributes to the major genotypic difference in cytokinin structure-activity relationships is the presence or absence of a double bond at the 2,3-position of the isoprenoid N(6) side chain. In Kingston, trans-zeatin was 3-fold more active than dihydrozeatin and 30-fold more active than cis-zeatin. The activities of N(6)-(Delta(2)-isopentenyl)adenine and N(6)-isopentyladenine were nearly the same. In Great Northern, however, dihydrozeatin was at least 30-fold more active than both trans-zeatin and cis-zeatin, and N(6)-isopentyladenine was 100-fold more active than N(6)-(Delta(2)-isopentenyl)adenine. The results suggest the possibility of employing cytokinin structure-activity relationships in distinguishing genotypic differences in cytokinin function and metabolism.


Ions doped melanin nanoparticle as a multiple imaging agent.
Multimodal nanomaterials are useful for providing enhanced diagnostic information simultaneously for a variety of in vivo imaging methods. According to our research findings, these multimodal nanomaterials offer promising applications for cancer therapy. Melanin nanoparticles can be used as a platform imaging material and they can be simply produced by complexation with various imaging active ions. They are capable of specifically targeting epidermal growth factor receptor (EGFR)-expressing cancer cells by being anchored with a specific antibody. Ion-doped melanin nanoparticles were found to have high bioavailability with long-term stability in solution, without any cytotoxicity in both in vitro and in vivo systems. By combining different imaging modalities with melanin particles, we can use the complexes to obtain faster diagnoses by computed tomography deep-body imaging and greater detailed pathological diagnostic information by magnetic resonance imaging. The ion-doped melanin nanoparticles also have applications for radio-diagnostic treatment and radio imaging-guided surgery, warranting further proof of concept experimental.


Atypical Laryngeal Infections: Localized Lesions from Unusual Organisms May Simulate Malignancy.
The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis [LTB]), Mycobacterium fortuitum (laryngeal Mycobacterium fortuitum [LMF]), and Blastomyces dermatiditis (laryngeal blastomycosis [LB]). Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms. Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF. Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.


The Pathfinder image-guided surgical robot.
This paper first describes the workflow of the Pathfinder image-guided surgical robot that has been designed to replace the stereotactic frame in neurosurgery, and then details the calibration stages employed in order to achieve submillimetre positioning accuracy of a tool tip. The process uses non-linear parameter identification techniques in conjunction with some procedures for camera calibration, which exploit the fact that the camera is mounted to a calibrated robot arm that executes precise motions.


A phase II trial of Didemnin B (NSC #335319) in patients with previously treated epithelial ovarian cancer. A Gynecologic Oncology Group Study.
Sixteen evaluable patients with advanced or recurrent epithelial ovarian carcinoma following progression on combination chemotherapy were treated with 4.2 mg/m2 of Didemnin B (NSC #325319) intravenously every 28 days until progression of disease. All patients had prior cisplatin-containing chemotherapy. There were no responders. Seven patients had stable disease (43.7%) and nine (53.3%) had increasing disease. The toxicities were significant, consisting of nausea and vomiting in seven patients (44%), one grade 3 hepatic toxicity, and three instances of grade 4 toxicities (1 leukopenia, 1 GI, and 1 GU). When used with this schedule Didemnin B is ineffective in patients with previously treated epithelial ovarian cancer.


Development of an assay for a biomarker of pregnancy and early fetal loss.
Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; alpha and beta, with molecular weights of 14 kD and 23 kD, respectively. Its alpha subunit is identical in primary structure to its glycoprotein homologs, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodies that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent. This methodology provides a valuable tool for the determination of the rate of early fetal loss.


Reported early separation anxiety symptoms in patients with panic and generalised anxiety disorders.
Attachment theory has proposed that early separation anxiety is a risk factor for adult anxiety disorder, with the recent focus being particularly on panic disorder. The results of empirical studies examining this link are, however, contradictory, possibly because of inconsistencies across studies in measuring memories of early separation anxiety. In the present study, a psychometrically sound measure, the Separation Anxiety Symptom Inventory (SASI) was used to compare memories of such early symptoms in panic disorder (including those with mild phobic-avoidance), generalised anxiety disorder and control subjects. Anxiety patients as a group returned higher SASI scores (p < 0.001) with a non-significant trend for panic disorder patients to score higher than those with generalised anxiety. These results suggest that early separation anxiety may be a harbinger of adult anxiety and that risk of panic disorder may be higher in the most severely affected youngsters. As a risk factor, early separation anxiety does not however appear to be uniquely related to adult panic disorder.


[Androgenetic alopecia, hirsutism and hypertrichosis].
Having too much hair on the face or the body and not enough on the scalp respectively, is generally not a mirror of a life-threatening disease. However, the emotional impact of such cosmetic problems may be remarkable in the individual case. Currently rational treatment options are becoming increasingly available to correct such hair problems. This review highlights the new therapeutic achievements in the treatment of both androgenetic alopecia and hirsutism. Oral treatment of male patterned hair loss with finasteride in men is emphasized, and the use of antiandrogens in women is discussed. In addition, the mode of action and clinical results of topical minoxidil treatment find mention. The second part of the review deals with hirsutism and hypertrichosis. The diagnostic steps and investigations are briefly reviewed, and the advances in laser treatment of hirsutism and hypertrichosis are presented.


Sexually-transmitted disease (STD) markers in multitransfused children in relation to human immunodeficiency virus type-1 (HIV-1) infection: impact of STD markers in blood donors.
Association of serological markers for various sexually transmitted diseases (STDs) with Human Immunodeficiency Virus type 1 (HIV-1) infection among heterosexually promiscuous blood donors is well recognized. However, possibility of similar association among children receiving transfusion from these donors has not been adequately explored. Study on the association of some STD markers with HIV-1 infection in multitransfused (MT) children showed that both HIV-1 positive and HIV-1 negative groups of children had significantly higher prevalence of hepatitis B virus (HBV) markers, i.e. HBsAg (23 and 30 per cent), anti-HBs (46 and 57 per cent), anti-HBc (18 and 23 per cent), antibodies to cytomegalovirus of IgM class (36 and 37 per cent) and IgG class (72.7 and 70 per cent), IgG antibodies to Herpes Simplex Virus type-2 (23 and 23 per cent) compared to control group. However, seropositivity for HIV-1 infection could not be attributed as a risk factor for any of these markers in the group of MT children. On the contrary, significant association of anti HBc, anti HCV, CMV IgG and antitreponemal antibody with HIV-1 infection could be recorded in the group of blood donors. It appeared that due to low prevalence of HIV-1 infection among blood donors in India, both HIV-1 positive and HIV-1 negative groups of MT children received transfusion from HIV negative donors predominantly resulting in a comparable prevalence of STD markers in both the groups of MT children due to cumulative effect of transfusion from HIV-1 negative donors.


Extrapyramidal plasticity predicts recovery after spinal cord injury.
Spinal cord injury (SCI) leads to wide-spread neurodegeneration across the neuroaxis. We explored trajectories of surface morphology, demyelination and iron concentration within the basal ganglia-thalamic circuit over 2 years post-SCI. This allowed us to explore the predictive value of neuroimaging biomarkers and determine their suitability as surrogate markers for interventional trials. Changes in markers of surface morphology, myelin and iron concentration of the basal ganglia and thalamus were estimated from 182 MRI datasets acquired in 17 SCI patients and 21 healthy controls at baseline (1-month post injury for patients), after 3, 6, 12, and 24 months. Using regression models, we investigated group difference in linear and non-linear trajectories of these markers. Baseline quantitative MRI parameters were used to predict 24-month clinical outcome. Surface area contracted in the motor (i.e. lower extremity) and pulvinar thalamus, and striatum; and expanded in the motor thalamus and striatum in patients compared to controls over 2-years. In parallel, myelin-sensitive markers decreased in the thalamus, striatum, and globus pallidus, while iron-sensitive markers decreased within the left caudate. Baseline surface area expansions within the striatum (i.e. motor caudate) predicted better lower extremity motor score at 2-years. Extensive extrapyramidal neurodegenerative and reorganizational changes across the basal ganglia-thalamic circuitry occur early after SCI and progress over time; their magnitude being predictive of functional recovery. These results demonstrate a potential role of extrapyramidal plasticity during functional recovery after SCI.


Optical tomography method that accounts for tilted chest wall in breast imaging.
The chest wall underneath breast tissue distorts light reflection measurements, especially measurements obtained from distant source-detector pairs. For patients with a chest wall located at a shallower depth, the chest-wall effect needs to be considered in the image reconstruction procedure. Following our previous studies, this work systemically evaluates the performance of a two-layer model-based reconstruction using the finite element method, and compares it with the performance of the semi-infinite model. The results obtained from simulations and phantom experiments show that the two-layer model improves the light quantification of the targets. The improvements are attributed to improved background estimation and more accurate weight matrix calculation using a two-layer model compared to the semi-infinite model. Fitted two-layer background optical properties obtained from a group of ten patients with chest walls located less than 2 cm deep are more representative of breast tissue and chest-wall optical properties.


Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection.
Studies analyzing the role of antiendothelial cell antibodies (AECAs) in large series of kidney transplant recipients are scarce, and HLA, MHC (major histocompatibility complex) class I-related chain A (MICA), and angiotensin II type 1 receptor have not been formally excluded as targets. Retrospective study of a cohort of kidney transplant recipients. 324 kidney transplant recipients who were negative for anti-HLA, anti-MICA, and anti-angiotensin II type 1 receptor antibodies were tested for AECAs in pre- and posttransplantation serum samples. AECA-positive (preformed [pre+/post+] vs de novo [pre-/post+]) versus AECA-negative (pre-/post-) before or after transplantation. Patient mortality, transplant loss, and acute rejection events. 66 (20%) patients were AECA positive (39 [12%] preformed, 27 [8%] de novo) and 258 (80%) were AECA negative. During a follow-up of 10 years, 7 (18%) AECA pre+/post+ patients had rejections compared with 14 (52%) AECA pre-/post+ and 57 (22%) AECA pre-/post- recipients (OR, 3.80; P=0.001). AECA pre-/post+ status emerged as an independent risk factor for transplant rejection compared to the AECA pre-/post- group (OR, 5.17; P<0.001). However, AECA pre+/post+ and AECA pre-/post+ patients did not show higher risk for either patient death (ORs of 1.49 [P=0.7] and 1.06 [P=0.9], respectively) or transplant loss (ORs of 1.22 and 0.86, respectively; P for both = 0.8) compared to the AECA pre-/post- population. Retrospective study. Posttransplantation sera were collected before or after rejection, entailing a nearly cross-sectional relationship between the exposure and outcome. Lack of identification of precise antigens for AECAs. De novo AECAs may be associated with rejection. These antibodies might serve as biomarkers of endothelium damage in kidney transplant recipients.


DNA topoisomerase 1 facilitates the transcription and replication of the Ebola virus genome.
Ebola virus (EBOV) protein L (EBOL) acts as a viral RNA-dependent RNA polymerase. To better understand the mechanisms underlying the transcription and replication of the EBOV genome, we sought to identify cellular factors involved in these processes via their coimmunoprecipitation with EBOL and by mass spectrometry. Of 65 candidate proteins identified, we focused on DNA topoisomerase 1 (TOP1), which localizes to the nucleus and unwinds helical DNA. We found that in the presence of EBOL, TOP1 colocalizes and interacts with EBOL in the cytoplasm, where transcription and replication of the EBOV genome occur. Knockdown of TOP1 markedly reduced virus replication and viral polymerase activity. We also found that the phosphodiester bridge-cleaving and recombination activities of TOP1 are required for the polymerase activity of EBOL. These results demonstrate that TOP1 is an important cellular factor for the transcription and replication of the EBOV genome and, as such, plays a key role in the EBOV life cycle.


Effect of thymopoietin and interleukin 2 on depressed mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia.
Previously, cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders were shown to be significantly depressed. Whole blood T lymphocyte colony formation and 3H-TdR incorporation were used to assess the effects of interleukin-2 (IL-2) and thymopoietin (TP-5) on the proliferation of lymphocytes from patients with preleukemia. There were no statistically significant differences (p greater than 0.05) between any of the test groups stimulated with mitogen alone when compared to groups stimulated with mitogen plus TP-5 and/or IL-2 in either assay system for either patient or control groups. Nevertheless, TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the patients studied, but in no case restored the proliferation response to the level of mitogen stimulated control lymphocytes. These findings suggest that other soluble mediators/factors may be needed to fully compensate for deficient mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemic disorders which may be multifactoria in origin. Of importance, enhancement of lymphocyte responsiveness to PHA/Con-A with TP-5 and IL-2 suggests the presence of maturational/functional defects in lymphocytes from some of these patients which may be compensated for in part by addition of TP-5 and IL-2.


Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila.
Branching morphogenesis is a widespread mechanism used to increase the surface area of epithelial organs. Many signaling systems steer development of branched organs, but it is still unclear which cellular processes are regulated by the different pathways. We have used the development of the air sacs of the dorsal thorax of Drosophila to study cellular events and their regulation via cell-cell signaling. We find that two receptor tyrosine kinases play important but distinct roles in air sac outgrowth. Fgf signaling directs cell migration at the tip of the structure, while Egf signaling is instrumental for cell division and cell survival in the growing epithelial structure. Interestingly, we find that Fgf signaling requires Ras, the Mapk pathway, and Pointed to direct migration, suggesting that both cytoskeletal and nuclear events are downstream of receptor activation. Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival, but Pointed is dispensable.


[The dosage calculation of very small irregular electron irradiation fields. 2. The dosage distribution at the edge of the field].
Cross beam dose distributions of the small square electron fields (1 x 1 to 6 x 6 cm2), used in the first part of this paper, have been measured at a linac equipped with metal diaphragms attached to a closed cone. They have been used for calculation of the mean square radial displacements sigma 2 of the corresponding pencil beams. Due to complicate electron scattering at the cone and the diaphragm, the pencil beam method could not be used with the simplicity and accuracy desired in practice. Therefore, the therapeutical sufficient field widths, field areas and integral doses have been determined directly from the measured dose distributions, and are represented in dependence from the geometric field size. For small fields we found considerable reductions of these values, which, in practice have to be compensated by enlargement of the geometric field size.


Combined effects of glycerol and petrolatum in an emollient cream: A randomized, double-blind, crossover study in healthy volunteers with dry skin.
The stratum corneum plays an important protective physiological role in providing a barrier to preventing skin desiccation and penetration of external agents. Emollients are used commonly to improve barrier function and skin hydration. The primary objective of this study was to evaluate the effect of an emollient, V0034CR cream, and its active ingredients, to restore the cutaneous barrier. Secondary objectives included assessment of the moisturizing activity of each product and tolerance. The study was not designed to evaluate therapeutic benefit. In this randomized, double-blind, 4-arm crossover, clinical pharmacology study, the full emollient V0034CR, its vehicle formulation alone, or with glycerol, or petrolatum, was applied to the forearms of healthy volunteers (n = 51) with dry skin (Kligman score of 2 or 3). Cutaneous permeability by Trans Epidermal Water Loss (TEWL) and skin moisture content by corneometry were serially measured for 12 hours following application. An analysis of variance with repeated measures was performed on the evolution of TEWL and corneometry. V0034CR emollient significantly reduced mean TEWL compared to vehicle (P = .0018) and vehicle + glycerol (P = .0001) and significantly increased mean corneometry scores compared to vehicle (P < .0001) and vehicle + petrolatum (P < .0001). The emollient V0034CR presented combined effects, with the petrolatum component improving skin barrier function, with a reduction in TEWL, and the glycerol component improving skin hydration.


Complex Blood Supply Patterns in Cesarean Scar Pregnancy: Insights from Digital Subtraction Angiography Imaging.
BACKGROUND Understanding the blood supply pattern of cesarean scar pregnancy (CSP) can effectively help to determine the best choice of treatment. The aim of this study was to investigate the blood supply pattern and outcomes of patients with CSP through digital subtraction angiography (DSA) imaging. MATERIAL AND METHODS This was a retrospective cohort study. Patients were divided into 2 groups according to the type of CSP. The DSA images of these patients were reviewed, including the type of blood supply, dominant vessel, and collateral blood supply to the gestational sac. The clinical outcomes were analyzed between the 2 groups. RESULTS Thirty-seven patients with type I and 29 patients with type II CSP were enrolled in this study. Type II CSP showed a higher proportion of rich blood supply than type I (44.83% vs 29.72%, P>0.05). Compared with type II CSP, type I CSP tended to have bilateral dominant blood supply predominance (67.57% vs 41.38%, P<0.05). The incidence of collateral blood supply was 5.41% in the type I CSP group and 31.03% in the type II CSP group (P<0.05). In the type II CSP group, multiple collateral blood vessels were found in 4 patients. The superior vesicle artery was the most common source of collateral blood supply in both groups. Two patients with type II CSP suffered massive bleeding during surgery after uterine artery embolization (UAE). None of the patients received a hysterectomy. CONCLUSIONS UAE is safe and effective for both types of CSP. The blood supply pattern is more complex and abnormal in type II CSP. More attention should be paid to the collateral blood supply to achieve complete embolization during the UAE procedure in the case of type II CSP.


Global Adversities, the Media, and Mental Health.
Global communities are currently confronted with a number of complex problems and threats, the reality of which is amplified by the media. These environmental and socio-political stressors have been accompanied by the spread of problematic psychological and behavioural tendencies, such as the growing polarisation of opinions and values, online radicalisation and extremism, deepening xenophobia and nationalism, the proliferation of irrational beliefs and conspiracy theories, and resistance to rational public policy measures. Here we argue that although they fall outside the scope of psychopathology, they nevertheless currently constitute a major challenge for psychiatry as a research domain and a clinical practise. To substantiate this claim, we outline the mechanisms by which media-transmitted stressors impact mental well-being and possibly psychopathology. The common denominator of these global problems and the media's construction of reality is the increase in uncertainty, unpredictability, and uncontrollability, which prompts defensive responding and, in predisposed individuals, functions as a potent source of chronic stress. These contribute to cognitive inflexibility, a strong predisposing factor for the development of rigid beliefs and attitudes, which to varying degrees underlie the adverse psychological and behavioural tendencies mentioned above. We suggest that the tightening of beliefs and ideas that is the result of cognitive rigidity may correspond to the clinical characteristics of induced delusional disorder. This can be seen as a (ultimately maladaptive) defensive strategy for coping with a high degree of uncertainty and unpredictability. We conclude by briefly outlining the possible ways in which psychiatry can face this challenge.


Acetylenic thiophenes from the roots of Escinops ellenbeckii from Ethiopia.
The hexane fraction from the roots of Echinops ellenbeckii O. Hoffm. from Ethiopia yielded seven acetylenic thiophenes of which five compounds (1, 3, 4, 6, 7) are reported for the first time in this species: the monothiophenes 5-(penta-1,3-diynyl)-2-(but-3-en-1-ynyl)-thiophene (1), 5-(penta-1,3-diynyl)-2-(4-acetoxy-but-1-ynyl)-thiophene (2), 5-(penta-1,3-diynyl)-2-(3-hydroxy-4-acetoxy-but-1-ynyl)-thiophene (3), 5-(penta-1,3-diynyl)-2-(3,4-diacetoxy-but-1-ynyl)-thiophene (4), 5-(penta-1,3-diynyl)-2-(3-chloro-4-acetoxy-but-1-ynyl)-thiophene (5), 5-(penta-1,3-diynyl)-2-(3,4-epoxy-but-1-ynyl)-thiophene (6) and the dithiophene 5-[(5-acetoxymethyl-2-thienyl)-2-(but-3-en-1-ynyl)]-thiophene (7). Additionally, four fatty acids (C14, C15, C16 and C18), seven fatty acid esters and three long-chain hydrocarbons could be identified. All the structures were elucidated on the basis of spectral data by GC-MS, HRMS and the NMR techniques.


The role of chemical sciences in 21st century cancer drug discovery.
Extract: The chemical sciences are increasingly overlapping with many aspects of the study of biological molecules at the molecular level. By contrast, the traditional view of chemistry, at least as far as cancer therapeutics is concerned, has been a much narrower one as a tool of the cancer drug discovery process, generally being solely concerned with synthesis. The thesis that we develop in this short review is that the role of the chemical sciences in cancer therapeutics increasingly covers far more than this, and requires the active involvement of many aspects of the subject if the full potential of our knowledge of the cellular, molecular, and genetic basis of cancer is to be translated into clinically useful therapeutics. Effective drug discovery requires an understanding of small molecule and macromolecule physico-chemical properties, mechanism of action, structure and reactivity of individual components (including targets) of pathways, and the ways in which they interact together by means of both covalent and non-covalent recognition and signal transfer. It is no coincidence that several effective clinical agents have been discovered by creative chemists who possess a deep understanding of these topics, especially of the relationships between the structure and reactivity properties of a particular class of molecules, leading to insights into their potential as anticancer agents.


Hepatobiliary transport of bile acids and organic anions.
Recent studies have elucidated the mechanism and regulation of hepatic transport of bile acids and organic anions. Bile acids are taken up into hepatocytes by basolateral transporters, Na+-dependently by Na+/taurocholate cotransporting polypeptide (NTCP) and Na+-independently by organic anion transporting polypeptide (OATP) families. Organic anions are taken up into hepatocytes by OATP families. These compounds are then transported in hepatocytes bound to cytosolic binders, and subjected to transport by ATP binding cassette (ABC) transporters at the canalicular membrane. Amidated bile acids are excreted into bile by bile salt export pump (BSEP), and organic anions and bile acid sulfates and glucuronides are excreted by multidrug resistance protein 2 (MRP2). Hepatic transporters are downregulated under cholestasis in rats and humans, except for MRP3, a basolateral ABC transporter, which is upregulated and may have a role in removing bile acids and organic anions from hepatocytes to the blood under cholestatic conditions. Nuclear receptors, which bind bile acids, have been shown to regulate the expression of hepatic transporters. Farnesoid X receptor (FXR), which downregulates CYP7A1, the rate-limiting enzyme of bile acid biosynthesis, upregulates BSEP and downregulates NTCP. MRP2 is upregulated by both FXR and pregnane X receptor (PXR), which upregulates CYP3A.


[CT staging of malignant lymphoma. How to avoid misinterpretations].
Therapeutic strategy and prognosis of malignant lymphoma are influenced by staging. Therefore, evaluation of pattern of lymphatic involvement is highly relevant. There are numerous pitfalls possible in detection and description when malignant lymphomas are visualized by computed tomography (CT). Normal anatomic structures may be interpreted as pathologic lymph nodes by inexperienced radiologists. Assessment and detection of lymphomas require precise knowledge of normal anatomic structures as well as roentgenological criteria and adequate methods of imaging. This report provides an overview of the relevant pitfalls and often overlooked areas in staging of malignant lymphomas.


Antioxidant activity, volatile composition and sensory profile of four new very-early apricots (Prunus armeniaca L.).
Very-early apricot cultivars are interesting owing to the fact that they will be available in markets before any other cultivar. In order to achieve good fruit quality, very-early apricots require appropriate size, weight and color, good balance of sugars and organic acids, proper content of bioactive compounds, relatively strong apricot aroma as well as acceptable sensory quality. Physical, chemical, antioxidant and sensory properties showed important variations among apricot cultivars. These differences were basically attributed to genetic reasons. Four very-early apricot cultivars were studied, namely 'Mirlo Blanco', 'Mirlo Anaranjado', 'Colorao' and 'Mogador'. All of them showed proper size and weight, but their contents of organic acids, sugars and bioactive compounds were low and the number of volatile compounds was also low. However, very-early apricots showed an appropriate sensory profile for fresh consumption. Regarding physical, chemical and volatile composition and sensory properties, very-early apricot cultivars could be recommended for fresh consumption. However, future research must be focused on increasing their contents of sugars, organic acids and bioactive and volatile compounds, perhaps via cultural practices such as deficit irrigation and/or mulching.


The effect of open and closed chain exercise and knee joint position on patellar tracking in lateral patellar compression syndrome.
There are numerous rehabilitation protocols for patellofemoral problems, but there is little objective data to determine the most effective exercise program to conservatively treat this disorder. The purpose of this study was to determine the effect of open and closed chain exercise and knee joint position on patellar tracking in lateral patellar compression syndrome. Computed tomography scans of the patellofemoral joint were performed with the leg in three muscle conditions and at five knee angles in 16 subjects with lateral patellar compression syndrome. Patellar tracking was evaluated by measuring congruence angle. Relaxed and closed chain conditions demonstrated improved congruence as compared with the open chain condition at 0, 10, and 20 degrees of knee flexion (p < .0001). Open chain strengthening techniques appear to be most appropriate after 30 degrees of knee flexion. The three muscle conditions demonstrated progressively improved patellar congruence from 0 to 40 degrees of knee flexion.


Characterization of an Ethylene Overproducing Mutant of Tomato (Lycopersicon esculentum Mill. Cultivar VFN8).
Ethylene production rates and tissue ethylene concentrations were determined for the single-gene, Epinastic (Epi) tomato (Lycopersicon esculentum Mill.) mutant, and its parent, cv VFN8. The Epi phenotype was characterized by severe leaf epinasty, thickened stems and petioles, and a compact growth habit. In 4-day-old seedlings, ethylene production was significantly higher in Epi than in VFN8. Ethylene production rates also were higher for excised root, hypocotyl, cotyledon, and shoot tissue of 14-day-old Epi seedlings as compared with VFN8. The greatest difference in the ethylene production rate was observed in excised Epi shoot tissue, which was more than 2.5 times higher than in VFN8. Tissue ethylene concentrations of 19-, 25-, and 31-day-old Epi plants were 8, 172, and 307% higher than for VFN8, corresponding to increasing expression of the Epi phenotypic characteristics with age. The highest ethylene concentrations occurred in the shoot apex of both genotypes. Higher ethylene concentrations in Epi resulted from greater 1-aminocyclopropane-1-carboxylic acid content rather than increased ethylene-forming enzyme activity. The elevated ethylene levels in Epi did not result from increased auxin sensitivity. The sensitivity of root growth to inhibition by ethylene did not differ between VFN8 and Epi. Although elevated levels of ethylene in Epi plants apparently exacerbate its epinastic growth characteristics, other evidence indicates that this may not be the fundamental lesion. This mutant may provide a unique system for investigating the regulation of ethylene biosynthesis and the role of target cell types in plant development.


Acute stress symptoms in young children with burns.
Posttraumatic stress disorder symptoms are a focus of much research with older children, but little research has been conducted with young children, who account for about 50% of all pediatric burn injuries. This is a 3-year study of 12- to 48-month-old acutely burned children to assess acute traumatic stress outcomes. The aims were to (1) assess the prevalence of acute traumatic stress symptoms and (2) develop a model of risk factors for these symptoms in these children. Acute stress symptoms were measured using the Posttraumatic Stress Disorder Semi-Structured Interview and Observational Record for Infants and Young Children. Children's responses were then assessed, including behavior and physiological measures for developmental/functional consequences. A path analysis strategy was used to build a model of risk factors. Risk factors assessed in this model included observed pain (Visual Analogue Scale), parent symptoms (Stanford Acute Stress Reaction Questionnaire), and magnitude of trauma (total body surface area burned). Of the 64 subjects meeting inclusion criteria, 52 subjects agreed to participate. These children were highly symptomatic; almost 30% of these children had acute stress symptoms. A path analysis model yielded two independent pathways to acute stress symptoms: (1) from the size of the burn to the mean pulse rate in the hospital to acute stress symptoms and (2) from the child's pain to the parents' stress symptoms to acute stress symptoms. This model accounted for 39% of the variance of acute stress symptoms and yielded excellent fit indexes. A high percentage of acute stress symptoms were identified in young children with burns. A model of risk factors, including the size of the burn, pain, pulse rate, and parents' symptoms, was identified.


The alpha-galactosyl epitope on human normal and autoimmune thyroid cells.
As much as 1% of circulating IgG in man (the natural anti-Gal antibody) is directed against the alpha-galactosyl epitope, with the structure Gal alpha 1----3Gal beta 1----4GlcNAc-R. The alpha-galactosyl epitope is abundantly expressed on cells of nonprimate mammals, prosimians, and New World monkeys. Its expression is diminished in Old World monkeys, apes, and humans. It has been previously suggested that interaction between anti-Gal and aberrantly expressed alpha-galactosyl epitopes on thyroid cells may contribute to the initiation of autoimmune thyroid disorders. To study this possibility, alpha-galactosyl epitope expression on thyroid cell membranes of normal individuals and patients with Graves' disease was assessed by a sensitive radioimmunoassay. alpha-Gal-actosyl epitopes were found both on normal and diseased thyroid cells. Whereas the concentration of these epitopes on Graves' disease thyroid membranes was somewhat higher than that observed in normal glands, the difference was not significant. The activity of the enzyme, alpha 1-3-galactosyltransferase, which synthesizes the alpha-galactosyl epitope, was higher in microsomal fractions obtained from some patients as compared with healthy controls, but not significantly different. In view of the abundance of anti-Gal antibody in the circulation, it is argued that, under physiologic conditions, the interaction of this antibody with alpha-galactosyl epitopes does not elicit pathologic effects. However, aberrant expression of the alpha-galactosyl epitope may result in effective anti-Gal binding to thyroid cells (e.g., rearrangement of this structure on the cell membrane or its increased expression).(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy and Safety of Olanzapine in Children Receiving Highly Emetogenic Chemotherapy: A Randomized, Double-blind Placebo-controlled Phase 3 Trial.
In this trial, we evaluated the safety and efficacy of olanzapine in children receiving highly emetogenic chemotherapy. In this study, patients aged 3 to 18 years were randomly assigned to either the olanzapine group or the placebo group. All patients received intravenous ondansetron and dexamethasone 30 minutes before highly emetogenic chemotherapy, followed by oral ondansetron for 48 hours. Participants in the olanzapine group received olanzapine once daily on days 1 and 2, while those in the control group received a placebo in the same dosage and schedule. The primary objective was: (a) to compare the complete control rates of vomiting in the delayed phase and (b) to compare the complete control rates of vomiting in acute and overall phases. The secondary objective was to evaluate the safety of olanzapine and the need for rescue medications. A total of 128 patients were randomly assigned either to the olanzapine group (n=63) or the control group (n=65). Complete control of vomiting between olanzapine and placebo group was 73% versus 48% ( P =0.005) in the delayed phase, 60% versus 54% ( P =0.46) in the acute phase, and 48% versus 34% ( P =0.117) in the overall phase, respectively. Grades 1 and 2 sedation was greater in the olanzapine group (46% vs. 14%; P <0.001). A significantly higher proportion of patients in the placebo group required rescue medications for vomiting compared with in the olanzapine group ( P =0.025). Olanzapine significantly improved complete control of vomiting in the delayed phase. A considerably lesser proportion of patients in the olanzapine group needed rescue medications.


Scaling of structure functions in homogeneous shear-flow turbulence.
We apply spectral dynamics and non-Gaussian statistical model of velocity difference to study the scaling of structure functions in homogeneous shear-flow turbulence. Let L(S) be the shear length scale and eta the viscous scale. It is found that, when L(S)/eta is finite, due to a combined effect of viscosity and mean shear, the scaling deviates from normal scaling, and the deviation increases as L(S)/eta decreases. In the presence of a strong shear (L(S)/eta<100), the deviation is substantially larger than the prediction of typical intermittency models, in agreement with recent experiments. As L(S)/eta-->infinity, the normal scaling is valid in the inertial range where viscous and shear effects are negligible.